TY - JOUR
T1 - Effectiveness of typhoid conjugate vaccine against culture-confirmed Salmonella enterica serotype Typhi in an extensively drug-resistant outbreak setting of Hyderabad, Pakistan
T2 - a cohort study
AU - Yousafzai, Mohammad Tahir
AU - Karim, Sultan
AU - Qureshi, Sonia
AU - Kazi, Momin
AU - Memon, Hina
AU - Junejo, Amber
AU - Khawaja, Zohra
AU - Ur Rehman, Najeeb
AU - Ansari, Muhammad Sajid
AU - Ali, Rafey
AU - Ujjan, Ikram Uddin
AU - Lohana, Heera Mani
AU - Memon, Naveed M.
AU - Hussain, Mudassar
AU - Nigar, Roohi
AU - Bar-Zeev, Naor
AU - Qamar, Farah Naz
N1 - Funding Information:
This study was funded by the Bill & Melinda Gates Foundation (grant number OPP1176356). We acknowledge the generosity of Bharat Biotech International for donating 50 000 doses of the vaccine. We also acknowledge the support of our local stakeholders in Hyderabad, Pakistan, including the Lady Health Worker Program; Director General Health office, DC Hyderabad; participants and their families; and our field staff who worked very hard to implement this project during an outbreak setting.
Funding Information:
This study was funded by the Bill & Melinda Gates Foundation (grant number OPP1176356). We acknowledge the generosity of Bharat Biotech International for donating 50?000 doses of the vaccine. We also acknowledge the support of our local stakeholders in Hyderabad, Pakistan, including the Lady Health Worker Program; Director General Health office, DC Hyderabad; participants and their families; and our field staff who worked very hard to implement this project during an outbreak setting.
Publisher Copyright:
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2021/8
Y1 - 2021/8
N2 - Background: Salmonella enterica serotype Typhi (S Typhi) is a major public health problem in low-income and middle-income countries. We aimed to investigate the effectiveness and impact of the typhoid conjugate vaccine Typbar-TCV against S Typhi among children in an outbreak setting of extensively drug-resistant (XDR) S Typhi in Pakistan. Methods: This cohort study was done from Feb 21, 2018, to Dec 31, 2019. A census survey of all households located in the Qasimabad and Latifabad subdistricts of Hyderabad, Pakistan, was done at baseline, and 174 005 households were registered in the census. The Typbar-TCV immunisation campaign was initiated at temporary vaccination centres and 207 000 children aged 6 months to 10 years were vaccinated from Feb 21, 2018, to Dec 31, 2018. Social mobilisers informed parents about the vaccination process. Vaccination records were maintained electronically and linked with the household census surveys. Active surveillance for suspected and blood-culture-confirmed S Typhi was established in hospitals, clinics, and laboratories to assess the following outcomes: cases of suspected typhoid fever, culture-confirmed S Typhi, and antimicrobial resistance. An age-stratified cohort of 1100 vaccinated children was randomly selected from the vaccination registry, tested for Vi-IgG antibodies (data not reported), and followed up fortnightly (via telephone calls or household visits) until Dec 31, 2019, for ascertainment of outcomes during the study period. 20 847 vaccinated and unvaccinated children were randomly selected from the census registry as a quality control cohort and followed up from Oct 1 to Dec 31, 2019, for ascertainment of outcomes. Vaccine effectiveness against suspected, culture-confirmed, and XDR S Typhi was calculated. Findings: 23 407 children from the census registry and surveillance system were included in the vaccine effectiveness analysis. 13 436 (57·4%) children were vaccinated, 12 214 (52·2%) were male, and 10 168 (43·4%) were aged 6–59 months. 5378 (23·0%) of 23 407 children had suspected S Typhi, among whom 775 (14·4%) had culture-confirmed S Typhi and 361 (68·6%) of 526 had XDR S Typhi. Vaccine effectiveness was 55% (95% CI 52–57) against suspected S Typhi (regardless of culture confirmation), 95% (93–96) against culture-confirmed S Typhi, and 97% (95–98) against XDR S Typhi. Interpretation: Typbar-TCV is effective in protecting children against S Typhi infection in an outbreak setting, and was able, with moderate deployment, to curtail a major XDR S Typhi outbreak in a densely populated setting. The vaccine shows efficacy against S Typhi irrespective of antimicrobial resistance. Funding: Bill & Melinda Gates Foundation.
AB - Background: Salmonella enterica serotype Typhi (S Typhi) is a major public health problem in low-income and middle-income countries. We aimed to investigate the effectiveness and impact of the typhoid conjugate vaccine Typbar-TCV against S Typhi among children in an outbreak setting of extensively drug-resistant (XDR) S Typhi in Pakistan. Methods: This cohort study was done from Feb 21, 2018, to Dec 31, 2019. A census survey of all households located in the Qasimabad and Latifabad subdistricts of Hyderabad, Pakistan, was done at baseline, and 174 005 households were registered in the census. The Typbar-TCV immunisation campaign was initiated at temporary vaccination centres and 207 000 children aged 6 months to 10 years were vaccinated from Feb 21, 2018, to Dec 31, 2018. Social mobilisers informed parents about the vaccination process. Vaccination records were maintained electronically and linked with the household census surveys. Active surveillance for suspected and blood-culture-confirmed S Typhi was established in hospitals, clinics, and laboratories to assess the following outcomes: cases of suspected typhoid fever, culture-confirmed S Typhi, and antimicrobial resistance. An age-stratified cohort of 1100 vaccinated children was randomly selected from the vaccination registry, tested for Vi-IgG antibodies (data not reported), and followed up fortnightly (via telephone calls or household visits) until Dec 31, 2019, for ascertainment of outcomes during the study period. 20 847 vaccinated and unvaccinated children were randomly selected from the census registry as a quality control cohort and followed up from Oct 1 to Dec 31, 2019, for ascertainment of outcomes. Vaccine effectiveness against suspected, culture-confirmed, and XDR S Typhi was calculated. Findings: 23 407 children from the census registry and surveillance system were included in the vaccine effectiveness analysis. 13 436 (57·4%) children were vaccinated, 12 214 (52·2%) were male, and 10 168 (43·4%) were aged 6–59 months. 5378 (23·0%) of 23 407 children had suspected S Typhi, among whom 775 (14·4%) had culture-confirmed S Typhi and 361 (68·6%) of 526 had XDR S Typhi. Vaccine effectiveness was 55% (95% CI 52–57) against suspected S Typhi (regardless of culture confirmation), 95% (93–96) against culture-confirmed S Typhi, and 97% (95–98) against XDR S Typhi. Interpretation: Typbar-TCV is effective in protecting children against S Typhi infection in an outbreak setting, and was able, with moderate deployment, to curtail a major XDR S Typhi outbreak in a densely populated setting. The vaccine shows efficacy against S Typhi irrespective of antimicrobial resistance. Funding: Bill & Melinda Gates Foundation.
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U2 - 10.1016/S2214-109X(21)00255-2
DO - 10.1016/S2214-109X(21)00255-2
M3 - Article
C2 - 34297962
AN - SCOPUS:85110563209
SN - 2214-109X
VL - 9
SP - e1154-e1162
JO - The Lancet Global Health
JF - The Lancet Global Health
IS - 8
ER -