Estimated reductions in hospitalizations and deaths from childhood diarrhea following implementation of rotavirus vaccination in Africa

<p><b>Introduction</b>: Rotavirus is the leading cause of hospitalizations and deaths from diarrhea. 33 African countries had introduced rotavirus vaccines by 2016. We estimate reductions in rotavirus hospitalizations and deaths for countries using rotavirus vaccination in national immunization programs and the potential of vaccine introduction across the continent.</p> <p><b>Areas covered</b>: Regional rotavirus burden data were reviewed to calculate hospitalization rates, and applied to under-5 population to estimate baseline hospitalizations. Rotavirus mortality was based on 2013 WHO estimates. Regional pre-licensure vaccine efficacy and post-introduction vaccine effectiveness studies were used to estimate summary effectiveness, and vaccine coverage was applied to calculate prevented hospitalizations and deaths. Uncertainties around input parameters were propagated using boot-strapping simulations. In 29 African countries that introduced rotavirus vaccination prior to end 2014, 134,714 (IQR 112,321–154,654) hospitalizations and 20,986 (IQR 18,924–22,822) deaths were prevented in 2016. If all African countries had introduced rotavirus vaccines at benchmark immunization coverage, 273,619 (47%) (IQR 227,260–318,102) hospitalizations and 47,741 (39%) (IQR 42,822–52,462) deaths would have been prevented.</p> <p><b>Expert commentary</b>: Rotavirus vaccination has substantially reduced hospitalizations and deaths in Africa; further reductions are anticipated as additional countries implement vaccination. These estimates bolster wider introduction and continued support of rotavirus vaccination programs.</p

Estimated impact of rotavirus vaccine on hospitalizations and deaths from rotavirus diarrhea among children <5 in Asia

<p><b>Background</b>: Of the 215,000 global deaths from rotavirus estimated in 2013, 41% occur in Asian countries. However, despite a recommendation for global rotavirus vaccination since 2009, only eight countries in Asia have introduced the rotavirus vaccine into their national immunization program as of September 2017. To help policy makers assess the potential value of vaccination, we projected the reduction in rotavirus hospitalizations and deaths following a hypothetical national introduction of rotavirus vaccines in all countries in Asia using data on national-level rotavirus mortality, <5 population, rotavirus hospitalizations rates, routine vaccination coverage, and vaccine effectiveness.</p> <p><b>Methods</b>: To quantify uncertainty, we generated 1,000 simulations of these inputs.</p> <p><b>Results</b>: Our model predicted 710,000 fewer rotavirus hospitalizations, a 49% decrease from the 1,452,000 baseline hospitalizations and 35,000 fewer rotavirus deaths, a 40% decrease from the 88,000 baseline deaths if all 43 Asian countries had introduced rotavirus vaccine. Similar reductions were projected in subanalyses by vaccine introduction status, subregion, and birth cohort size.</p> <p><b>Conclusion</b>: Rotavirus vaccines will substantially reduce morbidity and mortality due to rotavirus infections in Asia.</p

Estimated annual number and risk of <i>Cryptosporidium</i>-associated diarrheal episodes, hospitalizations and deaths in Indian children <2 years of age.

<p>The estimates are based on a population of 42,066,431 children comprising <2 years of age in India [per the 2011 Census of India data <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Office1" target="_blank">[30]</a>].</p

Rates and number of deaths due to all-cause diarrhea and <i>Cryptosporidium</i>-associated diarrhea in Indian children <2 years of age.

<p>* Per 1000 children.</p>Δ<p>Per 100,000 children.</p>†<p>Estimates based on a population of 42,066,431 children comprising <2 years of age in India [per the 2011 Census of India data <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Office1" target="_blank">[30]</a>].</p>¶<p>Obtained from the World Health Statistics 2012 data <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-WHO1" target="_blank">[20]</a>.</p>#<p>Obtained from Walker <i>et al.</i> (2013) estimates of diarrhea proportionate mortality in Indian children <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Walker1" target="_blank">[29]</a>.</p>§<p>Obtained from the GBD 2010 estimates <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Lozano1" target="_blank">[28]</a>; 95% CI represents the uncertainty intervals estimated in the GBD 2010 study.</p>‡<p>Obtained by multiplying the unadjusted rate, and upper and lower boundaries of the 95% CI with a factor of 2.5 (to adjust for the increased proportion of diarrheal mortality in Indian children <5 years of age <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Liu1" target="_blank">[1]</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Walker1" target="_blank">[29]</a>).</p

Details of Vellore-based studies used as primary data sources for the estimation of cryptosporidial disease burden in Indian children.

<p>* This was a multi-centric study. Data on diarrhea-related hospitalizations among the 1500 children recruited from rural and urban areas of Vellore district only was available and was used for this analysis.</p>†<p>Estimated indirectly by applying the 2.7% <i>Cryptosporidium</i> detection rate (using microscopy) in hospitalized children <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Ajjampur2" target="_blank">[16]</a> to the all-cause diarrhea hospitalization rate.</p>Δ<p>Rate obtained by multiplying the rate of hospitalization from <i>Cryptosporidium</i>-associated diarrhea using microscopy with a factor of 3 (to adjust for the increased sensitivity of PCR vis-à-vis microscopy <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Ajjampur4" target="_blank">[27]</a>).</p

Burden of all-cause diarrhea and <i>Cryptosporidium</i>-associated diarrhea in Indian children <2 years of age.

<p>* Estimates based on a population of 42,066,431 children comprising <2 years of age in India [per the 2011 Census of India data <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Office1" target="_blank">[30]</a>].</p>†<p>Adjusted for the background rate of asymptomatic cryptosporidiosis.</p

Rates and number of hospitalizations due to all-cause diarrhea and <i>Cryptosporidium</i>-associated diarrhea in Indian children <2 years of age.

<p>* Adjusted for state-specific differences in diarrhea and access to health-care.</p>†<p>Estimates based on a population of 42,066,431 children comprising <2 years of age in India [per the 2011 Census of India data <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003042#pntd.0003042-Office1" target="_blank">[30]</a>].</p

Risk Factors for Death among Children Less than 5 Years Old Hospitalized with Diarrhea in Rural Western Kenya, 2005–2007: A Cohort Study

<div><h3>Background</h3><p>Diarrhea is a leading cause of childhood morbidity and mortality in sub-Saharan Africa. Data on risk factors for mortality are limited. We conducted hospital-based surveillance to characterize the etiology of diarrhea and identify risk factors for death among children hospitalized with diarrhea in rural western Kenya.</p> <h3>Methods and Findings</h3><p>We enrolled all children <5 years old, hospitalized with diarrhea (≥3 loose stools in 24 hours) at two district hospitals in Nyanza Province, western Kenya. Clinical and demographic information was collected. Stool specimens were tested for bacterial and viral pathogens. Bivariate and multivariable logistic regression analyses were carried out to identify risk factors for death. From May 23, 2005 to May 22, 2007, 1,146 children <5 years old were enrolled; 107 (9%) children died during hospitalization. Nontyphoidal <em>Salmonella</em> were identified in 10% (118), <em>Campylobacter</em> in 5% (57), and <em>Shigella</em> in 4% (42) of 1,137 stool samples; rotavirus was detected in 19% (196) of 1,021 stool samples. Among stools from children who died, nontyphoidal <em>Salmonella</em> were detected in 22%, <em>Shigella</em> in 11%, rotavirus in 9%, <em>Campylobacter</em> in 5%, and <em>S</em>. Typhi in <1%. In multivariable analysis, infants who died were more likely to have nontyphoidal <em>Salmonella</em> (adjusted odds ratio [aOR] = 6·8; 95% CI 3·1–14·9), and children <5 years to have <em>Shigella</em> (aOR = 5·5; 95% CI 2·2–14·0) identified than children who survived. Children who died were less likely to be infected with rotavirus (OR = 0·4; 95% CI 0·2–0·8). Further risk factors for death included being malnourished (aOR = 4·2; 95% CI 2·1–8·7); having oral thrush on physical exam (aOR = 2·3; 95% CI 1·4–3·8); having previously sought care at a hospital for the illness (aOR = 2·2; 95% CI 1·2–3·8); and being dehydrated as diagnosed at discharge/death (aOR = 2·5; 95% CI 1·5–4·1). A clinical diagnosis of malaria, and malaria parasites seen on blood smear, were not associated with increased risk of death. This study only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home.</p> <h3>Conclusion</h3><p>Nontyphoidal <em>Salmonella</em> and <em>Shigella</em> are associated with mortality among rural Kenyan children with diarrhea who access a hospital. Improved prevention and treatment of diarrheal disease is necessary. Enhanced surveillance and simplified laboratory diagnostics in Africa may assist clinicians in appropriately treating potentially fatal diarrheal illness.</p> <h3></h3><p> <em>Please see later in the article for the Editors' Summary</em></p> </div

List of the data collected for each of the subsets, and the associated denominators.

a<p>Before initiating analysis data exploration (not shown) was carried out to compare the entire cohort of all enrolled children to the subset of children with available information from Health and Demographic Surveillance System data and no differences were noted.</p>b<p>For the multivariable logistic regression model, <i>n</i> = 84 for children who died and <i>n</i> = 781 for children who survived due to missing data.</p

Clinical information for children <5 y old hospitalized with diarrhea in rural western Kenya (HDSS subset: 85 children who died, 788 children who survived).

a<p>Unadjusted odds ratio from bivariate analysis.</p>b<p>Fisher exact test, and exact 95% CIs reported.</p>c<p>Where available included conjunctivitis, neonatal sepsis, meningitis, respiratory tract infection, pulmonary tuberculosis, sickle-cell disease.</p>d<p>Dehydration on physical exam defined as sunken eyes, loss of skin turgor (slow skin pinch return [≤2 s] or very slow return [>2 s]) or sunken fontenelle.</p>e<p>Fast breathing defined as ≥60 breaths per minute for children 0–<2 mo old, ≥50 breaths per minute for children 2–11 mo, and ≥40 breaths per minute for children 12–59 mo.</p>f<p>Lethargic and comatose were combined as being in a state of coma was rarely reported (<i>n</i> = 2 for children who died, <i>n</i> = 3 for children who survived).</p>g<p>Kruskal-Wallis test.</p>h<p>Cut-off based on the overall median parasite density (19,149 µl), high parasite density was defined as ≥20,000 parasites per µl.</p>i<p>Severe anemia defined as a hemoglobin concentration <5 g/dl.</p>j<p>Diagnoses considered to indicate HIV/AIDS were a diagnosis of immune suppression syndrome, or if a child was documented as being on antiretroviral therapy on their medical records. Classified separately due to non-routine data collection.</p