Impact of Vaccination With the SCB-2019 Coronavirus Disease 2019 Vaccine on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Household Contact Study in the Philippines.

BACKGROUND: An exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared the occurrence of confirmed COVID-19 infections between households and household contacts of infected SPECTRA placebo or SCB-2019 recipients. METHODS: SPECTRA participants at 8 study sites in the Philippines who developed real-time reverse transcriptase-polymerase chain reaction (rRT-PCR)-confirmed COVID-19 were contacted by a study team blinded to assignment of index cases to vaccine or placebo groups to enroll in this household transmission study. Enrolled households and household contacts were monitored for 3 weeks using rRT-PCR and anti-SARS-CoV-2 N-antigen IgG/IgM testing to detect new COVID-19 infections. RESULTS: One hundred fifty-four eligible COVID-19 index cases (51 vaccinees, 103 placebo) were included. The secondary attack rate per household for symptomatic COVID-19 infection was 0.76% (90% CI: .15-3.90%) if the index case was an SCB-2019 vaccinee compared with 5.88% (90% CI: 3.20-10.8%) for placebo index cases, a relative risk reduction (RRR) of 79% (90% CI: -28% to 97%). The RRR of symptomatic COVID-19 per household member was similar: 84% (90% CI: 28-97%). The impact on attack rates in household members if index cases were symptomatic (n = 130; RRR = 80%; 90% CI: 7-96%) or asymptomatic (n = 24; RRR = 100%; 90% CI: -76% to 100%) was measurable but the low numbers undermine the clinical significance. CONCLUSIONS: In this prospective household contact study vaccination with SCB-2019 reduced SARS-CoV-2 transmission compared with placebo in households and in household members independently of whether or not index cases were symptomatic.

Early Convalescent Plasma Therapy and Mortality Among US Veterans Hospitalized With Nonsevere COVID-19: An Observational Analysis Emulating a Target Trial.

BACKGROUND: Early convalescent plasma transfusion may reduce mortality in patients with nonsevere coronavirus disease 2019 (COVID-19). METHODS: This study emulates a (hypothetical) target trial using observational data from a cohort of US veterans admitted to a Department of Veterans Affairs (VA) facility between 1 May and 17 November 2020 with nonsevere COVID-19. The intervention was convalescent plasma initiated within 2 days of eligibility. Thirty-day mortality was compared using cumulative incidence curves, risk differences, and hazard ratios estimated from pooled logistic models with inverse probability weighting to adjust for confounding. RESULTS: Of 11 269 eligible person-trials contributed by 4755 patients, 402 trials were assigned to the convalescent plasma group. Forty and 671 deaths occurred within the plasma and nonplasma groups, respectively. The estimated 30-day mortality risk was 6.5% (95% confidence interval [CI], 4.0%-9.7%) in the plasma group and 6.2% (95% CI, 5.6%-7.0%) in the nonplasma group. The associated risk difference was 0.30% (95% CI, -2.30% to 3.60%) and the hazard ratio was 1.04 (95% CI, .64-1.62). CONCLUSIONS: Our target trial emulation estimated no meaningful differences in 30-day mortality between nonsevere COVID-19 patients treated and untreated with convalescent plasma. Clinical Trials Registration. NCT04545047.

Estimates of Inactivated Influenza Vaccine Effectiveness Among Children in Senegal: Results From 2 Consecutive Cluster-Randomized Controlled Trials in 2010 and 2011.

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.

Surge of Typhoid Intestinal Perforations as Possible Result of COVID-19-Associated Delays in Seeking Care, Madagascar.

During the coronavirus disease pandemic, we observed a 6.4-fold increase in typhoid intestinal perforation incidence in Antananarivo, Madagascar. Thirteen perforations occurred within 6 months (February 2020-July 2020), compared with 13 perforations during the previous 41 months (August 2016-January 2020). The increase may be attributable to delayed healthcare seeking during the pandemic.

Impact of Rotavirus Vaccine Introduction in Children Less Than 2 Years of Age Presenting for Medical Care With Diarrhea in Rural Matlab, Bangladesh.

BACKGROUND: Following the conclusion of a human rotavirus vaccine (HRV) cluster-randomized, controlled trial (CRT) in Matlab, Bangladesh, HRV was included in Matlab's routine immunization program. We describe the population-level impact of programmatic rotavirus vaccination in Bangladesh in children <2 years of age. METHODS: Interrupted time series were used to estimate the impact of HRV introduction. We used diarrheal surveillance collected between 2000 and 2014 within the 2 service delivery areas (International Centre for Diarrhoeal Disease Research, Bangladesh [icddr,b] service area [ISA] and government service area [GSA]) of the Matlab Health and Demographic Surveillance System, administered by icddr,b. Age group-specific incidence rates were calculated for both rotavirus-positive (RV+) and rotavirus-negative (RV-) diarrhea diagnoses of any severity presenting to the hospital. We used 2 models to assess the impact within each service area: Model 1 used the pre-vaccine time period in all villages (HRV- and control-only) and Model 2 combined the pre-vaccine time period and the CRT time period, using outcomes from control-only villages. RESULTS: Both models demonstrated a downward trend in RV+ diarrheal incidences in the ISA villages during 3.5 years of routine HRV use, though only Model 2 was statistically significant. Significant impacts of HRV on RV+ diarrhea incidences in GSA villages were not observed in either model. Differences in population-level impacts between the 2 delivery areas may be due to the varied rotavirus vaccine coverage and presentation rates to the hospital. CONCLUSIONS: This study provides initial evidence of the population-level impact of rotavirus vaccines in children <2 years of age in Matlab, Bangladesh. Further studies are needed of the rotavirus vaccine impact after the nationwide introduction in Bangladesh.

Effectiveness of Seasonal Influenza Vaccination in Children in Senegal During a Year of Vaccine Mismatch: A Cluster-randomized Trial.

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.

Effectiveness of a live oral human rotavirus vaccine after programmatic introduction in Bangladesh: A cluster-randomized trial.

BACKGROUND: Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO's Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia. METHODS AND FINDINGS: In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective) was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point estimate for total effectiveness was higher against ARD during the first year of life than during the second (45.2% versus 28.9%), but estimates for the second year of life lacked precision and did not reach statistical significance. Indirect effects were not detected. To check for bias in presentation to treatment facilities, we evaluated the effectiveness of HRV against acute diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI, -46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious adverse events were identified among recipients of HRV, but none were considered related to receipt of study vaccine. The main limitation of this study is that it was an open-label study with an observed-only control group (no placebo). CONCLUSIONS: The two-dose HRV rotavirus vaccination program significantly reduced medically attended ARD in this low-resource population in Asia. Protection among vaccinees was similar to that in other low-resource settings. In low-resource populations with high rotavirus incidence, large-scale vaccination across a wide population may be required to obtain the full benefit of rotavirus vaccination, including indirect effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00737503.

Hemagglutinin Gene Clade 3C.2a Influenza A(H3N2) Viruses, Alachua County, Florida, USA, 2014-15.

Influenza A(H3N2) strains isolated during 2014-15 in Alachua County, Florida, USA, belonged to hemagglutinin gene clade 3C.2a. High rates of influenza-like illness and confirmed influenza cases in children were associated with a decrease in estimated vaccine effectiveness. Illnesses were milder than in 2013-14; severe cases were concentrated in elderly patients with underlying diseases.

Hospital Volume of Emergency General Surgery and its Impact on Inpatient Mortality for Geriatric Patients: Analysis From 3994 Hospitals.

BACKGROUND: Previous investigations have shown a positive association between hospital volume of operations and clinical outcomes. However, it is unclear whether such relationships also apply to emergency surgery. We sought to examine the association between hospital case volume and inpatient mortality for 7 common emergency general surgery (EGS) operations among geriatric patients. METHODS: This is a population based retrospective cohort study using the Centers of Medicare and Medicaid Services (CMS) Limited Dataset Files (LDS) from 2011 to 2013. The 7 most common emergency surgeries included (1) partial colectomy, (2) small-bowel resection (SBR), (3) cholecystectomy, (4) appendectomy, (5) lysis of adhesions (LOA), (6) operative management of peptic ulcer disease (PUD), and (7) laparotomy with the primary outcome being inpatient mortality. Risk-adjusted inpatient mortality was plotted against operative volume. Subsequently an operative volume threshold was calculated using a best fit regression method. Based on these estimates, high- and low-volume hospitals were compared to examine significance of outcomes. Significance was defined as P-value < .05. RESULTS: The final cohort comprised of 414 779 patients from 3994 hospitals. The standardized mortality ratio (SMR) for high-volume centers were lower in 6 out of 8 surgeries examined. Small-bowel resection and partial colectomy operations had a significant decrease in mortality based on a volume threshold. CONCLUSION: We observed decreased mortality with higher surgical volume for small-bowel resection and partial colectomy operations. Such differences may be related to practice patterns during the perioperative period, as complications related to the perioperative care were significantly lower for high-volume centers.

Early Outcomes of SARS-CoV-2 Infection in a Multisite Prospective Cohort of Inpatient Veterans.

Background: Over 870 000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have occurred among Veterans Health Administration users, and 24 000 have resulted in death. We examined early outcomes of SARS-CoV-2 infection in hospitalized veterans. Methods: In an ongoing, prospective cohort study, we enrolled veterans age ≥18 tested for SARS-CoV-2 and hospitalized at 15 Department of Veterans Affairs medical centers between February 2021 and June 2022. We estimated adjusted odds ratios (aORs), adjusted incidence rate ratios (aIRRs), and adjusted hazard ratios (aHRs) for maximum illness severity within 30 days of study entry (defined using the 4-category VA Severity Index for coronavirus disease 2019 [COVID-19]), as well as length of hospitalization and rehospitalization within 60 days, in relationship with demographic characteristics, Charlson comorbidity index (CCI), COVID-19 vaccination, and calendar period of enrollment. Results: The 542 participants included 329 (61%) who completed a primary vaccine series (with or without booster; "vaccinated"), 292 (54%) enrolled as SARS-CoV-2-positive, and 503 (93%) men, with a mean age of 64.4 years. High CCI scores (≥5) occurred in 61 (44%) vaccinated and 29 (19%) unvaccinated SARS-CoV-2-positive participants. Severe illness or death occurred in 29 (21%; 6% died) vaccinated and 31 (20%; 2% died) unvaccinated SARS-CoV-2-positive participants. SARS-CoV-2-positive inpatients per unit increase in CCI had greater multivariable-adjusted odds of severe illness (aOR, 1.21; 95% CI, 1.01-1.45), more hospitalization days (aIRR, 1.06; 95% CI, 1.03-1.10), and rehospitalization (aHR, 1.07; 95% CI, 1.01-1.12). Conclusions: In a cohort of hospitalized US veterans with SARS-CoV-2 infection, those with a higher CCI had more severe COVID-19 illness, more hospital days, and rehospitalization, after adjusting for vaccination status, age, sex, and calendar period.

Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics.

The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10-27%. New diagnostics reduce incidence by 13-42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people.

Rice fortification: an emerging opportunity to contribute to the elimination of vitamin and mineral deficiency worldwide.

Vitamin and mineral deficiencies are ranked among the top causes of poor health and disability in the world. These deficiencies damage developing brains, impair learning ability, increase susceptibility to infections, and reduce the work productivity of nations. Food fortification is a sustainable, cost-effective approach to reducing vitamin and mineral deficiency. As the staple food for an estimated 3 billion people, rice has the potential to fill an obvious gap in current fortification programs. In recent years, new technologies have produced fortified rice kernels that are efficacious in reducing vitamin and mineral deficiency. There are opportunities to fortify a significant share of rice that comes from large mills supplying centralized markets and national welfare programs in major rice-growing countries. The rice export markets, which handle 30 million MT of rice annually, also present a key fortification opportunity. The cost of fortifying rice is only 1.5% to 3% of the current retail price of rice. Countries that mandate rice fortification have the strongest evidence for achieving wide coverage and impact. The Rice Fortification Resource Group (RiFoRG), a global network of public and private partners that offers technical and advocacy support for rice fortification, has a vision of promoting rice fortification worldwide. It has a targeted approach, engaging multisector partners in key countries where the opportunities are greatest and there is receptivity to early adoption of large-scale rice fortification. The challenges are real, the imperative to address them is powerful, and the opportunities to deliver the promise of rice fortification are clear.

Using social contact data to improve the overall effect estimate of a cluster-randomized influenza vaccination program in Senegal.

This study estimates the overall effect of two influenza vaccination programs consecutively administered in a cluster-randomized trial in western Senegal over the course of two influenza seasons from 2009-2011. We apply cutting-edge methodology combining social contact data with infection data to reduce bias in estimation arising from contamination between clusters. Our time-varying estimates reveal a reduction in seasonal influenza from the intervention and a nonsignificant increase in H1N1 pandemic influenza. We estimate an additive change in overall cumulative incidence (which was 6.13% in the control arm) of -0.68 percentage points during Year 1 of the study (95% CI: -2.53, 1.18). When H1N1 pandemic infections were excluded from analysis, the estimated change was -1.45 percentage points and was significant (95% CI, -2.81, -0.08). Because cross-cluster contamination was low (0-3% of contacts for most villages), an estimator assuming no contamination was only slightly attenuated (-0.65 percentage points). These findings are encouraging for studies carefully designed to minimize spillover. Further work is needed to estimate contamination - and its effect on estimation - in a variety of settings.

Planning for the control of pandemic influenza A (H1N1) in Los Angeles County and the United States.

Mathematical and computer models can provide guidance to public health officials by projecting the course of an epidemic and evaluating control measures. The authors built upon an existing collaboration between an academic research group and the Los Angeles County, California, Department of Public Health to plan for and respond to the first and subsequent years of pandemic influenza A (H1N1) circulation. The use of models allowed the authors to 1) project the timing and magnitude of the epidemic in Los Angeles County and the continental United States; 2) predict the effect of the influenza mass vaccination campaign that began in October 2009 on the spread of pandemic H1N1 in Los Angeles County and the continental United States; and 3) predict that a third wave of pandemic influenza in the winter or spring of 2010 was unlikely to occur. The close collaboration between modelers and public health officials during pandemic H1N1 spread in the fall of 2009 helped Los Angeles County officials develop a measured and appropriate response to the unfolding pandemic and establish reasonable goals for mitigation of pandemic H1N1.

The effect of age on transmission of 2009 pandemic influenza A (H1N1) in a camp and associated households.

BACKGROUND: A major portion of influenza disease burden during the 2009 pandemic was observed among young people. METHODS: We examined the effect of age on the transmission of influenza-like illness associated with the 2009 pandemic influenza A (H1N1) virus (pH1N1) for an April-May 2009 outbreak among youth-camp participants and household contacts in Washington State. RESULTS: An influenza-like illness attack rate of 51% was found among 96 camp participants. We observed a cabin secondary attack rate of 42% (95% confidence interval = 21%-66%) and a camp local reproductive number of 2.7 (1.7-4.1) for influenza-like illness among children (less than 18 years old). Among the 136 contacts in the 41 households with an influenza-like illness index case who attended the camp, the influenza-like illness secondary attack rate was 11% for children (5%-21%) and 4% for adults (2%-8%). The odds ratio for influenza-like illness among children versus adults was 3.1 (1.3-7.3). CONCLUSIONS: The strong age effect, combined with the low number of susceptible children per household (1.2), plausibly explains the lower-than-expected household secondary attack rate for influenza-like illness, illustrating the importance of other venues where children congregate for sustaining community transmission. Quantifying the effects of age on pH1N1 transmission is important for informing effective intervention strategies.

Epidemiology of tornado destruction in rural northern Bangladesh: risk factors for death and injury.

The epidemiology of tornado-related disasters in the developing world is poorly understood. An August 2005 post-tornado cohort study in rural Bangladesh identified elevated levels of death and injury among the elderly (≥ 60 years of age) (adjusted odds ratio (AOR) = 8.9 (95 per cent confidence interval (CI): 3.9-20.2) and AOR = 1.6 (95 per cent CI: 1.4-1.8), respectively), as compared to 15-24 year-olds, and among those outdoors versus indoors during the tornado (AOR = 10.4 (95 per cent CI: 5.5-19.9) and AOR = 6.6 (95 per cent CI: 5.8-7.5), respectively). Females were 1.24 times (95 per cent CI: 1.15-1.33) more likely to be injured than males. Elevated risk of injury was significantly associated with structural damage to the house and tin construction materials. Seeking treatment was protective against death among the injured, odds ratio = 0.08 (95 per cent CI: 0.03-0.21). Further research is needed to develop injury prevention strategies and to address disparities in risk between age groups and between men and women.

Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys.

BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA) Using a Cluster-Randomized Controlled Phase IV Trial: Trial Design and Population Baseline Characteristics.

Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).

Social contact patterns and implications for infectious disease transmission - a systematic review and meta-analysis of contact surveys.

Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focused on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys, we explored how contact characteristics (number, location, duration, and whether physical) vary across income settings. Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income strata on the frequency, duration, and type of contacts individuals made. Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens and the effectiveness of different non-pharmaceutical interventions. Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

Infectious diseases, particularly those caused by airborne pathogens like SARS-CoV-2, spread by social contact, and understanding how people mix is critical in controlling outbreaks. To explore these patterns, researchers typically carry out large contact surveys. Participants are asked for personal information (such as gender, age and occupation), as well as details of recent social contacts, usually those that happened in the last 24 hours. This information includes, the age and gender of the contact, where the interaction happened, how long it lasted, and whether it involved physical touch. These kinds of surveys help scientists to predict how infectious diseases might spread. But there is a problem: most of the data come from high-income countries, and there is evidence to suggest that social contact patterns differ between places. Therefore, data from these countries might not be useful for predicting how infections spread in lower-income regions. Here, Mousa et al. have collected and combined data from 27 contact surveys carried out before the COVID-19 pandemic to see how baseline social interactions vary between high- and lower-income settings. The comparison revealed that, in higher-income countries, the number of daily contacts people made decreased with age. But, in lower-income countries, younger and older individuals made similar numbers of contacts and mixed with all age groups. In higher-income countries, more contacts happened at work or school, while in low-income settings, more interactions happened at home and people were also more likely to live in larger, intergenerational households. Mousa et al. also found that gender affected how long contacts lasted and whether they involved physical contact, both of which are key risk factors for transmitting airborne pathogens. These findings can help researchers to predict how infectious diseases might spread in different settings. They can also be used to assess how effective non-medical restrictions, like shielding of the elderly and workplace closures, will be at reducing transmissions in different parts of the world.