This analysis of data from the Global Burden of Disease Study examines the extent of rotavirus infection and associated deaths among children younger than 5 years worldwide and whether the rotavirus vaccine has reduced the diarrhea-associated mortality.

Severe rotavirus diarrhea in children <5 years of age is a major public health problem; however, limited regional and country specific data on rotavirus disease burden are available from sub-Saharan Africa. In June 2006, the World Health Organization Regional Office for Africa initiated rotavirus surveillance in selected African countries. With use of standardized methodology developed by the World Health Organization, children <5 years of age who were hospitalized with severe diarrhea were enrolled, and stool specimens were collected for detection of rotavirus strains with use of a commercial enzyme immunoassay. Rotavirus strains were further characterized for G and P types with use of a reverse-transcriptase polymerase chain reaction. From June 2006 through December 2008, rotavirus surveillance was established at 14 sites in 11 African countries. Of 5461 stool samples collected from children enrolled in 8 countries with 1 or 2 complete years of data, 2200 (40%) were positive for rotavirus. Ninety percent of all rotavirus hospitalizations occurred among children aged 3-12 months. Predominant types included G1P[8] (21%), G2P[4] (7%), and P [8] (29%); however, unusual types were also detected, including G8P[6] (5%), G8P[8] (1%), G12P[6] (1%), and G12P[6] (1%). A high percentage of mixed rotavirus infections was also detected. These preliminary results indicate that rotavirus is a major cause of severe diarrheal disease in African children.

Background Rotavirus vaccine use in national immunisation programmes has led to declines in hospital admissions for rotavirus gastroenteritis among children; however, the global impact of rotavirus vaccine introduction has not been described using primary data. We describe the impact of rotavirus vaccine introduction on admissions for acute rotavirus gastroenteritis in primarily low-income and middle-income countries, using 9 years of data from the WHOcoordinated Global Rotavirus Surveillance Network (GRSN).

Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50-95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help to understand the effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern, and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.

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Transfection technology for malaria parasites provides a valuable tool for analyzing gene function and correlating genotype with phenotype. Transfection models are even more valuable when appropriate animal models are available in addition to complete in vitro systems to be able to fully analyze parasite-host interactions. Here we describe the development of such a model by using the nonhuman primate malaria Plasmodium knowlesi. Blood-stage parasites were adapted to long-term in vitro culture. In vitro-adapted parasites could readapt to in vivo growth and regain wild-type characteristics after a single passage through an intact rhesus monkey. P. knowlesi parasites, either in vitro adapted or in vivo derived, were successfully transfected to generate circumsporozoite protein (CSP) knockout parasites by double-crossover mechanisms. In vitro-transfected and cloned CSP knockout parasites were derived in a time span of only 18 days. Microscopic evaluation of developing oocysts from mosquitoes that had fed on CSP knockout parasites confirmed the impairment of sporozoite formation observed in P. berghei CSP knockout parasites. The P. knowlesi model currently is the only malaria system that combines rapid and precise double-crossover genetic manipulation procedures with complete in vitro as well as in vivo possibilities. This allows for full analysis of P. knowlesi genotype-phenotype relationships and host-parasite interactions in a system closely related to humans.The development of transfection technology for blood-stage malaria parasites (16, 23-25, 28, 29) is of great importance in the postgenomic era. It provides a direct way in which to correlate genotype with phenotype, and this enhances the further understanding of parasite biology. This will facilitate rational design of new vaccines and drugs, which are urgently needed to fight the malaria epidemic that kills annually between 1.5 and 2.7 million people, mainly young children, in Sub-Saharan Africa alone (7).Four species of Plasmodium are natural to humans (9), and two of them, Plasmodium falciparum and Plasmodium vivax, are the most prevalent and important in terms of disease. Phylogenetically, P. falciparum, the more deadly form of the two, forms a separate clade with Plasmodium reichenowi, which causes chimpanzee malaria, and P. vivax clusters with simian malarias (11). The nonhuman primate malaria, caused by Plasmodium knowlesi, a natural parasite of Macaca fascicularis, has a relatively broad host range extending to humans, where it causes a mild disease (8). The parasite is closely related to P. vivax (11), and many genes identified in P. vivax have homologues in P. knowlesi. To date, transfection techniques developed for malaria parasite blood stages (26) include episomal transfection and targeted integration with linear constructs for the rodent parasite Plasmodium berghei (24, 25), episomal transfection and targeted integration with circular DNA for the human parasite P. falciparum (28,29), and episomal transfection for the nonhuman primate malaria pa...

SummaryWe calculated pathogen-specific attributable fractions of acute watery diarrhea in children from 16 countries using quantitative polymerase chain reaction testing for a broad range of enteropathogens. Rotavirus remained the leading etiology, despite a clear impact of rotavirus vaccine introduction.

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