Detection of Salmonella Typhi nucleic acid by RT-PCR and anti-HlyE, -CdtB, -PilL, and -Vi IgM by ELISA at sites in Ghana, Madagascar and Ethiopia.

BACKGROUND: We aimed to assess the prevalence of Salmonella Typhi through DNA and IgM-antibody detection methods as a prelude to extended surveillance activities at sites in Ghana, Madagascar, and Ethiopia. METHODS: We performed species-specific real-time polymerase reaction (RT-PCR) to identify bacterial nucleic acid, and enzyme-linked immunosorbent assay (ELISA) for detecting HlyE/STY1498-, CdtB/STY1886-, pilL/STY4539- and Vi-antigens in blood and biopsy specimens of febrile and non-febrile subjects. We generated antigen-specific ELISA proxy cut-offs by change-point analyses, and utilized cumulative sum as detection method coupled with 1000 repetitive bootstrap analyses. We computed prevalence rates in addition to odds ratios to assess correlations between ELISA outcomes and participant characteristics. RESULTS: Definitive positive RT-PCR results were obtained from samples of febrile subjects originating from Adama Zuria/Ethiopia (1.9%, 2/104), Wolayita Sodo/Ethiopia (1.0%, 1/100), Diego/Madagascar (1.0%, 1/100), and Kintampo/Ghana (1.0%, 1/100), and from samples of non-febrile subjects from Wolayita Sodo/Ethiopia (1%, 2/201). While IgM antibodies against all antigens were identified across all sites, prevalence rates were highest at all Ethiopian sites, albeit in non-febrile populations. Significant correlations in febrile subjects aged < 15 years versus ≥ 15 years were detected for Vi (Odds Ratio (OR): 8.00, p = 0.034) in Adama Zuria/Ethiopia, STY1498 (OR: 3.21, p = 0.008), STY1886 (OR: 2.31, p = 0.054) and STY4539 (OR: 2.82, p = 0.022) in Diego/Madagascar, and STY1498 (OR: 2.45, p = 0.034) in Kintampo/Ghana. We found statistical significance in non-febrile male versus female subjects for STY1498 (OR: 1.96, p = 0.020) in Adama Zuria/Ethiopia, Vi (OR: 2.84, p = 0.048) in Diego/Madagascar, and STY4539 (OR: 0.46, p = 0.009) in Kintampo/Ghana. CONCLUSIONS: Findings indicate non-discriminatory stages of acute infections, though with site-specific differences. Immune responses among non-febrile, presumably healthy participants may mask recall and/or reporting bias leading to misclassification, or asymptomatic, subclinical infection signs induced by suppression of inflammatory responses. As most Ethiopian participants were ≥ 15 years of age and not at high-risk, the true S. Typhi burden was likely missed. Change-point analyses for generating ELISA proxy cut-offs appeared robust, though misclassification is possible. Our findings provided important information that may be useful to assess sites prior to implementing surveillance for febrile illness including Salmonella disease.

The HPAfrica protocol: Assessment of health behaviour and population-based socioeconomic, hygiene behavioural factors - a standardised repeated cross-sectional study in multiple cohorts in sub-Saharan Africa.

INTRODUCTION: The objective of the Health Population Africa (HPAfrica) study is to determine health behaviour and population-based factors, including socioeconomic, ethnographic, hygiene and sanitation factors, at sites of the Severe Typhoid Fever in Africa (SETA) programme. SETA aims to investigate healthcare facility-based fever surveillance in Burkina Faso, the Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar and Nigeria. Meaningful disease burden estimates require adjustment for health behaviour patterns, which are assumed to vary among a study population. METHODS AND ANALYSIS: For the minimum sample size of household interviews required, the assumptions of an infinite population, a design effect and age-stratification and sex-stratification are considered. In the absence of a population sampling frame or household list, a spatial approach will be used to generate geographic random points with an Aeronautical Reconnaissance Coverage Geographic Information System tool. Printouts of Google Earth Pro satellite imagery visualise these points. Data of interest will be assessed in different seasons by applying population-weighted stratified sampling. An Android-based application and a web service will be developed for electronic data capturing and synchronisation with the database server in real time. Sampling weights will be computed to adjust for possible differences in selection probabilities. Descriptive data analyses will be performed in order to assess baseline information of each study population and age-stratified and sex-stratified health behaviour. This will allow adjusting disease burden estimates. In addition, multivariate analyses will be applied to look into associations between health behaviour, population-based factors and the disease burden as determined in the SETA study. ETHICS AND DISSEMINATION: Ethic approvals for this protocol were obtained by the Institutional Review Board of the International Vaccine Institute (No. 2016-0003) and by all collaborating institutions of participating countries. It is anticipated to disseminate findings from this study through publication on a peer-reviewed journal.

Severe acute respiratory infection in children in a densely populated urban slum in Kenya, 2007-2011.

BACKGROUND: Reducing acute respiratory infection burden in children in Africa remains a major priority and challenge. We analyzed data from population-based infectious disease surveillance for severe acute respiratory illness (SARI) among children <5 years of age in Kibera, a densely populated urban slum in Nairobi, Kenya. METHODS: Surveillance was conducted among a monthly mean of 5,874 (range = 5,778-6,411) children <5 years old in two contiguous villages in Kibera. Participants had free access to the study clinic and their health events and utilization were noted during biweekly home visits. Patients meeting criteria for SARI (WHO-defined severe or very severe pneumonia, or oxygen saturation <90%) from March 1, 2007-February 28, 2011 had blood cultures processed for bacteria, and naso- and oro- pharyngeal swabs collected for quantitative real-time reverse transcription polymerase chain reaction testing for influenza viruses, parainfluenza viruses (PIV), respiratory syncytial virus (RSV), adenovirus, and human metapneumovirus (hMPV). Swabs collected during January 1, 2009 - February 28, 2010 were also tested for rhinoviruses, enterovirus, parechovirus, Mycoplasma pneumoniae, and Legionella species. Swabs were collected for simultaneous testing from a selected group of control-children visiting the clinic without recent respiratory or diarrheal illnesses. RESULTS: SARI overall incidence was 12.4 cases/100 person-years of observation (PYO) and 30.4 cases/100 PYO in infants. When comparing detection frequency in swabs from 815 SARI cases and 115 healthy controls, only RSV and influenza A virus were significantly more frequently detected in cases, although similar trends neared statistical significance for PIV, adenovirus and hMPV. The incidence for RSV was 2.8 cases/100 PYO and for influenza A was 1.0 cases/100 PYO. When considering all PIV, the rate was 1.1 case/100 PYO and the rate per 100 PYO for SARI-associated disease was 1.5 for adenovirus and 0.9 for hMPV. RSV and influenza A and B viruses were estimated to account for 16.2% and 6.7% of SARI cases, respectively; when taken together, PIV, adenovirus, and hMPV may account for >20% additional cases. CONCLUSIONS: Influenza viruses and RSV (and possibly PIV, hMPV and adenoviruses) are important pathogens to consider when developing technologies and formulating strategies to treat and prevent SARI in children.

Sustained high incidence of injuries from burns in a densely populated urban slum in Kenya: an emerging public health priority.

INTRODUCTION: Ninety-five percent of burn deaths occur in low- and middle-income countries (LMICs); however, longitudinal household-level studies have not been done in urban slum settings, where overcrowding and unsafe cook stoves may increase likelihood of injury. METHODS: Using a prospective, population-based disease surveillance system in the urban slum of Kibera in Kenya, we examined the incidence of household-level burns of all severities from 2006-2011. RESULTS: Of approximately 28,500 enrolled individuals (6000 households), we identified 3072 burns. The overall incidence was 27.9/1000 person-years-of-observation. Children <5 years old sustained burns at 3.8-fold greater rate compared to (p<0.001) those ≥5 years old. Females ≥5 years old sustained burns at a rate that was 1.35-fold (p<0.001) greater than males within the same age distribution. Hospitalizations were uncommon (0.65% of all burns). CONCLUSIONS: The incidence of burns, 10-fold greater than in most published reports from Africa and Asia, suggests that such injuries may contribute more significantly than previously thought to morbidity in LMICs, and may be increased by urbanization. As migration from rural areas into urban slums rapidly increases in many African countries, characterizing and addressing the rising burden of burns is likely to become a public health priority.