Margaret Pinder

Reduction of Malaria Transmission to Anopheles Mosquitoes with a Six-Dose Regimen of Co-Artemether

Background Resistance of malaria parasites to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) is increasing in prevalence in Africa. Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes. Thus, drug combinations must be identified which minimise gametocyte emergence in treated cases, and so prevent selective transmission of parasites resistant to any of the partner drugs. Methods and Findings In a randomised controlled trial, 497 children with uncomplicated falciparum malaria were treated with CQ and SP (three doses and one dose respectively; n = 91), or six doses of artemether in fixed combination with lumefantrine (co-artemether [Coartem, Riamet]) (n = 406). Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7, 14, and 28 d after treatment. The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes. Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP (30 of 378 [7.94%] versus 42 of 86 [48.8%]; p < 0.0001). Carriers in the co-artemether group harboured gametocytes at significantly lower densities, for shorter periods (0.3 d versus 4.2 d; p < 0.0001) and were less infectious to mosquitoes at day 7 (p < 0.001) than carriers who had received CQ/SP. Conclusions Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum. Our results suggest that co-artemether has specific activity against immature sequestered gametocytes, and has the capacity to minimise transmission of drug-resistant parasites.

Changes in house design reduce exposure to malaria mosquitoes

House design may affect an individuals exposure to malaria parasites, and hence to disease. We conducted a randomized‐controlled study using experimental huts in rural Gambia, to determine whether installing a ceiling or closing the eaves could protect people from malaria mosquitoes. Five treatments were tested against a control hut: plywood ceiling; synthetic‐netting ceiling; insecticide‐treated synthetic‐netting ceiling (deltamethrin 12.5u2003mg/m2); plastic insect‐screen ceiling; or the eaves closed with mud. The acceptability of such interventions was investigated by discussions with local communities. House entry by Anopheles gambiae, the principal African malaria vector, was reduced by the presence of a ceiling: plywood (59% reduction), synthetic‐netting (79%), insecticide‐treated synthetic‐netting (78%), plastic insect‐screen (80%, Pu2003<u20030.001 in all cases) and closed eaves (37%, ns). Similar reductions were also seen with Mansonia spp., vectors of lymphatic filariasis and numerous arboviruses. Netting and insect‐screen ceilings probably work as decoy traps attracting mosquitoes into the roof space, but not the room. Ceilings are likely to be well accepted and may be of greatest benefit in areas of low to moderate transmission and when used in combination with other malaria control strategies.

Efficacy of indoor residual spraying with dichlorodiphenyltrichloroethane against malaria in Gambian communities with high usage of long-lasting insecticidal mosquito nets: a cluster-randomised controlled trial

BACKGROUNDnAlthough many malaria control programmes in sub-Saharan Africa use indoor residual spraying with long-lasting insecticidal nets (LLINs), the two studies assessing the benefit of the combination of these two interventions gave conflicting results. We aimed to assess whether the addition of indoor residual spraying to LLINs provided a significantly different level of protection against clinical malaria in children or against house entry by vector mosquitoes.nnnMETHODSnIn this two-arm cluster, randomised, controlled efficacy trial we randomly allocated clusters of Gambian villages using a computerised algorithm to LLINs alone (n=35) or indoor residual spraying with dichlorodiphenyltrichloroethane plus LLINs (n=35). In each cluster, 65-213 children, aged 6 months to 14 years, were surveyed at the start of the 2010 transmission season and followed in 2010 and 2011 by passive case detection for clinical malaria. Exposure to parasite transmission was assessed by collection of vector mosquitoes with both light and exit traps indoors. Primary endpoints were the incidence of clinical malaria assessed by passive case detection and number of Anopheles gambiae sensu lato mosquitoes collected per light trap per night. Intervention teams had no role in data collection and the data collection teams were not informed of the spray status of villages. The trial is registered at the ISRCTN registry, number ISRCTN01738840.nnnFINDINGSnLLIN coverage in 2011 was 3510 (93%) of 3777 children in the indoor residual spraying plus LLIN group and 3622 (95.5%) of 3791 in the LLIN group. In 2010, 7845 children were enrolled, 7829 completed passive case detection, and 7697 (98%) had complete clinical and covariate data. In 2011, 7009 children remained in the study, 648 more were enrolled, 7657 completed passive case detection, and 7545 (98.5%) had complete data. Indoor residual spraying coverage per cluster was more than 80% for both years in the indoor residual spraying plus LLIN group. Incidence of clinical malaria was 0.047 per child-month at risk in the LLIN group and 0.044 per child-month at risk in the indoor residual spraying plus LLIN group in 2010, and 0.032 per child-month at risk in the LLIN group and 0.034 per child-month at risk in the indoor residual spraying plus LLIN group in 2011. The incident rate ratio was 1.08 (95% CI 0.80-1.46) controlling for confounders and cluster by mixed-effect negative binomial regression on all malaria attacks for both years. No significant difference was recorded in the density of vector mosquitoes caught in light traps in houses over the two transmission seasons; the mean number of A gambiae sensu lato mosquitoes per trap per night was 6.7 (4.0-10.1) in the LLIN group and 4.5 (2.4-7.4) in the indoor residual spraying plus LLIN group (p=0.281 in the random-effects linear regression model).nnnINTERPRETATIONnWe identified no significant difference in clinical malaria or vector density between study groups. In this area with high LLIN coverage, moderate seasonal transmission, and susceptible vectors, indoor residual spraying did not provide additional benefit.nnnFUNDINGnUK Medical Research Council.

Evidence-based vector control? Improving the quality of vector control trials

Vector-borne diseases (VBDs) such as malaria, dengue, and leishmaniasis cause a high level of morbidity and mortality. Although vector control tools can play a major role in controlling and eliminating these diseases, in many cases the evidence base for assessing the efficacy of vector control interventions is limited or not available. Studies assessing the efficacy of vector control interventions are often poorly conducted, which limits the return on investment of research funding. Here we outline the principal design features of Phase III vector control field studies, highlight major failings and strengths of published studies, and provide guidance on improving the design and conduct of vector control studies. We hope that this critical assessment will increase the impetus for more carefully considered and rigorous design of vector control studies.

Alternative treatments for indoor residual spraying for malaria control in a village with pyrethroid- and DDT-resistant vectors in The Gambia

Background Malaria vector control is threatened by resistance to pyrethroids, the only class of insecticides used for treating bed nets. The second major vector control method is indoor residual spraying with pyrethroids or the organochloride DDT. However, resistance to pyrethroids frequently confers resistance to DDT. Therefore, alternative insecticides are urgently needed. Methodology/Principal Findings Insecticide resistance and the efficacy of indoor residual spraying with different insecticides was determined in a Gambian village. Resistance of local vectors to pyrethroids and DDT was high (31% and 46% mortality, respectively) while resistance to bendiocarb and pirimiphos methyl was low (88% and 100% mortality, respectively). The vectors were predominantly Anopheles gambiae s.s. with 94% of them having the putative resistant genotype kdr 1014F. Four groups of eight residential compounds were each sprayed with either (1) bendiocarb, a carbamate, (2) DDT, an organochlorine, (3) microencapsulated pirimiphos methyl, an organophosphate, or (4) left unsprayed. All insecticides tested showed high residual activity up to five months after application. Mosquito house entry, estimated by light traps, was similar in all houses with metal roofs, but was significantly less in IRS houses with thatched roofs (p=0.02). Residents participating in focus group discussions indicated that IRS was considered a necessary nuisance and also may decrease the use of long-lasting insecticidal nets. Conclusion/Significance Bendiocarb and microencapsulated pirimiphos methyl are viable alternatives for indoor residual spraying where resistance to pyrethroids and DDT is high and may assist in the management of pyrethroid resistance.

‘Like sugar and honey’: The embedded ethics of a larval control project in The Gambia

This paper describes a malaria research project in The Gambia to provoke thinking on the social value of transnational research. The Larval Control Project (LCP) investigated the efficacy of a microbial insecticide to reduce vector density and, ultimately, clinical malaria in Gambian children. The LCP’s protocol delineated a clinical surveillance scheme that involved Village Health Workers (VHWs) supported by project nurses. Combining insights from ethnographic fieldwork conducted at the Medical Research Council (MRC) Laboratories in Farafenni from 2005 to 2009, open-ended interviews with project nurses, and eight focus group discussions held with participant mothers in October 2007, we consider the social impact of the LCP’s investigative method against the backdrop of several years of research activity. We found that while participants associated the LCP with the clinical care it provided, they also regarded the collaboration between the nurses and VHWs added additional benefits. Organised around the operational functions of the trial, small-scale collaborations provided the platform from which to build local capacity. While ethical guidelines emphasise the considerations that must be added to experimental endeavour in southern countries (e.g. elaborating processes of informed consent, developing strategies of community engagement or providing therapeutic access to participants after the trial concludes), these findings suggest that shifting attention from supplementing ethical protocols to the everyday work of research – embedding ethics through scientific activity – may provide a sounder basis to reinforce the relationship between scientific rigour and social value.

To assess whether indoor residual spraying can provide additional protection against clinical malaria over current best practice of long-lasting insecticidal mosquito nets in The Gambia: study protocol for a two-armed cluster-randomised trial

BackgroundRecently, there has been mounting interest in scaling-up vector control against malaria in Africa. It needs to be determined if indoor residual spraying (IRS with DDT) will provide significant marginal protection against malaria over current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in a controlled trial, given that DDT is currently the most persistent insecticide for IRS.MethodsA 2 armed cluster-randomised controlled trial will be conducted to assess whether DDT IRS and LLINs combined provide better protection against clinical malaria in children than LLINs alone in rural Gambia. Each cluster will be a village, or a group of small adjacent villages; all clusters will receive LLINs and half will receive IRS in addition. Study children, aged 6 months to 13 years, will be enrolled from all clusters and followed for clinical malaria using passive case detection to estimate malaria incidence for 2 malaria transmission seasons in 2010 and 2011. This will be the primary endpoint. Exposure to malaria parasites will be assessed using light and exit traps followed by detection of Anopheles gambiae species and sporozoite infection. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection and the prevalence of anaemia.DiscussionPractical issues concerning intervention implementation, as well as the potential benefits and risks of the study, are discussed.Trial RegistrationISRCTN01738840 - Spraying And Nets Towards malaria Elimination (SANTE)

Chrysomya putoria, a Putative Vector of Diarrheal Diseases

Background Chrysomya spp are common blowflies in Africa, Asia and parts of South America and some species can reproduce in prodigious numbers in pit latrines. Because of their strong association with human feces and their synanthropic nature, we examined whether these flies are likely to be vectors of diarrheal pathogens. Methodology/Principal Findings Flies were sampled using exit traps placed over the drop holes of latrines in Gambian villages. Odor-baited fly traps were used to determine the relative attractiveness of different breeding and feeding media. The presence of bacteria on flies was confirmed by culture and bacterial DNA identified using PCR. A median of 7.00 flies/latrine/day (IQRu200a=u200a0.0–25.25) was collected, of which 95% were Chrysomya spp, and of these nearly all were Chrysomya putoria (99%). More flies were collected from traps with feces from young children (medianu200a=u200a3.0, IQRu200a=u200a1.75–10.75) and dogs (medianu200a=u200a1.50, IQRu200a=u200a0.0–13.25) than from herbivores (medianu200a=u200a0.0, IQRu200a=u200a0.0–0.0; goat, horse, cow and calf; p<0.001). Flies were strongly attracted to raw meat (medianu200a=u200a44.5, IQRu200a=u200a26.25–143.00) compared with fish (medianu200a=u200a0.0, IQRu200a=u200a0.0–19.75, ns), cooked and uncooked rice, and mangoes (medianu200a=u200a0.0, IQRu200a=u200a0.0–0.0; p<0.001). Escherichia coli were cultured from the surface of 21% (15/72 agar plates) of Chrysomya spp and 10% of these were enterotoxigenic. Enteroaggregative E. coli were identified by PCR in 2% of homogenized Chrysomya spp, Shigella spp in 1.4% and Salmonella spp in 0.6% of samples. Conclusions/Significance The large numbers of C. putoria that can emerge from pit latrines, the presence of enteric pathogens on flies, and their strong attraction to raw meat and fish suggests these flies may be common vectors of diarrheal diseases in Africa.

The RooPfs study to assess whether improved housing provides additional protection against clinical malaria over current best practice in The Gambia: study protocol for a randomized controlled study and ancillary studies

BackgroundIn malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. This study will determine if modern housing provides incremental protection against clinical malaria over the current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in The Gambia, determine the incremental cost-effectiveness of the interventions, and analyze the housing market in The Gambia.Methods/designA two-armed, household, cluster-randomized, controlled study will be conducted to assess whether improved housing and LLINs combine to provide better protection against clinical malaria in children than LLINs alone in The Gambia. The unit of randomization will be the household, defined as a house and its occupants. A total of 800 households will be enrolled and will receive LLINs, and 400 will receive improved housing before clinical follow-up. One child aged 6xa0months to 13xa0years will be enrolled from each household and followed for clinical malaria using active case detection to estimate malaria incidence for two malaria transmission seasons. Episodes of clinical malaria will be the primary endpoint. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection, parasite density, and the prevalence of anemia. Exposure to malaria parasites will be assessed using light traps, followed by detection of Anopheles gambiae species and sporozoite infection. Ancillary economic and social science studies will undertake a cost-effectiveness analysis and use qualitative and participatory methods to explore the acceptability of the housing modifications and to design strategies for scaling-up housing interventions.DiscussionThe study is the first of its kind to measure the efficacy of housing on reducing clinical malaria, assess the incremental cost-effectiveness of improved housing, and identify mechanisms for scaling up housing interventions. Trial findings will help inform policy makers on improved housing for malaria control in sub-Saharan Africa.Trial registrationISRCTN Registry, ISRCTN02622179. Registered on 23 September 2014.

Development of Odour-Baited Flytraps for Sampling the African Latrine Fly, Chrysomya putoria, a Putative Vector of Enteric Diseases

African pit latrines produce prodigious numbers of the latrine fly, Chrysomya putoria, a putative vector of diarrhoeal pathogens. We set out to develop a simple, low-cost odour-baited trap for collecting C. putoria in the field. A series of field experiments was carried out in The Gambia to assess the catching-efficiency of different trap designs. The basic trap was a transparent 3L polypropylene box baited with 50 g of fish, with a white opaque lid with circular entrance holes. We tested variations of the number, diameter, position and shape of the entrance holes, the height of the trap above ground, degree of transparency of the box, its shape, volume, colour, and the attractiveness of gridded surfaces on or under the trap. Traps were rotated between positions on different sampling occasions using a Latin Square design. The optimal trapping features were incorporated into a final trap that was tested against commercially available traps. Features of the trap that increased the number of flies caught included: larger entrance holes (compared with smaller ones, p<0.001), using conical collars inside the holes (compared with without collars, pu200a=u200a0.01), entrance holes on the top of the trap (compared with the side or bottom, p<0.001), traps placed on the ground (compared with above ground, p<0.001), the box having transparent sides (compared with being opaque, p<0.001), and with no wire grids nearby (compared with those with grids, pu200a=u200a0.03). This trap collected similar numbers of C. putoria to other common traps for blow flies. The optimum trap design was a transparent box, with a white plastic lid on top, perforated with 10 conical entrance holes, placed on the ground. Our simple trap provides a cheap, low-maintenance and effective method of sampling C. putoria in the field.