The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

BackgroundMass anti-malarial administration has been proposed as a key component of the malaria elimination strategy in South East Asia. The success of this approach depends on the local malaria epidemiology, nature of the anti-malarial regimen and population coverage. Community engagement is used to promote population coverage but little research has systematically analysed its impact. This systematic review examines population coverage and community engagement in programmes of mass anti-malarial drug administration.MethodsThis review builds on a previous review that identified 3049 articles describing mass anti-malarial administrations published between 1913 and 2011. Further search and application of a set of criteria conducted in the current review resulted in 51 articles that were retained for analysis. These 51 papers described the population coverage and/or community engagement in mass anti-malarial administrations. Population coverage was quantitatively assessed and a thematic analysis was conducted on the community engagement activities.ResultsThe studies were conducted in 26 countries: in diverse healthcare and social contexts where various anti-malarial regimens under varied study designs were administered. Twenty-eight articles reported only population coverage; 12 described only community engagement activities; and 11 community engagement and population coverage. Average population coverage was 83% but methods of calculating coverage were frequently unclear or inconsistent. Community engagement activities included providing health education and incentives, using community structures (e.g. existing hierarchies or health infrastructure), mobilizing human resources, and collaborating with government at some level (e.g. ministries of health). Community engagement was often a process involving various activities throughout the duration of the intervention.ConclusionThe mean population coverage was over 80% but incomplete reporting of calculation methods limits conclusions and comparisons between studies. Various community engagement activities and approaches were described, but many articles contained limited or no details. Other factors relevant to population coverage, such as the social, cultural and study context were scarcely reported. Further research is needed to understand the factors that influence population coverage and adherence in mass anti-malarial administrations and the role community engagement activities and approaches play in satisfactory participation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1593-y) contains supplementary material, which is available to authorized users.

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Abstract.Mass drug administration (MDA) to interrupt malaria transmission requires the participation of entire communities. As part of a clinical trial in western Cambodia, four villages received MDA in 2015–2016. Before approaching study communities, a collaboration was established with the local health authorities, village leaders, and village malaria workers. Formative research guided the development of engagement strategies. In each village, a team of volunteers was formed to explain MDA to their neighbors and provide support during implementation. Public mobilization events featuring drama and music were used to introduce MDA. Villages comprised groups with different levels of understanding and interests; therefore, multiple tailored engagement strategies were required. The main challenges were explaining malaria transmission, managing perceptions of drug side effects, and reaching mobile populations. It was important that local leaders took a central role in community engagement. Coverage during each round of MDA averaged 84%, which met the target for the trial.

Abstract.With an unprecedented number of displaced persons worldwide, strategies for improving the health of migrating populations are critical. United States–bound refugees undergo a required overseas medical examination to identify inadmissible conditions (e.g., tuberculosis) 2–6 months before resettlement, but it is limited in scope and may miss important, preventable infectious, chronic, or nutritional causes of morbidity. We sought to evaluate the feasibility and health impact of diagnosis and management of such conditions before travel. We offered voluntary testing for intestinal parasites, anemia, and hepatitis B virus infection, to U.S.-bound refugees from three Thailand–Burma border camps. Treatment and preventive measures (e.g., anemia and parasite treatment, vaccination) were initiated before resettlement. United States refugee health partners received overseas results and provided post-arrival medical examination findings. During July 9, 2012 to November 29, 2013, 2,004 refugees aged 0.5–89 years enrolled. Among 463 participants screened for seven intestinal parasites overseas and after arrival, helminthic infections decreased from 67% to 12%. Among 118 with positive Strongyloides-specific antibody responses, the median fluorescent intensity decreased by an average of 81% after treatment. The prevalence of moderate-to-severe anemia (hemoglobin < 10 g/dL) was halved from 14% at baseline to 7% at departure (McNemar P = 0.001). All 191 (10%) hepatitis B–infected participants received counseling and evaluation; uninfected participants were offered vaccination. This evaluation demonstrates that targeted screening, treatment, and prevention services can be conducted during the migration process to improve the health of refugees before resettlement. With more than 250 million migrants globally, this model may offer insights into healthier migration strategies.

BackgroundCambodia has seen a marked reduction in the incidence of Plasmodium falciparum over the past decade without a corresponding decline in Plasmodium vivax incidence. It is unknown to what extent local transmission is sustained by a chain of clinical and sub-clinical infections or by continued re-introduction via migration. Using an ultrasensitive molecular technique, 20 villages in western Cambodia were surveyed to detect the low season prevalence of P. falciparum and P. vivax and local treatment records were reviewed.MethodsDuring March to May 2015 cross-sectional surveys were conducted in 20 villages in Battambang, western Cambodia. Demographic and epidemiological data and venous blood samples were collected from 50 randomly selected adult volunteers in each village. Blood was tested for Plasmodium infections by rapid diagnostic test (RDT), microscopy and high volume (0.5 ml packed red blood cell) quantitative polymerase chain reaction (uPCR). Positive samples were analysed by nested PCR to determine the Plasmodium species. Malaria case records were collected from the Provincial Health Department and village malaria workers to determine incidence and migration status.ResultsAmong the 1000 participants, 91 (9.1%) were positive for any Plasmodium infection by uPCR, seven (0.7%) by microscopy, and two (0.2%) by RDT. uPCR P. vivax prevalence was 6.6%, P. falciparum 0.7%, and undetermined Plasmodium species 1.8%. Being male (adjusted OR 2.0; 95% CI 1.2-3.4); being a young adult <30 years (aOR 2.1; 95% CI 1.3–3.4); recent forest travel (aOR 2.8; 95% CI 1.6–4.8); and, a history of malaria (aOR 5.2; 95% CI 2.5–10.7) were independent risk factors for parasitaemia. Of the clinical malaria cases diagnosed by village malaria workers, 43.9% (297/634) and 38.4% (201/523) were among migrants in 2013 and in 2014, respectively. Plasmodium vivax prevalence determined by uPCR significantly correlated with vivax malaria incidences in both 2014 and 2015 (p = 0.001 and 0.002, respectively), whereas no relationship was observed in falciparum malaria (p = 0.36 and p = 0.59, respectively).DiscussionThere was heterogeneity in the malaria parasite reservoir between villages, and Plasmodium prevalence correlated with subsequent malaria incidence. The association was attributable chiefly to P. vivax infections, which were nine-fold more prevalent than P. falciparum infections. In the absence of a radical cure with 8-aminoquinolines, P. vivax transmission will continue even as P. falciparum prevalence declines. Migration was associated with over a third of incident cases of clinical malaria. Trial registration clinicaltrials.gov (NCT01872702). Registered 4 June 2013Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1703-5) contains supplementary material, which is available to authorized users.

. Multidrug-resistant Plasmodium falciparum malaria on the Cambodia–Thailand border is associated with working in forested areas. Beyond broad recognition of “forest-going” as a risk factor for malaria, little is known about different forest-going populations in this region. In Oddar Meanchey Province in northwestern Cambodia, qualitative ethnographic research was conducted to gain an in-depth understanding of how different populations, mobility and livelihood patterns, and activities within the forest intersect with potentiate malaria risk and impact on the effectiveness of malaria control and elimination strategies. We found that most forest-going in this area is associated with obtaining precious woods, particularly Siamese rosewood. In the past, at-risk populations included large groups of temporary migrants. As timber supplies have declined, so have these large migrant groups. However, groups of local residents continue to go to the forest and are staying for longer. Most forest-goers had experienced multiple episodes of malaria and were well informed about malaria risk. However, economic realities mean that local residents continue to pursue forest-based livelihoods. Severe constraints of available vector control methods mean that forest-goers have limited capacity to prevent vector exposure. As forest-goers access the forest using many different entry and exit points, border screening and treatment interventions will not be feasible. Once in the forest, groups often converge in the same areas; therefore, interventions targeting the mosquito population may have a potential role. Ultimately, a multisectoral approach as well as innovative and flexible malaria control strategies will be required if malaria elimination efforts are to be successful.