SUMMARY Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease, resist infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic lifecycle of P. falciparum, a subset of erythrocyte microRNAs translocate into the parasite. Two microRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite mRNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical microRNA activity which may represent a unique host defense strategy against complex eukaryotic pathogens.

BackgroundTrends in the prevalence of acute myocardial infarction in sub-Saharan Africa have not been well described, despite growing recognition of the increasing burden of cardiovascular disease in low- and middle-income countries. The aim of this systematic review was to describe the prevalence of acute myocardial infarction in sub-Saharan Africa.MethodsWe searched PubMed, EMBASE, Global Health Archive, CINAHL, and Web of Science, and conducted reference and citation analyses. Inclusion criteria were: observational studies, studies that reported incidence or prevalence of acute myocardial infarction, studies conducted in sub-Saharan Africa, and studies that defined acute myocardial infarction by EKG changes or elevation of cardiac biomarkers. Studies conducted prior to 1992 were excluded. Two independent reviewers analyzed titles and abstracts, full-texts, and references and citations. These reviewers also performed quality assessment and data extraction. Quality assessment was conducted with a validated scale for observational studies.FindingsOf 2292 records retrieved, seven studies met all inclusion criteria. These studies included a total of 92,378 participants from highly heterogeneous study populations in five different countries. Methodological quality assessment demonstrated scores ranging from 3 to 7 points (on an 8-point scale). Prevalence of acute myocardial infarction ranged from 0.1 to 10.4% among the included studies.InterpretationThere is insufficient population-based data describing the prevalence of acute myocardial infarction in sub-Saharan Africa. Well-designed registries and surveillance studies that capture the broad and diverse population with acute myocardial infarction in sub-Saharan Africa using common diagnostic criteria are critical in order to guide prevention and treatment strategies.RegistrationRegistered in International Prospective Register of Systematic Reviews (PROSPERO) Database #CRD42012003161.

BackgroundAlthough fatal opioid poisonings tripled from 1999 to 2008, data describing nonfatal poisonings are rare. Public health authorities are in need of tools to track opioid poisonings in near real time.MethodsWe determined the utility of ICD-9-CM diagnosis codes for identifying clinically significant opioid poisonings in a state-wide emergency department (ED) surveillance system. We sampled visits from four hospitals from July 2009 to June 2012 with diagnosis codes of 965.00, 965.01, 965.02 and 965.09 (poisoning by opiates and related narcotics) and/or an external cause of injury code of E850.0-E850.2 (accidental poisoning by opiates and related narcotics), and developed a novel case definition to determine in which cases opioid poisoning prompted the ED visit. We calculated the percentage of visits coded for opioid poisoning that were clinically significant and compared it to the percentage of visits coded for poisoning by non-opioid agents in which there was actually poisoning by an opioid agent. We created a multivariate regression model to determine if other collected triage data can improve the positive predictive value of diagnosis codes alone for detecting clinically significant opioid poisoning.Results70.1 % of visits (Standard Error 2.4 %) coded for opioid poisoning were primarily prompted by opioid poisoning. The remainder of visits represented opioid exposure in the setting of other primary diseases. Among non-opioid poisoning codes reviewed, up to 36 % were reclassified as an opioid poisoning. In multivariate analysis, only naloxone use improved the positive predictive value of ICD-9-CM codes for identifying clinically significant opioid poisoning, but was associated with a high false negative rate.ConclusionsThis surveillance mechanism identifies many clinically significant opioid overdoses with a high positive predictive value. With further validation, it may help target control measures such as prescriber education and pharmacy monitoring.

Road traffic injuries (RTIs) continue to increase with the proliferation of motor vehicles, especially in low-income countries where safe road infrastructure is lacking Knowing where and why RTIs occur would allow for increased safety and prevention planning. In this study, police records of 300 motor vehicle collisions which occurred between February 2013 and January 2014 in Moshi, Tanzania, were reviewed. Analysis of variables including victim age, gender, type of collision, conditions, and use of safety equipment were analyzed. Geographic information system (GIS) analysis was performed to identify areas with the most collisions. Most injuries occurred at four intersections on two main corridor. Car crashes represented 48% of reports while motorcycle collisions were 35% of reports. Victims were predominantly male. The majority (64%) of RTI victims in cars used seatbelts while only 43% of motorcyclists wore helmets; none of those who used the helmet or seatbelt suffered a grievous injury. These data demonstrate that RTIs in Moshi occur in predictable high traffic locations. RTIs injure victims of all backgrounds and safety equipment is not universally utilized. More investment is needed in improved data collection methods, and a greater emphasis on intersection safety is needed to reduce these preventable injuries.

We quantified the time burden of alcohol-based handrub accompanying nonsterile-glove use among emergency physicians, through observation in controlled and clinical settings. We report gloving episodes per hour, gloving times with and without handrub, and handrub recommendations compliance. Handrub adds 46 seconds to each glove-use episode, and we provide national extrapolations.

Background Hepatitis B affects 257 million people worldwide. Mother-to-child hepatitis B virus (HBV) transmission is a preventable cause of substantial morbidity and mortality and poses greatest risk for developing chronic HBV infection. The World Health Organization recommends that all countries institute universal hepatitis B birth dose (HepB BD) vaccination during the first 24 h of life, followed by timely completion of routine immunization. The objective of this analysis was to assess the cost-effectiveness of adding HepB BD vaccination among sub-Saharan African refugee populations where the host country’s national immunization policy includes HepB BD. Methods We performed a cost-effectiveness analysis of three hepatitis B vaccination strategy scenarios for camp-based refugee populations in the African Region (AFR): routine immunization (RI), RI plus universal HepB BD, and RI plus HepB BD only for newborns of hepatitis B surface antigen-positive mothers identified through rapid diagnostic testing (RDT). We focused analyses on refugee populations living in countries that include HepB BD in national immunization schedules: Djibouti, Algeria and Mauritania. We used a decision tree model to estimate costs of vaccination and testing, and costs of life-years lost due to complications of chronic hepatitis B. Results Compared with RI alone, addition of HepB BD among displaced Somali refugees in Djibouti camps would save 9807 life-years/year, with an incremental cost-effectiveness ratio (ICER) of 0.15 USD (US dollars) per life-year saved. The RI plus HepB BD strategy among Western Saharan refugees in Algerian camps and Malian refugees in Mauritania camps would save 27,108 life-years/year with an ICER of 0.11 USD and 18,417 life-years/year with an ICER of 0.16 USD, respectively. The RI plus RDT-directed HepB BD was less cost-effective than RI plus delivery of universal HepB BD vaccination or RI alone. Conclusions Based on our model, addition of HepB BD vaccination is very cost-effective among three sub-Saharan refugee populations, using relative life-years saved. This analysis shows the potential benefit of implementing HepB BD vaccination among other camp-based refugee populations as more AFR countries introduce national HepB BD policies.

ABBV‐47D11 is a neutralizing monoclonal antibody that targets a mutationally conserved hydrophobic pocket distal to the ACE2 binding site of SARS‐CoV‐2. This first‐in‐human safety, pharmacokinetics, and antiviral pharmacodynamic assessment in patients with COVID‐19 provide an initial evaluation of this antibody that may allow further development. This multicenter, randomized, double‐blind, and placebo‐controlled single ascending dose study of ABBV‐47D11 (180, 600, or 2400 mg) as an intravenous infusion, was in hospitalized and non‐hospitalized (confined) adults with mild to moderate COVID‐19. Primary outcomes were grade 3 or higher study drug‐related adverse events and infusion‐related reactions. Secondary outcomes were pharmacokinetic parameters and concentration‐time profiles to Day 29, immunogenicity (anti‐drug antibodies), and antiviral activity (change in RT‐PCR viral load) from baseline to Days 15 and 29. ABBV‐47D11 single doses up to 2400 mg were safe and tolerated and no safety signals were identified. The pharmacokinetics of ABBV‐47D11 were linear and showed dose‐proportional increases in serum concentrations with ascending doses. The exploratory anti‐SARS‐CoV‐2 activity revealed a reduction of viral load at and above the 600 mg dose of ABBV‐47D11 regardless of patient demographics and baseline characteristics, however; because of the high inter‐individual variability and small sample size a statistical significance was not reached. There is potential for anti‐SARS‐CoV‐2 activity with ABBV‐47D11 doses of 600 mg or higher, which could be evaluated in future clinical trials designed and powered to assess viral load reductions and clinical benefit.

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