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Are we losing the fight against malaria one more time?

2011; Elsevier BV; Volume: 17; Issue: 11 Linguagem: Inglês

10.1111/j.1469-0691.2011.03666.x

1469-0691

Mical Paul,

Travel-related health issues

Historic events have occurred in the last decade in the battle against malaria, one of humanity's most ancient and deadly enemies. In 2000, 189 nations, under the United Nations Development Programme [1United Nations Millennium development goals.Available at: http://www.un.org/millenniumgoals/Date: 2011Google Scholar], defined malaria control as one of the Millennium Development Goals, with a target of reducing malaria cases and deaths by 50% in 2010 and by 75% in 2015. This issue's themed section is devoted to the ongoing efforts to control malaria, comprising vector control, surveillance, the development and distribution of drugs that are highly effective against malaria, intermittent preventive treatment, improved diagnosis, targeted case management, and vaccine development [2Gosling RD Okell L Mosha J Chandramohan D The role of antimalarial treatment in the elimination of malaria.Clin Microbiol Infect. 2011; 17: 1617-1623Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 3Greenwood BM Targett ATG Malaria vaccines and the new malaria agenda.Clin Microbiol Infect. 2011; 17: 1600-1607Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 4Karunamoorthi K Vector control: a cornerstone in the malaria elimination campaign.Clin Microbiol Infect. 2011; 17: 1608-1616Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar, 5McMorrow ML Aidoo M Kachur SP Malaria rapid diagnostic tests in elimination settings—can they find the last parasite?.Clin Microbiol Infect. 2011; 17: 1624-1631Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar]. These efforts have resulted in impressive achievements, mainly in sub-Saharan Africa that incurs the brunt of malaria-related child mortality. Bed-net coverage increased from approximately 5% in 2000 to more than 45% in 2010 in sub-Saharan Africa (Fig. 1). There was an estimated global reduction in deaths from malaria of 20%, from approximately 985 000 in 2000 to 781 000 in 2009 (data for sub-Saharan Africa are shown in Fig. 1). This is especially impressive considering that, in the previous decade, mortality had been increasing, because of chloroquine resistance. Although, in absolute numbers, the reductions are largest in sub-Saharan Africa, the relative reduction is most prominent in settings of low and moderate endemicity. Ultimately, the battle will be decided in those areas with the most intense transmission of malaria. However, a recently published study presents worrying findings: the recrudescence of malaria attacks within 30 months of the introduction of long-lasting insecticide (deltamethrin)-treated nets (LLINs) in an area of intense, perennial malaria transmission [7Trape JF Tall A Diagne N et al.Malaria morbidity and pyrethroid resistance after the introduction of insecticide‐treated bednets and artemisinin‐based combination therapies: a longitudinal study.Lancet Infect Dis. 2011; https://doi.org/10.1016/S1473-3099(11)70194-3Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar]. The study was conducted in Dielmo, a small village in the Sudan-savannah region of central Senegal, between 2007 and 2010, and included 405 participants at the start and 465 at the end. LLINs (Permanet 2.0) were introduced in July 2008. Throughout the study period, uncomplicated malaria was treated with the artesimin combination therapy artesunate–amodaquine, and no therapeutic failures were noted. The incidence of malaria decreased from 5.45 malaria attacks per 100 person-months in the 18 months before introduction of LLINs to 0.41 in the 24 months thereafter (incidence rate ratio adjusted for age and seasonality, 0.07 (95% CI 0.05–0.10)). However, the incidence increased back to 4.57 per 100 person-months in the following 4 months (up to December 2010), and the adjusted incidence rate ratio for this period, as compared with the baseline before the introduction of LLINs, was not significant (0.84 (95% CI 0.59–1.21)). Three explanations were given for the observed findings. The most important was pyrethroid resistance. The frequency of the kdr west allele (a mutation in the para-sodium channel gene of Anopheles gambiae conferring resistance to pyrethroids) increased from 8% in 2007 to 48% in 2010, and 37% of A. gambiae mosquitoes were resistant to deltamethrin in 2010. Second, the largest increase in malaria incidence occurred in participants >10 years of age. In this group, the incidence of malaria in the last 4 months of the study was higher than at baseline 3 years previously, which is compatible with the theory of decreased protective immunity following effective transmission interruption in infancy and early childhood. Finally, a slight shift was observed in mosquito biting times. In 2007 and 2008, the peak biting time was between 2 and 3 a.m., but in 2009 and 2010 the peak occurred between midnight and 2 a.m. Bed-net ownership, use and maintenance were high throughout the study, although there was a decreasing trend throughout the study period. Previous studies have also examined the sustainability of malaria control interventions over time and the hypothesis of an age shift related to delayed immunity acquisition [8Lindblade KA Eisele TP Gimnig JE et al.Sustainability of reductions in malaria transmission and infant mortality in western Kenya with use of insecticide‐treated bednets: 4 to 6 years of follow‐up.JAMA. 2004; 291: 2571-2580Crossref PubMed Scopus (129) Google Scholar, 9Diallo DA Cousens SN Cuzin‐Ouattara N Nebie I Ilboudo‐Sanogo E Esposito F Child mortality in a West African population protected with insecticide‐treated curtains for a period of up to 6 years.Bull World Health Organ. 2004; 82: 85-91PubMed Google Scholar, 10Ilboudo‐Sanogo E Cuzin‐Ouattara N Diallo DA et al.Insecticide‐treated materials, mosquito adaptation and mass effect: entomological observations after five years of vector control in Burkina Faso.Trans R Soc Trop Med Hyg. 2001; 95: 353-360Abstract Full Text PDF PubMed Scopus (37) Google Scholar, 11Binka FN Hodgson A Adjuik M Smith T Mortality in a seven‐and‐a‐half‐year follow‐up of a trial of insecticide‐treated mosquito nets in Ghana.Trans R Soc Trop Med Hyg. 2002; 96: 597-599Abstract Full Text PDF PubMed Scopus (47) Google Scholar, 12Ceesay SJ Casals‐Pascual C Nwakanma DC et al.Continued decline of malaria in The Gambia with implications for elimination.PLoS ONE. 2010; 5: e12242Crossref PubMed Scopus (107) Google Scholar, 13Ceesay SJ Casals‐Pascual C Erskine J et al.Changes in malaria indices between 1999 and 2007 in the Gambia: a retrospective analysis.Lancet. 2008; 372: 1545-1554Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar, 14Mnzava AE Sharp BL Mthembu DJ et al.Malaria control—two years’ use of insecticide‐treated bednets compared with insecticide house spraying in KwaZulu‐Natal.S Afr Med J. 2001; 91: 978-983PubMed Google Scholar, 15Fegan GW Noor AM Akhwale WS Cousens S Snow RW Effect of expanded insecticide‐treated bednet coverage on child survival in rural Kenya: a longitudinal study.Lancet. 2007; 370: 1035-1039Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar, 16Rowland M Hewitt S Durrani N Saleh P Bouma M Sondorp E Sustainability of pyrethroid‐impregnated bednets for malaria control in Afghan communities.Bull World Health Organ. 1997; 75: 23-29PubMed Google Scholar]. The results of these and the current study are shown in Table 1. In most, the benefit initially afforded by insecticide-treated bed-nets and other malaria control interventions (e.g. effective treatment and indoor residual spraying) was maintained throughout study periods of 2–9 years after introduction of the control measure. A rebound in mortality was noted in a trial in Burkina Faso, especially after 6 years of exposure to bed-nets, although to lower levels than baseline [9Diallo DA Cousens SN Cuzin‐Ouattara N Nebie I Ilboudo‐Sanogo E Esposito F Child mortality in a West African population protected with insecticide‐treated curtains for a period of up to 6 years.Bull World Health Organ. 2004; 82: 85-91PubMed Google Scholar]. In The Gambia, a rebound in parasitaemia was noted in two of ten nationwide study sites, but parasitaemia returned to the low levels achieved with the intervention at longer follow-up [12Ceesay SJ Casals‐Pascual C Nwakanma DC et al.Continued decline of malaria in The Gambia with implications for elimination.PLoS ONE. 2010; 5: e12242Crossref PubMed Scopus (107) Google Scholar]. A shift towards a higher age among those admitted for malaria was noted only in The Gambia [13Ceesay SJ Casals‐Pascual C Erskine J et al.Changes in malaria indices between 1999 and 2007 in the Gambia: a retrospective analysis.Lancet. 2008; 372: 1545-1554Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar]. Notably, most previous studies limited the age range assessed to children aged 10 years and adults [7Trape JF Tall A Diagne N et al.Malaria morbidity and pyrethroid resistance after the introduction of insecticide‐treated bednets and artemisinin‐based combination therapies: a longitudinal study.Lancet Infect Dis. 2011; https://doi.org/10.1016/S1473-3099(11)70194-3Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar]. LLINs were assessed only in this last study. Bed-net usage decreased with time in two of the three studies showing increased event rates [7Trape JF Tall A Diagne N et al.Malaria morbidity and pyrethroid resistance after the introduction of insecticide‐treated bednets and artemisinin‐based combination therapies: a longitudinal study.Lancet Infect Dis. 2011; https://doi.org/10.1016/S1473-3099(11)70194-3Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar, 9Diallo DA Cousens SN Cuzin‐Ouattara N Nebie I Ilboudo‐Sanogo E Esposito F Child mortality in a West African population protected with insecticide‐treated curtains for a period of up to 6 years.Bull World Health Organ. 2004; 82: 85-91PubMed Google Scholar], compliance was not assessed in one [12Ceesay SJ Casals‐Pascual C Nwakanma DC et al.Continued decline of malaria in The Gambia with implications for elimination.PLoS ONE. 2010; 5: e12242Crossref PubMed Scopus (107) Google Scholar], and others documented stable or increased usage (Table 1). Methods of surveillance and the outcomes examined in the studies were different. The study of Trape et al. accounted for every individual in a small study region throughout the study period, and included daily active assessment of all febrile episodes and entomological indices. Most other studies assessed mortality or other broader measures of effectiveness, but were conducted on much larger populations than the current study.TABLE 1Studies assessing the sustainability of malaria control interventions with timeAuthorLocation and malaria transmissionMethodsFollow-up durationOutcomes examinedBed-net usage during studyAge (years)ResultsLindblade [8Lindblade KA Eisele TP Gimnig JE et al.Sustainability of reductions in malaria transmission and infant mortality in western Kenya with use of insecticide‐treated bednets: 4 to 6 years of follow‐up.JAMA. 2004; 291: 2571-2580Crossref PubMed Scopus (129) Google Scholar]Kenya (west, shores of Lake Victoria). PerennialLong-term follow-up of an RCTa2-year RCT + 4-year follow-upAll-cause mortality, clinical malaria and entomological indicesIncreased<5Benefit maintained throughout the study periodDiallo and Ilboudo-Sanogo [9Diallo DA Cousens SN Cuzin‐Ouattara N Nebie I Ilboudo‐Sanogo E Esposito F Child mortality in a West African population protected with insecticide‐treated curtains for a period of up to 6 years.Bull World Health Organ. 2004; 82: 85-91PubMed Google Scholar, 10Ilboudo‐Sanogo E Cuzin‐Ouattara N Diallo DA et al.Insecticide‐treated materials, mosquito adaptation and mass effect: entomological observations after five years of vector control in Burkina Faso.Trans R Soc Trop Med Hyg. 2001; 95: 353-360Abstract Full Text PDF PubMed Scopus (37) Google Scholar]Burkina Faso (Oubritenga Province). SeasonalLong-term follow-up of an RCT2-year RCT + 4-year follow-upAll-cause mortality and entomological indicesDeclined from 78% to 43%<5Increased mortality in the last 2 years of the study to lower levels than baseline, more prominent in the original intervention group (6 years of exposure)Binka [11Binka FN Hodgson A Adjuik M Smith T Mortality in a seven‐and‐a‐half‐year follow‐up of a trial of insecticide‐treated mosquito nets in Ghana.Trans R Soc Trop Med Hyg. 2002; 96: 597-599Abstract Full Text PDF PubMed Scopus (47) Google Scholar]Ghana (Kassena-Nankana District). SeasonalLong-term follow-up of an RCT2-year RCT + 5-year follow-upAll-cause mortality and entomological indicesNot stated<5Benefit maintained throughout the study periodCeesay [12Ceesay SJ Casals‐Pascual C Nwakanma DC et al.Continued decline of malaria in The Gambia with implications for elimination.PLoS ONE. 2010; 5: e12242Crossref PubMed Scopus (107) Google Scholar]The Gambia. SeasonalLongitudinal surveys7 yearsParasitaemiaDistribution increased, but actual usage not statedAllBenefit maintained throughout the study period, except for two of ten locations, where an increase was followed by a return to the low levels achieved previouslyCeesay [13Ceesay SJ Casals‐Pascual C Erskine J et al.Changes in malaria indices between 1999 and 2007 in the Gambia: a retrospective analysis.Lancet. 2008; 372: 1545-1554Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar]The Gambia. SeasonalLongitudinal surveys9 yearsAdmissions and deaths attributed to malariaDistribution increased, but actual usage not stated<15Benefit maintained throughout the study period. Age shift in admissions for malaria from a mean of 3.9 years in the first study period to a mean of 5.6 years in the last study periodMnzava [14Mnzava AE Sharp BL Mthembu DJ et al.Malaria control—two years’ use of insecticide‐treated bednets compared with insecticide house spraying in KwaZulu‐Natal.S Afr Med J. 2001; 91: 978-983PubMed Google Scholar]KwaZulu-Natal (north). SeasonalLongitudinal survey2 yearsClinical malariaNot statedNSBenefit increased throughout the study periodFegan [15Fegan GW Noor AM Akhwale WS Cousens S Snow RW Effect of expanded insecticide‐treated bednet coverage on child survival in rural Kenya: a longitudinal study.Lancet. 2007; 370: 1035-1039Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar]Kenya (Bondo, Kwale, Makueni, and Kisii). PerennialLongitudinal surveys3 yearsAll-cause mortalityStable 10-year age groupLLIN, long-lasting insecticide-treated net; NS, not stated; RCT, randomized controlled trial. Open table in a new tab LLIN, long-lasting insecticide-treated net; NS, not stated; RCT, randomized controlled trial. The scenario presented by Trape et al. might defeat the immense efforts that have been invested in the last decade in malaria control. The results call into question many attempts to model the transmission and epidemiology of malaria [17The malERA Consultative Group on Modeling A research agenda for malaria eradication: modeling.PLoS Med. 2011; 8: e1000403Crossref PubMed Scopus (75) Google Scholar]. Models have incorporated climate, vegetation, other environmental factors, interactions between human immunodeficiency virus and malaria, vaccine introduction, drug efficacy, economic support, and other factors. However, one can hardly predict the behavioural response of mosquitoes to people sleeping under bed-nets. Our understanding of the timeline of the development of resistance to insecticides (in mosquitoes) and to antimalarial drugs (in the malaria parasite) is insufficient. The results of the current study stand largely in contrast to those of previous, larger studies, which showed stable and durable benefits of bed-nets and other malaria control interventions. Longer follow-up might show this to be a temporal fluctuation. The starting point of 8% resistance to pyrethroids might have been favourable for a rapid increase in further resistance acquisition. In any case, the results of this study emphasize the need for surveillance of malaria to detect such events early and enable appropriate intervention. Randomized controlled trials have shown the efficacy of insecticide-treated bed-nets [18Lengeler C Insecticide‐treated bed nets and curtains for preventing malaria.Cochrane Database Syst Rev. 2004; (Article No.: CD000363)https://doi.org/10.1002/14651858.CD000363.pub2Crossref PubMed Google Scholar]. However, their effectiveness in large-scale programme conditions over longer periods of time and long-term compliance in a situation of declining malaria incidence must be monitored. Intensive surveillance such as that conducted in the study in Dielmo [7Trape JF Tall A Diagne N et al.Malaria morbidity and pyrethroid resistance after the introduction of insecticide‐treated bednets and artemisinin‐based combination therapies: a longitudinal study.Lancet Infect Dis. 2011; https://doi.org/10.1016/S1473-3099(11)70194-3Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar] is obviously not feasible in large populations. National cross-sectional data are uninformative, because the prevalence of malaria is heterogeneous in different locations and seasons. However, small-scale intensive surveys coupled with the acquisition of cross-sectional data should be encouraged. Funding for malaria control at this time should take into consideration the increasing need for appropriate surveillance. Nothing to declare.