Burden of enteric fever at three urban sites in Africa and Asia: a multicentre population-based study.

BACKGROUND: Enteric 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. METHODS: In 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. FINDINGS: 423 618 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. INTERPRETATION: High 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. FUNDING: Wellcome Trust and the Bill & Melinda Gates Foundation.

Determinants and patterns of antibiotic consumption for children under five in Nepal: analysis and modelling of Demographic Health Survey data from 2006 to 2016.

OBJECTIVES: Our aims were to examine AMR-specific and AMR-sensitive factors associated with antibiotic consumption in Nepal between 2006 and 2016, to explore health care-seeking patterns and the source of antibiotics. METHODS: Cross-sectional data from children under five in households in Nepal were extracted from the 2006, 2011 and 2016 Demographic Health Surveys (DHS). Bivariable and multivariable analyses were carried out to assess the association of disease prevalence and antibiotic use with age, sex, ecological location, urban/rural location, wealth index, household size, maternal smoking, use of clean fuel, sanitation, nutritional status, access to health care and vaccinations. RESULTS: Prevalence of fever, acute respiratory infection (ARI) and diarrhoea decreased between 2006 and 2016, whilst the proportion of children under five receiving antibiotics increased. Measles vaccination, basic vaccinations, nutritional status, sanitation and access to health care were associated with antibiotic use. Those in the highest wealth index use less antibiotics and antibiotic consumption in rural areas surpassed urban regions over time. Health seeking from the private sector has overtaken government facilities since 2006 with antibiotics mainly originating from pharmacies and private hospitals. Adherence to WHO-recommended antibiotics has fallen over time. CONCLUSIONS: With rising wealth, there has been a decline in disease prevalence but an increase in antibiotic use and more access to unregulated sources. Understanding factors associated with antibiotic use will help to inform interventions to reduce inappropriate antibiotic use whilst ensuring access to those who need them.