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Background: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized., Methods: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital., Results: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001)., Conclusions: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high-mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV)., Methods: We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies., Results: We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12-59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (n = 20) had a median of 2 (range, 1-5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions., Conclusions: RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high-mortality rate settings., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The Child Health and Mortality Prevention Surveillance (CHAMPS) network aims to generate reliable data on the causes of death among children aged <5 years using all available information, including minimally invasive tissue sampling (MITS). The sensitive nature of MITS inevitably evokes religious, cultural, and ethical questions influencing the feasibility and sustainability of CHAMPS., Methods: Due to limited behavioral studies related to child MITS, we developed an innovative qualitative methodology to determine the barriers, facilitators, and other factors that affect the implementation and sustainability of CHAMPS surveillance across 7 diverse locations in sub-Saharan Africa and South Asia. We employed a multimethod grounded theory approach and analytical structure based on culturally specific conceptual frameworks. The methodology guided data interpretation and collective analyses confirming how to define dimensions of CHAMPS feasibility within the cultural context of each site while reducing subjectivity and bias in the process of interpretation and reporting., Results: Findings showed that the approach to gain consent to conduct the MITS procedure involves religious factors associated with timing of burial, use of certain terminology, and methods of transporting the body. Community misperceptions and uncertainties resulted in rumor surveillance and consistency in information sharing. Religious pronouncements, recognition of health priorities, attention to pregnancy, and advancement of child health facilitated community acceptability., Conclusions: These findings helped formulate program priorities, guided site-specific adaptations in surveillance procedures, and verified inferences drawn from CHAMPS epidemiological and formative research data. Results informed appropriate community sensitization and engagement activities for introducing and sustaining mortality surveillance, including MITS., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Knowing risk factors for household transmission of Ebola virus is important to guide preventive measures during Ebola outbreaks., Methods: We enrolled all confirmed persons with Ebola who were the first case in a household, December 2014-April 2015, in Freetown, Sierra Leone, and their household contacts. Cases and contacts were interviewed, contacts followed prospectively through the 21-day incubation period, and secondary cases confirmed by laboratory testing., Results: We enrolled 150 index Ebola cases and 838 contacts; 83 (9.9%) contacts developed Ebola during 21-day follow-up. In multivariable analysis, risk factors for transmission included index case death in the household, Ebola symptoms but no reported fever, age <20 years, more days with wet symptoms; and providing care to the index case (P < .01 for each). Protective factors included avoiding the index case after illness onset and a piped household drinking water source (P < .01 for each)., Conclusions: To reduce Ebola transmission, communities should rapidly identify and follow-up all household contacts; isolate those with Ebola symptoms, including those without reported fever; and consider closer monitoring of contacts who provided care to cases. Households could consider efforts to minimize risk by designating one care provider for ill persons with all others avoiding the suspected case.

Background: The international impact, rapid widespread transmission, and reporting delays during the 2014 Ebola outbreak in West Africa highlighted the need for a global, centralized database to inform outbreak response. The World Health Organization and Emerging and Dangerous Pathogens Laboratory Network addressed this need by supporting the development of a global laboratory database., Methods: Specimens were collected in the affected countries from patients and dead bodies meeting the case definitions for Ebola virus disease. Test results were entered in nationally standardized spreadsheets and consolidated onto a central server., Results: From March 2014 through August 2016, 256343 specimens tested for Ebola virus disease were captured in the database. Thirty-one specimen types were collected, and a variety of diagnostic tests were performed. Regular analysis of data described the functionality of laboratory and response systems, positivity rates, and the geographic distribution of specimens., Conclusion: With data standardization and end user buy-in, the collection and analysis of large amounts of data with multiple stakeholders and collaborators across various user-access levels was made possible and contributed to outbreak response needs. The usefulness and value of a multifunctional global laboratory database is far reaching, with uses including virtual biobanking, disease forecasting, and adaption to other disease outbreaks., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Sierra Leone has the most cases of Ebola virus disease (EVD) ever reported. Trends in laboratory-confirmed EVD, symptom presentation, and risk factors have not been fully described., Methods: EVD cases occurring from 23 May 2014 to 31 January 2015 are presented by geography, demographics, and risk factors for all persons who had laboratory-confirmed EVD, which was identified by Ebola virus-specific reverse-transcription polymerase chain reaction-based testing., Results: During the study period, 8056 persons had laboratory-confirmed EVD. Their median age was 28 years; 51.7% were female. Common symptoms included fever (90.4%), fatigue (88.3%), loss of appetite (87.0%), headache (77.9%), joint pain (73.7%), vomiting (71.2%), and diarrhea (70.6%). Among persons with confirmed cases, 47.9% reported having had contact with someone with suspected EVD or any sick person, and 25.5% reported having attended a funeral, of whom 66.2% reported touching the body. The incidence of EVD was highest during 1-30 November 2014, at 7.5 per 100 000 population per week, and decreased to 2.1 per week during 1-31 January 2015. Between 23 May and 30 August 2014, two districts had the highest incidence of 3.8 and 7.0 per 100 000 population per week which decreased >97% by 1-31 January 2015. In comparison, the districts that include the capital city reported a 10-fold increase in incidence per week during the same time periods., Conclusions: Almost half of patients with EVD in Sierra Leone reported physical contact with a person ill with EVD or a dead body, highlighting prevention opportunities., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: In May 2012, the twice-yearly Maternal and Child Health Week (MCHW) integrated vitamin A supplementation (VAS) and supplementary measles vaccination to reach all children 6-59 months in Sierra Leone. Following the MCHW, a post event coverage survey was conducted to validate VAS coverage and assess adverse events following immunization., Methods: Using the WHO Expanded Program on Immunization sampling methodology, 30 clusters were randomly selected using population proportionate to size sampling. Fourteen caregivers of children 6-59 months were interviewed per cluster for precision of ±5%. Responses were collected via mobile phones using EpiSurveyor., Results: Overall VAS and measles coverage was 91.9% and 91.6%, respectively, with no significant differences by age group, sex, religion or occupation. Major reasons given for not receiving VAS and measles vaccination were not knowing about the MCHW or being out of the area. Significantly more mild adverse events (fever, pain at injection site) were reported via the post event coverage survey (29.1%) than MCHW (0.01%) (p<0.0001)., Conclusion: The MCHW reached >90% of children in Sierra Leone with equitable coverage. Increased reporting of mild adverse events during the survey may be attributed to delayed onset after measles vaccination and/or direct inquiry from enumerators. Even mild adverse events following immunization requires strengthened reporting during and after vaccination campaigns., (© The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This study describes phenotypic, genotypic and antibiotic susceptibility patterns of the strains isolated from the 2012 Sierra Leone cholera outbreak. Rectal swabs were collected from patients and cultured for Vibrio cholerae O1., Methods: The isolates were subjected to multiplex PCR, mismatch amplification mutation assay (MAMA) PCR, pulsed field gel electrophoresis (PFGE), and antibiotic sensitivity tests using disk diffusion and minimum inhibitory concentration (MIC) E-test following standard procedures., Results: Out of 17 rectal swabs tested, 15 yielded V. cholerae O1 biotype El Tor, serotype Ogawa. All the strains belonged to 'altered' variants as MAMA PCR result showed the presence of classical cholera toxin B. PFGE result revealed four pulse types. Using antibiotic disk diffusion, all the isolates were resistant to erythromycin, chloramphenicol, furazolidone, and trimethoprim/sulfamethoxazole (SXT) except SL1 which was sensitive to chloramphenicol and SXT. All the isolates were sensitive to nalidixic acid, tetracycline, doxycycline, azithromycin, and ciprofloxacin except SL2 which was resistant to nalidixic acid. However, variable sensitivity patterns were observed for kanamycin. The ranges of MIC were 0.125-0.50 mg/l, 0.003-0.023 mg/l and 0.38-0.75 mg/l for azithromycin, ciprofloxacin and tetracycline, respectively., Conclusions: This study demonstrates that altered variants of V. cholerae O1 of four clonal types were responsible for the 2012 outbreak of cholera in Sierra Leone., (© The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality., Methods: We conducted an audit of patient files of suspected LF cases admitted to a pediatric and obstetric referral hospital in rural Sierra Leone (April 2011 to February 2012)., Results: There were 84 suspected LF cases; 36 (43%) were laboratory-confirmed cases, of whom only 20 (56%) received ribavirin after a median duration of eight days (IQR 314 days) of hospital admission. Of 16 patients who did not receive ribavirin, 14 (87%) died before ribavirin treatment could be commenced. Starting ribavirin within six days of admission was associated with a case fatality of 29% (2/7), while starting ribavirin later than six days was associated with a case fatality of 50% (6/12). Among the 48 suspected LF cases without laboratory confirmation, there were 21 (44%) deaths., Conclusions: These findings highlight shortcomings in LF management, including diagnostic and treatment delays. More research and development efforts should be devoted to this 'neglected disease'.