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Salmonella Infantis is presenting an increasing risk to public health. Of particular concern are the reports of pESI, a multidrug resistance (MDR) encoding megaplasmid, in isolates from multiple countries, but little is known about its presence or diversity in South Africa. Whole genome sequences of 387 S. Infantis isolates from South Africa (2004–2020) were analysed for genetic phylogeny, recombination frequency, antimicrobial resistance (AMR) determinants, plasmid presence and overall gene content. The population structure of South African S. Infantis was substantially different to S. Infantis reported elsewhere; only two thirds of isolates belonged to eBG31, while the remainder were identified as eBG297, a much rarer group globally. Significantly higher levels of recombination were observed in the eBG297 isolates, which was associated with the presence of prophages. The majority of isolates were putatively susceptible to antimicrobials (335/387) and lacked any plasmids (311/387); the megaplasmid pESI was present in just one isolate. A larger proportion of eBG31 isolates, 19% (49/263), contained at least one AMR determinant, compared to eBG297 at 2% (3/124). Comparison of the pan-genomes of isolates from either eBG identified 943 genes significantly associated with eBG, with 43 found exclusively in eBG31 isolates and 34 in eBG297 isolates. This, along with the single nucleotide polymorphism distance and difference in resistance profiles, suggests that eBG31 and eBG297 isolates occupy different niches within South Africa. If antibiotic-resistant S. Infantis emerges in South Africa, probably through the spread of the pESI plasmid, treatment of this infection would be compromised.

A cross-sectional study was conducted to determine the prevalence of and factors associated with Shiga toxin-producing Escherichia coli (STEC) in raw beef and ready-to-eat (RTE) beef products sold in 31 retail outlets in Pretoria, South Africa, and nearby areas. A total of 463 beef and RTE samples were screened for four STEC virulence genes (stx1, stx2, eaeA, and hlyA) and seven O-serogroups (O113, O157, O26, O91, O145, O111, and O103) with a multiplex PCR assay. The total aerobic plate count (TAPC) per gram was also determined. A total of 38 STEC isolates were recovered and characterized by conventional PCR assay and serotyping. The overall prevalence of STEC in the beef and RTE samples tested was 16.4% (76 of 463 samples; 95% confidence interval, 13 to 20%). The prevalence of STEC differed significantly by product type (P < 0.0001), with the highest prevalence (35%) detected in boerewors (spicy sausage). The STEC prevalences in minced beef, brisket, RTE cold beef, and biltong were 18, 13, 9, and 5%, respectively. The most frequently detected stx gene was stx2 (13%), and STEC serogroups from recovered isolates were detected at the following prevalences: O2, 15%; O8, 12%; O13, 15%; O20, 8%; O24, 3%; O39, 3%; O41, 8%; O71, 3%; O76, 3%; O150, 12%; and O174, 3%. A high proportion (77%) of the samples had TAPCs that exceeded the South African microbiological standards for meat export (5.0 log CFU/g). The prevalence of O157 STEC (16%) and the diversity of non-O157 STEC serogroups found in five common beef-based products from retail outlets in South Africa suggest exposure of raw beef and beef products to multiple contamination sources during carcass processing and/or cutting and handling at retail outlets. These data provide direct estimates of the potential health risk to consumers from undercooked contaminated products and indicate the need to improve sanitary practices during slaughter and processing of beef and beef-based RTE products. A risk-based surveillance system for STEC may be needed. HIGHLIGHTS

Despite efforts to reduce the global burden of childhood diarrhoea, 50% of all cases globally occur in children under five years in Low–Income and Middle- Income Countries (LMICs) and knowledge gaps remain regarding the aetiological diagnosis, introduction of diarrhoeal vaccines, and the role of environmental enteric dysfunction and severe acute malnutrition. Biomarkers may assist in understanding disease processes, from diagnostics, to management of childhood diarrhoea and the sequelae to vaccine development. Proteomics has the potential to assist in the identification of new biomarkers to understand the processes in the development of childhood diarrhoea and to aid in developing new vaccines. Centralised repositories that enable mining of large data sets to better characterise risk factors, the proteome of both the patient and the different diarrhoeal pathogens, and the environment, could inform patient management and vaccine development, providing a systems biological approach to address the burden of childhood diarrhoea in LMICs.

In South Africa, there is a shortage of epidemiologic data on Shiga toxin-producing Escherichia coli (STEC) in the beef production chain. This study was conducted to characterise STEC isolates originating from three studies conducted in a cattle feedlot, beef abattoirs and retail outlets in Gauteng province, South Africa. Polymerase chain reaction was used to detect virulence genes, the Epsilometer test to assess antimicrobial susceptibility, pulsed-field gel electrophoresis (PFGE) to investigate genetic relatedness of isolates, and conventional serotyping for phenotypic identification. Amongst the 86 STEC isolates, the eaeA gene was detected in 20 (23%), and 26 different serogroups were identified, including the clinically important O8, O174, O2, 020 and O117. The majority of the isolates (95%; 82/86) exhibited resistance to one or more antimicrobial agents, and 30 of the isolates (35%) exhibited multi-drug resistance (MDR), being resistant to at least three antimicrobial classes. The PFGE patterns showed a highly diverse but related STEC population, with 45 distinct patterns and evidence of horizontal transmission along the beef production chain. This is significant because it demonstrates continual environmental contamination and risk of contamination along the beef production chain and the food chain. To our knowledge, this is the first study that provides evidence of horizontal transmission of STEC along the beef production chain in South Africa. This epidemiological information could facilitate the development of a proactive strategy for reducing potential foodborne outbreaks and transmission of antimicrobial resistant pathogens in the food chain.

The interplay between tuberculosis and depression has been problematic since the humoralists. Over the centuries similarities in disease management have transpired. With the advent of isoniazid chemotherapy, transformation of tuberculosis patients from morbidly depressive to euphoric was noted. Isoniazid was thereafter widely prescribed for depression: hepatotoxicity ending its use as an antidepressant in 1961. Isoniazid monotherapy led to the emergence of drug resistant tuberculosis, stimulating new drug development. Vastly increased investment into antidepressants ensued thereafter while investment in new drugs for tuberculosis lagged. In the 21st century, both diseases independently contribute significantly to global disease burdens: renewed convergence and the resultant syndemic is detrimental to both patient groups. Ending the global tuberculosis epidemic and decreasing the burden of depression and will require multidisciplinary, patient-centered approaches that consider this combined co-morbidity. The emerging era of big data for health, digital interventions and novel and repurposed compounds promise new ways to treat both diseases and manage the syndemic, but absence of clinical structures to support these innovations may derail the treatment programs for both. New policies are urgently required optimizing use of the current advances in healthcare available in the digital era, to ensure that patient-centered care takes cognizance of both diseases.

Diarrhoea is an important cause of morbidity and mortality in children from low-income and middle-income countries (LMICs), despite advances in the management of this condition. Understanding of the causes of diarrhoea in children in LMICs has advanced owing to large multinational studies and big data analytics computing the disease burden, identifying the important variables that have contributed to reducing this burden. The advent of the mobile phone has further enabled the management of childhood diarrhoea by providing both clinical support to health-care workers (such as diagnosis and management) and communicating preventive measures to carers (such as breastfeeding and vaccination reminders) in some settings. There are still challenges in addressing the burden of diarrhoeal diseases, such as incomplete patient information, underrepresented geographical areas, concerns about patient confidentiality, unequal partnerships between study investigators, and the reactive approach to outbreaks. A transparent approach to promote the inclusion of researchers in LMICs could address partnership imbalances. A big data umbrella encompassing cloud-based centralised databases to analyse interlinked human, animal, agricultural, social, and climate data would provide an informative solution to the development of appropriate management protocols in LMICs.

Treatment outcomes among multidrug-resistant tuberculosis (MDR-TB) patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen were compared, determining occurrence of serious adverse drug events (SADEs). Newly diagnosed adult MDR-TB patients were enrolled between 2000 and 2004, receiving a standardized multidrug regimen for 18 to 24 months, including ethambutol, cycloserine, or terizidone. Cycloserine and terizidone were recorded individually. SADEs and factors associated with culture conversion and unfavorable treatment outcomes (default, death, treatment failure) were determined. Of 858 patients, 435 (51%) received ethambutol, 278 (32%) received cycloserine, and 145 (17%) received terizidone. Demographic and baseline clinical data were comparable. Successful treatment occurred in 56%, significantly more in patients receiving cycloserine (60%) and terizidone (62%) than in those receiving ethambutol (52% [P = 0.03]). Defaults rates were 30% in ethambutol patients versus 15% and 11% for cycloserine and terizidone patients, respectively. Terizidone was associated with fewer unfavorable outcomes (adjusted odds ratio [AOR], 0.4; P = 0.008; 95% confidence interval [CI], 0.2 to 0.8). Patients receiving cycloserine were more likely to achieve culture conversion than those receiving ethambutol or terizidone (AOR, 2.2; P = 0.02; 95% CI, 1.12 to 4.38). Failure to convert increased the odds of unfavorable outcomes (AOR, 23.7; P < 0.001; 95% CI, 13 to 44). SADEs were reported in two patients receiving ethambutol, seven patients receiving cycloserine, and three receiving terizidone (P = 0.05). Ethambutol was associated with high culture conversion and default rates. Cycloserine achieved higher culture conversion rates than terizidone. Fewer patients on terizidone experienced SADEs, with lower default rates. The differences that we observed between cycloserine and terizidone require further elucidation.

BackgroundInvasive nontyphoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. Multi-drug resistance (MDR) and further resistance to third generation cephalosporins and fluoroquinolones have emerged in multiple iNTS serotypes. Molecular epidemiological investigations of nontyphoidal Salmonella are needed to better understand the genetic characteristics and transmission dynamics associated with major MDR iNTS serotypes across the continent.MethodsA total of 166 nontyphoidal Salmonella isolates causing invasive disease were collected from a multi-centre study in eight African countries between 2010 and 2014, and whole-genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogeographical reconstruction was further conducted in context of the existing genomic framework of iNTS serotypes Typhimurium and Enteritidis. Population-based incidence of MDR-iNTS disease was also estimated.ResultsSalmonella enterica subsp. Enterica serotype Typhimurium (S. Typhimurium) sequence-type (ST) 313 and Salmonella enterica subsp. Enterica serotype Enteritidis (S. Enteritidis) ST11 were predominant, and both exhibited high frequencies of MDR. Salmonella enterica subsp. Enterica serotype Dublin (S. Dublin) ST10 emerged in West Africa. Mutations in the gyrA gene were identified in S. Enteritidis and S. Typhimurium in Ghana; and ST313 carrying blaCTX-M-15 was found in Kenya. Inter-country transmission of MDR ST313 lineage II and the West African Clade of MDR ST11 between Ghana and neighbouring countries including Mali, Burkina Faso, and Nigeria were evident. The incidence of MDR-iNTS disease exceeded 100/100,000-person years-of-observation (PYO) in children aged ConclusionsMultiple MDR iNTS serotypes-sequence types, predominantly S. Typhimurium ST313 and S. Enteritidis ST11, are co-circulating in sub-Saharan Africa with evidence of transmission between West African countries. The development of safe and effective iNTS vaccines coupled with appropriate antimicrobial stewardship and adequate epidemiological monitoring are essential to limit the impact of these pathogens in Africa.

Despite efforts to reduce the global burden of childhood diarrhoea, 50% of all cases globally occur in children under five years in Low-Income and Middle- Income Countries (LMICs) and knowledge gaps remain regarding the aetiological diagnosis, introduction of diarrhoeal vaccines, and the role of environmental enteric dysfunction and severe acute malnutrition. Biomarkers may assist in understanding disease processes, from diagnostics, to management of childhood diarrhoea and the sequelae to vaccine development. Proteomics has the potential to assist in the identification of new biomarkers to understand the processes in the development of childhood diarrhoea and to aid in developing new vaccines. Centralised repositories that enable mining of large data sets to better characterise risk factors, the proteome of both the patient and the different diarrhoeal pathogens, and the environment, could inform patient management and vaccine development, providing a systems biological approach to address the burden of childhood diarrhoea in LMICs.

Funder: Swedish International Development Cooperation Agency (SIDA), Funder: Government of Republic of Korea, Funder: US Centers for Disease Control and Prevention, Background: Invasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent. Methods: A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010–2014) and a fever study in Ghana (2007–2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes–genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site. Results: Salmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S. Enteritidis and S. Typhimurium in Ghana; an ST313 isolate carrying blaCTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged

Wave upon wave of diseaseThe cholera pathogen,Vibrio cholerae, is considered to be ubiquitous in water systems, making the design of eradication measures apparently fruitless. Nevertheless, local and globalVibriopopulations remain distinct. Now, Weillet al.and Dommanet al.show that a surprising diversity between continents has been established. Latin America and Africa bear different variants of cholera toxin with different transmission dynamics and ecological niches. The data are not consistent with the establishment of long-term reservoirs of pandemic cholera or with a relationship to climate events.Science, this issue p.785, p.789

Objectives Shigella sonnei is a globally important diarrhoeal pathogen tracked through the surveillance network PulseNet Latin America and Caribbean (PNLA&C), which participates in PulseNet International. PNLA&C laboratories use common molecular techniques to track pathogens causing foodborne illness. We aimed to demonstrate the possibility and advantages of transitioning to whole genome sequencing (WGS) for surveillance within existing networks across a continent where S. sonnei is endemic. Methods We applied WGS to representative archive isolates of S. sonnei (n = 323) from laboratories in nine PNLA&C countries to generate a regional phylogenomic reference for S. sonnei and put this in the global context. We used this reference to contextualise 16 S. sonnei from three Argentinian outbreaks, using locally generated sequence data. Assembled genome sequences were used to predict antimicrobial resistance (AMR) phenotypes and identify AMR determinants. Results S. sonnei isolates clustered in five Latin American sublineages in the global phylogeny, with many (46%, 149 of 323) belonging to previously undescribed sublineages. Predicted multidrug resistance was common (77%, 249 of 323), and clinically relevant differences in AMR were found among sublineages. The regional overview showed that Argentinian outbreak isolates belonged to distinct sublineages and had different epidemiologic origins. Conclusions Latin America contains novel genetic diversity of S. sonnei that is relevant on a global scale and commonly exhibits multidrug resistance. Retrospective passive surveillance with WGS has utility for informing treatment, identifying regionally epidemic sublineages and providing a framework for interpretation of prospective, locally sequenced outbreaks., Graphical abstract Image 1

Summary Zoonotic thermophilic Campylobacter and nontyphoidal Salmonella enterica are a major cause of foodborne human gastroenteritis worldwide. There is little information about reservoirs of these zoonotic agents in Africa. Thus, chicks of kelp gulls (Larus dominicanus, n=129) and greater crested terns (Thalasseus bergii, n=100) were studied at five colonies on the Western Cape coast (South Africa) during summer 2013/2014. Campylobacter spp. occurrence was 14.0% (CI95%: 9.9-19.3), with C. jejuni the most frequently isolated species, whilst that of Salmonella was 27.5% (CI95%: 21.9-33.9) overall, with a higher prevalence in gulls (43.0%, CI95%: 34.8-52.4) than terns (7.0%, CI95%: 3.1-14.4). Among the 16 different S. enterica serovars found, Anatum, Enteritidis and Hadar were the most frequent. The same or highly similar pulsed-field gel electrophoresis genotype was found in some Salmonella isolates from seabirds and humans presenting with salmonellosis in Cape Town hospitals. Both Campylobacter and Salmonella isolates exhibited antimicrobial resistance to several agents, including critically important antimicrobials (quinolones, tetracyclines and β-lactams) and multidrug resistance in Salmonella serovars from kelp gulls. Our results highlight the importance of seabirds as reservoirs of Campylobacter and Salmonella resistant strains and their role in the maintenance and transmission of these bacteria in the environment, with implications for public health. This article is protected by copyright. All rights reserved.

Purpose. Molecular epidemiological investigations of the highly clonal Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) are important in outbreak detection and in tracking disease transmission. In this study, we developed and evaluated a multiple-locus variable-number tandem-repeats (VNTR) analysis (MLVA) assay for characterization of S. Typhi isolates from sub-Saharan Africa. Methodology. Twelve previously reported VNTR loci were evaluated and an MLVA assay consisting of five polymorphic loci was adopted. The MLVA assay was developed for use on capillary electrophoresis systems by testing a collection of 50 S. Typhi isolates. This S. Typhi strain panel consisted of six outbreak related isolates and 44 epidemiologically unlinked isolates. Amongst these were nine S.Typhi haplotype H58 isolates. Results. The MLVA assay characterized the 50 isolates into 47 MLVA profiles while PFGE analysis of the same isolates revealed 34 pulsotypes. MLVA displayed higher discriminatory power (Simpson’s index of diversity (DI) 0.998 [95 % confidence interval (CI) 0.995–1.000)] as compared to pulsed-field gel electrophoresis [Simpson’s DI 0.984 (95 % CI 0.974–0.994)]. Conclusion. The MLVA assay presented in this study is a simple, rapid and more accessible tool that serves as a good alternative to other molecular subtyping methods for S. Typhi.

BackgroundIn light of rampant childhood diarrhoea, this study investigated bacterial pathogens from human and non-human sources in an urban informal settlement.Meat from informal abattoirs (n = 85), river water (n = 64), and diarrheic stool (n = 66) were collected between September 2015 and May 2016. A duplex real-time PCR, gel-based PCR, and CHROMagar™STEC were used to screen Tryptic Soy Broth (TSB) for diarrheicE. coli. Standard methods were used to screen for other selected food and waterborne bacterial pathogens.ResultsPathogens isolated from stool, meat, and surface water includedSalmonella enterica(6, 5, 0%),Plesiomonas shigelloides(9, 0, 17%),Aeromonas sobria(3, 3, 0%),Campylobacter jejuni(5, 5, 0%),Shigella flexneri(17, 5, 0%),Vibrio vulnificus(0, 0, 9%), and diarrheicE. coli(21, 3, 7%) respectively. All the isolates were resistant to trimethoprim–sulphamethoxazole.ConclusionsThere was a high burden of drug resistant diarrheal pathogens in the stool, surface water and meat from informal slaughter. Integrated control measures are needed to ensure food safety and to prevent the spread of drug resistant pathogens in similar settings.

Background Robust household sampling, commonly applied for population-based investigations, requires sampling frames or household lists to minimize selection bias. We have applied Google Earth Pro satellite imagery to constitute structure-based sampling frames at sites in Pikine, Senegal; Pietermaritzburg, South Africa; and Wad-Medani, Sudan. Here we present our experiences in using this approach and findings from assessing its applicability by determining positional accuracy. Methods Printouts of satellite imagery combined with Global Positioning System receivers were used to locate and to verify the locations of sample structures (simple random selection; weighted-stratified sampling). Positional accuracy was assessed by study site and administrative subareas by calculating normalized distances (meters) between coordinates taken from the sampling frame and on the ground using receivers. A higher accuracy in conjunction with smaller distances was assumed. Kruskal-Wallis and Dunn multiple pairwise comparisons were performed to evaluate positional accuracy by setting and by individual surveyor in Pietermaritzburg. Results The median normalized distances and interquartile ranges were 0.05 and 0.03–0.08 in Pikine, 0.09 and 0.05–0.19 in Pietermaritzburg, and 0.05 and 0.00–0.10 in Wad-Medani, respectively. Root mean square errors were 0.08 in Pikine, 0.42 in Pietermaritzburg, and 0.17 in Wad-Medani. Kruskal-Wallis and Dunn comparisons indicated significant differences by low- and high-density setting and interviewers who performed the presented approach with high accuracy compared to interviewers with poor accuracy. Conclusions The geospatial approach presented minimizes systematic errors and increases robustness and representativeness of a sample. However, the findings imply that this approach may not be applicable at all sites and settings; its success also depends on skills of surveyors working with aerial data. Methodological modifications are required, especially for resource-challenged sites that may be affected by constraints in data availability and area size.

Shiga toxin-producing Escherichia coli (STEC) isolates (N = 38) that were incriminated in human disease from 2006 to 2013 in South Africa were characterized by serotype, virulence-associated genes, antimicrobial resistance and pulsed-field gel electrophoresis (PFGE). The isolates belonged to 11 O:H serotypes. STEC O26:H11 (24%) was the most frequent serotype associated with human disease, followed by O111:H8 (16%), O157:H7 (13%) and O117:H7 (13%). The majority of isolates were positive for key virulence-associated genes including stx1 (84%), eaeA (61%), ehxA (68.4%) and espP (55%), but lacked stx2 (29%), katP (42%), etpD (16%), saa (16%) and subA (3%). stx2 positive isolates carried stx2c (26%) and/or stx2d (26%) subtypes. All pathogenicity island encoded virulence marker genes were detected in all (100%) isolates except nleA (47%), nleC (84%) and nleD (76%). Multidrug resistance was observed in 89% of isolates. PFGE revealed 34 profiles with eight distinct clusters that shared &ge, 80% intra-serotype similarity, regardless of the year of isolation. In conclusion, STEC isolates that were implicated in human disease between 2006 and 2013 in South Africa were mainly non-O157 strains which possessed virulence genes and markers commonly associated with STEC strains that have been incriminated in mild to severe human disease worldwide. Improved STEC monitoring and surveillance programs are needed in South Africa to control and prevent STEC disease in humans.

A cross-sectional study was conducted to determine the prevalence, risk factors, and molecular characteristics of Shiga toxin-producing Escherichia coli (STEC) in 12 beef abattoirs in Gauteng province, South Africa. The relationship between STEC contamination and aerobic bacterial counts on carcasses at various stages of processing was investigated. Multiplex PCR was used to detect virulence genes in broth-enriched samples, to determine O-serogroups in all samples positive for Shiga toxin-encoding genes (stx), and to characterize isolates of STEC. The overall prevalence of STEC determined by PCR in 419 selective enrichment broth samples was 35.1% (147/419), and was significantly higher (P = 0.037) in perineum hide swabs (50%) than in 24 h chilled carcass swabs (20%). The maximum total aerobic plate count (TAPC) was 3.8 log10 CFU/100 cm2 for carcass swabs, but was below the South African microbiological standard for meat export at all stages of carcass processing. There was no significant association between TAPC and STEC contamination. Serogroup O113 was the most prevalent serogroup (13.6%; 20/147) detected. Only 33 isolates, all non-O157 STEC, were recovered, amongst which six different genotype combinations were observed. Additionally, the clinically important serogroups O117, O8, and O2 were isolated. Multivariable logistic regression revealed that the odds of STEC contamination was lower in post-wash (OR = 0.42; 95% CI: 0.18–0.98; P = 0.045) and 24 h chilled (OR = 0.33; 95% CI: 0.12–0.91; P = 0.033) carcass swabs compared to pre- and post-evisceration swabs. It was concluded that non-O157 STEC serogroups more frequently colonize beef cattle slaughtered at abattoirs in our study area than O157 STEC, and therefore have a higher potential to enter the food chain during carcass processing, with food safety implications.

Background. Assessing healthcare utilization is important to identify weaknesses of healthcare systems, to outline action points for preventive measures and interventions, and to more accurately estimate the disease burden in a population. Methods. A healthcare utilization survey was developed for the Typhoid Fever Surveillance in Africa Program (TSAP) to adjust incidences of salmonellosis determined through passive, healthcare facility–based surveillance. This cross-sectional survey was conducted at 11 sites in 9 sub-Saharan African countries. Demographic data and healthcare-seeking behavior were assessed at selected households. Overall and age-stratified percentages of each study population that sought healthcare at a TSAP healthcare facility and elsewhere were determined. Results. Overall, 88% (1007/1145) and 81% (1811/2238) of the population in Polesgo and Nioko 2, Burkina Faso, respectively, and 63% (1636/2590) in Butajira, Ethiopia, sought healthcare for fever at any TSAP healthcare facility. A far smaller proportion— namely, 20%–45% of the population in Bissau, Guinea-Bissau (1743/3885), Pikine, Senegal (1473/4659), Wad-Medani, Sudan (861/ 3169), and Pietermaritzburg, South Africa (667/2819); 18% (483/2622) and 9% (197/2293) in Imerintsiatosika and Isotry, Madagascar, respectively; and 4% (127/3089) in Moshi, Tanzania—sought healthcare at a TSAP healthcare facility. Patients with fever preferred to visit pharmacies in Imerintsiatosika and Isotry, and favored self-management of fever in Moshi. Age-dependent differences in healthcare utilization were also observed within and across sites. Conclusions. Healthcare utilization for fever varied greatly across sites, and revealed that not all studied populations were under optimal surveillance. This demonstrates the importance of assessing healthcare utilization. Survey data were pivotal for the adjustment of the program’s estimates of salmonellosis and other conditions associated with fever.

Background New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries. Methods Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations. Results Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. Conclusions By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs.

BackgroundTuberculosis (TB) is amongst the top five causes of death in women of childbearing age (15-≤44 years). Little is known about treatment of pregnant women with drug-resistant TB (DR-TB). Treatment for pregnant women remains challenging and more complex in DR-TB/HIV co-infection, where an evidence-based guide to clinical practice is limited. The study reviewed treatment and pregnancy outcomes and birth outcomes of their new-born in a cohort of pregnant women with DR-TB from three MDR-TB hospitals during 2010 and 2018.Design/methodsData were extracted from: TB register and patient clinic notes using a standardized case record form. Information on DR-TB treatment, pregnancy and Adverse Drug Events (ADEs) of twenty-six pregnant women treated with individualized second-line TB medications were captured. The frequency of favourable and adverse outcomes regarding disease and pregnancy were evaluated.ResultsThe mean age was 29 years (SD ±5.1), with the minimum and maximum age of 21 and 40 years, respectively. Eleven (42.3%) were previously treated with first-line TB drugs, 11 (42.3%) never treated before and 4 (15.4%) were previously treated for DR-TB. Of the 26 women, 15 (57.7%) had at least one ADE, but most had more than one ADE. Seventeen women were successfully treated, and 22 live births recorded. Live birth outcome was significantly associated with trimester of initiation of DR-TB treatment (p = 0.036). The proportion of live births for the pregnancy trimester when DR-TB treatment was initiated, were 60.0%, 90.9% and 100.0%, for first, second and third trimester, respectively.ConclusionDR-TB treatment should be delayed until after the first trimester. Routine pharmacovigilance surveillance integrated antenatal and delivery services with an integrated record of DR-TB treatment during pregnancy is recommended. Prospective studies using standardised case record forms for DR-TB treatment for pregnant women could provide more insight on the effect of DR-TB treatment on the birth outcome.

Typhoid fever is notifiable in South Africa but clinical notification is notoriously poor. South Africa has an estimated annual incidence rate of 0.1 cases per 100,000 population of culture-confirmed typhoid fever, decreased from 17 cases per 100,000 population in the 1980s. This work was undertaken to identify the reasons for this decrease and identify potential weaknesses that may result in an increase of observed cases. Culture-confirmed cases, with additional demographic and clinical data have been collected from selected sentinel sites since 2003. Data on contextual factors (gross domestic product [GDP], sanitation, female education, and childhood diarrhea mortality) were collected. National incidence rates of culture-confirmed typhoid fever have remained constant for the past 13 years, with the exception of an outbreak in 2005: incidence was 0.4 per 100,000 population. Paratyphoid fever remains a rare disease. Antimicrobial susceptibility data suggest resistance to ciprofloxacin and azithromycin is emerging. The South African population increased from 27.5 million in 1980 to 55.0 million in 2015: urbanization increased from 50% to 65%, GDP increased from United States Dollar (USD) $2,910 to USD $6,167, access to sanitation improved from 64.4% to 70.0% in the urban population and 26.4% to 60.5% in rural areas. Female literacy levels improved from 74.8% to 92.6% over the period. Improved socioeconomic circumstances in South Africa have been temporally associated with decreasing incidence rates of typhoid fever over a 35-year period. Ongoing challenges remain including potential for large outbreaks, a large immigrant population, and emerging antimicrobial resistance. Continued active surveillance is mandatory.

Background Shiga toxin producing E. coli (STEC) is an emerging zoonotic pathogen that can cause acute renal failure, especially in children. Clinical microbiology laboratories may fail to detect STEC and other diarrhoeic E. coli unless purposive rigorous screening procedures are followed using appropriate diagnostic technology; CHROMagar™STEC has rarely been used for isolation of African diarrhoeic E. coli hence characteristics of isolates on this medium are not yet fully understood. This study aimed to determine the prevalence and characteristics of STEC and other diarrhoeic E. coli isolated on CHROMagar™STEC from stool samples submitted to the microbiology laboratory of a South African public sector tertiary care hospital. Results In total, 733 stool samples were tested. Of these, 4.5% (33/733) possessed diarrhoeic E. coli. Of the diarrheic E. coli, 5/33 (15.2%) were STEC, 15/33 (45.5%) EAggEC, 6/33 (18.2%) atypical EPEC, 5/33 (15.2%) typical EPEC, and 1/33 (3%) DAEC. None of the STEC isolates had been identified by routine testing (based on using sorbitol media to test for E. coli O157: H7 strains and not the other STEC) in the laboratory. Of the 33 strains, 55% (95% CI = 40.8–72.7) showed resistance to ampicillin. Conclusions CHROMagar™STEC enabled detection of tellurite - resistant diarrhoeic E. coli that would be missed using routine methods. Further studies are needed to determine the proportion and characteristics of those which might have been missed using this approach.

No abstract available.