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Introduction
Skills and Expertise
Publications
Publications (47)
Standard diagnostics used in longitudinal antimalarial studies are unable to characterize the complexity of submicroscopic parasite dynamics, particularly in high transmission settings. We use molecular markers and amplicon sequencing to characterize post-treatment stage-specific malaria parasite dynamics during a 42 day randomized trial of 3- vers...
Objective
To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low‐ and middle‐income countries (LMICs) from 2000 to 2017.
Design
Descriptive multi‐country secondary data analysis.
Setting
Nine LMICs in sub‐Saharan Africa, Southern and Eastern Asia, and Latin America.
Population
Live...
Background The World Health Organization (WHO) recommends seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) for children aged 3 to 59 months, living in areas where malaria transmission is highly seasonal. However, due to widespread prevalence of resistance markers, SMC has not been implemented at scale in...
Objective:
We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs).
Design:
Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000.
Setting:
Sixteen...
Objective:
To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021.
Design:
Descriptive multi-country secondary data analysis.
Setting:
Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021.
Population:
Liveborn infants....
The regulation of inflammation is a critical aspect of disease tolerance and naturally acquired immunity to malaria. Here, we demonstrate using RNA sequencing and epigenetic landscape profiling by cytometry by Time-Of-Flight (EpiTOF), that the regulation of inflammatory pathways during asymptomatic parasitemia occurs downstream of pathogen sensing...
Background
Until recently, due to widespread prevalence of molecular markers associated with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance in east and southern Africa, seasonal malaria chemoprevention (SMC) has not been used at scale in this region. This study assessed the protective effectiveness of monthly administration of SP +...
Background : The World Health Organization (WHO) recommends seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine for children aged 3 to 59 months, living in areas where malaria transmission is highly seasonal. However, due to widespread prevalence of resistance markers, SMC has not been implemented at scale in East...
Background: Until recently, due to widespread prevalence of molecular markers associated with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance in east and southern Africa, seasonal malaria chemoprevention (SMC) has not been used at scale in this region. This study assessed the protective effectiveness of monthly administration of SP+...
Artemisinin-based combination therapies (ACTs) are the primary treatment for malaria. It is essential to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of ACTs in vulnerable populations at risk of suboptimal dosing. We developed a population PK/PD model using data from our previous study of artemether-lumefantrine in HIV-uninfecte...
Background:
Artemether-lumefantrine (AL) is the most widely used artemisinin-based combination therapy (ACT) in sub-Saharan Africa and is threatened by the emergence of artemisinin resistance. Dosing is suboptimal in young children. We hypothesized that extending AL duration will improve exposure and reduce reinfection risks.
Methods:
We conduct...
Background
Intermittent preventive treatment with monthly dihydroartemisinin-piperaquine (DHA-PQ) is highly effective at preventing both malaria during pregnancy and placental malaria. Piperaquine prolongs the corrected QT interval (QTc), and it is possible that repeated monthly dosing could lead to progressive QTc prolongation. Intensive character...
Background
Young infants are protected against Plasmodium falciparum malaria. Mechanisms driving this protection remain unclear due to a poor understanding of malaria clinical phenotypes during infancy.
Methods
We enrolled a birth cohort of 678 infants in Busia, Uganda, an area of high malaria transmission. We followed infants through 12 months of...
Background
Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.
Methods
Data from a birth cohort of 656 infants b...
ABSTRACT
Intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine (SP) is recommended for malaria-endemic parts of Africa, but efficacy is compromised by resistance and, in recent trials, dihydroartemisinin-piperaquine (DP) has shown better antimalarial protective efficacy. We utilized blood samples from a recent...
Dihydroartemisinin-piperaquine (DHA-PQ) provides highly effective therapy and chemoprevention for malaria in pregnant African women. PQ concentrations >10.3 ng/mL have been associated with reduced maternal parasitemia, placental malaria and improved birth outcomes. We characterized the population pharmacokinetics (PK) of PQ in a post-hoc analysis o...
Objective
Placental malaria is a known risk factor for small for gestational age (SGA) neonates. However, currently utilized international and African birthweight standards have not controlled for placental malaria and/or lack obstetrical ultrasound dating. We developed a neonatal birthweight standard based on obstetrically dated pregnancies that e...
Background
Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.
Methods
Data from a birth cohort of 656 infants bo...
Background
Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.
Methods
Data from a birth cohort of 656 infants bo...
Background Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.
Methods Data from a birth cohort of 656 infants bo...
Background:
Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) significantly reduces the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (SP), the current standard of care, but its impact on the incidence of malaria during infancy is unknown.
Methods:
We conducte...
Background
Trials of intermittent preventive treatment (IPTp) of malaria in pregnant women that compared dihydroartemisinin-piperaquine with the standard of care, sulfadoxine-pyrimethamine, showed dihydroartemisinin-piperaquine was superior at preventing malaria infection, but not at improving birthweight. We aimed to assess whether sulfadoxine-pyr...
Background
A considerable challenge in quantification of the antimalarial piperaquine in plasma is carryover of analyte signal between assays. Current intensive pharmacokinetic studies often rely on the merging of venous and capillary sampling. Drug levels in capillary plasma may be different from those in venous plasma, Thus, correlation between c...
Background:
Clinical trials of interventions for preventing malaria in pregnancy often use measures of malaria at delivery as their primary outcome. Although the objective of these interventions is to improve birth outcomes, data on associations between different measures of malaria at delivery and adverse birth outcomes are limited.
Methods:
Da...
Background:
The choice of malaria treatment for HIV-infected pregnant women receiving efavirenz-based antiretroviral therapy must consider the potential impact of drug interactions on antimalarial exposure and clinical response. The aim of this study was to investigate the effects of efavirenz on artemether-lumefantrine (AL) because no studies hav...
Objective Placental malaria is a known risk factor for small for gestational age (SGA) neonates. However, currently utilized international and African birthweight standards have not controlled for placental malaria and/or lack obstetrical ultrasound dating. We developed a neonatal birthweight standard based on obstetrically dated pregnancies that e...
(Abstracted from Lancet 2019;393:1428–1439.)
In Africa, malaria in pregnancy presents a risk to 50 million women each year due to Plasmodium falciparum infection. Although women in endemic areas are typically asymptomatic when infected with malaria parasites, the infection is associated with maternal anemia and adverse birth outcomes including misc...
Background:
Blood smear microscopy remains the gold-standard method to diagnose and quantify malaria parasite density. In addition, parasite genotyping of select loci is the most utilized method for distinguishing recrudescent and new infections and to determine the number of strains per sample. In research settings, blood may be obtained from cap...
Dihydroartemisinin (DHA)‐piperaquine is being evaluated as intermittent preventive therapy for malaria, but dosing has not been optimized for children. We assessed exposure to DHA and piperaquine in Ugandan children at two ages during infancy. Intensive sampling was performed in 32 children at 32 weeks of age, 31 children at 104 weeks, and 30 femal...
Abstract Background Malaria in pregnancy is a major public health challenge, but its risk factors remain poorly understood in some settings. This study assessed the association between household and maternal characteristics and malaria among pregnant women in a high transmission area of Uganda. Methods A nested prospective study was conducted betwe...
Background
Intermittent treatment with sulfadoxine–pyrimethamine, recommended for prevention of malaria in pregnant women throughout sub-Saharan Africa, is threatened by parasite resistance. We assessed the efficacy and safety of intermittent preventive treatment with dihydroartemisinin–piperaquine as an alternative to sulfadoxine–pyrimethamine.
M...
Background:
Placental malaria is a major cause of adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of parasitemia during pregnancy and placental malaria.
Methods:
Data came from 637 women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy (IPT...
Dihydroartemisinin-piperaquine (DHA-PQ) is under study for intermittent preventive treatment during pregnancy (IPTp), but it may accelerate selection for drug resistance. Understanding the relationships between piperaquine concentration, prevention of parasitemia, and selection for decreased drug sensitivity can inform control policies and optimiza...
Background
Lumefantrine is a long-acting antimalarial drug with an elimination half-life of over 3 days and protein binding of 99 percent. Correlation of lumefantrine concentrations from capillary plasma via fingerprick (Cc) versus venous plasma (Cv) remains to be defined.
Methods
Venous and capillary plasma samples were collected simultaneously f...
Subgroup analysis.
Section 1, Subgroup analysis based on HIV status in Children; Section 2, Subgroup analysis based on HIV status in pregnant women; Section 3, Subgroup analysis based on sex in non-pregnant adults.
(DOCX)
Sample profile (Table A) and raw concentration data used for the correlation analysis (Table B and C).
(XLSX)
Background
Dihydroartemisinin-piperaquine (DHA-PQ) is highly efficacious as intermittent preventive therapy for malaria during pregnancy (IPTp). Determining associations between piperaquine (PQ) exposure, malaria risk, and adverse birth outcomes informs optimal dosing strategies.
Methods
Human immunodeficiency virus–uninfected pregnant women (n =...
Dihydroartemisinin (DHA)-piperaquine is promising for malaria chemoprevention in pregnancy. We assessed impacts of pregnancy and efavirenz-based antiretroviral therapy on exposure to DHA and piperaquine in pregnant Ugandan women. Intensive sampling was performed at 28 weeks gestation in 31 HIV-uninfected pregnant women, in 27 HIV-infected pregnant...
Background
Artemisinins are primarily responsible for initial parasite clearance. Antimalarial pharmacokinetics (PK), HIV infection, and antiretroviral therapy have been shown to impact treatment outcomes, though their impact on early parasite clearance in children has not been well characterized.
Methods
Parasite clearance parameters were generat...
Background:
The optimal treatment of malaria in HIV-infected children requires consideration of critical drug-drug interactions in co-infected children, as these may significantly impact drug exposure and clinical outcomes.
Methods:
We conducted an intensive and sparse pharmacokinetic and pharmacodynamic study in Uganda of the most widely adopte...
Artemether-lumefantrine is a first-line regimen for the treatment of uncomplicated malaria during the second and third trimesters of pregnancy. Previous studies have reported changes in the pharmacokinetics and clinical outcomes following treatment with artemether-lumefantrine in pregnant populations, however results are inconclusive. We conducted...
