• Evidence for a genetic basis for much of the observed resistance – are molecular markers in sight?
• Another combination therapy trial with prolonged clearance in both treatment arms among patients from Western Cambodia
• Longer clearance half-lives among patients with a high parasite load treated with just artemisinin on the Thai-Burma border, it’s already spread
• An accessible narrative providing a glimpse of the operations of the Thai-Cambodia containment program (thanks Matt)

There is one important caveat here – IPTc is only “effective” where the transmission is quite high. In the communities in Burkina Faso and Mali where the study was conducted transmission was  very intense (3-13 infective mosquito bites per person per month). At medium and low levels of transmission (last two rows of the table) the strategy becomes rather untenable, expending a lot of drug (which wastes money and risks side effects and resistance), for preventing a single case. Caveat to my caveat – the interpretation of rates differences in number needed to treat calculations is not always straightforward though I believe valid in this case.

Table: Number need to treat (NNT) and post-intervention incidence rate across varying baseline transmission and IPTc efficacy

Interestingly, similar to the famous Garki project the reductions in incidence appear to be much greater than reductions in prevalence – likely due to the seasonal nature of the intervention against a high vectorial capacity and thus risk of exposure.  Since the focus here is burden reduction, and not transmission reduction as in Garki, it doesn’t matter though.

]]> http://topnaman.com/treatment/new-results-for-intermittant-preventative-therapy-in-children/feed/ 0 http://topnaman.com/research/malaria-deaths-in-india/ http://topnaman.com/research/malaria-deaths-in-india/#comments Fri, 18 Mar 2011 14:01:51 +0000 naman http://topnaman.com/?p=933 Malaria mortality in India caused much controversy last fall. The study estimated almost 10 times the number malaria deaths in India during 2001-2003 compared to the estimates of the Government of India and WHO. The key strength of the work by Dhingra et al. was the use of a nationally representative sample of deaths during that period. However, the method for assigning the cause of death, verbal autopsy, is known to be problematic particularly for non-specific illness such as malaria and has come under much criticism. Some good early critiques appeared in Nature and Tropika and now The Lancet has published our reply as well as four others. The authors have also responded and the Government of India is setting up a panel to examine the findings and reconcile the available data.

To enable a proper assessment of research involving burden estimates, The Lancet and other journals should require authors to: 1) perform a validation exercise of the study instrument 2) conduct sensitivity analysis using validation results and other parameters of uncertainty and 3) make the underlying sample, or at least fully disaggregated tables, available for external verification. Otherwise we risk appearing to promote sensationalism over science. It is surprising such standards are not already in place.

• Looks like RDTs through drug shops won’t work. The same story with subsidized drugs?
• Mass drug administration with ivermectin to reduce mosquito survival (very novel research with a drug better known for river blindness control)
• World Malaria Report 2010 – at a glance looks great but do we need a new report annually? I know it’s a lot of work for the WHO staff…
• The malaria eradication research agenda in PloS from the malERA group – better than the Lancet series but many read like meeting reports

via Gizmodo, the ‘brutal’ invasion of a red blood cell by a malaria parasite (thanks to Saket)!

Last month Liu et al described the evolutionary origins of P. falciparum, the deadliest of human malaria parasites, which arose from a zoonotic (animal to human) transmission of a gorilla parasite. Before the general belief was that P. falciparum and its related simian parasites diverged at the same time as the ancestors of humans and chimpanzees did so.

Why do we care about monkey malaria? Animal reservoirs of human parasites renders the possibility of malaria eradication near impossible as the risk of reintroduction looms.  So even if falciparum arose from a single or few chance events thousands of years ago, the key question remains: Are ape populations a source for recurring human infection?

Scientists, using molecular assays,  reported gorillas infected with P. falciparum in Gabon. However, the samples were from captive animals, though originally born in the wild, living on an island sanctuary. Whether the finding represents a reverse-zoonotic event from exposure to humans or if the infection can be maintained in the wild is of critical importance. In the latest issue of Emerging Infectious Diseases we seem to have an answer. A survey of wild chimpanzees living in an undisturbed tropical rainforest habitat found five parasites including the human Plasmodia species malariae, vivax, and ovale.

While local elimination in many settings may be feasible, it seems that malaria is here to stay.

As someone within the research confines, Dr Knol’s comments ring true. Even in malaria research institutions in endemic countries, where  presumably there is greater pressure to focus on applied and operational questions, most new young scientists are taken by the latest molecular method.

These topics reminds me of a letter to the editor I came across a few years back:

Maintaining health in the tropics requires more than medical intervention after disease strikes. It requires more than drugs and vaccines to prevent disease. It requires something else, hygiene. Next year will be the 100th anniversary of the commencement of the work of Dr. William Gorgas in Panama. That 10-year effort was not accomplished with medicine or global health, it was hygiene: spraying insecticides, eliminating breeding sites, creating efficient drainage, building homes that keep mosquitoes at bay, and many other measures unrelated to clinical or laboratory medicine. Today many of the tropical infectious agents our Society investigates creep out of the conditions created by ignorance of hygiene.

The neglect of hygiene as a tool of disease prevention is lamentable. A simple hygienic practice that could prevent endemic disease often doesn’t happen because no one thought of it. We fly into areas of endemic disease bearing rapid diagnostics and effective therapies, but we neglect to bring the idea for a simple measure of hygiene that could prevent most of the infections being diagnosed and treated. Hygiene has no cache. No one funds research aimed at improving hygiene, and that’s too bad. Hygiene comes with no microsatellite arrays, ELISA wells, or dramatic recoveries in the clinic. Sound hygiene quietly creates communities of healthy people.

Recently, I browsed through a malaria journal article (open access!) whose potential I have difficulty understanding. Can someone explain to me how research on variation in chromosomal inversions and their relationship with stress responses will improve malaria control? Looking carefully through the manuscript, the sole rationale that I could find was:

Polymorphism for the 2La inversion creates heterogeneity in the stress response within A.gambiae, which could directly or indirectly reduce the efficacy of vector control measures, and influence the reaction of vector populations to environmental variation including climate change.

I find this single sentence advanced by the authors both incomplete and unsatisfying. It tells you very little. So let’s think through the rationale ourselves. Understanding the ability of a vector to exploit different habitats is certainly useful – we could predict how mosquito ranges and other characteristics may change with the climate. Understanding the molecular basis of that ability might further help – if the molecular changes had a clear association with a phenotype of interest (i.e. real world characteristics of the mosquito) and were such that they could easily be monitored. Understanding polymorphisms in those molecular mechanisms and their relationship to stress response variation however is not intuitively valuable (perhaps for modelling purposes?). To be clear, my aim is not cast the research as meaningless (though it may be). Sometimes the impact of basic science take years or decades to be realized. Rather, I’m surprised the authors, and especially the reviewers, did not seek to clearly convey the value of the work. If the purpose of public health research is to improve health, then the communication of such research should describe its relevance in explicit and detailed language.