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WHO recommends routine use of rotavirus vaccines in all countries, particularly in those with high mortality attributable to diarrhoeal diseases. To establish the burden of life-threatening rotavirus disease before the introduction of a rotavirus vaccine, we aimed to update the estimated number of deaths worldwide in children younger than 5 years due to diarrhoea attributable to rotavirus infection. We used PubMed to identify studies of at least 100 children younger than 5 years who had been admitted to hospital with diarrhoea. Additionally, we required the studies to have a data collection midpoint of the year 2000 or later, to be done in full-year increments, and to assesses diarrhoea attributable to rotavirus with EIAs or polyacrylamide gel electrophoresis. We also included data from countries that participated in the WHO-coordinated Global Rotavirus Surveillance Network (consisting of participating member states during 2009) and that met study criteria. For countries that have introduced a rotavirus vaccine into their national immunisation programmes, we excluded data subsequent to the introduction. We classified studies into one of five groups on the basis of region and the level of child mortality in the country in which the study was done. For each group, to obtain estimates of rotavirus-associated mortality, we multiplied the random-effect mean rotavirus detection rate by the 2008 diarrhoea-related mortality figures for countries in that group. We derived the worldwide mortality estimate by summing our regional estimates. Worldwide in 2008, diarrhoea attributable to rotavirus infection resulted in 453 000 deaths (95% CI 420 000–494 000) in children younger than 5 years—37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than 5 years. Five countries accounted for more than half of all deaths attributable to rotavirus infection: Democratic Republic of the Congo, Ethiopia, India, Nigeria, and Pakistan; India alone accounted for 22% of deaths (98 621 deaths). Introduction of effective and available rotavirus vaccines could substantially affect worldwide deaths attributable to diarrhoea. Our new estimates can be used to advocate for rotavirus vaccine introduction and to monitor the effect of vaccination on mortality once introduced. None.

► Prevalence data on ∼110,000 rotavirus strains identified from 100 countries worldwide during a 12-year period preceding introduction of rotavirus vaccines were collected and presented in this systematic review ► The paper summarizes (i) baseline strain prevalence data for the pre-vaccine era, (ii) analyzes spatiotemporal trends in distribution of circulating strains, and (iii) provides a weighted model to describe a more reliable estimate on the medical importance of individual rotavirus strains. Recently, two rotavirus vaccines have been recommended for routine immunization of infants worldwide. These vaccines proved efficacious during clinical trials and field use in both developing and developed countries, and appear to provide good protection against a range of rotavirus genotypes, including some that are not included in the vaccines. However, since conclusive data that the vaccines will protect against a wide variety of rotavirus strains are still lacking and since vaccines may exert some selection pressure, a detailed picture of global strain prevalence from the pre-rotavirus vaccine era is important to evaluate any potential changes in circulating strains observed after widespread introduction of rotavirus vaccines. Thus, we systematically reviewed rotavirus genotyping studies spanning a 12-year period from 1996 to 2007. In total, ∼110,000 strains were genotyped from 100 reporting countries. Five genotypes (G1–G4, and G9) accounted for 88% of all strains, although extensive geographic and temporal differences were observed. For example, the prevalence of G1 strains declined from 2000 onward, while G3 strains re-emerged, and G9 and G12 strains emerged during the same period. When crude strain prevalence data were weighted by region based on the region's contribution to global rotavirus mortality, the importance of genotypes G1 and G9 strains that were more prevalent in regions with low mortality was reduced and conversely the importance of G8 strains that were more prevalent in African settings with greater contribution to global rotavirus mortality was increased. This study provides the most comprehensive, up-to-date information on rotavirus strain surveillance in the pre-rotavirus vaccine era and will provide useful background to examine the impact of rotavirus vaccine introduction on future strain prevalence.

We identified differences in the peripheral cellular immune response between mild and severe influenza. Our findings suggest that individuals with severe influenza may experience immune activation that, despite a slow start, is prolonged, compared with those with mild influenza. Abstract Background The immunologic factors underlying severe influenza are poorly understood. To address this, we compared the immune responses of influenza-confirmed hospitalized individuals with severe acute respiratory illness (SARI) to those of nonhospitalized individuals with influenza-like illness (ILI). Methods Peripheral blood lymphocytes were collected from 27 patients with ILI and 27 with SARI, at time of enrollment and then 2 weeks later. Innate and adaptive cellular immune responses were assessed by flow cytometry, and serum cytokine levels were assessed by a bead-based assay. Results During the acute phase, SARI was associated with significantly reduced numbers of circulating myeloid dendritic cells, CD192+ monocytes, and influenza virus–specific CD8+ and CD4+ T cells as compared to ILI. By the convalescent phase, however, most SARI cases displayed continued immune activation characterized by increased numbers of CD16+ monocytes and proliferating, and influenza virus–specific, CD8+ T cells as compared to ILI cases. SARI was also associated with reduced amounts of cytokines that regulate T-cell responses (ie, interleukin 4, interleukin 13, interleukin 12, interleukin 10, and tumor necrosis factor β) and hematopoiesis (interleukin 3 and granulocyte-macrophage colony-stimulating factor) but increased amounts of a proinflammatory cytokine (tumor necrosis factor α), chemotactic cytokines (MDC, MCP-1, GRO, and fractalkine), and growth-promoting cytokines (PDGFBB/AA, VEGF, and EGF) as compared to ILI. Conclusions Severe influenza cases showed a delay in the peripheral immune activation that likely led prolonged inflammation, compared with mild influenza cases.

Background: Hand hygiene is an important strategy for reducing healthcare-associated infections. While efforts to improve nursing home (NH) staff hand hygiene have been prioritized, there are few if any policies in-place to improve resident hand hygiene. Further, CMS guidance requires that residents be bathed “twice a week.” The objective of this study was to characterize resident hand hygiene knowledge and habits as well as bathing practices to identify barriers in a setting where new intervention strategies could be aimed. Methods: The survey was administered at 20 NHs across the United States between December 2023 and July 2024. Verbal consent was obtained from residents before survey administration. Survey questions explored residents’ hand hygiene knowledge and differences in hand hygiene habits and bathing practices since entering the NH from their last place of residence. Three knowledge-based questions assessed residents’ understanding of the recommended length of time to wash hands and use hand sanitizer in addition to when hand washing should be utilized instead of hand sanitizer. Frequency of hand washing, either through soap and water or hand sanitizer, instances of when and how residents wash and dry their hands, and whether resident’s faced challenges were assessed. Results:Of the 495 residents who completed the survey, only 142 (29%) residents answered all three knowledge-based questions correctly. Residents who answered two or three questions correctly reported washing their hands more frequently at their previous residence compared to residents who answered zero or one correct (Figure 1). Frequency of hand hygiene was lower at the NH compared to their previous residence across a variety of indications (Figure 2). More residents faced challenges with washing their hands at the NH compared to their previous residence (30% vs. 7%, P<.001). The most common challenges included: mobility limitations, medical issues, need for assistance, bathroom accessibility and inadequate bathroom supplies/equipment. About half the residents (53%) reported never being reminded to wash their hands; 60% reported that they would use hand sanitizer if it was easily accessible. 51% of residents reported bathing with soap and water less at the NH compared to their previous residence with reported causes being needing help and not receiving it, nursing home policy, medical issues, and mobility limitations. Conclusions: Survey results indicate opportunities for interventions aimed at reducing the barriers to hand hygiene practice and improving bathing practices in NHs. Policy changes and hand hygiene educational opportunities addressing these barriers could serve as potential strategies.

Background. Data on causes of death due to respiratory illness in Africa are limited. Methods. From January to April 2013,28 African countries were invited to participate in a review of severe acute respiratory illness (SARI)-associated deaths identified from influenza surveillance during 2009-2012. Results. Twenty-three countries (82%) responded, 11 (48%) collect mortality data, and 8 provided data. Data were collected from 37 714 SARI cases, and 3091 (8.2%; range by country, 5.1%-25.9%) tested positive for influenza virus. There were 1073 deaths (2.8%; range by country, 0.1%-5.3%) reported, among which influenza virus was detected in 57 (5.3%). Case-fatality proportion (CFP) was higher among countries with systematic death reporting than among those with sporadic reporting. The influenza-associated CFP was 1.8% (57 of 3091), compared with 2.9% (1016 of 34 623) for influenza virus-negative cases (P < .001). Among 834 deaths (77.7%) tested for other respiratory pathogens, rhinovirus (107 [12.8%]), adenovirus (64 [6.0%]), respiratory syncytial virus (60 [5.6%]), and Streptococcus pneumoniae (57 [5.3%]) were most commonly identified. Among 1073 deaths, 402 (37.5%) involved people aged 0-4 years, 462 (43.1%) involved people aged 5-49 years, and 209 (19.5%) involved people aged ≥50 years. Conclusions. Few African countries systematically collect data on outcomes of people hospitalized with respiratory illness. Stronger surveillance for deaths due to respiratory illness may identify risk groups for targeted vaccine use and other prevention strategies.

Background We estimated the cost-per-episode and the annual economic burden associated with influenza in Kenya. Methods From July 2013–August 2014, we recruited patients with severe acute respiratory illness (SARI) or influenza-like illness (ILI) associated with laboratory-confirmed influenza from 5 health facilities. A structured questionnaire was used to collect direct costs (medications, laboratory investigations, hospital bed fees, hospital management costs, transportation) and indirect costs (productivity losses) associated with an episode of influenza. We used published incidence of laboratory-confirmed influenza associated with SARI and ILI, and the national population census data from 2014, to estimate the annual national number of influenza-associated hospitalizations and outpatient visits and calculated the annual economic burden by multiplying cases by the mean cost. Results We enrolled 275 patients (105 inpatients and 170 outpatients). The mean cost-per-episode of influenza was US$117.86 (standard deviation [SD], 88.04) among inpatients; US$114.25 (SD, 90.03) for children < 5 years, and US$137.45 (SD, 76.24) for persons aged ≥5 years. Among outpatients, the mean cost-per-episode of influenza was US$19.82 (SD, 27.29); US$21.49 (SD, 31.42) for children < 5 years, and US$16.79 (SD, 17.30) for persons aged ≥5 years. National annual influenza-associated cost estimates ranged from US$2.96–5.37 million for inpatients and US$5.96–26.35 million for outpatients. Conclusions Our findings highlight influenza as causing substantial economic burden in Kenya. Further studies may be warranted to assess the potential benefit of targeted influenza vaccination strategies.,

The South African Department of Health (DOH) publishes annual guidelines identifying priority groups, including immunosuppressed individuals and healthcare workers (HCW), for influenza vaccination and treatment. How these guidelines have impacted HCW and their patients, particularly those infected with HIV, remains unknown. We aimed to describe the knowledge, attitudes and practices regarding influenza and the vaccine among South African HCW. Surveys were distributed by two local non-governmental organizations in public health clinics and hospitals in 21 districts/municipalities (5 of 9 provinces). There were 1164 respondents; median age 41 years; 978/1126 (87%) female; 801/1122 (71%) nurses. One-third (34%) of HCW reported getting influenza vaccine 2013/2014 and most (94%) recommended influenza vaccine to patients infected with HIV. Ability to get vaccine free of charge (aOR 1.69; 95% CI 1.21-2.37) and having received influenza government training (aOR 1.50; 95% CI 1.04-2.15) were significantly associated with self-reported vaccination in 2013/2014. Self-reported 2013/2014 vaccination (aOR 3.76; 95% CI 1.28-11.03) and availability of influenza vaccine during the healthcare visit (aOR 2.56; 95% CI 1.18-5.57) were significantly associated with recommending influenza vaccine to patients infected with HIV/AIDS. Only one-third of participants were vaccinated in 2013-2014 but those who were vaccinated were more likely to recommend vaccination to their patients. Free and close access to influenza vaccine were associated with a higher likelihood of getting vaccinated in 2013/2014. HCW who reported getting the influenza vaccine themselves, had vaccine to offer during the patient consult and were familiar with DOH guidelines/trainings were more likely to recommend vaccine to HIV-infected patients.

Background Over the last decade, capacity for influenza surveillance and research in West Africa has strengthened. Data from these surveillance systems showed influenza A(H1N1)pdm09 circulated in West Africa later than in other regions of the continent. Methods We contacted 11 West African countries to collect information about their influenza surveillance systems (number of sites, type of surveillance, sampling strategy, populations sampled, case definitions used, number of specimens collected and number of specimens positive for influenza viruses) for the time period January 2010 through December 2012. Results Of the 11 countries contacted, 8 responded: Burkina Faso, Cote d’Ivoire, Mali, Mauritania, Niger, Nigeria, Sierra Leone and Togo. Countries used standard World Health Organization (WHO) case definitions for influenza-like illness (ILI) and severe acute respiratory illness (SARI) or slight variations thereof. There were 70 surveillance sites: 26 SARI and 44 ILI. Seven countries conducted SARI surveillance and collected 3114 specimens of which 209 (7%) were positive for influenza viruses. Among influenza-positive SARI patients, 132 (63%) were influenza A [68 influenza A(H1N1)pdm09, 64 influenza A(H3N2)] and 77 (37%) were influenza B. All eight countries conducted ILI surveillance and collected 20,375 specimens, of which 2278 (11%) were positive for influenza viruses. Among influenza-positive ILI patients, 1431 (63%) were influenza A [820 influenza A(H1N1)pdm09, 611 influenza A(H3N2)] and 847 (37%) were influenza B. A majority of SARI and ILI case-patients who tested positive for influenza (72% SARI and 59% ILI) were children aged 0–4 years, as were a majority of those enrolled in surveillance. The seasonality of influenza and the predominant influenza type or subtype varied by country and year. Conclusions Influenza A(H1N1)pdm09 continued to circulate in West Africa along with influenza A(H3N2) and influenza B during 2010–2012. Although ILI surveillance systems produced a robust number of samples during the study period, more could be done to strengthen surveillance among hospitalized SARI case-patients. Surveillance systems captured young children but lacked data on adults and the elderly. More data on risk groups for severe influenza in West Africa are needed to help shape influenza prevention and clinical management policies and guidelines.

Background: Nursing home (NH) residents are at high risk of COVID-19 from exposure to infected staff and other residents. Understanding SARS-CoV-2 viral RNA kinetics in residents and staff can guide testing, isolation, and return to work recommendations. We sought to determine the duration of antigen test and polymerase chain reaction (PCR) positivity in a cohort of NH residents and staff. Methods: We prospectively collected data on SARS-CoV-2 viral kinetics from April 2023 through November 2023. Staff and residents could enroll prospectively or upon a positive test (identified through routine clinical testing, screening, or outbreak response testing). Participating facilities performed routine clinical testing; asymptomatic testing of contacts was performed within 48 hours if an outbreak or known exposure occurred and upon (re-) admission. Enrolled participants who tested positive for SARS-CoV-2 were re-tested daily for 14 days with both nasal antigen and nasal PCR tests. All PCR tests were run by a central lab with the same assay. We conducted a Kaplan-Meier survival analysis on time to first negative test restricted to participants who initially tested positive (day zero) and had at least one test ≥10 days after initially testing positive with the same test type; a participant could contribute to both antigen and PCR survival curves. We compared survival curves for staff and residents using the log-rank test. Results: Twenty-four nursing homes in eight states participated; 587 participants (275 residents, 312 staff) enrolled in the evaluation, participants were only tested through routine clinical or outbreak response testing. Seventy-two participants tested positive for antigen; of these, 63 tested PCR-positive. Residents were antigen- and PCR-positive longer than staff (Figure 1), but this finding is only statistically significant (p=0.006) for duration of PCR positivity. Five days after the first positive test, 56% of 50 residents and 59% of 22 staff remained antigen-positive; 91% of 44 residents and 79% of 19 staff were PCR-positive. Ten days after the first positive test, 22% of 50 residents and 5% of 22 staff remained antigen-positive; 61% of 44 residents and 21% of 19 staff remained PCR-positive. Conclusions: Most NH residents and staff with SARS-CoV-2 remained antigen- or PCR-positive 5 days after the initial positive test; however, differences between staff and resident test positivity were noted at 10 days. These data can inform recommendations for testing, duration of NH resident isolation, and return to work guidance for staff. Additional viral culture data may strengthen these conclusions. Disclosure: Stefan Gravenstein: Received consulting and speaker fees from most vaccine manufacturers (Sanofi, Seqirus, Moderna, Merck, Janssen, Pfizer, Novavax, GSK, and have or expect to receive grant funding from several (Sanofi, Seqirus, Moderna, Pfizer, GSK). Lona Mody: NIH, VA, CDC, Kahn Foundation; Honoraria: UpToDate; Contracted Research: Nano-Vibronix

Influenza-associated disease burden among children in tropical sub-Saharan Africa is not well established, particularly outside of the 2009 pandemic period. We estimated the burden of influenza in children aged 0-4 years through population-based surveillance for influenza-like illness (ILI) and acute lower respiratory tract illness (ALRI). Household members meeting ILI or ALRI case definitions were referred to health facilities for evaluation and collection of nasopharyngeal and oropharyngeal swabs for influenza testing by real-time reverse transcription polymerase chain reaction. Estimates were adjusted for health-seeking behavior and those with ILI and ALRI who were not tested. During 2008-2012, there were 9,652 person-years of surveillance among children aged 0-4 years. The average adjusted rate of influenza-associated hospitalization was 4.3 (95% CI 3.0-6.0) per 1,000 person-years in children aged 0-4 years. Hospitalization rates were highest in the 0-5 month and 6-23 month age groups, at 7.6 (95% CI 3.2-18.2) and 8.4 (95% CI 5.4-13.0) per 1,000 person-years, respectively. The average adjusted rate of influenza-associated medically attended (inpatient or outpatient) ALRI in children aged 0-4 years was 17.4 (95% CI 14.2-19.7) per 1,000 person-years. Few children who had severe laboratory-confirmed influenza were clinically diagnosed with influenza by the treating clinician in the inpatient (0/33, 0%) or outpatient (1/109, 0.9%) settings. Influenza-associated hospitalization rates from 2008-2012 were 5-10 times higher than contemporaneous U.S. estimates. Many children with danger signs were not hospitalized; thus, influenza-associated severe disease rates in Kenyan children are likely higher than hospital-based estimates suggest.