Malaria Journal - Latest Comments

New, effective insecticides against malaria vectors: a solid field test

Edward Walker — 2010-03-03T00:00:00Z

The wonderful results of this nicely designed and summarized field study are balanced by the sobering conclusions, not found in the abstract but rather appearing at the end of the article.

They are that industry has indeed been forthcoming with a highly promising and nearly immediately available insecticide formulation for control of malaria vectors through the indoor residual spray method, with demonstrated high efficacy against pyrethroid resistance populations. Yet, the manufacturer, for reasons unknown but perhaps related to product stewardship, out of concern of backlash from the public with regard to perceived health risks, or for some combination of reasons; does not intend to move the product into the vector control market, according to this paper's conclusions. On the one hand, their decision is understandable; and on the other, it runs counter to the prevailing philosophy of both the WHO and of organizations such as the Innovative Vector Control Consortium, which is to engage industry into registering their old and new products from agricultural and urban pest management uses to vector control uses (see M Zaim and P Guillet. 2002. Alternative insecticides: an urgent need. Trends in Parasitology 18:161-163; and http://www.ivcc.com/workwithus/strategy_portfolio.htm). Given the rise in pyrethroid resistance in field populations of malaria vectors, it does raise ethical and humanitarian concerns.

Certainly a company cannot be forced to cross list its product registrations. But if the current model is to depend upon the private sector to be forthcoming with new and readily implemented tools; and that model falters as this scenario indicates, then what is the fallback plan? This commentator wholeheartedly agrees with the authors that: "The comparatively small size of the market and the unpredictability of winning tenders is a major deterrent to companies not already engaged in malaria control. The manufacturer should be encouraged by international donors and technical authorities to pursue further development and evaluation against malaria indicators in endemic settings where An. gambiae is pyrethroid-resistant or IRS is being considered for malaria control."

prescription practices and national antimalarial treatment guideline

folasade lawal — 2010-01-01T00:00:00Z

A research of great interest considering the enormity of the problem of resistance to antimalarials. I just wish to add that we need to find out how many prescribers are aware or have access to the national antimalarial treatment guideline and how many make use of it especially against the background that prescriptions for malaria are generated by varied healthcare providers since most antimalarials in Nigeria are available over-the-counter.

Halofantrine is too dangerous

Francois Nosten — 2009-12-27T00:00:00Z

Halofantrine was discovered by the Walter Reed Army Institute of Research, developed by SmithKline Beecham (now GlaxoSmithKline), and registered in many countries. Despite this rigorous development, it was discovered after the general release of halofantrine that this effective antimalarial markedly prolongs ventricular repolarisation and thereby predisposes to potentially lethal ventricular tachyarrhythmias. Bouchaud et al (Malaria Journal; 2009, 8:289) review the fatalities associated with halofantrine reported to the manufacturer, and point out that the majority of patients who died had cofactors which would have predisposed them to lethal cardiotoxicity (this is also the case for other drugs with this property which have been withdrawn). They conclude that “in the rare situations in which halofantrine is the only therapeutic option, it can still be given after carefully checking for contraindications, such as underlying cardiac disease, bradycardia, metabolic disorders, personal or family history of long QT-interval or concomitant use of another QT-prolonging drug (e.g., mefloquine), especially in females”. We do not believe today that halofantrine is ever the only therapeutic option. Safe and highly effective alternative artemisinin-combination treatments are available. Mefloquine, lumefantrine, piperaquine, atovaquone and the artemisinins are not cardiotoxic. Careful exclusion of cardiac risk factors is unrealistic in most tropical settings. The case series presented here is likely to be an underestimate of the fatalities caused by the drug. Halofantrine should long ago have joined the list of drugs which prolong the QT interval and were withdrawn when their lethal potential became evident: terfenadine (1998), sertindole (1998), astemizole (1999), grepafloxacin (1999), and cisapride (2000). As much safer effective alternatives are available halofantrine is simply too dangerous still to be deployed.

Francois Nosten (SMRU/MORU)
Christine Luxemburger (SMRU)
Feiko ter Kuile (Liverpool School Tropical Medicine)
Charles Woodrow (MORU)
Nicholas J White (MORU)

Thin edge of the wedge

Raymond Jacobson — 2009-12-01T00:00:00Z

This is an excellent article that should be circulated widely. Many of my students from developing countries, who have worked with NGOs and MoHs report that they rely totally on RDT and seldom use blood smears to confirm the diagnosis. Microscopy may seem old fashioned, but is still vital in endemic areas.

Small corrections

Anand Patil — 2009-11-18T00:00:00Z

We spotted a couple of small errors after the article had already gone into press.

In the caption of Figure 5, 'any given year' should be replaced with 'any given two-year period'.

Similarly, in B.11.1, 'predictions for a given year in a single population' should be 'predictions for a given two-year period in a single population'.

Response

David Wright — 2009-10-05T00:00:00Z

The control or eventual elimination of malaria is not possible without a thorough understanding of the disease as an integrated process. While biological studies traditionally examine a subset of molecular indicators, the dynamic nature of malaria infection (i.e., vector, parasite, and host interactions) lends itself to technologies utilized by the field of systems biology: transcriptomics, proteomics, and metabolomics. The transcriptional approach presented here is reductionist by nature, systematically examining the global response to constituent components of hemozoin (the detoxification product generated in response to heme liberated during hemoglobin catabolism) in order to better understand the individual players responsible for macrophage immunomodulation. The studies focus on a specific component of hemozoin, 15-HETE, mapping the macrophage response to this biologically active lipid peroxidation product. It is our hope that this global analysis, with a focus on 15-HETE, will aid in further advancing the malaria knowledge-base with regard to hemozoin's biological activity.

Please help me out...

Bart Knols — 2009-08-12T00:00:00Z

Dear authors,

I have not the slightest hesitation to assume that the work you reported in this article is of high quality; it would not have been published in Malaria J if this wasn't the case.

But for me and those thousands of other readers of the journal, can you please explain to me what this is all about? I have been in the field of malaria for 20 years (on the vector side), sit on the editorial board of this and several other journals, but had a really really hard time to understand the crux of your story.

Would it not be good for Malaria J to co-publish a few hundred words (in a box) in a language that we all speak and understand alongside every article? Explain in simple terms to those not directly engaged at this level what this study was all about, what was found, and how it contributes to our knowledge and ultimately the goal of controlling if not eliminating malaria.

US Army Modifies Policy on Mefloquine Prophylaxis in Afghanistan

Remington Nevin — 2009-05-11T00:00:00Z

The references for the previous comment (US Army Modifies Policy on Mefloquine Prophylaxis in Afghanistan, 09 May 2009) were inadvertently truncated, and appear below:

[1] Department of the Army Office of the Surgeon General Memorandum. Subject: Updated Guidance on the Use of Mefloquine Hydrochloride (Lariam®) for Malaria Prophylaxis. February 2, 2009. Available at http://www.pdhealth.mil/downloads/DASG_Memorandum.pdf

[2] Sonmez A, Harlak A, Kilic S, Polat Z, Hayat L, Keskin O, Dogru T, Yilmaz MI, Acikel CH, Kocar IH. The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan. J Infect. 2005;51:253-8.

US Army Modifies Policy on Mefloquine Prophylaxis in Afghanistan

Remington Nevin — 2009-05-09T00:00:00Z

One year following the publication of this study, the US Army modified its official policy on mefloquine prophylaxis to read as follows:

"In areas where doxycycline and mefloquine are equally efficacious in preventing malaria, doxycycline is the drug of choice. Mefloquine should only be used for personnel with contraindications to doxycycline and [who] do not have any contraindications to the use of mefloquine... Mefloquine should not be given to Soldiers with [a] recent history of Traumatic Brain Injury (TBI) or [who] have symptomatic TBI." [1]

A recent study by Sonmez et al [2] demonstrated that mefloquine and doxycycline are equally efficacious in preventing malaria among military personnel in Afghanistan; in light of this new policy guidance these findings suggest doxycycline should now be considered the drug of choice for US Army service members stationed there.

The study of contraindications to mefloquine use was made possible through a one-time merge of pharmacy data from the Pharmacy Data Transaction Service (PDTS) with data obtained from the Defense Medical Surveillance System (DMSS). Formal integration of PDTS data into DMSS would permit more routine analyses of this type and permit improved monitoring of mefloquine prescribing trends.

Potential overestimation of parasite loss in thick smears

Georges Snounou — 2008-10-21T00:00:00Z

The loss of parasite material during staining had been recognized early on by malariologists when it was noted that parasites transferred from smears of malaria-infected persons to those of uninfected individuals when staining was carried out in the same container (Brooke and Donaldson, 1948, Public Health Reports, 63:991).

The molecular analysis presented in the article by Bejon et al. led them to conclude that thick smears counts underestimate the true parasite levels by ten-fold (the log difference from Fig. 1). This implies that 9 out of 10 parasites are lost when the thick smear is stained (the authors discount the probability of parasites being obscured in the thick smear). The calculations were based on a the assumption that 100 high powered fields correspond to 1 microlitre of blood. In the reference quoted for this value ([7] Greenwood and Armstrong, 1991, Transactions of the Royal Society of Tropical Medicine and Hygiene, 85:186), the equivalent figure was 500 high powered fields.

We suggest the value of 500 is the correct one, thus the actual loss in the sensitivity of thick smear microscopy for parasite load evaluation would be two-fold rather than ten-fold. We feel that the loss observed is mainly due to difficulties in identifying parasites when these are present in very low numbers in a thick smear, rather than because of a massive loss of parasite material during Giemsa staining. This could be easily confirmed by comparing DNA content in blood at high parasite levels (> 10 000 parasites per ml of blood) with thick smear counts.

In conclusion, we agree that thick smears at low parasite densities underestimate true parasite loads but not to the extent concluded in the article. On the other hand we agree that the more sensitive molecular techniques of parasite detection should be applied when measuring intervention outcomes, such as those of vaccination studies.

Georges Snounou (CNRS, Paris, France; National University of Singapore, Singapore) and Mehul Dhorda (Epicentre, Mbarara, Uganda)