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Human movement drives spatial transmission patterns of infectious diseases. Population-level mobility patterns are often quantified using aggregated data sets, such as census migration surveys or mobile phone data. These data are often unable to quantify individual-level travel patterns and lack the information needed to discern how mobility varies by demographic groups. Individual-level datasets can capture additional, more precise, aspects of mobility that may impact disease risk or transmission patterns and determine how mobility differs across cohorts; however, these data are rare, particularly in locations such as sub-Saharan Africa. Using detailed GPS logger data collected from three sites in southern Africa, we explore metrics of mobility such as percent time spent outside home, number of locations visited, distance of locations, and time spent at locations to determine whether they vary by demographic, geographic, or temporal factors. We further create a composite mobility score to identify how well aggregated summary measures would capture the full extent of mobility patterns. Although sites had significant differences in all mobility metrics, no site had the highest mobility for every metric, a distinction that was not captured by the composite mobility score. Further, the effects of sex, age, and season on mobility were all dependent on site. No factor significantly influenced the number of trips to locations, a common way to aggregate datasets. When collecting and analyzing human mobility data, it is difficult to account for all the nuances; however, these analyses can help determine which metrics are most helpful and what underlying differences may be present.

The geographic and evolutionary origins of the SARS-CoV-2 Omicron variant (BA.1), which was first detected mid-November 2021 in Southern Africa, remain unknown. We tested 13,097 COVID-19 patients sampled between mid-2021 to early 2022 from 22 African countries for BA.1 by real-time RT-PCR. By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a peak Rt of 4.1. Polymerase chain reaction and near-full genome sequencing data revealed genetically diverse Omicron ancestors already existed across Africa by August 2021. Mutations, altering viral tropism, replication and immune escape, gradually accumulated in the spike gene. Omicron ancestors were therefore present in several African countries months before Omicron dominated transmission. These data also indicate that travel bans are ineffective in the face of undetected and widespread infection.

For a decade, the Southern and Central Africa International Center of Excellence for Malaria Research has operated with local partners across study sites in Zambia and Zimbabwe that range from hypo- to holoendemic and vary ecologically and entomologically. The burden of malaria and the impact of control measures were assessed in longitudinal cohorts, cross-sectional surveys, passive and reactive case detection, and other observational designs that incorporated multidisciplinary scientific approaches: classical epidemiology, geospatial science, serosurveillance, parasite and mosquito genetics, and vector bionomics. Findings to date have helped elaborate the patterns and possible causes of sustained low-to-moderate transmission in southern Zambia and eastern Zimbabwe and recalcitrant high transmission and fatality in northern Zambia. Cryptic and novel mosquito vectors, asymptomatic parasite reservoirs in older children, residual parasitemia and gametocytemia after treatment, indoor residual spraying timed dyssynchronously to vector abundance, and stockouts of essential malaria commodities, all in the context of intractable rural poverty, appear to explain the persistent malaria burden despite current interventions. Ongoing studies of high-resolution transmission chains, parasite population structures, long-term malaria periodicity, and molecular entomology are further helping to lay new avenues for malaria control in southern and central Africa and similar settings.

Malaria control has stalled in a number of African countries and novel approaches to malaria control are needed for these areas. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali in which a combination of the RTS,S/AS01E malaria vaccine and seasonal malaria chemoprevention led to a substantial reduction in clinical cases of malaria, severe malaria, and malaria deaths compared with the administration of either intervention given alone suggests that there may be other epidemiological/clinical situations in which a combination of malaria vaccination and chemoprevention could be beneficial. Some of these potential opportunities are considered in this paper. These include combining vaccination with intermittent preventive treatment of malaria in infants, with intermittent preventive treatment of malaria in pregnancy (through vaccination of women of child-bearing age before or during pregnancy), or with post-discharge malaria chemoprevention in the management of children recently admitted to hospital with severe anaemia. Other potential uses of the combination are prevention of malaria in children at particular risk from the adverse effects of clinical malaria, such as those with sickle cell disease, and during the final stages of a malaria elimination programme when vaccination could be combined with repeated rounds of mass drug administration. The combination of a pre-erythrocytic stage malaria vaccine with an effective chemopreventive regimen could make a valuable contribution to malaria control and elimination in a variety of clinical or epidemiological situations, and the potential of this approach to malaria control needs to be explored.

Background Human movement is a driver of malaria transmission and has implications for sustainable malaria control. However, little research has been done on the impact of fine-scale movement on malaria transmission and control in high-transmission settings. As interest in targeted malaria control increases, evaluations are needed to determine the appropriateness of these strategies in the context of human mobility across a variety of transmission settings. Methods A human mobility study was conducted in Nchelenge District, a high-transmission setting in northern Zambia. Over 1 year, 84 participants were recruited from active malaria surveillance cohorts to wear a global positioning system data logger for 1 month during all daily activity. Participants completed a survey questionnaire and underwent malaria testing and treatment at the time of logger distribution and at collection 1 month later. Incident malaria infections were identified using polymerase chain reaction. Participant movement was characterized throughout the study area and across areas targeted for an indoor residual spraying (IRS) intervention. Participant movement patterns were compared using movement intensity maps, activity space plots, and statistical analyses. Malaria risk was characterized across participants using spatial risk maps and time spent away from home during peak vector biting hours. Results Movement data were collected from 82 participants, and 63 completed a second study visit. Participants exhibited diverse mobility patterns across the study area, including movement into and out of areas targeted for IRS, potentially mitigating the impact of IRS on parasite prevalence. Movement patterns did not differ significantly by season or age, but male participants traveled longer distances and spent more time away from home. Monthly malaria incidence was 22%, and malaria risk was characterized as high across participants. Participants with incident parasitemia traveled a shorter distance and spent more time away from home during peak biting hours; however, these relationships were not statistically significant, and malaria risk score did not differ by incident parasitemia. Conclusions Individual movement patterns in Nchelenge District, Zambia have implications for malaria control, particularly the effectiveness of targeted IRS strategies. Large and fine-scale population mobility patterns should be considered when planning intervention strategies across transmission settings. Electronic supplementary material The online version of this article (10.1186/s12942-019-0183-y) contains supplementary material, which is available to authorized users.

Since the late nineteenth century, the importance of house structure as a determinant of malaria risk has been recognized. Few studies to date have examined the association of housing and malaria in clinical populations. We conducted a cross-sectional study of febrile patients (n = 282) at two rural health clinics in a high malaria-transmission area of northern Zambia. Participants underwent testing for Plasmodium falciparum infection by PCR. Demographic and other risk factors including house structure, indoor residual spraying (IRS), bed net use, education level, and household income were collected. Data were fitted to logistic regression models for relational and mediation analyses. Residing in a house with a thatch roof was associated with higher odds of malaria than residing in a house with corrugated metal (odds ratio: 2.6; 95% CI: 1.0–6.3, P = 0.04). Lower income and educational attainment were also associated with greater odds of malaria. Living under a thatch roof accounted for 24% (95% CI: 14–82) of the effect of household income on malaria risk, and income accounted for 11% (95% CI: 8–19) of the effect of education. Neither IRS nor bed net use was associated with malaria risk despite large, local investments in these vector control interventions. The findings testify to malaria as a disease of rural poverty and contribute further evidence to the utility of housing improvements in vector control programs.

Severe malaria, caused by the protozoan Plasmodium, is the leading parasitic cause of mortality worldwide. Plasmodium falciparum, the most lethal among human malaria parasites, predominates in sub-Saharan Africa where it causes a disconcerting 1,200 child deaths per day concentrated in regions where malaria has proven recalcitrant to control measures or where control measures are tenuous or absent.1,2 In Zambia, there were an estimated 3.1 million cases of malaria (severe and uncomplicated) in 2016 among its population of 16.7 million and it was most prevalent in northern Zambia where it persists year round despite the recent scale-up of vector control efforts.2,3 Severe malaria can feature one or more of severe anemia (hemoglobin < 5 g/dL), cerebral edema, lactic acidosis, respiratory failure, or shock. In high-transmission, resource-limited settings, malaria evades easy case definition and is often clinically indistinguishable from bacterial meningitis, pneumonia, bacteremia, and other febrile diseases which can conflate or confuse diagnosis.4 Only a small proportion (∼2%) of P. falciparum infections progress to severe malaria, but in highly malarious regions where children may experience several infections a year, the absolute number of cases is large.5 Prompt initiation of treatment is vital. Rapid disease progression is fueled by an exponential expansion of parasites and an exuberant host immune response, and hospital deaths occur most often within 24 hours of admission.5,6 The preferred treatment is intravenous artesunate and supportive care as indicated (e.g., fluid resuscitation, blood transfusion, anticonvulsants, and ventilator and vasopressor support), but even with appropriate care, mortality can reach 20%.5 Delayed presentation to allopathic health providers on account of logistical constraints or health-seeking behaviors compounds the danger.7 Distinguishing factors that contribute to poor outcomes for children with malaria can inform clinical and programmatic strategies to lessen its toll. However, research is limited by the inherent challenges of conducting intrahospital epidemiologic studies in rural centers where malaria prevalence is greatest. We present results of a retrospective, time-matched, case-control study of hospitalized children with malaria who died (cases) and those who survived (controls) at a rural, district-level hospital in a high-transmission region of northern Zambia to identify and evaluate demographic and clinical factors associated with increased risk of death.

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.

Antibodies to Plasmodium falciparum are specific biomarkers that can be used to monitor parasite exposure over broader time frames than microscopy, rapid diagnostic tests, or molecular assays. Consequently, seroprevalence surveys can assist with monitoring the impact of malaria control interventions, particularly in the final stages of elimination, when parasite incidence is low. The protein array format to measure antibodies to diverse P. falciparum antigens requires only small sample volumes and is high throughput, permitting the monitoring of malaria transmission on large spatial and temporal scales. We expanded the use of a protein microarray to assess malaria transmission in settings beyond those with a low malaria incidence. Antibody responses in children and adults were profiled, using a P. falciparum protein microarray, through community-based surveys in three areas in Zambia and Zimbabwe at different stages of malaria control and elimination. These three epidemiological settings had distinct serological profiles reflective of their malaria transmission histories. While there was little correlation between transmission intensity and antibody signals (magnitude or breadth) in adults, there was a clear correlation in children younger than 5 years of age. Antibodies in adults appeared to be durable even in the absence of significant recent transmission, whereas antibodies in children provided a more accurate picture of recent levels of transmission intensity. Seroprevalence studies in children could provide a valuable marker of progress toward malaria elimination. IMPORTANCE As malaria approaches elimination in many areas of the world, monitoring the effect of control measures becomes more important but challenging. Low-level infections may go undetected by conventional tests that depend on parasitemia, particularly in immune individuals, who typically show no symptoms of malaria. In contrast, antibodies persist after parasitemia and may provide a more accurate picture of recent exposure. Only a few parasite antigens—mainly vaccine candidates—have been evaluated in seroepidemiological studies. We examined antibody responses to 500 different malaria proteins in blood samples collected through community-based surveillance from areas with low, medium, and high malaria transmission intensities. The breadth of the antibody responses in adults was broad in all three settings and was a poor correlate of recent exposure. In contrast, children represented a better sentinel population for monitoring recent malaria transmission. These data will help inform the use of multiplex serology for malaria surveillance.

Malarial infection and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are important causes of adverse birth outcomes. Reducing the burden of these infections in pregnancy requires interventions that can be easily integrated into the antenatal care (ANC) package. However, efforts to integrate the control of malarial infection and curable STIs/RTIs in pregnancy have been hampered by a lack of evidence related to their coinfection. Thus, we investigated the prevalence of coinfection among pregnant women of rural Zambia. A prospective cohort study was conducted in Nchelenge District, Zambia, involving 1,086 first ANC attendees. We screened participants for peripheral malarial infection and curable STIs/RTIs (syphilis, Chlamydia, gonorrhea, trichomoniasis, and bacterial vaginosis), and collected relevant sociodemographic data at booking. Factors associated with malarial and STI/RTI coinfection were explored using univariate and multivariate regression models. Among participants with complete results (N = 1,071), 38.7% (95% confidence interval [CI] = 35.7–41.6) were coinfected with malaria parasites and at least one STI/RTI; 18.9% (95% CI = 16.5–21.2) were infected with malaria parasites only; 26.0% (95% CI = 23.5–28.8) were infected with at least one STI/RTI but no malaria parasites, and 16.4% (95% CI = 14.1–18.6) had no infection. Human immunodeficiency virus (HIV)-infected women had a higher risk of being coinfected than HIV-uninfected women (odds ratio [OR] = 3.59 [95% CI = 1.73–7.48], P < 0.001). The prevalence of malarial and STI/RTI coinfection was high in this population. An integrated approach to control malarial infection and STIs/RTIs is needed to reduce this dual burden in pregnancy.

We attempted to identify Plasmodium falciparum histidine–rich protein 2/3 (pfhrp2/3) deletions among rapid diagnostic test (RDT)–negative but PCR- or microscopy-positive P. falciparum–infected individuals in areas of low transmission (Choma District, 2009–2011) and high transmission (Nchelenge District, 2015–2017) in Zambia. Through community-based surveys, 5,167 participants were screened at 1,147 households by P. falciparum histidine-rich protein 2 (PfHRP2)-based RDTs. Slides were made and dried blood spots were obtained for molecular analysis. Of 28 samples with detectable P. falciparum DNA, none from Nchelenge District were pfhrp2/3 negative. All eight samples from Choma District had detectable pfhrp3 genes, but pfhrp2 was undetectable in three. DNA concentrations of pfhrp2-negative samples were low (< 0.001 ng/μL). These findings suggest that PfHRP2-based RDTs remain effective tools for malaria diagnosis in Nchelenge District, but further study is warranted to understand the potential for pfhrp2/3 deletions in southern Zambia where malaria transmission declined over the past decade.

A large proportion of ongoing malaria parasite transmission is attributed to low-density subclinical infections not readily detected by available rapid diagnostic tests (RDTs) or microscopy. Plasmodium falciparum gametocyte carriage is subclinical, but gametocytemic individuals comprise the parasite reservoir that leads to infection of mosquitoes and local transmission. Effective detection and quantification of these carriers can help advance malaria elimination strategies. However, no point-of-need (PON) RDTs for gametocyte detection exist, much less one that can perform noninvasive sampling of saliva outside a clinical setting. Here, we report on the discovery of 35 parasite markers from which we selected a single candidate for use in a PON RDT. We performed a cross-sectional, multi-omics study of saliva from 364 children with subclinical infection in Cameroon and Zambia and produced a prototype saliva-based PON lateral flow immunoassay test for P. falciparum gametocyte carriers. The test is capable of identifying submicroscopic carriage in both clinical and nonclinical settings and is compatible with archived saliva samples.

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.

The RTS,S/AS01 malaria vaccine encompasses the central repeats and C-terminal of Plasmodium falciparum circumsporozoite protein (PfCSP). Although no Phase II clinical trial studies observed evidence of strain-specific immunity, recent studies show a decrease in vaccine efficacy against non-vaccine strain parasites. In light of goals to reduce malaria morbidity, anticipating the effectiveness of RTS,S/AS01 is critical to planning widespread vaccine introduction. We deep sequenced C-terminal Pfcsp from 77 individuals living along the international border in Luapula Province, Zambia and Haut-Katanga Province, the Democratic Republic of the Congo (DRC) and compared translated amino acid haplotypes to the 3D7 vaccine strain. Only 5.2% of the 193 PfCSP sequences from the Zambia-DRC border region matched 3D7 at all 84 amino acids. To further contextualize the genetic diversity sampled in this study with global PfCSP diversity, we analyzed an additional 3,809 Pfcsp sequences from the Pf3k database and constructed a haplotype network representing 15 countries from Africa and Asia. The diversity observed in our samples was similar to the diversity observed in the global haplotype network. These observations underscore the need for additional research assessing genetic diversity in P. falciparum and the impact of PfCSP diversity on RTS,S/AS01 efficacy.

Background Insecticide-treated nets (ITNs) reduce malaria morbidity and mortality in endemic areas. Despite increasing availability, the use of ITNs remains limited in some settings. Poor malaria knowledge is a barrier to the widespread use of ITNs. The goal of this study was to assess the levels of malaria knowledge and evaluate factors associated with bed net use among individuals residing in three regions of southern Africa with different levels of malaria transmission and control. Methods A cross-sectional study was conducted on a sample of 7535 residents recruited from 2066 households in Mutasa District, Zimbabwe (seasonal malaria transmission), Choma District, Zambia (low transmission) and Nchelenge District, Zambia (high transmission), between March 2012 and March 2017. A standardized questionnaire was used to collect data on demographics, malaria-related knowledge and use of preventive measures. Multivariate logistic regression analyses were used to assess determinants of bed net use. Results Most of the 3836 adult participants correctly linked mosquito bites to malaria (85.0%), mentioned at least one malaria symptom (95.5%) and knew of the benefit of sleeping under an ITN. Bed net ownership and use were highest in Choma and Nchelenge Districts and lowest in Mutasa District. In multivariate analyses, knowledge of ITNs was associated with a 30–40% increased likelihood of bed net use after adjusting for potential confounders across all sites. Other factors significantly associated with bed net use were age, household size and socioeconomic status, although the direction, strength and size of association varied by study site. Importantly, participants aged 5–14 years had reduced odds of sleeping under a bed net compared to children younger than 5 years. Conclusion Relevant knowledge of ITNs translated into the expected preventive behaviour of sleeping under a bed net, underscoring the need for continued health messaging on malaria prevention. The implementation and delivery of malaria control and elimination interventions needs to consider socioeconomic equity gaps, and target school-age children to ensure access to and improve utilization of ITNs.

The last decade has witnessed a substantial increase of multi-centre, public health-oriented clinical trials in poor countries. However, non-commercial research groups have less staff and financial resources than traditional commercial sponsors, so the trial teams have to be creative to comply with Good Clinical Practices (GCP) requirements. According to the recent experience of a large multicentre trial on antimalarials, major challenges result from the complexity of multiple ethical review, the costs of in-depth monitoring at several sites, setting up an adequate Good Clinical Laboratory Practices (GCLP) framework, lack of insurers in host countries, and lack of adequate non-commercial data management software. Public research funding agencies need to consider these challenges in their funding policies. They also could support common spaces where North-South collaborative research groups may share critical information, such as on research insurance and open-source, GCP-compliant software. WHO should update its GCP guidelines, which date back to 1995, to incorporate the perspectives and needs of non-commercial clinical research. ispartof: Tropical Medicine & International Health vol:18 issue:2 pages:237-241 ispartof: location:England status: published

Background The scale-up of malaria control interventions has resulted in substantial declines in transmission in some but not all regions of sub-Saharan Africa. Understanding factors associated with persistent malaria transmission despite control efforts may guide targeted interventions to high-risk areas and populations. Methods Household malaria surveys were conducted in Nchelenge District, Luapula Province, in northern Zambia. Structures that appeared to be households were enumerated from a high-resolution satellite image and randomly sampled for enrollment. Households were enrolled into cross-sectional (single visit) or longitudinal (visits every other month) cohorts but analyses were restricted to cross-sectional visits and the first visit to longitudinal households. During study visits, a questionnaire was administered to adults and caretakers of children and a blood sample was collected for a malaria rapid diagnostic test (RDT) from all household residents. Characteristics associated with RDT positivity were analyzed using multi-level models. Results A total of 2,486 individuals residing within 742 households were enrolled between April 2012 and July 2015. Over this period, 51% of participants were RDT positive. Forty-three percent of all RDT positive individuals were between the ages of 5 and 17 years although this age group comprised only 30% of study participants. In a multivariable model, the odds being RDT positive were highest in 5–17 year olds and did not vary by season. Children 5–17 years of age had 8.83 higher odds of being RDT positive compared with those >18 years of age (95% CI: 6.13, 12.71); there was an interaction between age and report of symptoms, with an almost 50% increased odds of report of symptoms with decreasing age category (OR = 1.49; 95% CI 1.11, 2.00). Conclusions Children and adolescents between the ages of 5 and 17 were at the highest risk of malaria infection throughout the year. School-based programs may be effective at targeting this high-risk group.

Background: Malaria control interventions have been scaled-up in Zambia in conjunction with a malaria surveillance system. Although substantial progress has been achieved in reducing morbidity and mortality, national and local information demonstrated marked heterogeneity in the impact of malaria control across the country. This study reports the high burden of malaria in Nchelenge District, Luapula Province, Zambia from 2006 to 2012 after seven years of control measures. Methods: Yearly aggregated information on cases of malaria, malaria deaths, use of malaria diagnostics, and malaria control interventions from 2006 to 2012 were obtained from the Nchelenge District Health Office. Trends in the number of malaria cases, methods of diagnosis, malaria positivity rate among pregnant women, and intervention coverage were analysed using descriptive statistics. Results: Malaria prevalence remained high, increasing from 38% in 2006 to 53% in 2012. Increasing numbers of cases of severe malaria were reported until 2010. Intense seasonal malaria transmission was observed with seasonal declines in the number of cases between April and August, although malaria transmission continued throughout the year. Clinical diagnosis without accompanying confirmation declined from 95% in 2006 to 35% in 2012. Intervention coverage with long-lasting insecticide-treated nets and indoor residual spraying increased from 2006 to 2012. Conclusions: Despite high coverage with vector control interventions, the burden of malaria in Nchelenge District, Zambia remained high. The high parasite prevalence could accurately reflect the true burden, perhaps in part as a consequence of population movement, or improved access to care and case reporting. Quality information at fine spatial scales will be critical for targeting effective interventions and measurement of progress.

The pharmacokinetics of antiretroviral drugs in pregnancy is poorly understood. We reviewed the use of therapeutic drug monitoring (TDM) in clinical settings to document plasma concentrations of lopinavir during pregnancy and investigated how clinicians acted upon TDM results. A retrospective review was carried out of all HIV-infected pregnant women taking boosted lopinavir-based highly active antiretroviral therapy (HAART) at five National Health Service (NHS) centres in the UK between May 2004 and March 2007. Seventy-three women in receipt of lopinavir were identified, of whom 89% had plasma lopinavir concentrations above the suggested minimum recommended for wild-type HIV. Initial TDM results prompted dosage change in 10% and assessment of adherence and/or pharmacist review in 11%. TDM was repeated in 29%. TDM can play an important role in the clinical management of HIV-positive pregnant women, allowing informed dose modification and an alternative measure of adherence.

Background Malaria in Zambia remains a public health and developmental challenge, affecting mostly children under five and pregnant women. In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL) that has proved to be highly efficacious against multidrug resistant Plasmodium falciparum. Objective The study objective was to determine whether dihydroartemisinin-piperaquine (DHA/PQP) had similar efficacy, safety and tolerability as AL for the treatment of children with uncomplicated P. falciparum malaria in Ndola, Zambia. Methods Between 2005 and 2006, 304 children (6-59 months old) with uncomplicated P. falciparum were enrolled, randomized to AL (101) or DHA/PQP (203) and followed up for 42 days. Outcome of treatment was defined according to the standard WHO classification, i.e. early treatment failure (ETF), late clinical failure (LCF, late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR). Recurrent infections were genotyped to distinguish between recrudescence and new infection. Results No ETF was observed. At day 28, PCR-uncorrected ACPR was 92% in the DHA/PQP and 74% in the AL arm (OR: 4.05; 95%CI: 1.89-8.74; p < 0.001). Most failure were new infections and PCR-corrected ACPR was similar in the two study arms (OR: 0.69; 95%CI: 0.22-2.26; p = 0.33). Similar results were observed for day 42, i.e. higher PCR-uncorrected ACPR for DHA/PQP, mainly due to the difference observed up to day 28, while the PCR-corrected ACPR was similar: DHA/PQP: 93% (179/192), AL: 93% (84/90), (OR: 0.92; 95%CI: 0.30-2.64; p = 0.85). Except for cough, more frequent in the DHA/PQP arm (p = 0.04), there were no differences between treatment arms in the occurrence of adverse events. Two serious adverse events were probably associated to AL treatment. Conclusion DHA/PQP was as efficacious, safe and well tolerated in treatment of uncomplicated malaria as AL, though in the latter group more new infections during the follow up were observed. DHA/PQP seems a potential candidate to be used as an alternative first-line or rescue treatment in Zambia. Trial Registration ISRCTN16263443, at http://www.controlled-trials.com/isrctn