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We initiated a nationwide prospective study to monitor respiratory syncytial virus (RSV)–related pediatric hospitalizations in 46 hospitals throughout the Netherlands between May 2021 and August 2022. We showed year-round RSV transmission in the Netherlands after an initial 2021 summer outbreak. The pattern was unprecedented and distinct from neighboring countries. We extended a dynamic simulation model to evaluate the impact of waning immunity on pediatric RSV hospitalizations in the Netherlands using 4 different scenarios. Our results suggest that the observed continuous RSV transmission pattern could be associated with waning immunity due to the period of very low RSV circulation during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background Although a substantial fraction of the US population was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during December 2021–February 2022, the subsequent evolution of population immunity reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations. Methods Using a Bayesian evidence synthesis model of reported coronavirus disease 2019 (COVID-19) data (diagnoses, hospitalizations), vaccinations, and waning patterns for vaccine- and infection-acquired immunity, we estimate population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States, by location (national, state, county) and week. Results By 9 November 2022, 97% (95%–99%) of the US population were estimated to have prior immunological exposure to SARS-CoV-2. Between 1 December 2021 and 9 November 2022, protection against a new Omicron infection rose from 22% (21%–23%) to 63% (51%–75%) nationally, and protection against an Omicron infection leading to severe disease increased from 61% (59%–64%) to 89% (83%–92%). Increasing first booster uptake to 55% in all states (current US coverage: 34%) and second booster uptake to 22% (current US coverage: 11%) would increase protection against infection by 4.5 percentage points (2.4–7.2) and protection against severe disease by 1.1 percentage points (1.0–1.5). Conclusions Effective protection against SARS-CoV-2 infection and severe disease in November 2022 was substantially higher than in December 2021. Despite this high level of protection, a more transmissible or immune evading (sub)variant, changes in behavior, or ongoing waning of immunity could lead to a new SARS-CoV-2 wave. [ABSTRACT FROM AUTHOR]

Background Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination contribute to population-level immunity against SARS-CoV-2. This study estimated the immunological exposure and effective protection against future SARS-CoV-2 infection in each US state and county over 2020–2021 and how this changed with the introduction of the Omicron variant. Methods We used a Bayesian model to synthesize estimates of daily SARS-CoV-2 infections, vaccination data and estimates of the relative rates of vaccination conditional on infection status to estimate the fraction of the population with (1) immunological exposure to SARS-CoV-2 (ever infected with SARS-CoV-2 and/or received ≥1 doses of a COVID-19 vaccine), (2) effective protection against infection, and (3) effective protection against severe disease, for each US state and county from 1 January 2020 to 1 December 2021. Results The estimated percentage of the US population with a history of SARS-CoV-2 infection or vaccination as of 1 December 2021 was 88.2% (95% credible interval [CrI], 83.6%–93.5%). Accounting for waning and immune escape, effective protection against the Omicron variant on 1 December 2021 was 21.8% (95% CrI, 20.7%–23.4%) nationally and ranged between 14.4% (13.2%–15.8%; West Virginia) and 26.4% (25.3%–27.8%; Colorado). Effective protection against severe disease from Omicron was 61.2% (95% CrI, 59.1%–64.0%) nationally and ranged between 53.0% (47.3%–60.0%; Vermont) and 65.8% (64.9%–66.7%; Colorado). Conclusions While more than four-fifths of the US population had prior immunological exposure to SARS-CoV-2 via vaccination or infection on 1 December 2021, only a fifth of the population was estimated to have effective protection against infection with the immune-evading Omicron variant. [ABSTRACT FROM AUTHOR]

Background The short-term effectiveness of a 2-dose regimen of the BioNTech/Pfizer BNT162b2 vaccine for adolescents has been demonstrated. However, little is known about the long-term effectiveness in this age group. It is known, however, that waning of vaccine-induced immunity against infection in adult populations is evident within a few months. Methods Leveraging the database of Maccabi Healthcare Services (MHS), we conducted a matched case-control design for evaluating the association between time since vaccination and the incidence of infections, where 2 outcomes were evaluated: documented SARS-CoV-2 infection (regardless of symptoms) and symptomatic infection (COVID-19). Cases were defined as individuals aged 12–16 with a positive polymerase chain reaction (PCR) test occurring between 15 June and 8 December 2021, when the Delta variant was dominant in Israel. Controls were adolescents who had not tested positive previously. Results We estimated a peak vaccine effectiveness between 2 weeks and 3 months following receipt of the second dose, with 85% (95% confidence interval [CI]: 84–86%) and 90% (95% CI: 89–91%) effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19), respectively. However, in line with findings for adults, waning effectiveness was evident. Long-term protection was reduced to 73% (95% CI: 68–77%) against infection and 79% (95% CI: 73–83%) against COVID-19 3–5 months after the second dose and waned to 53% (95% CI: 46–60%) against infection and 66% (95% CI: 59–72%) against COVID-19 after 5 months. Conclusions Although vaccine-induced protection against both infection and COVID-19 continues over time in adolescents, the protection wanes with time since vaccination, starting 3 months after inoculation and continuing for more than 5 months. [ABSTRACT FROM AUTHOR]

Background: Estimates of the relative contribution of different pathogens to all-cause diarrhoea mortality are needed to inform global diarrhoea burden models and prioritize interventions. We aimed to investigate and estimate heterogeneity in the case fatality risk (CFR) of different diarrhoeal pathogens.Methods: We conducted a systematic review and meta-analysis of studies that reported cases and deaths for 15 enteric pathogens published between 1990 and 2019. The primary outcome was the pathogen-specific CFR stratified by age group, country-specific under-5 mortality rate, setting, study year and rotavirus vaccine introduction status. We developed fixed-effects and multilevel mixed-effects logistic regression models to estimate the pooled CFR overall and for each pathogen, controlling for potential predictors of heterogeneity.Results: A total of 416 studies met review criteria and were included in the analysis. The overall crude CFR for all pathogens was 0.65%, but there was considerable heterogeneity between and within studies. The overall CFR estimated from a random-effects model was 0.04% (95% CI: 0.026%-0.062%), whereas the pathogen-specific CFR estimates ranged from 0% to 2.7%. When pathogens were included as predictors of the CFR in the overall model, the highest and lowest odds ratios were found for enteropathogenic Escherichia coli (EPEC) [odds ratio (OR) = 3.0, 95% CI: 1.28-7.07] and rotavirus (OR = 0.23, 95% CI: 0.13-0.39), respectively.Conclusion: We provide comprehensive estimates of the CFR across different diarrhoeal pathogens and highlight pathogens for which more studies are needed. The results motivate the need for diarrhoeal interventions and could help prioritize pathogens for vaccine development. [ABSTRACT FROM AUTHOR]

Background: Rotavirus vaccine (Rotarix [RV1]) has reduced diarrhea-associated hospitalizations and deaths in Malawi. We examined the trends in circulating rotavirus genotypes in Malawi over a 22-year period to assess the impact of RV1 introduction on strain distribution.Methods: Data on rotavirus-positive stool specimens among children aged <5 years hospitalized with diarrhea in Blantyre, Malawi before (July 1997-October 2012, n = 1765) and after (November 2012-October 2019, n = 934) RV1 introduction were analyzed. Rotavirus G and P genotypes were assigned using reverse-transcription polymerase chain reaction.Results: A rich rotavirus strain diversity circulated throughout the 22-year period; Shannon (H') and Simpson diversity (D') indices did not differ between the pre- and postvaccine periods (H' P < .149; D' P < .287). Overall, G1 (n = 268/924 [28.7%]), G2 (n = 308/924 [33.0%]), G3 (n = 72/924 [7.7%]), and G12 (n = 109/924 [11.8%]) were the most prevalent genotypes identified following RV1 introduction. The prevalence of G1P[8] and G2P[4] genotypes declined each successive year following RV1 introduction, and were not detected after 2018. Genotype G3 reemerged and became the predominant genotype from 2017 onward. No evidence of genotype selection was observed 7 years post-RV1 introduction.Conclusions: Rotavirus strain diversity and genotype variation in Malawi are likely driven by natural mechanisms rather than vaccine pressure. [ABSTRACT FROM AUTHOR]

Estimates of the reproductive number for novel pathogens, such as severe acute respiratory syndrome coronavirus 2, are essential for understanding the potential trajectory of epidemics and the levels of intervention that are needed to bring the epidemics under control. However, most methods for estimating the basic reproductive number (R 0) and time-varying effective reproductive number (Rt) assume that the fraction of cases detected and reported is constant through time. We explored the impact of secular changes in diagnostic testing and reporting on estimates of R 0 and Rt using simulated data. We then compared these patterns to data on reported cases of coronavirus disease 2019 and testing practices from different states in the United States from March 4, 2020, to August 30, 2020. We found that changes in testing practices and delays in reporting can result in biased estimates of R 0 and Rt. Examination of changes in the daily numbers of tests conducted and the percentages of patients who tested positive might be helpful for identifying the potential direction of bias. Changes in diagnostic testing and reporting processes should be monitored and taken into consideration when interpreting estimates of the reproductive number of coronavirus disease. [ABSTRACT FROM AUTHOR]

Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and coronavirus disease 2019 (COVID-19). We seek to clarify confusion in 3 areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 "mortality rate," each useful for specific purposes; and implications for student return strategies from preschool through university settings. [ABSTRACT FROM AUTHOR]

Quantifying rotavirus shedding among vaccinated individuals will aid understanding of vaccine indirect effects. Serial stool samples were collected from 196 children who presented with rotavirus gastroenteritis to health facilities in Blantyre, Malawi, and were tested for rotavirus using a VP6 semi-quantitative, real-time polymerase chain reaction. The median duration of fecal shedding was 28 days (95% CI, 19-28). The median copy numbers for peak shedding were 1.99 × 107 (interquartile range, 3.39 × 106 to 6.37 × 107). The fecal viral load was positively associated with disease severity and negatively associated with serum anti-rotavirus immunoglobin A. High and persistent rotavirus shedding among vaccinated children with breakthrough disease may contribute to ongoing transmission in this setting. [ABSTRACT FROM AUTHOR]

Background A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of postvaccine serum antirotavirus immunoglobulin A (IgA) as an individual-level immune correlate of protection against rotavirus gastroenteritis. Methods Individual-level data on 5074 infants in 9 GlaxoSmithKline Rotarix Phase 2/3 clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis. Results Seroconversion (IgA ≥ 20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis to age 1 year. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR, 0.04; 95% confidence interval [CI],.01–.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (HR, 0.46; 95% CI,.25–.86). As IgA threshold increased, risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings. Discussion Postvaccination antirotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis to age 1 year. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance. [ABSTRACT FROM AUTHOR]

Despite rotavirus vaccination, diarrhea remains a leading cause of child mortality. We collected stool specimens from 684 children <5 years of age hospitalized with diarrhea (cases) and 527 asymptomatic community controls for 4 years after rotavirus vaccine introduction in Malawi. Specimens were tested for 29 pathogens, using polymerase chain reaction analysis. Three or more pathogens were detected in 71% of cases and 48% of controls. Pathogens significantly associated with diarrhea included rotavirus (in 34.7% of cases and 1.5% of controls), enteric adenovirus (in 29.1% and 2.7%, respectively), Cryptosporidium (in 27.8% and 8.2%, respectively), heat-stable enterotoxin-producing Escherichia coli (in 21.2% and 8.5%, respectively), typical enteropathogenic E. coli (in 18.0% and 8.3%, respectively), and Shigella/enteroinvasive E. coli (in 15.8% and 5.7%, respectively). Additional interventions are required to prevent diarrhea due to rotavirus and other common causal pathogens. [ABSTRACT FROM AUTHOR]

Horizontal transmission of rotavirus vaccine virus may contribute to indirect effects of rotavirus vaccine, but data are lacking from low-income countries. Serial stool samples were obtained from Malawian infants who received 2 doses of monovalent human rotavirus vaccine (RV1) (days 4, 6, 8, and 10 after vaccination) and from their household contacts (8-10 days after vaccine). RV1 vaccine virus in stool was detected using semiquantitative real-time reverse-transcription polymerase chain reaction. RV1 fecal shedding was detected in 41 of 60 vaccinated infants (68%) and in 2 of 147 household contacts (1.4%). Horizontal transmission of vaccine virus within households is unlikely to make a major contribution to RV1 indirect effects in Malawi. [ABSTRACT FROM AUTHOR]

Background Shedding of Salmonella Typhi or Paratyphi in the stool or urine leads to contamination of food or water, which is a prerequisite for transmission of enteric fever. Currently, there are limited data on the effect of vaccination or prior exposure on stool shedding. Methods Six Salmonella Typhi or Paratyphi human challenge studies were conducted between 2011 and 2017. Participants were either unvaccinated or vaccinated with 1 of 4 vaccines: Vi-polysaccharide (Vi-PS), Vi-tetanus-toxoid conjugate vaccine (Vi-TT), live oral Ty21a vaccine, or an experimental vaccine (M01ZH09). Daily stool cultures were collected for 14 days after challenge. Results There were 4934 stool samples collected from 430 volunteers. Participants who received Vi-PS or Vi-TT shed less than unvaccinated participants (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.15–0.77; P =.010 and OR, 0.41; 95% CI, 0.19–0.91, P =.029 for Vi-PS and Vi-TT, respectively). Higher anti-Vi immunoglobulin G titers were associated with less shedding of S. Typhi (P <.0001). A nonsignificant reduction in shedding was associated with Ty21a vaccine (OR, 0.57; 95% CI, 0.27–1.20; P =.140). Individuals previously exposed to S. Typhi shed less than previously unexposed individuals (OR, 0.30; 95% CI, 0.1–0.8; P =.016). Shedding of S. Typhi was more common than S. Paratyphi. Conclusions Prior vaccination with Vi vaccines, or natural infection, reduces onward transmission of S. Typhi. Field trials of Vi-TT should be designed to detect indirect protection, reflecting the consequence of reduced stool shedding observed in the human challenge model. [ABSTRACT FROM AUTHOR]

Background Demonstrating the efficacy of new Vi-conjugate typhoid vaccines is challenging, due to the cost of field trials requiring tens of thousands of participants. New trial designs that use serologically defined typhoid infections (seroefficacy trials) rather than blood culture positivity as a study endpoint may be useful to assess efficacy using small trials. Methods We developed a model for Vi–immunoglobin G antibody responses to a Vi-vaccine, incorporating decay over time and natural boosting due to endemic exposures. From this, we simulated clinical trials in which 2 blood samples were taken during follow-up and the relative risk of a serologically defined typhoid infection (seroefficacy) was computed. We aimed to determine (1) whether seroefficacy trial designs could substantially reduce sample sizes, compared with trials using blood culture–confirmed cases; (3) whether the rate of case detection was higher in seroefficacy trials; and (3) the optimal timing of sample collection. Results The majority (>90%) of blood culture–positive typhoid cases remain unobserved in surveillance studies. In contrast, under-detection in simulated seroefficacy trials of equivalent vaccines was as little as 26%, and estimates of the relative risk of typhoid infection were unbiased. For simulated trials of non-equivalent vaccines, relative risks were slightly inflated by at least 5%, depending on the sample collection times. Seroefficacy trials required as few as 460 participants per arm, compared with 10 000 per arm for trials using blood culture–confirmed cases. Conclusions Seroefficacy trials can establish the efficacy of new conjugate vaccines using small trials that enroll hundreds rather than thousands of participants, and without the need for resource-intensive typhoid fever surveillance programs. [ABSTRACT FROM AUTHOR]

Background Empiric prescribing of antimicrobials in typhoid-endemic settings has increased selective pressure on the development of antimicrobial-resistant Salmonella enterica serovar Typhi. The introduction of typhoid conjugate vaccines (TCVs) in these settings may relieve this selective pressure, thereby reducing resistant infections and improving health outcomes. Methods A deterministic transmission dynamic model was developed to simulate the impact of TCVs on the number and proportion of antimicrobial-resistant typhoid infections and chronic carriers. One-way sensitivity analyses were performed to ascertain particularly impactful model parameters influencing the proportion of antimicrobial-resistant infections and the proportion of cases averted over 10 years. Results The model simulations suggested that increasing vaccination coverage would decrease the total number of antimicrobial-resistant typhoid infections but not affect the proportion of cases that were antimicrobial resistant. In the base-case scenario with 80% vaccination coverage, 35% of all typhoid infections were antimicrobial resistant, and 44% of the total cases were averted over 10 years by vaccination. Vaccination also decreased both the total number and proportion of chronic carriers of antimicrobial-resistant infections. The prevalence of chronic carriers, recovery rates from infection, and relative fitness of resistant strains were identified as crucially important parameters. Conclusions Model predictions for the proportion of antimicrobial resistant infections and number of cases averted depended strongly on the relative fitness of the resistant strain(s), prevalence of chronic carriers, and rates of recovery without treatment. Further elucidation of these parameter values in real-world typhoid-endemic settings will improve model predictions and assist in targeting future vaccination campaigns and treatment strategies. [ABSTRACT FROM AUTHOR]

Background The World Health Organization (WHO) released a position paper in March 2018 calling for integration of a novel typhoid conjugate vaccine (TCV) into routine immunization along with catch-up campaigns for children up to age 15. Gavi, the Vaccine Alliance, has committed funding to help resource-constrained countries introduce this vaccine. In this article, the Typhoid Vaccine Acceleration Consortium forecasts demand if WHO recommendations are followed. Methods We built a model of global TCV introductions between 2020 and 2040 to estimate the demand of the vaccine for 133 countries. We estimated each country's year of introduction by examining its estimated incidence of typhoid fever, its history of introducing new vaccines, and any knowledge we have of its engagement with typhoid prevention, including intention to apply for Gavi funding. Our model predicted use in routine infant vaccination as well as campaigns targeting varying proportions of the unvaccinated population up to 15 years of age. Results Between 2020 and 2025, demand will predominantly come from African countries, many receiving Gavi support. After that, Asian countries generate most demand until 2030, when campaigns are estimated to end. Demand will then track the birth cohort of participating countries, suggesting an annual routine demand between 90 and 100 million doses. Peak demand is likely to occur between 2023 and 2026, approaching 300 million annual doses if campaign implementation is high. Conclusions In our analysis, target population for catch-up campaigns is the main driver of uncertainty. At peak demand, there is some risk of exceeding presently estimated peak production capacity. Therefore, it will be important to carefully coordinate introductions, especially when accompanied by campaigns targeting large proportions of the eligible population. [ABSTRACT FROM AUTHOR]

Vaccinating children with pneumococcal conjugate vaccine (PCV) disrupts transmission, reducing disease rates in unvaccinated adults. When considering changes in vaccine dosing strategies (e.g. removing doses), it is critical to understand which groups of children contribute most to transmission to adults. We used data from Israel (2009–2016) to evaluate how the buildup of vaccine-associated immunity in children was associated with declines in invasive pneumococcal disease (IPD) due to vaccine-targeted serotypes in unimmunized adults. Data on vaccine uptake and prevalence of colonization with PCV-targeted serotypes were obtained from children visiting an emergency department in southern Israel and from surveys of colonization from central Israel. Data on IPD in adults were obtained from a nationwide surveillance study carried out in Israel. We compared the trajectory of decline of IPD due to PCV-targeted serotypes in adults with the decline of colonization prevalence and increase in vaccine-derived protection against pneumococcal carriage among different age groupings of children. The declines in IPD in adults were most closely associated with the declines in colonization and increased vaccination coverage among children in the age range of 36–59 months. This suggests that preschool-aged children, rather than infants, are responsible for maintaining the indirect benefits of PCVs. [ABSTRACT FROM AUTHOR]

Background: Blood culture is the standard diagnostic method for typhoid and paratyphoid (enteric) fever in surveillance studies and clinical trials, but sensitivity is widely acknowledged to be suboptimal. We conducted a systematic review and meta-analysis to examine sources of heterogeneity across studies and quantified the effect of blood volume.Methods: We searched the literature to identify all studies that performed blood culture alongside bone marrow culture (a gold standard) to detect cases of enteric fever. We performed a meta-regression analysis to quantify the relationship between blood sample volume and diagnostic sensitivity. Furthermore, we evaluated the impact of patient age, antimicrobial use, and symptom duration on sensitivity.Results: We estimated blood culture diagnostic sensitivity was 0.59 (95% confidence interval [CI], 0.54-0.64) with significant between-study heterogeneity (I2, 76% [95% CI, 68%-82%]; P < .01). Sensitivity ranged from 0.51 (95% CI, 0.44-0.57) for a 2-mL blood specimen to 0.65 (95% CI, 0.58-0.70) for a 10-mL blood specimen, indicative of a relationship between specimen volume and sensitivity. Subgroup analysis showed significant heterogeneity by patient age and a weak trend towards higher sensitivity among more recent studies. Sensitivity was 34% lower (95% CI, 4%-54%) among patients with prior antimicrobial use and 31% lower after the first week of symptoms (95% CI, 19%-41%). There was no evidence of confounding by patient age, antimicrobial use, symptom duration, or study date on the relationship between specimen volume and sensitivity.Conclusions: The relationship between the blood sample volume and culture sensitivity should be accounted for in incidence and next-generation diagnostic studies. [ABSTRACT FROM AUTHOR]

Enteric fever is a febrile illness, occurring mostly in Asia and Africa, which can present as a severe and possibly fatal disease. Currently, a case fatality rate (CFR) of 1% is assumed when evaluating the global burden of enteric fever. Until now, no meta-analysis has been conducted to summarize mortality from enteric fever. Therefore, we conducted a systematic review and meta-analysis to aggregate all available evidence. We estimated an overall CFR of 2.49% (95% confidence interval, 1.65%–3.75%; n = 44), and a CFR in hospitalized patients of 4.45% (2.85%–6.88%; n = 21 of 44). There was considerably heterogeneity in estimates of the CFR from individual studies. Neither age nor antimicrobial resistance were significant prognostic factors, but limited data were available for these analyses. The combined estimate of the CFR for enteric fever is higher than previously estimated, and the evaluation of prognostic factors, including antimicrobial resistance, urgently requires more data. [ABSTRACT FROM AUTHOR]

Background: Although cholera is considered the quintessential long-cycle waterborne disease, studies have emphasized the existence of short-cycle (food, household) transmission. We investigated singular Danish cholera epidemics (in 1853) to elucidate epidemiological parameters and modes of spread.Methods: Using time series data from cities with different water systems, we estimated the intrinsic transmissibility (R0). Accessing cause-specific mortality data, we studied clinical severity and age-specific impact. From physicians' narratives we established transmission chains and estimated serial intervals.Results: Epidemics were seeded by travelers from cholera-affected cities; initial transmission chains involving household members and caretakers ensued. Cholera killed 3.4%-8.9% of the populations, with highest mortality among seniors (16%) and lowest in children (2.7%). Transmissibility (R0) was 1.7-2.6 and the serial interval was estimated at 3.7 days (95% confidence interval, 2.9-4.7 days). The case fatality ratio (CFR) was high (54%-68%); using R0 we computed an adjusted CFR of 4%-5%.Conclusions: Short-cycle transmission was likely critical to early secondary transmission in historic Danish towns. The outbreaks resembled the contemporary Haiti outbreak with respect to transmissibility, age patterns, and CFR, suggesting a role for broader hygiene/sanitation interventions to control contemporary outbreaks. [ABSTRACT FROM AUTHOR]

Background: Observational studies in socioeconomically distinct populations have yielded conflicting conclusions about the strength of naturally acquired immunity against rotavirus gastroenteritis (RVGE), mirroring vaccine underperformance in low-income countries. We revisited birth cohort studies to understand naturally acquired protection against rotavirus infection and RVGE.Methods: We reanalyzed data from 200 Mexican and 373 Indian children followed from birth to 2 and 3 years of age, respectively. We reassessed protection against RVGE, decomposing the incidence rate into the rate of rotavirus infection and the risk of RVGE given infection, and tested for serum antibody correlates of protection using regression models.Results: Risk for primary, secondary, and subsequent infections to cause RVGE decreased per log-month of age by 28% (95% confidence interval [CI], 12%-41%), 69% (95% CI, 30%-86%), and 64% (95% CI, -186% to 95%), respectively, in Mexico City, and by 10% (95% CI, -1% to 19%), 51% (95% CI, 41%-59%) and 67% (95% CI, 57%-75%), respectively, in Vellore. Elevated serum immunoglobulin A and immunoglobulin G titers were associated with partial protection against rotavirus infection. Associations between older age and reduced risk for RVGE or moderate-to-severe RVGE given infection persisted after controlling for antibody levels.Conclusions: Dissimilar estimates of protection against RVGE may be due in part to age-related, antibody-independent risk for rotavirus infections to cause RVGE. [ABSTRACT FROM AUTHOR]

The article examines the immunological phenomenon of rotavirus epidemiology. Challenges in the progression to reduce and burden of rotavirus disease and recommendation pf rotavirus vaccination to prevent deaths and severe diarrheal disease, is highlighted. Also investigated are the responses of vaccines in children with high-income settings compared to low-income settings.

Background. Multiyear epidemics of Salmonella enterica serovar Typhi have been reported from countries across eastern and southern Africa in recent years. In Blantyre, Malawi, a dramatic increase in typhoid fever cases has recently occurred, and may be linked to the emergence of the H58 haplotype. Strains belonging to the H58 haplotype often exhibit multidrug resistance and may have a fitness advantage relative to other Salmonella Typhi strains. Methods. To explore hypotheses for the increased number of typhoid fever cases in Blantyre, we fit a mathematical model to culture-confirmed cases of Salmonella enterica infections at Queen Elizabeth Central Hospital, Blantyre. We explored 4 hypotheses: (1) an increase in the basic reproductive number (R0) in response to increasing population density; (2) a decrease in the incidence of cross-immunizing infection with Salmonella Enteritidis; (3) an increase in the duration of infectiousness due to failure to respond to first-line antibiotics; and (4) an increase in the transmission rate following the emergence of the H58 haplotype. Results. Increasing population density or decreasing cross-immunity could not fully explain the observed pattern of typhoid emergence in Blantyre, whereas models allowing for an increase in the duration of infectiousness and/or the transmission rate of typhoid following the emergence of the H58 haplotype provided a good fit to the data. Conclusions. Our results suggest that an increase in the transmissibility of typhoid due to the emergence of drug resistance associated with the H58 haplotype may help to explain recent outbreaks of typhoid in Malawi and similar settings in Africa. [ABSTRACT FROM AUTHOR]

Background. Respiratory syncytial virus (RSV) is a major cause of respiratory infections among young children and can lead to severe disease among some infants. Infants at high risk for severe RSV infection receive monthly injections of a prophylactic monoclonal antibody during the RSV season based on national guidelines. We considered whether a reduced- dose schedule tailored to the local RSV season in the continental United States would provide adequate protection. Methods. Hospitalization data for 1942 counties across 38 states from 1997 to 2009 were obtained from the State Inpatient Databases (Agency for Healthcare Research and Quality).We assessed the timing of RSV epidemics at the county and state levels using a 2-stage hierarchical Bayesian change point model. We used a simple summation approach to estimate the fraction of RSV cases that occur during the window of protection provided by initiating RSV prophylaxis during different weeks of the year. Results. The timing of RSV epidemic onset varied significantly at the local level. Nevertheless, the national recommendations for initiation of prophylaxis provided near-optimal coverage of the RSV season in most of the continental United States. Reducing from 5 to 4 monthly doses (with a later initiation) provides near-optimal coverage (<5% decrease in coverage) in most settings. Earlier optimal dates for initiating 4 doses of prophylaxis were associated with being farther south and east, higher population density, and having a higher percentage of the population that was black orHispanic. Conclusions. A 4-dose schedule of prophylactic injections timed with local RSV epidemics could provide protection comparable to 5 doses and could be considered as a way to improve the cost-effectiveness of prophylaxis. [ABSTRACT FROM AUTHOR]