Enhanced surveillance for adverse events following immunization during the 2019 typhoid conjugate vaccine campaign in Harare, Zimbabwe

Abstract

Background: During February 25-March 4, 2019, Zimbabwe's Ministry of Health and Child Care conducted an emergency campaign using 342,000 doses of typhoid conjugate vaccine (TCV) targeting individuals 6 months-15 years of age in eight high-risk suburbs of Harare and up to 45 years of age in one suburb of Harare. The campaign represented the first use of TCV in Africa outside of clinical trials.

Methods: Three methods were used to capture adverse events during the campaign and for 42 days following the last dose administered: (1) active surveillance in two Harare hospitals, (2) national passive surveillance, and (3) a post-campaign coverage survey.

Results: Thirty-nine adverse events were identified during active surveillance, including 19 seizure cases (16 were febrile), 16 hypersensitivity cases, 1 thrombocytopenia case, 1 anaphylaxis case, and two cases with two conditions. Only 21 (54%) of 39 patients were hospitalized and 38 recovered without sequelae. Attack rates per 100,000 TCV doses administered were highest for seizures (6.27) and hypersensitivity (5.02). Only 6 adverse events were reported through passive surveillance by facilities other than the two active surveillance hospitals. A total of 177 (10%) of 1,817 vaccinees surveyed reported experiencing an adverse event during the post-campaign coverage survey, of which 25 (14%) sought care.

Conclusions: In line with previous evaluations of TCV, enhanced adverse event monitoring during an emergency campaign supports the safety of TCV. The majority of reported events were minor or resulted in recovery without long-term sequelae. Attack rates for seizures and hypersensitivity were low compared with previous active surveillance studies conducted in Kenya and Burkina Faso. Strengthening adverse event monitoring in Zimbabwe and establishing background rates of conditions of interest in the general population may improve future safety monitoring during new vaccine introductions.

Keywords: Active surveillance; Adverse events following immunization; Typhoid outbreak; Typhoid vaccine; Vaccine campaign; Vaccine safety.

Fig. 1.

Diagram of 130 cases reported through active surveillance at two tertiary referral hospitals, following a vaccination campaign with typhoid conjugate vaccine (TCV), Harare, Zimbabwe, February 25–April 15, 2019. Abbreviations: AESI = Adverse event of special interest, TCV = Typhoid Conjugate Vaccine. ^a Discharge diagnoses for excluded cases were gastroenteritis (14), upper respiratory tract infection (11), pneumonia (6), multiple diagnoses (4), bronchiolitis (3), meningitis (2), asthma (1), burn (1), hepatitis (1), Kawasaki’s Disease (1), local injection site reaction (1), and pancreatitis (1). 44/46 received TCV vaccine. ^b Time from vaccination to onset for these 4 cases ranged from 7 to 35 days.^c 7 TCV-vaccinated cases also received other vaccines in the previous 42 days: Oral Cholera Vaccine (OCV) (5 cases), Measles Rubella Vaccine (MR) (1), and multiple vaccines including OCV, MR, Oral Polio Vaccine and Diphtheria, Tetanus Pertussis Vaccine (1). ^d Two TCV-non-vaccinated cases received OCV.

Fig. 2.

Onset dates of febrile and afebrile seizures among 20 cases following vaccination with typhoid conjugate vaccine (TCV)^a, and in some cases oral cholera vaccine (OCV), Harare, Zimbabwe, February 25–April 15, 2019. Dates of the TCV and subsequent OCV campaigns are represented on the X-axis. Abbreviations: TCV = Typhoid Conjugate Vaccine, OCV = Oral Cholera Vaccine. a One seizure case was also diagnosed with thrombocytopenia. * Indicates the case also received OCV.