Weekly Research Round Up #2: January 8-14

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Welcome to the second week of research round up, where I look back on some of the interesting research papers I happened to read this week. Notice a pattern yet? Yeah… I am working on a lot of antimicrobial resistance related stuff!

1. Series on Antimicrobial Resistance in The Lancet:

The series on the rising tide of antimicrobial resistance had been published by The Lancet online ahead of print to coincide with the World Antimicrobial Awareness week (November 16-22, 2015), but these articles have come out in print this week, and comprise of the following, must read, articles:

Animal production and antimicrobial resistance in the clinic: Keeping aside my biases arising from the fact that my boss is a co-author of this leading comment on the antimicrobial issue of The Lancet, this article makes the case for focusing our attention on antimicrobial resistance as a One Health problem. The comment sets the tone for the series in which the articles focus on use and misuse of antimicrobials in human medicine, environmental contamination from pharmaceutical industrial wastes, animal rearing, agriculture, and the evolutionary advantage microbes have over us!

Access to effective antimicrobials: a worldwide challenge: Another article in which one of the lead authors belongs to the higher echelons of the institute that currently employs me (the Public Health Foundation of India). This article speaks to the importance of access to effective antimicrobials, the flip side of which is restriction of access to ineffective, or higher level antimicrobials. Often, in clinical practice, we have seen how hyper-defensive prescribing behavior can occur. In such a case, a physician tends to prescribe antimicrobials of more recent development, or of a higher class, rather than a tried and tested drug that may be equally efficient. This article also assesses the impact of limited access to antimicrobials and emergence of antimicrobial resistance and the disease burden that can be attributed to them. Overall, a highly captivating read for those who are interested in the business of antimicrobial resistance.

Understanding the mechanisms and drivers of antimicrobial resistance: From the article summary: “Minimising resistance should therefore be considered comprehensively, by resistance mechanism, microorganism, antimicrobial drug, host, and context; parallel to new drug discovery, broad ranging, multidisciplinary research is needed across these five levels, interlinked across the health-care, agriculture, and environment sectors. Intelligent, integrated approaches, mindful of potential unintended results, are needed to ensure sustained, worldwide access to effective antimicrobials.” – ‘Nuff said!

Maximising access to achieve appropriate human antimicrobial use in low-income and middle-income countries: I remember sitting in on an interesting discussion in which the problems of access and excess were both incriminated as factors responsible for precipitating the global crisis of antimicrobial resistance. This article, which is co-authored by Manica Balasegaram of the Access Campaign of MSF, reasons along similar lines as well.

2. CDC Fights TB

This one is not research, per se, but falls bang in the middle of a current interest of mine – data/concept visualization. This infographic speaks of the CDC commitment to fight against TB

CDC Global Health

3. Plasmid-mediated carbapenem and colistin resistance in a clinical isolate of Escherichia coli

Continuing along the theme of antimicrobial resistance, this is another offering from the Lancet Infectious Diseases. And the title is blood curdling enough… I have lamented, at length, about this finding in a previous post on this blog.

4. Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea

This is an original article from the NEJM this week. The study is not the most methodologically sound study that you will come across, but there is a certain amount of appeal to the medical romanticism in the way the authors have conducted a trial in the midst of a raging outbreak of Ebola Virus Disease. I have spoken about this study at length in a previous post on this blog.

5. Group B Streptococcal Prophylaxis and Neonatal Listeriosis: Correlation or Causation?

The authors of the paper “Reductions in Neonatal Listeriosis: “Collateral Benefit” of Group B Streptococcal Prophylaxis?” tested the hypothesis that decline in early-onset Group B Streptococcus infections associated with widespread prophylactic use of antimicrobials with anti-Listeria activity is associated with declines in Listeria monocytogenes infection in infants.

A retrospective cohort analysis of the Pediatric Health Information System revealed that along with a rapid decline in the numbers of early-onset GBS, there was a parallel reduction in the number of cases of listeriosis in infants as well.

However, I could not access the paper as it was behind a paywall, and would like to mention this XKCD comic as a precaution before jumping to conclusions:

Correlation is not causation… maybe!

6. Zika in the Americas: The NEJM Weighs in

Right on the heels of the declaration in BMJ of an imported case of Zika virus in the US, in Harris County, Texas, the NEJM has published a review/perspectives article on the appoaching era of Zika Virus disease. The authors state, it appears with some trepidation:

“With its recent appearance in Puerto Rico, Zika virus forces us to confront a potential new disease-emergence phenomenon: pandemic expansion of multiple, heretofore relatively unimportant arboviruses previously restricted to remote ecologic niches. To respond, we urgently need research on these viruses and the ecologic, entomologic, and host determinants of viral maintenance and emergence. Also needed are better public health strategies to control arboviral spread, including vaccine platforms for flaviviruses, alphaviruses, and other arbovirus groups that can be quickly modified to express immunogenic antigens of newly emerging viruses. With respect to treatment, the arbovirus pandemics suggest that the one-bug–one-drug approach is inadequate; broad-spectrum antiviral drugs effective against whole classes of viruses are urgently needed.”

7. Investing in Pandemic Preparedness

A special report in the NEJM this week, titled “The Neglected Dimension of Global Security — A Framework for Countering Infectious-Disease Crises” outlines the recommendations of a Special Commission on a Global Health Risk Framework for the Future sponsored by eight agencies. The recommendations of the Commission are classed under four heads:

  1. The case for investing in pandemic preparedness
  2. Strengthening public health as the foundation of the health system and the first line of defense
  3. Strengthening the global and regional system for outbreak preparedness, alert, and response
  4. Accelerating research and development to counter the threat of infectious diseases

The emerging consensus about the need to invest in neglected tropical diseases and emerging infectious diseases rides on the back of a fear perception. There needs to be a systematic approach to identify and ameliorate the breaches in the policy structure and to establish robust response systems.

emerging reemerging infections

8. The Puzzle of Tubercular Meningitis

Yet another article this week’s NEJM that caught my eye: Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis (and its accompanying Editorial).

This was a large randomized controlled trial that compared a standard, 9-month ATD regimen (including rifampicin at the dose of 10 mg/kg/day) with an intensified regimen (including a higher dose of rifampin – 15 mg/kg/day, and an added dose of Levofloxacin at 20 mg/kg/day) and assessed death by 9 months p[ost-randomization.

Unfortunately, there were no significant differences in either the primary or the secondary outcomes. Though the Intense Treatment group had a higher number of adverse events leading to treatment interruption, they were not statistically significantly different from those in the standard therapy group.

The puzzle of how best to approach tubercular meningitis, which causes significant morbidity, mortality and post-recovery sequelae, still remains to be unravelled.

9. Bankruptcy and AMI in Canada: The Chicken or Egg Conundrum

So with this one, I am heading out into the wild west as it is slightly beyond my scope of usual readings – both from the viewpoint of the discipline (non-communicable diseases) and methodology (advanced statistics!). However, this study, published in the BMC Public Health, titled “The intersection of health and wealth: association between personal bankruptcy and myocardial infarction rates in Canada”, has a rather interesting premise.

The researchers used a cross-lagged structural equation model to ascertain that for every 100 bankruptcy cases filed in Canada, there was an associated increase of 1.5 in AMI counts the following year. This was statistically significant. Interestingly, the authors also point out that for every 100 increase in AMI counts, there is an increase of 7 in bankruptcy filings in the following year.

The study, quite eloquently describes a phenomenon, that epidemiology students are taught about time and time again in class… association is not proof enough to judge causation, and sometimes, the association, when turned on its head, may make causal sense in both directions!

So what came first, the chicken or the egg?

10. Word of the Week: Zika

Zika virus is sweeping through the Latin Americas, claiming thousands of children to microcephaly. In fact, the BMJ has reported that the first US based case of Zika Virus has been isolated from Texas (in a man who had a recent history of traveling to different Latin American countries). A perspective article was also published by the NEJM, indicating that there is recognition of the risks posed by the emerging and rapidly spreading arbovirus.

The name Zika is derived from the Zika Forests, a tropical forest near Entebbe, Uganda. This forest, which is an amazing center of biodiversity, and houses scores of species of moths and mosquitoes, is protected and restricted to scientific inquiries. The Uganda Virus Research Institute oversees activities in these forestlands covering almost 62 hectares.

zika forest
Image Credits: Kaddumukasa MA, Mutebi JP, Lutwama JJ, Masembe C, Akol AM. Mosquitoes of Zika Forest, Uganda: species composition and relative abundance. J Med Entomol. 2014 Jan;51(1):104-13. PubMed PMID: 24605459.

In 1947, scientists researching yellow fever in the Zika Forest put a rhesus monkey in a cage. The monkey developed symptoms suggestive of arboviral febrile diseases. Subsequently, the agent isolated from the serum of the monkey was identified in 1952 as a new kind of hemorrhagic viral fever causing agent, called the Zika Virus. Soon after that, in 1954, the virus was isolated from a man in Nigeria, underlining the zoonotic potential of the virus, which we have come to appreciate in recent years through the ordeal of the Latin countries. However, it was a rare and exotic diagnosis till the late 2000s and only recently has it hit the headlines as a major contributor to morbidity.

The etymological root of the word can be traced to the local Luganda language, in which it means overgrown (which, I guess, is typical of a forested area!).

Skeptic Oslerphile, Scientist at the Indian Council of Medical Research, National Institute of Cholera and Enteric Diseases. Interests include: Emerging Infections, Public Health, Antimicrobial Resistance, One Health and Zoonoses, Diarrheal Diseases, Medical Education, Medical History, Open Access, Healthcare Social Media and Health2.0. Opinions are my own!

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