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.

Pilot to evaluate the feasibility of measuring seasonal influenza vaccine effectiveness using surveillance platforms in Central-America, 2012.

BACKGROUND: Since 2004, the uptake of seasonal influenza vaccines in Latin America and the Caribbean has markedly increased. However, vaccine effectiveness (VE) is not routinely measured in the region. We assessed the feasibility of using routine surveillance data collected by sentinel hospitals to estimate influenza VE during 2012 against laboratory-confirmed influenza hospitalizations in Costa-Rica, El Salvador, Honduras and Panama. We explored the completeness of variables needed for VE estimation. METHODS: We conducted the pilot case-control study at 23 severe acute respiratory infections (SARI) surveillance hospitals. Participant inclusion criteria included children 6 months-11 years and adults ≥60 years targeted for vaccination and hospitalized for SARI during January-December 2012. We abstracted information needed to estimate target group specific VE (i.e., date of illness onset and specimen collection, preexisting medical conditions, 2012 and 2011 vaccination status and date, and pneumococcal vaccination status for children and adults) from SARI case-reports and for children ≤9 years, inquired about the number of annual vaccine doses given. A case was defined as an influenza virus positive by RT-PCR in a person with SARI, while controls were RT-PCR negative. We recruited 3 controls per case from the same age group and month of onset of symptoms. RESULTS: We identified 1,186 SARI case-patients (342 influenza cases; 849 influenza-negative controls), of which 994 (84 %) had all the information on key variables sought. In 893 (75 %) SARI case-patients, the vaccination status field was missing in the SARI case-report forms and had to be completed using national vaccination registers (36 %), vaccination cards (30 %), or other sources (34 %). After applying exclusion criteria for VE analyses, 541 (46 %) SARI case-patients with variables necessary for the group-specific VE analyses were selected (87 cases, 236 controls among children; 64 cases, 154 controls among older adults) and were insufficient to provide precise regional estimates (39 % for children and 25 % for adults of minimum sample size needed). CONCLUSIONS: Sentinel surveillance networks in middle income countries, such as some Latin American and Caribbean countries, could provide a simple and timely platform to estimate regional influenza VE annually provided SARI forms collect all necessary information.

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.