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Background: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) RVA vaccine introduction., Methods: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes., Results: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters., Conclusion: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.

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.

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.

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.