Elizabeth Juma

Kenya Medical Research Institute | KEMRI · Centre for Clinical Research

Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimala...

Background The World Health Organization recommends quinine plus clindamycin as first-line treatment of malaria in the first trimester of pregnancy and as a second-line treatment for uncomplicated falciparum malaria when artemisinin-based drug combinations are not available. The efficacy of quinine plus clindamycin was compared with that of artemet...

Background: World Health Organisation recommends quinine plus clindamycin as first-line treatment of malaria in the first trimester of pregnancy and as a second-line treatment for uncomplicated falciparum malaria when artemisinin-based drug combinations are not available. We compared the efficacy of quinine plus clindamycin with that of artemether-...

Background Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of unco...

Background Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy...

Background: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin der...

Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods: Antimalarial studies typically report the...

Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) are the most commonly-used treatments against Plasmodium falciparum malaria in Africa. The lumefantrine and amodiaquine partner drugs may provide differing durations of post-treatment prophylaxis, an important additional benefit to patients. Analyzing 4214 individuals from clinical tri...

We have developed and validated a sensitive, selective and reproducible reversed-phase high-performance liquid chromatography method coupled with electrospray ionization mass spectrometry (HPLC–ESI-MS/MS) for the simultaneous quantitation of artemether (ART), dihydroartemisinin (DHA), lumefantrine (LUM) and desbutyl-lumefantrine (DBL) in human plas...

Background: Few longitudinal studies have examined associations between risk factors during pregnancy and mental health outcomes during the postpartum period. We used a cohort study design to estimate the prevalence, incidence and correlates of significant postpartum depressive symptoms in Kenyan women. Methods: We recruited adult women residing...

We have developed and validated a sensitive, selective and reproducible reversed-phase high-performance liquid chromatography method coupled with electrospray ionization mass spectrometry (HPLC–ESI-MS/MS) for the simultaneous quantitation of artemether (ART), dihydroartemisinin (DHA), lumefantrine (LUM) and desbutyl-lumefantrine (DBL) in human plas...

Background The PfEMP1 family of Plasmodium falciparum antigens play a key role in pathogenesis of severe malaria through their insertion into the surface of parasite infected erythrocytes, and adhesion to host cells. Previous studies have suggested that parasites expressing PfEMP1 subclasses group A and DC8, associated with severe malaria, may have...

( Lancet . 2015;386:2507–2519) In sub-Saharan Africa, there are >32 million pregnancies annually. As this is a malaria-endemic region, it is estimated approximately 12 million women who have live births (45% of live births) would be exposed to malaria infection each year. The World Health Organization (WHO) recommends intermittent preventive treatm...

Parasite multiplication rates for all volunteers in KCS. 95% Confidence intervals for each value are indicated. PMR, parasite multiplication rate (fold change in parasites over 48 h). Volunteer 110 is highlighted in red. These data have been reported previously (Hodgson et al., 2014) but are replotted here for completeness.

Kaplan Meier plots of time to diagnosis in VAC049 and KCS. (A) VAC049 where median pre-patent period = 13.19 days for 2500 SPZ ID; 17.8 days for 2500 SPZ IM; and 12.72 days for 25,000 SPZ IM. Comparison between all groups: p = 0.024, Log rank test. (B) KCS where median pre-patient period = 12.2 days for minimally exposed and 12.1 days for definitel...

Serum IgG antibody responses pre- and post-CHMI for VAC049 and volunteers with minimal prior exposure to malaria in KCS. (A) VAC049 (n = 14). Responses are shown before (C−1) and after (C+35) CHMI. (B) Antibody responses at C−1 for VAC049 and volunteers with minimal prior exposure to malaria (MinExp) in KCS (n = 14). (C) Antibody responses at C+35...

Analysis of antibody responses, GIA and ADRB activity for VAC049: Only subjects infected in VAC049 were included (n = 14). GIA was not available for VAC049 volunteer 1224 at C−1. ELISA responses for RH5 were not included in the table as most values were negative. Correlations were performed using Spearman rank test. Comparisons were performed using...

Comparison of Liver to Blood inoculum between volunteers diagnosed with malaria in KCS and VAC049. LBI, liver to blood inoculum—total number of parasites released from liver on C+6.5 as modeled from the qPCR data.

Background: The timing of infection is closely determined in controlled human malaria infection (CHMI) studies, and as such they provide a unique opportunity to dissect changes in immunological responses before and after a single infection. The first Kenyan Challenge Study (KCS) (Pan African Clinical Trial Registry: PACTR20121100033272) was perform...

Background: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual pa...

Background Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual pati...

Additional file 2: Figure S1. Relationship between gametocytaemia on enrolment and baseline haemoglobin concentration, parasitaemia and patient age. The predicted probability of gametocyte carriage at enrolment is plotted from the multivariate model; the line indicates the best fit, the shaded area the 95 % CI. Only patients from studies with gamet...

Additional file 3: Table S2. Independent risk factors for the prevalence of gametocytaemia at enrolment in children aged 1–5 years. Logistic multivariable analysis by region with prevalence of gametocytaemia at enrolment as dependent variable. Nobs, Number of observations; Npos, Number of positive observations. The relationship between gametocyte p...

Additional file 8: Table S7. Sensitivity analysis: variation in model coefficients after exclusion of individual studies. 1 Estimates as obtained in the final multivariate models and listed in main tables. 2 RSD, Relative standard deviation was calculated as a ratio of standard deviation to mean of the estimates (odds ratio or hazard ratio) calcula...

Additional file 9: Figure S2. Development of gametocytaemia after treatment evaluated in patients with no gametocytaemia on enrolment and full 28-day follow-up. A: Development of gametocytaemia by artemisinin combination therapy. B: Development of gametocytaemia by treatment outcome. (TIF 284 kb)

Additional file 4: Table S3. The effect of treatment dosing on the appearance of gametocytaemia in participants without microscopically detected gametocytaemia before treatment (time to gametocytaemia) and clearance of gametocytaemia in participants with gametocytaemia at enrolment (time to clearance). All analyses of time to clearance are adjusted...

Additional file 7: Table S6. Factors associated with the development of gametocytaemia after enrolment in individuals who were gametocyte-free before treatment with artemisinin combination therapy. Cox regression model for time to gametocytaemia. Only patients with complete 28-day follow-up are included. (DOC 35 kb)

Additional file 1: Table S1. Overview of all included studies. 1 The sensitivity of microscopy methods was classified into one of four categories: 1 = studies in which slides were specifically read for gametocytes, reviewing at least 100 microscopic high power fields or against ≥ 1000 white blood cells (WBC); 2 = microscopists specifically instruct...

Additional file 5: Table S4. Factors associated with the clearance of gametocytaemia after enrolment in individuals who were gametocytaemic before treatment with artemisinin combination therapy. Nobs, Number of observations; N cleared, Number of patients with day of clearance of gametocytaemia recorded. Derived haemoglobin, conversion from haematoc...

Additional file 6: Table S5. Risk of bias in individual studies included in the analysis. ACT, Artemisinin combination therapy. 1 For trials with non-ACTs, data were only analysed for gametocytaemia on enrolment and regimens, arms, randomization, concealment of treatment, sequence generation and treatment blinding are given as not applicable (NA)....

BACKGROUND: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual pat...

Introduction: Longitudinal studies that assess antepartum risk factors and outcome in the postpartum period can help provide a wealth of information in understanding maternal depression. In addition to collecting information on prevalence and correlates of antepartum depression, such studies reveal postpartum outcomes of depression as well as its r...

Rising reports of exophagic malaria vectors make even more pressing the need for alternatives to traditional, mesh, long-lasting insecticidal nets (LLINs) designed for indoor sleeping and they are often inadequate in the protection of outdoor-sleeping populations. This study tests and evaluates the retention, utilization, and durability of novel, n...

Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference...

Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials including current artemisinin-based combination therapies.A...

Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan Afri...

References of all clinical trials and their study designs

Maps showing locations of published clinical efficacy studies and the studies included in the pooled analysis

Transmission classification

Additional tables and figures

Authors and contributions

Background: Every year, more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences. The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance. We aimed to assess the efficacy and...

Background Artemether–lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. Methods We searched PubMed for clinical trials...

Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development. CHMI studies provide a cost-effective and expeditious way to circumvent the use of large-scale field e...

Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to t reat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient d...

Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Individual patient data from AS-AQ clinica...

Current day malaria cases and deaths are indicative of a lack of access to both methods of prevention, diagnosis and treatment; an important determinant of treatment efficacy is adherence. This study is a follow up to the baseline study of adherence to artemether-lumefantrine (AL) carried out in Garissa District in 2010. The study presented evaluat...

To describe the state of the public and private malaria diagnostics market shortly after WHO updated its guidelines for testing all suspected malaria cases prior to treatment. 10 nationally representative cross-sectional cluster surveys were conducted in 2011 among public and private health facilities, community health workers, and retail outlets (...