Asymptomatic malaria and anemia during pregnancy increase the risk of negative birth outcomes. This cross-sectional study investigated the prevalence and correlates of asymptomatic malaria and anemia during first antenatal care (ANC) visit among pregnant women in a rural district, Tanzania. HIV-uninfected pregnant women without symptoms of malaria (n = 819) attending their first ANC at Kibiti Health Centre were enrolled from February 2017 to February 2018. Asymptomatic malaria was detected by malaria rapid-diagnostic tests (mRDT) and real-time PCR. Hemoglobin concentration was determined by HemoCue Hemoglobin 201+. The study outcomes were the prevalence of asymptomatic malaria and anemia (Hemoglobin level 25% throughout the year, and the highest prevalence (40%) was recorded during the rainy season. Asymptomatic malaria was significantly associated with primigravida, younger maternal age, and anemia. The prevalence of anemia was 68.5% (95% CI: 65.2, 71.6). Asymptomatic malaria, primigravida, younger maternal age and low Body Mass Index were significant predictors of low hemoglobin concentration. We report high prevalence of asymptomatic malaria and anemia among pregnant women on the first ANC visit. Screening of malaria and anemia during the first ANC visit is recommended for targeted interventions.

HIV-malaria co-infected patients in most parts of sub-Saharan Africa are treated with both artemether-lumefantrine (AL) and efavirenz (EFV) or nevirapine (NVP)-based antiretroviral therapy (ART). EFV, NVP, artemether and lumefantrine are substrates, inhibitors or inducers of CYP3A4 and CYP2B6, creating a potential for drug-drug interactions. The effect of EFV and/or NVP on lumefantrine pharmacokinetic profile among HIV-malaria co-infected patients on ART and treated with AL was investigated. Optimal lumefantrine dosage regimen for patients on EFV-based ART was determined by population pharmacokinetics and simulation. This was a non-randomized, open label, parallel, prospective cohort study in which 128, 66 and 75 HIV-malaria co-infected patients on NVP-based ART (NVP-arm), EFV-based ART (EFV-arm) and ART naïve (control-am) were enrolled, respectively. Patients were treated with AL and contributed sparse venous plasma samples. Pharmacokinetic analysis of lumefantrine was done using non-linear mixed effect modelling. Of the evaluated models, a two-compartment pharmacokinetic model with first order absorption and lag-time described well lumefantrine plasma concentrations time profile. Patients in the EFV-arm but not in the NVP-arm had significantly lower lumefantrine bioavailability compared to that in the control-arm. Equally, 32% of patients in the EFV-arm had day-7 lumefantrine plasma concentrations below 280 ng/ml compared to only 4% in the control-arm and 3% in the NVP-arm. Upon post hoc simulation of lumefantrine exposure, patients in the EFV-arm had lower exposure (median (IQR)) compared to that in the control-arm; AUC0-inf; was 303,130 (211,080–431,962) versus 784,830 (547,405–1,116,250); day-7 lumefantrine plasma concentrations was: 335.5 (215.8-519.5) versus 858.7 (562.3-1,333.8), respectively. The predictive model through simulation of lumefantrine exposure at different dosage regimen scenarios for patients on EFV-based ART, suggest that AL taken twice daily for five days using the current dose could improve lumefantrine exposure and consequently malaria treatment outcomes. Co-treatment of AL with EFV-based ART but not NVP-based ART significantly reduces lumefantrine bioavailability and consequently total exposure. To ensure adequate lumefantrine exposure and malaria treatment success in HIV-malaria co-infected patients on EFV-based ART, an extension of the duration of AL treatment to five days using the current dose is proposed.

Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI: 5.1–6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age (p < 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA (p < 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of <1% mf and <2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.

Intermittent preventive treatment in pregnancy with sulfadoxine‐pyrimethamine (IPTp‐SP) to prevent malaria and adverse birth outcomes is threatened by Plasmodium falciparum resistance to sulfadoxine‐pyrimethamine. We investigated the effectiveness of intermittent preventive treatment in pregnancy with monthly dihydroartemisinin‐piperaquine (IPTp‐DHP) as an alternative option to IPTp‐SP. A total of 956 malaria‐free (malaria rapid diagnostic test (MRDT) negative) pregnant women from moderate malaria transmission areas in Tanzania were enrolled and randomized to receive monthly IPTp‐DHP (n = 478) or IPTp‐SP (n = 478) and followed for maternal and birth outcomes. The primary outcome was the prevalence of histopathologically confirmed placental malaria (active or past infection). Secondary outcomes were overall malaria at delivery, symptomatic‐malaria, parasitemia during pregnancy, and adverse birth outcomes as a composite of spontaneous‐abortion, premature birth, stillbirth, and low birth weight (LBW) fetal anemia. Outcome differences between treatment groups were expressed as the protective efficacy (PE), defined as 1‐prevalence ratios or 1‐incidence rate ratio. The prevalence of histopathologically confirmed placental malaria was significantly lower in IPTp‐DHP (2.5%, 12/478) than IPTp‐SP (8.2%, 39/478); PE = 69% (95% confidence interval (CI): 42–84, P < 0.001). The prevalence of maternal malaria at delivery was significantly lower in IPTp‐DHP (8.2%) than IPTp‐SP (18.2%, P < 0.001). The incidence per person‐years at risk for symptomatic‐malaria (0.02 vs. 0.12, P = 0.002) and parasitemia during pregnancy (0.28 vs. 0.67, P < 0.001) were significantly lower in the IPTp‐DHP group than in the IPTp‐SP group. The prevalence of any adverse birth outcomes (composite) was not significantly (P = 0.06) different between IPTp‐DHP (17.9%) and IPTp‐SP (23.8%). However, the prevalence of LBW (4.6% vs. 9.6%, P = 0.003) was significantly lower in IPTp‐DHP compared with IPTp‐SP. We report superior protective efficacy of monthly IPTp‐DHP against malaria in pregnancy and LBW than IPTp‐SP.

Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed to examine the effect of pharmacogenetics on lumefantrine (LF) pharmacokinetics and treatment outcome in pregnant women. Pregnant women with uncomplicated falciparum malaria were enrolled and treated with artemether-lumefantrine (ALu) at Mkuranga and Kisarawe district hospitals in Coast Region of Tanzania. Day-7 LF plasma concentration and genotyping forCYP2B6 (c.516G>T, c.983T>C), CYP3A4*1B, CYP3A5 (*3, *6, *7) and ABCB1 c.4036A4G were determined. Blood smear for parasite quantification by microscopy, and dried blood spot for parasite screening and genotyping using qPCR and nested PCR were collected at enrolment up to day 28 to differentiate between reinfection from recrudescence. Treatment response was recorded following the WHO protocol. In total, 92 pregnant women in their second and third trimester were included in the study and 424 samples were screened for presence of P. falciparum. Parasites were detected during the follow up period in 11 (12%) women between day 7 and 28 after treatment and PCR genotyping confirmed recrudescent infection in 7 (63.3%) women. The remaining four (36.4%) pregnant women had reinfection: one on day 14 and three on day 28. The overall PCR-corrected treatment failure rate was 9.0% (95% CI 4.4–17.4). Day 7 LF concentration was not significantly influenced by CYP2B6, CYP3A4*1B and ABCB1 c.4036A>G genotypes. Significant associations between CYP3A5 genotype and day 7 plasma LF concentrations was found, being higher in carriers of CYP3A5 defective variant alleles than CYP3A5*1/*1 genotype. No significant influence of CYP2B6, CYP3A5 and ABCB1 c.4036A>Genotypes on malaria treatment outcome were observed. However, CYP3A4*1B did affect malaria treatment outcome in pregnant women followed up for 28 days (P = 0.018). Genetic variations in CYP3A4 and CYP3A5may influence LF pharmacokinetics and treatment outcome in pregnant women.

Peer reviewed article authored by (Minzi OM, Manyilizu VS). Read article or submit your manuscript for publishing.