In a placebo-controlled, phase 2–3 trial, one dose of mRNA-1345 led to a lower incidence of RSV disease among adults 60 years of age or older. Solicited local and systemic adverse reactions occurred ...more often with the vaccine.
Background Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only ...reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce. Methods We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models. Results We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs 95% CI: 0.8, 1.6) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection. Conclusion In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of ...causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls. Methods. In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. Results. The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. Conclusions. Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.
Abstract
Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in Southeast Asia. Several studies have suggested that antibody persistence after HEV infection may be transient, possibly ...increasing the risk of reinfection and contributing to the frequency of outbreaks in HEV-endemic regions. The specific conditions under which antibodies to HEV are lost, or “seroreversion” occurs, are poorly understood. Here, 100 participants from population-based studies in rural Bangladesh were revisited in 2015, 10 years after a documented HEV infection, to examine long-term antibody persistence. Twenty percent (95% confidence interval: 12.0, 28.0) of the participants no longer had detectable antibodies at follow-up, suggesting that antibodies generally persist for at least a decade after infection in rural Bangladesh. Persons who were seronegative at follow-up were generally younger at infection than those who remained positive (14.4 years vs. 33.6 years; P < 0.0001). This age-dependent antibody loss could partially explain cross-sectional seroprevalence data from Southeast Asia, where children have reportedly low antibody prevalence. The results of this study provide new insight into the immunological persistence of HEV infection in a micronutrient-deficient rural population of South Asia, highlighting the importance of age at infection in the ability to produce long-lasting antibodies against HEV.
Poliomyelitis infection continues to be endemic in few countries despite rigorous efforts for eradication. A new Bivalent Oral Polio Vaccine (BBio bOPV) was tested in a Phase III Clinical study.
An ...observer blind, randomized, controlled clinical study was conducted comparing BBio bOPV with a licensed bOPV (SII bOPV). Initially in Part 1, 40 children 5–6 years of age were given a single dose of either vaccine in 1:1 ratio. In Part 2, 1080 infants of 6–8 weeks of age were received in 1:1:1:1 ratio one of the 3 lots of BBio bOPV or SII bOPV at 6, 10 and 14 weeks of age. Blood samples were collected to assess neutralizing antibody responses against Polio Type 1 and 3 viruses. Safety of the vaccines were recorded.
All children were seroprotected against both Type 1 and Type 3 polioviruses post-vaccination. More than 96% of the infants demonstrated seroconversion as well as seroprotection against both types of polioviruses. The geometric mean titres (GMT) for Type 1 and Type 3 antibodies were comparable between the groups. The 3 lots of BBio bOPV generated similar GMTs of Type 1 and Type 3 antibodies. In total 387 participants reported at least one adverse event and 18 serious adverse events. None of these events were vaccine related.
The new bOPV vaccine demonstrated immunogenicity that was non-inferior to a licensed bOPV vaccine. Consistency in immune response by 3 consecutively manufactured lots was also demonstrated. The vaccine did not cause any adverse event.
Clinicaltrials.gov.identifier: NCT02766816.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background
Several studies have shown that inactivated, whole-cell oral cholera vaccines (OCVs) confer both direct protection on vaccinees and herd protection on populations. Because our ...earlier cluster-randomized effectiveness trial (CRT) in urban Bangladesh failed to detect OCV herd protection, we reanalysed the trial to assess whether herd effects were masked in our original analysis.
Methods
A total of 267 270 persons were randomized to 90 approximately equal-sized clusters. In 60 clusters persons aged 1 year and older were eligible to receive OCV and in 30 clusters persons received no intervention and served as controls. We analysed OCV protection against severely dehydrating cholera for the entire clusters, as in our original analysis, and for subclusters consisting of residents of innermost households. We hypothesized that if OCV herd protection was attenuated by cholera transmission into the clusters from the outside in this densely populated setting, herd protection would be most evident in the innermost households.
Results
During 2 years of follow-up of all residents of the clusters, total protection (protection of OCV recipients relative to control residents) was 58% 95% confidence interval (CI): 43%, 70%; P<0.0001, indirect protection (protection of non-OCV recipients in OCV clusters relative to control participants) was 16% (95% CI: –20%, 41%; P=0.35) and overall OCV protection (protection of all residents in the OCV clusters relative to control residents) was 46% (95% CI: 30%, 59%; P<0.0001). Analyses of the inner 75% and 50% households of the clusters showed similar findings. However, total protection was 75% (95% CI: 50%, 87%, P<0.0001), indirect protection 52% (95% CI: –9%, 79%; P=0.08) and overall protection 72% (95% CI: 49%, 84%; P<0.0001) for the innermost 25% households.
Conclusion
Consistent with past studies, substantial OCV herd protective effects were identified, but were unmasked only by analysing innermost households of the clusters. Caution is needed in defining clusters for analysis of vaccine herd effects in CRTs of vaccines.
Abstract
Background
Typhoid fever contributes to approximately 135 000 deaths annually. Achievable improvements in household water, sanitation, and hygiene (WASH) combined with vaccination using ...typhoid conjugate vaccines (TCVs) may be an effective preventive strategy. However, little is known about how improved WASH and vaccination interact to lower the risk of typhoid.
Methods
A total of 61 654 urban Bangladeshi children aged 9 months to <16 years, residing in 150 clusters with a baseline population of 205 760 residents, were randomized 1:1 by cluster to Vi-tetanus toxoid TCV or Japanese encephalitis (JE) vaccine. Surveillance for blood culture–confirmed typhoid fever was conducted over 2 years. Existing household WASH status was assessed at baseline as Better or Not Better using previously validated criteria. The reduction in typhoid risk among all residents associated with living in TCV clusters, Better WASH households, or both was evaluated using mixed-effects Poisson regression models.
Results
The adjusted reduced risk of typhoid among all residents living in the clusters assigned to TCV was 55% (95% confidence interval CI, 43%–65%; P < .001), and that of living in Better WASH households, regardless of cluster, was 37% (95% CI, 24%–48%; P < .001). The highest risk of typhoid was observed in persons living in households with Not Better WASH in the JE clusters. In comparison with these persons, those living in households with Better WASH in the TCV clusters had an adjusted reduced risk of 71% (95% CI, 59%–80%; P < .001).
Conclusions
Implementation of TCV programs combined with achievable and culturally acceptable household WASH practices were independently associated with a significant reduction in typhoid risk.
Clinical Trials Registration
ISRCTN11643110.
Better preexisting household water, sanitation, and hygiene and delivering Vi-TT vaccine act independently to reduce typhoid risk, so that the combination of both yields greater protection against typhoid at the population level (71%) than either vaccination (55%) or improved WASH alone (37%).
Abstract
Background
The true burden of lower respiratory tract infections (LRTIs) due to respiratory syncytial virus (RSV) remains unclear. This study aimed to provide more robust, multinational data ...on RSV-LRTI incidence and burden in the first 2 years of life.
Methods
This prospective, observational cohort study was conducted in Argentina, Bangladesh, Canada, Finland, Honduras, South Africa, Thailand, and United States. Children were followed for 24 months from birth. Suspected LRTIs were detected via active (through regular contacts) and passive surveillance. RSV and other viruses were detected from nasopharyngeal swabs using PCR-based methods.
Results
Of 2401 children, 206 (8.6%) had 227 episodes of RSV-LRTI. Incidence rates (IRs) of first episode of RSV-LRTI were 7.35 (95% confidence interval CI, 5.88–9.08), 5.50 (95% CI, 4.21–7.07), and 2.87 (95% CI, 2.18–3.70) cases/100 person-years in children aged 0–5, 6–11, and 12–23 months. IRs for RSV-LRTI, severe RSV-LRTI, and RSV hospitalization tended to be higher among 0–5 month olds and in lower-income settings. RSV was detected for 40% of LRTIs in 0–2 month olds and for approximately 20% of LRTIs in older children. Other viruses were codetected in 29.2% of RSV-positive nasopharyngeal swabs.
Conclusions
A substantial burden of RSV-LRTI was observed across diverse settings, impacting the youngest infants the most.
Clinical Trials Registration. NCT01995175.
In a prospective, observational cohort study conducted in 8 countries across diverse settings, we found that RSV-LRTI burden is substantial during the first 2 years of life and tends to be higher among 0–5 month olds and in lower-income settings.
Graphical Abstract
Graphical Abstract
Lay Summary
Respiratory syncytial virus (RSV) is a common pathogen that causes respiratory illnesses. Although symptoms are usually mild, young children can have more serious diseases such as bronchiolitis and pneumonia. The number of children with RSV illnesses and the need for health care differ by country and are likely underestimated. In a study conducted in 8 countries, we followed 2401 children from birth to 2 years to determine the frequency of lower respiratory tract infections (LRTIs) and hospitalizations due to RSV. We found that 206 children had these infections. Approximately 7 in 100 children had an RSV-LRTI in the first 6 months of life. Furthermore, the youngest children had more serious symptoms and were hospitalized more often than children older than 6 months. While RSV-LRTI incidence and hospitalization rates varied among countries, they were higher in low- or middle-income countries or regions than in high-income countries. We found that approximately 1 in 3 children with RSV-LRTIs also had other viruses that could cause respiratory illness. These results show that children younger than 2 years are greatly affected by RSV, especially in low- and middle-income countries. Programs to prevent RSV infections in young children around the world would likely bring health benefits.
Abstract
Informal slums are growing exponentially in the developing world and these will serve as the breeding ground for a future global pandemic. Virtually every sustainable development goal is ...unmet in slums around the globe thus we must act now to divert a global humanitarian crisis.
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