Julia Nanteza Mwesigwa

PATH · Malaria and NTDs

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 b...

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 co...

As part of the New Nets Project, new insecticide-treated net (ITN) types, Interceptor® G2 (BASF) (IG2) and PermaNet® 3.0 (Vestergaard SA) (PBO), were included in a select number of districts during the 2019 universal coverage campaign in Burkina Faso. This manuscript describes the results of the observational study that accompanied the IG2 and PBO...

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 a...

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, a...

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 dua...

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...

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 vil...

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...

Background: Antibody responses have been used to characterise transmission and exposure history in malaria-endemic settings for over a decade. Such studies have typically been conducted on well-standardised enzyme-linked immunosorbent assays (ELISAs). However, recently developed quantitative suspension array technologies (qSAT) are now capable of h...

Background As The Gambia aims to achieve elimination by 2030, serological assays can be a useful surveillance tool to monitor trends in malaria incidence and evaluate community-based interventions. Methods Spatio-temporal variation in transmission in four Gambian study villages was measured using a panel of novel recombinant Pf antigens on a multi...

Background Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system b...

Malaria has declined significantly in The Gambia and determining transmission dynamics of Plasmodium falciparum can help targeting control interventions towards elimination. This can be inferred from genetic similarity between parasite isolates from different sites and timepoints. Here, we imposed a P. falciparum life cycle time on a genetic distan...

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 vill...

In The Gambia, metal-roof houses were hotter during the day than thatched-roof houses. After 24 h, the mortality of Anopheles gambiae, the principal African malaria vector, was 38% higher in metal-roof houses than thatched ones. During the day, mosquitoes in metal-roof houses moved from the hot roof to cooler places near the floor, where the temper...

Background Mass drug administration (MDA) may reduce malaria transmission in low-transmission areas and interrupt transmission. The impact of MDA with dihydroartemisinin-piperaquine (DP) on malaria infection and clinical malaria was determined in a prospective cohort study in The Gambia. Methods Single annual MDA rounds with DP were done in 2014 a...

Background: Antibody responses have been used to characterise transmission and exposure history in malaria-endemic settings for over a decade. Such studies have typically been conducted on well-standardised enzyme-linked immunosorbent assays (ELISAs). However, recently developed quantitative suspension array technologies (qSAT) are now capable of h...

Background: Mass drug administration (MDA) may further reduce malaria transmission in low transmission areas. The impact of MDA on dynamics of malaria transmission was determined in a prospective cohort study. Methods: Annual rounds of MDA with dihydroartemisinin-piperaquine (DP) were implemented over two years (2014 and 2015) in six village pai...

Mass drug administration (MDA) may further reduce malaria transmission in low transmission areas. The impact of MDA on dynamics of malaria transmission was determined in a prospective cohort study. Annual rounds of MDA with dihydroartemisinin-piperaquine (DP) were implemented over two years (2014 and 2015) in six village pairs before the malaria tr...

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...

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. Data from a longitudinal cohort in T...

Amodiaquine plus artesunate is the recommended antimalarial treatment in many malaria-endemic countries. 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...

Over the last decades, malaria has declined substantially in The Gambia but its transmission has not been interrupted. In order to better target control interventions, it is essential to understand the dynamics of residual transmission. This prospective cohort study was conducted between June 2013 and April 2014 in six pairs of villages across The...

Proportion of infections with gametocyte by month. (DOCX)

Introduction: Antimalarial drugs are essential weapons to fight malaria and have been used effectively since the 17th century. However, P.falciparum resistance has been reported to almost all available antimalarial drugs, including artemisinin derivatives, raising concerns that this could jeopardize malaria elimination. Areas covered: In this artic...

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...

Background Children born to mothers who had malaria in pregnancy have an increased risk of malaria infection in the first 24 months of life and they also experience earlier episodes of malaria compared to their counterparts. This study compared the pre- and post-seasonal prevalence of P. falciparum infection and anti-malarial antibodies among child...

Background The reduction in the malaria burden previously reported in The Gambia is largely due to the successful scaling up of control interventions. Understanding the current dynamics of malaria transmission in a context of high coverage of control interventions is critical to inform pre-elimination efforts. Methods A cohort study was conducted...

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. Using WHO susceptibility bioassays, insecticide res...

The potential benefits of Mass Drug Administration (MDA) for malaria elimination are being considered in several malaria endemic countries where a decline in malaria transmission has been reported. For this strategy to work, it is important that a large proportion of the target population participates, requiring an in-depth understanding of factors...

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...

Food insecurity is associated with poor virologic outcomes, but this has not been studied during pregnancy and breastfeeding. We assessed sustained viral suppression from 8 weeks on ART to 48 weeks postpartum among 171 pregnant and breastfeeding Ugandan women; 74.9% experienced food insufficiency (FI). In multivariable analysis, FI (adjusted odds r...

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. A nationwide cross-sectional survey was conducted in 2012 to determine the prevalence of P. falciparum infec...

Hair concentrations are a noninvasive measure of cumulative antiretroviral exposure and the strongest predictor of viral suppression in large cohorts of nonpregnant patients. We examined hair concentrations of antiretrovirals in relation to virologic outcomes in pregnant and breastfeeding women for the first time. The Prevention of Malaria and HIV...

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...

Combination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4 cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda. Randomized clinical trial. We performed a planned seconda...

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-c...

Background: Protease inhibitor-based antiretroviral therapy (ART) has been associated with preterm birth in some studies. We examined risk factors for preterm birth among women randomized to lopinavir/ritonavir (LPV/r)- or efavirenz (EFV)-based ART. Methods: This was a planned secondary analysis of the PROMOTE-Pregnant Women and Infants Study, a...

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...

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, s...

Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot...

Background: As efforts intensify to eliminate perinatal HIV transmission, understanding kinetics of maternal-to-child transfer of antiretrovirals during pregnancy and breastfeeding is critical. Antiretroviral levels in plasma, cord blood, and breastmilk reflect exposure over short intervals. Hair concentrations reflect cumulative exposure and can u...

Background: As efforts intensify to eliminate perinatal HIV transmission, understanding kinetics of maternal-to-child transfer of antiretrovirals during pregnancy and breastfeeding is critical. Antiretroviral levels in plasma, cord blood, and breastmilk reflect exposure over short intervals. Hair concentrations reflect cumulative exposure and can...

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...

Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration...

Univariate and multivariate linear regression models of weekly gestational weight gain. (DOC)

Univariate and multivariate logistic regression models of small for gestational age. (DOC)

Univariate and multivariate logistic regression models of head-sparing growth restriction. (DOC)

CONSORT 2010 flow diagram for NCT00993031. (TIFF)

Univariate and multivariate logistic regression models of low birthweight. (DOC)

CONSORT checklist. (PDF)

Univariate and multivariate logistic regression models of stunting. (DOC)

Univariate and multivariate logistic regression models of preterm delivery. (DOC)

Trial protocol. (DOC)

Ugandan guidelines recommend 6 months of exclusive breastfeeding (EBF) for HIV‐infected women on antiretroviral therapy (ART), with continued breastfeeding (BF) for at least 1 year. We explored infant feeding (IF) practices and beliefs among HIV‐infected pregnant and BF women on ART in the PROMOTE trial (NCT00993031) in Tororo, Uganda. IF practices...

The World Health Organization recommends the use of artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria. The two most widely adopted ACT regimens are artemether (AR)-lumefantrine (LR) (the combination is abbreviated AL) and amodiaquine (AQ)-artesunate (AS). Pharmacokinetic (PK) data informing the optimum dosing...