Generating the evidence base for malaria elimination: the situation in Haiti
Authors: L C Okell, T S Churcher
Journal: The Lancet Global Health (2016)

Insecticide-treated bed nets (ITNs) are thought to be the key driver of the large reductions in malaria transmission observed over the past 10–15 years.1Bhatt S Weiss DJ Cameron E et al.The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.Nature. 2015; 526: 207-211Crossref PubMed Scopus (1554) Google Scholar ITNs work particularly well where the local Anopheles vectors usually bite indoors late at night, on average halving cases of malaria disease.2Lengeler C Insecticide-treated bed nets and curtains for preventing malaria.Cochrane Database Syst Rev. 2004; 2 (CD000363)Google Scholar However, the effect of ITN is less consistently shown in Latin America where some local mosquito vectors often bite outdoors (exophagic behaviour) or earlier in the evening before people go to bed. In The Lancet Global Health, Laura Steinhardt and colleagues3Clinton Health Access InitiativeThe feasibility of malaria elimination on the island of Hispaniola, with a focus on Haiti.http://globalhealthsciences.ucsf.edu/global-health-group/malaria-elimination-initiative/mei-publicationsGoogle Scholar report the first evaluation of ITN in Haiti, where the goal is to eliminate malaria by 2020. The ideal way to assess the effect of ITN on malaria transmission, as noted by the authors, is a cluster-randomised controlled trial. However, now that ITNs are a routine intervention against malaria, it is hard to have a control group without nets. In Haiti, such a study would also require an extremely large sample size in view of the low malaria incidence. In the face of these challenges, Steinhardt and colleagues used a case-control study design to measure association between ITN use and positivity for Plasmodium falciparum infection in patients with fever at health facilities following a mass distribution of ITNs. They found no significant effect of ITN despite using different indicators of ITN use and a sophisticated set of analyses designed to minimise confounding and bias. The authors conclude that “alternative malaria control strategies should be prioritised” in Haiti.3Clinton Health Access InitiativeThe feasibility of malaria elimination on the island of Hispaniola, with a focus on Haiti.http://globalhealthsciences.ucsf.edu/global-health-group/malaria-elimination-initiative/mei-publicationsGoogle Scholar Although the study is of a high quality given the constraints of the case-control design, we question whether it alone provides sufficient evidence for this policy recommendation. Observational studies of ITNs are notoriously fraught with challenges. Even in settings in which randomised trials show ITN provide good protection, it is not unusual for case-control analyses to find a lack of protection or even ITN use being associated with increased risk of malaria. This counterintuitive finding can happen because people who live in houses more exposed to mosquitoes are more likely to use ITNs, or, when cases are recruited in health facilities, because individuals who have good health-seeking behaviour are more likely to use nets than those who tend to not attend health facilities. What is commendable about the Haiti study3Clinton Health Access InitiativeThe feasibility of malaria elimination on the island of Hispaniola, with a focus on Haiti.http://globalhealthsciences.ucsf.edu/global-health-group/malaria-elimination-initiative/mei-publicationsGoogle Scholar is the lengths to which Steinhardt and colleagues went to control for such factors. These efforts included campaigns to encourage anyone with fever to come to free health facilities and a propensity scoring analysis, for which individuals were matched on a range of demographic, health behavioural, and socioeconomic indicators, enabling comparison of people who were similar with respect to many risk factors but not their recent ITN use. Nonetheless, even well conducted observational studies can fail to capture the true effect of interventions. For example, in sub-Saharan Africa where the impact of ITNs has been well established by cluster randomised trials,2Lengeler C Insecticide-treated bed nets and curtains for preventing malaria.Cochrane Database Syst Rev. 2004; 2 (CD000363)Google Scholar a multi-country, individually-matched analysis4Lim SS Fullman N Stokes A et al.Net benefits: a multicountry analysis of observational data examining associations between insecticide-treated mosquito nets and health outcomes.PLoS Med. 2011; 8: e1001091Crossref PubMed Scopus (122) Google Scholar of cross-sectional data found that only two of seven country datasets showed a significant association between ITN use and reduced parasite prevalence, and two showed no reduction at all. Another complication in areas approaching local elimination such as Haiti is high spatiotemporal variation in transmission.5Cohen JM Ernst KC Lindblade KA Vulule JM John CC Wilson ML Local topographic wetness indices predict household malaria risk better than land-use and land-cover in the western Kenya highlands.Malar J. 2010; 9: 328Crossref PubMed Scopus (49) Google Scholar Steinhardt and colleagues made every effort to match malaria exposure in cases and controls by comparing individuals experiencing fever close in time and living in the same commune. Nevertheless, a commune still equates to a relatively large geographical area relative to the focality of malaria transmission.6Sturrock HJ Novotny JM Kunene S et al.Reactive case detection for malaria elimination: real-life experience from an ongoing program in Swaziland.PLoS One. 2013; 8: e63830Crossref PubMed Scopus (88) Google Scholar Cases could have also acquired infection outside the local area. The lack of recent entomological data from the study sites on biting times and exophagy of the primary vector, Anopheleles albimanus, hampers interpretation of the results. These data gaps are currently being addressed. Historical data suggest that although outdoor biting is more common, a non-negligible proportion of bites occurs indoors.7Frederick J Saint Jean Y Lemoine JF et al.Malaria vector research and control in Haiti: a systematic review.Malar J. 2016; 15: 376Crossref PubMed Scopus (26) Google Scholar Existence of indoor biting is suggested by the finding in Steinhardt's study3Clinton Health Access InitiativeThe feasibility of malaria elimination on the island of Hispaniola, with a focus on Haiti.http://globalhealthsciences.ucsf.edu/global-health-group/malaria-elimination-initiative/mei-publicationsGoogle Scholar that good-quality roofing material on houses (but not other socioeconomic indicators) was protective against malaria. Furthermore, some randomised studies8Richards Jr, FO Klein RE Flores RZ et al.Permethrin-impregnated bed nets for malaria control in northern Guatemala: epidemiologic impact and community acceptance.Am J Trop Med Hyg. 1993; 49: 410-418Crossref PubMed Scopus (35) Google Scholar of ITNs in areas where A albimanus is the primary vector have shown significant effect, although this effect is not consistent across studies.9Zimmerman RH Voorham J Use of insecticide-impregnated mosquito nets and other impregnated materials for malaria control in the Americas.Rev Panam Salud Publica. 1997; 2: 18-25Crossref PubMed Scopus (26) Google Scholar Steinhardt reported surprisingly low ITN use given the recent mass distribution of ITN and issues around this low use might need further investigation. Such coverage is probably too low to substantially suppress the vector population, which can be an important component of the impact of ITNs on malaria transmission.10Killeen GF Smith TA Ferguson HM et al.Preventing childhood malaria in Africa by protecting adults from mosquitoes with insecticide-treated nets.PLoS Med. 2007; 4: e229Crossref PubMed Scopus (242) Google Scholar Steinhardt's study emphasises the difficulty of measuring the effect of ITN in low-transmission settings. Nevertheless, the quantification of ITN effect in different settings is essential to inform malaria elimination. Observational studies like this3Clinton Health Access InitiativeThe feasibility of malaria elimination on the island of Hispaniola, with a focus on Haiti.http://globalhealthsciences.ucsf.edu/global-health-group/malaria-elimination-initiative/mei-publicationsGoogle Scholar need to be considered together with good-quality local entomological monitoring and evidence from other relevant studies of ITNs. Indeed, ITNs have been shown to be effective in parts of Southeast Asia with exophagic vectors.2Lengeler C Insecticide-treated bed nets and curtains for preventing malaria.Cochrane Database Syst Rev. 2004; 2 (CD000363)Google Scholar The Haiti context highlights the absence of a one-size-fits-all solution for malaria control and the difficulties of providing the evidence-base for locally appropriate strategies against diverse vectors. LCO declares grant funding from WHO and Medicines for Malaria Venture (MMV), and has received a consultancy contract in the past 5 years from MMV. TSC receives grant funding from the Wellcome Trust, Malaria Vaccine Initiative and Innovative Vector Control Consortium. We would like to acknowledge the comments and insight given by five anonymous reviewers. LCO is funded by a UK Royal Society Dorothy Hodgkin fellowship. Effectiveness of insecticide-treated bednets in malaria prevention in Haiti: a case-control studyWe found no evidence that mass ITN campaigns reduce clinical malaria in this observational study in Haiti; alternative malaria control strategies should be prioritised. Full-Text PDF Open Access