A qualitative look at bed net access and use in Burkina Faso, Mozambique, Nigeria, and Rwanda following piloted distributions of dual-active ingredient insecticide-treated nets.

BACKGROUND: Universal coverage with insecticide-treated nets (ITNs) is important for malaria control and elimination. The emergence and intensification of insecticide resistance threatens progress made through the deployment of these interventions and has required the development of newer, more expensive ITN types. Understanding malaria prevention behaviour, including barriers and facilitators to net access and use, can support effective decision-making for the promotion and distribution of ITNs. METHODS: In-depth interviews and focus group discussions were conducted in 3 to 4 villages per district, in 13 districts across Burkina Faso, Mozambique, Nigeria and Rwanda from 2019 to 2022. Interviews were conducted in the local language, translated and transcribed in English, French or Portuguese. Transcripts were coded and analysed using Nvivo and ATLAS.ti. RESULTS: ITNs were obtained from mass distribution campaigns, antenatal care and immunization visits, and purchased on the private market in some locations. While there were divergent perspectives in whether the number of distributed nets were adequate, participants consistently expressed concerns of bias, discrimination, and a lack of transparency with the distribution process. ITNs were frequently used alongside other malaria prevention methods. The primary motivation for use was malaria prevention. While some participants reported using nets nightly throughout the year, other participants reported seasonal use, both due to the perceived higher density of mosquitoes and discomfort of sleeping under a net in the increased heat. Other barriers to consistent net use included activities that take place away from the home, sleeping patterns and arrangements, and sensitivity to the insecticides on the nets. CONCLUSIONS: ITNs remain an important malaria control intervention. To ensure adequate and increased net access, distribution campaigns should consider family structures, available sleeping spaces, and other bed sharing preferences when identifying the number of nets needed for distribution. In addition, campaigns should allow for multiple options for net distribution points and timing to accommodate households remote to health services. Continuous distribution channels and complimentary distribution through the private sector could help fill gaps in coverage. Solutions are needed for outdoor malaria transmission, including alternative designs for ITNs, and improving access to complementary personal protective measures.

Using antenatal care as a platform for malaria surveillance data collection: study protocol.

BACKGROUND: While many malaria-endemic countries have health management information systems that can measure and report malaria trends in a timely manner, these routine systems have limitations. Periodic community cross-sectional household surveys are used to estimate malaria prevalence and intervention coverage but lack geographic granularity and are resource intensive. Incorporating malaria testing for all women at their first antenatal care (ANC) visit (i.e., ANC1) could provide a more timely and granular source of data for monitoring trends in malaria burden and intervention coverage. This article describes a protocol designed to assess if ANC-based surveillance could be a pragmatic tool to monitor malaria. METHODS: This is an observational, cross-sectional study conducted in Benin, Burkina Faso, Mozambique, Nigeria, Tanzania, and Zambia. Pregnant women attending ANC1 in selected health facilities will be tested for malaria infection by rapid diagnostic test and administered a brief questionnaire to capture key indicators of malaria control intervention coverage and care-seeking behaviour. In each location, contemporaneous cross-sectional household surveys will be leveraged to assess correlations between estimates obtained using each method, and the use of ANC data as a tool to track trends in malaria burden and intervention coverage will be validated. RESULTS: This study will assess malaria prevalence at ANC1 aggregated at health facility and district levels, and by gravidity relative to current pregnancy (i.e., gravida 1, gravida 2, and gravida 3 +). ANC1 malaria prevalence will be presented as monthly trends. Additionally, correlation between ANC1 and household survey-derived estimates of malaria prevalence, bed net ownership and use, and care-seeking will be assessed. CONCLUSION: ANC1-based surveillance has the potential to provide a cost-effective, localized measure of malaria prevalence that is representative of the general population and useful for tracking monthly changes in parasite prevalence, as well as providing population-representative estimates of intervention coverage and care-seeking behavior. This study will evaluate the representativeness of these measures and collect information on operational feasibility, usefulness for programmatic decision-making, and potential for scale-up of malaria ANC1 surveillance.

Design and methods for a quasi-experimental pilot study to evaluate the impact of dual active ingredient insecticide-treated nets on malaria burden in five regions in sub-Saharan Africa.

BACKGROUND: Vector control tools have contributed significantly to a reduction in malaria burden since 2000, primarily through insecticidal-treated bed nets (ITNs) and indoor residual spraying. In the face of increasing insecticide resistance in key malaria vector species, global progress in malaria control has stalled. Innovative tools, such as dual active ingredient (dual-AI) ITNs that are effective at killing insecticide-resistant mosquitoes have recently been introduced. However, large-scale uptake has been slow for several reasons, including higher costs and limited evidence on their incremental effectiveness and cost-effectiveness. The present report describes the design of several observational studies aimed to determine the effectiveness and cost-effectiveness of dual-AI ITNs, compared to standard pyrethroid-only ITNs, at reducing malaria transmission across a variety of transmission settings. METHODS: Observational pilot studies are ongoing in Burkina Faso, Mozambique, Nigeria, and Rwanda, leveraging dual-AI ITN rollouts nested within the 2019 and 2020 mass distribution campaigns in each country. Enhanced surveillance occurring in select study districts include annual cross-sectional surveys during peak transmission seasons, monthly entomological surveillance, passive case detection using routine health facility surveillance systems, and studies on human behaviour and ITN use patterns. Data will compare changes in malaria transmission and disease burden in districts receiving dual-AI ITNs to similar districts receiving standard pyrethroid-only ITNs over three years. The costs of net distribution will be calculated using the provider perspective including financial and economic costs, and a cost-effectiveness analysis will assess incremental cost-effectiveness ratios for Interceptor® G2, Royal Guard®, and piperonyl butoxide ITNs in comparison to standard pyrethroid-only ITNs, based on incidence rate ratios calculated from routine data. CONCLUSIONS: Evidence of the effectiveness and cost-effectiveness of the dual-AI ITNs from these pilot studies will complement evidence from two contemporary cluster randomized control trials, one in Benin and one in Tanzania, to provide key information to malaria control programmes, policymakers, and donors to help guide decision-making and planning for local malaria control and elimination strategies. Understanding the breadth of contexts where these dual-AI ITNs are most effective and collecting robust information on factors influencing comparative effectiveness could improve uptake and availability and help maximize their impact.

Antibody responses to a suite of novel serological markers for malaria surveillance demonstrate strong correlation with clinical and parasitological infection across seasons and transmission settings in The Gambia.

BACKGROUND: As malaria transmission declines, sensitive diagnostics are needed to evaluate interventions and monitor transmission. Serological assays measuring malaria antibody responses offer a cost-effective detection method to supplement existing surveillance tools. METHODS: A prospective cohort study was conducted from 2013 to 2015 in 12 villages across five administrative regions in The Gambia. Serological analysis included samples from the West Coast Region at the start and end of the season (July and December 2013) and from the Upper River Region in July and December 2013 and April and December 2014. Antigen-specific antibody responses to eight Plasmodium falciparum (P. falciparum) antigens-Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175 RIII-V, PfMSP119, PfAMA1, and PfGLURP.R2-were quantified using a multiplexed bead-based assay. The association between antibody responses and clinical and parasitological endpoints was estimated at the individual, household, and population level. RESULTS: Strong associations were observed between clinical malaria and concurrent sero-positivity to Etramp5.Ag1 (aOR 4.60 95% CI 2.98-7.12), PfMSP119 (aOR 4.09 95% CI 2.60-6.44), PfAMA1 (aOR 2.32 95% CI 1.40-3.85), and PfGLURP.R2 (aOR 3.12, 95% CI 2.92-4.95), while asymptomatic infection was associated with sero-positivity to all antigens. Village-level sero-prevalence amongst children 2-10 years against Etramp5.Ag1, HSP40.Ag1, and PfMSP119 showed the highest correlations with clinical and P. falciparum infection incidence rates. For all antigens, there were increased odds of asymptomatic P. falciparum infection in subjects residing in a compound with greater than 50% sero-prevalence, with a 2- to 3-fold increase in odds of infection associated with Etramp5.Ag1, GEXP18, Rh2.2030, PfMSP119, and PfAMA1. For individuals residing in sero-positive compounds, the odds of clinical malaria were reduced, suggesting a protective effect. CONCLUSIONS: At low transmission, long-lived antibody responses could indicate foci of malaria transmission that have been ongoing for several seasons or years. In settings where sub-patent infections are prevalent and fluctuate below the detection limit of polymerase chain reaction (PCR), the presence of short-lived antibodies may indicate recent infectivity, particularly in the dry season when clinical cases are rare. Serological responses may reflect a persistent reservoir of infection, warranting community-targeted interventions if individuals are not clinically apparent but have the potential to transmit. Therefore, serological surveillance at the individual and household level may be used to target interventions where there are foci of asymptomatically infected individuals, such as by measuring the magnitude of age-stratified antibody levels or identifying areas with clustering of above-average antibody responses across a diverse range of serological markers.

Sero-epidemiological evaluation of malaria transmission in The Gambia before and after mass drug administration.

BACKGROUND: As The Gambia aims to achieve malaria elimination by 2030, serological assays are a useful surveillance tool to monitor trends in malaria incidence and evaluate community-based interventions. METHODS: Within a mass drug administration (MDA) study in The Gambia, where reduced malaria infection and clinical disease were observed after the intervention, a serological sub-study was conducted in four study villages. Spatio-temporal variation in transmission was measured with a panel of recombinant Pf antigens on a multiplexed bead-based assay. Village-level antibody levels were quantified as under-15 sero-prevalence, sero-conversion rates, and age-adjusted antibody acquisition rates. Antibody levels prior to MDA were assessed for association with persistent malaria infection after community chemoprophylaxis. RESULTS: Seasonal changes in antibodies to Etramp5.Ag1 were observed in children under 15 years in two transmission settings-the West Coast and Upper River Regions (4.32% and 31.30% Pf prevalence, respectively). At the end of the malaria season, short-lived antibody responses to Etramp5.Ag1, GEXP18, HSP40.Ag1, EBA175 RIII-V, and Rh2.2030 were lower amongst 1-15 year olds in the West Coast compared to the Upper River, reflecting known differences in transmission. Prior to MDA, individuals in the top 50th percentile of antibody levels had two-fold higher odds of clinical malaria during the transmission season, consistent with previous findings from the Malaria Transmission Dynamics Study, where individuals infected before the implementation of MDA had two-fold higher odds of re-infection post-MDA. CONCLUSIONS: Serological markers can serve dual functions as indicators of malaria exposure and incidence. By monitoring age-specific sero-prevalence, the magnitude of age-stratified antibody levels, or identifying groups of individuals with above-average antibody responses, these antigens have the potential to complement conventional malaria surveillance tools. Further studies, particularly cluster randomised trials, can help establish standardised serological protocols to reliably measure transmission across endemic settings.

Mass Drug Administration With Dihydroartemisinin-piperaquine and Malaria Transmission Dynamics in The Gambia: A Prospective Cohort Study.

BACKGROUND: Mass drug administration (MDA) may further reduce malaria transmission in low-transmission areas. The impact of MDA on the dynamics of malaria transmission was determined in a prospective cohort study. METHODS: Annual rounds of MDA with dihydroartemisinin-piperaquine (DP) were implemented were implemented in 2014 and 2015 in six village pairs before the malaria transmission season. Blood samples were collected from residents between July and December for microscopy and nested PCR. Incidence and prevalence of infection, clinical disease, and risk of malaria reinfection post-MDA were determined. RESULTS: Coverage of three DP doses was 68.2% (2014) and 65.6% (2015), compliance was greater than 80%. Incidence of infection was significantly lower in 2014 (incidence rate [IR] = 0.2 per person year [PPY]) than in 2013 (IR = 1.1 PPY; P < .01); monthly infection prevalence declined in the first three months post-MDA. Clinical malaria incidence was lower in 2014 (IR = 0.1 PPY) and 2015 (IR = 0.2 PPY) than in 2013 (IR = 0.4 PPY; P < .01), but remained higher in eastern Gambia. Individuals infected before MDA had a 2-fold higher odds of reinfection post-MDA (adjusted odds ratio = 2.5, 95% confidence interval 1.5-4.3; P < .01). CONCLUSIONS: MDA reduced malaria infection and clinical disease during the first months. The reduction was maintained in low-transmission areas, but not in eastern Gambia. Annual MDA could be followed by focal MDA targeting individuals infected during the dry season. Repeated MDA rounds, some during the dry season over larger geographical areas, may result in a more marked and sustained decrease of malaria transmission.

Field performance of the malaria highly sensitive rapid diagnostic test in a setting of varying malaria transmission.

BACKGROUND: The Gambia has successfully reduced malaria transmission. The human reservoir of infection could further decrease if malaria-infected individuals could be identified by highly sensitive, field-based, diagnostic tools and then treated. METHODS: A cross-sectional survey was done at the peak of the 2017 malaria season in 47 Gambian villages. From each village, 100 residents were randomly selected for finger-prick blood samples to detect Plasmodium falciparum infections using highly sensitive rapid diagnostic tests (HS-RDT) and PCR. The sensitivity and specificity of the HS-RDT were estimated (assuming PCR as the gold standard) across varying transmission intensities and in different age groups. A deterministic, age-structured, dynamic model of malaria transmission was used to estimate the impact of mass testing and treatment (MTAT) with HS-RDT in four different scenarios of malaria prevalence by PCR: 5, 15, 30, and 60%, and with seasonal transmission. The impact was compared both to MTAT with conventional RDT and mass drug administration (MDA). RESULTS: Malaria prevalence by HS-RDT was 15% (570/3798; 95% CI 13.9-16.1). The HS-RDT sensitivity and specificity were 38.4% (191/497, 95% CI 34.2-42.71) and 88.5% (2922/3301; 95% CI 87.4-89.6), respectively. Sensitivity was the highest (50.9%, 95% CI 43.3-58.5%) in high prevalence villages (20-50% by PCR). The model predicted that in very low transmission areas (≤ 5%), three monthly rounds of MTAT with HS-RDT, starting towards the end of the dry season and testing 65 or 85% of the population for 2 consecutive years, would avert 62 or 78% of malaria cases (over 2 years), respectively. The effect of the intervention would be lower in a moderate transmission setting. In all settings, MDA would be superior to MTAT with HS-RDT which would be superior to MTAT with conventional RDT. CONCLUSION: The HS-RDT's field sensitivity was modest and varied by transmission intensity. In low to very low transmission areas, three monthly rounds per year of MTAT with HS-RDT at 85% coverage for 2 consecutive years would reduce malaria prevalence to such low levels that additional strategies may achieve elimination. The model prediction would need to be confirmed by cluster-randomized trials.

Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing.

Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and >62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation.

Do hotspots fuel malaria transmission: a village-scale spatio-temporal analysis of a 2-year cohort study in The Gambia.

BACKGROUND: Despite the biological plausibility of hotspots fueling malaria transmission, the evidence to support this concept has been mixed. If transmission spreads from high burden to low burden households in a consistent manner, then this could have important implications for control and elimination program development. METHODS: Data from a longitudinal cohort in The Gambia was analyzed. All consenting individuals residing in 12 villages across the country were sampled monthly from June (dry season) to December 2013 (wet season), in April 2014 (mid dry season), and monthly from June to December 2014. A study nurse stationed within each village recorded passively detected malaria episodes between visits. Plasmodium falciparum infections were determined by polymerase chain reaction and analyzed using a geostatistical model. RESULTS: Household-level observed monthly incidence ranged from 0 to 0.50 infection per person (interquartile range = 0.02-0.10) across the sampling months, and high burden households exist across all study villages. There was limited evidence of a spatio-temporal pattern at the monthly timescale irrespective of transmission intensity. Within-household transmission was the most plausible hypothesis examined to explain the observed heterogeneity in infections. CONCLUSIONS: Within-village malaria transmission patterns are concentrated in a small proportion of high burden households, but patterns are stochastic regardless of endemicity. Our findings support the notion of transmission occurring at the household and village scales but not the use of a targeted approach to interrupt spreading of infections from high to low burden areas within villages in this setting.

Community sensitization and decision-making for trial participation: A mixed-methods study from The Gambia.

BACKGROUND: Ensuring individual free and informed decision-making for research participation is challenging. It is thought that preliminarily informing communities through 'community sensitization' procedures may improve individual decision-making. This study set out to assess the relevance of community sensitization for individual decision-making in research participation in rural Gambia. METHODS: This anthropological mixed-methods study triangulated qualitative methods and quantitative survey methods in the context of an observational study and a clinical trial on malaria carried out by the Medical Research Council Unit Gambia. RESULTS/DISCUSSION: Although 38.7% of the respondents were present during sensitization sessions, 91.1% of the respondents were inclined to participate in the trial when surveyed after the sensitization and prior to the informed consent process. This difference can be explained by the informal transmission of information within the community after the community sensitization, expectations such as the benefits of participation based on previous research experiences, and the positive reputation of the research institute. Commonly mentioned barriers to participation were blood sampling and the potential disapproval of the household head. CONCLUSION: Community sensitization is effective in providing first-hand, reliable information to communities as the information is cascaded to those who could not attend the sessions. However, further research is needed to assess how the informal spread of information further shapes people's expectations, how the process engages with existing social relations and hierarchies (e.g. local political power structures; permissions of heads of households) and how this influences or changes individual consent.

Does insecticide resistance contribute to heterogeneities in malaria transmission in The Gambia?

BACKGROUND: Malaria hotspots, areas with consistently higher than average transmission, may become increasingly common as malaria declines. This phenomenon, currently observed in The Gambia, may be caused by several factors, including some related to the local vectors, whose contribution is poorly understood. METHODS: Using WHO susceptibility bioassays, insecticide resistance status was determined in vector populations sampled from six pairs of villages across The Gambia, each pair contained a low and high prevalence village. RESULTS: Three vector species were observed (23.5% Anopheles arabiensis, 31.2% Anopheles gambiae, 43.3% Anopheles coluzzii and 2.0% An. coluzzii × An. gambiae hybrids). Even at a fine scale, significant differences in species composition were detected within village pairs. Resistance to both DDT and deltamethrin was more common in An. gambiae, most markedly in the eastern part of The Gambia and partly attributable to differing frequencies of resistance mutations. The Vgsc-1014F target site mutation was strongly associated with both DDT (OR = 256.7, (95% CI 48.6-6374.3, p < 0.001) and deltamethrin survival (OR = 9.14, (95% CI 4.24-21.4, p < 0.001). A second target site mutation, Vgsc-1575Y, which co-occurs with Vgsc-1014F, and a metabolic marker of resistance, Gste2-114T, conferred additional survival benefits to both insecticides. DDT resistance occurred significantly more frequently in villages with high malaria prevalence (p = 0.025) though this did not apply to deltamethrin resistance. CONCLUSION: Whilst causality of relationships requires further investigation, variation in vector species and insecticide resistance in The Gambia is associated with malaria endemicity; with a notably higher prevalence of infection and insecticide resistance in the east of the country. In areas with heterogeneous malaria transmission, the role of the vector should be investigated to guide malaria control interventions.

Seasonal variation in haematological and biochemical reference values for healthy young children in The Gambia.

BACKGROUND: Haematological and biochemistry reference values for children are important for interpreting clinical and research results however, differences in demography and environment poses a challenge when comparing results. The study defines reference intervals for haematological and biochemistry parameters and examines the effect of seasonality in malaria transmission. METHODS: Blood samples collected from clinically healthy children, aged 12-59 months, in two surveys during the dry and wet season in the Upper River region of The Gambia were processed and the data analysed to generate reference intervals based on the 2.5(th) and 97.5(th) percentiles of the data. RESULTS: Analysis was based on data from 1141 children with median age of 32 months. The mean values for the total white cell count and differentials; lymphocyte, monocyte and neutrophil decreased with increasing age, were lower in males and higher in the wet season survey. However, platelet values declined with age (p < 0.0001). There was no evidence of effect of gender on mean values of AST, ALT, lymphocytes, monocytes, platelets and haemoglobin. CONCLUSION: Mean estimates for haematological and biochemistry reference intervals are affected by age and seasonality in the first five years of life. This consistency is important for harmonisation of reference values for clinical care and interpretation of trial results.

Foul wind, spirits and witchcraft: illness conceptions and health-seeking behaviour for malaria in the Gambia.

BACKGROUND: As the disease burden in the Gambia has reduced considerably over the last decade, heterogeneity in malaria transmission has become more marked, with infected but asymptomatic individuals maintaining the reservoir. The identification, timely diagnosis and treatment of malaria-infected individuals are crucial to further reduce or eliminate the human parasite reservoir. This ethnographic study focused on the relationship between local beliefs of the cause of malaria and treatment itineraries of suspected cases. METHODS: An ethnographic qualitative study was conducted in twelve rural communities in the Upper River Region and the Central River Region in the Gambia. The data collection methods included in-depth interviews, participant observation, informal conversations, and focus group discussions. RESULTS: While at first glance, the majority of people seek biomedical treatment for 'malaria', there are several constraints to seeking treatment at health centres. Certain folk illnesses, such as Jontinooje and Kajeje, translated and interpreted as 'malaria' by healthcare professionals, are often not considered to be malaria by local populations but rather as self-limiting febrile illnesses--consequently not leading to seeking care in the biomedical sector. Furthermore, respondents reported delaying treatment at a health centre while seeking financial resources, and consequently relying on herbal treatments. In addition, when malaria cases present symptoms, such as convulsions, hallucinations and/or loss of consciousness, the illness is often interpreted as having a supernatural aetiology, leading to diagnosis and treatment by traditional healers. CONCLUSION: Although malaria diagnostics and treatment-seeking in the biomedical sector has been reported to be relatively high in the Gambia compared to other sub-Saharan African countries, local symptom interpretation and illness conceptions can delay or stop people from seeking timely biomedical treatment, which may contribute to maintaining a parasite reservoir of undiagnosed and untreated malaria patients.

On-going malaria transmission in The Gambia despite high coverage of control interventions: a nationwide cross-sectional survey.

BACKGROUND: As indicators of burden of malaria have substantially decreased in The Gambia, reaching a pre-elimination status may be attainable. Achieving this goal requires in-depth understanding of the current burden of Plasmodium falciparum infection. METHODS: A nationwide cross-sectional survey was conducted in 2012 to determine the prevalence of P. falciparum infection, and to describe its heterogeneity and associated risk factors. Finger-prick blood samples were collected for microscopy, species-specific PCR and haemoglobin measurement. RESULTS: A total of 9,094 participants were included and median age was 11.9 years (IQR 5, 28). Overall prevalence of P. falciparum was 16.01 % with marked heterogeneity between sites (4.32-36.75 %) and within villages in each site (1.63-49.13 %). Across all sites, 51.17 % (745/1,456) of infections were asymptomatic and 35.61 % (448/1,258) were sub-microscopic. The odds of P. falciparum infection were higher in older children; 5-15 years (OR = 1.90; 95 % CI 1.60-2.26), adults (OR = 1.48; 95 % CI 1.24-1.78) and participants with moderate anaemia (OR = 1.62; 95 % CI 1.32-1.99). CONCLUSIONS: The current malaria control interventions are not sufficient to interrupt transmission in The Gambia as malaria prevalence is still relatively high in the eastern part of the country. New interventions aiming at interrupting transmission are needed and should be urgently evaluated.

Lopinavir/ritonavir-based antiretroviral treatment (ART) versus efavirenz-based ART for the prevention of malaria among HIV-infected pregnant women.

BACKGROUND: Human immunodeficiency virus (HIV)-infected pregnant women are at increased risk of malaria and its complications. In vitro and in vivo data suggest that the HIV protease inhibitors lopinavir/ritonavir may have potent antimalarial activity. We sought to evaluate whether lopinavir/ritonavir-based antiretroviral therapy (ART) reduced the risk of placental malaria. METHODS: HIV-infected, ART-naive pregnant women were enrolled between gestational weeks 12 and 28 and randomly assigned to receive lopinavir/ritonavir-based or efavirenz-based ART. Women received daily trimethoprim-sulfamethoxazole prophylaxis and insecticide-treated bed nets at enrollment and were followed up to 1 year after delivery. The primary outcome was placental malaria, defined by the detection of malaria parasites, using microscopy or polymerase chain reaction (PCR) analysis of placental blood specimens. Secondary outcomes included placental malaria, defined by histopathologic results; adverse birth outcomes; incidence of malaria; and prevalence of asymptomatic parasitemia. Analyses were done using an intention-to-treat approach. RESULTS: Of 389 subjects randomly assigned to a treatment group, 377 were followed through to delivery. There was no significant difference in the risk of placental malaria, as defined by thick smear or PCR findings, between the lopinavir/ritonavir-based and efavirenz-based ART arms (7.4% vs 9.8%; P = .45). Similarly, there were no differences in secondary outcomes between the 2 treatment arms. CONCLUSIONS: Lopinavir/ritonavir-based ART did not reduce the risk of placental or maternal malaria or improve birth outcomes, compared with efavirenz-based ART. CLINICAL TRIALS REGISTRATION: NCT00993031.

A comparative case control study of the determinants of clinical malaria in The Gambia.

BACKGROUND: The massive deployment of life saving malaria interventions has not only resulted in a decline in disease burden but a change in the risk of infection and disease. The study reassesses the importance of known risk factors and reviews demographic and socio-economic determinants of malaria risk in the population. METHODS: This was a case-control study involving 150 children with test-confirmed malaria infection recruited from the outpatient clinics of three health facilities (cases) in the Greater Banjul area, The Gambia. One hundred and fifty controls, negative for malaria were matched on age, residence. Information was collected from respondents on the use of long lasting insecticidal nets, occupation, housing structure, knowledge of malaria and socio-demographic factors. RESULTS: The mean age of study participants was 6.8 (SD 3.3) years with 147 (49%) being males. Significant determinants of malaria risk were parent's occupation: mother as trader (OR 0.18, 95% CI 0.04 - 0.73, p = 0.017), father as trader (OR 0.02, 95% CI 0.002- 0.193, p = 0.001), civil servants (OR 0.04, 95% CI 0.008- 0.257, p =0.001) or handyman (OR 0.03, 95% CI 0.005- 0.182, p < 0.001). Children sleeping in rooms with windowpanes had a 76% reduction in their odds of malaria (OR 0.24, 95%CI 0.07- 0.82, p = 0.022. CONCLUSION: Household socio-economic status plays an important role in management of illnesses. The ability of mothers to engage in an occupation increases household resources to access healthcare and on time. The balance between the type of mother's occupation and her time available to supervise the child is an interesting emerging issue that needs further investigation.

Household food insecurity, maternal nutritional status, and infant feeding practices among HIV-infected Ugandan women receiving combination antiretroviral therapy.

Household food insecurity (HHFI) may be a barrier to both optimal maternal nutritional status and infant feeding practices, but few studies have tested this relationship quantitatively, and never among HIV-infected individuals. We therefore described the prevalence of HHFI and explored if it was associated with poorer maternal nutritional status, shorter duration of exclusive breastfeeding (EBF) and fewer animal-source complementary foods. We assessed these outcomes using bivariate and multivariate analyses among 178 HIV-infected pregnant and breastfeeding (BF) women receiving combination antiretroviral therapy in the PROMOTE trial (NCT00993031), a prospective, longitudinal cohort study in Tororo, Uganda. HHFI was common; the prevalence of severe, moderate, and little to no household hunger was 7.3, 39.9, and 52.8 %, respectively. Poor maternal nutritional status was common and women in households experiencing moderate to severe household hunger (MSHH) had statistically significantly lower body mass index (BMIs) at enrollment (21.3 vs. 22.5, p < 0.01) and prior to delivery (22.6 vs. 23.8, p < 0.01). BMI across time during pregnancy, but not gestational weight gain, was significantly lower for MSHH [adjusted beta (95 % CI) -0.79 (-1.56, -0.02), p = 0.04; -2.06 (-4.31, 0.19), p = 0.07], respectively. The prevalence (95 % CI) of EBF at 6 months was 67.2 % (59.7-73.5 %), and the proportion of women BF at 12 months was 80.4 % (73.3-85.7 %). MSHH was not associated with prevalence of EBF at 6 months or BF at 12 months. However, among those women still EBF at 4 months (81.4 % of population), those experiencing MSHH were significantly more likely to cease EBF between 4 and 6 months (aHR 2.38, 95 % CI 1.02-5.58). The prevalence of HHFI, maternal malnutrition, and suboptimal infant feeding practices are high and the causal relationships among these phenomena must be further explored.

Neonatal mortality in HIV-exposed infants born to women receiving combination antiretroviral therapy in Rural Uganda.

As human immunodeficiency virus (HIV)-infected women gain access to combination antiretroviral therapy throughout sub-Saharan Africa, a growing number of infants are being born HIV-exposed but uninfected. Data about neonatal mortality and the impact of premature delivery, in this population are limited. We describe the 28-day mortality outcomes in a cohort of HIV-exposed infants who had ultrasound-confirmed gestational age in rural Uganda. There were 13 deaths among 351 infants, including 9 deaths in the perinatal period. Premature delivery was a strong predictor of mortality. The prevention of HIV transmission to infants is now possible in rural low-resource settings but the frequency of neonatal death among HIV-exposed infants remains extremely high, calling for new comprehensive interventions to reduce mortality in this growing population.

Routine Healthcare Facility- and Antenatal Care-Based Malaria Surveillance: Challenges and Opportunities.

Most monitoring and evaluation tools for measuring malaria burden, intervention coverage, and impact of interventions use periodic nationally representative cross-sectional household surveys. These provide advantages in terms of selecting a large, unbiased, population-based sample; however, they are infrequently conducted, are resource-intensive, and do not provide longitudinal data with sufficient granularity. Given the heterogeneity of malaria transmission within most endemic countries, systems with the capacity to provide more granular and frequent data would be more actionable by national malaria control programs and local implementing partners. There is increasing interest in using routine health facility data, usually from outpatient department visits, for monitoring malaria burden. Data from pregnant women attending antenatal care (ANC) could minimize bias related to fever care-seeking among outpatient department visits and provide more granular parasite prevalence data. Most pregnant women attend ANC at least once and are thus highly representative of the overall pregnant population. A growing body of evidence suggests that malaria parasitemia in pregnant women is correlated with parasitemia in children aged < 5 years in moderate to high transmission areas, allowing for monitoring parasitemia in real time. Additional data are needed to assess whether pregnant women are sufficiently representative of the overall population to yield valid malaria prevalence and intervention coverage estimates. Although use of routinely collected ANC data faces many of the same challenges experienced by other routinely collected health facility data, the opportunity to improve parasite prevalence monitoring and the associated health benefits to mothers and infants of early detection of parasitemia make these efforts valuable.

Process and Methodological Considerations for Observational Analyses of Vector Control Interventions in Sub-Saharan Africa Using Routine Malaria Data.

Progress in malaria control has stalled in recent years. With growing resistance to existing malaria vector control insecticides and the introduction of new vector control products, national malaria control programs (NMCPs) increasingly need to make data-driven, subnational decisions to inform vector control deployment. As NMCPs are increasingly conducting subnational stratification of malaria control interventions, including malaria vector control, country-specific frameworks and platforms are increasingly needed to guide data use for vector control deployment. Integration of routine health systems data, entomological data, and vector control program data in observational longitudinal analyses offers an opportunity for NMCPs and research institutions to conduct evaluations of existing and novel vector control interventions. Drawing on the experience of implementing 22 vector control evaluations across 14 countries in sub-Saharan Africa, as well as published and gray literature on vector control impact evaluations using routine health information system data, this article provides practical guidance on the design of these evaluations, makes recommendations for key variables and data sources, and proposes methods to address challenges in data quality. Key recommendations include appropriate parameterization of impact and coverage indicators, incorporating explanatory covariates and contextual factors from multiple sources (including rapid diagnostic testing stockouts; insecticide susceptibility; vector density measures; vector control coverage, use, and durability; climate and other malaria and non-malaria health programs), and assessing data quality before the evaluation through either on-the-ground or remote data quality assessments. These recommendations may increase the frequency, rigor, and utilization of routine data sources to inform national program decision-making for vector control.