Effectiveness of Typhoid Conjugate Vaccine in Zimbabwe used in response to an outbreak among children and young adults: a matched case control study

Abstract

(249 words) Background Zimbabwe suffers from regular outbreaks of typhoid fever (TF), worse since 2017. Most cases were in Harare and a vaccination campaign with Typhoid Conjugate Vaccine (TCV) was conducted in March 2019. The vaccine effectiveness (VE) was assessed against culture-confirmed S. Typhi in children six months to 15 years and in individuals six months to 45 years in Harare. Methods A matched case-control study was conducted in three urban suburbs of Harare targeted by the TCV vaccination campaign. Suspected TF cases were enrolled prospectively in four health facilities and were matched to facility (1:1) and community (1:5) controls. Findings Of 504 suspected cases from July 2019 to March 2020, 148 laboratory-confirmed TF cases and 153 controls confirmed-negative were identified. One hundred and five (47 aged six months to 15 years) cases were age, sex, and residence matched with 105 facility-based controls while 96 cases were matched 1:5 by age, sex, and immediate-neighbour with 229 community controls. The adjusted VE against confirmed TF was 75% (95%CI: 1-94, p=0.049) compared to facility controls, and 84% (95%CI: 57-94, p<0.001) compared to community controls in individuals six months to 15 years. The adjusted VE against confirmed TF was 46% (95%CI: 26-77, p=0.153) compared to facility controls, and 67% (95%CI: 35-83, p=0.002) compared to community controls six months to 45 years old. Interpretation This study confirms that one vaccine dose of TCV is effective to control TF in children between six months and 15 years old in an African setting.

Population structure and evolution of Salmonella enterica serotype Typhi in Zimbabwe before a typhoid conjugate vaccine immunization campaign

“…The common ancestor of all S . Typhi 4.3.1.1EA1 isolates from Zimbabwe was estimated to have existed around 2009 [95% confidence interval: 2008.5 – 2010.0], consistent with epidemiological records indicating increased outbreaks of typhoid fever from this time (11, 13). Additional evolution of AMR was also exclusively observed in isolates from Zimbabwe with the apparent acquisition of dfrA 14, qnrS and tetA AMR genes whose presence coincided with the presence of IncN replicon genes.…”

“…The emergence and escalating antimicrobial resistance throughout the world have focused increasing attention on the use of typhoid vaccines (6,8,9). Multiple outbreaks of typhoid fever have been reported in Zimbabwe since 2009, with most beginning during the rainy season (10,11). A typhoid outbreak caused by a ciprofloxacinresistant strain of S. Typhi was detected in Harare, Zimbabwe, in September 2018 (12).…”

“…Multiple outbreaks of typhoid fever have been reported in Zimbabwe since 2009, with most beginning during the rainy season (10, 11). A typhoid outbreak caused by a ciprofloxacin-resistant strain of S .…”

“…In response, an emergency reactive vaccination campaign using Typhoid Conjugate Vaccine (TCV) was implemented from February to March 2019, targeting more than 323 000 persons who were at high risk for typhoid infection in Harare. Initial reports suggested that the vaccine provided moderate protection against typhoid fever, with an adjusted vaccine effectiveness of up to 67% (11). Further epidemiological investigation of the effect of the vaccine program on S. Typhi incidence and population structure of the pathogen are needed to fully evaluate the outcome (14).…”

Typhoid fever control in the 21st century: where are we now?

“…Several observational studies have since reinforced data on the effectiveness of TCVs (Table 1) [29 ▪▪ ,30,55,56]. The Navi Mumbai Municipal Corporation (NMMC) conducted the first public-sector TCV campaign with Typbar-TCV in 2018 [55].…”