Abstract
SummaryBackgroundEnteric fever is a serious public health concern in many low-income and middle-income countries. Numerous data gaps exist concerning the epidemiology of Salmonella enterica serotype Typhi (S Typhi) and Salmonella enterica serotype Paratyphi (S Paratyphi), which are the causative agents of enteric fever. We aimed to determine the burden of enteric fever in three urban sites in Africa and Asia.MethodsIn this multicentre population-based study, we did a demographic census at three urban sites in Africa (Blantyre, Malawi) and Asia (Kathmandu, Nepal and Dhaka, Bangladesh) between June 1, 2016, and Sept 25, 2018. Households were selected randomly from the demographic census. Participants from within the geographical census area presenting to study health-care facilities were approached for recruitment if they had a history of fever for 72 h or more (later changed to >48 h) or temperature of 38·0°C or higher. Facility-based passive surveillance was done between Nov 11, 2016, and Dec 31, 2018, with blood-culture collection for febrile illness. We also did a community-based serological survey to obtain data on Vi-antibody defined infections. We calculated crude incidence for blood-culture-confirmed S Typhi and S Paratyphi infection, and calculated adjusted incidence and seroincidence of S Typhi blood-culture-confirmed infection.Findings423 618 individuals were included in the demographic census, contributing 626 219 person-years of observation for febrile illness surveillance. 624 S Typhi and 108 S Paratyphi A isolates were collected from the blood of 12 082 febrile patients. Multidrug resistance was observed in 44% S Typhi isolates and fluoroquinolone resistance in 61% of S Typhi isolates. In Blantyre, the overall crude incidence of blood-culture confirmed S Typhi was 58 cases per 100 000 person-years of observation (95% CI 48–70); the adjusted incidence was 444 cases per 100 000 person-years of observation (95% credible interval [CrI] 347–717). The corresponding rates were 74 (95% CI 62–87) and 1062 (95% CrI 683–1839) in Kathmandu, and 161 (95% CI 145–179) and 1135 (95% CrI 898–1480) in Dhaka. S Paratyphi was not found in Blantyre; overall crude incidence of blood-culture-confirmed S Paratyphi A infection was 6 cases per 100 000 person-years of observation (95% CI 3–11) in Kathmandu and 42 (95% CI 34–52) in Dhaka. Seroconversion rates for S Typhi infection per 100 000 person-years estimated from anti-Vi seroconversion episodes in serological surveillance were 2505 episodes (95% CI 1605–3727) in Blantyre, 7631 (95% CI 5913–9691) in Kathmandu, and 3256 (95% CI 2432–4270) in Dhaka.InterpretationHigh disease incidence and rates of antimicrobial resistance were observed across three different transmission settings and thus necessitate multiple intervention strategies to achieve global control of these pathogens.FundingWellcome Trust and the Bill & Melinda Gates Foundation.
Highlights
The human-restricted pathogens Salmonella enterica serovars Typhi (S Typhi) and Paratyphi A, B, and C cause enteric fever, which presents as a non-specific febrile illness after the oral ingestion of contaminated food or water, with a reported case fatality rate of around 2·5% despite antimicrobial treatment.[3]
Evidence before this study We considered evidence from a systematic review of typhoid fever incidence studies published in February, 2017, in addition to a PubMed search for articles done on Jan 1, 2021, using the search terms “(typhoid OR Salmonella Typhi) AND seroincidence”
We found a high incidence of typhoid fever, with overall crude and adjusted incidence of blood-culture-confirmed serotype Typhi (S Typhi) per 100 000 person-years of observation of 58 cases and 477 cases (95% credible interval [CrI] 372–770) in Blantyre, 74 and 1065 (95% CrI 687–1824) in Kathmandu, and 161 and 1138 (95% CrI 889–1477) in Dhaka, respectively
Summary
Enteric fever is estimated to cause 11–18 million infections and 100 000–200 000 deaths globally each year, resulting in a considerable public health burden in many low-income and middle-income countries in Africa and Asia.[1,2] The human-restricted pathogens Salmonella enterica serovars Typhi (S Typhi) and Paratyphi A, B, and C cause enteric fever, which presents as a non-specific febrile illness after the oral ingestion of contaminated food or water, with a reported case fatality rate of around 2·5% despite antimicrobial treatment.[3]. The cross-continental introduction of the H58 pathovar from Asia has coincided with a documented increase in cases of S Typhi, often associated with large outbreaks, persisting for years, at multiple African sites[6] and a concerning increase in antimicrobial resistance.[7,8] The age profile for disease burden differs across different epidemiological contexts.[4]
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