Parasitological Clearance Rates and Drug Concentrations of a Fixed Dose Combination of Azithromycin-Chloroquine in Asymptomatic Pregnant Women with Plasmodium Falciparum Parasitemia: An Open-Label, Non-Comparative Study in Sub-Saharan Africa.

BACKGROUND: Malaria remains one of the most important causes of morbidity and mortality in pregnant women and their newborn babies in sub-Saharan Africa. Intermittent preventive treatment in pregnancy (IPTp) is recommended by the World Health Organization (WHO) to reduce the burden of disease and improve maternal and neonatal survival and general health. Due to the growing resistance to sulfadoxine-pyrimethamine (SP), the current WHO-recommended drug for IPTp, identification of new and effective drugs is an urgent priority. METHODS AND FINDINGS: This was an open-label, non-comparative study (NCT01103713) in 5 countries in East and sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda) to assess parasitological response and drug concentrations of a single, 3-day course of four tablets of a fixed-dose combination of azithromycin-chloroquine (AZCQ) 250/155 mg given during the second or third trimester to women with asymptomatic Plasmodium falciparum parasitemia in their first or second pregnancy. Parasitemia was determined by microscopy and molecular genotyping was performed to characterize parasites relative to the baseline infection. Weekly follow-up visits took place until day 42 after first dose and additional follow-up occurred after delivery. Systemic concentrations of azithromycin (AZ), chloroquine (CQ), and the CQ metabolite, desethyl CQ (DECQ) were evaluated at Day 0 (pre-dose), at Day 2 (pre-dose, 2 and 8 hours) and randomly at Days 7 and 14. Systemic concentrations of CQ and DECQ were also measured randomly at Day 21 and Day 28. In total, 404 women were screened for eligibility and 168 were treated, 155 of whom completed the study. PCR-adjusted parasitological response in the modified intent-to-treat population at day 28 (the primary efficacy endpoint) was estimated by the Kaplan-Meier method as 99.35% (95% confidence interval [CI]: 97.76, 100.00). PCR-adjusted parasitological response remained high at day 42 (95.19%; 95% CI: 91.35, 99.03). In general, the mean concentrations of serum AZ, plasma CQ, and plasma DECQ showed large CV% values (ranges of 33-156%, 42-228%, and 57-109%, respectively). There were 157 live births, three stillbirths, and eight pregnancies of unknown outcome: 7 due to withdrawal of participant consent and 1 lost to follow-up. The most frequent treatment-emergent adverse events were vomiting (20.8%) and dizziness (19.6%). CONCLUSIONS: These results suggest that a 3-day course of AZCQ can lead to an adequate 28-day parasitological response.

Multiplex 5' nuclease-quantitative PCR for diagnosis of relapsing fever in a large Tanzanian cohort.

Relapsing fever (RF) is caused by tick- and louse-borne Borrelia spp., is characterized by recurrent fever, and is often misdiagnosed as malaria. Because of submicroscopic bacteremia, microscopy can be insensitive between febrile bouts. We designed a multiplex quantitative PCR (qPCR) assay to distinguish RF Borrelia from Plasmodium falciparum and P. vivax. The assay specifically (100%) amplified pathogenic RF Borrelia (1 copy/reaction). We then tested blood from participants within a Tanzanian cohort assessed at scheduled intervals and with fever. Among 8,617 blood samples from 2,057 participants surveyed routinely, 7 (0.08%) samples and 7 (0.3%) participants had RF DNA (median, 4.4 × 10(3) copies/ml). Of 382 samples from 310 febrile persons, 15 (3.9%) samples from 13 (4.2%) participants had RF DNA (median, 7.9 × 10(2) copies/ml). Five (1.3%) samples from 4 (1.3%) participants were found to harbor Borrelia by microscopy. We conclude that multiplex qPCR holds promise for improved clinical diagnosis and epidemiologic assessment of RF.