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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

Abstract Background Typhoid fever remains a major public health problem in Zimbabwe with recurrent outbreaks reported since 2009. To provide guidance on appropriate treatment choice in order to minimise the morbidity and mortality of typhoid fever and prevent large scale outbreaks, we investigated the antimicrobial susceptibility patterns, prevalence of Salmonella enterica serotype Typhi (S. Typhi) H58 haplotype and molecular subtypes of S. Typhi from outbreak strains isolated from 2009 to 2017 in Zimbabwe and compared these to isolates from neighbouring African countries. Methods Antimicrobial susceptibility testing was performed on all isolates using the disk diffusion, and E-Test, and results were interpreted using Clinical and Laboratory Standards Institute (CLSI) guidelines (2017). S. Typhi H58 haplotype screening was performed on 161 (58.3%) isolates. Pulsed-field gel electrophoresis (PFGE) was performed on 91 selected isolates across timelines using antibiotic susceptibility results and geographical distribution (2009 to 2016). Results Between 2009 and 2017, 16,398 suspected cases and 550 confirmed cases of typhoid fever were notified in Zimbabwe. A total of 276 (44.6%) of the culture-confirmed S. Typhi isolates were analysed and 243 isolates (88.0%) were resistant to two or more first line drugs (ciprofloxacin, ampicillin and chloramphenicol) for typhoid. The most common resistance was to ampicillin-chloramphenicol (172 isolates; 62.3%). Increasing ciprofloxacin resistance was observed from 2012 to 2017 (4.2 to 22.0%). Out of 161 screened isolates, 150 (93.2%) were haplotype H58. Twelve PFGE patterns were observed among the 91 isolates analysed, suggesting some diversity exists among strains circulating in Zimbabwe. PFGE analysis of 2013, 2014 and 2016 isolates revealed a common strain with an indistinguishable PFGE pattern (100% similarity) and indistinguishable from PFGE patterns previously identified in strains isolated from South Africa, Zambia and Tanzania. Conclusions Resistance to first line antimicrobials used for typhoid fever is emerging in Zimbabwe and the multidrug resistant S. Typhi H58 haplotype is widespread. A predominant PFGE clone circulating in Zimbabwe, South Africa, Zambia and Tanzania, argues for cross-border cooperation in the control of this disease.

Typhoid fever is caused by the bacterium Salmonella Typhi. Here, Park et al. analyse the genomes of 249 S. Typhi isolates from 11 sub-Saharan African countries, identifying genes and plasmids associated with antibiotic resistance and showing that multi-drug resistance is highly pervasive in sub-Saharan Africa.

Summary: Background: Available incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents. Methods: We established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment. Findings: Between March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0–0) in Sudan to 383 (274–535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178–316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau. Interpretation: Typhoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study. Funding: Bill & Melinda Gates Foundation.

BACKGROUND:HIV-infected persons are at increased risk of opportunistic infections, including invasive nontyphoidal Salmonella (iNTS) infections; antiretroviral therapy (ART) reduces this risk. We explored changing iNTS incidence associated with increasing ART availability in South Africa. METHODS:Laboratory-based surveillance for iNTS was conducted in Gauteng Province, South Africa, with verification using the National Health Laboratory Service's Central Data Warehouse (CDW), between 2003 and 2013. Isolates were serotyped at the Centre for Enteric Diseases. CDW data on patient numbers obtaining HIV viral load measurements provided estimates of numbers of HIV-infected patients receiving ART. A Poisson regression model was used to measure the changing incidence of iNTS infection from 2003 to 2013. The correlation between the incidence of iNTS and ART use from 2004 to 2013 was determined using Pearson's correlation coefficient. RESULTS:From 2003-2013, the incidence of iNTS per 100,000 population per year decreased from 5.0 to 2.2 (p < .001). From 2004 to 2013, the incidence per 100,000 population of HIV viral load testing increased from 75.2 to 3,620.3 (p < .001). The most common serotypes causing invasive disease were Salmonella enterica serovar Typhimurium (Salmonella Typhimurium), and Salmonella Enteritidis: 2,469 (55.4%) and 1,156 (25.9%) of 4,459 isolates serotyped, respectively. A strong negative correlation was observed between decreasing iNTS incidence and increasing ART use from 2004 to 2013 (r = -0.94, p < .001). Similarly, decreasing incidence of invasive Salmonella Typhimurium infection correlated with increasing ART use (r = -0.93, p < .001). Incidence of invasive Salmonella Enteritidis infection increased, however (r = 0.95, p < .001). Between 2003 and 2004, fewer adult men than women presented with iNTS (male-to-female rate ratio 0.73 and 0.89, respectively). This was reversed from 2005 through 2013 (ranging from 1.07 in 2005 to 1.44 in 2013). Adult men accessed ART less (male-to-female rate ratio ranging from 0.61 [2004] to 0.67 [2013]). CONCLUSIONS:The incidence of iNTS infections including Salmonella Typhimurium decreased significantly in Gauteng Province in association with increased ART utilization. Adult men accessed ART programs less than women, translating into increasing iNTS incidence in this group. Monitoring iNTS incidence may assist in monitoring the ART program. Increasing incidence of invasive Salmonella Enteritidis infections needs further elucidation.

Typhoid fever remains an important disease in Africa, associated with outbreaks and the emerging multidrug resistant Salmonella enterica serotype Typhi (Salmonella Typhi) haplotype, H58. This study describes the incidence of, and factors associated with mortality due to, typhoid fever in South Africa, where HIV prevalence is high.Nationwide active laboratory-based surveillance for culture-confirmed typhoid fever was undertaken from 2003-2013. At selected institutions, additional clinical data from patients were collected including age, sex, HIV status, disease severity and outcome. HIV prevalence among typhoid fever patients was compared to national HIV seroprevalence estimates. The national reference laboratory tested Salmonella Typhi isolates for antimicrobial susceptibility and haplotype. Unadjusted and adjusted logistic regression analyses were conducted determining factors associated with typhoid fever mortality. We identified 855 typhoid fever cases: annual incidence ranged from 0.11 to 0.39 per 100,000 population. Additional clinical data were available for 369 (46.8%) cases presenting to the selected sites. Among typhoid fever patients with known HIV status, 19.3% (29/150) were HIV-infected. In adult females, HIV prevalence in typhoid fever patients was 43.2% (19/44) versus 15.7% national HIV seroprevalence (P < .001); in adult males, 16.3% (7/43) versus 12.3% national HIV seroprevalence (P = .2). H58 represented 11.9% (22/185) of Salmonella Typhi isolates tested. Increased mortality was associated with HIV infection (AOR 10.7; 95% CI 2.3-50.3) and disease severity (AOR 9.8; 95% CI 1.6-60.0) on multivariate analysis.Typhoid fever incidence in South Africa was largely unchanged from 2003-2013. Typhoid fever mortality was associated disease severity. HIV infection may be a contributing factor. Interventions mandate improved health care access, including to HIV management programmes as well as patient education. Further studies are necessary to clarify relationships between HIV infection and typhoid fever in adults.

To determine the origin of >4,000 suspected diarrheagenic Escherichia coli strains isolated during 2004–2011 in South Africa, we identified 7 isolates as serotype O104; 5 as enteroaggregative E. coli O104:H4, and 2 as enteropathogenic E. coli O104:non-H4. Pulsed-field gel electrophoresis showed that these isolates were unrelated to the 2011 E. coli O104:H4 outbreak strain from Germany.

OBJECTIVE: To evaluate three commercial typhoid rapid antibody tests for Salmonella Typhi antibodies in patients suspected of having typhoid fever in Mpumalanga, South Africa, and Moshi, United Republic of Tanzania. METHODS: The diagnostic accuracy of Cromotest® (semiquantitative slide agglutination and single tube Widal test),TUBEX®and Typhidot® was assessed against that of blood culture. Performance was modelled for scenarios with pretest probabilities of 5% and 50%. FINDINGS: In total 92 patients enrolled: 53 (57.6%) from South Africa and 39 (42.4%) from the United Republic of Tanzania. Salmonella Typhi was isolated from the blood of 28 (30.4%) patients. The semiquantitative slide agglutination and single-tube Widal tests had positive predictive values (PPVs) of 25.0% (95% confidence interval, CI: 0.6-80.6) and 20.0% (95% CI: 2.5-55.6), respectively. The newer typhoid rapid antibody tests had comparable PPVs: TUBEX®, 54.1% (95% CI: 36.9-70.5); Typhidot® IgM, 56.7% (95% CI: 37.4-74.5); and Typhidot® IgG, 54.3% (95% CI: 36.6-71.2). For a pretest probability of 5%, PPVs were: TUBEX®, 11.0% (95% CI: 6.6-17.9); Typhidot® IgM, 9.1% (95% CI: 5.8-14.0); and Typhidot® IgG, 11.0% (6.3-18.4). For a pretest probability of 50%, PPVs were: TUBEX®, 70.2% (95% CI: 57.3-80.5); Typhidot® IgM, 65.6% (95% CI: 54.0-75.6); and Typhidot® IgG, 70.0% (95% CI: 56.0-81.1). CONCLUSION: Semiquantitative slide agglutination and single-tube Widal tests performed poorly. TUBEX® and Typhidot® may be suitable when pretest probability is high and blood cultures are unavailable, but their performance does not justify deployment in routine care settings in sub-Saharan Africa.

To determine the prevalence of invasive nontyphoid salmonellosis and typhoid fever in Malawi and South Africa, we compared case frequency and patient age distribution. Invasive nontyphoid salmonellosis showed a clear bimodal age distribution; the infection developed in women at a younger age than in men. Case frequency for typhoid fever was lower than for salmonellosis.

We used standardized methodologies to characterize Vibrio cholerae O1 isolates from Guinea, Democratic Republic of the Congo (DRC), Togo, Côte d'Ivoire and Mozambique. We investigated 257 human isolates collected in 2010 to 2013. DRC isolates serotyped O1 Inaba, while isolates from other countries serotyped O1 Ogawa. All isolates were biotype El Tor and positive for cholera toxin. All isolates showed multidrug resistance but lacked ciprofloxacin resistance. Antimicrobial susceptibility profiles of isolates varied between countries. In particular, the susceptibility profile of isolates from Mozambique (East-Africa) included resistance to ceftriaxone and was distinctly different to the susceptibility profiles of isolates from countries located in West- and Central-Africa. Molecular subtyping of isolates using pulsed-field gel electrophoresis (PFGE) analysis showed a complex relationship among isolates. Some PFGE patterns were unique to particular countries and clustered by country; while other PFGE patterns were shared by isolates from multiple countries, indicating that the same genetic lineage is present in multiple countries. Our data add to a better understanding of cholera epidemiology in Africa.

Introduction: Organophosphate poisoning occurs frequently, and despite treatment, increased severity and intensive care unit (ICU) admissions have been observed. We hypothesized that early hemoperfusion/hemadsorption (HA) therapy would change the clinical course of the disease. Methods: We performed a prospective, open, randomized controlled study at an academic ICU. Adult patients referred for an acute cholinergic toxidrome were screened. Patients meeting inclusion and exclusion criteria were randomized to standard of care (SoC) or HA therapy plus SoC, which included 2 6-h cycles of HA 12 h apart beginning within the first 24 h of ICU admission. The primary outcome was a comparison of ICU length of stay (LOS). Results: There were no significant baseline differences between the groups. The median ICU LOS was 6.5 days (IQR 4.5–10) in the HA group compared to 8 days (IQR 3.5–17) for the control group, p = 0.58. Among patients with an excess ICU LOS ≥7 days, the median ICU LOS was significantly shorter for the HA group, 10 days (IQR 8–12) compared to 17 days (IQR 14–22) for the control group, p = 0.001, resulting in a cost saving of EUR 7308 per patient. Duration (8 days vs. 13.5 days) and cumulative dosage (316 mg vs. 887 mg) of atropine among patients with excess ICU LOS were significantly lower in the HA group compared to the SoC group, respectively. A similar reduction in the duration of mechanical ventilation (HA = 6 days vs. SoC = 15 days, p = 0.001) was found. The combination of day 28 mortality and severe complications was lower in the HA group (10%, n = 2/20) compared to the SoC group (42%, 14/33) p = 0.01. Conclusion: HA therapy resulted in significant cost savings driven by a reduced LOS among patients with excess ICU LOS ≥7 days. This therapy was also associated with a significant reduction in the combination of day 28 mortality and severe complications including cardiac arrest, organ dysfunction, reintubation, and tracheostomy. [ABSTRACT FROM AUTHOR]

Escherichia coli is the predominant microorganism of human colonic flora (1). It is mostly harmless to the intestinal lumen. However, some strains (diarrheagenic E. coli [DEC]) can cause disease ranging [...]

Objective To evaluate three commercial typhoid rapid antibody tests for Salmonella Typhi antibodies in patients suspected of having typhoid fever in Mpumalanga, South Africa, and Moshi, United Republic of Tanzania. Methods The diagnostic accuracy of Cromotest[R] (semiquantitative slide agglutination and single tube Widal test), TUBEX[R] and Typhidote was assessed against that of blood culture. Performance was modelled for scenarios with pretest probabilities of 5% and 50%. Findings In total 92 patients enrolled: 53 (57.6%) from South Africa and 39 (42.4%) from the United Republic of Tanzania. Salmonella Typhi was isolated from the blood of 28 (30.4%) patients. The semiquantitative slide agglutination and single-tube Widal tests had positive predictive values (PPVs) of 25.0% (95% confidence interval, CI: 0.6-80.6) and 20.0% (95% CI: 2.5-55.6), respectively. The newer typhoid rapid antibody tests had comparable PPVs: TUBEX[R], 54.1% (95% CI: 36.9-70.5); Typhidot[R] IgM, 56.7% (95% CI: 37.4-74.5); and Typhidote IgG, 54.3% (95% CI: 36.6-71.2). For a pretest probability of 5%, PPVs were: TUBEX[R], 11.0% (95% CI: 6.6-17.9); Typhidot[R] IgM, 9.1% (95% Ch 5.8-14.0); and Typhidot[R] IgG, 11.0% (6.3-18.4). For a pretest probability of 50%, PPVs were: TUBEX[R], 70.2% (95% CI: 57.3-80.5); Typhidot[R] IgM, 65.6% (95% CI: 54.0-75.6); and Typhidot[R] IgG, 70.0% (95% CI: 56.0-81.1). Conclusion Semiquantitative slide agglutination and single-tube Widal tests performed poorly. TUBEX[R] and Typhidot[R] may be suitable when pretest probability is high and blood cultures are unavailable, but their performance does not justify deployment in routine care settings in sub-Saharan Africa. Objectif Evaluer trois tests d'anticorps rapides de la typhoide commercialises pour rechercher les anticorps de type Salmonella typhi chez des patients soupconnes d'avoir contracte la fievre typhdde a Mpumalanga, en Afrique du Sud, et a Moshi, en Republique-Unie de Tanzanie. Methodes La precision du diagnostic de Cromotest[R] (test d'agglutination sur lame semi-quantitative et test de Widal a tube unique), de TUBEX[R] et de Typhidot[R] a ete evaluee par rapport a celle de rhemoculture. Les resultats ont ete modelises pour des scenarios avec des probabilites pre-test de 5% et 50%. Resultats Un total de 92 patients ont participe: 53 (57,6%) d'Afrique du Sud et 39 (42,4%) de la Republique-Unie de Tanzanie. Le germe Salmonellatyphi a ete isole dans le sang de 28 (30,4%) patients. Les tests d'agglutination sur lame semi-quantitative et de Widal a tube unique presentaient des valeurs predictives positives (VPP) de 25% (intervalle de confiance, IC, de 95%: 0,6-80,6) et de 20% (IC de 95%: 2,5-55,6), respectivement. Les tests d'anticorps rapides de la typhdlde les plus recents presentaient des VPP comparables: TUBEX[R], 54,1% (IC de 95%: 36,9-70,5); Typhidot[R] IgM, 56,7% (IC de 95%: 37,4-74,5); et Typhidot[R] IgG, 54,3% (IC de 95%: 36,6-71,2). Pour une probabilite pre-test de 5%, les VPP etaient les suivantes: TUBEX[R], 11% (IC de 95%: 6,6-17,9); Typhidot[R] IgM, 9,1% (IC de 95%: 5,8-14,0); et Typhidot[R] IgG, 11% (6,3-18,4). Pour une probabilite pre-test de 50%, les VPP etaient les suivantes: TUBEX[R], 70,2% (IC de 95%: 57,3-80,5); Typhidote[R] IgM, 65,6% (IC de 95%: 54,0-75,6); et Typhidot[R] IgG, 70% (IC de 95%: 56,0-81,1). Conclusion Les tests d'agglutination sur lame semi-quantitative et de Widal a tube unique ont donne des resultats mediocres. TUBEX[R] et Typhidot[R] peuvent etre adaptes Iorsqu'une probabilite pre-test est elevee et que les hemocultures ne sont pas disponibles, mais leurs resultats ne justifient pas le deploiement d'un environnement de soins de routine en Afrique subsaharienne. Objetivo Evaluar tres pruebas comerciales rapidas de anticuerpos tifoideos para detectar anticuerpos de Salmonella typhien pacientes de los que se sospecha que sufren fiebre tifoidea en Mpumalanga, Sudafrica y Moshi, Republica Unida de Tanzania. Metodos Se evaluo la precision diagnostica del Cromotest[R] (pruebas semicuantitativas de aglutinacion en laminas y de Widal en tubo unico), el TUBEX[R] y el Typhidot[R]. en comparacion con el hemocultivo. Se elaboraron modelos de funcionamiento de los supuestos, con probabilidades de las pruebas iniciales del 5% y el 50%. Resultados Se recluto a un total de 92 pacientes: 53 (57,6%) de Sudafrica y 39 (42,4%) de la Republica Unida de Tanzania. La Salmonella iyphise aislo en la sangre de 28 pacientes (30,4%). Las pruebas semicuantitativas de aglutinacion en lamina y de Widal en tubo unico ofrecieron valores predictivos positivos (VPP) del 25,0% (intervalo de confianza [IC] del 95%: 0,6-80,6) y del 20,0% (IC del 95%: 2,5-55,6), respectivamente. Las pruebas rapidas de anticuerpos tifoideos mas novedosas presentaron VPP comparables: TUBEX[R], 54,1% (IC del 95%: 36,9-70,5); Typhidot[R] IgM, 56,7% (IC del 95%: 37,4-74,5); Typhidot[R] IgM, 54,3% (IC del 95%: 36,6-71,2). Para una probabilidad de la prueba inicial del 5%, los VPP fueron: TUBEX[R], 11,0% (IC del 95%: 6,6-17,9); Typhidot[R] IgM, 9,1% (IC del 95%: 5,8-14,0) y Typhidot[R] IgG, 11,0% (6,3-18,4). Para una probabilidad de la prueba inicial del 50%, los VPP fueron: TUBEX[R], 70,2% (IC del 95%: 57,3-80,5); Typhidot[R] IgM, 65,6% (IC del 95%: 54,0-75,6); y Typhidot[R] IgM, 70,0% (IC del 95%: 56,0-81,1). Conclusion Las pruebas semicuantitativas de aglutinacion en lamina y de Widal en tubo unico no funcionaron bien. TUBEX[R] y Typhidot[R] podrian ser aptos cuando la probabilidad de la prueba inicial es alta y los hemocultivos no estan disponibles, pero su funcionamiento no justifica su uso en los centros de asistencia sanitaria habituales en el Africa subsahariana., Introduction Typhoid fever remains an important cause of disease in developing countries. In 2002, it caused an estimated 408 837 episodes of illness in Africa. (1) Salmonella Typhi, the causative [...]

Invasive nontyphoid salmonellosis (iNTS) was first described as an AIDS-related illness in Africa and the United States in the 1980s. Although incidence in industrialized countries declined, nontyphoid Salmonella (NTS) spp. [...]

Abstract Background Infections due to nontyphoidal Salmonella have increased worldwide over the last couple of decades. Salmonella enterica serotype Blockley (Salmonella Blockley) infections is associated with chickens and is a rarely isolated serotype in human infections in most countries. Case presentation We report a case of human infections due to Salmonella Blockley in KwaZulu-Natal, South Africa in 2011. Three African males (aged 4, 14 and 16) presented to a clinic with diarrhoea, stomach cramps and headache. They started experiencing signs of illness a day after they consumed a common meal, consisting of meat, rice and potatoes. Stool specimens from the patients cultured Salmonella Blockley. The strains showed an indistinguishable pulsed-field gel electrophoresis pattern. Conclusion This is the first recorded case of human infections due to Salmonella Blockley in South Africa.