Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-treatment prophylaxis, whereas dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.).

Malaria transmission in northern Zambia has increased in the past decade, despite malaria control activities. Evidence-based intervention strategies are needed to effectively reduce malaria transmission. Zambia’s National Malaria Control Centre conducted targeted indoor residual spraying (IRS) in Nchelenge District, Luapula Province, from 2014 to 2016 using the organophosphate insecticide pirimiphos-methyl. An evaluation of the IRS campaign was conducted by the Southern Africa International Centers of Excellence for Malaria Research using actively detected malaria cases in bimonthly household surveys carried out from April 2012 to July 2017. Changes in malaria parasite prevalence after IRS were assessed by season using Poisson regression models with robust standard errors, controlling for clustering of participants in households and demographic, geographical, and climatological covariates. In targeted areas, parasite prevalence declined approximately 25% during the rainy season following IRS with pirimiphos-methyl but did not decline during the dry season or in the overall study area. Within targeted areas, parasite prevalence declined in unsprayed households, suggesting both direct and indirect effects of IRS. The moderate decrease in parasite prevalence within sprayed areas indicates that IRS with pirimiphos-methyl is an effective malaria control measure, but a more comprehensive package of interventions is needed to effectively reduce the malaria burden in this setting.

Background Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy. Many countries have observed decreases in the prevalence of chloroquine resistance with the discontinuation of chloroquine use. In Zambia, chloroquine was used as first-line treatment for uncomplicated malaria until treatment failures led the Ministry of Health to replace it with artemether-lumefantrine in 2003. Specimens from a recent study were analysed to evaluate prevalence of chloroquine-resistant malaria in Nchelenge district a decade after chloroquine use was discontinued.MethodsParasite DNA was extracted from dried blood spots collected by finger-prick in pregnant women who were enrolling in a clinical trial. The specimens underwent pyrosequencing to determine the genotype of the P. falciparum chloroquine resistance transporter, the gene that is associated with CQ resistance.ResultsThree-hundred and two specimens were successfully analysed. No chloroquine-resistant genotypes were detected.ConclusionThe study found the disappearance of chloroquine-resistant malaria after the removal of chloroquine drug pressure. Chloroquine may have a role for malaria prevention or treatment in Zambia and throughout the region in the future.

Purpose of Review Five years have passed since the World Health Organization released its Global Technical Strategy for Malaria (GTS). In that time, progress against malaria has plateaued. This review focuses on the implications of antimalarial drug resistance for the GTS and how interim progress in parasite genomics and antimalarial pharmacology offer a bulwark against it. Recent Findings For the first time, drug resistance–conferring genes have been identified and validated before their global expansion in malaria parasite populations. More efficient methods for their detection and elaboration have been developed, although low-density infections and polyclonality remain a nuisance to be solved. Clinical trials of alternative regimens for multidrug-resistant malaria have delivered promising results. New agents continue down the development pipeline, while a nascent infrastructure in sub-Saharan Africa for conducting phase I trials and trials of transmission-blocking agents has come to fruition after years of preparation. Summary These and other developments can help inform the GTS as the world looks ahead to the next two decades of its implementation. To remain ahead of the threat that drug resistance poses, wider application of genomic-based surveillance and optimization of existing and forthcoming antimalarial drugs are essential.

BackgroundDetermining gestational age in resource-poor settings is challenging because of limited availability of ultrasound technology and late first presentation to antenatal clinic. Last menstrual period (LMP), symphysio-pubis fundal height (SFH) and Ballard Score (BS) at delivery are therefore often used. We assessed the accuracy of LMP, SFH, and BS to estimate gestational age at delivery and preterm birth compared to ultrasound (US) using a large dataset derived from a randomized controlled trial in pregnant malaria patients in four African countries.MethodsMean and median gestational age for US, LMP, SFH and BS were calculated for the entire study population and stratified by country. Correlation coefficients were calculated using Pearson’s rho, and Bland Altman plots were used to calculate mean differences in findings with 95% limit of agreements. Sensitivity, specificity, positive predictive value and negative predictive value were calculated considering US as reference method to identify term and preterm babies.ResultsA total of 1630 women with P. falciparum infection and a gestational age > 24 weeks determined by ultrasound at enrolment were included in the analysis. The mean gestational age at delivery using US was 38.7 weeks (95%CI: 38.6–38.8), by LMP, 38.4 weeks (95%CI: 38.0–38.9), by SFH, 38.3 weeks (95%CI: 38.2–38.5), and by BS 38.0 weeks (95%CI: 37.9–38.1) (p < 0.001). Correlation between US and any of the other three methods was poor to moderate. Sensitivity and specificity to determine prematurity were 0.63 (95%CI 0.50–0.75) and 0.72 (95%CI, 0.66–0.76) for LMP, 0.80 (95%CI 0.74–0.85) and 0.74 (95%CI 0.72–0.76) for SFH and 0.42 (95%CI 0.35–0.49) and 0.77 (95%CI 0.74–0.79) for BS.ConclusionsIn settings with limited access to ultrasound, and in women who had been treated with P. falciparum malaria, SFH may be the most useful antenatal tool to date a pregnancy when women present first in second and third trimester. The Ballard postnatal maturation assessment has a limited role and lacks precision. Improving ultrasound facilities and skills, and early attendance, together with the development of new technologies such as automated image analysis and new postnatal methods to assess gestational age, are essential for the study and management of preterm birth in low-income settings.Electronic supplementary materialThe online version of this article (10.1186/s12884-018-2128-z) contains supplementary material, which is available to authorized users.

Malaria transmission is dependent on the density and distribution of mosquito vectors, but drivers of vector abundance have not been adequately studied across a range of transmission settings. To inform intervention strategies for high-burden areas, further investigation is needed to identify predictors of vector abundance. Active household (HH) surveillance was conducted in Nchelenge district, Luapula Province, northern Zambia, a high-transmission setting with limited impact of malaria control. Between April 2012 and July 2017, mosquitoes were collected indoors during HH visits using CDC light traps. Demographic, environmental, and climatological correlates of vector abundance were identified using log-binomial regression models with robust standard errors. The primary malaria vectors in this setting were Anopheles funestus sensu stricto (s.s.) and Anopheles gambiae s.s. Anopheles funestus predominated in both seasons, with a peak in the dry season. Anopheles gambiae peaked at lower numbers in the rainy season. Environmental, climatic, and demographic factors were correlated with HH vector abundance. Higher vector counts were found in rural areas with low population density and among HHs close to roads and small streams. Vector counts were lower with increasing elevation and slope. Anopheles funestus was negatively associated with rainfall at lags of 2-6 weeks, and An. gambiae was positively associated with rainfall at lags of 3-10 weeks. Both vectors had varying relationships with temperature. These results suggest that malaria vector control in Nchelenge district should occur throughout the year, with an increased focus on dry-season transmission and rural areas.

Abstract.Malaria remains a public health crisis in areas where it has resisted control efforts. In Nchelenge District, a high-transmission area in northern Zambia, malaria accounts for more than one-third of pediatric hospitalizations and nearly one-half of hospital deaths in children. To identify risk factors for death due to malaria, we conducted a retrospective, time-matched case-control study of 126 children hospitalized with malaria who died (cases) and 126 children who survived (controls). There were no differences in age, gender, hemoglobin concentration, or prevalence of severe anemia between cases and controls. Children who died were more likely to come from villages located at greater distances from the hospital than children who survived (median 13.5 versus 3.2 km). Each additional kilometer of distance from the hospital increased the odds of death by 4% (odds ratio 1.04, 95% confidence interval 1.01–1.07, P < 0.01). Extent of anemia and admission during periods when blood was unavailable for transfusion were associated with early death (P ≤ 0.03). Delays in initiation of treatment of severe malaria contribute to the increased odds of death in children referred from more distant health centers, and might be mitigated by transportation improvements, capacity at rural health posts to administer treatment before transfer, hospital triage systems that minimize time to treatment, and reliable blood product stores at referral hospitals.

BackgroundIn Zambia, malaria is one of the leading causes of morbidity and mortality, especially among under five children and pregnant women. For the latter, the World Health Organization recommends the use of artemisinin-based combination therapy (ACT) in the second and third trimester of pregnancy. In a context of limited information on ACT, the safety and efficacy of three combinations, namely artemether–lumefantrine (AL), mefloquine–artesunate (MQAS) and dihydroartemisinin–piperaquine (DHAPQ) were assessed in pregnant women with malaria.MethodsThe trial was carried out between July 2010 and August 2013 in Nchelenge district, Luapula Province, an area of high transmission, as part of a multi-centre trial. Women in the second or third trimester of pregnancy and with malaria were recruited and randomized to one of the three study arms. Women were actively followed up for 63 days, and then at delivery and 1 year post-delivery.ResultsNine hundred pregnant women were included, 300 per arm. PCR-adjusted treatment failure was 4.7% (12/258) (95% CI 2.7–8.0) for AL, 1.3% (3/235) (95% CI 0.4–3.7) for MQAS and 0.8% (2/236) (95% CI 0.2–3.0) for DHAPQ, with significant risk difference between AL and DHAPQ (p = 0.01) and between AL and MQAS (p = 0.03) treatments. Re-infections during follow up were more frequent in the AL (HR: 4.71; 95% CI 3.10–7.2; p < 0.01) and MQAS (HR: 1.59; 95% CI 1.02–2.46; p = 0.04) arms compared to the DHAPQ arm. PCR-adjusted treatment failure was significantly associated with women under 20 years [Hazard Ratio (HR) 5.35 (95% CI 1.07–26.73; p = 0.04)] and higher malaria parasite density [3.23 (95% CI 1.03–10.10; p = 0.04)], and still women under 20 years [1.78, (95% CI 1.26–2.52; p < 0.01)] had a significantly higher risk of re-infection. The three treatments were generally well tolerated. Dizziness, nausea, vomiting, headache and asthenia as adverse events (AEs) were more common in MQAS than in AL or DHAPQ (p < 0.001). Birth outcomes were not significantly different between treatment arms.ConclusionAs new infections can be prevented by a long acting partner drug to the artemisinins, DHAPQ should be preferred in places as Nchelenge district where transmission is intense while in areas of low transmission intensity AL or MQAS may be used.