The U.S. Centers for Disease Control and Prevention in collaboration with the National Malaria Elimination Program and the African Field Epidemiology Network established the Malaria Frontline Project to provide innovative approaches to improve the malaria program implementation in Kano and Zamfara States, Nigeria. Innovative approaches such as malaria bulletin, malaria monitoring wall chart, conduct of ward level data validation meetings and malaria dashboard have helped improve the use of data for decision making at all levels. Innovative approaches deployed during the project implementation facilitated data analysis and a better understanding of malaria program performance and data utilization for decision making at all levels. These innovative approaches may improve malaria control program performance in Nigeria and other resource limited countries. © Adefisoye Adewole et al. Pan African Medical Journal (ISSN: 1937-8688).

BACKGROUND: The Malaria Frontline Project (MFP) supported the National Malaria Elimination Program for effective program implementation in the high malaria-burden states of Kano and Zamfara adapting the National Stop Transmission of Polio (NSTOP) program elimination strategies. PROJECT IMPLEMENTATION: The MFP was implemented in 34 LGAs in the two states (20 out of 44 in Kano and all 14 in Zamfara). MFP developed training materials and job aids tailored to expected service delivery for primary and district health facilities and strengthened supportive supervision. Pre- and post-implementation assessments of intervention impacts were conducted in both states. RESULTS: A total of 158 (Kano:83; Zamfara:75) and 180 (Kano:100; Zamfara:80) healthcare workers (HCWs), were interviewed for pre-and post-implementation assessments, respectively. The proportions of HCWs with correct knowledge on diagnostic criteria were Kano: 97.5% to 92.0% and Zamfara: 94.7% to 98.8%; and knowledge of recommended first line treatment of uncomplicated malaria were Kano: 68.7% to 76.0% and Zamfara: 69.3% to 65.0%. The proportion of HCWs who adhered to national guidelines for malaria diagnosis and treatment increased in both states (Kano: 36.1% to 73.0%; Zamfara: 39.2% to 67.5%) and HCW knowledge to confirm malaria diagnosis slightly decreased in Kano State but increased in Zamfara State (Kano: 97.5% to 92.0%; Zamfara: 94.8% to 98.8%). HCWs knowledge of correct IPTp drug increased in both states (Kano: 81.9% to 94.0%; Zamfara: 85.3% to 97.5%). CONCLUSION: MFP was successfully implemented using tailored training materials, job aids, supportive supervision, and data use. The project strategy can likely be adapted to improve the effectiveness of malaria program implementation in other Nigerian states, and other malaria endemic countries.

BACKGROUND: Studies evaluating mass drug administration (MDA) in malarious areas have shown reductions in malaria immediately following the intervention. However, these effects vary by endemicity and are not sustained. Since the 2013 version of this Cochrane Review on this topic, additional studies have been published. OBJECTIVES: Primary objectives To assess the sustained effect of MDA with antimalarial drugs on: - the reduction in malaria transmission in moderate- to high-transmission settings; - the interruption of transmission in very low- to low-transmission settings. Secondary objective To summarize the risk of drug-associated adverse effects following MDA. SEARCH METHODS: We searched several trial registries, citation databases, conference proceedings, and reference lists for relevant articles up to 11 February 2021. We also communicated with researchers to identify additional published and unpublished studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) and non-randomized studies comparing MDA to no MDA with balanced co-interventions across study arms and at least two geographically distinct sites per study arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and extracted data. We calculated relative risk (RR) and rate ratios with corresponding 95% confidence intervals (CIs) to compare prevalence and incidence, respectively, in MDA compared to no-MDA groups. We stratified analyses by malaria transmission and by malaria species. For cluster-randomized controlled trials (cRCTs), we adjusted standard errors using the intracluster correlation coefficient. We assessed the certainty of the evidence using the GRADE approach. For non-randomized controlled before-and-after (CBA) studies, we summarized the data using difference-in-differences (DiD) analyses. MAIN RESULTS: Thirteen studies met our criteria for inclusion. Ten were cRCTs and three were CBAs. Cluster-randomized controlled trials Moderate- to high-endemicity areas (prevalence ≥ 10%) We included data from two studies conducted in The Gambia and Zambia.  At one to three months after MDA, the Plasmodium falciparum (hereafter, P falciparum) parasitaemia prevalence estimates may be higher compared to control but the CIs included no effect (RR 1.76, 95% CI 0.58 to 5.36; Zambia study; low-certainty evidence); parasitaemia incidence was probably lower (RR 0.61, 95% CI 0.40 to 0.92; The Gambia study; moderate-certainty evidence); and confirmed malaria illness incidence may be substantially lower,  but the CIs included no effect (rate ratio 0.41, 95% CI 0.04 to 4.42; Zambia study; low-certainty evidence).  At four to six months after MDA, MDA showed little or no effect on P falciparum parasitaemia prevalence (RR 1.18, 95% CI 0.89 to 1.56; The Gambia study; moderate-certainty evidence) and, no persisting effect was demonstrated with parasitaemia incidence (rate ratio 0.91, 95% CI 0.55 to 1.50; The Gambia study). Very low- to low-endemicity areas (prevalence < 10%) Seven studies from Cambodia, Laos, Myanmar (two studies), Vietnam, Zambia, and Zanzibar evaluated the effects of multiple rounds of MDA on P falciparum. Immediately following MDA (less than one month after MDA), parasitaemia prevalence was reduced (RR 0.12, 95% CI 0.03 to 0.52; one study; low-certainty evidence). At one to three months after MDA, there was a reduction in both parasitaemia incidence (rate ratio 0.37, 95% CI 0.21 to 0.55; 1 study; moderate-certainty evidence) and prevalence (RR 0.25, 95% CI 0.15 to 0.41; 7 studies; low-certainty evidence). For confirmed malaria incidence, absolute rates were low, and it is uncertain whether MDA had an effect on this outcome (rate ratio 0.58, 95% CI 0.12 to 2.73; 2 studies; very low-certainty evidence).  For P falciparum prevalence, the relative differences declined over time, from RR 0.63 (95% CI 0.36 to 1.12; 4 studies) at four to six months after MDA, to RR 0.86 (95% CI 0.55 to 1.36; 5 studies) at 7 to 12 months after MDA. Longer-term prevalence estimates showed overall low absolute risks, and relative effect estimates of the effect of MDA on prevalence varied from RR 0.82 (95% CI 0.20 to 3.34) at 13 to 18 months after MDA, to RR 1.25 (95% CI 0.25 to 6.31) at 31 to 36 months after MDA in one study. Five studies from Cambodia, Laos, Myanmar (2 studies), and Vietnam evaluated the effect of MDA on Plasmodium vivax (hereafter, P vivax). One month following MDA, P vivax prevalence was lower (RR 0.18, 95% CI 0.08 to 0.40; 1 study; low-certainty evidence). At one to three months after MDA, there was a reduction in P vivax prevalence (RR 0.15, 95% CI 0.10 to 0.24; 5 studies; low-certainty evidence). The immediate reduction on P vivax prevalence was not sustained over time, from RR 0.78 (95% CI 0.63 to 0.95; 4 studies) at four to six months after MDA, to RR 1.12 (95% CI 0.94 to 1.32; 5 studies) at 7 to 12 months after MDA. One of the studies in Myanmar provided estimates of longer-term effects, where overall absolute risks were low, ranging from RR 0.81 (95% CI 0.44 to 1.48) at 13 to 18 months after MDA, to RR 1.20 (95% CI 0.44 to 3.29) at 31 to 36 months after MDA. Non-randomized studies Three CBA studies were conducted in moderate- to high-transmission areas in Burkina Faso, Kenya, and Nigeria. There was a reduction in P falciparum parasitaemia prevalence in MDA groups compared to control groups during MDA (DiD range: -15.8 to -61.4 percentage points), but the effect varied at one to three months after MDA (DiD range: 14.9 to -41.1 percentage points).  AUTHORS' CONCLUSIONS: In moderate- to high-transmission settings, no studies reported important effects on P falciparum parasitaemia prevalence within six months after MDA. In very low- to low-transmission settings, parasitaemia prevalence and incidence were reduced initially for up to three months for both P falciparum and P vivax; longer-term data did not demonstrate an effect after four months, but absolute risks in both intervention and control groups were low. No studies provided evidence of interruption of malaria transmission.

We appreciate the thoughtful commentary provided by Hamer and Miller [1] and are pleased that they arrived at many of the same conclusions that we did; however, we would like to clarify a few points. | | First, we wish to correct the statement that, in our trial, mass testing and treatment (MTaT) was only implemented within the core areas of clusters. Rather, MTaT was implemented throughout intervention clusters, which included a core area ranging between 1 and 3 Km in diameter, and a 300-m buffer. As described, to limit contamination, inclusion criteria for the analytic sample required residence within the core area [2, 3].

BACKGROUND: In 2013, the Nigeria Federal Ministry of Health established a Master Health Facility List (MHFL) as recommended by WHO. Since then, some health facilities (HFs) have ceased functioning and new facilities were established. We updated the MHFL and assessed service delivery parameters in the Malaria Frontline Project implementing areas in Kano and Zamfara States. METHODS: We assessed all HFs in each of the 34 project local government areas (LGAs) between July and September 2017. Project staff administered a semi-structured questionnaire developed for this assessment to heads of HFs about the type of facility, category and number of staff working at the facility and to record geo-coordinates of facility. RESULTS: In the Kano State project area, 726 HFs were identified and geo-located: 31 were new facilities, 608 (84%), 116 (16%) and two (0.3%) were Primary Health Care (PHC), secondary and tertiary facilities respectively. Using the national definition, there were 710 (98%) functional facilities and 644 (91%) of these reported to the national health information platform, District Health Information System, version 2 (DHIS2). The Zamfara project area had 739 HFs: eight were new, 715 (97%), 22 (3.0%) and two (0.2%) PHCs, secondary and tertiary facilities respectively. There were 695 (94%) functional facilities with 656 (94%) of these reporting to DHIS2. Using national criteria for primary health care designation, only 95 (9%) of all PHCs in the two States met the minimum human resource requirements. CONCLUSION: Most HFs were functional and reported to DHIS2. A comprehensive MHFL having all the important parameters that should be established and updated regularly by authorities to make it more useful for health services administration and management. Most functional facilities are understaffed.

Progress with malaria control in western Kenya has stagnated since 2007. Additional interventions to reduce the high burden of malaria in this region are urgently needed. We conducted a two-arm, community-based, cluster-randomized, controlled trial of active case detection and treatment of malaria infections in all residents mass testing and treatment (MTaT) of 10 village clusters (intervention clusters) for two consecutive years to measure differences in the incidence of clinical malaria disease and malaria infections compared with 20 control clusters where MTaT was not implemented. All residents of intervention clusters, irrespective of history of fever or other malaria-related symptoms, were tested three times per year before the peak malaria season using malaria rapid diagnostic tests. All positive cases were treated with dihydroartemisinin-piperaquine. The incidence of clinical malaria was measured through passive surveillance, whereas the cumulative incidence of malaria infection was measured using active surveillance in a cohort comprising randomly selected residents. The incidence of clinical malaria was 0.19 cases/person-year (p-y, 95% CI: 0.13-0.28) in the intervention arm and 0.24 cases/p-y (95% CI: 0.15-0.39) in the control arm (incidence rate ratio [IRR] 0.79, 95% CI: 0.61-1.02). The cumulative incidence of malaria infections was similar between the intervention (2.08 infections/p-y, 95% CI: 1.93-2.26) and control arms (2.19 infections/p-y, 95% CI: 2.02-2.37) with a crude IRR of 0.95 (95% CI: 0.87-1.04). Six rounds of MTaT over 2 years did not have a significant impact on the incidence of clinical malaria or the cumulative incidence of malaria infection in this area of high malaria transmission.

Tropical splenomegaly is often associated with malaria and schistosomiasis. In 2014 and 2015, 145 Congolese refugees in western Uganda diagnosed with splenomegaly during predeparture medical examinations underwent enhanced screening for various etiologies. After anecdotal reports of unresolved splenomegaly and complications after U.S. arrival, patients were reassessed to describe long-term clinical progression after arrival in the United States. Post-arrival medical information was obtained through medical chart abstraction in collaboration with state health partners in nine participating states. We evaluated observed splenomegaly duration and associated clinical sequelae between 130 case patients from eastern Congo and 102 controls through adjusted hierarchical Poisson models, accounting for familial clustering. Of the 130 case patients, 95 (73.1%) had detectable splenomegaly after arrival. Of the 85 patients with records beyond 6 months, 45 (52.9%) had persistent splenomegaly, with a median persistence of 14.7 months (range 6.0-27.9 months). Of the 112 patients with available results, 65 (58.0%) patients had evidence of malaria infection, and the mean splenomegaly duration did not differ by Plasmodium species. Refugees with splenomegaly on arrival were 43% more likely to have anemia (adjusted relative risk [aRR]: 1.43, 95% CI: 1.04-1.97). Those with persistent splenomegaly were 60% more likely (adjusted relative risk [aRR]: 1.60, 95% CI: 1.15-2.23) to have a hematologic abnormality, particularly thrombocytopenia (aRR: 5.53, 95% CI: 1.73-17.62), and elevated alkaline phosphatase (aRR: 1.57, 95% CI: 1.03-2.40). Many patients experienced persistent splenomegaly, contradicting literature describing resolution after treatment and removal from an endemic setting. Other possible etiologies should be investigated and effective treatment, beyond treatment for malaria and schistosomiasis, explored.

BACKGROUND: Global gains towards malaria elimination have been heterogeneous and have recently stalled. Interventions targeting afebrile malaria infections may be needed to address residual transmission. We studied the efficacy of repeated rounds of community-based mass testing and treatment (MTaT) on malaria infection prevalence in western Kenya. METHODS: Twenty clusters were randomly assigned to three rounds of MTaT per year for two years or control (standard-of-care for testing and treatment at public health facilities along with government sponsored mass long-lasting insecticidal net (LLIN) distributions). During rounds community health volunteers visited all households in intervention clusters and tested all consenting individuals with a rapid diagnostic test. Those positive were treated with dihydroartemisinin-piperaquine. Cross-sectional community infection prevalence surveys were performed in both study arms at baseline and each year after three rounds of MTaT. The primary outcome was the effect size of MTaT on parasite prevalence by microscopy between arms by year adjusted for age, reported LLIN use, enhanced vegetative index, and socio-economic status. RESULTS: Demographic and behavioral characteristics, including LLIN usage, were similar between arms at each survey. MTaT coverage ranged between 75.0-77.5% and 81.9-94.3% between the three rounds in year 1 and year 2, respectively. The adjusted effect size of MTaT on the prevalence of parasitemia between arms was 0.93 (CI: 0.79-1.08) and 0.92 (0.76-1.10) after year 1 and 2, respectively. CONCLUSIONS: MTaT performed three times per year over two years did not reduce malaria parasite prevalence in this high-transmission area.

BACKGROUND: The whole sporozoite PfSPZ Vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous inoculation (DVI) with PfSPZ Vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited. METHODS: We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (5-9 years, 13-59 months, and 5-12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35x105, 2.7x105, 4.5x105, 9.0x105, and 1.8x106Plasmodium falciparum sporozoites (PfSPZ), with the two highest doses given twice, 8 weeks apart. Solicited adverse events (AEs) were monitored for eight days after vaccination; unsolicited AEs for 29 days; and serious AEs (SAEs) throughout the study. Blood taken pre-vaccination and one-week post-vaccination was tested for IgG antibodies to Pf circumsporozoite protein (PfCSP) using enzyme-linked immunosorbent assay (ELISA). RESULTS: Rates of AEs were similar in vaccinees and controls for solicited (35.7% vs. 41.5%) and unsolicited (83.9% vs. 92.5%) AEs, respectively. No related grade 3 AEs, SAEs, or grade 3 laboratory abnormalities occurred. Most (79.0%) vaccinations were administered by a single DVI. Among those in the 9.0x105 and 1.8x106 PfSPZ groups, 36/45 (80.0%) vaccinees and 4/21 (19.0%) placebo controls developed antibodies to PfCSP, p<0.001. CONCLUSIONS: PfSPZ Vaccine in doses as high as 1.8x106 can be administered to infants and children by DVI, and was safe, well tolerated, and immunogenic.

OBJECTIVE: The objective of this analysis was to examine trends in malaria parasite prevalence and related socioeconomic inequalities in malaria indicators from 2006 to 2013 during a period of intensification of malaria control interventions in Siaya County, western Kenya. METHODS: Data were analysed from eight independent annual cross-sectional surveys from a combined sample of 19 315 individuals selected from 7253 households. Study setting was a health and demographic surveillance area of western Kenya. Data collected included demographic factors, household assets, fever and medication use, malaria parasitaemia by microscopy, insecticide-treated bed net (ITN) use and care-seeking behaviour. Households were classified into five socioeconomic status and dichotomised into poorest households (poorest 60%) and less poor households (richest 40%). Adjusted prevalence ratios (aPR) were calculated using a multivariate generalised linear model accounting for clustering and cox proportional hazard for pooled data assuming constant follow-up time. RESULTS: Overall, malaria infection prevalence was 36.5% and was significantly higher among poorest individuals compared with the less poor (39.9% vs 33.5%, aPR=1.17; 95% CI 1.11 to 1.23) but no change in prevalence over time (trend p value <0.256). Care-seeking (61.1% vs 62.5%, aPR=0.99; 95% CI 0.95 to 1.03) and use of any medication were similar among the poorest and less poor. Poorest individuals were less likely to use Artemether-Lumefantrine or quinine for malaria treatment (18.8% vs 22.1%, aPR=0.81, 95% CI 0.72 to 0.91) while use of ITNs was lower among the poorest individuals compared with less poor (54.8% vs 57.9%; aPR=0.95; 95% CI 0.91 to 0.99), but the difference was negligible. CONCLUSIONS: Despite attainment of equity in ITN use over time, socioeconomic inequalities still existed in the distribution of malaria. This might be due to a lower likelihood of treatment with an effective antimalarial and lower use of ITNs by poorest individuals. Additional strategies are necessary to reduce socioeconomic inequities in prevention and control of malaria in endemic areas in order to achieve universal health coverage and sustainable development goals.

Background: Impact evaluations allow countries to assess public health gains achieved through malaria investments. This study uses routine health management information system (HMIS) data from Zanzibar to describe changes in confirmed malaria incidence and impact of case management and vector control interventions during 2000-2015. Method(s): HMIS data from 129 (82%) public outpatient facilities were analyzed using interrupted time series models to estimate the impact of artemisinin-based combination therapy (ACT), indoor residual spray, and long-lasting insecticidal nets. Evaluation periods were defined as pre-intervention (January 2000 to August 2003), ACT-only (September 2003 to December 2005) and ACT plus vector control (2006-2015). Finding(s): After accounting for climate, seasonality, diagnostic testing rates, and outpatient attendance, average monthly incidence of confirmed malaria showed no trend over the pre-intervention period 2000-2003 (incidence rate ratio (IRR) 0.998, 95% CI 0.995-1.000). During the ACT-only period (2003-2005), the average monthly malaria incidence rate declined compared to the pre-intervention period, showing an overall declining trend during the ACT-only period (IRR 0.984, 95% CI 0.978-0.990). There was no intercept change at the start of the ACT-only period (IRR 1.081, 95% CI 0.968-1.208), but a drop in intercept was identified at the start of the ACT plus vector control period (IRR 0.683, 95% CI 0.597-0.780). During the ACT plus vector control period (2006-2015), the rate of decline in average monthly malaria incidence slowed compared to the ACT-only period, but the incidence rate continued to show an overall slight declining trend during 2006-2015 (IRR 0.993, 95% CI 0.992-0.994). Interpretation(s): This study presents a rigorous approach to the use of HMIS data in evaluating the impact of malaria control interventions. Evidence is presented for a rapid decline in malaria incidence during the period of ACT roll out compared to pre-intervention, with a rapid drop in malaria incidence following introduction of vector control and a slower declining incidence trend thereafter.

BACKGROUND: Malaria transmission is high in western Kenya and the asymptomatic infected population plays a significant role in driving the transmission. Mathematical modelling and simulation programs suggest that interventions targeting asymptomatic infections through mass testing and treatment (MTaT) or mass drug administration (MDA) have the potential to reduce malaria transmission when combined with existing interventions. OBJECTIVE: This paper describes the study site, capacity development efforts required, and lessons learned for implementing a multi-year community-based cluster-randomized controlled trial to evaluate the impact of MTaT for malaria transmission reduction in an area of high transmission in western Kenya. METHODS: The study partnered with Kenya's Ministry of Health (MOH) and other organizations on community sensitization and engagement to mobilize, train and deploy community health volunteers (CHVs) to deliver MTaT in the community. Within the health facilities, the study availed staff, medical and laboratory supplies and strengthened health information management system to monitor progress and evaluate impact of intervention. RESULTS: More than 80 Kenya MOH CHVs, 13 clinical officers, field workers, data and logistical staff were trained to carry out MTaT three times a year for 2 years in a population of approximately 90,000 individuals. A supply chain management was adapted to meet daily demands for large volumes of commodities despite the limitation of few MOH facilities having ideal storage conditions. Modern technology was adapted more to meet the needs of the high daily volume of collected data. CONCLUSIONS: In resource-constrained settings, large interventions require capacity building and logistical planning. This study found that investing in relationships with the communities, local governments, and other partners, and identifying and equipping the appropriate staff with the skills and technology to perform tasks are important factors for success in delivering an intervention like MTaT.

BACKGROUND: Health inequality is a recognized barrier to achieving health-related development goals. Health-equality data are essential for evidence-based planning and assessing the effectiveness of initiatives to promote equity. Such data have been captured but have not always been analysed or used to manage programming. Health data were examined for microeconomic differences in malaria indices and associated malaria control initiatives in western Kenya. METHODS: Data was analysed from a malaria cross-sectional survey conducted in July 2012 among 2719 people in 1063 households in Siaya County, Kenya. Demographic factors, history of fever, malaria parasitaemia, malaria medication usage, insecticide-treated net (ITN) use and expenditure on malaria medications were collected. A composite socioeconomic status score was created using multiple correspondence analyses (MCA) of household assets; households were classified into wealth quintiles and dichotomized into poorest (lowest 3 quintiles; 60%) or less-poor (highest 2 quintiles; 40%). Prevalence rates were calculated using generalized linear modelling. RESULTS: Overall prevalence of malaria infection was 34.1%, with significantly higher prevalence in the poorest compared to less-poor households (37.5% versus 29.2%, adjusted prevalence ratio [aPR] 1.23; 95% CI = 1.08-1.41, p = 0.002). Care seeking (aPR = 0.95; 95% CI 0.87-1.04, p = 0.229), medication use (aPR = 0.94; 95% CI 0.87-1.00, p = 0.087) and ITN use (aPR = 0.96; 95% CI = 0.87-1.05, p = 0.397) were similar between households. Among all persons surveyed, 36.4% reported taking malaria medicines in the prior 2 weeks; 92% took artemether-lumefantrine, the recommended first-line malaria medication. In the poorest households, 4.9% used non-recommended medicines compared to 3.5% in less-poor (p = 0.332). Mean and standard deviation [SD] for expenditure on all malaria medications per person was US$0.38 [US$0.50]; the mean was US$0.35 [US$0.52] amongst the poorest households and US$0.40 [US$0.55] in less-poor households (p = 0.076). Expenditure on non-recommended malaria medicine was significantly higher in the poorest (mean US$1.36 [US$0.91]) compared to less-poor households (mean US$0.98 [US$0.80]; p = 0.039). CONCLUSIONS: Inequalities in malaria infection and expenditures on potentially ineffective malaria medication between the poorest and less-poor households were evident in rural western Kenya. Findings highlight the benefits of using MCA to assess and monitor the health-equity impact of malaria prevention and control efforts at the microeconomic level.

Background: Response to antimalarial treatment is assessed using serial microscopy. New techniques for accurate measurement of the Plasmodium falciparum histidine rich protein 2 (HRP2) antigen have made monitoring antigen concentration over time a potential alternative for assessing treatment response. Methods: Post-treatment HRP2 concentration was measured in longitudinal samples from 537 participants with P. falciparum malaria from efficacy trials in Angola, Tanzania, and Senegal. The HRP2 half-life was estimated using a first-order kinetics clearance model. The association between HRP2 concentration three days post-treatment and recrudescence of infection was assessed. Results: Despite substantial variation in HRP2 concentration at baseline, HRP2 concentration in patients consistently showed a first-order exponential decline. The median half-life of HRP2 was estimated to be 4.5 days (interquartile range: 3.3-6.6) in Angola, 4.7 days (4.0-5.9) in Tanzania, and 3.0 days (2.1-4.5) in Senegal. The day 3 HRP2 concentration was predictive of eventual recrudescence, with an area under the receiver operating characteristic curve of 0.86 (95% confidence interval: 0.73-0.99). Conclusions: Consistent HRP2 clearance dynamics following successful antimalarial treatment imply a common underlying biological clearance mechanism. Patients that ultimately failed treatment did not exhibit this same pattern of clearance, even in the absence of other indications of inadequate response to treatment.

Haiti is committed to malaria elimination by 2020. Following a 2010 earthquake and cholera epidemic, Haiti capitalized on investments in its health system to refocus on malaria elimination. Efforts, including expanding diagnostics, ensuring efficacy of standard treatments, building institutional capacity, and strengthening surveillance were undertaken to complement the broad health system strengthening activities. These efforts led to the adoption and scale-up of malaria rapid diagnostic tests as a diagnostic modality. In addition, drug-resistant monitoring has been established in the country, along with the development of molecular testing capacity for the Plasmodium falciparum parasite at the National Public Health Laboratory. The development and piloting of surveillance activities to include an enhanced community-based approach for testing and treatment of patients has increased the ability of the Ministry of Health to map foci of transmission and respond promptly to outbreaks. The reinforcement of evidence-based approaches coupled with strong collaboration among the Ministry of Health and partners has demonstrated that malaria elimination by 2020 is a realistic prospect.

Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400-432,513). mRDTs were associated with significantly lower ACT prescription (range 8-69% versus 20-100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.

The recent article describing apparent artemether-lumefantrine (AL) treatment failure in four travelers returning to the United Kingdom (1) is well detailed. Passive surveillance for treatment failures, particularly in countries where malaria is not endemic and where greater attention and resources can be directed at individual malaria cases, is an important tool for antimalarial resistance monitoring. In fact, chloroquine resistance in sub-Saharan Africa was first documented in travelers returning to Europe and North America prior to being confirmed through efficacy trials at clinical sites in Africa (2). Toward this goal, the U.S. Centers for Disease Control and Prevention performs molecular resistance testing of samples from passively reported imported cases and investigates cases of suspected treatment failure. | However, treatment failures detected passively must be interpreted with caution and an attempt should be made to estimate the relevant denominator—the total number of cases treated with an antimalarial during the same period. Without denominator information, it is difficult to know whether the four cases reported by Sutherland et al. are indicative of a trend of decreasing AL efficacy or are consistent with the known background rate of AL treatment failure.

BACKGROUND: Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia. METHODS AND FINDINGS: Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI 0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI 2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9-9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia. CONCLUSIONS: Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y. TRIAL REGISTRATION: ClinicalTrials.gov NCT01680406.

Objectives To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia.Design Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).Setting Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.Participants 522 480 children and adults with acute febrile illness.Interventions Rapid diagnostic tests for malaria.Main outcome measures Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings.Results Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole.Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined.

BACKGROUND: Ranong Province in southern Thailand is one of the primary entry points for migrants entering Thailand from Myanmar, and borders Kawthaung Township in Myanmar where artemisinin resistance in malaria parasites has been detected. Areas of high population movement could increase the risk of spread of artemisinin resistance in this region and beyond. METHODS: A respondent-driven sampling (RDS) methodology was used to compare migrant populations coming from Myanmar in urban (Site 1) vs. rural (Site 2) settings in Ranong, Thailand. The RDS methodology collected information on knowledge, attitudes, and practices for malaria, travel and occupational histories, as well as social network size and structure. Individuals enrolled were screened for malaria by microscopy, Real Time-PCR, and serology. RESULTS: A total of 619 participants were recruited in Ranong City and 623 participants in Kraburi, a rural sub-district. By PCR, a total of 14 (1.1%) samples were positive (2 P. falciparum in Site 1; 10 P. vivax, 1 Pf, and 1 P. malariae in Site 2). PCR analysis demonstrated an overall weighted prevalence of 0.5% (95% CI, 0-1.3%) in the urban site and 1.0% (95% CI, 0.5-1.7%) in the rural site for all parasite species. PCR positivity did not correlate with serological positivity; however, as expected there was a strong association between antibody prevalence and both age and exposure. Access to long-lasting insecticidal treated nets remains low despite relatively high reported traditional net use among these populations. CONCLUSIONS: The low malaria prevalence, relatively smaller networks among migrants in rural settings, and limited frequency of travel to and from other areas of malaria transmission in Myanmar, suggest that the risk for the spread of artemisinin resistance from this area may be limited in these networks currently but may have implications for regional malaria elimination efforts.

Since 2010, the World Health Organization has recommended universal malaria diagnostic testing to guide treatment of febrile illness as a fundamental component of malaria case management (1). Malaria control programs and their partners have been gradually expanding diagnostic testing, largely through point-of-care rapid diagnostic tests (RDTs). For the past 2 years, global purchases of malaria RDTs have equaled or slightly exceeded treatment doses of artemisinin-based combination therapies (ACT), and nearly half of globally reported malaria cases have been diagnostically confirmed (2). Emily White Johansson's doctoral thesis – summarized in this issue (3) – examined early experience expanding malaria diagnostic testing across sub-Saharan Africa and points to some key directions for additional scholarship and program implementation. | Johansson and her colleagues (4–7) interrogated nationwide malaria coverage surveys from more than a dozen countries, conducted original qualitative and quantitative research in Uganda, and unleashed powerful big data approaches on a comprehensive health service assessment data set from Malawi – all with the goal of expanding the previously limited understanding of malaria diagnostic practices just as malaria RDTs were being introduced for routine practice. Collectively, it is an analytical tour de force. The resulting publications demonstrate program-relevant observations. Access to malaria diagnostic testing was poor and wildly inequitable shortly following the universal diagnosis policy – particularly in peripheral health facilities. None of the nationwide surveys showed the promised reductions in ACT consumption at a population level, at least not at first. Moreover, countries varied greatly in terms of what impact malaria diagnostic testing had on fever management overall. While clinical guidelines for antibiotic use appeared straightforward, they still required considerable judgment on the part of health workers – who were frequently left feeling unsupported, especially when malaria test results were negative. Once malaria diagnostic testing had become established, however, a majority of health workers adapted to using the results to guide malaria-specific treatment. But antibiotic overtreatment was common, especially among children testing negative for malaria, and was influenced by the presence of other symptoms such as cough or difficult breathing. Arriving at each of these discrete findings, Dr. Johansson establishes an approach that she and others can revisit as new evidence and experience accumulate.

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 patient clinical data meta-analysis was undertaken to identify the determinants of gametocyte carriage and the comparative effects of four ACTs: artemether-lumefantrine (AL), artesunate/amodiaquine (AS-AQ), artesunate/mefloquine (AS-MQ), and dihydroartemisinin-piperaquine (DP). METHODS: Factors associated with gametocytaemia prior to, and following, ACT treatment were identified in multivariable logistic or Cox regression analysis with random effects. All relevant studies were identified through a systematic review of PubMed. Risk of bias was evaluated based on study design, methodology, and missing data. RESULTS: The systematic review identified 169 published and 9 unpublished studies, 126 of which were shared with the WorldWide Antimalarial Resistance Network (WWARN) and 121 trials including 48,840 patients were included in the analysis. Prevalence of gametocytaemia by microscopy at enrolment was 12.1 % (5887/48,589), and increased with decreasing age, decreasing asexual parasite density and decreasing haemoglobin concentration, and was higher in patients without fever at presentation. After ACT treatment, gametocytaemia appeared in 1.9 % (95 % CI, 1.7-2.1) of patients. The appearance of gametocytaemia was lowest after AS-MQ and AL and significantly higher after DP (adjusted hazard ratio (AHR), 2.03; 95 % CI, 1.24-3.12; P = 0.005 compared to AL) and AS-AQ fixed dose combination (FDC) (AHR, 4.01; 95 % CI, 2.40-6.72; P < 0.001 compared to AL). Among individuals who had gametocytaemia before treatment, gametocytaemia clearance was significantly faster with AS-MQ (AHR, 1.26; 95 % CI, 1.00-1.60; P = 0.054) and slower with DP (AHR, 0.74; 95 % CI, 0.63-0.88; P = 0.001) compared to AL. Both recrudescent (adjusted odds ratio (AOR), 9.05; 95 % CI, 3.74-21.90; P < 0.001) and new (AOR, 3.03; 95 % CI, 1.66-5.54; P < 0.001) infections with asexual-stage parasites were strongly associated with development of gametocytaemia after day 7. CONCLUSIONS: AS-MQ and AL are more effective than DP and AS-AQ FDC in preventing gametocytaemia shortly after treatment, suggesting that the non-artemisinin partner drug or the timing of artemisinin dosing are important determinants of post-treatment gametocyte dynamics.

BACKGROUND: Insecticide-treated bednets (ITNs) are effective in preventing malaria where vectors primarily bite indoors and late at night, but their effectiveness is uncertain where vectors bite outdoors and earlier in the evening. We studied the effectiveness of ITNs following a mass distribution in Haiti from May to September, 2012, where the Anopheles albimanus vector bites primarily outdoors and often when people are awake. METHODS: In this case-control study, we enrolled febrile patients presenting to outpatient departments at 17 health facilities throughout Haiti from Sept 4, 2012, to Feb 27, 2014, who were tested with malaria rapid diagnostic tests (RDTs), and administered questionnaires on ITN use and other risk factors. Cases were defined by positive RDT and controls were febrile patients from the same clinic with a negative RDT. Our primary analysis retrospectively matched cases and controls by age, sex, location, and date, and used conditional logistic regression on the matched sample. A sensitivity analysis used propensity scores to match patients on ITN use propensity and analyse malaria among ITN users and non-users. Additional ITN bioefficacy and entomological data were collected. FINDINGS: We enrolled 9317 patients, including 378 (4%) RDT-positive cases. 1202 (13%) patients reported ITN use. Post-hoc matching of cases and controls yielded 362 cases and 1201 matched controls, 19% (333) of whom reported consistent campaign net use. After using propensity scores to match on consistent campaign ITN use, 2298 patients, including 138 (7%) RDT-positive cases, were included: 1149 consistent campaign ITN users and 1149 non-consistent campaign ITN users. Both analyses revealed that ITNs did not significantly protect against clinical malaria (odds ratio [OR]=0.95, 95% CI 0.68-1.32, p=0.745 for case-control analysis; OR=0.95, 95% CI 0.45-1.97, p=0.884 for propensity score analysis). ITN and entomological data indicated good ITN physical integrity and bioefficacy, and no permethrin resistance among local mosquitoes. INTERPRETATION: We found no evidence that mass ITN campaigns reduce clinical malaria in this observational study in Haiti; alternative malaria control strategies should be prioritised. FUNDING: The Global Fund to Fight AIDS, Tuberculosis, and Malaria, and the US-based Centers for Disease Control and Prevention (CDC).

BACKGROUND: Recent reports of Plasmodium vivax associated with severe syndromes and mortality from malaria endemic areas questions the "benign" course of non-falciparum malarias. METHODS: We retrospectively analyzed data from patients reported to the US Centers for Disease Control and Prevention with a diagnosis of malaria parasite single-species infection between 1985 and 2011. Patients classified as having severe illness were further classified according to outcome (survival versus death) and clinical syndrome. RESULTS: Among all cases, .9% of Plasmodium falciparum cases resulted in death and 9.3% were classified as severe, whereas .09% of P. vivax cases resulted in death and 1.3% were classified as severe. The odds ratios for severe illness among 15 272 diagnoses of P. falciparum relative to patients diagnosed with P. vivax (n = 12 152), Plasmodium malariae (n = 1254), or Plasmodium ovale (n = 903) was 7.5, 5.7, and 5.0, respectively (P < .0001 for all); in contrast, the corresponding odds ratios for death among those severely ill was 1.6, 1.1, and .8 (P > .1 for all), respectively. Compared with P. vivax (n = 163), the odds of P. falciparum cases classified as severely ill (n = 1416) were 1.9 (P = .0006), .5 (P = .001), and 1.3 times (P = .1) as likely to present as cerebral, acute respiratory distress, and renal syndromes, respectively. CONCLUSIONS: Although less common, patients presenting with non-falciparum even in the United States can develop severe illness, and severe illness in patients having malaria of any species threatens life.

Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341 P. falciparum infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures.

Ensuring that artemisinin-containing antimalarials (ACAs) are of good quality is a key component of effective malaria treatment. There are concerns that a high proportion of ACAs are falsified or substandard, though estimates are rarely based on representative data. During a nationally representative survey in Tanzania, ACAs were purchased from private retail drug outlets, and the active pharmaceutical ingredient (API) was measured. All 1,737 ACAs contained the labeled artemisinin derivative, with 4.1% being outside the 85-115% artemisinin API range defined as acceptable quality. World Health Organization (WHO) prequalified drugs had 0.1 times the odds of being poor quality compared with non-prequalified ACAs for the artemisinin component. When partner components of combination therapies were also considered, 12.1% were outside the acceptable API range, and WHO prequalified ACAs had 0.04 times the odds of being poor quality. Although the prevalence of poor quality ACAs was lower than reported elsewhere, the minority of samples found to be substandard is a cause for concern. Improvements in quality could be achieved by increasing the predominance of WHO prequalified products in the market. Continued monitoring of quality standards is essential.

BACKGROUND: Quinidine gluconate, the only U.S. Food and Drug Administration-approved treatment for life-threatening malaria in the United States, has a problematic safety profile and is often unavailable in hospitals. OBJECTIVE: To assess the safety and clinical benefit of intravenous artesunate as an alternative to quinidine. DESIGN: Retrospective case series. SETTING: U.S. hospitals. PATIENTS: 102 patients aged 1 to 72 years (90% adults; 61% men) with severe and complicated malaria. Patients received 4 weight-based doses of intravenous artesunate (2.4 mg/kg) under a treatment protocol implemented by the Centers for Disease Control and Prevention between January 2007 and December 2010. At baseline, 35% had evidence of cerebral malaria, and 17% had severe hepatic impairment. Eligibility required the presence of microscopically confirmed malaria, need for intravenous treatment, and an impediment to quinidine. MEASUREMENTS: Clinical and laboratory data from each patient's hospital records were abstracted retrospectively, including information from baseline through a maximum 7-day follow-up, and presented before a physician committee to evaluate safety and clinical benefit outcomes. RESULTS: 7 patients died (mortality rate, 6.9%). The most frequent adverse events were anemia (65%) and elevated hepatic enzyme levels (49%). All deaths and most adverse events were attributed to the severity of malaria. Patients' symptoms generally improved or resolved within 3 days, and the median time to discharge from the intensive care unit was 4 days, even for patients with severe liver disease or cerebral malaria. More than 100 concomitant medications were used, with no documented drug-drug interactions. LIMITATION: Potential late-presenting safety issues might occur outside the 7-day follow-up. CONCLUSION: Artesunate was a safe and clinically beneficial alternative to quinidine. PRIMARY FUNDING SOURCE: Office of the Surgeon General, Department of the U.S. Army.

OBJECTIVE: Universal coverage with insecticide-treated bed nets is a cornerstone of modern malaria control. Mozambique has developed a novel bed net allocation strategy, where the number of bed nets allocated per household is calculated on the basis of household composition and assumptions about who sleeps with whom. We set out to evaluate the performance of the novel allocation strategy. METHODS: 1,994 households were visited during household surveys following two universal coverage bed net distribution campaigns in Sofala and Nampula Provinces in 2010-2013. Each sleeping space was observed for the presence of a bed net, and the sleeping patterns for each household were recorded. The observed coverage and efficiency were compared to a simulated coverage and efficiency had conventional allocation strategies been used. A composite indicator, the product of coverage and efficiency, was calculated. Observed sleeping patterns were compared with the sleeping pattern assumptions. RESULTS: In households reached by the campaign, 93% (95% CI: 93-94%) of sleeping spaces in Sofala and 84% (82-86%) in Nampula were covered by campaign bed nets. The achieved efficiency was high, with 92% (91-93%) of distributed bed nets in Sofala and 93% (91-95%) in Nampula covering a sleeping space. Using the composite indicator, the novel allocation strategy outperformed all conventional strategies in Sofala and was tied for best in Nampula. The sleeping pattern assumptions were completely satisfied in 66% of households in Sofala and 56% of households in Nampula. The most common violation of the sleeping pattern assumptions was that male children 3-10 years of age tended not to share sleeping spaces with female children 3-10 or 10-16 years of age. CONCLUSIONS: The sleeping pattern assumptions underlying the novel bed net allocation strategy are generally valid, and net allocation using these assumptions can achieve high coverage and compare favorably with conventional allocation strategies.

BACKGROUND: Self-report is the most common and feasible method for assessing patient adherence to medication, but can be prone to recall bias and social desirability bias. Most studies assessing adherence to artemisinin-based combination therapies (ACTs) have relied on self-report. In this study, we use a novel customised electronic monitoring device-termed smart blister packs-to examine the validity of self-reported adherence to artemether-lumefantrine (AL) in southern Tanzania. METHODS: Smart blister packs were designed to look identical to locally available AL blister packs and to record the date and time each tablet was removed from packaging. Patients obtaining AL at randomly selected health facilities and drug stores were followed up at home three days later and interviewed about each dose of AL taken. Blister packs were requested for pill count and extraction of smart blister pack data. RESULTS: Data on adherence from both self-report verified by pill count and smart blister packs were available for 696 of 1,204 patients. There was no difference between methods in the proportion of patients assessed to have completed treatment (64% and 67%, respectively). However, the percentage taking the correct number of pills for each dose at the correct times (timely completion) was higher by self-report than smart blister packs (37% vs. 24%; p<0.0001). By smart blister packs, 64% of patients completing treatment did not take the correct number of pills per dose or did not take each dose at the correct time interval. CONCLUSION: Smart blister packs resulted in lower estimates of timely completion of AL and may be less prone to recall and social desirability bias. They may be useful when data on patterns of adherence are desirable to evaluate treatment outcomes. Improved methods of collecting self-reported data are needed to minimise bias and maximise comparability between studies.

BACKGROUND: The ongoing west Africa Ebola-virus-disease epidemic has disrupted the entire health-care system in affected countries. Because of the overlap of symptoms of Ebola virus disease and malaria, the care delivery of malaria is particularly sensitive to the indirect effects of the current Ebola-virus-disease epidemic. We therefore characterise malaria case management in the context of the Ebola-virus-disease epidemic and document the effect of the Ebola-virus-disease epidemic on malaria case management. METHODS: We did a cross-sectional survey of public health facilities in Guinea in December, 2014. We selected the four prefectures most affected by Ebola virus disease and selected four randomly from prefectures without any reported cases of the disease. 60 health facilities were sampled in Ebola-affected and 60 in Ebola-unaffected prefectures. Study teams abstracted malaria case management indicators from registers for January to November for 2013 and 2014 and interviewed health-care workers. Nationwide weekly surveillance data for suspect malaria cases reported between 2011 and 2014 were analysed independently. Data for malaria indicators in 2014 were compared with previous years. FINDINGS: We noted substantial reductions in all-cause outpatient visits (by 23 103 [11%] of 214 899), cases of fever (by 20249 [15%] of 131 330), and patients treated with oral (by 22 655 [24%] of 94 785) and injectable (by 5219 [30%] of 17 684) antimalarial drugs in surveyed health facilities. In Ebola-affected prefectures, 73 of 98 interviewed community health workers were operational (74%, 95% CI 65-83) and 35 of 73 were actively treating malaria cases (48%, 36-60) compared with 106 of 112 (95%, 89-98) and 102 of 106 (96%, 91-99), respectively, in Ebola-unaffected prefectures. Nationwide, the Ebola-virus-disease epidemic was estimated to have resulted in 74 000 (71 000-77 000) fewer malaria cases seen at health facilities in 2014. INTERPRETATION: The reduction in the delivery of malaria care because of the Ebola-virus-disease epidemic threatens malaria control in Guinea. Untreated and inappropriately treated malaria cases lead to excess malaria mortality and more fever cases in the community, impeding the Ebola-virus-disease response. FUNDING: Global Fund to Fight AIDS, Tuberculosis and Malaria, and President's Malaria Initiative.