The clinical efficacy of artemether/lumefantrine (Coartem®)

Background

In March 2008, the Solomon Islands and Vanuatu governments raised the goal of their National Malaria Programmes from control to elimination. Vector control measures, such as indoor residual spraying (IRS) and long-lasting insecticidal bed nets (LLINs) are key integral components of this programme. Compliance with these interventions is dependent on their acceptability and on the socio-cultural context of the local population. These factors need to be investigated locally prior to programme implementation.

Method

Twelve focus group discussions (FGDs) were carried out in Malaita and Temotu Provinces, Solomon Islands in 2008. These discussions explored user perceptions of acceptability and preference for three brands of long-lasting insecticide-treated bed nets (LLINs) and identified a number of barriers to their proper and consistent use.

Results

Mosquito nuisance and perceived threat of malaria were the main determinants of bed net use. Knowledge of malaria and the means to prevent it were not sufficient to guarantee compliance with LLIN use. Factors such as climate, work and evening social activities impact on the use of bed nets, particularly in men. LLIN acceptability plays a varying role in compliance with their use in villages involved in this study. Participants in areas of reported high and year round mosquito nuisance and perceived threat of malaria reported LLIN use regardless of any reported unfavourable characteristics. Those in areas of low or seasonal mosquito nuisance were more likely to describe the unfavourable characteristics of LLINs as reasons for their intermittent or non-compliance. The main criterion for LLIN brand acceptability was effectiveness in preventing mosquito bites and malaria. Discussions highlighted considerable confusion around LLIN care and washing which may be impacting on their effectiveness and reducing their acceptability in Solomon Islands.

Conclusion

Providing LLINs that are acceptable will be more important for improving compliance in areas of low or seasonal mosquito nuisance and malaria transmission. The implications of these findings on malaria elimination in Solomon Islands are discussed.     

Modelling the cost-effectiveness of mass screening and treatment for reducing Plasmodium falciparum malaria burden

Background

Past experience and modelling suggest that, in most cases, mass treatment strategies are not likely to succeed in interrupting Plasmodium falciparum malaria transmission. However, this does not preclude their use to reduce disease burden. Mass screening and treatment (MSAT) is preferred to mass drug administration (MDA), as the latter involves massive over-use of drugs. This paper reports simulations of the incremental cost-effectiveness of well-conducted MSAT campaigns as a strategy for P. falciparum malaria disease-burden reduction in settings with varying receptivity (ability of the combined vector population in a setting to transmit disease) and access to case management.

Methods

MSAT incremental cost-effectiveness ratios (ICERs) were estimated in different sub-Saharan African settings using simulation models of the dynamics of malaria and a literature-based MSAT cost estimate. Imported infections were simulated at a rate of two per 1,000 population per annum. These estimates were compared to the ICERs of scaling up case management or insecticide-treated net (ITN) coverage in each baseline health system, in the absence of MSAT.

Results

MSAT averted most episodes, and resulted in the lowest ICERs, in settings with a moderate level of disease burden. At a low pre-intervention entomological inoculation rate (EIR) of two infectious bites per adult per annum (IBPAPA) MSAT was never more cost-effective than scaling up ITNs or case management coverage. However, at pre-intervention entomological inoculation rates (EIRs) of 20 and 50 IBPAPA and ITN coverage levels of 40 or 60%, respectively, the ICER of MSAT was similar to that of scaling up ITN coverage further.

Conclusions

In all the transmission settings considered, achieving a minimal level of ITN coverage is a “best buy”. At low transmission, MSAT probably is not worth considering. Instead, MSAT may be suitable at medium to high levels of transmission and at moderate ITN coverage. If undertaken as a burden-reducing intervention, MSAT should be continued indefinitely and should complement, not replace, case management and vector control interventions.     

Community participation for malaria elimination in Tafea Province, Vanuatu: Part I. Maintaining motivation for prevention practices in the context of disappearing disease

Background

In Uganda, long-lasting insecticidal nets (LLIN) have been predominantly delivered through two public sector channels: targeted campaigns or routine antenatal care (ANC) services. Their combination in a mixed-model strategy is being advocated to quickly increase LLIN coverage and maintain it over time, but there is little evidence on the efficiency of each system. This study evaluated the two delivery channels regarding LLIN retention and use, and estimated the associated costs, to contribute towards the evidence-base on LLIN delivery channels in Uganda.

Methods

Household surveys were conducted 5-7 months after LLIN distribution, combining questionnaires with visual verification of LLIN presence. Focus groups and interviews were conducted to further investigate determinants of LLIN retention and use. Campaign distribution was evaluated in Jinja and Adjumani while ANC distribution was evaluated only in the latter district. Costs were calculated from the provider perspective through retrospective analysis of expenditure data, and effects were estimated as cost per LLIN delivered and cost per treated-net-year (TNY). These effects were calculated for the total number of LLINs delivered and for those retained and used.

Results

After 5-7 months, over 90% of LLINs were still owned by recipients, and between 74% (Jinja) and 99% (ANC Adjumani) were being used. Costing results showed that delivery was cheapest for the campaign in Jinja and highest for the ANC channel, with economic delivery cost per net retained and used of USD 1.10 and USD 2.31, respectively. Financial delivery costs for the two channels were similar in the same location, USD 1.04 for campaign or USD 1.07 for ANC delivery in Adjumani, but differed between locations (USD 0.67 for campaign delivery in Jinja). Economic cost for ANC distribution were considerably higher (USD 2.27) compared to campaign costs (USD 1.23) in Adjumani.

Conclusions

Targeted campaigns and routine ANC services can both achieve high LLIN retention and use among the target population. The comparatively higher economic cost of delivery through ANC facilities was at least partially due to the relatively short time this system had been in existence. Further studies comparing the cost of well-established ANC delivery with LLIN campaigns and other delivery channels are thus encouraged.     

Time Series Analysis of Trends in Malaria Cases and Deaths at Hospitals and the Effect of Antimalarial Interventions, 2001–2011, Ethiopia

Background

The Government of Ethiopia and its partners have deployed artemisinin-based combination therapies (ACT) since 2004 and long-lasting insecticidal nets (LLINs) since 2005. Malaria interventions and trends in malaria cases and deaths were assessed at hospitals in malaria transmission areas during 2001–2011.

Methods

Regional LLINs distribution records were used to estimate the proportion of the population-at-risk protected by LLINs. Hospital records were reviewed to estimate ACT availability. Time-series analysis was applied to data from 41 hospitals in malaria risk areas to assess trends of malaria cases and deaths during pre-intervention (2001–2005) and post-interventions (2006–2011) periods.

Findings

The proportion of the population-at-risk potentially protected by LLINs increased to 51% in 2011. The proportion of facilities with ACTs in stock exceeded 87% during 2006–2011. Among all ages, confirmed malaria cases in 2011 declined by 66% (95% confidence interval [CI], 44–79%) and SPR by 37% (CI, 20%–51%) compared to the level predicted by pre-intervention trends. In children under 5 years of age, malaria admissions and deaths fell by 81% (CI, 47%–94%) and 73% (CI, 48%–86%) respectively. Optimal breakpoint of the trendlines occurred between January and June 2006, consistent with the timing of malaria interventions. Over the same period, non-malaria cases and deaths either increased or remained unchanged, the number of malaria diagnostic tests performed reflected the decline in malaria cases, and rainfall remained at levels supportive of malaria transmission.

Conclusions

Malaria cases and deaths in Ethiopian hospitals decreased substantially during 2006–2011 in conjunction with scale-up of malaria interventions. The decrease could not be accounted for by changes in hospital visits, malaria diagnostic testing or rainfall. However, given the history of variable malaria transmission in Ethiopia, more data would be required to exclude the possibility that the decrease is due to other factors.     

Possession and Usage of Insecticidal Bed Nets among the People of Uganda: Is BRAC Uganda Health Programme Pursuing a Pro-Poor Path?

Background

The use of insecticidal bed nets is found to be an effective public health tool for control of malaria, especially for under-five children and pregnant women. BRAC, an indigenous Bangladeshi non-governmental development organization, started working in the East African state of Uganda in June 2006. As part of its efforts to improve the health and well-being of its participants, BRAC Uganda has been distributing long lasting insecticide-treated bed nets (LLIN) at a subsidized price through health volunteers since February 2008. This study was conducted in March-April 2009 to examine how equitable the programme had been in consistence with BRAC Uganda''s pro-poor policy.

Methodology/Principal Findings

Information on possession of LLINs and relevant knowledge on its proper use and maintenance was collected from households either with an under-five child and/or a pregnant woman. The sample included three villages from each of the 10 branch offices where BRAC Uganda''s community-based health programme was operating. Data were collected by trained enumerators through face-to-face interviews using a hand-held personal digital assistant (PDA). Findings reveal that the study population had superficial knowledge on malaria and its transmission, including the use and maintenance of LLINs. The households'' rate of possession of bed nets (41–59%), and the proportion of under-five children (17–19%) and pregnant women (25–27%) who reported sleeping under an LLIN were not encouraging. Inequity was observed in the number of LLINs possessed by the households, in the knowledge on its use and maintenance, and between the two programme areas.

Conclusions/Significance

The BRAC Uganda''s LLINs distribution at a subsidized price appeared to be inadequate and inequitable, and BRAC''s knowledge dissemination is insufficient for initiating preventive actions such as proper use of LLINs to interrupt malaria transmission. Findings contribute to the on-going debate on LLINs distribution in Africa and make a strong case for its free distribution.     

Highly focused anopheline breeding sites and malaria transmission in Dakar

Background

Urbanization has a great impact on the composition of the vector system and malaria transmission dynamics. In Dakar, some malaria cases are autochthonous but parasite rates and incidences of clinical malaria attacks have been recorded at low levels. Ecological heterogeneity of malaria transmission was investigated in Dakar, in order to characterize the Anopheles breeding sites in the city and to study the dynamics of larval density and adult aggressiveness in ten characteristically different urban areas.

Methods

Ten study areas were sampled in Dakar and Pikine. Mosquitoes were collected by human landing collection during four nights in each area (120 person-nights). The Plasmodium falciparum circumsporozoite (CSP) index was measured by ELISA and the entomological inoculation rates (EIR) were calculated. Open water collections in the study areas were monitored weekly for physico-chemical characterization and the presence of anopheline larvae. Adult mosquitoes and hatched larvae were identified morphologically and by molecular methods.

Results

In September-October 2007, 19,451 adult mosquitoes were caught among which, 1,101 were Anopheles gambiae s.l. The Human Biting Rate ranged from 0.1 bites per person per night in Yoff Village to 43.7 in Almadies. Seven out of 1,101 An. gambiae s.l. were found to be positive for P. falciparum (CSP index = 0.64%). EIR ranged from 0 infected bites per person per year in Yoff Village to 16.8 in Almadies. The An. gambiae complex population was composed of Anopheles arabiensis (94.8%) and Anopheles melas (5.2%). None of the An. melas were infected with P. falciparum. Of the 54 water collection sites monitored, 33 (61.1%) served as anopheline breeding sites on at least one observation. No An. melas was identified among the larval samples. Some physico-chemical characteristics of water bodies were associated with the presence/absence of anopheline larvae and with larval density. A very close parallel between larval and adult densities was found in six of the ten study areas.

Conclusion

The results provide evidence of malaria transmission in downtown Dakar and its surrounding suburbs. Spatial heterogeneity of human biting rates was very marked and malaria transmission was highly focal. In Dakar, mean figures for transmission would not provide a comprehensive picture of the entomological situation; risk evaluation should therefore be undertaken on a small scale.     

Traditional Nets Interfere with the Uptake of Long-Lasting Insecticidal Nets in the Peruvian Amazon: The Relevance of Net Preference for Achieving High Coverage and Use

Background

While coverage of long-lasting insecticide-treated nets (LLIN) has steadily increased, a growing number of studies report gaps between net ownership and use. We conducted a mixed-methods social science study assessing the importance of net preference and use after Olyset® LLINs were distributed through a mass campaign in rural communities surrounding Iquitos, the capital city of the Amazonian region of Peru.

Methods

The study was conducted in the catchment area of the Paujil and Cahuide Health Centres (San Juan district) between July 2007 and November 2008. During a first qualitative phase, participant observation and in-depth interviews collected information on key determinants for net preference and use. In a second quantitative phase, a survey among recently confirmed malaria patients evaluated the acceptability and use of both LLINs and traditional nets, and a case control study assessed the association between net preference/use and housing structure (open vs. closed houses).

Results

A total of 10 communities were selected for the anthropological fieldwork and 228 households participated in the quantitative studies. In the study area, bed nets are considered part of the housing structure and are therefore required to fulfil specific architectural and social functions, such as providing privacy and shelter, which the newly distributed Olyset® LLINs ultimately did not. The LLINs'' failure to meet these criteria could mainly be attributed to their large mesh size, transparency and perceived ineffectiveness to protect against mosquitoes and other insects, resulting in 63.3% of households not using any of the distributed LLINs. Notably, LLIN usage was significantly lower in houses with no interior or exterior walls (35.2%) than in those with walls (73.8%) (OR = 5.2, 95CI [2.2; 12.3], p<0.001).

Conclusion

Net preference can interfere with optimal LLIN use. In order to improve the number of effective days of LLIN protection per dollar spent, appropriate quantitative and qualitative methods for collecting information on net preference should be developed before any LLIN procurement decision is made.     

Dry season determinants of malaria disease and net use in Benin, West Africa

Background

To achieve malaria eradication, control efforts have to be sustained even when the incidence of malaria cases becomes low during the dry season. In this work, malaria incidence and its determinants including bed net use were investigated in children of under 5 years of age in 28 villages in southern Benin during the dry season.

Methods and Findings

Mean malaria clinical incidence was measured in children aged 0–5 years by active case detection in 28 villages of the Ouidah-Kpomasse-Tori Bossito sanitary district between November 2007 and March 2008. Using Poisson mixed-effect models, malaria incidence was assessed according to the level of transmission by different vector species, and Long-Lasting Insecticide-treated mosquito Nets (LLIN) use and ownership. Then, a Binomial mixed-effect model was developed to assess whether nighttime temperature (derived from MODIS remote sensing data), biting nuisance and LLIN ownership are good predictors of LLIN use >60%. Results suggested that Anopheles funestus (Incidence Rates Ratio (IRR) = 3.38 [IC95 1.91–6]) rather than An. gambiae s.s. is responsible for malaria transmission. A rate of LLIN use >60% was associated with a lower risk of malaria (IRR = 0.6 [IC95 0.37–0.99]). Low nocturnal temperature and high biting nuisance were good predictors of LLIN use >60%.

Conclusions

As recommended by the Malaria Eradication (MalERA) Consultative Group on Modelling, there is a need to understand better the effects of seasonality on malaria morbidity. This study highlights the need to take into account the specificity of malaria epidemiology during the dry-hot season and get a better understanding of the factors that influence malaria incidence and net use. These findings should help National Malaria Control Programmes to implement more effective and sustainable malaria control strategies in Africa.     

Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination

Background

Malaria remains a major public health problem in Ethiopia. Pyrethroid-treated mosquito nets are one of the major tools available for the prevention and control of malaria transmission. PermaNet^® is a long-lasting insecticide-treated net (LLIN) recommended by WHO for malaria control.

Objective

The objective of the study was to assess utilization and retention of PermaNet^® nets distributed for malaria control in Buie and Fentalie districts and monitor the bio-efficacy of the nets using the WHO cone bioassay test procedures.

Methods

A cross sectional study was carried out by interviewing household heads or their representative in Buie and Fentalie districts. The two districts were selected based on a priori knowledge of variations on ethnic background and housing construction. Clusters of houses were chosen within each of the study villages for selection of households. 20 households that had received one or more PermaNet^® nets were chosen randomly from the clusters in each village. A total of eight used PermaNet^® nets were collected for the bio-efficacy test. The bio-efficacy of PermaNet^® nets was monitored according to the standard WHO procedures using a susceptible colony of Anopheles arabiensis to deltamethrin.

Results

A total of 119 household heads were interviewed during the study. The retention rate of nets that were distributed in 2005 and 2006 season was 72%. A total of 62.2% of the interviewees claimed children under five years of age slept under LLIN, while only 50.7% of the nets were observed to be hanged inside houses when used as a proxy indicator of usage of LLIN. For the bio-efficacy test the mean knock-down was 94% and 100%, while the mean mortality rate observed after 24 hr holding period was 72.2% and 67% for Buie and Fentalie districts respectively.

Conclusion

The study revealed a moderately high retention of PermaNet^® in the study villages and effectiveness of the nets when tested according to the standard WHO procedure.     

Modelling entomological-climatic interactions of Plasmodium falciparum malaria transmission in two Colombian endemic-regions: contributions to a National Malaria Early Warning System

Background

Malaria has recently re-emerged as a public health burden in Colombia. Although the problem seems to be climate-driven, there remain significant gaps of knowledge in the understanding of the complexity of malaria transmission, which have motivated attempts to develop a comprehensive model.

Methods

The mathematical tool was applied to represent Plasmodium falciparum malaria transmission in two endemic-areas. Entomological exogenous variables were estimated through field campaigns and laboratory experiments. Availability of breeding places was included towards representing fluctuations in vector densities. Diverse scenarios, sensitivity analyses and instabilities cases were considered during experimentation-validation process.

Results

Correlation coefficients and mean square errors between observed and modelled incidences reached 0.897–0.668 (P > 0.95) and 0.0002–0.0005, respectively. Temperature became the most relevant climatic parameter driving the final incidence. Accordingly, malaria outbreaks are possible during the favourable epochs following the onset of El Niño warm events. Sporogonic and gonotrophic cycles showed to be the entomological key-variables controlling the transmission potential of mosquitoes' population. Simulation results also showed that seasonality of vector density becomes an important factor towards understanding disease transmission.

Conclusion

The model constitutes a promising tool to deepen the understanding of the multiple interactions related to malaria transmission conducive to outbreaks. In the foreseeable future it could be implemented as a tool to diagnose possible dynamical patterns of malaria incidence under several scenarios, as well as a decision-making tool for the early detection and control of outbreaks. The model will be also able to be merged with forecasts of El Niño events to provide a National Malaria Early Warning System.     

Long-Lasting Insecticidal Nets Are Synergistic with Mass Drug Administration for Interruption of Lymphatic Filariasis Transmission in Nigeria

In central Nigeria Anopheles mosquitoes transmit malaria and lymphatic filariasis (LF). The strategy used for interrupting LF transmission in this area is annual mass drug administration (MDA) with albendazole and ivermectin, but after 8 years of MDA, entomological evaluations in sentinel villages showed continued low-grade mosquito infection rates of 0.32%. After long-lasting insecticidal net (LLIN) distribution by the national malaria program in late 2010, however, we were no longer able to detect infected vectors over a 24-month period. This is evidence that LLINs are synergistic with MDA in interrupting LF transmission.     

Human Exposure to Early Morning Anopheles funestus Biting Behavior and Personal Protection Provided by Long-Lasting Insecticidal Nets

A shift towards early morning biting behavior of the major malaria vector Anopheles funestus have been observed in two villages in south Benin following distribution of long-lasting insecticidal nets (LLINs), but the impact of these changes on the personal protection efficacy of LLINs was not evaluated. Data from human and An. funestus behavioral surveys were used to measure the human exposure to An. funestus bites through previously described mathematical models. We estimated the personal protection efficacy provided by LLINs and the proportions of exposure to bite occurring indoors and/or in the early morning. Average personal protection provided by using of LLIN was high (≥80% of the total exposure to bite), but for LLIN users, a large part of remaining exposure occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoué) and/or in the early morning (38.5% in Tokoli-V and 69.4% in Lokohoué). This study highlights the crucial role of LLIN use and the possible need to develop new vector control strategies targeting malaria vectors with outdoor and early morning biting behavior. This multidisciplinary approach that supplements entomology with social science and mathematical modeling illustrates just how important it is to assess where and when humans are actually exposed to malaria vectors before vector control program managers, policy-makers and funders conclude what entomological observations imply.     

Are Long-Lasting Insecticidal Nets Effective for Preventing Childhood Deaths among Non-Net Users? A Community-Based Cohort Study in Western Kenya

Background

Increasing the distribution and use of insecticide-treated nets (ITNs) in Sub-Saharan Africa has made controlling malaria with ITNs more practical. We evaluated community effects induced by ITNs, specifically long-lasting insecticidal nets (LLINs), under ordinary conditions in an endemic malaria area of Western Kenya.

Methods

Using the database from Mbita Health and Demographic Surveillance System (HDSS), children younger than 5 years old were assessed over four survey periods. We analyzed the effect of bed net usage, LLIN density and population density of young people around a child on all-cause child mortality (ACCM) rates using Cox PH models.

Results

During the study, 14,554 children were followed and 250 deaths were recorded. The adjusted hazard ratios (HRs) for LLIN usage compared with no net usage were not significant among the models: 1.08 (95%CI 0.76–1.52), 1.19 (95%CI 0.69–2.08) and 0.92 (95%CI 0.42–2.02) for LLIN users, untreated net users, and any net users, respectively. A significant increasing linear trend in risk across LLIN density quartiles (HR = 1.25; 95%CI 1.03–1.51) and a decreasing linear trend in risk across young population density quartiles among non-net user children (HR = 0.77; 95%CI 0.63–0.94) were observed.

Conclusions

Although our data showed that current LLIN coverage level (about 35%) could induce a community effect to protect children sleeping without bed nets even in a malaria-endemic area, it appears that a better system is needed to monitor the current malaria situation globally in order to optimize malaria control programs with limited resources.     

Bed Net Durability Assessments: Exploring a Composite Measure of Net Damage

Background

The durability of Long Lasting Insecticidal Nets (LLINs) in field conditions is of great importance for malaria prevention and control efforts; however, the physical integrity of the net fabric is not well understood making it challenging to determine overall effectiveness of nets as they age. The 2011 World Health Organization Pesticide Evaluation Scheme (WHOPES) guidelines provide a simple, standardized method using a proportional hole index (PHI) for assessing net damage with the intent to provide national malaria control programs with guidelines to assess the useful life of LLINS and estimate the rate of replacement.

Methods

We evaluated the utility of the PHI measure using 409 LLINs collected over three years in Nampula Province, Mozambique following a mass distribution campaign in 2008. For each LLIN the diameter and distance from the bottom of the net were recorded for every hole. Holes were classified into four size categories and a PHI was calculated following WHOPES guidelines. We investigate how the size, shape, and location of holes influence the PHI. The areas of the WHOPES defined categories were compared to circular and elliptical areas based on approximate shape and actual measured axes of each hole and the PHI was compared to cumulative damaged surface area of the LLIN.

Results

The damaged area of small, medium, large, and extra-large holes was overestimated using the WHOPES categories compared to elliptical areas using the actual measured axes. Similar results were found when comparing to circular areas except for extra-large holes which were underestimated. (Wilcoxon signed rank test of differences p< 0.0001 for all sizes). Approximating holes as circular overestimated hole surface area by 1.5 to 2 times or more. There was a significant difference in the mean number of holes < 0.5 cm by brand and there were more holes of all sizes on the bottom of nets than the top. For a range of hypothetical PHI thresholds used to designate a “failed LLIN”, roughly 75 to 80% of failed LLINs were detected by considering large and extra-large holes alone, but sensitivity varied by brand.

Conclusions

Future studies may refine the PHI to better approximate overall damaged surface area. Furthermore, research is needed to identify whether or not appropriate PHI thresholds can be used to deem a net no longer protective. Once a cutoff is selected, simpler methods of determining the effective lifespan of LLINs can help guide replacement strategies for malaria control programs.     

Malaria vectors and transmission dynamics in coastal south-western Cameroon

Background

Malaria is a major public health problem in Cameroon. Unlike in the southern forested areas where the epidemiology of malaria has been better studied prior to the implementation of control activities, little is known about the distribution and role of anophelines in malaria transmission in the coastal areas.

Methods

A 12-month longitudinal entomological survey was conducted in Tiko, Limbe and Idenau from August 2001 to July 2002. Mosquitoes captured indoors on human volunteers were identified morphologically. Species of the Anopheles gambiae complex were identified using the polymerase chain reaction (PCR). Mosquito infectivity was detected by the enzyme-linked immunosorbent assay and PCR. Malariometric indices (plasmodic index, gametocytic index, parasite species prevalence) were determined in three age groups (<5 yrs, 5–15 yrs, >15 yrs) and followed-up once every three months.

Results

In all, 2,773 malaria vectors comprising Anopheles gambiae (78.2%), Anopheles funestus (17.4%) and Anopheles nili (7.4%) were captured. Anopheles melas was not anthropophagic. Anopheles gambiae had the highest infection rates. There were 287, 160 and 149 infective bites/person/year in Tiko, Limbe and Idenau, respectively. Anopheles gambiae accounted for 72.7%, An. funestus for 23% and An. nili for 4.3% of the transmission. The prevalence of malaria parasitaemia was 41.5% in children <5 years of age, 31.5% in those 5–15 years and 10.5% in those >15 years, and Plasmodium falciparum was the predominant parasite species.

Conclusion

Malaria transmission is perennial, rainfall dependent and An. melas does not contribute to transmission. These findings are important in the planning and implementation of malaria control activities in coastal Cameroon and West Africa.

     

Ensemble Modeling of the Likely Public Health Impact of a Pre-Erythrocytic Malaria Vaccine

Background

The RTS,S malaria vaccine may soon be licensed. Models of impact of such vaccines have mainly considered deployment via the World Health Organization''s Expanded Programme on Immunization (EPI) in areas of stable endemic transmission of Plasmodium falciparum, and have been calibrated for such settings. Their applicability to low transmission settings is unclear. Evaluations of the efficiency of different deployment strategies in diverse settings should consider uncertainties in model structure.

Methods and Findings

An ensemble of 14 individual-based stochastic simulation models of P. falciparum dynamics, with differing assumptions about immune decay, transmission heterogeneity, and treatment access, was constructed. After fitting to an extensive library of field data, each model was used to predict the likely health benefits of RTS,S deployment, via EPI (with or without catch-up vaccinations), supplementary vaccination of school-age children, or mass vaccination every 5 y. Settings with seasonally varying transmission, with overall pre-intervention entomological inoculation rates (EIRs) of two, 11, and 20 infectious bites per person per annum, were considered. Predicted benefits of EPI vaccination programs over the simulated 14-y time horizon were dependent on duration of protection. Nevertheless, EPI strategies (with an initial catch-up phase) averted the most deaths per dose at the higher EIRs, although model uncertainty increased with EIR. At two infectious bites per person per annum, mass vaccination strategies substantially reduced transmission, leading to much greater health effects per dose, even at modest coverage.

Conclusions

In higher transmission settings, EPI strategies will be most efficient, but vaccination additional to the EPI in targeted low transmission settings, even at modest coverage, might be more efficient than national-level vaccination of infants. The feasibility and economics of mass vaccination, and the circumstances under which vaccination will avert epidemics, remain unclear. The approach of using an ensemble of models provides more secure conclusions than a single-model approach, and suggests greater confidence in predictions of health effects for lower transmission settings than for higher ones. Please see later in the article for the Editors'' Summary     

Community screening and treatment of asymptomatic carriers of <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis

Background

Asymptomatic carriers of Plasmodium falciparum serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area.

Methods

Using computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of P. falciparum asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell et al (originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions.

Results

The simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention.

Conclusions

Community screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.

     

Large-scale use of mosquito larval source management for malaria control in Africa: a cost analysis

Background

At present, large-scale use of two malaria vector control methods, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) is being scaled up in Africa with substantial funding from donors. A third vector control method, larval source management (LSM), has been historically very successful and is today widely used for mosquito control globally, except in Africa. With increasing risk of insecticide resistance and a shift to more exophilic vectors, LSM is now under re-evaluation for use against afro-tropical vector species. Here the costs of this intervention were evaluated.

Methods

The 'ingredients approach' was used to estimate the economic and financial costs per person protected per year (pppy) for large-scale LSM using microbial larvicides in three ecologically diverse settings: (1) the coastal metropolitan area of Dar es Salaam in Tanzania, (2) a highly populated Kenyan highland area (Vihiga District), and (3) a lakeside setting in rural western Kenya (Mbita Division). Two scenarios were examined to investigate the cost implications of using alternative product formulations. Sensitivity analyses on product prices were carried out.

Results

The results show that for programmes using the same granular formulation larviciding costs the least pppy in Dar es Salaam (US$0.94), approximately 60% more in Vihiga District (US$1.50) and the most in Mbita Division (US$2.50). However, these costs are reduced substantially if an alternative water-dispensable formulation is used; in Vihiga, this would reduce costs to US$0.79 and, in Mbita Division, to US$1.94. Larvicide and staff salary costs each accounted for approximately a third of the total economic costs per year. The cost pppy depends mainly on: (1) the type of formulation required for treating different aquatic habitats, (2) the human population density relative to the density of aquatic habitats and (3) the potential to target the intervention in space and/or time.

Conclusion

Costs for LSM compare favourably with costs for IRS and LLINs, especially in areas with moderate and focal malaria transmission where mosquito larval habitats are accessible and well defined. LSM presents an attractive tool to be integrated in ongoing malaria control effort in such settings. Further data on the epidemiological health impact of larviciding is required to establish cost effectiveness.     

Species Shifts in the Anopheles gambiae Complex: Do LLINs Successfully Control Anopheles arabiensis?

Introduction

High coverage of conventional and long-lasting insecticide treated nets (ITNs and LLINs) in parts of E Africa are associated with reductions in local malaria burdens. Shifts in malaria vector species ratio have coincided with the scale-up suggesting that some species are being controlled by ITNs/LLINs better than others.

Methods

Between 2005–2006 six experimental hut trials of ITNs and LLINs were conducted in parallel at two field stations in northeastern Tanzania; the first station was in Lower Moshi Rice Irrigation Zone, an area where An. arabiensis predominates, and the second was in coastal Muheza, where An. gambiae and An. funestus predominate. Five pyrethroids and one carbamate insecticide were evaluated on nets in terms of insecticide-induced mortality, blood-feeding inhibition and exiting rates.

Results

In the experimental hut trials mortality of An. arabiensis was consistently lower than that of An. gambiae and An. funestus. The mortality rates in trials with pyrethroid-treated nets ranged from 25–52% for An. arabiensis, 63–88% for An. gambiae s.s. and 53–78% for An. funestus. All pyrethroid-treated nets provided considerable protection for the occupants, despite being deliberately holed, with blood-feeding inhibition (percentage reduction in biting rates) being consistent between species. Veranda exiting rates did not differ between species. Percentage mortality of mosquitoes tested in cone bioassays on netting was similar for An. gambiae and An. arabiensis.

Conclusions

LLINs and ITNs treated with pyrethroids were more effective at killing An. gambiae and An. funestus than An. arabiensis. This could be a major contributing factor to the species shifts observed in East Africa following scale up of LLINs. With continued expansion of LLIN coverage in Africa An. arabiensis is likely to remain responsible for residual malaria transmission, and species shifts might be reported over larger areas. Supplementary control measures to LLINs may be necessary to control this vector species.