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Objective To determine why health workers fail to follow integrated management of childhood illness (IMCI) guidelines for severely ill children at first-level outpatient health facilities in rural areas of the United Republic of Tanzania. Methods Retrospective and prospective case reviews of severely ill children aged < 5 years were conducted at health facilities in four districts. We ascertained treatment and examined the characteristics associated with referral, conducted follow-up interviews with parents of severely ill children, and gave health workers questionnaires and interviews. Findings In total, 502 cases were reviewed at 62 facilities. Treatment with antimalarials and antibiotics was consistent with the diagnosis given by health workers. However, of 240 children classified as having "very severe febrile disease", none received all IMCI-recommended therapies, and only 25% of severely ill children were referred. Lethargy and anaemia diagnoses were independently associated with referral. Most (91%) health workers indicated that certain severe conditions can be managed without referral. Conclusion The health workers surveyed rarely adhered to IMCI treatment and referral guidelines for children with severe illness. They administered therapy based on narrow diagnoses rather than IMCI classifications, disagreed with referral guidelines and often considered referral unnecessary. To improve implementation of IMCI, attention should focus on the reasons for health worker non-adherence. [ABSTRACT FROM AUTHOR]

Objective To assess the validity of health facility (HF)-based data on bednet and insecticide-treated bednet possession and use by children <5 years old. Methods We compared estimates based on data collected via HF surveys of under-5s attending well-child visits (e.g. immunizations) and sick-child visits vs. representative household surveys (a ‘gold standard’ method for measuring insecticide-treated net coverage). In Lindi region, Tanzania, we collected contemporaneous data on 637 under-5s via a HF survey (444 well-child visits and 193 sick-child visits), and on 305 households with an under-5 (including 354 children) via a household survey. In Rufiji district, Tanzania, we collected contemporaneous data on 1433 under-5s via a HF survey (911 well-child visits and 522 sick-child visits), and on 328 households with an under-5 (including 455 children) via a household survey. Results Possession of bednets by households with an under-5 was similar using HF data and household data in both Lindi region and Rufiji district. However, reported use of bednets was significantly higher in HF data than household data in both Lindi and Rufiji, as was reported use of insecticide-treated bednets. HF-based data accurately estimated community-level bednet possession in households with an under-5, but overestimated community-level bednet use by 9–35% and insecticide-treated bednet use by 15–21%. Conclusions Information bias rather than selection bias appears to be a key cause for the overestimation of bednet and insecticide-treated bednet use (e.g. social desirability bias: caretakers of under-5s attending health facilities might be more likely to report using bednets and insecticide-treated bednets). Additional studies of the validity, cost and utility of HF-based data to monitor insecticide-treated bednet use are needed before recommending this monitoring strategy for widespread use. Overestimating insecticide-treated bednet use could lead to inappropriate public health actions and missed opportunities for achieving local and global public health goals. [ABSTRACT FROM AUTHOR]

Presents the report on the surveillance of malaria cases in the United States in 1997. Interval between arrival and illness; Use of antimalarial chemoprophylaxis; Malaria acquired in the United States; Deaths attributed to malaria.

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. [ABSTRACT FROM AUTHOR]

Background: There are few community-level behaviors change interventions for reducing diabetes and hypertension risk in Africa, despite increasing cases of type 2 diabetes and cardiovascular diseases. Thus, this study was designed to adapt the United States Centers for Disease Control and Prevention's "Diabetes Prevention Program Power to Prevent" (DPP-P2P) for use in low-income urban communities of Bamako, Mali., Methods: Feedback was elicited on an initial French PowerPoint adaptation of the DPP-P2P session guidelines from stakeholders at the ministry of health, organizational partners, and medical care providers. Two community health centers in districts with high levels of diabetes or hypertension were selected to assist in developing the Malian adaptation. Focus groups were conducted with 19 community health workers (CHWs) of these centers. Based on feedback from these discussions, more graphics, demonstrations, and role plays were added to the PowerPoint presentations. The 19 CHWs piloted the proposed 12 sessions with 45 persons with diabetes or at-risk patients over a one-month period. Feedback discussions were conducted after each session, and changes in dietary and exercise habits were assessed pre and post participation in the program. This feedback contributed to finalization of a 14-session sequence., Results: The DPP-P2P session guidelines were adapted for use by low-literacy CHWs, converting the written English guidelines into French PowerPoint presentations with extensive use of pictures, role plays and group discussions to introduce diabetes, diet, and exercise concepts appropriately for the Bamako context. CHWs recommendations for a strong family-oriented program led to expanded sessions on eliciting support from all adults in the household. The 45 participants in the pilot adaptation were enthusiastic about the program. At the end of the program, there were significant increases in the frequency of daily exercise, efforts to limit fat intake, and goals for more healthy diets and exercise levels., Conclusion: This study documents how an iterative process of developing the DPP-P2P adaptation led to the development of a culturally appropriate set of materials welcomed by participants and having promise for reaching the low-income, low-literacy population with or at risk for diabetes in Bamako, Mali., (© 2024. The Author(s).)

Ever since the 1990s, implementation research in Ghana has guided the development of policies and practices that are essential to establishing community-based primary health care. In response to evidence emerging from this research, the Community-based Health Planning and Services (CHPS) policy was promulgated in 1999 to scale-up results. However, during the first decade of CHPS operation, national monitoring showed that its pace of coverage expansion was unacceptably slow. In 2010, the Ghana Health Service launched a 5-year plausibility trial of CHPS reform for testing ways to accelerate scale-up. This initiative, known as the Ghana Essential Health Intervention Program (GEHIP), included a knowledge management component for establishing congruence of knowledge generation and flow with the operational system that GEHIP evidence was intended to reform. Four Upper East Region districts served as trial areas, while seven districts were comparison areas. Interventions tested means of developing the upward flow of information based on perspectives of district managers, sub-district supervisors and community-level workers. GEHIP also endeavoured to improve procedures for the downward flow and utilization of policy guidelines. Field exchanges were convened for providing national, regional and district leaders with opportunities for participatory learning about GEHIP implementation innovations. This systems approach facilitated the process of augmenting the communication of evidence with practical field experience. Scientific rigor associated with the production of evidence was thereby integrated into management decision-making processes in ways that institutionalized learning at all levels. The GEHIP knowledge management system functioned as a prototype for guiding the planning of a national knowledge management strategy. A follow-up project transferred its mechanisms from the Upper East Regional Health Administration to the Policy Planning Monitoring and Evaluation Division of the Ghana Health Service in Accra., (© The Author(s) 2022. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: It has been hypothesized that in high-transmission settings, malaria control in early childhood (<5 years of age) might delay the acquisition of functional immunity and shift child deaths from younger to older ages., Methods: We used data from a 22-year prospective cohort study in rural southern Tanzania to estimate the association between early-life use of treated nets and survival to adulthood. All the children born between January 1, 1998, and August 30, 2000, in the study area were invited to enroll in a longitudinal study from 1998 through 2003. Adult survival outcomes were verified in 2019 through community outreach and mobile telephones. We used Cox proportional-hazards models to estimate the association between the use of treated nets in early childhood and survival to adulthood, adjusting for potential confounders., Results: A total of 6706 children were enrolled. In 2019, we verified information on the vital status of 5983 participants (89%). According to reports of early-life community outreach visits, approximately one quarter of children never slept under a treated net, one half slept under a treated net some of the time, and the remaining quarter always slept under a treated net. Participants who were reported to have used treated nets at half the early-life visits or more had a hazard ratio for death of 0.57 (95% confidence interval [CI], 0.45 to 0.72) as compared with those who were reported to have used treated nets at less than half the visits. The corresponding hazard ratio between 5 years of age and adulthood was 0.93 (95% CI, 0.58 to 1.49)., Conclusions: In this long-term study of early-life malaria control in a high-transmission setting, the survival benefit from early-life use of treated nets persisted to adulthood. (Funded by the Eckenstein-Geigy Professorship and others.)., (Copyright © 2022 Massachusetts Medical Society.)

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., (Copyright © 2021 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Most countries have implemented restrictions on mobility to prevent the spread of Coronavirus disease-19 (COVID-19), entailing considerable societal costs but, at least initially, based on limited evidence of effectiveness. We asked whether mobility restrictions were associated with changes in the occurrence of COVID-19 in 34 OECD countries plus Singapore and Taiwan. Our data sources were the Google Global Mobility Data Source, which reports different types of mobility, and COVID-19 cases retrieved from the dataset curated by Our World in Data. Beginning at each country's 100th case, and incorporating a 14-day lag to account for the delay between exposure and illness, we examined the association between changes in mobility (with January 3 to February 6, 2020 as baseline) and the ratio of the number of newly confirmed cases on a given day to the total number of cases over the past 14 days from the index day (the potentially infective 'pool' in that population), per million population, using LOESS regression and logit regression. In two-thirds of examined countries, reductions of up to 40% in commuting mobility (to workplaces, transit stations, retailers, and recreation) were associated with decreased cases, especially early in the pandemic. Once both mobility and incidence had been brought down, further restrictions provided little additional benefit. These findings point to the importance of acting early and decisively in a pandemic.

Implementation research often fails to have its intended impact on what programs actually do. Embedding research within target organizational systems represents an effective response to this problem. However, contradictions associated with the approach often prevent its application. We present case studies of the application of embedded implementation research in Bangladesh, Ghana, and Tanzania where initiatives to strengthen community-based health systems were conducted using the embedded science model. In 2 of the cases, implementation research standards that are typically embraced without question were abandoned to ensure pursuit of embedded science. In the third example, statistical rigor was sustained, but this feature of the design was inconsistent with embedded science. In general, rigorous statistical designs employ units of observation that are inconsistent with organizational units that managers can control. Structural contradictions impede host institution ownership of research processes and utilization of results. Moreover, principles of scientific protocol leadership are inconsistent with managerial leadership. These and other embedded implementation science attributes are reviewed together with contradictions that challenged their pursuit in each case. Based on strategies that were effectively applied to offsetting challenges, a process of merging research with management is proposed that is derived from computer science. Known as "agile science," this paradigm combines scientific rigor with management decision making. This agile embedded research approach is designed to sustain scientific rigor while optimizing the integration of learning into managerial decision making., (© Phillips et al.)

Background: The whole Plasmodium falciparum 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 (aged 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: 1.35 × 105, 2.7 × 105, 4.5 × 105, 9.0 × 105, and 1.8 × 106 PfSPZ, with the 2 highest doses given twice, 8 weeks apart. Solicited adverse events (AEs) were monitored for 8 days after vaccination, unsolicited AEs for 29 days, and serious AEs throughout the study. Blood taken prevaccination and 1 week postvaccination was tested for immunoglobulin G antibodies to P. falciparum circumsporozoite protein (PfCSP) using enzyme-linked immunosorbent assay., 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, serious AEs, or grade 3 laboratory abnormalities occurred. Most (79.0%) vaccinations were administered by a single DVI. Among those in the 9.0 × 105 and 1.8 × 106 PfSPZ groups, 36 of 45 (80.0%) vaccinees and 4 of 21 (19.0%) placebo controls developed antibodies to PfCSP (P < .001)., Conclusions: PfSPZ vaccine in doses as high as 1.8 × 106 can be administered to infants and children by DVI, and was safe, well tolerated, and immunogenic., Clinical Trials Registration: NCT02687373., (Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

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: 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., Methods: 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)., Findings: 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: 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., Competing Interests: The authors declare no conflicts of interest.

In 2014, panel physicians from the International Organization for Migration (IOM), who conduct Department of State-required predeparture examinations for U.S.-bound refugees at resettlement sites in Uganda, noticed an unusually high number of Congolese refugees with enlarged spleens, or splenomegaly. Many conditions can cause splenomegaly, such as various infections, liver disease, and cancer. Splenomegaly can result in hematologic disturbances and abdominal pain and can increase the risk for splenic rupture from blunt trauma, resulting in life-threatening internal bleeding. On CDC's advice, panel physicians implemented an enhanced surveillance and treatment protocol that included screening for malaria (through thick and thin smears and rapid diagnostic testing), schistosomiasis, and several other conditions; treatment of any condition identified as potentially associated with splenomegaly; and empiric treatment for the most likely etiologies, including malaria and schistosomiasis. CDC recommended further treatment for malaria with primaquine after arrival, after glucose-6-phosphate dehydrogenase testing, to target liver-stage parasites. Despite this recommended treatment protocol, 35 of 64 patients with available follow-up records had splenomegaly that persisted beyond 6 months after resettlement. Among 85 patients who were diagnosed with splenomegaly through abdominal palpation or ultrasound at any point after resettlement, 53 had some hematologic abnormality (leukopenia, anemia, or thrombocytopenia), 16 had evidence of current or recent malaria infection, and eight had evidence of schistosomiasis. Even though primaquine was provided to a minority of patients in this cohort, it should be provided to all eligible patients with persistent splenomegaly, and repeated antischistosomal therapy should be provided to patients with evidence of current or recent schistosomiasis. Given substantial evidence of familial clustering of cases, family members of patients with known splenomegaly should be proactively screened for this condition., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

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)., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2016 The Author(s).)

Background: In vivo efficacy assessments of antimalarials are essential for ensuring effective case management. In Ethiopia, chloroquine (CQ) without primaquine is the first-line treatment for Plasmodium vivax in malarious areas, but artemether-lumefantrine (AL) is also commonly used., Methods and Findings: In 2009, we conducted a 42-day efficacy study of AL or CQ for P. vivax in Oromia Regional State, Ethiopia. Individuals with P. vivax monoinfection were enrolled. Primary endpoint was day 28 cure rate. In patients with recurrent parasitemia, drug level and genotyping using microsatellite markers were assessed. Using survival analysis, uncorrected patient cure rates at day 28 were 75.7% (95% confidence interval (CI) 66.8-82.5) for AL and 90.8% (95% CI 83.6-94.9) for CQ. During the 42 days of follow-up, 41.6% (47/113) of patients in the AL arm and 31.8% (34/107) in the CQ arm presented with recurrent P. vivax infection, with the median number of days to recurrence of 28 compared to 35 days in the AL and CQ arm, respectively. Using microsatellite markers to reclassify recurrent parasitemias with a different genotype as non-treatment failures, day 28 cure rates were genotype adjusted to 91.1% (95% CI 84.1-95.1) for AL and to 97.2% (91.6-99.1) for CQ. Three patients (2.8%) with recurrent parasitemia by day 28 in the CQ arm were noted to have drug levels above 100 ng/ml., Conclusions: In the short term, both AL and CQ were effective and well-tolerated for P. vivax malaria, but high rates of recurrent parasitemia were noted with both drugs. CQ provided longer post-treatment prophylaxis than AL, resulting in delayed recurrence of parasitemia. Although the current policy of species-specific treatment can be maintained for Ethiopia, the co-administration of primaquine for treatment of P. vivax malaria needs to be urgently considered to prevent relapse infections., Trial Registration: ClinicalTrials.gov NCT01052584.

Problem/condition: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquito-borne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers., Period Covered: This report summarizes cases in persons with onset of illness in 2010 and summarizes trends during previous years., Description of System: Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are mandated to be reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consults. Data from these reporting systems serve as the basis for this report., Results: CDC received 1,691 reported cases of malaria, including 1,688 cases classified as imported, one transfusion-related case, and two cryptic cases, with an onset of symptoms in 2010 among persons in the United States. The total number of cases represents an increase of 14% from the 1,484 cases reported for 2009. Plasmodium falciparum, P. vivax, P. malariae, and P. ovale were identified in 58%, 19%, 2%, and 2% of cases, respectively. Thirteen patients were infected by two or more species. The infecting species was unreported or undetermined in 18% of cases. Among the 898 cases in U.S. civilians for whom information on chemoprophylaxis use and travel area was known, 45 (5%) reported that they had followed and adhered to a chemoprophylactic drug regimen recommended by CDC for the areas to which they had traveled. Forty-one cases were reported in pregnant women, among whom only two (5%) adhered to chemoprophylaxis. Among all reported cases, 176 (10%) were classified as severe infections, of which nine were fatal., Interpretation: The number of cases reported in 2010 marked the largest number of cases reported since 1980. Despite the apparent progress in reducing the global burden of malaria, many areas remain malaria endemic and the use of appropriate prevention measures by travelers is still inadequate., Public Health Actions: Travelers visiting friends and relatives (VFR) continue to be a difficult population to reach with effective malaria prevention strategies. Evidence-based prevention strategies that effectively target VFR travelers need to be developed and implemented to have a substantial impact on the numbers of imported malaria cases in the United States. A large number of pregnant travelers diagnosed with malaria did not take any chemoprophylaxis. Pregnant women traveling to areas in which malaria is endemic are at higher risk for severe malaria and must use appropriate malaria prevention strategies including chemoprophylaxis. Malaria prevention recommendations are available online (http://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Clinicians should consult the CDC Guidelines for Treatment of Malaria and contact the CDC's Malaria Hotline for case management advice, when needed. Malaria treatment recommendations can be obtained online (http://www.cdc.gov/malaria/diagnosis&#95;treatment) or by calling the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713).

Background: In vivo efficacy assessments of the first-line treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated P. falciparum malaria since 2004., Methods: Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for P. falciparum in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented P. falciparum mono-infection were enrolled and followed according to the standard 2009 World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively., Results: Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight P. falciparum patients (6.7%) presented with Plasmodium vivax infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events., Conclusions: AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with P. vivax possibly from relapse or new infection was observed., Trial Registration: NCT01052584.

Background: In 2005, the Ministry of Health in Ethiopia launched a major effort to distribute over 20 million long-lasting insecticidal nets, provide universal access to artemisinin-based combination therapy (ACTs), and train 30,000 village-based health extension workers., Methods and Findings: A cross-sectional, nationally representative Malaria Indicator Survey was conducted during the malaria transmission season in 2007. Multivariate logistic regression analyses were performed to assess the effect of women's malaria knowledge on household ITN ownership and women's ITN use. In addition, we investigated the effect of mothers' malaria knowledge on their children under 5 years of age's (U5) ITN use and their access to fever treatment on behalf of their child U5. Malaria knowledge was based on a composite index about the causes, symptoms, danger signs and prevention of malaria. Approximately 67% of women (n=5,949) and mothers of children U5 (n=3,447) reported some knowledge of malaria. Women's knowledge of malaria was significantly associated with household ITN ownership (adjusted Odds Ratio [aOR]=2.1; 95% confidence interval [CI] 1.6-2.7) and with increased ITN use for themselves (aOR=1.8; 95% CI 1.3-2.5). Knowledge of malaria amongst mothers of children U5 was associated with ITN use for their children U5 (aOR=1.6; 95% CI 1.1-2.4), but not significantly associated with their children U5 seeking care for a fever. School attendance was a significant factor in women's ITN use (aOR=2.0; 95% CI 1.1-3.9), their children U5's ITN use (aOR=4.4; 95% CI 1.6-12.1), and their children U5 having sought treatment for a fever (aOR=6.5; 95% CI 1.9-22.9)., Conclusions: Along with mass free distribution of ITNs and universal access to ACTs, delivery of targeted malaria educational information to women could improve ITN ownership and use. Efforts to control malaria could be influenced by progress towards broader goals of improving access to education, especially for women.

Background: The Centers for Disease Control and Prevention (CDC) is in the process of integrating the existing dual mechanisms for reporting cases of malaria diagnosed in the United States into a single electronic reporting mechanism. Before adoption of this new system, an evaluation of the existing systems for state-level reporting of malaria data to the CDC was conducted., Methods: CDC guidelines for evaluating surveillance systems were used to assess the attributes of the National Malaria Surveillance System (NMSS), the current National Notifiable Diseases Surveillance System (NNDSS), and the projected fully integrated NNDSS. We analyzed data collected from NMSS and NNDSS from 2001 to 2005 using the Chandra-Sekar-Deming method to estimate completeness of reporting., Results: The projected fully integrated system was assessed likely to perform better than either of the existing systems on all attributes except stability. The overall completeness of reporting was estimated to be 80.3 percent for NNDSS and 74.7 percent for NMSS., Conclusions: Both existing systems have reasonably high ascertainment of cases. A fully integrated system with malaria-specific data fields would improve upon existing systems if it proved to be stable.

Malaria is a leading cause of morbidity and mortality worldwide. Prompt diagnosis and treatment are critical factors in reducing morbidity and mortality, as delayed treatment of malaria increases the risk of death. Microscopy has long been the standard of malaria diagnosis, but newer diagnostic tests now offer advantages in certain settings. Malaria diagnosis is complicated by the fact that acquired immunity to malaria can result in asymptomatic infections. In a symptomatic (febrile) patient, no existing malaria diagnostic test can distinguish malarial illness from parasitemia with concomitant fever of another cause. In this review we discuss the available malaria diagnostic tests, appropriate applications for each, and the challenges of malaria diagnosis in both endemic and non-endemic settings.

Background: The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y ("under five") and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar., Methods and Findings: Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28-1.08), and for 2006, 0.03 (0.00-0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1-4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period., Conclusions: Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.

Regulatory infringements are extremely common in low-income countries, especially with respect to retail pharmaceutical sales. There have been few practical suggestions on public policy responses other than stricter regulatory enforcement, which governments are often unable, or unwilling, to do. This paper explores the challenges of regulating retail drug sellers, and potential solutions, through a case study of malaria treatment in rural Tanzania where small drug shops are a common source of medicine. Infringement of health-related regulation was extremely common. Most stores lacked valid permits, and illegal stocking of prescription-only medicines and unpackaged tablets was the norm. Most stocked unregistered drugs, and no serving staff met the qualification requirements. Infringements are likely to have reflected infrequent regulatory inspections, a failure of regulatory authorities to implement sanctions, successful concealment of regulatory violations, and the tacit permission of local regulatory staff. Eliminating regulatory infringements is unlikely to be feasible, and could be undesirable if access to essential medicines is reduced. Alternatives include bringing official drug regulation closer into line with locally legitimate practices; greater use of positive incentives for providers; and consumer involvement. Such a change in approach has the potential to provide a firmer platform for public-private collaboration to improve shop-based treatment.