BackgroundComplications from typhoid fever disease have been estimated to occur in 10%–15% of hospitalized patients, with evidence of a higher risk in children and when delaying the implementation of effective antimicrobial treatment. We estimated the prevalence of complications in hospitalized patients with culture-confirmed typhoid fever and the effects of delaying the implementation of effective antimicrobial treatment and age on the prevalence and risk of complications.MethodsA systematic review and meta-analysis were performed using studies in the PubMed database. We rated risk of bias and conducted random-effects meta-analyses. Days of disease at hospitalization (DDA) was used as a surrogate for delaying the implementation of effective antimicrobial treatment. Analyses were stratified by DDA (DDA <10 versus ≥10 mean/median days of disease) and by age (children versus adults). Differences in risk were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity and publication bias were evaluated with the I2 value and funnel plot analysis, respectively.ResultsThe pooled prevalence of complications estimated among hospitalized typhoid fever patients was 27% (95% CI, 21%–32%; I2 = 90.9%, P < .0001). Patients with a DDA ≥ 10 days presented higher prevalence (36% [95% CI, 29%–43%]) and three times greater risk of severe disease (OR, 3.00 [95% CI, 2.14–4.17]; P < .0001) than patients arriving earlier (16% [95% CI, 13%– 18%]). Difference in prevalence and risk by age groups were not significant.ConclusionsThis meta-analysis identified a higher overall prevalence of complications than previously reported and a strong association between duration of symptoms prior to hospitalization and risk of serious complications.

BackgroundThe relative contribution of bacterial infections to febrile disease is poorly understood in many African countries due to diagnostic limitations. This study screened pediatric and adult patients attending 4 healthcare facilities in Ibadan, Nigeria, for bacteremia and malaria parasitemia.MethodsFebrile patients underwent clinical diagnosis, malaria parasite testing, and blood culture. Bacteria from positive blood cultures were isolated and speciated using biochemical and serological methods, and Salmonella subtyping was performed by polymerase chain reaction. Antimicrobial susceptibility was tested by disk diffusion.ResultsA total of 682 patients were recruited between 16 June and 16 October 2017; 467 (68.5%) were <18 years of age. Bacterial pathogens were cultured from the blood of 117 (17.2%) patients, with Staphylococcus aureus (69 [59.0%]) and Salmonella enterica (34 [29.1%]) being the most common species recovered. Twenty-seven (79.4%) of the Salmonella isolates were serovar Typhi and the other 7 belonged to nontyphoidal Salmonella serovarieties. Thirty-four individuals were found to be coinfected with Plasmodium falciparum and bacteria. Five (14.7%) of these coinfections were with Salmonella, all in children aged <5 years. Antimicrobial susceptibility testing revealed that most of the Salmonella and Staphylococcus isolates were multidrug resistant.ConclusionsThe study demonstrates that bacteria were commonly recovered from febrile patients with or without malaria in this location. Focused and extended epidemiological studies are needed for the introduction of typhoid conjugate vaccines that have the potential to prevent a major cause of severe community-acquired febrile diseases in our locality.

Background Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. Methods A prospective healthcare facility–based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. Results Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. Conclusions SETA supports public health policy on typhoid immunization strategy in Africa.

The interaction between schistosomiasis and Salmonella is a particularly important issue in Africa, where dual infection by the parasite and the bacterium are likely common. In this review, the ways in which schistosomiasis affects human biology as it relates to Salmonella are described. Those who are infected by both organisms experience reduced immunological functioning, exhibit irreversible organ damage due to prolonged schistosomiasis infection, and become latent carriers of Salmonella enterica serotypes Typhi and Paratyphi and S. Typhimurium. The sequestration of the bacteria in the parasite leads to ineffective antibiotic treatment because the bacteria cannot be completely killed, and lingering infection may then lead to antimicrobial resistance. These manifestations are likely not just for those dually infected but also for those first infected with schistosomes and, later, Salmonella. More data are needed to better understand dual infection, particularly as it may impact treatment and prevention of schistosomiasis and Salmonella in sub-Saharan Africa.

IRs of Salmonella bloodstream infections in children <15 years old in AAN, Ghana, differed by setting, with 2 to nearly 3 times higher rates in the less populated setting. Variations in the distribution of the disease should be considered to implement future studies and intervention strategies.

The proportion of patients with culture-proven BSIs in children compared with adults was similar across the TSAP study population; however, outpatient children were more likely to have Salmonella Typhi infections than outpatient adults. This finding points to the importance of including outpatient facilities in surveillance efforts, particularly for the surveillance of typhoid fever. Strategies to reduce contamination among pediatric blood cultures are needed across the continent to prevent the misdiagnosis of BSI cases in children.

BackgroundAntimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum β-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa.MethodsData were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for β-lactamase were performed on all pathogens.ResultsFive hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR amplicon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity.ConclusionsOur findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed.

IntroductionThe 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 analysisFor 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 disseminationEthic 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.