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Background: Non-typhoidal Salmonella (NTS) is a common cause of gastroenteritis in young children, with limited data on NTS serovars and antimicrobial resistance in Africa. Methods: We determined the prevalence of Salmonella spp. and frequency of antimicrobial resistance among serovars identified in stools of 0–59 month-old children with moderate-to-severe diarrhea (MSD) and controls enrolled in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in The Gambia, Mali, and Kenya in 2015–2018, and compared with data from the Global Enteric Multicenter Study (GEMS; 2007–2010) and the GEMS-1A study (2011). Salmonella spp. was detected by quantitative real-time PCR (qPCR) and culture-based methods. Identification of serovars was determined by microbiological methods. Results: By qPCR, the prevalence of Salmonella spp. among MSD cases was 4.0%, 1.6%, and 1.9% and among controls was 4.6%, 2.4%, and 1.6% in The Gambia, Mali, and Kenya, respectively, during VIDA. We observed year-to-year variation in serovar distribution and variation between sites. In Kenya, Salmonella enterica serovar Typhimurium decreased (78.1% to 23.1%; P <.001) among cases and controls from 2007 to 2018, whereas serogroup O:8 increased (8.7% to 38.5%; P =.04). In The Gambia, serogroup O:7 decreased from 2007 to 2018 (36.3% to 0%; P =.001) but S. enterica serovar Enteritidis increased during VIDA (2015 to 2018; 5.9% to 50%; P =.002). Only 4 Salmonella spp. were isolated in Mali during all 3 studies. Multidrug resistance was 33.9% in Kenya and 0.8% in The Gambia across all 3 studies. Ceftriaxone resistance was only observed in Kenya (2.3%) ; NTS isolates were susceptible to ciprofloxacin at all sites. Conclusions: Understanding variability in serovar distribution will be important for the future deployment of vaccines against salmonellosis in Africa. [ABSTRACT FROM AUTHOR]

Background: Pediatric exposures to unsafe sources of water, unsafely managed sanitation, and animals are prevalent in low- and middle-income countries. In the Vaccine Impact on Diarrhea in Africa case-control study, we examined associations between these risk factors and moderate-to-severe diarrhea (MSD) in children <5 years old in The Gambia, Kenya, and Mali. Methods: We enrolled children <5 years old seeking care for MSD at health centers; age-, sex-, and community-matched controls were enrolled at home. Conditional logistic regression models, adjusted for a priori confounders, were used to evaluate associations between MSD and survey-based assessments of water, sanitation, and animals living in the compound. Results: From 2015 to 2018, 4840 cases and 6213 controls were enrolled. In pan-site analyses, children with drinking water sources below "safely managed" (onsite, continuously accessible sources of good water quality) had 1.5–2.0-fold higher odds of MSD (95% confidence intervals [CIs] ranging from 1.0 to 2.5), driven by rural site results (The Gambia and Kenya). In the urban site (Mali), children whose drinking water source was less available (several hours/day vs all the time) had higher odds of MSD (matched odds ratio [mOR]: 1.4, 95% CI: 1.1, 1.7). Associations between MSD and sanitation were site-specific. Goats were associated with slightly increased odds of MSD in pan-site analyses, whereas associations with cows and fowl varied by site. Conclusions: Poorer types and availability of drinking water sources were consistently associated with MSD, whereas the impacts of sanitation and household animals were context-specific. The association between MSD and access to safely managed drinking water sources post-rotavirus introduction calls for transformational changes in drinking water services to prevent acute child morbidity from MSD. We assessed water, sanitation, and animal-associated risk factors for moderate-to-severe diarrhea in children in a matched case-control study. Less availability (hours/day) and access to quality drinking water were consistent risk factors; poor sanitation and animal ownership were context-specific risk factors. [ABSTRACT FROM AUTHOR]

Background: We evaluated the burden of Shigella spp from children aged 0–59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa (VIDA) study from 2015 to 2018. Methods: Shigella spp were identified using coprocultures and serotyping in addition to quantitative polymerase chain reaction (qPCR). Episode-specific attributable fractions (AFe) for Shigella were calculated using Shigella DNA quantity; cases with AFe ≥0.5 were considered to have shigellosis. Results: The prevalence of Shigella was determined to be 359 of 4840 (7.4%) cases and 83 of 6213 (1.3%) controls by culture, and 1641 of 4836 (33.9%) cases and 1084 of 4846 (22.4%) controls by qPCR (cycle threshold <35); shigellosis was higher in The Gambia (30.8%) than in Mali (9.3%) and Kenya (18.7%). Bloody diarrhea attributed to Shigella was more common in 24- to 59-month-old children (50.1%) than 0- to 11-month-old infants (39.5%). The Shigella flexneri serogroup predominated among cases (67.6% of isolates), followed by Shigella sonnei (18.2%), Shigella boydii (11.8%), and Shigella dysenteriae (2.3%). The most frequent S. flexneri serotypes were 2a (40.6%), 1b (18.8%), 6 (17.5%), 3a (9.0%), and 4a (5.1%). Drug-specific resistance among 353 (98.3%) Shigella cases with AMR data was as follows: trimethoprim-sulfamethoxazole (94.9%), ampicillin (48.4%), nalidixic acid (1.7%), ceftriaxone (0.3%), azithromycin (0.3%), and ciprofloxacin (0.0%). Conclusions: A high prevalence of shigellosis continues in sub-Saharan Africa. Strains are highly resistant to commonly used antibiotics while remaining susceptible to ciprofloxacin, ceftriaxone, and azithromycin. We evaluated the burden of Shigella spp from children 0–59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa study from 2015 to 2018. [ABSTRACT FROM AUTHOR]

Background: Giardia has been associated with reduced risk of diarrhea in children in low-resource settings, but the mechanism underlying this association is unknown. To assess whether Giardia may shape colonization or infection with other enteric pathogens and impact associations with diarrhea, we examined Giardia and enteric pathogen codetection among children <5 years old in Kenya, The Gambia, and Mali as part of the Vaccine Impact on Diarrhea in Africa study. Methods: We tested for Giardia and other enteric pathogens using enzyme-linked immunosorbent assays and real-time polymerase chain reaction (PCR) on stool, respectively. We evaluated associations between Giardia and enteric pathogen detection using multivariable logistic regression models separately for children with moderate-to-severe diarrhea (MSD, cases) and free of diarrhea (controls). Results: Among 11 039 enrolled children, Giardia detection was more common among controls (35%) than cases (28%, P <.001). Campylobacter coli/jejuni detection was associated with Giardia in controls in The Gambia (adjusted odds ratio [aOR] [95% confidence interval {CI}]: 1.51 [1.22‒1.86]) and cases across all sites (1.16 [1.00‒1.33]). Among controls, the odds of astrovirus (1.43 [1.05‒1.93]) and Cryptosporidium spp. (1.24 [1.06‒1.46]) detection were higher among children with Giardia. Among cases, the odds of rotavirus detection were lower in children with Giardia in Mali (.45 [.30‒.66]) and Kenya (.31 [.17‒.56]). Conclusions: Giardia was prevalent in children <5 years old and was associated with detection of other enteric pathogens, with differing associations in cases versus controls and by site. Giardia may affect colonization or infection by certain enteric pathogens associated with MSD, suggesting an indirect mechanism of clinical impact. Giardia was prevalent in children <5 years old and was associated with detection of other enteric pathogens, including rotavirus. Giardia may affect colonization or infection by certain enteric pathogens associated with MSD, suggesting an indirect mechanism of clinical impact. [ABSTRACT FROM AUTHOR]

Background: The magnitude of pediatric enteric pathogen exposures in low-income settings necessitates substantive water and sanitation interventions, including animal feces management. We assessed associations between pediatric enteric pathogen detection and survey-based water, sanitation, and animal characteristics within the Vaccine Impact on Diarrhea in Africa case-control study. Methods: In The Gambia, Kenya, and Mali, we assessed enteric pathogens in stool of children aged <5 years with moderate-to-severe diarrhea and their matched controls (diarrhea-free in prior 7 days) via the TaqMan Array Card and surveyed caregivers about household drinking water and sanitation conditions and animals living in the compound. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using modified Poisson regression models, stratified for cases and controls and adjusted for age, sex, site, and demographics. Results: Bacterial (cases, 93%; controls, 72%), viral (63%, 56%), and protozoal (50%, 38%) pathogens were commonly detected (cycle threshold <35) in the 4840 cases and 6213 controls. In cases, unimproved sanitation (RR, 1.56; 95% CI, 1.12–2.17), as well as cows (RR, 1.61; 95% CI, 1.16–2.24) and sheep (RR, 1.48; 95% CI, 1.11–1.96) living in the compound, were associated with Shiga toxin–producing Escherichia coli. In controls, fowl (RR, 1.30; 95% CI, 1.15–1.47) were associated with Campylobacter spp. In controls, surface water sources were associated with Cryptosporidium spp., Shigella spp., heat-stable toxin-producing enterotoxigenic E. coli, and Giardia spp. Conclusions: Findings underscore the importance of enteric pathogen exposure risks from animals alongside more broadly recognized water and sanitation risk factors in children. We assessed survey-based water, sanitation, and animal factors associated with enteric pathogens in cases of moderate to severe diarrhea and controls. Animals, cows and sheep (cases) and fowl (controls), were associated with bacterial carriage; surface water was associated with bacteria and protozoa in controls. [ABSTRACT FROM AUTHOR]

Background: Stunting affects >20% of children <5 years old worldwide and disproportionately impacts underserved communities. The Vaccine Impact on Diarrhea in Africa (VIDA) Study examined the association between an episode of moderate-to-severe diarrhea (MSD) and the risk of subsequent stunting in children <5 years living in 3 sub-Saharan African countries. Methods: In this prospective, matched, case-control study among children <5 years, data were collected over 36 months from 2 groups. "Children with MSD" visited a health center within 7 days of illness onset experiencing ≥3 loose stools/day plus sunken eyes, poor skin turgor, dysentery, intravenous rehydration, or hospitalization. "Children without MSD" were enrolled from the community within 14 days of the index MSD child; they were diarrhea-free during the previous 7 days and were matched to the index case by age, sex, and residence. Using generalized linear mixed-effects models, we estimated the effect of an MSD episode on odds of being stunted, defined as height-for-age z-scores <−2, at a follow-up visit 2–3 months post-enrollment. Results: The proportion of stunting at enrollment was similar when 4603 children with MSD and 5976 children without MSD were compared (21.8% vs 21.3%; P =.504). Among children not stunted at enrollment, those with MSD had 30% higher odds of being stunted at follow-up than children without MSD after controlling for age, sex, study site, and socioeconomic status (adjusted OR: 1.30; 95% CI: 1.05–1.62: P =.018). Conclusions: Children <5 years in sub-Saharan Africa without stunting experienced an increased likelihood of stunting during 2–3 months following an episode of MSD. Strategies for control of early childhood diarrhea should be integrated into programs intended to reduce childhood stunting. Stunting disproportionately impacts young children living in low-income countries. In the VIDA study among children <5 years old living in sub-Saharan Africa, an episode of moderate-to-severe diarrhea conferred a 30% higher odds of becoming stunted during 60 days of follow-up. [ABSTRACT FROM AUTHOR]

Background: The impact of human immunodeficiency virus (HIV) on pregnancy outcomes for women on antiretroviral therapy (ART) in sub-Saharan Africa remains unclear.Methods: Pregnant women in Kenya were enrolled in the second trimester and followed up to delivery. We estimated effects of treated HIV with 3 pregnancy outcomes: loss, premature birth, and low birth weight and factors associated with HIV-positive status.Results: Of 2113 participants, 311 (15%) were HIV infected and on ART. Ninety-one of 1762 (5%) experienced a pregnancy loss, 169/1725 (10%) a premature birth (<37 weeks), and 74/1317 (6%) had a low-birth-weight newborn (<2500 g). There was no evidence of associations between treated HIV infection and pregnancy loss (adjusted relative risk [aRR], 1.19; 95% confidence interval [CI], .65-2.16; P = .57), prematurity (aRR, 1.09; 95% CI, .70-1.70; P = .69), and low birth weight (aRR, 1.36; 95% CI, .77-2.40; P = .27). Factors associated with an HIV-positive status included older age, food insecurity, lower education level, higher parity, lower gestation at first antenatal clinic, anemia, and syphilis. Women who were overweight or underweight were less likely to be HIV infected compared to those with normal weight.Conclusions: Currently treated HIV was not significantly associated with adverse pregnancy outcomes. HIV-infected women, however, had a higher prevalence of other factors associated with adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is an important cause of respiratory illness worldwide; however, burden data on mother-infant pairs remain sparse in sub-Saharan Africa, where human immunodeficiency virus (HIV) is prevalent. We evaluated the impact of maternal HIV infection on the burden of RSV among mothers and their infants in western Kenya.Methods: We enrolled pregnant women (≤20 weeks' gestation) and followed them and their newborns weekly for up to 3-6 months postpartum, to document cases of acute respiratory illness (ARI). Nasal/oropharyngeal swabs were collected and tested for RSV using polymerase chain reaction. Analyses were stratified by maternal HIV status and incidence was computed per 1000 person-months.Results: Compared to RSV-negative ARI cases, RSV-positive cases were associated with cough, apnea, and hospitalization among infants. RSV incidence per 1000 person-months among mothers was 4.0 (95% confidence interval [CI], 3.2-4.4), and was twice that among the HIV-infected mothers (8.4 [95% CI, 5.7-12.0]) compared to the HIV-uninfected mothers (3.1 [95% CI, 2.3-4.0]). Among infants, incidence per 1000 person-months was 15.4 (95% CI, 12.5-18.8); incidence did not differ by HIV exposure or prematurity.Conclusions: HIV infection may increase the risk of RSV illness among pregnant women. Future maternal RSV vaccines may have added benefit in areas with high HIV prevalence. [ABSTRACT FROM AUTHOR]

Background We used postmortem minimally invasive tissue sampling (MITS) to assess the effect of time since death on molecular detection of pathogens among respiratory illness–associated deaths. Methods Samples were collected from 20 deceased children (aged 1–59 months) hospitalized with respiratory illness from May 2018 through February 2019. Serial lung and/or liver and blood samples were collected using MITS starting soon after death and every 6 hours thereafter for up to 72 hours. Bodies were stored in the mortuary refrigerator for the duration of the study. All specimens were analyzed using customized multipathogen TaqMan® array cards (TACs). Results We identified a median of 3 pathogens in each child's lung tissue (range, 1–8; n = 20), 3 pathogens in each child's liver tissue (range, 1–4; n = 5), and 2 pathogens in each child's blood specimen (range, 0–4; n = 5). Pathogens were not consistently detected across all collection time points; there was no association between postmortem interval and the number of pathogens detected (P  = .43) and no change in TAC cycle threshold value over time for pathogens detected in lung tissue. Human ribonucleoprotein values indicated that specimens collected were suitable for testing throughout the study period. Conclusions Results suggest that lung, liver, and blood specimens can be collected using MITS procedures up to 4 days after death in adequately preserved bodies. However, inconsistent pathogen detection in samples needs careful consideration before drawing definitive conclusions on the etiologic causes of death. [ABSTRACT FROM AUTHOR]

Background: The effect of malaria infection on the immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein (GP) vaccine (rVSVΔG-ZEBOV-GP) (ERVEBO) is unknown.Methods: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) vaccinated 7998 asymptomatic adults with rVSVΔG-ZEBOV-GP during the 2014-2016 Ebola epidemic. In STRIVE's immunogenicity substudy, participants provided blood samples at baseline and at 1, 6, and 9-12 months. Anti-GP binding and neutralizing antibodies were measured using validated assays. Baseline samples were tested for malaria parasites by polymerase chain reaction.Results: Overall, 506 participants enrolled in the immunogenicity substudy and had ≥1 postvaccination antibody titer. Of 499 participants with a result, baseline malaria parasitemia was detected in 73 (14.6%). All GP enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT) geometric mean titers (GMTs) at 1, 6, and 9-12 months were above baseline, and 94.1% of participants showed seroresponse by GP-ELISA (≥2-fold rise and ≥200 ELISA units/mL), while 81.5% showed seroresponse by PRNT (≥4-fold rise) at ≥1 postvaccination assessment. In participants with baseline malaria parasitemia, the PRNT seroresponse proportion was lower, while PRNT GMTs and GP-ELISA seroresponse and GMTs showed a trend toward lower responses at 6 and 9-12 months.Conclusion: Asymptomatic adults with or without malaria parasitemia had robust immune responses to rVSVΔG-ZEBOV-GP, persisting for 9-12 months. Responses in those with malaria parasitemia were somewhat lower. [ABSTRACT FROM AUTHOR]

Background Salmonella Enteritidis and Salmonella Typhimurium are major causes of bloodstream infection and diarrheal disease in East Africa. Sources of human infection, including the role of the meat pathway, are poorly understood. Methods We collected cattle, goat, and poultry meat pathway samples from December 2015 through August 2017 in Tanzania and isolated Salmonella using standard methods. Meat pathway isolates were compared with nontyphoidal serovars of Salmonella enterica (NTS) isolated from persons with bloodstream infections and diarrheal disease from 2007 through 2017 from Kenya by core genome multi-locus sequence typing (cgMLST). Isolates were characterized for antimicrobial resistance, virulence genes, and diversity. Results We isolated NTS from 164 meat pathway samples. Of 172 human NTS isolates, 90 (52.3%) from stool and 82 (47.7%) from blood, 53 (30.8%) were Salmonella Enteritidis sequence type (ST) 11 and 62 (36.0%) were Salmonella Typhimurium ST313. We identified cgMLST clusters within Salmonella Enteritidis ST11, Salmonella Heidelberg ST15, Salmonella Typhimurium ST19, and Salmonella II 42:r:- ST1208 that included both human and meat pathway isolates. Salmonella Typhimurium ST313 was isolated exclusively from human samples. Human and poultry isolates bore more antimicrobial resistance and virulence genes and were less diverse than isolates from other sources. Conclusions Our findings suggest that the meat pathway may be an important source of human infection with some clades of Salmonella Enteritidis ST11 in East Africa, but not of human infection by Salmonella Typhimurium ST313. Research is needed to systematically examine the contributions of other types of meat, animal products, produce, water, and the environment to nontyphoidal Salmonella disease in East Africa. [ABSTRACT FROM AUTHOR]

Background We report results of years 2 and 3 of consecutive cluster-randomized controlled trials of trivalent inactivated influenza vaccine (IIV3) in Senegal. Methods We cluster-randomized (1:1) 20 villages to annual vaccination with IIV3 or inactivated poliovirus vaccine (IPV) of age-eligible residents (6 months–10 years). The primary outcome was total vaccine effectiveness against laboratory-confirmed influenza illness (LCI) among age-eligible children (modified intention-to-treat population [mITT]). Secondary outcomes were indirect (herd protection) and population (overall community) vaccine effectiveness. Results We vaccinated 74% of 12 408 age-eligible children in year 2 (June 2010–April 11) and 74% of 11 988 age-eligible children in year 3 (April 2011–December 2011) with study vaccines. Annual cumulative incidence of LCI was 4.7 (year 2) and 4.2 (year 3) per 100 mITT child vaccinees of IPV villages. In year 2, IIV3 matched circulating influenza strains. The total effectiveness was 52.8% (95% confidence interval [CI], 32.3–67.0), and the population effectiveness was 36.0% (95% CI, 10.2–54.4) against LCI caused by any influenza strain. The indirect effectiveness against LCI by A/H3N2 was 56.4% (95% CI, 39.0–68.9). In year 3, 74% of influenza detections were vaccine-mismatched to circulating B/Yamagata and 24% were vaccine-matched to circulating A/H3N2. The year 3 total effectiveness against LCI was −14.5% (95% CI, −81.2–27.6). Vaccine effectiveness varied by type/subtype of influenza in both years. Conclusions IIV3 was variably effective against influenza illness in Senegalese children, with total and indirect vaccine effectiveness present during the year when all circulating strains matched the IIV3 formulation. Clinical Trials Registration NCT00893906. [ABSTRACT FROM AUTHOR]

Background Data on pneumococcal conjugate vaccine (PCV) indirect effects in low-income countries with high human immunodeficiency virus (HIV) burden are limited. We examined adult pneumococcal pneumonia incidence before and after PCV introduction in Kenya in 2011. Methods From 1 January 2008 to 31 December 2016, we conducted surveillance for acute respiratory infection (ARI) among ~12 000 adults (≥18 years) in western Kenya, where HIV prevalence is ~17%. ARI cases (cough or difficulty breathing or chest pain, plus temperature ≥38.0°C or oxygen saturation <90%) presenting to a clinic underwent blood culture and pneumococcal urine antigen testing (UAT). We calculated ARI incidence and adjusted for healthcare seeking. The proportion of ARI cases with pneumococcus detected among those with complete testing (blood culture and UAT) was multiplied by adjusted ARI incidence to estimate pneumococcal pneumonia incidence. Results Pre-PCV (2008–2010) crude and adjusted ARI incidences were 3.14 and 5.30/100 person-years-observation (pyo), respectively. Among ARI cases, 39.0% (340/872) had both blood culture and UAT; 21.2% (72/340) had pneumococcus detected, yielding a baseline pneumococcal pneumonia incidence of 1.12/100 pyo (95% confidence interval [CI]: 1.0–1.3). In each post-PCV year (2012–2016), the incidence was significantly lower than baseline; with incidence rate ratios (IRRs) of 0.53 (95% CI: 0.31–0.61) in 2012 and 0.13 (95% CI: 0.09–0.17) in 2016. Similar declines were observed in HIV-infected (IRR: 0.13; 95% CI: 0.08–0.22) and HIV-uninfected (IRR: 0.10; 95% CI: 0.05–0.20) adults. Conclusions Adult pneumococcal pneumonia declined in western Kenya following PCV introduction, likely reflecting vaccine indirect effects. Evidence of herd protection is critical for guiding PCV policy decisions in resource-constrained areas. [ABSTRACT FROM AUTHOR]

Background The population effects of influenza vaccination in children have not been extensively studied, especially in tropical, developing countries. In rural Senegal, we assessed the total (primary objective) and indirect effectiveness of a trivalent inactivated influenza vaccine (IIV3). Methods In this double-blind, cluster-randomized trial, villages were randomly allocated (1:1) for the high-coverage vaccination of children aged 6 months through 10 years with either the 2008–09 northern hemisphere IIV3 or an inactivated polio vaccine (IPV). Vaccinees were monitored for serious adverse events. All village residents, vaccinated and unvaccinated, were monitored for signs and symptoms of influenza illness using weekly home visits and surveillance in designated clinics. The primary outcome was all laboratory-confirmed symptomatic influenza. Results Between 23 May and 11 July 2009, 20 villages were randomized, and 66.5% of age-eligible children were enrolled (3918 in IIV3 villages and 3848 in IPV villages). Follow-up continued until 28 May 2010. There were 4 unrelated serious adverse events identified. Among vaccinees, the total effectiveness against illness caused by the seasonal influenza virus (presumed to all be drifted A/H3N2, based on antigenic characterization data) circulating at high rates among children was 43.6% (95% confidence interval [CI] 18.6–60.9%). The indirect effectiveness against seasonal A/H3N2 was 15.4% (95% CI -22.0 to 41.3%). The total effectiveness against illness caused by the pandemic influenza virus (A/H1N1pdm09) was -52.1% (95% CI -177.2 to 16.6%). Conclusions IIV3 provided statistically significant, moderate protection to children in Senegal against circulating, pre-2010 seasonal influenza strains, but not against A/H1N1pdm09, which was not included in the vaccine. No indirect effects were measured. Further study in low-resource populations is warranted. Clinical Trials Registration NCT00893906. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are prioritized for seasonal influenza vaccination, but the evidence on the risk of influenza during pregnancy that is used to inform these policies is limited.Methods: Individual-level administrative data sets and active surveillance data were joined to estimate influenza-associated hospitalization and outpatient visit rates by pregnancy, postpartum, and trimester status.Results: During 2012-2015, 46 of 260 (17.7%) influenza-confirmed hospitalizations for acute respiratory infection and 13 of 294 (4.4%) influenza-confirmed outpatient visits were among pregnant and postpartum women. Pregnant and postpartum women experienced higher rates of influenza-associated hospitalization than nonpregnant women overall (rate ratio [RR], 3.4; 95% confidence interval [CI], 2.5-4.7) and by trimester (first, 2.5 [95% CI, 1.2-5.4]; second, 3.9 [95% CI, 2.4-6.3]; and third, 4.8 [95% CI, 3.0-7.7]); the RR for the postpartum period was 0.7 (95% CI, 3.0-7.7). Influenza A viruses were associated with an increased risk (RR for 2009 pandemic influenza A[H1N1] virus, 5.3 [95% CI, 3.2-8.7]; RR for influenza A(H3N2) virus, 3.0 [95% CI, 1.8-5.0]), but influenza B virus was not (RR, 1.8; 95% CI, .7-4.6). Influenza-associated hospitalization rates in pregnancy were significantly higher for Māori women (RR, 3.2; 95% CI, 1.3-8.4), compared with women of European or other ethnicity. Similar risks for influenza-confirmed outpatient visits were not observed.Conclusion: Seasonal influenza poses higher risks of hospitalization among pregnant women in all trimesters, compared with nonpregnant women. Hospitalization rates vary by influenza virus type and ethnicity among pregnant women. [ABSTRACT FROM AUTHOR]

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at ≤-60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity.Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. [ABSTRACT FROM AUTHOR]

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. [ABSTRACT FROM AUTHOR]

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. [ABSTRACT FROM AUTHOR]

This study was aimed to develop an instrument to assess infectious disease-specific health literacy (IDSHL) in the general population of Tibet, China and identify the association between IDSHL and reported infectious disease-related symptoms. A survey using a standardized questionnaire, which included 25 questions on knowledge, behaviors and skills regarding infectious diseases, was conducted in the general population of Tibet, China between September 2011 and November 2011. The 25 questions formed the index system of the instrument assessing IDSHL (total scores: 25 scores). Factors associated with index scores of IDSHL were identified by general linear model. The association between the index score of IDSHL and the occurrence of the five selected infectious disease symptoms (fever, diarrhea, rash, jaundice or conjunctivitis) were investigated using multivariate unconditional logistic regression. Among 5717 eligible participants in the survey, 4631 participants completed all of the 25 questions in the instrument. The instrument was reliable and valid as measured by the Cronbach's alpha coefficient and split-half coefficient, and the confirmatory factor analysis. Only 1.0% (48/4631) answered ≥80% of the 25 questions correctly (score ≥ 20). Significant factors associated with lower health literacy score included female gender, older age, Tibetan group, lower education level, underlying diseases and more undeveloped area. For each increasing score of IDSHL, reports of fever, diarrhea or jaundice in the prior year were significantly decreased by 3% (p = 0.015), 4% (p = 0.004) and 16% (p < 0.001), respectively. Accurately measuring IDSHL could help identify those individuals with poor IDSHL, who could be targeted with specific interventions to improve health. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. There are limited data on the burden of disease posed by influenza in low- and middle-income countries. Furthermore, most estimates of influenza disease burden worldwide rely on passive sentinel surveillance at health clinics and hospitals that lack accurate population denominators. Methods. We documented influenza incidence, seasonality, health-system utilization with influenza illness, and vaccination coverage through active community-based surveillance in 4 ecologically distinct regions of Peru over 6 years. Approximately 7200 people in 1500 randomly selected households were visited 3 times per week. Naso- and oropharyngeal swabs were collected from persons with influenza-like illness and tested for influenza virus by real-time reverse-transcription polymerase chain reaction. Results. We followed participants for 35 353 person-years (PY). The overall incidence of influenza was 100 per 1000 PY (95% confidence interval [CI], 97-104) and was highest in children aged 2-4 years (256/1000 PY [95% CI, 236-277]). Seasonal incidence trends were similar across sites, with 61% of annual influenza cases occurring during the austral winter (May-September). Of all participants, 44 per 1000 PY (95% CI, 42-46) sought medical care, 0.7 per 1000 PY (95% CI, 0.4-1.0) were hospitalized, and 1 person died (2.8/100 000 PY). Influenza vaccine coverage was 27% among children aged 6-23 months and 26% among persons aged ≤65 years. Conclusions. Our results indicate that 1 in 10 persons develops influenza each year in Peru, with the highest incidence in young children. Active community-based surveillance allows for a better understanding of the true burden and seasonality of disease that is essential to plan the optimal target groups, timing, and cost of national influenza vaccination programs. [ABSTRACT FROM AUTHOR]

Animal influenza viruses can reassort or mutate to infect and spread sustainably among people and cause a devastating worldwide pandemic. Since the first evidence of human infection with an animal influenza virus, in 1958, 16 different novel, zoonotic influenza A virus subtype groups in 29 countries, Taiwan, and Hong Kong have caused human infections, with differing severity and frequency. The frequency of novel influenza virus detection is increasing, and human infections with influenza A(H5N1) and A(H7N9) viruses are now annual seasonal occurrences in Asia. The study of the epidemiology and virology of animal influenza viruses is key to understanding pandemic risk and informing preparedness. This supplement brings together select recent articles that look at the risk of emergence and transmission of and approaches to prevent novel influenza virus infections. [ABSTRACT FROM AUTHOR]

Multiple clusters of human infections with novel avian influenza A(H7N9) virus have occurred since the virus was first identified in spring 2013. However, in many situations it is unclear whether these clusters result from person-to-person transmission or exposure to a common infectious source. We analyzed the possibility of person-to-person transmission in each cluster and developed a framework to assess the likelihood that person-to-person transmission had occurred. We described 21 clusters with 22 infected contact cases that were identified by the Chinese Center for Disease Control and Prevention from March 2013 through June 2015. Based on detailed epidemiological information and the timing of the contact case patients' exposures to infected persons and to poultry during their potential incubation period, we graded the likelihood of person-to-person transmission as probable, possible, or unlikely. We found that person-to-person transmission probably occurred 12 times and possibly occurred 4 times; it was unlikely in 6 clusters. Probable nosocomial transmission is likely to have occurred in 2 clusters. Limited person-to-person transmission is likely to have occurred on multiple occasions since the H7N9 virus was first identified. However, these transmission events represented a small fraction of all identified cases of H7N9 human infection, and sustained person-to-person transmission was not documented. [ABSTRACT FROM AUTHOR]

Background. Individuals infected with human immunodeficiency virus (HIV) are at increased risk for severe influenza, yet immune responses to standard-dose intramuscular (IM) influenza vaccine are suboptimal in this population. Intradermal (ID) delivery of influenza vaccine might improve immune response through enhanced stimulation of dendritic cells. Methods. We conducted a randomized, double-blind, controlled trial to compare the immunogenicity of off-label standard-dose (15 μg) ID vs standard-dose (15 μg) IM inactive influenza vaccine in HIV-infected men in Bangkok, Thailand. The primary study outcome was seroconversion (minimum titer of 1:40 and ≥4-fold rise in antibody titer) at 1 month postvaccination based on serum hemagglutination inhibition antibody titers against each vaccine strain. Adverse events (AEs) in the 7 days following vaccination were also assessed. Results. We enrolled 400 HIV-infected participants; 200 were randomly assigned to receive IM and 200 ID vaccine. Vaccine arms were well-balanced with respect to age, CD4 cell count, HIV RNA load, and antiretroviral treatment. Percentage of seroconversion to all (ID 14% vs IM 15%; P = .8) or at least 1 (ID 69% vs IM 68%; P = .7) of the 3 vaccine strains did not differ significantly between ID vs IM vaccine recipients. A higher proportion of participants who received ID vaccine had mild injection-site AEs compared with participants who received IM vaccine (77% vs 27%). Conclusions. There were no significant differences in the immunogenicity of standard-dose ID vs IM influenza vaccine in this HIVinfected population in Thailand. Additional strategies to enhance immune responses to influenza vaccine among HIV-infected persons are needed. [ABSTRACT FROM AUTHOR]

We evaluated the added value of collecting both nasal and oropharyngeal swabs, compared with collection of nasal swabs alone, for detection of common respiratory viruses by reverse transcription-polymerase chain reaction in hospitalized children aged <10 years. Nasal swabs had equal or greater sensitivity than oropharyngeal swabs for detection of respiratory syncytial virus, adenovirus, human metapneumovirus, rhinovirus, and influenza virus but not parainfluenza virus. The addition of an oropharyngeal swab, compared with use of a nasal swab alone, increased the frequency of detection of each respiratory virus by no more than 10% in children aged <10 years. [ABSTRACT FROM AUTHOR]

Background. Although influenza is a vaccine-preventable disease that annually causes substantial disease burden, data on virus activity in tropical countries are limited. We analyzed publicly available influenza data to better understand the global circulation of influenza viruses.Methods. We reviewed open-source, laboratory-confirmed influenza surveillance data. For each country, we abstracted data on the percentage of samples testing positive for influenza each epidemiologic week from the annual number of samples testing positive for influenza. The start of influenza season was defined as the first week when the proportion of samples that tested positive remained above the annual mean. We assessed the relationship between percentage of samples testing positive and mean monthly temperature with use of regression models.Findings. We identified data on laboratory-confirmed influenza virus infection from 85 countries. More than one influenza epidemic period per year was more common in tropical countries (41%) than in temperate countries (15%). Year-round activity (ie, influenza virus identified each week having ≥10 specimens submitted) occurred in 3 (7%) of 43 temperate, 1 (17%) of 6 subtropical, and 11 (37%) of 30 tropical countries with available data (P = .006). Percentage positivity was associated with low temperature (P = .001).Interpretation. Annual influenza epidemics occur in consistent temporal patterns depending on climate. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Background. Adenoviruses can cause outbreaks of febrile respiratory illness in military trainees, but until 2007, adenovirus serotype 14 (Ad14) was never associated with such outbreaks. From April through June 2007, 15 trainees at one base were hospitalized for pneumonia due to Ad14. Subsequent reports of febrile respiratory illness among health care personnel suggested nosocomial transmission. Methods. Health care personnel participants completed a questionnaire and provided blood and nasal wash specimens for Ad14 diagnostic testing. We defined a confirmed case of Ad14 infection as one with titers ⩾1:80 or nasal wash specimens positive for Ad14 by polymerase chain reaction, whereas a possible case was defined by titers of 1:20 or 1:40. We also collected environmental samples. Results. Among 218 tested health care personnel, 35 (16%) had titers ⩾1:20; of these, 7 had possible cases and 28 had confirmed cases of infection. Confirmed case patients were more likely to report febrile respiratory illness (57% vs 11%; P < .001) and to have had direct contact with patients with Ad14 infection (82% vs 62%; P=.04). Of the 23 confirmed case patients with direct contact with Ad14-infected patients, 52% reported that patients were not in contact and droplet precautions at the time of exposure. Ad14 was recovered from several hospital surfaces. Conclusion. Our findings of possible nosocomial transmission of Ad14 highlight the need to reinforce infection control guidelines. [ABSTRACT FROM AUTHOR]

Rotavirus remains the most common cause of severe childhood diarrhea worldwide and of diarrheal mortality in poor countries. In 2003, the GAVI Alliance launched the Rotavirus Vaccine Program and the Accelerated Development and Introduction Plan to close the gap of access to rotavirus vaccines in industrialized and developing countries by generating data on rotavirus disease burden, projected impact, and cost-effectiveness of vaccination and by conducting clinical trials of existing vaccines in impoverished settings. By the end of 2008, rotavirus vaccines were licensed in >100 countries, although only 17 countries have introduced routine rotavirus vaccination. Increased uptake of the vaccine by countries with the highest childhood mortality will depend in part on a solid evidence base of estimated burden and cost of rotavirus illness. Since 2001, regional surveillance networks worldwide have generated burden and strain data from 196 sites in 59 countries. Among children aged <5 years who are hospitalized for severe diarrhea in different regions of the world, a regional median of 39% (range by country, 20%-73%) test positive for rotavirus. Rotavirus vaccines are a cost-effective intervention and may be cost saving with a GAVI Alliance subsidy from the health care perspective. Punctual vaccination and high coverage of populations at highest risk of mortality will maximize the impact of vaccination. Surveillance platforms will allow measurement of the rapid impact of rotavirus vaccine introduction on the heavy burden of rotavirus on child health worldwide. [ABSTRACT FROM AUTHOR]

Background. Effective rotavirus vaccines could substantially reduce the ∼500,000 deaths due to rotavirus disease per year worldwide, although the impact will depend on vaccine effectiveness, timing of administration, and coverage. We modeled vaccine impact on rotavirus-associated mortality in rural Ghana. Methods. All deaths due to acute diarrhea among children during 1998-2004 in the Kassena-Nankana District of Ghana were identified, and the number of deaths due to rotavirus disease was estimated using hospital laboratory surveillance data. Assuming rotavirus vaccine would be included in the current Expanded Program on Immunization schedule, we estimated the reduction in rotavirus-associated mortality with use of the current coverage and timing of diphtheria, tetanus, and pertussis vaccine administration and various age-restricted schedules. Results. Of the 381 deaths due to diarrhea, 131 (34%) were estimated to be caused by rotavirus infection. On the basis of current diphtheria, tetanus, and pertussis vaccine coverage and timing, a 90% efficacious 3-dose rotavirus vaccine would prevent 70% of deaths due to rotavirus infection if administered without age restrictions, 53% if only initiated among children <12 weeks of age, and 52% if the course also was completed by 32 weeks of age. Conclusions. Rotavirus vaccine has the potential to substantially reduce rotavirus-associated mortality in rural Ghana. Although timely vaccination should be encouraged, extending the current age recommendation for initiation of rotavirus vaccination could increase the coverage and impact of vaccination. [ABSTRACT FROM AUTHOR]

Globally, rotavirus is the leading cause of diarrhea-related hospitalizations and deaths among young children, but the burden of rotavirus disease in Indonesia is poorly documented. From January through December 2006, we conducted prospective surveillance (inpatient and outpatient) among children aged <5 years at 6 hospitals in 6 provinces of Indonesia, using standardized methodology. Of 2240 enrolled children hospitalized for diarrhea, 1345 (60%) were rotavirus positive. Of 176 children enrolled in outpatient clinics in 3 hospitals, 73 (41%) were rotavirus positive. Among children hospitalized for diarrhea, dehydration was more common among those who tested positive for rotavirus than among those who did not (91% vs 82%; P< .05), as was vomiting (86% vs 67%; P< .05). Children aged 6-23 months experienced 72% of all rotavirus episodes. Rotavirus prevalence increased slightly in the cool, dry season. The most commonly detected genotypes were G9 (30%) and P[6] (56%). G1P[6] and G9P[6] accounted for 34% and 21% of strains, respectively. A high proportion of genotype P[6] was detected, in combination with the common G types G1 and G9. Available rotavirus vaccines would likely be efficacious against the most common circulating strains, but continued monitoring of uncommon genotypes is needed. [ABSTRACT FROM AUTHOR]

Background. The projected impact and cost-effectiveness of rotavirus vaccination are important for supporting rotavirus vaccine introduction in Africa, where limited health intervention funds are available. Methods. Hospital records, health utilization surveys, verbal autopsy data, and surveillance data on diarrheal disease were used to determine rotavirus-specific rates of hospitalization, clinic visits, and deaths due to diarrhea among children <5 years of age in Nyanza Province, Kenya. Rates were extrapolated nationally with use of provincespecific data on diarrheal illness. Direct medical costs were estimated using record review and World Health Organization estimates. Household costs were collected through parental interviews. The impact of vaccination on health burden and on the cost-effectiveness per disability-adjusted life-year and lives saved were calculated. Results. Annually in Kenya, rotavirus infection causes 19% of hospitalizations and 16% of clinic visits for diarrhea among children <5 years of age and causes 4471 deaths, 8781 hospitalizations, and 1,443,883 clinic visits. Nationally, rotavirus disease costs the health care system $10.8 million annually. Routine vaccination with a 2- dose rotavirus vaccination series would avert 2467 deaths (55%), 5724 hospitalizations (65%), and 852,589 clinic visits (59%) and would save 58 disability-adjusted life-years per 1000 children annually. At $3 per series, a program would cost $2.1 million in medical costs annually; the break-even price is $2.07 per series. Conclusions. A rotavirus vaccination program would reduce the substantial burden of rotavirus disease and the economic burden in Kenya. [ABSTRACT FROM AUTHOR]

The burden of rotavirus disease in the Latin American region has been poorly understood despite the promise of effective vaccines. We describe here the implementation and results of a rotavirus surveillance network in the Latin American and Caribbean region. From 2005 through 2007, stool specimens and epidemiologic information were gathered from children <5 years of age who were hospitalized for acute diarrhea (⩾3 looser-than-normal stools within <24 h) lasting <14 days with use of a standardized generic protocol. Stool samples were tested for rotavirus, and a proportion of detected strains were typed. The proportion of samples positive for rotavirus was applied to World Health Organization diarrhea-related mortality estimates to calculate rotavirus-associated mortality. In 2007, the network comprised 54 sites in 11 countries. During 2006-2007, specimens were collected from 19,817 children; 8141 of these specimens were positive for rotavirus. The median percentage of positive specimens in the country was 31.5% (range, 24%-47%). The risk of death from rotavirus diarrhea by age 5 years was 1 of 2874. Strong rotavirus winter seasonality was apparent, even in tropical Central America. Globally common strains (P[8] G1, P[8] G9, and P[4] G2) accounted for >75% of strains, although unusual strains, including G12, were detected at low levels. As rotavirus vaccines continue to be introduced in Latin America, maintenance of surveillance will provide robust pre-introduction data and a platform for estimating vaccine effectiveness and other measures of impact. [ABSTRACT FROM AUTHOR]

Background. In anticipation of vaccine introduction, we assessed the epidemiology, burden, and genotype of infecting strains of rotavirus disease among Moroccan children hospitalized for acute gastroenteritis. Methods. From June 2006 through May 2007, 345 children <5 years of age who had acute gastroenteritis and were admitted to 4 sentinel hospitals in different regions of Morocco were enrolled in this surveillance study, and stool specimens were tested for the presence of rotavirus with use of enzyme immunoassay. RNA from positive samples was genotyped by reverse-transcriptase polymerase chain reaction. Results. Overall, 314 children had complete data available, and among these, 138 (44%) tested positive for rotavirus. Rotavirus infection was most common among children <24 months of age (95% of all hospitalizations for rotavirus infection). Rotavirus infection was detected year-round at all 4 sites but was most prevalent from September through January. Genotype analysis demonstrated that 30.6% of samples were G1[P8], 26% were G9[P8], 7.5% were G2[P6], 3.7% were G1[P6], and 0.7% were G2[P8]. Nucleotide sequencing analysis of G- or P-untypeable strains showed that 4.5% were G9[P8], 2.2% were G1[8], 2.2% were G2[P6], and 1.5% were G2[P4]. A high frequency of mixed infection (21%) was found, of which G1G2[P8] accounted for the majority (16.4%). Conclusions. Rotavirus was responsible for 44% of all hospitalizations for diarrhea among young children at these 4 separate sites in Morocco. These data will help inform a decision on the introduction of rotavirus vaccine in Morocco. Continued and extended surveillance in Morocco will be important to monitor changes in the epidemiology of rotavirus disease and the impact of vaccination after introduction. [ABSTRACT FROM AUTHOR]

Background. Recent data on the burden of hospitalization and clinic visits for rotavirus gastroenteritis are needed to support the decision to introduce rotavirus vaccine in the Philippines. Methods. From 2005 through 2006, children aged <5 years with acute diarrhea who attended 1 of 7 clinics and/or hospitals in Muntinlupa City, the Philippines, were enrolled. Clinical and demographic data were collected, and a stool specimen was obtained for rotavirus testing and typing for G and P antigens. The incidences of different clinical outcomes of rotavirus gastroenteritis were determined for 3 townships under surveillance and were extrapolated to the Philippines with use of national data sets. Results. The prevalence of rotavirus was 31% (171/560) among children hospitalized with diarrhea, 30% (155/ 520) among those who presented to the emergency department, and 15% (56/385) among those who presented to a clinic. The annual estimated incidence (per 100,000 children aged <5 years) of rotavirus gastroenteritis in outpatient, emergency department, and inpatient settings was 755, 451, and 279, respectively. Of 274 strains, 50 (18%) were nontypeable. Of the 128 strains that underwent G and P typing, 98% belong to the globally common strains G3P[P], G2P[4], and G1P[8]. Conclusions. The burden of rotavirus gastroenteritis in the Philippines is high and is predominantly caused by strains against which current vaccines have shown good efficacy, suggesting that routine immunization will have a large impact on rotavirus disease burden. [ABSTRACT FROM AUTHOR]

Rotaviruses cause acute diarrhea worldwide. Previous studies of rotavirus diarrhea in China found that rotavirus infection is the most common cause of severe diarrhea in young children. In the present study, surveillance of rotavirus diarrhea was conducted involving 9549 children aged < years who were admitted for treatment of diarrhea at 11 sentinel hospitals in China from August 2003 through July 2007. Group A rotavirus was detected in 3749 (47.8%) of the 7846 fecal specimens by using enzyme-linked immunosorbent assay. Rotavirus isolates were characterized by reverse-transcriptase polymerase chain reaction to determine G and P genotypes. All the strains that are common worldwide were detected; G3P[8] was the most common. An unusual G5 strain was detected in 2 specimens. Of all episodes of rotavirus diarrhea, 94% occurred during the first 2 years of life, peaking at 6-23 months of age. Our findings indicate that globally common rotavirus strains continue to be a major cause of severe childhood diarrhea in China. Introduction of routine immunization with effective rotavirus vaccines would substantially reduce this burden. [ABSTRACT FROM AUTHOR]

Background. In 2007, a US Air Force training facility reported a cluster of severe respiratory illnesses associated with a rare human adenovirus (Ad) serotype, Ad14. We investigated this outbreak to better understand its epidemiology, clinical spectrum, and associated risk factors. Methods. Data were collected from ongoing febrile respiratory illness (FRI) surveillance and from a retrospective cohort investigation. Because an Ad7 vaccine is in development, Ad7 antibody titers in pretraining serum samples from trainees with mild and those with severe Ad14 illness were compared. Results. During 2007, an estimated 551 (48%) of 1147 trainees with FRI were infected with Ad14; 23 were hospitalized with pneumonia, 4 required admission to an intensive care unit, and 1 died. Among cohort members (n = 173), the Ad14 infection rate was high (50%). Of those infected, 40% experienced FRI.Nocohort members were hospitalized. Male sex (risk ratio [RR], 4.7 [95% confidence interval {CI}, 2.2-10.1]) and an ill close contact (RR, 1.6 [95% CI, 1.2-2.2]) were associated with infection. Preexisting Ad7 neutralizing antibodies were found in 7 (37%) of 19 Ad14-positive trainees with mild illness but in 0 of 16 trainees with Ad14 pneumonia (P = .007). Conclusions. Emergence of Ad14, a rare Ad serotype, caused a protracted outbreak of respiratory illness among military recruits. Most infected recruits experienced FRI or milder illnesses. Some required hospitalization, and 1 died. Natural Ad7 infection may protect against severe Ad14 illness. [ABSTRACT FROM AUTHOR]

Background. Norovirus is often transmitted by infected food handlers at the point of service, whereas reports of food contamination before wholesale distribution are rare. In September 2005, we investigated reports of gastroenteritis among rafters who went on unrelated trips on the Colorado River. Methods. We surveyed all companies that launched rafting trips during the period from 14 August through 19 September 2005 to identify trips in which ≥3 rafters became ill. We conducted a case-control study. Case patients were persons who experienced diarrhea or vomiting that commenced ≤72 h after the trip launch; control subjects were persons who did not become ill ≤72 h after launch. We tested stool samples and food specimens for norovirus. We performed a traceback investigation of the suspected food vehicle and inspected the implicated processing plant. Results. Three or more rafters developed gastroenteritis during 13 (14%) of 91 trips, for a total of 137 ill persons. Of the 57 case patients who became ill ≤72 h after trip launch, 55 (96%) reported eating delicatessen meat, compared with 75 (79%) of 95 control subjects (odds ratio, 7.3; 95% confidence interval, 1.7−66.7). All delicatessen meat eaten by case patients came from 1 batch purchased from 1 processing plant and had been sliced, vacuum-packed, and frozen (temperature, −23°C) for 7-28 days. An employee sliced this batch with bare hands 1 day after recovery from gastroenteritis. Identical norovirus sequences were identified in stool specimens obtained from rafters on 3 different trips; 2 of 5 meat packages also tested positive for norovirus by reverse-transcriptase polymerase chain reaction and DNA hybridization. Conclusions. Food handlers can contaminate ready-to-eat meats with norovirus during processing. Meat-processing practices should include specific measures to prevent contamination with enteric viruses and subsequent widespread outbreaks. [ABSTRACT FROM AUTHOR]

Background. During May 2004, the Vessel Sanitation Program (VSP) investigated an outbreak of norovirus gastroenteritis on board a cruise ship sailing in Alaska waters. The objectives were to identify a common food item source and explore behavioral risk factors for person-to-person transmission among passengers. Methods. A case was defined as three or more episodes of loose stools within 24 hours or two or fewer episodes of loose stools accompanied by one or more episodes of vomiting. Vomitus and stool samples from affected passengers were tested for norovirus by reverse transcriptase–polymerase chain reaction. Environmental health officers performed an environmental investigation following VSP protocol. Questionnaires about food items consumed and behavioral risk factors were placed in cabin mailboxes ( n = 2,018). A case-control study design using multivariable logistic regression tested associations between risk factors and disease. Results. A total of 359 passengers (24.1% of respondents) met the case definition. Four of seven clinical specimens tested positive for norovirus. No significant deficiencies in environmental health practices were identified, and no meal servings were associated with disease. Having a cabin mate sick with diarrhea or vomiting [odds ratio (OR): 3.40; 95% confidence interval (CI) = 1.80–6.44] and using a specific women’s toilet that was contaminated with vomit (OR: 5.13; 95% CI = 1.40–18.78) were associated with disease. Washing hands before meals was protective (OR: 0.25; 95% CI = 0.12–0.54) against disease. Conclusions. Widespread person-to-person norovirus outbreaks can occur on board cruise ships, even with appropriate environmental health practices. Programs to prevent and control norovirus outbreaks on board cruise ships should involve strategies that disrupt person-to-person spread and emphasize hand washing. [ABSTRACT FROM AUTHOR]

Background. Noroviruses are believed to be the most common etiologic agent of foodborne outbreaks of gastroenteritis, yet diagnostic tests for these agents are not readily available in the United States. In the absence of assays to detect norovirus, several clinical and epidemiologic profiles—the criteria of Kaplan et al. (vomiting in 150% of patients, mean incubation period of 24–48 h, mean duration of illness of 12–60 h, and no bacterial pathogen) and the ratios of fever to vomiting and diarrhea to vomiting—have been used to distinguish foodborne outbreaks of gastroenteritis caused by noroviruses from those caused by bacteria. Methods. To examine how well clinical and epidemiological profiles discriminate between foodborne outbreaks of gastroenteritis due to noroviruses and those due to bacteria and to estimate the proportion of reported outbreaks that might be attributable to noroviruses, we reviewed subsets of the 4050 outbreaks reported from 1998 to 2000. Results. The set of criteria of Kaplan et al. is highly specific (99%) and moderately sensitive (68%) in discriminating confirmed outbreaks due to bacteria from those due to norovirus and was the most useful diagnostic aid evaluated. Each individual component of the criteria, the fever-to-vomiting ratio, and the diarrhea-to-vomiting ratio were more sensitive, yet less specific, and therefore less useful, than the criteria of Kaplan et al. We estimated that, at a minimum, 28% of all the foodborne outbreaks reported to the Centers for Disease Control and Prevention may be attributed to norovirus on the basis of these criteria. Conclusion. Until norovirus diagnostic tests become widely available, the criteria of Kaplan et al. remain the most useful and discriminating diagnostic aid to identify foodborne outbreaks of gastroenteritis due to noroviruses. [ABSTRACT FROM AUTHOR]

Between July 2000 and June 2004, fecal specimens from 270 outbreaks of acute gastroenteritis were sent to the Centers for Disease Control and Prevention by local or state health departments for calicivirus testing. Of the 226 outbreaks that met the criteria for inclusion in the present study, caliciviruses were detected in 184 (81%) by reverse-transcription polymerase chain reaction and nucleotide sequencing. Nursing homes, retirement centers, and hospitals were the most frequently reported settings, and person-to-person contact was the most common mode of transmission, followed by foodborne spread. Overall, genogroup II norovirus (NoV) strains were the most abundant (79%), followed by genogroup I NoV strains (19%) and sapovirus (2%). Nucleotide-sequence analysis indicated a great diversity of NoV strains and implicated the emergence of one particular sequence variant in outbreaks occurring between July 2002 and June 2003. The public health impact of caliciviruses will not be fully appreciated, nor will interventions be completely evaluated, until methods to detect these viruses are more routinely used. [ABSTRACT FROM AUTHOR]

Although rotavirus infections are generally considered to be confined to the intestine, recent reports suggest that extraintestinal disease occurs. We studied whether rotavirus infection was associated with antigenemia during a major outbreak of gastroenteritis in the Kingston metropolitan area, during July–August 2003. Rotavirus antigen was identified in 30 of 70 acute-phase serum samples (including from 2 deceased individuals) but in only 1 of 53 control samples. Serum antigen levels were inversely associated with time since symptom onset and were directly associated with antigen levels in stool (P = .02). Serum antigen levels were significantly elevated during primary infections (acute-phase serum immunoglobulin G [IgG] titers, <25), compared with those in subsequent infections (acute-phase serum IgG titers, ≥25) (P = .02). Antigenemia was common in this outbreak and might provide a mechanism to help explain rare but well-documented reports of findings of extraintestinal rotavirus. In situations in which stool samples are not readily available (i.e., patients with severe dehydration or those recently recovered or deceased), serum testing by enzyme immunoassay offers a new and practical diagnostic tool. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that hepatitis E virus (HEV) infection may occur in developed countries and that swine may act as a reservoir. We report a cluster of 2 confirmed cases and 1 presumptive case of hepatitis associated with HEV. The typed strain from 1 case was related to HEV strains found in North America and Europe, and it was also related to a cluster of swine HEV strains found in The Netherlands. Our findings indicate that locally acquired HEV infections in industrialized countries may be overlooked. Routine testing for HEV infection in patients with acute hepatitis in The Netherlands should be considered before a diagnosis of autoimmune hepatitis is reached and steroid therapy is initiated. [ABSTRACT FROM AUTHOR]

Norwalk-like viruses (NLVs) are estimated to be the most common causes of foodborne disease in the United States, accounting for two-thirds of all food-related illnesses. The epidemiologic features and disease burden associated with NLVs have, until recently, been poorly understood because of the lack of sensitive detection assays and the underuse of available diagnostic tools. However, the application of molecular techniques to diagnose and investigate outbreaks of infection during recent years has led to a growing appreciation of the importance of these agents. NLVs are a principal cause of outbreaks of acuteonset vomiting and diarrhea in all age groups—most commonly, via contamination of uncooked foods by infected foodhandlers, but also via foods contaminated at their sources, such as oysters and raspberries. NLVs may also account for >10% of sporadic cases of gastroenteritis in children and adults. Future research will focus on the development of easy-to-use diagnostic assays based on antigen and antibody detection as well as vaccine development. Implementation of simple prevention measures, including correct food-handling practices, will continue to be a priority. [ABSTRACT FROM AUTHOR]

Background. During October 2006, an outbreak of norovirus gastroenteritis sickened 200 (59%) of the 379 passengers and 26 (18%) of the 144 crew members on a riverboat. In November 2006, CDC was notified that a group of ill passengers had boarded a commercial flight from St Louis, Missouri, to Atlanta, Georgia. A recent study demonstrated probable norovirus transmission from eight symptomatic flight attendants to passengers on board an aircraft during an international flight; however, there are no published reports of transmission of norovirus on flights of short duration. Methods. We investigated the risk of norovirus transmission on a short flight as part of an outbreak response. Using a standardized questionnaire, we conducted interviews of passengers and flight attendants who were on the flight. We collected information on traveler demographics and illness before, during, and after the flight. We also collected information about potential onboard risk factors for norovirus transmission, such as proximity and contact with ill appearing persons during the flight, as well as use of onboard lavatories and hand hygiene. Results. We were able to complete questionnaires for 50 (56%) of the 89 passengers on the flight and 2 (67%) of the 3 flight attendants. Two (5%) of 42 possible secondary cases were identified. These two passengers neither sat in proximity to an index-case passenger during the flight nor reported use of an onboard lavatory. Conclusions. Although onboard transmission cannot be excluded, likelihood of norovirus transmission on a short flight when ill travelers do not have episodes of vomiting or diarrhea appears minimal. [ABSTRACT FROM AUTHOR]

Background Maternal influenza vaccination protects infants against influenza virus infection. Impaired transplacental transfer of influenza antibodies may reduce this protection. Methods We conducted a cross-sectional study of influenza vaccine–naïve pregnant women recruited at delivery from Blantyre (urban, low malaria transmission) and Chikwawa (rural, high malaria transmission) in Southern Malawi. HIV-infected mothers were excluded in Chikwawa. Maternal and cord blood antibodies against circulating influenza strains A/California/7/2009, A/Victoria/361/2011, B/Brisbane/60/2008, and B/Wisconsin/1/2010 were measured by hemagglutination inhibition (HAI). We studied the impact of maternal HIV infection and placental malaria on influenza antibody levels in mother–infant pairs in Blantyre and Chikwawa, respectively. Results We included 454 mother–infant pairs (Blantyre, n = 253; Chikwawa, n = 201). HIV-infected mothers and their infants had lower seropositivity (HAI titer ≥1:40) against influenza A(H1N1)pdm09 (mothers, 24.3 vs 45.4%; P =.02; infants, 24.3 vs 50.5%; P =.003) and A(H3N2) (mothers, 37.8% vs 63.9%; P =.003; infants, 43.2 vs 64.8%; P =.01), whereas placental malaria had an inconsistent effect on maternal and infant seropositivity. In multivariable analyses, maternal HIV infection was associated with reduced infant seropositivity (A(H1N1)pdm09: adjusted odds ratio [aOR], 0.34; 95% confidence interval [CI], 0.15–0.79; A(H3N2): aOR, 0.43; 95% CI, 0.21–0.89). Transplacental transfer was not impaired by maternal HIV or placental malaria. Conclusions Maternal HIV infection influenced maternal antibody response to influenza A virus infection, and thereby antibody levels in newborns, but did not affect transplacental antibody transfer. [ABSTRACT FROM AUTHOR]

The article offers information regarding the epidemiology of influenza in Africa. It mentions that mortality rates due to respiratory disease among children are higher in Africa than anywhere else in the world. It reports presence of HIV infection, AIDS, tuberculosis, and malaria residents of Africa. It discusses the increase in influenza vaccine manufacturing which will affect the cost of influenza vaccines and vaccines that are currently cost-prohibitive in African countries.

To provide vaccination against infection due to 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) to resource-constrained countries with otherwise very little access to the A(H1N1)pdm09 vaccine, the World Health Organization (WHO) coordinated distribution of donated vaccine to selected countries worldwide, including those in Africa. From February through November 2010, 32.2 million doses were delivered to 34 countries in Africa. Of the 19.2 million doses delivered to countries that reported their vaccination activities to WHO, 12.2 million doses (64%) were administered. Population coverage in these countries varied from 0.4% to 11%, with a median coverage of 4%. All countries targeted pregnant women (median proportion of all vaccine doses administered [mpv], 21% [range, 4%–72%]) and healthcare workers (mpv, 9% [range, 1%–73%]). Fourteen of 19 countries targeted persons with chronic conditions (mpv, 26% [range, 5%–66%]) and 10 of 19 countries vaccinated children (mpv, 54% [range, 17%–75%]). Most vaccine was distributed after peak A(H1N1)pdm09 transmission in the region. The frequency and severity of adverse events were consistent with those recorded after other inactivated influenza vaccines. Pandemic preparedness plans will need to include strategies to ensure more-rapid procedures to identify vaccine supplies and distribute and import vaccines to countries that may bear the brunt of a future pandemic. [ABSTRACT FROM AUTHOR]