Telehealth Will Change the Healthcare Industry in the US

There are a lot of unfortunate realities about life in capitalist societies, particularly in the United States – one of the main issues being that corporations try to profit off anything and everything.

What’s one of the most important things for a human being? Their health and well-being. This, sadly, means that those in charge of Big Pharma and the healthcare industries can charge an arm and a leg – sometimes quite literally – for people who are simply interested in keeping themselves healthy.

Fortunately, things may soon be changing. With the advent of technology, more and more people are beginning to offer more affordable alternatives to the traditional model of healthcare. Telehealth, for example, is currently changing the entire industry. 

What Is Telehealth?

Telehealth is a branch of medicine that deals with providing services to patients through the use of information technology, like the telephone or the Internet. Telehealth is able to provide people with a number of services, including:

  • The diagnosis of certain ailments
  • Prescribing medication, which can be sent to the nearest pharmacy
  • Helping patients manage mental illnesses
  • Offering advice and education about certain ailments or conditions
  • Monitoring the condition of certain patients
  • Providing intervention in cases where this is necessary

Why Is Telehealth Beneficial?

There are a number of reasons that telehealth could be beneficial for both patients and doctors or therapists. 

  • It’s much more accessible. Patients are able to get prescribed medication, have their conditions diagnosed, or otherwise receive medical assistance from the comfort of their homes or while they’re on-the-go.
  • It’s more affordable. Many people are overwhelmed by the high costs of healthcare, and while telehealth might not presently be considered cheap, it can certainly be more affordable than the alternative. In addition, transportation costs are reduced.
  • It is not stigmatized. This is particularly important for people who are seeking treatment for mental health and may be concerned about the stigma surrounding mental health treatment. With telehealth, they can seek treatment without being seen or judged by anyone, primarily via what’s known as e-counseling.

How Does This Impact Healthcare Practitioners?

It’s not just the patients who are going to experience changes by switching to telehealth. Doctors, therapists, and other healthcare practitioners may see some changes as well. 

  • Doctors and therapists may be able to make more money. While they might initially make less for each patient that they see through telehealth, the convenience of scheduling and information storage means that they might actually be able to see more patients, thus earning more money.
  • Healthcare workers can reach a wider audience. By providing an easy system through which practitioners can connect with patients, telehealth is able to allow doctors and therapists to offer their services to more people than they would be able to otherwise.

There’s little doubt that the advent of telehealth has made huge changes in the healthcare industry, and it seems like these changes will only continue to manifest in new and exciting ways. If you think that these benefits could improve your life, don’t hesitate to sign up for telehealth.

Credit for Featured Image: mHealth Intelligence Blog

#DTMH Strategies: An Introduction to the Test

The Royal College of Physicians, London, administers the examination for the award of the Diploma in Tropical Medicine and Hygiene, to examine and certify physicians who “wish to practice medicine effectively in developing countries.” I recently took the exam, and managed to clear it. This year, I am serving as a Moderator for the students in the Global Health and Humanitarian Medicine course, run by Medecins Sans Frontieres, qualifying which enables one to be eligible to sit for the exam.

Who can take the exam?

According to the eligibility criteria mentioned on the RCP’s website:

Candidates for the Diploma in Tropical Medicine and Hygiene must hold a primary medical qualification recognized by the Royal College of Physicians of London (RCP). The RCP will accept applications from candidates who are in the process of completing, or have completed within the last 5 years, the approved tropical medicine courses in the following locations (which are recognized as appropriate training centers for the examination):

  • Glasgow Diploma in Tropical Medicine and Hygiene course
  • Sheffield Diploma in Tropical Medicine and Hygiene course
  • Oxford University MSc course in International Health and Tropical Medicine
  • Liverpool School of Tropical Medicine: DTMH course, MSc in Tropical and Infectious Diseases, or MSc in Tropical Paediatrics
  • London School of Hygiene and Tropical Medicine: DTMH course or MSc in Tropical Medicine and International Health
  • Médecins Sans Frontières Course in Global Health and Humanitarian Medicine (GHHM)
  • ASTMH-approved diploma courses satisfying the requirements for CTropMed.

Confirmation of attendance on one of the appropriate tropical medicine courses (as above), and of proficiency in microscopy (requiring a minimum of 12 hours of microscopy / practical parasitology teaching) within the last 5 years will be required for each candidate before taking the examination.

Examination Structure

The examination is marked out of 500 marks. The break up for the marks is as below

Morning Exam Session

100 ‘best of five’ questions to be answered in 3 hours. Of these, 16 will be based on clinical images designed to test the candidate’s knowledge of tropical medicine and hygiene over a wide area. Each question carries 2.5 marks and the whole paper is for 250 marks (50% of total). No negative marks for any answer which is marked incorrectly. After the BOF paper, the lunch break is scheduled, which is usually for about a hour.

Afternoon Exam Session

The afternoon exam session is for 2.5 hours and consists of two separate examination papers: Preventive Medicine and Parasitology/Entomology.

The Preventive Medicine short answer paper lasts for 1 hour. The candidate has to choose 5 questions from a total of 10 questions. Each question is valued at 20 marks, and may consist of multiple sub-questions and sub-sub-question, for which additional break-ups in marks will be given. The total value of the paper is 100 marks (20% of total).

The Parasitology/Entomology short answer paper lasts for 1.5 hours. This paper usually takes place after a short break after the Preventive Medicine paper. The paper consists of 50 very short answer questions, carrying a total of 150 marks (30% of total). The questions usually consist of three parts, all inter-related, and often with an image with or without a clinical vignette to go along. The answers need to be inscribed in really small boxes – so there is no space or time for fluff.

Results

Roughly, about 60% marks need to be scored overall, to gain a passing score. In addition, one has to secure passing marks (50%) on the Best of Five paper and the Preventive Medicine+Parasitology/Entomology papers. So, for the afternoon exam sessions, there is some leeway in that if one of them is an utter disaster, one still has a chance to recover from it.

Exam results are declared after 6 weeks or so, and the diploma is sent by ordinary post. So, if your area has iffy postal services, be prepared for a long wait. They do communicate the results by email, and I have been told that the attached attestation that you have passed the exam is credible enough for prospective employers who know the value of the examination.

Source for Featured Image: MSF Transformational Investment Capacity

Infectious Disease Outbreaks in Kerala: May 2018 – May 2019

Of late, Kerala has been in the news quite a bit, first for the Nipah virus scare, and then the floods and disease spikes in their wake. However, the state has remained extremely well prepared to respond to these public health and infectious disease challenges. As I was perusing some of the statistics reported from the state for the past year, for some other work, I thought of putting down my reflections in the form of a quick blog post analyzing the outbreaks reported from the state in the past 12 months. I have sourced the data from the Integrated Disease Surveillance Program website’s weekly outbreaks reports. Of course, the validity of any and all analysis and reflections depends on the accuracy and validity of these data, but since I have no other standard to that I can compare with (without having to invest extra time, effort and money), I am going to work off these data points. Further, since these are government generated data, they are more likely to find their way into the policy making realms. I looked at the outbreaks reported between the 21st week of 2018 (21st May to 27th May, 2018) to the 20th week of 2019 (13th May to 19th May 2019), which is the most recent data available at the time of writing this post.

Demographics of Kerala

Kerala, India

The southern Indian state of Kerala is home to about 33 million people, and was the 13th largest state in terms of population according to the 2011 census. It is divided into 14 districts, which form the administrative and policy making units in most public health programming. Kerala has the highest literacy rate in India, almost 94%, and the gender ratio stands at 1.084, in comparison to the national ratio of 0.940. Kerala has the highest life expectancy of all states in India. Kerala also boasts of sub-replacement fertility rates. In this one year period, there were 104 reported outbreaks of various infectious diseases from Kerala.

Outbreaks: Locations

District-wise number of outbreaks

The outbreaks represented a fairly large part of the state, although almost 60% of the outbreaks could be accounted for by Ernakulum, Malappuram, Kozhikode, Wayanad and Kollam. Interestingly, Wayanad, which is the least populous district of Kerala, figures prominently, with a skewed number of outbreaks happening there. Ernakulum and Malappuram are one and three in the population ranking for the most populous districts in Kerala, according to the 2011 census.

District-wise population of Kerala: 2011 census (Wikipedia)

Outbreaks: Diseases

Number of Outbreaks in Kerala May 2018-May 2019

The most commonly reported outbreaks were hepatitis A and food poisoning, accounting for almost half of all the outbreaks. There was only one outbreak of cholera, and interestingly, there was even an outbreak of Crimean Congo Hemorrhagic Fever (admittedly represented by a single patient), which was something that surprised me. The IDSP provides some details related to this case. It seems that the case began its clinical trajectory whilst in UAE, and culminated in India. A lot of doubts still remain after reading the IDSP narrative; I am providing it in full (edited only for grammar and syntax) below.

CCHF in Kerala

A 31-year old male native of Malappurum, working as a butcher in Abu Dhabi, UAE, returned to Cochin on 29th November 2018. During his journey he presented with headache and was admitted to a Private Hospital in Cochin. District RRT (Rapid Response Team) investigated the outbreak.

IDSP Weekly Outbreaks report
  • On 15th November 2018 the case was admitted in a hospital in Abu Dhabi, UAE with symptoms of high grade fever, headache, body pain, myalgia and vomiting.
  • Blood sample was positive for CCHF (by PCR).
  • He was treated in a hospital at Abu Dhabi, UAE. On 25th November 2018, the blood sample was negative for CCHF and was discharged from the hospital.
  • 3 more cases were reported from the affected area and were treated in locally in Abu Dhabi, UAE.

Active search for cases conducted and contacts were traced. 2 blood samples were collected and sent to Manipal Center for Virus Research, Manipal. They were both negative for CCHF. Infection control measures were undertaken at the hospital where the patient was admitted. No new cases were reported. Health education given.

District-wise outbreaks in Kerala

Some other interesting trends can be picked up if one looks at the spread of the outbreaks over the various districts. In the table above I have provided some of the major outbreaks in a district wise pattern. I have left out a few diseases, hence the total will not make it up to 104, which was the total number of reported outbreaks. Interestingly, there were 5 outbreaks of West Nile Fever, and in all five occasions, they took place in Kozhikode. Although there were only three outbreaks of Leptospirosis, one of them was in the wake of the floods, and resulted in 590 cases and 8 deaths in Ernakulum (35th reporting week, 2018).

Post-Flood Leptospirosis

The IDSP report for the 35th reporting week, 2018, identifies a large outbreak of leptospirosis. Although the report attributes the cases to Ernakulum, the narrative appended along with it provides a slightly different picture. I am providing the comment in full, edited only slightly for grammar and syntax, with no change in its sense.

Cases were reported from multiple flood affected districts: Ernakulam, Alappuha, Pathanamthitta, Thrissur, Palakkad, Malappuram and Kozhikode. District RRT investigated the outbreak. House to house surveys were done. 158 cases were confirmed using IgM ELISA for Leptospirosis at DPHL (District Public Health Laboratory), Medical College and referral labs. All cases were treated symptomatically. Intensive preventive measures were implemented. Arrangements were made for early recognition and treatment. Chemoprophylaxis using Doxycyclin capsules was given to all persons exposed to flood water as well as to those engaged in rescue activities. Community was made aware of signs and symptoms of disease and measures of prevention.

IDSP Weekly Outbreaks report

Outbreaks: Case Counts

Now I realize that this is perhaps the least reliable metric, since they are subject to a lot of variability, but since the data was available, I decided to quickly summarize it anyway.

Case counts from Kerala Outbreaks

Food poisoning, which was one of the commonly occurring reported outbreak, naturally accounted for the highest number of cases, with the post-flood tide of Leptospirosis claiming the second largest number of cases.

Nipah Virus Outbreak in Kerala

So, amidst all of this, where is the Nipah virus outbreak, one may ask… or at least I was asking. I checked the WHO website, and it states that the Nipah Virus outbreak began in Kerala on 19th May, 2018, which falls in the period for which I extracted the data. It is not mentioned in any of the weekly reports (or if it is mentioned, I may have missed it – do let me know if that is indeed the case). The WHO website mentions:

On 19 May 2018, a Nipah virus disease (NiV) outbreak was reported from Kozhikode district of Kerala, India. This is the first NiV outbreak in South India. There have been 17 deaths and 18 confirmed cases as of 1 June 2018. The two affected districts are Kozhikode and Mallapuram. A multi-disciplinary team led by the Indian Government’s National Centre for Disease Control (NCDC) is in Kerala in response to the outbreak. WHO is providing technical support to the Government of India as needed. WHO does not recommend the application of any travel or trade restrictions or entry screening related to NiV outbreak.

WHO Website

However, if one navigates to the website of the Directorate of Health Services, Kerala, and looks up the reports generated for the year of 2018, one can find that there is clearly the mention of the devastating Nipah Virus outbreak there. Yet, this did not figure in the weekly report published for the corresponding week on the IDSP website and the reason for the same is not quite clear to me.

Data on communicable diseases: Kerala

Summing up…

Whilst the limitations of outbreak reporting remains clearly documented, and the challenges in providing up to the date data on outbreaks as they happen is a problem a lot of resilient systems have not been able to solve, there still remains a lot of value that can be attached to perusal of outbreaks data from the IDSP system. The large threat of infectious diseases clearly remains; on an average, about 9 infectious disease outbreaks hit one part of another of Kerala, throughout the last year. This number is likely to be similar to data being reported from other parts of the country as well. If nothing else, then this is a strong indicator that whilst the non-communicable disease challenge needs to be met with a strong and decisive hand, it should not come at the cost of resources allocated to meeting the infectious disease threats looming large over India. We are still at that uncomfortable cusp, where we have to deal with the dual threats of communicable and non-communicable disease burdens.

AMR Goes Global: Detection of Allochthonous Anthropogenic AMR Genes in High Arctic Regions

This study has been popping up all over the AMR radar for me for the past week; so, when I was stuck in traffic today, I decided to sit down and give the article a read. An interesting read, which does provide insights into the rapid global spread of AMR, this article, however, has been taken way out of context by the headlines of tabloids screaming the end-of-the-world prophecies. Now, I am the last person to discount the threat of AMR, but at the same time, perhaps this is not as bad as the tabloids made it out to be. The worrisome thing remains that we are no strangers to the introduction of “invasive” pathogens in previously naïve settings, which end up wreaking havoc over the years. Perhaps the cholera experience of Haiti stands out to be one of the most remarkable examples of this mishap. Finding antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) which are definitely not of local origin does raise the specter of an invasive, allochthonous route, but before hitting the panic bells, we need more evidence on the routes and sources for the emergence of these unlikely tourists in the wintry north.

In the study, the authors looked at forty samples from across 8 soil clusters, as highlighted in the image below.

Sampling locations of the eight soil clusters in Kongsfjorden. Topographic map has been adapted from the Norwegian Polar Institute.
Sampling locations of the eight soil clusters in Kongsfjorden. Topographic map has been adapted from the Norwegian Polar Institute.

Barely a stone’s throw away from the North Pole, the study area provided a unique geoclimatic ecosystem in which to study the presence of AMR genes in the soil. Located on a remote island, with no native agriculture or industry, the small resident population (n=120) of Kingsfjorden, Svalbard, live in an area which is cold enough to preserve DNA in soil for a prolonged period, yet, never freezes over due to Gulf currents. The area is, thus, exposed to importation of ARGs and MGEs, piggybacking on migratory birds or travelers who may pass through this Arctic sentinel.

The authors report that they identified 131 ARGs in the forty areas studied, and of these, they found 39 in all the clusters – these likeluy represented the autochthonous ARGs which were likely background presence, irrespective of anthropogenic threats. The study does not clearly define a strategy to understand and define whether an ARG is autochthonous or allochthonous. The definition used by the authors to designate particular ARGs as allochthonous include the fact that the ones so labelled were isolated from only a few of the sampled clusters and were associated with resistance against antibiotics which are of critical importance for human health (aminoglycosides, macrolides, carbapenems, penicillin, and cephalosporins). This definition, whereby the putative allochthonous versus autochthonous status is ascertained based on the presence or absence of each ARG compared across the sampled clusters, could potentially be rife with controversies. Although such a definition allowed the authors to pin point the presence of “foreign” ARGs and MGEs in the Arctic environment, it will also feed into the uncertainties about the sources of the same.

Resistance genes were detected against nine major classes of antibiotics, though the predominating ones were against aminoglycosides and beta-lactams. In five out of the eight soil clusters sampled, the researchers detected the blaNDM-1 gene. This gene, which produces the New Delhi metallo-β-lactamase (NDM-1) enzyme, which confers resistance against carbapenems, is definitely not a local entity and has likely traveled over on biological vehicles. Isolation of blaNDM-1 virtually seals the case for the international migration of AMR. This report is also the first time that this resistance gene has been demonstrated in the High Arctic areas. More concerning was the fact that in one of the locations, SL3, shown in green circle above, the authors discovered a painful secret:

Levels of both blaNDM-1 and FabK were approximately 100× greater in
SL3 than in the other clusters. Indeed, relative abundances of blaNDM-1
at SL3 were similar to levels found in environments impacted by hospital
and urban wastewaters.

This, in combination with the fact that the authors found an “AMR gradient” across the study site, points to issues which need to be studied in more details. Despite the absence of any local, AMR producing drivers, the fact that there is differential occurrence of ARGs and MGEs in the soil, indicates some differential levels of “AR pollution” in the area, according to the authors. I wholeheartedly agree with this contention of the authors, and in fact, find it more troubling than the mere presence of the blaNDM-1 genes in the area. The presence of “Indian origin” AMR genes in the Arctic makes for sensational headlines and clickbait traps, but far greater is the implication hidden in the small sentence where the authors ponder on why the differential ARG gradient was observed in an area where the traditional drivers and determinants of AMR are not at play.

Distribution and abundance of ARGs in the eight High Arctic clusters classified by antibiotic class and cluster location. The Chord diagram presents the abundance of ARGs in each sample that associate with each respective antibiotic class among the eight soil clusters (top). Presented below the diagram is the relative abundance of ARGs normalized to the total abundance of 16S rRNA gene (bottom right) and relative proportions of ARG classes in each cluster (bottom left). MLSB denotes Macrolide-Lincosamide-Streptogramin B. Other labels represent ARGs that do not have a direct antibiotic class. F/C/A denotes florcholoram-phenicol antibiotic class.
Distribution and abundance of ARGs in the eight High Arctic clusters classified by antibiotic class and cluster location. The Chord diagram presents the abundance of ARGs in each sample that associate with each respective antibiotic class among the eight soil clusters (top). Presented below the diagram is the relative abundance of ARGs normalized to the total abundance of 16S rRNA gene (bottom right) and relative proportions of ARG classes in each cluster (bottom left). MLSB denotes Macrolide-Lincosamide-Streptogramin B. Other labels represent ARGs that do not have a direct antibiotic class. F/C/A denotes florcholoram-phenicol antibiotic class.

The authors have adequately focused on the opportunity presented by these scantily populated outer fringes of human civilization as sentinels of globalization of AMR; however, without a better understanding of how the ARGs got there within a mere 2-3 years of their identification, such a sentinel surveillance will provide minimal actionable evidence.

This study, which has captured the attention of the popular media, points to a deeper malady which is getting buried under all the noise around blaNDM-1 and its geopolitical connotations. One can only hope that the scientific enquiries, which should be precipitated by this publication, are not derailed or disorientated by the surrounding brouhaha.

Mapping Infectious Diseases Using Crowdsourced Data Collected With Open-Source Tools

One of the challenges that is ubiquitous for infectious disease epidemiology researchers is getting access to correct, up-to-date mapping data which can be reliably used. Often, the existing data is out of date, or plain wrong. Hence, each time we initiate a study in a new area, we undertake a rapid assessment of the study area to get a sense of the place and persons living there. One can imagine how important this exercise is, and understandably so. The fly in the ointment is that this is a process which is expensive, and time taking, and is often not considered to be a part of the main research agenda or research question, making it all that more difficult to allocate adequate resources to get it done. The problem gets even worse when, instead of a research activity, we are considering an outbreak or an emergency situation, where even time is not there!

This paper, published in PLOS ONE earlier this year, piqued my interest, and I have been meaning to write about it for a while now. This work was done in the course of the Ebola outbreak in West Africa, and reflects on the feasibility and cost of undertaking mapping the source villages of the Ebola Virus Disease (EVD) afflicted people, using open source tools, installed on self-owned smartphones, belonging to people living in and around the target communities.

The study itself was born in an environment which I can clearly see happening. In the African context, where this study was done, chiefdoms and other levels may not be analogous to the political stratification in India. However, tracing patients and their contacts is a challenging problem in either setting. Whoever has worked with infectious disease patients in low- and middle-income countries (LMICs) will thoroughly agree with the authors’ words:

Information regarding EVD positive cases was shared with the local Ministry of Health and Sanitation (MoHS) and Ebola response partners. However, MSF staff and partners were often confronted with challenges in obtaining reliable geographical information to enable the immediate tracing of EVD contacts and follow-up of discharged survivors. This was because the village of origin given by the patient could sometimes not be located on the available district maps, as some villages had similar names but were in different chiefdoms, or villages had both an official and an alternate village name. In addition, information about new villages, including satellite villages and up-to-date population numbers, were not available. This delayed the response, and MSF and MoHS staff often relied on knowledge of their local drivers, or had to stop and ask local residents for village locations.

Timely and effective containment of EVD relies on multiple interventions: isolation, surveillance, contact tracing, decontamination, health promotion, psychosocial support and community engagement [4]. These interventions cannot be implemented without accurately locating potentially affected areas. Therefore, accurate maps are an important tool for outbreak investigation and response, and facilitate visualising the extent of an outbreak [5].

Perhaps the strongest words in the entire paper are in the last sentence of the section I have quoted above.

This study basically trained community-level volunteers, who owned their own Android Smartphones, and installed two open source software on it: survey software (OpenDataKit (ODK)) and navigation software (OpenStreetMap Automated Navigation Directions (OsmAnd)). These surveyors were trained in the use of the software, and trained to collect a simple set of data. They were then paired off with local motorbike riders to go to the target villages and collect the data. Validation was done by  “comparing the village names against a pre-existing village name and location list using a geographic distance and text string-matching algorithm”.

Process of validation of mapping data.
Process of validation of mapping data.

The impact of this process was astounding:

Following de-duplication, the surveyors collected data from 891 villages with an estimated 127,021 households. The overall survey cost was €3,395; €3.80 per village surveyed.

The main expenses were related to HR and travel, as can be expected:

Costs were calculated considering the fixed daily cost of Okada drivers, which included fuel and vehicle maintenance costs. The daily cost for surveyors was calculated based on a fixed daily rate, which included costs for phone credit and recharging their smartphone battery. Both Okada riders and surveyors were reimbursed if they had overnight costs due to travel to distant chiefdoms.

‘Okada’ drivers refer to commercial local motorbike drivers, who are very conversant with the local terrain, and have the expertise to navigate the unpredictable and difficult roads of Sierra Leone. Their in-depth knowledge of the local language, affordability, and ability converse both in English as well as the local languages (Temne and Mende), made them an important part of the study.

The Okada drivers were paid €25 (SLL 120,000) daily to cover fuel, their daily worker rate and vehicle maintenance. The surveyors were paid €10 (SLL 50,000) daily to cover their daily worker rate, phone credit and smartphone battery recharging. The overall cost for collecting this survey data was €3,395; which equates to €3.80 per village surveyed.

In addition, the study built on the relatively high smartphone ownership in the region to minimize HR costs. Further equipment needed to maintain, transmit, store and manage the data also was not elaborate, and can easily be obtained even in several challenging situations.

The advantage of this survey was the minimal set of requirements necessary to securely collect data: one laptop; a server, such as a small mobile device which can operate via internet and range in cost from €10–25; a local web-based aggregation platform; ODK, OsmAnd and QGIS®open source software; Android smartphones and affordable local transport. The open-source software used in this survey is known to be virus-free, does not have any advertisement or need for payment, and the collected data belongs to MSF and is secured on an MSF password protected server.

Naturally, on reading this study, I started to consider if it would be possible to deploy a similar approach in the settings that I work in. It would probably not be out of question. And the only problem that I can foresee in the Indian setting is that a considerable number of slums have started to grow vertically in space-constrained Indian urban slums. Unless there is some sort of height data, it is likely to be problematic to de-duplicate families based on the two-dimensional locational coordinates. However, this is a very cost-effective, efficient, and community-oriented process that we could try out in some future study. Last year, I supported the Practicum Research work done by a Master’s Student from the Emory University, who worked on mapping of the local drainage systems. Whilst that is a more complex issue than mapping families of putting a locational dot where cases exist, in hindsight, we could have used some of these techniques!

John Snow’s famous map of the 1854 Broad Street epidemic attempted to positively correlate disease intensity with proximity to a single water source, the Broad Street well and pump.
John Snow’s famous map of the 1854 Broad Street epidemic attempted to positively correlate disease intensity with proximity to a single water source, the Broad Street well and pump.

It has been over 150 years now since John Snow revolutionized the process of disease determinant detection simply by putting a dot on the map where there were cases of cholera. The entire field of epidemiology and spatial analysis perhaps owe their origin story to him! From cholera to ebola virus, the principles remain same, the challenges remain, although now we are much better at finding disruptive solutions for them!

Reference:

Nic Lochlainn LM, Gayton I, Theocharopoulos G, Edwards R, Danis K, Kremer R, Kleijer K, Tejan SM, Sankoh M, Jimissa A, Greig J, Caleo G. Improving mapping for Ebola response through mobilising a local community with self-owned smartphones: Tonkolili District, Sierra Leone, January 2015. PLoS One. 2018 Jan 3;13(1):e0189959. doi: 10.1371/journal.pone.0189959. eCollection 2018. PubMed PMID: 29298314; PubMed Central PMCID: PMC5752033.

The Abyss Stares Back: Silos in One Health and the Emergent Need to Breach them

The One Health approach, widely adopted and acknowledged as the way forward in dealing with issues which cut across sectoral compartments, has sometimes being criticized for inadvertently promoting the very approach of silo-ism in the name of specialization, that it was developed to breach. In a not-so-recent bibliometric analysis of published One Health literature, this very claim is put to test, using social network analysis to measure interdisciplinarity in One Health studies constructing dynamic pathogen transmission models.

The study finds that the dynamic disease modelling community not only grew in size but also in diversity, in keeping with the growing range of calls for One Health proposals. A walk trap algorithm was used to identify the communities within a large number of peer-reviewed publications (n=2258); three separate communities were identified. Two of them corresponded to very clear cut disciplinary silos: ecology and veterinary sciences – the disciplines which have contributed maximally to the development and understanding of the One Health approach. The third was a more heterogeneous group, which defied a clearer disciplinary epithet. Efforts to identify sub-communities in this group identified two clear sub-communities: epidemiology and mathematical biology. This third group, perhaps, comes closest to the definition of One Health research as we in public health have been using.

Venn diagrams of cross-community authorship through time. Each year’s Venn diagram is scaled to reflect the number of authors with two or more papers in our paper bank over the preceding 5 y. Number of authors with two papers in the same journal community are represented by disjointed regions of the circles, and number of authors with papers in two different communities are represented by the area of the intersections. Each circle is scaled to reflect the total number of authors with papers in that community during the 5 y prior to the label year. Areas are on a log-scale, and total number of authors with multiple papers each year is reported below each Venn diagram.

This paper, which was published in PLOS Biology, is heavy on the mathematics, but yet, is not completely unintelligible. Leaving aside the social network analysis bit – which is a topic I am not very conversant in – the rest of the results are quite plausible and intuitive. In fact, they reinforce some of the assertions and criticisms levelled against the One Health approach in a recent commentary published in the BMJ Global Health.

Some of the trends were positive, encouraging, and in line with the perceived growth of One Health as a recognized research appraoch. Also encouraging was the fact that more and more authors were contributing to journals in two or more communities (as identified above). This indicates not only an expanding One Health researcher base but also, the fact that they are doing more interdisciplinary work over time.

However, the authors identify limited evidence of information movement between the three research groups – the very problem which spawned the discipline of One Health. As I have long-suspected, the authors identify that there is limited engagement from the medical research community, creating hurdles in strengthened interactions across the human medicine interface of human-animal-environment interface issues.

The study further reinforces the assertion that we had placed in one of our earlier publications on the need to restructure One Health/EcoHealth education, perhaps by disrupting the medical curricula a little bit to introduce students to the concept earlier in their medical careers. In addition, moves to create platforms for allowing better interaction between scientists and clinicians from various interfacing disciplines is an aspect which has remained poorly acknowledged. There is very limited funding for this type of work, especially in a world where research funding is ever contracting. In addition, the trend of siloed existence of ecology and veterinary researchers within the One Health community does little to address the lack of involvement of the human health partners. It thus becomes a matter of vital importance to enable cross-disciplinary efforts, and although there is germinating traces of a “One Health” group, without continued funding support, and dedicated resources allocated to capacity building, it is likely to meet with limited success and stunted growth. However, one hs to guard against the temptation to be overly critical, for, it would be perhaps the most foolhardy to throw the baby out with the bathwater.

Addressing Cholera Under-Reporting Key to Mounting Proportionate Public Health Response

Cholera remains a cause of public health concern, not only causing explosive outbreaks in settings with disrupted socio-political and health infrastructure, but also exacting a huge burden in endemic settings with ongoing transmission. The development of a cheap, effective and easy to administer Oral Cholera Vaccine (OCV) has been a breakthrough development and in combination with effective water, sanitation and hygiene (WaSH), can be used to design a package of comprehensive cholera control interventions. This may be used for targeted control of cholera, especially in known, vulnerable hotspots. However, the public health response to cholera remains hamstrung by the lack of accurate data on the burden of cholera, especially in vulnerable areas. Weak surveillance systems, inconsistent case definitions, lack of laboratory capacity, and apprehensions about the negative impacts on travel, trade and commerce have led to consistent under-reporting of cholera globally.

India, particularly the Gangetic belt, has been identified as the cradle of cholera, with six of the seven cholera pandemics originating here. Cholera strains isolated from global sources have shown remarkable genetic similarity to the strains isolated from these areas, indicating that obtaining control of the cholera menace in this region could potentially have a global positive impact.

Transmission events inferred for the 7th Pandemic phylogenetic tree drawn on a global map. The date ranges shown for transmission events are taken from the BEAST analysis, and represent the median values for the MRCA of the transmitted strains (later bound), and the MRCA of the transmitted strains and their closest relative from the source location (earlier bound). (1)

A potential strategy to address this shortcoming could be to develop capacity across a network of institutions with the objective of enabling them to undertake cholera diagnostics. An effective, facility- and indicator-based hybrid surveillance system could then be deployed within these facilities, for collection of structured data, to monitor the occurrence of cholera, over time, in high vulnerability settings. The problem with this approach is that it does not really provide a good estimate of the “denominator”, that is, the total population which is likely to have been the source of the identified cases of cholera. Without this metric, it becomes virtually impossible to develop any epidemiologically intelligible information.

A strategy to overcome this shortcoming could be to supplement the facility-based surveillance with healthcare utilization surveys in catchment communities to estimate adjusted incidence of cholera. An approach to do that has been highlighted by Prof. Stephen Luby and his collaborators in a previous publication. They have termed it as “Hybrid Surveillance” – an efficient compromise between the resource-intense cohort studies which can provide accurate estimates of the disease burden and the inexpensive facility-based surveillance, which is extremely likely to underestimate the magnitude of a problem. Hybrid surveillance is situated somewhere in between these extremes – and involves pairing the facility-based surveillance with healthcare utilization surveys in the catchment communities. The authors elucidate the concept in great detail to enable other researchers to endeavor to replicate the method. 

Typhoid disease pyramid, where the base represents all typhoid patients in a catchment area and the apex represents culture-positive cases detected at study sites. Culture sensitivity is estimated from the literature, enrollment capture is estimated at facilities, and facility coverage is estimated by a household survey. These factors are utilized to adjust the crude incidence. (2)

Hybrid surveillance may be thought of as characterizing the layers of a disease detection pyramid, where all typhoid patients within a catchment area represent the base, and culture-confirmed cases detected at surveillance facilities represent the apex. A fraction of all typhoid patients in the community will seek care at study sites, a proportion of those are recruited and enrolled into the surveillance system, and the sensitivity of blood culture will determine how many cases are detected among those enrolled. Hybrid surveillance involves adjusting cases detected for these factors.

With cholera being under-reported, often by a factor of as much as 100x, it is perhaps of critical importance to establish a system which will deliver reliable and timely data on the burden of cholera at the national level. This will help to monitor the morbidity and mortality due to cholera and allow health policymakers get an estimate of the extent of under-reporting of cholera at the national level. The accurate burden estimates will have a major impact on reorienting cholera control plans, specifically with respect to vulnerable areas within the catchment areas under surveillance. This would also help in planning the most optimal approach for effectively implementing OCVs in hotspots. 

The silence around declaring cholera as a national priority has slowly begun to be breached in Africa. It is perhaps the time for the other vulnerable geographic areas to join in the growing clamor to end cholera by 2030. 

References:

  1. Mutreja A, Kim DW, Thomson NR, et al. Evidence for several waves of global transmission in the seventh cholera pandemic. Nature. 2011;477(7365):462-5. Published 2011 Aug 24. doi:10.1038/nature10392
  2. Andrews JR, Barkume C, Yu AT, Saha SK, Qamar FN, Garrett D, Luby SP. Integrating Facility-Based Surveillance With Healthcare Utilization Surveys to Estimate Enteric Fever Incidence: Methods and Challenges. J Infect Dis. 2018 Nov 10;218(suppl_4):S268-S276. doi: 10.1093/infdis/jiy494. PubMed PMID: 30184162; PubMed Central PMCID: PMC6226762.

Ending Cholera by 2030: Case Management Remains a Key Priority

The Case Management Work Group of the Global Task Force for Cholera Control met for the third time in Veyrier du Lac, France, at the picturesque facilities of Les Pensieres, on 5th and 6th November, 2018, with the following stated objectives:

  • Provide an update on the implementation of the Ending Cholera Roadmap and country engagement
  • Provide an update on the GTFCC research agenda and priorities for the Case Management WG
  • Present new training and case management tools and agree on a dissemination strategy
  • Discuss a review of Rapid Response Teams during cholera outbreaks and lessons learnt
  • Present an update on the treatment of cholera in patients with Severe Acute Malnutrition (SAM)
  • Discuss opportunities for coordination with other GTFCC Working Groups, including areas requiring the development of technical guidance
The almost magical grounds of Les Pensieres, Fondation Merieux, at Veyrier du Lac

Dominique Legros spoke about the update on the implementation of the Ending Cholera Roadmap in cholera endemic countries, and appreciated the changing policy environment around cholera. He specially highlighted two aspects:

  • The exponential increase in the demand and use of OCVs globally, justifying the investment in the vaccine made by the Vaccine Alliance (GAVI), to enable its deployment in areas of need at low costs.
  • The engagement of the political leaders and the positive political will in bringing out into the open the discussions about cholera, in a bid to end cholera once and for all.

The second achievement has been especially significant in light of the fact that conventionally,cholera has been viewed as an anathema. Often the outcome of poverty, poor access to safer water, sanitation and hygiene; and an issue inviting financial and political sanctions, cholera has remained under-reported and hidden away for fear of the repercussions. Therefore, active engagement from the political leadership of the cholera-affected countries is a major step in the right direction.

Leadership to End Cholera is crucial
(Picture from presentation by Dominique Legros)

The partner updates were presented from: India (by me!), Haiti (Kenia Vissieres, Partners in Health), Nigeria (Seabstian Yennan, Nigeria CDC), UNHCR (Allen GK Maina), Alima (Eric Barte de Sante Faire), and Bangladesh (Azharul Khan, ICDDRB). All the presentations made at the meeting are available from the Fondation Merieux website.

Case Management challenges in healthcare facilities and at the community level were discussed at length. The model of the Malawi healthcare workers, which has also recently been discussed in an article in the BMJ Global Health, was presented. I had my reservations about the model, which had a lot of similarities with the ASHA worker model in India. I was concerned that as in India, too many responsibilities were being shouldered by the community level healthcare workers, and as a side effect, the quality of services provided by them could be compromised. The good thing was that there was a systematic training program planned for these workers. However, the quality control measures were not very clear to me.

My presentation on cholera case management status in India

In course of the second day’s discussions, the two groups which emerged as neglected groups, with little evidence base to guide clinical practice, particularly in difficult settings, like in the case of humanitarian crises, were pregnant women and children with severe acute malnutrition. Presentations from Medecins Sans Frontieres highlighted the plight of pregnant women, who were purging, and went into labor, in the cholera treatment centers. Thankfully, this is a small proportion of patients, but the clinical and humanitarian challenges in ensuring the dispensing of dignified care to these women is indeed a major challenge.

A presentation by the WHO Country Office representative from Yemen reiterated the scale of the cholera problem in the war torn country and the major hurdles in providing even basic healthcare. It was appreciable that even with such insurmountable challenges as were faced by the healthcare providers in Yemen, the reported mortality from cholera remained at less than 1%, around 0.3%. 

The meeting also dedicated some time to discuss and network between members (both present at the meeting and those that called in) in response to the call for proposals from Wellcome Trust-DFID, UK, for cholera control as part of the epidemic preparedness program.

Although significant achievements have been made in the past year, there still remain significant challenges to providing adequate, evidence based care to all, in difficult settings, particularly in cholera endemic areas experiencing war or political unrest or other humanitarian crises. 

Dermatology Topics for ICMR-STS

Can you suggest ideas for ICMR research (STS) in dermatology?

For ICMR-STS, you have to depend on a guide from your medical school. So, it would largely be guided by her/his experience of working in the medical school. The topic that you can do, would depend on what kind of clinical materials, patients and mentorship you have access to in your medical school.

First, I would suggest that you come up with a set of research questions which interest you. Then you go through the list and see which of your questions can be answered through the stipulations of ICMR-STS – limited time, money and resources. A good test would be to see if your research question would fulfill the FINER criteria.

– It should be Feasible (F), with adequate number of subjects, adequate technical expertise, affordable given the time and money available, and manageable in scope.
– The question should be Interesting (I), intriguing the investigator (which is YOU!) and other researchers, clinicians and experts working on similar topics.
– It should be Novel (N), generating some new content, which can add to the existing body of knowledge. However, for ICMR-STS projects, given the limited resources and time, this is one criteria which can be compromised on.
– The question should be answerable in an Ethical (E) manner. It should not breach the principles of non-maleficence, beneficence, autonomy and respect.
– It should be Relevant (R), particularly to the public health and clinical needs of India.

research-question-18-638.jpg

Image Source: Dr. Tarek Tawfik Amin, Slideshare

An example of such an idea would be to try and understand the burden of a particular disease in a section of an at risk community – a typical example being the range of dermatological diseases in HIV+ patients and the coping mechanisms that the patients use to deal with the problems. You could explore, in addition to the medical issues, the social determinants affecting outcomes in dermatological diseases in people living with HIV/AIDS (PLWHA). You could ask about their clinical trajectories, stigma experiences, barriers and facilitators to healthcare access, cost implications – particularly out of pocket (OOP) expenses, and others. These are just ones I could think of on the go!

To summarize, your research question should have a clinical or public health implication for society at large.

Best of luck in your search for a good research question in dermatology for the ICMR-STS program!

PSM as a Career Option #5: Community Medicine Senior Residency in AIIMS

What are the pros and cons of joining as a senior resident (Community Medicine) in All India Institute of Medical Sciences?

Which AIIMS are you referring to? There are several now!

It is always a BIG plus to work in AIIMS, New Delhi. Not only do you get to work closely with the doyens of the discipline, but also gain an invaluable toehold in the city, which is pretty much the hub of public health excellence in India. There are a few cons, specially the fact that if it is AIIMS, New Delhi, you will probably be sent away to two years to the rural outpost. The pro of that is that there are ample opportunities to do good research and keep your clinical skills sharpened by treating patients at the secondary healthcare level.
About the other AIIMS, I do not have much idea! A good idea would be to approach someone already working there to get an idea of how things are. Nowadays there are several channels on WhatsApp groups and Facebook which can be used to find such a person.

And finally, these discussions on pros and cons are moot until you specify what your goal is. Like in the exchange between Alice and the Cheshire Cat in Lewis Carroll’s immortal Alice in Wonderland book:

“Would you tell me, please, which way I ought to go from here?”
“That depends a good deal on where you want to get to,” said the Cat.
“I don’t much care where—” said Alice.
“Then it doesn’t matter which way you go,” said the Cat.
“—so long as I get SOMEWHERE,” Alice added as an explanation.
“Oh, you’re sure to do that,” said the Cat, “if you only walk long enough.”

All the best in finding your place in the world!

The Ills of Rattlesnake Pills

In the weird news section of the day, comes this one: child falls sick with lethal salmonella infection after consuming rattlesnake pills.

Yeah, you got that right. Someone was feeding a child rattlesnake meat, all dried up and powdered, in the form of pills, hoping something miraculous woould happen. This media release from the CDC retains a stiff upper lip while proclaiming:

The Centers for Disease Control and Prevention and the Kansas Department of Health and Environment have linked one person’s SalmonellaOranienburg infection to taking rattlesnake pills. Rattlesnake pills are often marketed as remedies for various conditions, such as cancer and HIV infection. These pills contain dehydrated rattlesnake meat ground into a powder and put into pill form. CDC recommends that you talk to your health care provider if you are considering taking rattlesnake pills, especially if you are in a group more likely to get a severe Salmonella infection.

I do not know what you (assuming the reader is a medical care provider) would advise, but I would, for sure, be asking my patients to abstain from consuming rattlesnake pills!

There have been anecdotal evidence linking the consumption of reptile meats with Salmonella, and a long time ago, I remember blogging about the rise of exotic reptilian pets as one of the drivers behind the rising number of Salmonella infections in the UK. My incredulity is no less now that I discover that another reason for this affliction is the intentional consumption of something that is basically a placebo!

The ABC News quotes an Infectious Disease researcher who shares my sentiment of disbelief and general aghastness at this news. Here is what they state:

John James, a microbial epidemiologist at Children’s Hospital in Denver, said the life-threatening strain of bacteria — Salmonella arizonae — in capsules of dried rattlesnake meat caused a child to become seriously ill. The child survived.

James talked about that case and the overall issue on Saturday at the annual scientific sessions of the Society for Healthcare Epidemiology of America in Baltimore.

“Anecdotal evidence linking capsules of dried rattlesnake meat to salmonella poisoning has been reported for years. For the first time, however, we’ve used DNA molecular testing to prove definitively that the salmonella bacteria found in the dried meat was the cause of a life-threatening case of salmonella blood poisoning in a patient treated at our hospital,” James said in a prepared statement.

Salmonella arizonae is commonly found in snakes and lizards.

“Unfortunately, the rattlesnake capsules — believed by some to treat many types of diseases — are often given to people whose immune systems already are compromised,” James said. The child in this case had systemic lupus.

“These capsules should be removed from the market, or the manufacturers should be required by the U.S. Food and Drug Administration to irradiate the product before it is sold,” James said.

I think they should be banned outright!

Anyway, another interesting observation I made while reading this piece is the fact that the incriminated serovar is called Oranienburg, which is a city in Prussia. This was one of the first places in Prussia where the Nazi Germans established a concentration camp when they were usurping power in 1933. This facility was meant for a very specific demography according to Wikipedia, which states:

 It held the political opponents of German Nazism from the Berlin region, mostly members of the Communist Party of Germany and social-democrats, as well as a number of homosexual men and scores of the so-called undesirables.

The prison was taken over by the SS on 4 July 1934, when the SA was suppressed by the regime. It was closed and subsequently replaced in the area by Sachsenhausen concentration camp in 1936. At closure, the prison had held over 3,000 inmates, of whom 16 had died.

For documentary purposes the German Federal Archive often retained the original image captions, which may be erroneous, biased, obsolete or politically extreme.

Coming back to the issue at hand, to summarise, if you are going to consume dried rattlesnake meat powder, I have just one word for you: DON’T!

Mapping Kolkata’s Hospitals with Google Maps: Crowdsourced GeoHealth

I received an email update from Google Maps about a brilliant initiative that is going to be of special importance in this season of “unknown” acute febrile illness affecting a large cross-section of the society. I am reproducing the full text of the linked post from the Google Maps Local Guides Connect web page. Do let me know if this is breaching copyright issues and I shall initiate the appropriate corrective measures. I can be reached via email at pranab.chatterjee AT outlook.com.

India has more than 35,000 hospitals spread across the country, and even more clinics and pharmacies. That’s a lot of places to sift through when you’re trying to figure out where to go for the right kind of care or medications. And when it’s about health, getting the most accurate information quickly is important.

Shaunak Das (a.k.a. @DrShaunak) is a doctor and a native of Calcutta. A few months after becoming a Local Guide in 2015, Das began to notice that many of the hospitals and clinics he visited for were not listed on Google Maps, or that their listings contained the wrong contact information. “In Calcutta, the phone number is more important than a website address. People look for a phone number,” says Das.

This worried Das, who knew that people might look to Google to quickly find urgent medical care. So Das began adding to and correcting the information on Google Maps using a directory of hospitals and clinics he had at home. His efforts have made it easier for people all over Calcutta to find nearby clinics and hospitals.

You can help your neighbors and visitors find the best, most convenient healthcare in your community by adding your local pharmacy or your preferred hospital to Google Maps. By including extra details, like the type of payments a hospital accepts or the hours of operation, make it easier for other people to decide where to go. Got a favorite medical shop or a great dentist? Help other people find their business by adding them on Google Maps!

You can easily add a hospital, clinic, or pharmacy by:

  1. Open Google Maps on your phone
  2. Touch the location on the map
  3. Tap the address at the bottom, or the dropped pin
  4. Tap Add Missing Place
  5. Enter the details about the location, like the name, the hours of operation, and the kinds of payments the place accepts

If your family doctor, local pharmacy, or preferred hospital has already been added but you notice there are details you would like to include, you can quickly add any missing information by:

  1. Open Google Maps on your phone
  2. Search for the place in Google Maps and tap the name to open it
  3. Above the address, select Know what features this places has?
  4. Tap the info you’d like to add (think about the things you’d find most useful to know)
  5. When you’ve finished, tap the arrow to the right. Your updates have been saved!

As a Local Guide you can help make your community more accessible to everyone by sharing your most trusted places.

Leptospirosis Hits Puerto Rico in the Aftermath of Hurricane Maria

As expected, the news of rising numbers of leptospirosis cases are trickling in from Puerto Rico. Since Hurricane Maria hit Puerto Rico, there have been areas which have experienced over 30 inches of rain, which, subsequently, led to flooding. As has been often observed, following the exposure to potentially contaminated water, the reported number of leptospirosis cases has been on the rise. Leptospirosis is a water borne zoonosis, with humans being unwitting targets in its transmission cycle.

Leptospirosis Transmission Cycle: Image Credits Georgia Gwinnet College Wiki
Leptospirosis Transmission Cycle: Image Credits Georgia Gwinnet College Wiki


This week, a news outlet has reported that there have been two confirmed fatalities from leptospirosis. The news article further elaborates:

“This bacteria, like any other bacteria, can kill you,” Deseda said.

The island typically sees between 63 and 95 cases per year, she said. Health officials had expected that there would be a jump after the hurricane.

“It’s neither an epidemic nor a confirmed outbreak,” Public Affairs Secretary Ramon Rosario Cortes said at a news conference Sunday. “But obviously, we are making all the announcements as though it were a health emergency.”

Although it has not assumed epidemic or outbreak proportions yet, the problem with leptospirosis is that this is a largely mild disease. That means that this is one of the conditions in which the actual magnitude of the issue is much larger than what falls within the clinically visible spectrum. In epidemiology, this is often hailed as (or depending on your viewpoint, trivialized as) the iceberg phenomenon.]

Iceberg Phenomenon (Image Credits: Community Medicine Blog)
The Iceberg Phenomenon Image Credits: Community Medicine Blog

Although there is limited evidence to give an exact accounting of the asymptomatic:symptomatic infection ratio for leptospirosis in outbreak settings, an oft-cited paper states that less than 30% of seropositive individuals, studied in Nicaragua, reported a febrile illness in the two months prior to the testing. The suggestion of this paper, that asymptomatic leptospiral infection is common in endemic situations, is further backed up by the conclusions presented in the Laboratory Manual on Leptospirosis (2007), published by the Indian Council of Medical Research, Regional Medical Research Center at Port Blair, Andaman and the South East Asia Regional Office of the WHO. The manual states:

In endemic areas, the incidence of asymptomatic infection could also be very high. A survey conducted in Seychelles (17) showed 9% point prevalence of asymptomatic leptospiral infection as proved by positive Polymerase Chain Reaction Test (PCR). In a study conducted in the North Andaman, 27% of the 396 persons followed up serologically had evidence of leptospiral infection during the follow up period of 12 weeks in the postmonsoon season (22). [Refer to document for cited reference; link]

There has been some accumulating evidence on what factors might potentially modulate the emergence of leptospirosis. As is often (or should I say always?) the case with zoonotic infections, the disease manifests especially well when there is a constellation of “favorable” factors present. A review attempted to graphically present the related risks in a Venn diagram, as below:

Factors contributing to leptospirosis. Development of leptospirosis depends on three types of factors (epidemiology, host, and pathogen) and their interactions. Epidemiologic factors include sanitation, housing, rainfall, and whether flooding occurs. Incidence is linked to income level, occupation, and travel, representing epidemiologic factors linked to specific hosts. Hosts vary in susceptibility depending on age, genetic factors (e.g., HLA-DQ6), skin integrity, and whether protective clothing (e.g., gloves and boots) are worn. The ways in which the host and leptospires interact determine the route, exposure, and dose of the pathogen. Leptospiral pathogens differ in their ability to cause disease, a reflection of their virulence, motility, and ability to survive in the host, a reflection (at least in part) of complement resistance. The types of reservoir hosts determine the types of pathogens present in a particular epidemiologic setting
Factors contributing to leptospirosis. 

Development of leptospirosis depends on three types of factors (epidemiology, host, and pathogen) and their interactions. Epidemiologic factors include sanitation, housing, rainfall, and whether flooding occurs. Incidence is linked to income level, occupation, and travel, representing epidemiologic factors linked to specific hosts. Hosts vary in susceptibility depending on age, genetic factors (e.g., HLA-DQ6), skin integrity, and whether protective clothing (e.g., gloves and boots) are worn. The ways in which the host and leptospires interact determine the route, exposure, and dose of the pathogen. Leptospiral pathogens differ in their ability to cause disease, a reflection of their virulence, motility, and ability to survive in the host, a reflection (at least in part) of complement resistance. The types of reservoir hosts determine the types of pathogens present in a particular epidemiologic setting.


Public Health Response to Leptospirosis

The following excerpt from the ““WHO recommended standards and strategies for surveillance, prevention and control of communicable diseases” are applicable for the management of potential outbreaks of leptospirosis.

Control activities

Case management

  • Early treatment with antibiotics. Severe cases usually treated with high doses of IV benzylpenicillin (30 mg/kg up to 1.2 g IV 6-hourly for 5-7 days). Less severe cases treated orally with antibiotics such as doxycycline (2 mg/kg up to 100 mg 12-hourly for 5-7 days), tetracycline, ampicillin or amoxicillin.
  • Third-generation cephalosporins, such as ceftriaxone and cefotaxime, and quinolone antibiotics may also be
    effective. Jarisch-Herxheimer reactions may occur after the start of antimicrobial therapy.
  • Monitoring and supportive care as appropriate, e.g. dialysis, mechanical ventilation.

Prevention

The large number of serovars and of infection sources and the wide difference in transmission conditions make
leptospirosis an unlikely candidate for national eradication. Preventive measures should be based on knowledge of
those groups at higher risk of infection and of local epidemiological factors; they include:

  • Identifying and controlling the source of infection (e.g. open sewers, contaminated wells).
  • Control of feral reservoirs is often not feasible but control measures can be highly effective in small, defined animal populations (dogs, certified cattle herds) Selective rodent control may be important.
  • Interrupting transmission, thereby preventing infection or disease in the human host: ƒ
    • wearing protective clothes and equipment;
    • disinfecting contaminated surfaces such as stable and abattoir floors;
    • marking areas with increased risk exposure (warning signs).
  • Preventing infection or disease in human hosts:
    • antibiotic prophylaxis of exposed persons in areas of high exposures may be effective, e.g. soldiers (doxycyclin 200mg in one weekly dose);
    • raising awareness of the disease and its of modes of transmission.

Epidemics

Conditions under which epidemics may occur

  • Conditions leading to an increase of contaminated surface water or soil, such as rain, floods and disasters
    increase the risk of leptospirosis and may lead to epidemics. During periods of drought both humans and animal reservoirs may be attracted to spare water places, hence increasing the risk of infection.
  • Social and recreational activities that expose persons to a contaminated environment.

Management of epidemics

In a suspected outbreak, attempts to diagnose leptospirosis must be encouraged to enable prompt treatment. For
outbreaks in remote or areas with poor access, local use of screening tests to detect antibody is helpful. When an
outbreak of leptospirosis is suspected or identified, and if it has been possible to identify the serovar concerned, the
source must be identified and appropriate environmental measures implemented, with public information to people at risk (including clinicians and health care workers and health authorities).

Drug-resistance monitoring

No reports of resistance for common antibiotics (see Case management above) and no guidelines for monitoring.
Testing of antibiotic resistance in individual clinical cases is not useful since it requires considerable time.

Performance indicators for control activities

  • Number of new cases per 100 000 population over time.
  • Seropositivity in selected populations.

The Diagnostic Dilemma of Leptospirosis

The challenge of reaching a diagnostic conclusion with a suspected case of leptospirosis is no less daunting than the public health activity of controlling an outbreak of this disease. Aside from the fact that it is not always on the diagnostic radar of clinicians, especially if they are not hyper-vigilant (which can sometimes come off as over-diagnostics or defensive medicine) or are not aware of the relevant exposure history, the complex immune response also plays a part in the diagnostic prevarication that often may accompany leptospirosis in areas where it is not always on the first list of differential diagnoses. In India, we were taught a “truism” which works well for identifying patients potentially exposed to a higher degree of risk of leptospirosis: “It is a disease of ‘rats, rains and rice’!”

This helpful schematic, from a review on Leptospirosis, can shed some light on the diagnostic approaches to managing leptospirosis:

Biphasic nature of leptospirosis and relevant investigations at different stages of disease. Specimens 1 and 2 for serology are acute-phase specimens, 3 is a convalescent-phase sample which may facilitate detection of a delayed immune response, and 4 and 5 are follow-up samples which can provide epidemiological information, such as the presumptive infecting serogroup. Adapted from Turner LH (1969). Leptospirosis. Br Med J i:231–235. Copyright © American Society for Microbiology, (Clin Microbiol Rev 2001, 14 (2):296–326. doi:10.1128/CMR.14.2.296-326.2001)
Biphasic nature of leptospirosis and relevant investigations at different stages of disease. 

Specimens 1 and 2 for serology are acute-phase specimens, 3 is a convalescent-phase sample which may facilitate detection of a delayed immune response, and 4 and 5 are follow-up samples which can provide epidemiological information, such as the presumptive infecting serogroup. Adapted from Turner LH (1969). Leptospirosis. Br Med J i:231–235. Copyright © American Society for Microbiology, (Clin Microbiol Rev 2001, 14 (2):296–326. doi:10.1128/CMR.14.2.296-326.2001)


Leptospirosis in India

India has had its own share of misfortunes with outbreaks of leptospirosis, with case in point being outbreaks in Mumbai and Chennai after massive rains led to a deluge. The National Centers for Disease Control, in collaboration with the Country Office for WHO, came up with a comprehensive document to address the public health challenge of leptospirosis outbreaks: Guidelines for the Prevention and Control of Leptospirosis. One interesting factor which has been addressed in these guidelines is the use of chemoprophylaxis for potentially exposed individuals. The document states:

15.8 Chemoprophylaxis

During the peak transmission season Doxycycline 200 mg, once a week, may be given to agricultural workers (eg. paddy field workers, canal cleaning workers in endemic areas) from where clustering of cases has been reported. The chemoprophylaxis should not be extended for more than six weeks.

There is some room to potentially study the beneficial impact of this strategy, and balance it against the potential adverse effects of basically exposing a large number of people to a mass drug administration strategy. As always, my personal interest is always inclined towards understanding the potential for the emergence of antimicrobial resistance, not only in Leptospires, but also other pathogens for which Doxycycline is a viable therapeutic alternative, which may get caught up in the crossfire – but not be entirely eliminated, thus helping to select for the resistant strains.

Antibiotic Resistance: Image Credits Beatrice the Biologist
Antibiotic Resistance: Image Credits Beatrice the Biologist

Hepatitis Outbreak in Syrian IDP Camp Follows Cholera Case Detection

In a matter of hours since I wrote about the diagnosis of a child suffering from cholera in the camp for housing the displaced population from Homs, I received yet another ProMED missive, informing us about the diagnosis of a hepatitis outbreak in the same settings. In fact, in addition to the information, there is a request for more information, especially data on the serologic diagnosis of these patients. The ProMED alert, translated by moderators, stands as below:

Viral hepatitis has started to spread among tens of displaced people in Zogra camp near Jarabulus city (125 km or 78 miles north of Aleppo) at the Syrian-Turkish border, which accommodates people displaced from Homs.

A medical source told Smart News on [Thu 19 Oct 2017] that jaundice or viral hepatitis has begun to spread among the displaced people aged 10 to 40 years in the camp. Around 100 cases of the disease have been identified in addition to almost the same number of suspected cases. It is expected that the cause of infection is water pollution, potential contamination of the distributed food or vegetables, and not washing them properly.

The source warned of the spread of infection among a larger number of people if preventive measures are not taken through awareness campaigns and maintenance of sewage networks as soon as possible.

The 10 200 persons living in the camp have previously complained of lack of food and health assistance and lack of water and electricity.


Now, this is not surprising at all, given that the risk of one water borne infection, especially in a conflict setting, is likely to increase the threat of other water borne infections, especially ones following the fecal-oral transmission pathway. Although the post does seek more information on the serology of the patients, one would not be too misplaced if they were to hazard a guess that the likely culprit was Hepatitis E, especially if a large proportion of the sickened population were adults. Hepatitis A is an omnipresent pathogen, especially in settings with inadequate sanitation barrier and constrains on water (both quality and quantity). Consequently, most people acquire the infection in their childhood and bring along the immune response alongwith them. The other worry with Hepatitis E is that although it is usually self-limiting, much like Hepatitis A, in one situation it can precipitate disasters – in pregnant women. Mortality rates in the ~30% are not unforeseen, especially if the diagnosis has been delayed.

 

Given the disorder which is expected in refugee camps, and the burgeoning numbers of water borne infections starting to crop up, one does feel like this is the beginning of a bad nightmare. With minimal infrastructure and sociopolitical stability available, it is likely that such an outbreak could prove difficult to contain. Immediate reassurance of water quality and quantity, and focusing on breaking the fecal-oral transmission cycle are, therefore, of vital importance.

It remains to be seen how this situation proceeds.

Cholera Case in Syrian Refugee Camp: Ominous Signals

According to a report disseminated by the ProMED mail service, a case of cholera has been detected in a refugee camp housing displaced people from Homs. The translated report reads as below:

The 1st case of cholera has been recorded in Zogra camp near Jarabulus city (125 km or 78 mi north of Aleppo) at the Syrian-Turkish border, which accommodates people displaced from Homs. A medical source told Smart News on [Thu 19 Oct 2017] that cholera symptoms have been identified in a 4-month-old girl who had a severe form of rice water diarrhea, accompanied by dehydration and hypotension.

The cause of the cholera outbreak is possibly related to polluted water sources in the camp and the exposed sewage system that provides a source for flies to transmit the disease. The source pointed out that they have communicated with the Directorate of Health, which promised to take appropriate action. The source warned of the spread of infection among a larger number of people if preventive measures are not taken through awareness campaigns and maintenance of sewage networks as soon as possible.

The 10 200 persons living in Zogra camp have previously complained of lack of food and health assistance and lack of water and electricity in the camp.

As the experience from Yemen has adequately demonstrated, a broken healthcare system, in conflict situations, with risks of water contamination and inadequate food and water supply provides the perfect storm for cholera to manifest as explosive outbreaks.

Image Credits: AA

The Global Task Force for Cholera Control highlights the following for cholera control:


Control

Among people developing symptoms, 80% of episodes are of mild or moderate severity. The remaining 10%-20% of cases develop severe watery diarrhoea with signs of dehydration. Once an outbreak is detected, the usual intervention strategy aims to reduce mortality – ideally below 1% – by ensuring access to treatment and controlling the spread of disease. To achieve this, all partners involved should be properly coordinated and those in charge of water and sanitation must be included in the response strategy. Recommended control methods, including standardized case management, have proven effective in reducing the case-fatality rate.

The main tools for cholera control are:

  • proper and timely case management in cholera treatment centres;
  • specific training for proper case management, including avoidance of nosocomial infections;
  • sufficient pre-positioned medical supplies for case management (e.g. diarrhoeal disease kits);
  • improved access to water, effective sanitation, proper waste management and vector control;
  • enhanced hygiene and food safety practices;
  • improved communication and public information.

WHO recommendations to unaffected neighbouring countries

Countries neighbouring an area affected by cholera should implement the following measures:

  • improve preparedness to rapidly respond to an outbreak, should cholera spread accross borders, and limit its consequences;
  • improve surveillance to obtain better data for risk assessment and early detection of outbreaks, including establishing an active surveillance system.

However, the following measures should be avoided, as they have been proven ineffective, costly and counter-productive:

  • routine treatment of a community with antibiotics, or mass chemoprophylaxis, has no effect on the spread of cholera, can have adverse effects by increasing antimicrobial resistance and provides a false sense of security;
  • restrictions in travel and trade between countries or between different regions of a country;
  • set up a cordon sanitaire at borders, a measure that diverts resources, hampers good cooperation spirit between institutions and countries instead of uniting efforts.

Image Credits: Oxfam on Medium

Drawing on the Yemen experience, and recent experience from conflict-ridden areas of South Sudan, using a single-dose based approach with oral cholera vaccines potentially presents a strategy to contain potential explosive outbreaks. On the bright side, the early detection of the case could help to staunch the potential cascade of cases that could follow. The appropriate actions being taken need to be established on an emergency basis so that the situation does not spiral out of control.

A girl fills a container with water from a public tap in the old city of Sanaa, Yemen (AP Photo/Hani Mohammed) Image Credits: Center for International Governance Innovation

The worry is that once an outbreak of cholera is in full swing, too much of effort and resources get redirected to case detection and management, and prevention of mortality, and little is left over to dedicate to preventive actions, especially to break the transmission cycle, which means not only interrupting transmission of infections, but also ensuring safe water provision across the board, which is, even at the best of times, a challenging affair.

Clinical Research in Times of Ebola… and other Epidemics

As the news trickles in about the raging cholera outbreak in Yemen, and an emerging outbreak is being dealt with urgently in North-Eastern Nigeria, we are more frequently being confronted with the uncomfortable question of leveraging these situations to conduct clinical research activities. The National Academies of Science, Engineering and Medicine (NASEM) have come out with a report dealing with exactly this quandary. This report, aptly titled, “Integrating Clinical Research into Epidemic Response: The Ebola Experience”, deals with this ethically challenging issue. In the blurb to this report, the authors succinctly hint at the importance of this publication:

The 2014 Ebola epidemic in western Africa was the longest and deadliest Ebola outbreak in history, resulting in 28,616 cases and 11,310 deaths. In the midst of the rapidly spreading, highly dangerous contagious disease—with no Ebola-specific vaccines or therapeutics available to help curb the epidemic—the international community implemented clinical trials on investigational agents, not yet studied in humans for safety or efficacy. Within that context, the Office of the Assistant Secretary for Preparedness and Response, the National Institute of Allergy and Infectious Disease, and the U.S. Food and Drug Administration, supported the National Academies of Sciences, Engineering, and Medicine to convene a committee to analyze the clinical trials that were conducted during the epidemic and consider the many scientific, ethical and practical issues related to the conduct of research in similar contexts. The resulting report, Integrating Clinical Research into Epidemic Response: The Ebola Experience, assesses the value of the trials and makes recommendations about how the conduct of trials could be improved in the context of a future international emerging or re-emerging infectious disease event.

The NASEM have further outlined a set of recommendations based on their Ebola experience. The highlights of these include:

RECOMMENDATION 1:
Support the development of sustainable health systems and research capacities—Inter-epidemic

RECOMMENDATION 2
A. Develop memoranda of understanding to facilitate data collection and sharing—Inter-epidemic
B. Provide resources to enable data collection and sharing—Epidemic

RECOMMENDATION 3
Facilitate capacity for rapid ethics reviews and legal agreements—Inter-epidemic

RECOMMENDATION 4
Ensure that capacity-strengthening efforts bene t the local population—Epidemic

RECOMMENDATION 5
Enable the incorporation of research into national health systems—Inter-epidemic

RECOMMENDATION 6
A. Prioritize community engagement in research and response—Epidemic
B. Fund training and research into community engagement and communication for research and response—Inter-epidemic

RECOMMENDATION 7
A. Coordinate international efforts in research and development for infectious disease pathogens—Inter-epidemic
B. Establish and implement a cooperative international clinical research agenda—Epidemic

 

The Manhattan Principles

From the CDC Webpage on the twelve Manhattan Principles:

These “Manhattan Principles” urge world leaders, civil society, the global health community, and institutions of science to holistically approach the prevention of epidemic/epizootic disease and the maintenance of ecosystem integrity by:

  1. Recognizing the link between human, domestic animal, and wildlife health, and the threat disease poses to people, their food supplies and economies, and the biodiversity essential to maintaining the healthy environments and functioning ecosystems we all require.
  2. Recognizing that decisions regarding land and water use have real implications for health. Alterations in the resilience of ecosystems and shifts in patterns of disease emergence and spread manifest themselves when we fail to recognize this relationship.
  3. Including wildlife health science as an essential component of global disease prevention, surveillance, monitoring, control, and mitigation.
  4. Recognizing that human health programs can greatly contribute to conservation efforts.
  5. Devising adaptive, holistic, and forward-looking approaches to the prevention, surveillance, monitoring, control, and mitigation of emerging and resurging diseases that fully account for the complex interconnections among species.
  6. Seeking opportunities to fully integrate biodiversity conservation perspectives and human needs (including those related to domestic animal health) when developing solutions to infectious disease threats.
  7. Reducing demand for and better regulating the international live wildlife and bushmeat trade, not only to protect wildlife populations but to lessen the risks of disease movement, crossspecies transmission, and the development of novel pathogen-host relationships. The costs of this worldwide trade in terms of impacts on public health, agriculture, and conservation are enormous, and the global community must address this trade as the real threat it is to global socioeconomic security.
  8. Restricting the mass culling of free-ranging wildlife species for disease control to situations where there is a multidisciplinary, international scientific consensus that a wildlife population poses an urgent, significant threat to human health, food security, or wildlife health more broadly.
  9. Increasing investment in the global human and animal health infrastructure commensurate with the serious nature of emerging and resurging disease threats to people, domestic animals and wildlife. Enhanced capacity for global human and animal health surveillance and for clear, timely information-sharing (that takes language barriers into account) can only help improve coordination of responses among governmental and nongovernmental agencies, public and animal health institutions, vaccine / pharmaceutical manufacturers, and other stakeholders.
  10. Forming collaborative relationships among governments, local people, and the private and public (i.e. non-profit) sectors to meet the challenges of global health and biodiversity conservation.
  11. Providing adequate resources and support for global wildlife health surveillance networks that exchange disease information with the public health and agricultural animal health communities as part of early warning systems for the emergence and resurgence of disease threats.
  12. Investing in educating and raising awareness among the world’s people and in influencing the policy process to increase recognition that we must better understand the relationships between health and ecosystem integrity to succeed in improving prospects for a healthier planet.

Comparing the Rotavirus Vaccines in India

Comparisons of different rotavirus vaccines are difficult to make with a lot of precision because of the differing populations, protocols, attack rates, and study procedures which have been employed to assess the efficacy of the vaccines. Given the rather recent deployment of the vaccines, there are very limited evidence on their effectiveness in the population/community-setting.

Features Rotavac Rotasiil
Type Live attenuated vaccine Live attenuated vaccine
Composition Monovalent liquid frozen vaccine containing live rotavirus 116E strain [G9 P(11)] prepared in Vero cells The vaccine contains serotypes G1, G2, G3, G4 and G9.
Manufacturer Bharat Biotech, India Serum Institute, India
Constituents Naturally occurring reassortant containing one bovine rotavirus gene P(11) and ten human rotavirus gene. Bovine rotavirus UK-Compton strain (G6P5[7]) is the backbone. Different VP7 encoding genes to generate different G-types (G1, G2, G3, G4 & G9).
Route of Administration Oral, liquid Oral, liquid
Dosing schedule Rotavac should be given in a 3 dose series starting at 6 weeks at 4-week intervals. Rotavac may be given together with the other routine childhood vaccinations. Rotasiil is given in a 3-dose schedule, where the first dose is provided at the age of 6 weeks, and subsequent doses are given at 4-week intervals.
Immunogenicity or Efficacy • India: (1) • Niger study:(5)
– Vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) – Per protocol analysis: Vaccine efficacy of 66.7% (95% CI 49.9 to 77.9)
– In the first year of life 56·4% (36·6-70·1; p<0·0001) – Intention to treat analysis: Vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7)
– Number needed to prevent one severe RVGE case: 55 (95% CI 37-97)
• Ongoing Phase III trial (SIIPL presentation) (6)
• India: (2) – No solicited reactions within 7 days of post- vaccination.
– Vaccine efficacy against severe RVGE in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; p < 0.0001) – No unsolicited and serious adverse events within 28 days after vaccination.
– Vaccine efficacy in the second year of life was 48.9% (95% CI 17.4 to 68.4; p = 0.0056) – Study completion around Q2 2017
– Number needed to be immunized to prevent one episode of severe RVGE in the first 2 years of life was 40 (95% CI 28.0 to 63.0) and for RVGE of any severity, it was 21 (95% CI 16.0 to 32.0).
• Awaiting publication: (personal communication from Kanungo S)
Immunogenicity: – Vaccine efficacy 36% (95% CI: 11.7-53.6%, p=0.0067) against SRVGE
– Serum IgA seroconversion rates were 73%, and 20% in the 116E and placebo groups, respectively. (3) – Vaccine efficacy 60.5% (95% CI:17.7-81.0%, p=0.0131) against very SRVGE.
– A 4-fold increase in rotavirus immunoglobulin A titer was observed in 66.7% and 64.5% of infants after the first administration and in 62.1% and 89.7% of infants after 3 administrations of doses of 104 ffu and 105 ffu, respectively. (4)
Safety profile and Adverse Events Following Immunization • India:(1) • Awaiting publication: (personal communication from Kanungo S)
– Six (<1%) cases of intussusception were reported in the vaccine group and two (<1%) were reported in the placebo group: difference NOT statistically significant – Incidence of solicited, unsolicited and serious adverse events were similar in both the groups.
– No statistically significant difference in severe adverse events between vaccine and placebo groups. – A total of 1722 SAEs were reported in 1318 subjects (17.5%) by the time of primary analysis; they were experienced by 644 (17.17%) subjects in the BRV-PV group and 674 (17.97%) subjects in the Placebo group.
– No vaccine-related deaths
• India: (7)
– Incidence rate of confirmed intussusception among vac- cine recipients was 94/100,000 child-years (95% CI, 41, 185) and 71/100,000 child-years (95% CI, 15, 206) among those receiving placebo. No temporal association; not statistically significant (p = 0.76).
Current status of product WHO prequalified WHO prequalified

References:

  1. Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial. Lancet [Internet]. 2014 Jun [cited 2017 Jul 18];383(9935):2136–43. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0140673613626306
  2. Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life for the India Rotavirus Vaccine Group. Vaccine [Internet]. 2014;32:A110–6. Available from: http://dx.doi.org/10.1016/j.vaccine.2014.04.079
  3. Bhandari N, Sharma P, Glass RI, Ray P, Greenberg H, Taneja S, et al. Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: Results of a randomised controlled trial. Vaccine. 2006;
  4. Bhandari N, Sharma P, Taneja S, Kumar T, Rongsen-Chandola T, Appaiahgari MB, et al. A Dose-Escalation Safety and Immunogenicity Study of Live Attenuated Oral Rotavirus Vaccine 116E in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial.
  5. Isanaka S, Guindo O, Langendorf C, Matar Seck A, Plikaytis BD, Sayinzoga-Makombe N, et al. Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger. N Engl J Med [Internet]. 2017 Mar 23 [cited 2017 Jul 18];376(12):1121–30. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1609462
  6. Kulkarni P. Phase 3 efficacy study of a new pentavalent bovine-human reassortant rotavirus vaccine in India. In: 12th International Rotavirus Symposium. Melbourne; 2016. p. 28.
  7. John J, Kawade A, Rongsen-Chandola T, Bavdekar A, Bhandari N, Taneja S, et al. Active surveillance for intussusception in a phase III efficacy trial of an oral monovalent rotavirus vaccine in India. Vaccine. 2014;

Bill Gates vs Donald Trump: Foreign Aid No More?

The 45th POTUS, in the 2018 budget, has made deep cuts in programs that fund foreign aid. In keeping with his tradition, he tweeted about the #AmericaFirst budget, which has seen a massive infusion of funds in defense programs. Funds have been reallocated from the State Department, NASA and of course, the EPA, to boost the defense spending by $54 billion. This defense budget includes $2.6 billion earmarked for the building of the wall, one of the issues which has marked his successful campaign for the top spot in global politics.

maga budget

In a piece in Time, the basic principle of President Trump’s budget has been outlined:

Trump’s Administration is working to dramatically roll back the regulatory state, as well as a host of grant programs that either don’t jibe with Trump’s policy positions or that the White House believes to be unnecessary. Trump has been outspoken in criticizing the Environmental Protection Agency, and his EPA administrator, Scott Pruitt, denied the scientific link between carbon dioxide emissions and global warming.

The blueprint of the budget, labeled “America First: A Budget Blueprint to Make America Great Again”, has naturally created a lot of flutter. One of the voices of criticism has been raised by billionaire philanthropist, Bill Gates, who, in a post on his Gates Notes blog, has raised the issue of foreign aid being a vital component of American security and well being. In addition, he argues that this aid provides the US with the leadership in global issues that it seeks to foster freedom and democracy around the world. In a strongly worded opening paragraph, he states:

Foreign aid is often in the hot seat, but today the heat is cranked up especially high. The United States government, one of the world’s most influential donors, is considering dramatic cuts to health and development programs around the world. I understand why some Americans watch their tax dollars going overseas and wonder why we’re not spending them at home. Here’s my answer: These projects keep Americans safe. And by promoting health, security, and economic opportunity, they stabilize vulnerable parts of the world.

If Bill Gates is talking about money, I, for one, am going to pay attention. He concludes the piece hammering home the fact that aid is a minor fraction of the total American exchequer and provides the bang for the buck that everyone is looking for:

Protecting Americans, preventing epidemics, strengthening markets, saving lives: aid delivers phenomenal benefits, and for a bargain. It represents less than 1 percent of the federal budget, not even a penny out of every dollar. It is some of the best return on investment anywhere in government. This money is well spent, it has an enormous impact, and it ought to be maintained.

Gates met with President Trump yesterday and details are trickling in; whether that meeting will be enough to provide some much needed succor to USAID and EPA and a host of other agencies involved in making the world a better place, remains to be seen. One can just hope that in the drive to Make America Great Again, the Trump administration does not become too isolationist and too cloistered – because there will be a hard battle to fulfill the vacuum left by the US in global leadership. This might not always end in a satisfactory conclusion, as has been demonstrated by the continuing unrest in the Middle East. In today’s connected world, it is no longer a theoretical premise that a butterfly flapping its wings in China can set off thunderstorms in US, it is the reality.

How things turn up, whether pragmatism and short-term benefits win over idealism and long-term investments remains to be seen. In the meantime, with dwindling US global aid funds, we need to see who are stepping up and how they are going to make a difference. Of if not, and what the adverse impacts are on global public health and well being.

BGR-34 for Diabetes: Where is the evidence?

An herbal drug, developed jointly by the National Botanical Research Institute (NBRI) and the Central Institute of Medicinal and Aromatic Plants (CIMAP), branded as BGR-34, has been commercialized by Delhi-based Aimil Pharmaceuticals and marketed as a potentially side-effect free treatment for diabetes. However, a search for publications outlining trials conducted to support the claimed “67% success rate”, came up empty for me. And I am not the only one, as it appears that there have been several outlets questioning the veracity of these incredible numbers.

The online magazine The Wire states:

The literature published by AIMIL Pharmaceuticals quotes a number of studies performed on the different components of BGR-34 – daruharidra, vijaysar, methi, gudmar, giloe and majeeth – and quoting various sources, although CSIR, NBRI and CIMAP aren’t among them. Upon looking up the websites of these organisations, there is no specific literature available on the research undertaken by these organisations leading to BGR-34.

It provides the following accompanying table highlighting the evidence:

Berberis aristata (Daruharidra)
Pterocarpus marsupium (Vijaysar)
Trigonella foenum-graecum, Methi
Gymnema sylvestre (Gudmar)
Tinospora cordifolia (Giloe)
Rubia cordifolia (Majeeth)

a_large

Another skeptical article in LiveMint highlights the concern that should bug many a medical practitioner:

“Herbal medicines are not cheap, we don’t know the long-term side-effects of these drugs, the mechanism of action; there is hardly any data available, and we hear these things from newspapers over reputed scientific journals,” said Shyam Kalavalapalli, a Hyderabad-based endocrinologist. Contrary to the claims of no side-effects, herbal medicines were found to have high concentrations of heavy metals in many studies, Kalavalapalli said.

At five bucks a tablet, with four tablets to be taken daily, this is not a cheap alternative. Many generic drugs, like Metformin and some of the sulfonylureas, are likely to be cheaper, more intensely researched, and have more well-understood adverse effect profiles. Apparently, the drug has been approved by the Ministry of AYUSH, lending it a seal of credibility.

Now personally, I have nothing against the movement of mainstreaming AYUSH practitioners into the public and clinical health system in India. If anything, I believe that given the desperate shortage of doctors we face, maybe this might be a good move to balance out the doctor:patient ratio disparity in rural areas. But I will not go into it as it is a debate for another day. I am truly concerned about the fact that when I search for information on this drug, all I get is marketing material, and no hard science. The lack of published, peer reviewed, double-blinded, controlled trials proving the veracity of the claims being made by the drug makers is seriously damaging to the credibility of the AYUSH practitioners. The alternative medicine practitioners have been getting more attention thanks to the support being lent to them through the health system. But if they fail to come up with credible evidence to support their incredible claims, it just makes them look more like pseudoscientific practitioners than anything else.

Now if you go online and look hard enough, you will find stories both for and against the effectiveness of the medication. But that is NOT how science works! Personal narratives and anecdotes, though they come with the personal touch that makes it easy to convince people, should not dictate the standards for determining drug approval processes.

With an estimated 62 million adult diabetics, almost 1 in 14 adult Indians are diabetic. Second only to China, India adds 2 million diabetics every year to its burden of morbidity. It is expected that by 2030, India will have crossed the 100 million mark for diabetic patients! With such numbers, it is hardly a wonder that India has earned the unenviable epithet of being the diabetes capital of the world. Add to that the affinity of people for things like “natural cure” and “herbal drugs” and “side effect free”, and we have a dangerous combination. (Data Source: CCEBDM, PHFI)

As a public health skeptic, I demand to see the evidence, the data that goes behind such a massive declaration. The LiveMint article highlights another comment which worries me no ends:

Aimil Pharmaceuticals said the drug will be sold in Delhi and Himachal Pradesh to begin with, and later in the rest of the country. It has already been approved for sale in Delhi and Himachal Pradesh. “We are planning to reach around 100,000 doctors through 800 medical representatives to explain the benefits of our drug,” said Anil Kumar Sharma, vice president of Aimil Pharmaceuticals.

If this is true, then it is time that as educated consumers, we must demand the data. If we do not judge the merits of what we use to treat ourselves based on cold, hard facts, then we are fooling ourselves, and all I can say is caveat emptor!

Disclaimer: It is possible that I have missed out on the published data if it has been recently published or published in a journal which is not indexed or one which is indexed with an agency I did not look into. If that is the case, please point me in the right direction. I shall look up the data and analyze and comment on it. I tried searching the major databases for the drug but came up empty.

Turning to the “Infected Jelly” to Treat Ebola

ResearchBlogging.orgThe NEJM has come out with a very interesting paper: Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea. The explosive outbreak of Ebola Virus Disease in West Africa last year had hijacked the headlines and media space in a big way. Multiple solutions were touted, including the vaccine trial STRIVE. Few articles, however, looked at the systems response to the crisis. Although the current study maintains that trend, yet, it plays with a therapeutic ploy which has the potential to become the breakthrough approach in raising generic response to similar disease outbreaks.

Before you go any further in this account, you should check out the Now@NEJM article written by my dear friend Bhavna Seth if you are interested in a more balanced, more authoritative review of the study. Mine is totally colored by my own biases!

This article makes the epidemiologist-in-training in me squirm with discomfort, while the medical romantic in me just breaks out into a jig. It is an elegant study, designed and conducted in the eye of the storm: in the middle of the Ebola Outbreak in Guinea. As someone with a little bit of experience of handling small scale outbreak-situation cases of gastroenteritis and dengue, I know how difficult it is to keep the clinical scaffoldings held up in the middle of such crises – imagining a full scale study in the middle of all this: simply astounding!

Picture1

Anyway, the study is methodologically seriously flawed in a couple of ways. Most obvious of these is the fact that the control and intervention groups are, technically speaking, not comparable, but it gives us some insight into the business of managing, or at least stemming the tide of a violent outbreak of infectious diseases. Another major concern is the “goodness” of the plasma being used to treat the patients as none of them were checked for antibody titers. Given that our knowledge of the immunology of Ebola is emerging and taking shape only recently, this is a field that needs further enquiry.

Eventually, however, the study fails to establish the role of convalescent plasma as a therapeutic choice, but, I think a part of that could be attributed to the fact that the study design is slightly flawed, as pointed out earlier. One of the biggest concerns of launching investigations into therapeutic options using blood and blood products is the risk of adverse effects, some of which can be immediately lethal. This study at least showed reassuring evidence that the adverse event rates were much lower than expected when using such treatment plans.

Read it: it makes for a surprisingly effortless read compared to the pharmaceutical-sponsored trials we read nowadays. The simplicity of the design is its strength (and weakness!). So, to conclude, though the study could not establish the primary objective it set out to satisfy, it has raised some questions, had a stab at answering a couple others, and overall, has enchanted the medical romantic in me!

Reference

ResearchBlogging.orgvan Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P, Baize S, Horby PW, Raoul H, Magassouba N, Antierens A, Lomas C, Faye O, Sall AA, Fransen K, Buyze J, Ravinetto R, Tiberghien P, Claeys Y, De Crop M, Lynen L, Bah EI, Smith PG, Delamou A, De Weggheleire A, Haba N, & Ebola-Tx Consortium (2016). Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea. The New England journal of medicine, 374 (1), 33-42 PMID: 26735992

If Carbapenems Go, Can Colistin be Far Behind?

ResearchBlogging.orgI wrote about the disaster-in-the-making discovery of transmissible resistance to colistin, a last resort antibiotic, when the Lancet Infectious Diseases published a paper based on data coming out from surveillance in China. At that point of time, the isolation of the transmissible gene providing resistance (mcr1 gene) gained a lot of attention. Maryn McKenna’s blog post went viral and there was a lot of tornadoes in Twitter. Unfortunately, that did not quite stall the relentless progress of the rise of antimicrobial resistance.

Yesterday, another correspondence article, published in the same journal, The Lancet Infectious Diseases, has rung the doorbell to the gateway of the post-antibiotic era: Laurent Poirel, Nicolas Keiffer, Nadia Liassine, Dang Thanh, and Patrice Nordmann have published a letter in the journal outlining the emergence of plasmid-mediated carbapenem and colistin resistance in a clinical isolate of the dreaded bug, Escherichia coli. This uropathogenic strain of E coli was recovered from the urine of an 83 year old man who was admitted to a hospital in Switzerland for diverticulitis. He suffered from renal insufficiency, necessitating the institution of regular dialysis. The authors describe the horrifying sensitivity profile of the strain isolated from the urine of the patient in a typically cold, sciencey, matter of fact manner when they state:

E coli isolate KRI was resistant to most β-lactams (remaining susceptible to aztreonam) and resistant or of intermediate susceptibility to carbapenems (minimum inhibitory concentrations were 4 μg/mL for imipenem, 4 μg/mL for ertapenem, and 2 μg/mL for meropenem).2 This isolate was also resistant to chloramphenicol, gentamicin, kanamycin, tobramycin, sulfonamides, tetracycline, co-trimoxazole, and fluoroquinolones, remaining susceptible only to amikacin, tigecycline, and fosfomycin. Noteworthy, it was resistant to colistin, with a minimum inhibitory concentration of 4 μg/mL.

Though the authors could not identify the source of the strain definitively, their conjecture is that it could be from an animal source owing to the extensive use of polymyxins in food animals.

The emergence of combined resistance against carbapenems and colistin is indeed concerning, and what is more worrisome is that there does not seem to be the sense of urgency in policy makers in addressing this matter. Unfortunately, bacterial genes percolate through international borders with ease, and in this era of globalization, industrialization and global travel, there is no way in which we can tighten the already porous borders. So, until a comprehensive, global, regional, national and local action plan is enacted to combat this rising menace, the problem will continue to grow unabated.

antibiotic-resistance-comic-650x552

References:

ResearchBlogging.org1. Poirel, L., Kieffer, N., Liassine, N., Thanh, D., & Nordmann, P. (2016). Plasmid-mediated carbapenem and colistin resistance in a clinical isolate of Escherichia coli The Lancet Infectious Diseases DOI: 10.1016/S1473-3099(16)00006-2

 

Update/Edit:

Hat Tip to Mike the Mad Biologist for calling my careless mistake in the title of this post. I had originally titled this post as “If Colistin Goes, Can Carbapenems be Far Behind”, which did not make much sense (once Mike pointed it out on his blog). Hence, for the sake of chronological consistency, I have changed the title around to the more correct version! Thanks Mike!

What's your p-value?

Ronald Fisher and Some Thoughts on the p-Value

One of the most discussed, debated and controversial issues in medical research is the p-value. I came across Ronald Fisher’s take on this matter in his work, Statistical Methods for the Research Worker, 1925 (the text of this work has been made available online by Christopher D. Green of the York University):

“The value for which P=0.05, or 1 in 20, is 1.96 or nearly 2; it is convenient to take this point as a limit in judging whether a deviation ought to be considered significant or not. Deviations exceeding twice the standard deviation are thus formally regarded as significant. Using this criterion we should be led to follow up a false indication only once in 22 trials, even if the statistics were the only guide available. Small effects will still escape notice if the data are insufficiently numerous to bring them out, but no lowering of the standard of significance would meet this difficulty.”

Further, in 1926, Fisher, in his work, The Arrangement of Field Experiments, published in the Journal of the Ministry of Agriculture of Great Britain, states:

… it is convenient to draw the line at about the level at which we can say: “Either there is something in the treatment, or a coincidence has occurred such as does not occur more than once in twenty trials.”…

If one in twenty does not seem high enough odds, we may, if we prefer it, draw the line at one in fifty (the 2 per cent point), or one in a hundred (the 1 per cent point). Personally, the writer prefers to set a low standard of significance at the 5 per cent point, and ignore entirely all results which fail to reach this level. A scientific fact should be regarded as experimentally established only if a properly designed experiment rarely fails to give this level of significance.

Two things clearly emerge from the writings of Fisher in this period:

Biologist_and_statistician_Ronald_Fishera. Values slightly smaller and slightly larger than 0.05 need to be interpreted with caution. He shows a lot of flexibility in calling the shots on statistical significance in his book The Statistical Manural for Research Workers (linked above); this should be the groundwork of statistics in medicine. In an era where medicine and research is largely driven by numbers, we need to focus on the fact that clinical or epidemiological significance is as important (if not more important), than statistical significance.

b. In the last sentence of the quote above, Fisher states something which has slipped the attention of the current crop of medical researchers: reproducibility of results. In our pursuit of novelty, we have forgotten the fact that it is still essential to be able to test and re-test hypotheses. This is particularly crucial for medical research and public health research, where a number of extraneous/external factors may be at play.

All said and done, the holy grail of statistical significance, the deeply sought after p-value, was basically an empiric decision based on the assumptions of one person (albeit a great person!). The fact that we have been using it without major changes over the last almost a hundred years goes a long way, empirically, to prove that it was not a very bad assumption to begin with. But this should serve as a reminder, especially for clinical and public health researchers, that statistics is a tool, and not the only one in our decision-making toolbox.

p value

Towards Universal Health Coverage: The Lancet Commission and Some Personal Thoughts

ResearchBlogging.orgThe Lancet Commission on Investing in Health (CIH) has come up with an ambitious framework (1) and an editorial comment accompanying it (2) in the recent issue of the journal.

The Editorial makes a strong pitch for a systematic adoption of pro-poor strategies to bolster the adoption of UHC. In this commentary authored by the participants of the Bellagio Workshop on Implementing Pro-Poor Universal Health Coverage, the authors state (emphasis mine):

We call on national governments committed to UHC to adopt three key principles as the foundation of UHC: aim for pro-poor universalism from the start (ie, ensure that poor people are covered as the first priority on the road to covering the entire population), provide adequate financial protection, and strengthen the health service delivery system to be accessible by all, especially poor and vulnerable individuals. National governments should provide vocal political leadership to implement pro-poor policy reforms; successful reforms will result in greater use of needed services by the poor, which is the foundation for pro-poor UHC outcomes. Governments should also show political commitment by ensuring that, as the economy grows, there is a corresponding rise in domestic resources dedicated to health (with financial risk protection) and high priority health-related investments (eg, water and sanitation, education). Governments also need to ensure that the political leadership of the health sector has adequate capacity and technical skills, and to establish explicit, transparent national decision-making mechanisms and processes for deciding how best to allocate resources to UHC. Adequate resources should be directed to the development of strong health systems; in particular, functioning primary health care is a cornerstone of UHC. Governments should actively work with citizens in designing UHC and they should ensure that they are responsive to public demands through participatory multistakeholder governance. Finally, they should monitor progress towards and achievement of UHC goals, and document and publish experiences of successes and setbacks on the pro-poor path to UHC.

While this makes for reasonable theoretical approach to the problem, pondering on the evolving situation in India, certain thoughts pop into my mind. Here are some of the proverbial spanners that can jam up the wheels of the juggernaut of UHC in India.

(Disclaimer: I realise that healthcare can be a charged topic. Please do consider the fact that these are my personal opinion and if you detect any elements of error in them, kindly point them out politely. Let us have a decent conversation here!)

A Complex Healthcare System

India has a largely heterogeneous sort of medical care provision environment. We have a whole host of service providers, right from the practitioners of modern medicine (allopathic doctors) to state-authorized practitioners of AYUSH (Ayurveda, Yoga, Unani, Siddha, and Homeopathy: a legion of practitioners of alternative medicine) and the most ubiquitous of rural service providers, the euphemestically named “registered medical practitioners” (RMPs).

A brief note on the RMPs before I proceed further: They are basically non-licensed practitioners, who, having worked with doctors previously, or having worked in a hospital in a non-clinical capacity have subsequently winged it out on their own to practice medicine as local physicians. There is a slowly growing movement, led by some physicians, who, jaded with the system’s inability to incentivize “rural service”, have given up on the hope of providing these underserved areas with a licensed crop of doctors. Instead, they have decided to focus on training and retraining the RMPs to the highest level of their capacity to act as first responders and referral agents. This is a system that has had me in two minds… maybe food for thought for a future post!

With such a complex system of overlapping medical capacities, the best way forward remains a very calculated progress where equitable distribution of health work force needs to be ensured. The prolonged failure of the system to be able to formulate a non-punitive approach to deploy medical workforce in this area is a dangerous precedence, which endangers the concept of provision of healthcare where it is needed the most.

The Affinity for Quick Fixes

In the Indian policy setting, where quick fixes are a crowd favorite, the rapid answer to a lack of medical healthcare is deploying only healthcare workers in the underserved area. This narrow and myopic interpretation of health coverage needs to be amended before any further meaningful progress can be made in this domain.

Healthcare provided without systematic infrastructural support is unlikely to be sustainable in the long term or make meaningful impact in the short term. Without investing in the infrastructure of the existing three-tiered healthcare system already in place, moving to establish healthcare coverage will be difficult.

Systemic Evil of Corruption

Of late, the Indian healthcare system has come under the scrutiny for corruption and there has been quite a fair bit of clamour about it in the popular media, as well as within academic circles. Without uprooting the systemic evil of corruption that pervades the environment, it is difficult to ensure proper implementation of policies. Just framing a policy is not adequate; ensuring that it is effectively implemented is the real challenge.

Establishing self-sustaining monitoring and evaluation frameworks, creating policies and programs in a transparent fashion, engendering a culture of accountability, and most importantly, addressing corruption swiftly and mercilessly are essential to ensure that the benefits outlined in the reams of documents that are authored by the think tanks actually reach the intended targets.

Political Will: Poor Demand, Poor Supply

I have my doubts when the discussion veers in the direction of health as a political priority. With only 1.04% of the GDP being committed to the healthcare system from the publicly funded coffers, it continues to live in the shadow of other priority areas like agriculture, technology, development, etc.

This is, in my view, a symptom of the fact that we, as citizens of the nation, do not consider health as a major priority. To a majority of Indians, the bare essentials of life are yet to be assured. The lure of two square meals a day puts octogenarian women, bent over with arthritis and age, on the pavement, begging for alms. The country has grown, and not everyone has been a part of the growth. Naturally, health has been viewed as the disposable one amongst the essential services. Only now, of late, have we been clamoring for better care. Yet, amidst the clamor for food and shelter, this need for money in the health sector is (legitimately) drowned out.

In Conclusion…

The health of the nation, unfortunately, is not viewed within the holistic framework and continues to work within isolated silos. Instead of tying up agriculture, development, health and a vast network of other determinants within a single implementation framework, they continue to function within isolated framework, working in isolation, often in duplicative circles, inefficiently replicating work that could have powered intersectoral growth.

UHC in India will be a pipe dream till the day we realize that universal coverage should bring a meaningful array of services to those that need it the most. Until that day, the pursuit of the inflexible, utopian definition of health shall be an exercise in futility.

References:

ResearchBlogging.org

    1. Jamison, DT, Summers, LH, Alleyne, G et al. Global Health 2035: a world converging within a generation. Lancet. 2013; 382: 1898–1955
    2. Bump, J., Cashin, C., Chalkidou, K., Evans, D., González-Pier, E., Guo, Y., Holtz, J., Htay, D., Levin, C., Marten, R., Mensah, S., Pablos-Méndez, A., Rannan-Eliya, R., Sabignoso, M., Saxenian, H., Feachem, N., Soucat, A., Tangcharoensathien, V., Wang, H., Woldemariam, A., & Yamey, G. (2016). Implementing pro-poor universal health coverage The Lancet Global Health, 4 (1) DOI: 10.1016/S2214-109X(15)00274-0

Doctors for You: Urgent Appeal to Volunteers for Chennai Flood Response, 2015

The state of Tamil Nadu has witnessed the worst and most relentless rainstorm in a 100 years that started in November, 2015. More than 10 lakhs people are estimated to be affected by this flood. The post flood situation is grave in the metropolis as confronted water sanitation and hygiene is posing threats to the public health system and the affected population is prone to disease outbreak.

Doctors For You (DFY) a India based NGO is currently providing healthcare relief operations in Chennai from 6th of December and has signed agreement with the government of Tamilnadu to provide public health recovery services in two districts of the metropolis i.e. Chennai and Cuddalore. DFY is currently providing primary health care services (general health check-ups and supply of medicines); health care outreach activities in Chennai and its adjoining suburbs through mobile medical vans and water sanitation and hygiene awareness in close association with Minakshi Mission Hospital and Research centre.

For this cause we are currently recruiting volunteers (MBBS/MD/MPH) to support us in our relief work in Chennai. The expanses of the volunteers (Food, accommodation and travel) will be taken care by Doctors For You.

Therefore we appeal to all doctors to come forward in this humanitarian crisis situation and volunteer with for Chennai flood relief operation, 2015.

Doctors For You is an humanitarian organization based in India, formed by doctors, medical students and likeminded people. The thrust of DFY’s work is to provide medical relief, sustainable healthcare services, capacity building and risk reduction activities during crisis and non-crisis situations. The organization has vast experience of working in disasters which include Mumbai floods 2005, Bihar floods 2008, Andhra Pradesh-Karnataka floods 2009, Orissa floods 2011, Assam ethnic violence 2012 and Uttarakhand floods 2013, Jammu and Kashmir Floods, 2015 and Nepal Earthquake, 2015. The organisation has received several awards such as The SAARC Award (2010) and The British Medical Journal Group Award (2011) for its outstanding contribution to the humanitarian field.  Doctors for You is a registered society, registered under the Societies Registration Act 1860 Section 21 (Society Registration No. : 1695/2007/GBBSD).

For more information contact us@ 08473093237, 08123885139, 09954191991, Or email us @ info@doctorsforyou.org  visit us at www.doctorsforyou.org

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The Apocalypse is HERE: Transmissible Resistance to Last Resort Antibiotic (Colistin)

ResearchBlogging.orgPolymyxins are a group of bacterial origin cyclic polypeptides with antibacterial properties. It was isolated by a Japanese researcher in 1949 from a jar of fermenting bacteria. Colistin, also known as Polymyxin E, which is produced by the bacteria Paenibacillus polymyxa var. colistinus, is a polypeptide antibiotic, which is effective against almost all gram-negative bacilli. Owing to its nephrotoxocity and the subsequent development of more targeted and safe antibiotics, colistin never really went on to have massive usage in clinical medicine. However, also owing to the fact that it was an old, cheap and readily available antibiotic, it started to figure more in agro-livestock use.

In livestock rearing, especially in case of piggeries, prophylactic, sub-therapeutic use of antibiotics is a major problem. These animals are reared in industry-mode, highly intense farming situations, which have questionable hygiene and sanitation facilities, making them susceptible to multiple infectious insults. Adding prophylactic doses of antibiotics has long been one way to ward off such issues and promote growth and productivity in farm animals.

The other side of the coin is that, such indiscriminate use has precipitated the risk of emerging antimicrobial resistance in bacteria. Colistin was reclassified by the WHO as a critically important antibiotic for human medicine in 2o12, mainly in view of the rapid emergence of antimicrobial resistance in gram negative agents, tending towards pan-drug resistance. However, there have not been similar stress been put on curbing the use of antibiotic use in veterinary and animal husbandry sectors.

The emergence of Colistin resistance through its overuse and abuse in farm animals is eerily reminiscent of the emergence of Vancomycin Resistant Enterobacteriaceae in Denmark; in Denmark, Avoparcin, a glycopeptide drug sharing a lot of properties with the critical drug Vancomycin (another last line antibiotic), was used in farms (especially piggeries) for growth promotion and productivity increase. This soon resulted in the emergence of Vancomycin Resistant Enterococcus faecium in clinical and community isolates.

A recent paper in the Lancet Infectious Diseases has found something similarly alarming: plasmic mediated genes for conferring colistin resistance (mcr-1) in commensal Escherichia coli in food animals in China. This was unearthed during a routine surveillance project to monitor the emergence of antibiotic resistance. (2)

This is not the first instance of Colistin resistance being isolated from community or clinical isolates. The fact that this resistance is plasmid mediated is what makes it more dangerous.

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Previously, resistant isolates were conferred resistance through chromosomal genes. From the biological point, this has a major ramification: resistance conferred by plasmids maybe transfered from one strain of bacteria to another since plasmids, which are small fragments of circular DNA, can shuttle across from one bacterial strain to another. Chromosomally mediated genes are limited to the same strain of bacteria. Thus, though in both the cases there is a clinical risk and emergent antimicrobial resistance, the plasmid mediated resistance appears to be of a higher risk profile for the long term damage it can cause.

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The current trends that are emerging with respect to antimicrobial resistance getting in through selection pressure caused by indiscriminate use of critical, human-medicine-related antibiotics for growth promotion and productivity-increment in farm animals is a major concern. In developing countries which are experiencing rapid urbanization, economic and market pressures, including concerns for food security, has resulted in worsening of antibiotic overuse in farm animals.

Until such time as adequate concerns about the emerging post-antibiotic apocalypse is generated in the minds of our policy makers, this downhill trend is going to continue till the emergence of a pan-drug resistant strain of bacteria emerges.

Suggested Reads:

Maryn McKenna’s blog on the National Geographic: Apocalypse Pig: The Last Antibiotic Begins to Fail

Mike the Mad Biologist: Last Line of Antimicrobial Defense is Falling: Colistin Resistance Transmission

ResearchBlogging.orgReferences:

1. Bager F, Madsen M, Christensen J, Aarestrup FM. Avoparcin used as a growth promoter is associated with the occurrence of vancomycin-resistant Enterococcus faecium on Danish poultry and pig farms. Prev Vet Med. 1997 Jul;31(1-2):95-112. PubMed PMID: 9234429.

2. Liu, Y., Wang, Y., Walsh, T., Yi, L., Zhang, R., Spencer, J., Doi, Y., Tian, G., Dong, B., Huang, X., Yu, L., Gu, D., Ren, H., Chen, X., Lv, L., He, D., Zhou, H., Liang, Z., Liu, J., & Shen, J. (2015). Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study The Lancet Infectious Diseases DOI: 10.1016/S1473-3099(15)00424-7

FDA Approves Lisdexamfetamine dimesylate (Vyvanse) for Binge Eating Disorder

The FDA has expanded the range of approved uses of Vyvanse (lisdexamfetamine dimesylate) for control of binge-eating disorder in adults. According to the media release from the FDA:

In binge-eating disorder, patients have recurrent episodes of compulsive overeating during which they consume larger amounts of food than normal and experience the sense that they lack control. Patients with this condition eat when they are not hungry and often eat to the point of being uncomfortably full. Patients may feel ashamed and embarrassed by how much they are eating, which can result in social isolation. Binge-eating disorder may lead to weight gain and to health problems related to obesity.

The efficacy of Vyvanse in treating binge-eating disorder was shown in two clinical studies that included 724 adults with moderate-to-severe binge-eating disorder. In the studies, participants taking Vyvanse experienced a decrease in the number of binge eating days per week and had fewer obsessive-compulsive binge eating behaviors compared to those on the inactive pill (placebo).

This drug, however, is not recommended for weight loss.

Image Credits: Wikipedia

Polio Vaccine Team Killed in Pakistan

According to the Al Arabiya News, four members of a polio vaccination team were killed on February 18, 2015, after being kidnapped from Southwest Pakistan.

This issue has been a teething problem, especially since poor vaccination coverage means immense risk to India and Global eradication status.

Fake WHO Certificates of Yellow Fever Vaccination in Zimbabwe and Zambia Endangers Global Populations

Here is a great example of how a Governmental Policy and Implementation may impact global health issues! According to the New Zimbabwe report, fake WHO certificates crediting Yellow Fever vaccinations are sold openly in bus terminals of Zimbabwe and Zambia (a problem which was previously also noted to exist in Nigeria).

The main reason why people have to resort to these fraudulent measures is because of the prohibitively expensive tag associated with the yellow fever vaccine, which can cost between 60-70 US$ in a private pharmacy, which are the most important providers of the vaccine. A fake certificate, on the other hand, comes for a mere 5 US$!
The failure of governmental policy implementation has not only failed to protect the health of the people in these nations, but has created a potential health hazard for all those countries in which the vector mosquitoes are present, but the disease has not yet made an appearance simply because the virus is absent.
Considering that we are rapidly moving towards a global village, it is these kinds of activities that, occurring beyond the radar of detection, inflates the risk of a global infectious catastrophe!

Illegal Synthetic Cannabinoid Spiked Bread Strikes 40 Ill in California

The Orange County Register has reported a strange news piece in which it claims that bread, spiked (knowingly!) with a synthetic cannabinoid (that goes in the market by different names such as Spice, K-2, Bliss, etc.), technically called JWH-122, has caused a spectrum of illness in 40 consumers, ranging from palpitations, dizziness and numbness to frank hallucinations.

An individual who was convinced that the bread was laced with something that caused his/her symptoms recruited an FDA approved laboratory to test the bread sample, which is how this misdemeanor came to notice.

The police has taken up the investigation.