Browsing by Author "Baker, Stephen"

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    A Multicountry Molecular Analysis of Salmonella enterica Serovar Typhi With Reduced Susceptibility to Ciprofloxacin in Sub-Saharan Africa.
    (Clin Infect Dis, 2016-03-15) Al-Emran, Hassan M; Eibach, Daniel; Krumkamp, Ralf; Ali, Mohammad; Baker, Stephen; Biggs, Holly M; Bjerregaard-Andersen, Morten; Breiman, Robert F; Clemens, John D; Crump, John A; Cruz Espinoza, Ligia Maria; Deerin, Jessica; Dekker, Denise Myriam; Gassama Sow, Amy; Hertz, Julian T; Im, Justin; Ibrango, Samuel; von Kalckreuth, Vera; Kabore, Leon Parfait; Konings, Frank; Løfberg, Sandra Valborg; Meyer, Christian G; Mintz, Eric D; Montgomery, Joel M; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Se Eun; Razafindrabe, Jean Luco Tsiriniaina; Rabezanahary, Henintsoa; Rakotondrainiarivelo, Jean Philibert; Rakotozandrindrainy, Raphaël; Raminosoa, Tiana Mirana; Schütt-Gerowitt, Heidi; Sampo, Emmanuel; Soura, Abdramane Bassiahi; Tall, Adama; Warren, Michelle; Wierzba, Thomas F; May, Jürgen; Marks, Florian
    BACKGROUND: Salmonella enterica serovar Typhi is a predominant cause of bloodstream infections in sub-Saharan Africa (SSA). Increasing numbers of S. Typhi with resistance to ciprofloxacin have been reported from different parts of the world. However, data from SSA are limited. In this study, we aimed to measure the ciprofloxacin susceptibility of S. Typhi isolated from patients with febrile illness in SSA. METHODS: Febrile patients from 9 sites within 6 countries in SSA with a body temperature of ≥38.0°C were enrolled in this study. Blood samples were obtained for bacterial culture, and Salmonella isolates were identified biochemically and confirmed by multiplex polymerase chain reaction (PCR). Antimicrobial susceptibility of all Salmonella isolates was performed by disk diffusion test, and minimum inhibitory concentrations (MICs) against ciprofloxacin were measured by Etest. All Salmonella isolates with reduced susceptibility to ciprofloxacin (MIC > 0.06 µg/mL) were screened for mutations in quinolone resistance-determining regions in target genes, and the presence of plasmid-mediated quinolone resistance (PMQR) genes was assessed by PCR. RESULTS: A total of 8161 blood cultures were performed, and 100 (1.2%) S. Typhi, 2 (<0.1%) Salmonella enterica serovar Paratyphi A, and 27 (0.3%) nontyphoid Salmonella (NTS) were isolated. Multidrug-resistant S. Typhi were isolated in Kenya (79% [n = 38]) and Tanzania (89% [n = 8]) only. Reduced ciprofloxacin-susceptible (22% [n = 11]) S. Typhi were isolated only in Kenya. Among those 11 isolates, all had a Glu133Gly mutation in the gyrA gene combined with either a gyrA (Ser83Phe) or gyrB mutation (Ser464Phe). One Salmonella Paratyphi A isolate with reduced susceptibility to ciprofloxacin was found in Senegal, with 1 mutation in gyrA (Ser83Phe) and a second mutation in parC (Ser57Phe). Mutations in the parE gene and PMQR genes were not detected in any isolate. CONCLUSIONS: Salmonella Typhi with reduced susceptibility to ciprofloxacin was not distributed homogenously throughout SSA. Its prevalence was very high in Kenya, and was not observed in other study countries. Continuous monitoring of antimicrobial susceptibility is required to follow the potential spread of antimicrobial-resistant isolates throughout SSA.
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    Bloodstream Infections and Frequency of Pretreatment Associated With Age and Hospitalization Status in Sub-Saharan Africa.
    (Clin Infect Dis, 2015-11-01) Nichols, Chelsea; Cruz Espinoza, Ligia Maria; von Kalckreuth, Vera; Aaby, Peter; Ahmed El Tayeb, Muna; Ali, Mohammad; Aseffa, Abraham; Bjerregaard-Andersen, Morten; Breiman, Robert F; Cosmas, Leonard; Crump, John A; Dekker, Denise Myriam; Gassama Sow, Amy; Gasmelseed, Nagla; Hertz, Julian T; Im, Justin; Kabore, Leon Parfait; Keddy, Karen H; Konings, Frank; Valborg Løfberg, Sandra; Meyer, Christian G; Montgomery, Joel M; Niang, Aissatou; Njariharinjakamampionona, Andriamampionona; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Jin Kyung; Park, Se Eun; Rabezanahary, Henintsoa; Rakotondrainiarivelo, Jean Philibert; Rakotozandrindrainy, Raphaël; Raminosoa, Tiana Mirana; Rubach, Matthew P; Teferi, Mekonnen; Seo, Hye Jin; Sooka, Arvinda; Soura, Abdramane; Tall, Adama; Toy, Trevor; Yeshitela, Biruk; Clemens, John D; Wierzba, Thomas F; Baker, Stephen; Marks, Florian
    BACKGROUND: The clinical diagnosis of bacterial bloodstream infections (BSIs) in sub-Saharan Africa is routinely confused with malaria due to overlapping symptoms. The Typhoid Surveillance in Africa Program (TSAP) recruited febrile inpatients and outpatients of all ages using identical study procedures and enrollment criteria, thus providing an opportunity to assess disease etiology and pretreatment patterns among children and adults. METHODS: Inpatients and outpatients of all ages with tympanic or axillary temperatures of ≥38.0 or ≥37.5°C, respectively, and inpatients only reporting fever within the previous 72 hours were eligible for recruitment. All recruited patients had one blood sample drawn and cultured for microorganisms. Data from 11 TSAP surveillance sites in nine different countries were used in the analysis. Bivariate analysis was used to compare frequencies of pretreatment and BSIs in febrile children (<15 years old) and adults (≥15 years old) in each country. Pooled Cochran Mantel-Haenszel odds ratios (ORs) were calculated for overall trends. RESULTS: There was no significant difference in the odds of a culture-proven BSI between children and adults among inpatients or outpatients. Among both inpatients and outpatients, children had significantly higher odds of having a contaminated blood culture compared with adults. Using country-pooled data, child outpatients had 66% higher odds of having Salmonella Typhi in their bloodstream than adults (OR, 1.66; 95% confidence interval [CI], 1.01-2.73). Overall, inpatient children had 59% higher odds of pretreatment with analgesics in comparison to inpatient adults (OR, 1.59; 95% CI, 1.28-1.97). CONCLUSIONS: 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.
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    Differential prevalence and geographic distribution of hepatitis C virus genotypes in acute and chronic hepatitis C patients in Vietnam.
    (PloS one, 2019-01) Le Ngoc, Chau; Tran Thi Thanh, Thanh; Tran Thi Lan, Phuong; Nguyen Mai, Trinh; Nguyen Hoa, Trang; Nghiem My, Ngoc; Le Van, Tan; Le Manh, Hung; Le Thanh, Phuong; Nguyen Van Vinh, Chau; Thwaites, Guy; Cooke, Graham; Heilek, Gabrielle M; Shikuma, Cecilia; Le, Thuy; Baker, Stephen; Rahman, Motiur; VIZIONS consortium
    BACKGROUND:The highest burden of disease from hepatitis C virus (HCV) is found in Southeast Asia, but our understanding of the epidemiology of infection in many heavily burdened countries is still limited. In particular, there is relatively little data on acute HCV infection, the outcome of which can be influenced by both viral and host genetics which differ within the region. We studied HCV genotype and IL28B gene polymorphism in a cohort of acute HCV-infected patients in Southern Vietnam alongside two other cohorts of chronic HCV-infected patients to better understand the epidemiology of HCV infection locally and inform the development of programs for therapy with the increasing availability of directly acting antiviral therapy (DAAs). METHODS:We analysed plasma samples from patients with acute and chronic HCV infection, including chronic HCV mono-infection and chronic Human Immunodeficiency Virus (HIV)-HCV coinfection, who enrolled in four epidemiological or clinical research studies. HCV infection was confirmed with RNA testing. The 5' UTR, core and NSB5 regions of HCV RNA positive samples were sequenced, and the genotype and subtype of the viral strains were determined. Host DNA from all HCV positive patients and age- and sex-matched non-HCV-infected control individuals were analysed for IL28B single nucleotide polymorphism (SNP) (rs12979860 and rs8099917). Geolocation of the patients were mapped using QGIS. RESULTS:355 HCV antibody positive patients were analysed; 54.6% (194/355) and 46.4% (161/355) were acute and chronic infections, respectively. 50.4% (81/161) and 49.6.4% (80/161) of chronic infections had HCV mono-infection and HIV-HCV coinfection, respectively. 88.7% (315/355) and 10.1% (36/355) of the patients were from southern and central regions of Vietnam, respectively. 92.4% (328/355) of patients were HCV RNA positive, including 86.1% (167/194) acute and 100% (161/161) chronic infections. Genotype could be determined in 98.4% (322/328) patients. Genotypes 1 (56.5%; 182/322) and 6 (33.9%; 109/322) predominated. Genotype 1 including genotype 1a was significantly higher in HIV-HCV coinfected patients compared to acute HCV patients [43.8% (35/80) versus 20.5% (33/167)], (p = <0.001), while genotype 6 was significantly higher in chronic HCV mono-infected patients [(44.4% (36/81) versus 20.0% (16/80)] (p = < 0.004) compared to HIV-HCV coinfected patients. The prevalence of IL28B SNP (rs12979860) homozygous CC was 86.46% (83/96) in control individuals and was significantly higher in acutely-infected compared to chronically-infected patients [93.2 (82/88) versus 76.1% (35/46)] (p = < 0.005). CONCLUSION:HCV genotype 6 is highly prevalent in Vietnam and the high prevalence in treatment naïve chronic HCV patients may results from poor spontaneous clearance of acute HCV infection with genotype 6.
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    Invasive Non-typhoidal Salmonella Infections in Asia: Clinical Observations, Disease Outcome and Dominant Serovars from an Infectious Disease Hospital in Vietnam
    (PLOS Neglected Tropical Diseases, 2016-08-11) Phu Huong Lan, Nguyen; Le Thi Phuong, Tu; Nguyen Huu, Hien; Thuy, Le; Mather, Alison E; Park, Se Eun; Marks, Florian; Thwaites, Guy E; Van Vinh Chau, Nguyen; Thompson, Corinne N; Baker, Stephen
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    The decline of typhoid and the rise of non-typhoid salmonellae and fungal infections in a changing HIV landscape: bloodstream infection trends over 15 years in southern Vietnam
    (Transactions of the Royal Society of Tropical Medicine and Hygiene, 2012-01) Nga, Tran Vu Thieu; Parry, Christopher M; Le, Thuy; Lan, Nguyen Phu Huong; Diep, To Song; Campbell, James I; Hoang, Nguyen Van Minh; Dung, Le Thi; Wain, John; Dolecek, Christiane; Farrar, Jeremy J; Chau, Nguyen Van Vinh; Hien, Tran Tinh; Day, Jeremy N; Baker, Stephen
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    The Relationship Between Invasive Nontyphoidal Salmonella Disease, Other Bacterial Bloodstream Infections, and Malaria in Sub-Saharan Africa.
    (Clin Infect Dis, 2016-03-15) Park, Se Eun; Pak, Gi Deok; Aaby, Peter; Adu-Sarkodie, Yaw; Ali, Mohammad; Aseffa, Abraham; Biggs, Holly M; Bjerregaard-Andersen, Morten; Breiman, Robert F; Crump, John A; Cruz Espinoza, Ligia Maria; Eltayeb, Muna Ahmed; Gasmelseed, Nagla; Hertz, Julian T; Im, Justin; Jaeger, Anna; Parfait Kabore, Leon; von Kalckreuth, Vera; Keddy, Karen H; Konings, Frank; Krumkamp, Ralf; MacLennan, Calman A; Meyer, Christian G; Montgomery, Joel M; Ahmet Niang, Aissatou; Nichols, Chelsea; Olack, Beatrice; Panzner, Ursula; Park, Jin Kyung; Rabezanahary, Henintsoa; Rakotozandrindrainy, Raphaël; Sampo, Emmanuel; Sarpong, Nimako; Schütt-Gerowitt, Heidi; Sooka, Arvinda; Soura, Abdramane Bassiahi; Sow, Amy Gassama; Tall, Adama; Teferi, Mekonnen; Yeshitela, Biruk; May, Jürgen; Wierzba, Thomas F; Clemens, John D; Baker, Stephen; Marks, Florian
    BACKGROUND: Country-specific studies in Africa have indicated that Plasmodium falciparum is associated with invasive nontyphoidal Salmonella (iNTS) disease. We conducted a multicenter study in 13 sites in Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania to investigate the relationship between the occurrence of iNTS disease, other systemic bacterial infections, and malaria. METHODS: Febrile patients received a blood culture and a malaria test. Isolated bacteria underwent antimicrobial susceptibility testing, and the association between iNTS disease and malaria was assessed. RESULTS: A positive correlation between frequency proportions of malaria and iNTS was observed (P = .01; r = 0.70). Areas with higher burden of malaria exhibited higher odds of iNTS disease compared to other bacterial infections (odds ratio [OR], 4.89; 95% CI, 1.61-14.90; P = .005) than areas with lower malaria burden. Malaria parasite positivity was associated with iNTS disease (OR, 2.44; P = .031) and gram-positive bacteremias, particularly Staphylococcus aureus, exhibited a high proportion of coinfection with Plasmodium malaria. Salmonella Typhimurium and Salmonella Enteritidis were the predominant NTS serovars (53/73; 73%). Both moderate (OR, 6.05; P = .0001) and severe (OR, 14.62; P < .0001) anemia were associated with iNTS disease. CONCLUSIONS: A positive correlation between iNTS disease and malaria endemicity, and the association between Plasmodium parasite positivity and iNTS disease across sub-Saharan Africa, indicates the necessity to consider iNTS as a major cause of febrile illness in malaria-holoendemic areas. Prevention of iNTS disease through iNTS vaccines for areas of high malaria endemicity, targeting high-risk groups for Plasmodium parasitic infection, should be considered.
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    The Typhoid Fever Surveillance in Africa Program (TSAP): Clinical, Diagnostic, and Epidemiological Methodologies.
    (Clin Infect Dis, 2016-03-15) von Kalckreuth, Vera; Konings, Frank; Aaby, Peter; Adu-Sarkodie, Yaw; Ali, Mohammad; Aseffa, Abraham; Baker, Stephen; Breiman, Robert F; Bjerregaard-Andersen, Morten; Clemens, John D; Crump, John A; Cruz Espinoza, Ligia Maria; Deerin, Jessica Fung; Gasmelseed, Nagla; Sow, Amy Gassama; Im, Justin; Keddy, Karen H; Cosmas, Leonard; May, Jürgen; Meyer, Christian G; Mintz, Eric D; Montgomery, Joel M; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Se Eun; Rakotozandrindrainy, Raphaël; Schütt-Gerowitt, Heidi; Soura, Abdramane Bassiahi; Warren, Michelle R; Wierzba, Thomas F; Marks, Florian
    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.
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    Utilization of Healthcare in the Typhoid Fever Surveillance in Africa Program.
    (Clin Infect Dis, 2016-03-15) Panzner, Ursula; Pak, Gi Deok; Aaby, Peter; Adu-Sarkodie, Yaw; Ali, Mohammad; Aseffa, Abraham; Baker, Stephen; Bjerregaard-Andersen, Morten; Crump, John A; Deerin, Jessica; Cruz Espinoza, Ligia Maria; Gasmelseed, Nagla; Heriniaina, Jean Noël; Hertz, Julian T; Im, Justin; von Kalckreuth, Vera; Keddy, Karen H; Lankoande, Bruno; Løfberg, Sandra; Meyer, Christian G; Oresto, Michael Munishi; Park, Jin Kyung; Park, Se Eun; Rakotozandrindrainy, Raphaël; Sarpong, Nimako; Soura, Abdramane Bassiahi; Gassama Sow, Amy; Tall, Adama; Teferi, Mekonnen; Worku, Alemayehu; Yeshitela, Biruk; Wierzba, Thomas F; Marks, Florian
    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.