Rates of hospitalization and death for all-cause and rotavirus acute gastroenteritis before rotavirus vaccine introduction in Kenya, 2010-2013.

BACKGROUND: Rotavirus vaccine was introduced in Kenya immunization program in July 2014. Pre-vaccine disease burden estimates are important for assessing vaccine impact. METHODS: Children with acute gastroenteritis (AGE) (≥3 loose stools and/or ≥ 1 episode of unexplained vomiting followed by loose stool within a 24-h period), hospitalized in Siaya County Referral Hospital (SCRH) from January 2010 through December 2013 were enrolled. Stool specimens were tested for rotavirus (RV) using an enzyme immunoassay (EIA). Hospitalization rates were calculated using person-years of observation (PYO) from the Health Demographic Surveillance System (HDSS) as a denominator, while adjusting for healthcare utilization at household level and proportion of stool specimen collected from patients who met the case definition at the surveillance hospital. Mortality rates were calculated using PYO as the denominator and number of deaths estimated using total deaths in the HDSS, proportion of deaths attributed to diarrhoea by verbal autopsy (VA) and percent positive for rotavirus AGE (RVAGE) hospitalizations. RESULTS: Of 7760 all-cause hospitalizations among children < 5 years of age, 3793 (49%) were included in the analysis. Of these, 21% (805) had AGE; RV was detected in 143 (26%) of 541 stools tested. Among children < 5 years, the estimated hospitalization rates per 100,000 PYO for AGE and RVAGE were 2413 and 429, respectively. Mortality rate associated with AGE and RVAGE were 176 and 45 per 100,000 PYO, respectively. CONCLUSION: AGE and RVAGE caused substantial health care burden (hospitalizations and deaths) before rotavirus vaccine introduction in Kenya.

Evaluation of case definitions to detect respiratory syncytial virus infection in hospitalized children below 5 years in Rural Western Kenya, 2009-2013.

BACKGROUND: In order to better understand respiratory syncytial virus (RSV) epidemiology and burden in tropical Africa, optimal case definitions for detection of RSV cases need to be identified. METHODS: We used data collected between September 2009 - August 2013 from children aged <5 years hospitalized with acute respiratory Illness at Siaya County Referral Hospital. We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of individual signs, symptoms and standard respiratory disease case definitions (severe acute respiratory illness [SARI]; hospitalized influenza-like illness [hILI]; integrated management of childhood illness [IMCI] pneumonia) to detect laboratory-confirmed RSV infection. We also evaluated an alternative case definition of cough or difficulty breathing plus hypoxia, in-drawing, or wheeze. RESULTS: Among 4714 children hospitalized with ARI, 3810 (81 %) were tested for RSV; and 470 (12 %) were positive. Among individual signs and symptoms, cough alone had the highest sensitivity to detect laboratory-confirmed RSV [96 %, 95 % CI (95-98)]. Hypoxia, wheezing, stridor, nasal flaring and chest wall in-drawing had sensitivities ranging from 8 to 31 %, but had specificities >75 %. Of the standard respiratory case definitions, SARI had the highest sensitivity [83 %, 95 % CI (79-86)] whereas IMCI severe pneumonia had the highest specificity [91 %, 95 % CI (90-92)]. The alternative case definition (cough or difficulty breathing plus hypoxia, in-drawing, or wheeze) had a sensitivity of [55 %, 95 % CI (50-59)] and a specificity of [60 %, 95 % CI (59-62)]. The PPV for all case definitions and individual signs/symptoms ranged from 11 to 20 % while the negative predictive values were >87 %. When we stratified by age <1 year and 1- < 5 years, difficulty breathing, severe pneumonia and the alternative case definition were more sensitive in children aged <1 year [70 % vs. 54 %, p < 0.01], [19 % vs. 11 %, p = 0.01] and [66 % vs. 43 %, p < 0.01] respectively, while non-severe pneumonia was more sensitive [14 % vs. 26 %, p < 0.01] among children aged 1- < 5 years. CONCLUSION: The sensitivity and specificity of different commonly used case definitions for detecting laboratory-confirmed RSV cases varied widely, while the positive predictive value was consistently low. Optimal choice of case definition will depend upon study context and research objectives.

A sham case-control study of effectiveness of DTP-Hib-hepatitis B vaccine against rotavirus acute gastroenteritis in Kenya.

BACKGROUND: In many GAVI-eligible countries, effectiveness of new vaccines will be evaluated by case-control methodology. To inform the design and assess selection bias of a future case-control study of rotavirus vaccine effectiveness (VE) in western Kenya, we performed a sham case-control study evaluating VE of pentavalent vaccine (DTP-Hib-HepB) against rotavirus acute gastroenteritis (AGE). METHODS: From ongoing rotavirus surveillance, we defined cases as children 12 weeks to 23 months old with EIA-confirmed rotavirus AGE. We enrolled one community-based and two hospital-based control groups. We collected vaccination status from cards at enrollment, or later in homes, and evaluated VE by logistic regression. RESULTS: We enrolled 91 cases (64 inpatient, 27 outpatient), 252 non-rotavirus AGE facility-based controls (unmatched), 203 non-AGE facility-based controls (age-matched) and 271 community controls (age-matched). Documented receipt of 3 pentavalent doses was 77% among cases and ranged from 81-86% among controls. One percent of cases and 0-2% of controls had no pentavalent doses. The adjusted odds ratio of three versus zero doses for being a case was 3.27 (95% CI 0.01-1010) for community controls and 0.69 (95% CI 0.06-7.75) for non-rotavirus hospital-based AGE controls, translating to VE of -227% and 31%, respectively, with wide confidence intervals. (No facility-based non-AGE controls were unvaccinated.) Similar results were found for ≥2 pentavalent doses and for severe rotavirus AGE. CONCLUSIONS: The study showed that it is feasible to carry out a real case control in the study area, but this needs to be done as soon as the vaccine is introduced to capture the real impact. Sham case-control or pilot studies before vaccine introduction can be useful in designing case-control VE studies.

High burden of rotavirus gastroenteritis in young children in rural western Kenya, 2010-2011.

BACKGROUND: Diarrhea is a leading cause of hospitalization and death in children <5 years of age. OBJECTIVES: To facilitate evaluation of the impact of rotavirus vaccine introduction in western Kenya, we estimated baseline rates of rotavirus-associated hospitalization and mortality among children <5 years of age. METHODS: From January 2010 to December 2011, we collected demographic, clinical and laboratory data for children <5 years of age seeking care at the district hospital and 2 outpatient facilities within a Health and Demographic Surveillance System (HDSS). Children with acute gastroenteritis (AGE), defined as ≥3 loose stools and/or ≥1 episode of unexplained vomiting followed by loose stool within a 24-hour period, were asked to provide a stool sample for rotavirus ELISA testing. Rates of rotavirus-associated hospitalization and mortality were estimated using time of residence in the HDSS to calculate person-years of observation. To estimate the rotavirus-associated mortality rate, we applied the percentage positive for rotavirus among AGE hospitalizations to verbal autopsy estimates of diarrhea deaths in the HDSS. RESULTS: There were 4991 hospitalizations of children <5 years of age; 1134 (23%) were for AGE and stool specimens were obtained from 790 (70%). Rotavirus was detected in 211 (27%) specimens. Among 4951 <5 outpatient sick visits, 608 (12%) were for AGE; 320 (51%) provided specimens and 62 (20%) were positive for rotavirus. Rotavirus AGE accounted for 501 <5 hospitalizations per 100,000 person-years of observation. Rotavirus-associated <5 mortality was 136 deaths per 100,000 person-years of observation. CONCLUSIONS: Continued surveillance of rotavirus AGE will provide timely data on the population-level impact of rotavirus vaccine following its likely introduction in 2014.