Disproportionality analysis of reported drug adverse events to assess a potential safety signal for pentavalent vaccine in 2019 in El Salvador.

Detection and surveillance of vaccine safety hazards is a public health staple. In the post-marketing phase, when vaccines are used in mass, it is crucial to monitor potential signals of adverse reactions that may have been missed in the pre-marketing phase. We analysed spontaneous reports of drug adverse events in El Salvador to assess a potential safety signal related to an increase in febrile seizures following the pentavalent (diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae Type B) vaccine in 2019. This was a retrospective observational study of adverse event notifications in the national electronic drug safety database from 2011 to 2019. We performed standard disproportionality analysis computing Proportional Reporting Risk (PRR), Reporting Odds Ratio (ROR), Relative Reporting Ratio (RRR), Chi-squared, and Information Component (IC), comparing the pairing of febrile seizures and pentavalent vaccine to all other drugs and adverse events recorded in 2019. The occurrence of febrile seizures following pentavalent vaccination exceeded the WHO expected rate of six cases × 100 000 doses administered from April 2019, with a maximum of 9.2 in September. IC was 4.3, ORR 421.9 (95% Confidence Interval, CI: 123.8-1437.7), PRR 223.5 (95 %CI: 70.2-710.9), RRR was 19.5. The first booster presented the highest rate (14.6 per 100,000 doses) of febrile seizures, more than double than expected. Rates for 2018 remained below expected. Reports of febrile seizures following pentavalent vaccine were also on the increase globally since 2014, with highest rates in 2018 and 2019. There was a disproportion of febrile seizures notifications following pentavalent in El Salvador in 2019, suggesting the existence of a safety signal. This may be due to the change in provider. Further studies should assess the causes of the increase and compute costs and benefits of this vaccination to determine if switching to a less reactogenic vaccine formulation is indicated.

Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador.

Rotavirus vaccine was introduced in El Salvador in 2006 and is recommended to be given concomitantly with DTP-HepB-Haemophilus influenzae type b (pentavalent) vaccine at ages 2 months (upper age limit 15 weeks) and 4 months (upper age limit 8 months) of age. However, rotavirus vaccination coverage continues to lag behind that of pentavalent vaccine, even in years when national rotavirus vaccine stock-outs have not occurred. We analyzed factors associated with receipt of oral rotavirus vaccine among children who received at least 2 doses of pentavalent vaccine in a stratified cluster survey of children aged 24-59 months conducted in El Salvador in 2011. Vaccine doses included were documented on vaccination cards (94.4%) or in health facility records (5.6%). Logistic regression and survival analysis were used to assess factors associated with vaccination status and age at vaccination. Receipt of pentavalent vaccine by age 15 weeks was associated with rotavirus vaccination (OR: 5.1; 95% CI 2.7, 9.4), and receipt of the second pentavalent dose by age 32 weeks was associated with receipt of two rotavirus vaccine doses (OR: 5.0; 95% CI 2.1-12.3). Timely coverage with the first pentavalent vaccine dose was 88.2% in the 2007 cohort and 91.1% in the 2008 cohort (p=0.04). Children born in 2009, when a four-month national rotavirus vaccine stock-out occurred, had an older median age of receipt of rotavirus vaccine and were less likely to receive rotavirus on the same date as the same dose of pentavalent vaccine than children born in 2007 and 2008. Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage. Survey data suggest that late rotavirus vaccination and co-administration with later doses of pentavalent vaccine among children born in 2009 helped increase rotavirus vaccine coverage following shortages.

Routine childhood vaccination programme coverage, El Salvador, 2011-In search of timeliness.

While assessing immunization programmes, not only vaccination coverage is important, but also timely receipt of vaccines. We estimated both vaccination coverage and timeliness, as well as reasons for non-vaccination, and identified predictors of delayed or missed vaccination, for vaccines of the first two years of age, in El Salvador. We conducted a cluster survey among children aged 23-59 months. Caregivers were interviewed about the child immunization status and their attitudes towards immunization. Vaccination dates were obtained from children immunization cards at home or at health facilities. We referred to the 2006 vaccination schedule for children below two years: one dose of BCG (Bacillus Calmette-Guérin) at birth; rotavirus at two and four months; three doses of pentavalent - DTP (diphtheria-tetanus-pertussis), hepatitis B, and Haemophilus influenzae type b (Hib) - and of oral poliomyelitis vaccine (polio) at two, four, and six months; first MMR (measles-mumps-rubella) at 12 months; and first boosters of DTP and OPV at 18 months. Timeliness was assessed with Kaplan-Meier analysis; Cox and logistic regression were used to identify predictors of vaccination. We surveyed 2550 children. Coverage was highest for BCG (991%; 95% CI: 98.8-99.5) and lowest for rotavirus, especially second dose (86.3%; 95% CI: 84.2-88.4). The first doses of MMR and DTP had 991% (95% CI: 98.5-99.6) and 977% (95% CI: 970-985), respectively. Overall coverage was 837% (95% CI: 81.4-86.0); 96.4% (95% CI: 95.4-97.5), excluding rotavirus. However, only 26.7% (95% CI: 24.7-28.8) were vaccinated within the age interval recommended by the Expanded Programme on Immunization. Being employed and using the bus for transport to the health facility were associated with age-inappropriate vaccinations; while living in households with only two residents and in the "Paracentral", "Occidental", and "Oriental" regions was associated with age-appropriate vaccinations. Vaccination coverage was high in El Salvador, but general timeliness and rotavirus uptake could be improved.

Cluster-sample surveys and lot quality assurance sampling to evaluate yellow fever immunisation coverage following a national campaign, Bolivia, 2007.

OBJECTIVE: To estimate the yellow fever (YF) vaccine coverage for the endemic and non-endemic areas of Bolivia and to determine whether selected districts had acceptable levels of coverage (>70%). METHODS: We conducted two surveys of 600 individuals (25 x 12 clusters) to estimate coverage in the endemic and non-endemic areas. We assessed 11 districts using lot quality assurance sampling (LQAS). The lot (district) sample was 35 individuals with six as decision value (alpha error 6% if true coverage 70%; beta error 6% if true coverage 90%). To increase feasibility, we divided the lots into five clusters of seven individuals; to investigate the effect of clustering, we calculated alpha and beta by conducting simulations where each cluster's true coverage was sampled from a normal distribution with a mean of 70% or 90% and standard deviations of 5% or 10%. RESULTS: Estimated coverage was 84.3% (95% CI: 78.9-89.7) in endemic areas, 86.8% (82.5-91.0) in non-endemic and 86.0% (82.8-89.1) nationally. LQAS showed that four lots had unacceptable coverage levels. In six lots, results were inconsistent with the estimated administrative coverage. The simulations suggested that the effect of clustering the lots is unlikely to have significantly increased the risk of making incorrect accept/reject decisions. CONCLUSIONS: Estimated YF coverage was high. Discrepancies between administrative coverage and LQAS results may be due to incorrect population data. Even allowing for clustering in LQAS, the statistical errors would remain low. Catch-up campaigns are recommended in districts with unacceptable coverage.