R&D for Healthy Futures: Five Experts Pick Their Top Malaria Paper From Today

[This blog is part of the #DefeatMalaria World Malaria Day blog series hosted by Roll Back Malaria, to be published between April 8 and May 1, 2015]

As Margaret Chan wrote in the World Malaria Report last year, " Each year, more people are being reached with core malaria interventions, and as a result, more lives are being saved".¹ The progress has been phenomenal, however, our core interventions are threatened by emerging drug and insecticide resistance. Maintaining investment in R&D is essential to counter this threat and continue to drive down malaria deaths and infection.

At MESA (Malaria Eradication Scientific Alliance), we are marking World Malaria Day 2015 by highlighting some of the research which is helping us achieve our goals and combat malaria. We asked five experts from different fields to recommend an open access paper from the last 18 months. Here are their top picks:

Wendy O'Meara (Duke Univeristy, USA) enthusiastically recommended a whole reading list! The paper we chose to share for special attention is ' The impact of pyrethroid resistance on the efficacy of insecticide-treated bed nets against African Anopheline mosquitoes: Systematic review and meta-analysis (link is external) ' from Clare Strode, Sarah Donegan, Paul Garner, Ahmad Ali Enayati and Janet Hemingway, published in PLOS Medicine.² One of the take home messages from the review is that the lack of standardised methods to measure insecticide resistance and entomological outcomes in the studies (especially in the field studies) is a real barrier to elucidating the true relationship between insecticide resistance and insecticide treated net (ITN) efficacy. The authors analyzed 25 study reports including lab and field studies with experimental huts. " Cone tests...showed reduced levels of mosquito knock-down associated with higher levels of resistance. Laboratory tunnel test results demonstrated a reduced effect of ITNs in mosquitoes with higher resistance levels...In experimental hut trials the RD (risk difference) for mortality for ITNs compare to UTNs (untreated nets) showed that ITNs continued to have an effect in all categories of resistance ". Since there was such a high level of heterogeniety between the studies, the authors caution the interpretation of the meta-analytic results. The authors conclude by calling for international agreement to standardise methods for measuring the impact of resistance on ITNs and put forward a set of suggestions for experimental hut study design and reporting.

Lisa White (Mahidol-Oxford Research Unit, Thailand) chose ' Factors determining the occurrence of submicroscopic malaria infections and their relevance for control (link is external) ' from Lucy C. Okell, Teun Bousema, Jamie T. Griffin, André Lin Ouédraogo, Azra C. Ghani and Chris J. Drakeley.³ Published in Nature Communications. The paper analyses 106 PCR prevalence surveys and 4 human-to-mosquito transmission studies to explore questions around the epidemiologiy of sub-microscopic infections and estimate their contribution to malaria transmission. For Lisa, this is an important paper because " to eliminate malaria, an understanding of the natural history of infection and especially asymptomatic infection is essential." And from the modelling point of view, "the information in this paper is extremely useful for model design. Mathematical models for malaria should be capable of reproducing the relationships described in this paper before they are used to simulate interventions."

Ashwani Kumar (National Institute of Malaria Research, India) is another enthusiastic reader and from the set of papers he liked, we highlight ' Novel approaches to risk stratification to support malaria elimination: an example from Cambodia (link is external) ' from Jonathan Cox, Siv Sovannaroth, Lek Dy Soley, Pengby Ngor, Steven Mellor and Arantxa Roca-Feltrer, published in Malaria Journal.4 The paper documents how the 'Malaria Information System' was set up in Cambodia and how it is enabling village-level malaria data to be captured routinely. The data generated highlight just how heterogeneous malaria transmission is even between individual villages in Cambodia "...over half (51.6%) of all malaria cases originated from 5% of villages, while 85.9% of cases came from 20% of villages". The authors discuss ongoing pilot studies to link the Malaria Information System with private sector health facilities and pharmacies and to allow the military and police to be able to report malaria cases through the system. Authors highlight that the purpose of stratifying malaria transmission is to then target interventions effectively including the dynamic network of village malaria workers.

The number one publication last year, according to Fredros Okumu (Ifakara Health Institute, Tanzania) was the paper by Gerry F Killen ' Characterizing, controlling and eliminating residual malaria transmission (link is external) ' in Malaria Journal.⁵ It describes the phenomenon of ‘residual malaria transmission’; namely transmission that persists in the face of full coverage of insecticide-containing vector control tools. The paper challenges our ‘stereotype’ of the behaviour of malaria transmitting mosquitoes and discusses how varied vector behaviours and adaptations contribute to residual transmission. Fredros commented that this paper " offered great insights on what should best be done to move from where we are now towards zero transmission, and also presented very practical/actionable plans on how the people in charge should tackle the ongoing residual transmission…highlighting the kinds of data necessary for National Control programs to decide on whether or not they should scale these options up .” Killeen explores potential solutions and highlights the opportunities to ‘learn by doing’. Novel approaches to eliminate residual transmission do exist and national programmes can use pilot studies to assess, monitor, and evaluate the novel vector control strategies to combat this ongoing residual transmission.

Last, but by no means least, Francisco Saute (Manhiça Health Research Centre, Mozambique) reminds us not to think about malaria in isolation from other infectious diseases, " People in malaria endemic countries are also at high risk of co-infection with TB and HIV/AIDs as well as chronic diseases. This paper reminds us of that, and that co-infection can have consequences on the drugs we use for malaria ". He recommends the PLOS Medicine paper ' Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial (link is external) ' from Raquel González, Meghna Desai , Eusebio Macete , Peter Ouma , Mwaka A. Kakolwa , Salim Abdulla, John J. Aponte, Helder Bulo, Abdunoor M. Kabanywanyi, Abraham Katana, Sonia Maculuve, Alfredo Mayor, Arsenio Nhacolo, Kephas Otieno, Golbahar Pahlavan, María Rupérez, Esperança Sevene, Laurence Slutsker, Anifa Vala, John Williamsom and Clara Menéndez.⁶ The multi-centre randomized trial shows that by adding an effective antimalarial to the existing package of interventions (ITNs and cotrimoxazole prophylaxis) both malaria prevention and maternal health were improved. However, mefloquine, the drug used in the study, was associated with an increased risk of mother to child transmission of HIV and the authors call for " specifically designed studies to fully understand the implications of coadministration of antimalarials and ARVs (antiretovirals)". Francisco concluded that "To eliminate malaria, we need to be able to eliminate the parasites from all people, including people with HIV and TB."

[Thank you to the experts who recommended papers and to Bea Galatas who inspired the blog.

This blog was written by Kate Whitfield, MESA Coordinator. MESA is hosted at ISGlobal, Barcelona Institute for Global Health.]

¹ World Malaria Report 2014, World Health Organization, http://www.who.int/malaria/publications/world_malaria_report/en/

² Strode C, Donegan S, Garner P, Enayati AA, Hemingway J (2014) The Impact of Pyrethroid Resistance on the Efficacy of Insecticide-Treated Bed Nets against African Anopheline Mosquitoes: Systematic Review and Meta-Analysis. PLoS Med 11(3): e1001619. doi:10.1371/journal.pmed.1001619

3Okell LC, Bousema T, Griffin JT, Ouédraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nature Communications. 2012;3:1237-. doi:10.1038/ncomms2241.

⁴ Cox J, Sovannaroth S, Soley LD, Ngor P, Mellor S and Roca-Feltrer A (2014) Novel approaches to risk stratification to support malaria elimination: an example from Cambodia. Malaria Journal 2014, 13:371 doi:10.1186/1475-2875-13-371

⁵ Killeen GF (2014) Characterizing, controlling and eliminating residual malaria transmission. Malaria Journal 2014, 13:330 doi:10.1186/1475-2875-13-330

⁶ González R, Desai M, Macete E, Ouma P, Kakolwa MA, et al. (2014) Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial. PLoS Med 11(9): e1001735. doi:10.1371/journal.pmed.1001735