Benjamin G. Koudou

Multiple-Insecticide Resistance in Anopheles gambiae Mosquitoes, Southern Côte d’Ivoire

Preventing malaria used to seem as simple as killing the vector, the mosquito; however, a recent study shows that this concept is now anything but simple. The highly effective use of insecticide-treated bed nets and indoor insecticide spraying is being challenged by mosquito resistance to insecticides. In West Africa, populations of this mosquito vector are now resistant to all 4 classes of insecticide approved for this use. And no new classes of insecticide are anticipated until 2020, at the earliest. Development of newer classes of insecticide is crucial because if resistance continues unchecked, the hard-earned progress in malaria control in Africa could be quickly reversed.

Effects of pyrethroid resistance on the cost effectiveness of a mass distribution of long-lasting insecticidal nets: a modelling study

BackgroundThe effectiveness of insecticide-treated nets in preventing malaria is threatened by developing resistance against pyrethroids. Little is known about how strongly this affects the effectiveness of vector control programmes.MethodsData from experimental hut studies on the effects of long-lasting, insecticidal nets (LLINs) on nine anopheline mosquito populations, with varying levels of mortality in World Health Organization susceptibility tests, were used to parameterize malaria models. Both simple static models predicting population-level insecticidal effectiveness and protection against blood feeding, and complex dynamic epidemiological models, where LLINs decayed over time, were used. The epidemiological models, implemented in OpenMalaria, were employed to study the impact of a single mass distribution of LLINs on malaria, both in terms of episodes prevented during the effective lifetime of the batch of LLINs, and in terms of net health benefits (NHB) expressed in disability-adjusted life years (DALYs) averted during that period, depending on net type (standard pyrethroid-only LLIN or pyrethroid-piperonyl butoxide combination LLIN), resistance status, coverage and pre-intervention transmission level.ResultsThere were strong positive correlations between insecticide susceptibility status and predicted population level insecticidal effectiveness of and protection against blood feeding by LLIN intervention programmes. With the most resistant mosquito population, the LLIN mass distribution averted up to about 40% fewer episodes and DALYs during the effective lifetime of the batch than with fully susceptible populations. However, cost effectiveness of LLINs was more sensitive to the pre-intervention transmission level and coverage than to susceptibility status. For four out of the six Anopheles gambiae sensu lato populations where direct comparisons between standard LLINs and combination LLINs were possible, combination nets were more cost effective, despite being more expensive. With one resistant population, both net types were equally effective, and with one of the two susceptible populations, standard LLINs were more cost effective.ConclusionDespite being less effective when compared to areas with susceptible mosquito populations, standard and combination LLINs are likely to (still) be cost effective against malaria even in areas with strong pyrethroid resistance. Combination nets are likely to be more cost effective than standard nets in areas with resistant mosquito populations.

Mapping malaria risk among children in Côte d’Ivoire using Bayesian geo-statistical models

BackgroundIn Côte d’Ivoire, an estimated 767,000 disability-adjusted life years are due to malaria, placing the country at position number 14 with regard to the global burden of malaria. Risk maps are important to guide control interventions, and hence, the aim of this study was to predict the geographical distribution of malaria infection risk in children aged <16 years in Côte d’Ivoire at high spatial resolution.MethodsUsing different data sources, a systematic review was carried out to compile and geo-reference survey data on Plasmodium spp. infection prevalence in Côte d’Ivoire, focusing on children aged <16 years. The period from 1988 to 2007 was covered. A suite of Bayesian geo-statistical logistic regression models was fitted to analyse malaria risk. Non-spatial models with and without exchangeable random effect parameters were compared to stationary and non-stationary spatial models. Non-stationarity was modelled assuming that the underlying spatial process is a mixture of separate stationary processes in each ecological zone. The best fitting model based on the deviance information criterion was used to predict Plasmodium spp. infection risk for entire Côte d’Ivoire, including uncertainty.ResultsOverall, 235 data points at 170 unique survey locations with malaria prevalence data for individuals aged <16 years were extracted. Most data points (n = 182, 77.4%) were collected between 2000 and 2007. A Bayesian non-stationary regression model showed the best fit with annualized rainfall and maximum land surface temperature identified as significant environmental covariates. This model was used to predict malaria infection risk at non-sampled locations. High-risk areas were mainly found in the north-central and western area, while relatively low-risk areas were located in the north at the country border, in the north-east, in the south-east around Abidjan, and in the central-west between two high prevalence areas.ConclusionThe malaria risk map at high spatial resolution gives an important overview of the geographical distribution of the disease in Côte d’Ivoire. It is a useful tool for the national malaria control programme and can be utilized for spatial targeting of control interventions and rational resource allocation.

Diversity and transmission competence in lymphatic filariasis vectors in West Africa, and the implications for accelerated elimination of Anopheles-transmitted filariasis

Lymphatic Filariasis (LF) is targeted for elimination by the Global Programme for the Elimination of Lymphatic Filariasis (GPELF). The strategy adopted is based on the density dependent phenomenon of Facilitation, which hypothesizes that in an area where the vector species transmitting Wuchereria bancrofti are Anopheles mosquitoes, it is feasible to eliminate LF using Mass Drug Administration (MDA) because of the inability of Anopheles species to transmit low-density microfilaraemia. Even though earlier studies have shown Anopheles species can exhibit the process of Facilitation in West Africa, observations point towards the process of Limitation in certain areas, in which case vector control is recommended. Studies on Anopheles species in West Africa have also shown genetic differentiation, cryptic taxa and speciation, insecticide resistance and the existence of molecular and chromosomal forms, all of which could influence the vectorial capacity of the mosquitoes and ultimately the elimination goal. This paper outlines the uniqueness of LF vectors in West Africa and the challenges it poses to the 2020 elimination goal, based on the current MDA strategies.

Cross-reactivity of filariais ICT cards in areas of contrasting endemicity of Loa loa and Mansonella perstans in Cameroon: Implications for shrinking of the lymphatic filariasis map in the central African region

Background Immunochromatographic card test (ICT) is a tool to map the distribution of Wuchereria bancrofti. In areas highly endemic for loaisis in DRC and Cameroon, a relationship has been envisaged between high L. loa microfilaria (Mf) loads and ICT positivity. However, similar associations have not been demonstrated from other areas with contrasting levels of L. loa endemicity. This study investigated the cross-reactivity of ICT when mapping lymphatic filariasis (LF) in areas with contrasting endemicity levels of loiasis and mansonellosis in Cameroon. Methodology/Principal Findings A cross-sectional study to assess the prevalence and intensity of W. bancrofti, L. loa and M. perstans was carried out in 42 villages across three regions (East, North-west and South-west) of the Cameroon rainforest domain. Diurnal blood was collected from participants for the detection of circulating filarial antigen (CFA) by ICT and assessment of Mf using a thick blood smear. Clinical manifestations of LF were also assessed. ICT positives and patients clinically diagnosed with lymphoedema were further subjected to night blood collection for the detection of W. bancrofti Mf. Overall, 2190 individuals took part in the study. Overall, 24 individuals residing in 14 communities were tested positive by ICT, with prevalence rates ranging from 0% in the South-west to 2.1% in the North-west. Lymphoedema were diagnosed in 20 individuals with the majority of cases found in the North-west (11/20), and none of them were tested positive by ICT. No Mf of W. bancrofti were found in the night blood of any individual with a positive ICT result or clinical lymphoedema. Positive ICT results were strongly associated with high L. loa Mf intensity with 21 subjects having more than 8,000 L. loa Mf ml/blood (Odds ratio = 15.4; 95%CI: 6.1–39.0; p < 0.001). Similarly, a strong positive association (Spearman’s rho = 0.900; p = 0.037) was observed between the prevalence of L. loa and ICT positivity by area: a rate of 1% or more of positive ICT results was found only in areas with an L. loa Mf prevalence above 15%. In contrast, there was no association between ICT positivity and M. perstans prevalence (Spearman’s rho = - 0.200; p = 0.747) and Mf density (Odds ratio = 1.8; 95%CI: 0.8–4.2; p = 0.192). Conclusions/Significance This study has confirmed the strong association between the ICT positivity and L. loa intensity (Mf/ml of blood) at the individual level. Furthermore, the study has demonstrated that ICT positivity is strongly associated with high L. loa prevalence. These results suggest that the main confounding factor for positive ICT test card results are high levels of L. loa. The findings may indicate that W. bancrofti is much less prevalent in the Central African region where L. loa is highly endemic than previously assumed and accurate re-mapping of the region would be very useful for shrinking of the map of LF distribution.

Combining Organophosphate Treated Wall Linings and Long-lasting Insecticidal Nets for Improved Control of Pyrethroid Resistant Anopheles gambiae

Background New approaches to delivering insecticides need to be developed to improve malaria vector control. Insecticidal durable wall lining (DL) and net wall hangings (NWH) are novel alternatives to indoor residual spraying which can be produced in a long-lasting format. Non-pyrethroid versions could be used in combination with long-lasting insecticidal nets for improved control and management of insecticide resistant vector populations. Methods Experimental hut trials were carried out in Valley du Kou, Burkina Faso to evaluate the efficacy of pirimiphos methyl treated DL and NWH either alone or in combination with LLINs against pyrethroid resistant Anopheles gambiae ss. Comparison was made with pyrethroid DL. Mosquitoes were genotyped for kdr and ace-1R resistant genes to investigate the insecticide resistance management potential of the combination. Results The overall kdr and ace-1R allele frequencies were 0.95 and 0.01 respectively. Mortality with p-methyl DL and NWH alone was higher than with pyrethroid DL alone (>95% vs 40%; P<0.001). Combining pyrethroid DL with LLINs did not show improvement in mortality (48%) compared to the LLIN alone (44%) (P>0.1). Combining p-methyl DL or NWH with LLINs reduced biting rates significantly (8–9%) compared to p-methyl DL and NWH alone (>40%) and killed all An gambiae that entered the huts. Mosquitoes bearing the ace-1R gene were more likely to survive in huts with p-methyl DL alone (p<0.03) whereas all resistant and susceptible genotypes were killed by the combination. Conclusion P-methyl DL and NWH outperformed pyrethroid DL. Combining p-methyl DL and NWH with LLINs could provide significant epidemiological benefits against a vector population which is resistant to pyrethroids but susceptible to organophosphates. There was evidence that the single intervention would select kdr and ace-1R resistance genes and the combination intervention might select less strongly. Technology to bind organophosphates to plastic wall lining would be worth developing.

Willingness to use a rapid diagnostic test for malaria in a rural area of central Côte d’Ivoire

BackgroundMalaria mortality is mainly a direct consequence of inadequate and/or delayed diagnosis and case management. Some important control interventions (e.g. long-lasting insecticidal nests) have contributed to reduce malaria morbidity and mortality in different parts of the world. Moreover, the development and effective use of rapid diagnostic tests (RDTs) hold promise to further enhance the control and elimination of malaria, particularly in areas where health services are deficient. The aim of this study was to determine knowledge, attitudes, practices and beliefs in relation to RDTs for malaria in rural Côte d’Ivoire.MethodsOne hundred individuals from Bozi and Yoho who sought care at the health centre in Bozi and were offered an RDT for malaria were interviewed in April 2010 using a pre-tested questionnaire on practice and perceptions in relation to RDTs for malaria. The relationships between acceptance of RDTs and factors related to opinions were identified, using generalized linear mixed models. Qualitative data from open-ended questions complemented the quantitative analysis.ResultsOnly 34 out of 100 patients who were offered an RDT for malaria were willing to undergo the test. People who perceived blood as a sacred body fluid were less likely to comply with an RDT. The concurrent availability and use of RDTs for HIV and malaria was associated with an unwilling attitude towards RDTs for malaria (Fisher’s exact test, p <0.001). The initial willingness of patients to accept malaria testing with RDTs was significantly related to general fear and wanting to know malaria infection status. For further and regular use of RDTs, a strong relationship was observed between acceptance and the idea that an RDT is a pretext used by health worker to know HIV status (odds ratio (OR) = 16.61, 95% confidence interval (CI) = 1.03-268.5). Those thinking that blood samples were useful for medical diagnoses were 8.31-times (95% CI = 2.22-31.1) more likely to undergo an RDT compared to those rejecting blood sampling as a diagnostic strategy.ConclusionSocio-cultural factors might be barriers for accepting RDTs in general health services. There are social representations of malaria and HIV/AIDS, symbolic for blood or experiences in relation to blood taking and blood-related diseases in relation to the introduction and routine use of RDTs. Special attention should be given to these barriers as otherwise the promotion of RDTs for prompt and effective diagnosis and subsequent management of malaria is hampered.

Combining organophosphate-treated wall linings and long-lasting insecticidal nets fails to provide additional control over long-lasting insecticidal nets alone against multiple insecticide-resistant Anopheles gambiae in Côte d’Ivoire: an experimental hut trial

BackgroundInsecticide-treated wall lining (ITWL) is a new concept in malaria vector control. Some Anopheles gambiae populations in West Africa have developed resistance to all the main classes of insecticides. It needs to be demonstrated whether vector control can be improved or resistance managed when non-pyrethroid ITWL is used alone or together with long-lasting insecticidal nets (LLINs) against multiple insecticide-resistant vector populations.MethodsTwo experimental hut trials were carried out as proofs of concept to evaluate pirimiphos methyl (p-methyl)-treated plastic wall lining (WL) and net wall hangings (NWH) used alone and in combination with LLINs against multiple insecticide-resistant An. gambiae in Tiassalé, Côte d’Ivoire. Comparison was made to commercial deltamethrin WL and genotypes for kdr and ace-1R resistance were monitored.ResultsThe kdr and ace-1R allele frequencies were 0.83 and 0.44, respectively. Anopheles gambiae surviving discriminating concentrations of deltamethrin and p-methyl in WHO resistance tests were 57 and 96%, respectively. Mortality of free-flying An. gambiae in huts with p-methyl WL and NWH (66 and 50%, respectively) was higher than with pyrethroid WL (32%; P < 0.001). Mortality with LLIN was 63%. Mortality with the combination of LLIN plus p-methyl NWH (61%) or LLIN plus p-methyl WL (73%) did not significantly improve upon the LLIN alone or p-methyl WL or NWH alone. Mosquitoes bearing the ace-1R were more likely to survive exposure to p-methyl WL and NWH. Selection of heterozygote and homozygote ace-1R or kdr genotypes was not less likely after exposure to combined LLIN and p-methyl treatments than to single p-methyl treatment. Blood-feeding rates were lower in huts with the pyrethroid LLIN (19%) than with p-methyl WL (72%) or NWH (76%); only LLIN contributed to personal protection.ConclusionsCombining p-methyl WL or NWH with LLINs provided no improvement in An. gambiae control or personal protection over LLIN alone in southern Côte d’Ivoire; neither did the combination manage resistance. Additional resistance mechanisms to kdr and ace-1R probably contributed to the survival of pyrethroid and organophophate-resistant mosquitoes. The study demonstrates the challenge that malaria control programmes will face if resistance to multiple insecticides continues to spread.

Disparities of Plasmodium falciparum infection, malaria-related morbidity and access to malaria prevention and treatment among school-aged children: a national cross-sectional survey in Côte d’Ivoire

BackgroundThere is limited knowledge on the malaria burden of school-aged children in Côte d’Ivoire. The aim of this study was to assess Plasmodium falciparum infection, malaria-related morbidity, use of preventive measures and treatment against malaria, and physical access to health structures among school-aged children across Côte d’Ivoire.MethodsA national, cross-sectional study was designed, consisting of clinical and parasitological examinations and interviews with schoolchildren. More than 5,000 children from 93 schools in Côte d’Ivoire were interviewed to determine household socioeconomic status, self-reported morbidity and means of malaria prevention and treatment. Finger-prick blood samples were collected and Plasmodium infection and parasitaemia determined using Giemsa-stained blood films and a rapid diagnostic test (RDT). Haemoglobin levels and body temperature were measured. Children were classified into wealth quintiles using household assets and principal components analysis (PCA). The concentration index was employed to determine significant trends of health variables according to wealth quintiles. Logistic and binomial negative regression analyses were done to investigate for associations between P. falciparum prevalence and parasitaemia and any health-related variable.ResultsThe prevalence of P. falciparum was 73.9% according to combined microscopy and RDT results with a geometric mean of parasitaemia among infected children of 499 parasites/μl of blood. Infection with P. falciparum was significantly associated with sex, socioeconomic status and study setting, while parasitaemia was associated with age. The rate of bed net use was low compared to the rate of bed net ownership. Preventive measures (bed net ownership, insecticide spray and the reported use of malaria treatment) were more frequently mentioned by children from wealthier households who were at lower risk of P. falciparum infection. Self-reported morbidity (headache) and clinical morbidity (anaemia) were more often reported by children from less wealthy households.ConclusionSeven out of ten school-aged children in Côte d’Ivoire are infected with P. falciparum and malaria-related morbidity is considerable. Furthermore, this study points out that bed net usage is quite low and there are important inequalities in preventive measures and treatment. These results can guide equity-oriented malaria control strategies in Côte d’Ivoire.

No Evidence for Lymphatic Filariasis Transmission in Big Cities Affected by Conflict Related Rural-Urban Migration in Sierra Leone and Liberia

Background In West Africa, the principal vectors of lymphatic filariasis (LF) are Anopheles species with Culex species playing only a minor role in transmission, if any. Being a predominantly rural disease, the question remains whether conflict-related migration of rural populations into urban areas would be sufficient for active transmission of the parasite. Methodology/Principal Findings We examined LF transmission in urban areas in post-conflict Sierra Leone and Liberia that experienced significant rural-urban migration. Mosquitoes from Freetown and Monrovia, were analyzed for infection with Wuchereria bancrofti. We also undertook a transmission assessment survey (TAS) in Bo and Pujehun districts in Sierra Leone. The majority of the mosquitoes collected were Culex species, while Anopheles species were present in low numbers. The mosquitoes were analyzed in pools, with a maximum of 20 mosquitoes per pool. In both countries, a total of 1731 An. gambiae and 14342 Culex were analyzed for W. bancrofti, using the PCR. Two pools of Culex mosquitoes and 1 pool of An. gambiae were found infected from one community in Freetown. Pool screening analysis indicated a maximum likelihood of infection of 0.004 (95% CI of 0.00012–0.021) and 0.015 (95% CI of 0.0018–0.052) for the An. gambiae and Culex respectively. The results indicate that An. gambiae is present in low numbers, with a microfilaria prevalence breaking threshold value not sufficient to maintain transmission. The results of the TAS in Bo and Pujehun also indicated an antigen prevalence of 0.19% and 0.67% in children, respectively. This is well below the recommended 2% level for stopping MDA in Anopheles transmission areas, according to WHO guidelines. Conclusions We found no evidence for active transmission of LF in cities, where internally displaced persons from rural areas lived for many years during the more than 10 years conflict in Sierra Leone and Liberia.