RESUMEN
In sub-Saharan Africa, the burden of typhoid fever, caused by Salmonella enterica serovar Typhi, remains largely unknown, in part because of a lack of blood or bone marrow culture facilities. We characterized a total of 323 S. Typhi isolates from outbreaks in Kenya over the period 1988 to 2008 for antimicrobial susceptibilities and phylogenetic relationships using single-nucleotide polymorphism (SNP) analysis. There was a dramatic increase in the number and percentage of multidrug-resistant (MDR) S. Typhi isolates over the study period. Overall, only 54 (16.7%) S. Typhi isolates were fully sensitive, while the majority, 195 (60.4%), were multiply resistant to most commonly available drugs-ampicillin, chloramphenicol, tetracycline, and cotrimoxazole; 74 (22.9%) isolates were resistant to a single antimicrobial, usually ampicillin, cotrimoxazole, or tetracycline. Resistance to these antibiotics was encoded on self-transferrable IncHI1 plasmids of the ST6 sequence type. Of the 94 representative S. Typhi isolates selected for genome-wide haplotype analysis, sensitive isolates fell into several phylogenetically different groups, whereas MDR isolates all belonged to a single haplotype, H58, associated with MDR and decreased ciprofloxacin susceptibility, which is also dominant in many parts of Southeast Asia. Derivatives of the same S. Typhi lineage, H58, are responsible for multidrug resistance in Kenya and parts of Southeast Asia, suggesting intercontinental spread of a single MDR clone. Given the emergence of this aggressive MDR haplotype, careful selection and monitoring of antibiotic usage will be required in Kenya, and potentially other regions of sub-Saharan Africa.
Asunto(s)
Antibacterianos/farmacología , Técnicas de Tipificación Bacteriana , Farmacorresistencia Bacteriana Múltiple , Salmonella typhi/clasificación , Salmonella typhi/efectos de los fármacos , Fiebre Tifoidea/epidemiología , Fiebre Tifoidea/microbiología , Adulto , Asia Sudoriental/epidemiología , Niño , Preescolar , Análisis por Conglomerados , Genes Bacterianos , Genotipo , Haplotipos , Humanos , Kenia/epidemiología , Filogenia , Plásmidos/análisis , Polimorfismo de Nucleótido Simple , Salmonella typhi/genética , Salmonella typhi/aislamiento & purificaciónRESUMEN
In Africa, multidrug-resistant non-typhoidal salmonellae (NTS) are one of the leading causes of morbidity and high mortality in children under 5 years of age, second in importance only to pneumococcal disease. The authors studied NTS isolates from paediatric admissions at two hospitals in Nairobi, Kenya, and followed the index cases to their homes, where rectal swabs and stools from parents and siblings, and from animals in close contact, were obtained. The majority of NTS obtained from cases were Salmonella enterica serotype Typhimurium (106 out of 193; 54.9%) and Salmonella enterica serotype Enteritidis (64; 33.2%), a significant proportion (34.2%) of which were multiply resistant to three or more antibiotics, including ampicillin, tetracycline, cotrimoxazole and chloramphenicol. Only 23.4% of NTS were fully susceptible to all 10 antibiotics tested. Of the 32 NTS obtained from contacts (nine adults and 23 children) at the homes of index cases, 21 (65.6%) isolates were similar by antibiotic-susceptibility profiles and plasmid content, and their XbaI- and SpeI-digested chromosomal DNA patterns were indistinguishable from those of the corresponding index cases. Only three out of 180 (1.7%) samples from environmental sources, including animals, soil, sewers and food, contained NTS matching those from corresponding index cases. The carriage of NTS in an asymptomatic population was represented by 6.9% of human contacts from 27 out of 127 homes sampled. This population of carriers may represent an important reservoir of NTS that would play a significant role in the epidemiology of community-acquired NTS bacteraemia in children.
Asunto(s)
Portador Sano/microbiología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Salmonella/microbiología , Infecciones por Salmonella/transmisión , Salmonella enterica/efectos de los fármacos , Antibacterianos/farmacología , Niño , Preescolar , Dermatoglifia del ADN , ADN Bacteriano/análisis , ADN Bacteriano/genética , Salud de la Familia , Heces/microbiología , Humanos , Lactante , Recién Nacido , Kenia/epidemiología , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Plásmidos/análisis , Recto/microbiología , Infecciones por Salmonella/epidemiología , Infecciones por Salmonella/patología , Salmonella enterica/clasificación , Salmonella enterica/aislamiento & purificación , Salmonella enterica/patogenicidad , Salmonella enteritidis/clasificación , Salmonella enteritidis/efectos de los fármacos , Salmonella enteritidis/aislamiento & purificación , Salmonella enteritidis/patogenicidad , Salmonella typhimurium/clasificación , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/aislamiento & purificación , Salmonella typhimurium/patogenicidad , ZoonosisRESUMEN
Over the last decade there has been a steady increase in the proportion of multidrug resistance among non-typhoidal salmonellae (NTS) isolated from adult patients with bacteraemia in Kenya. The prevalence of NTS multiply resistant to all commonly available drugs including ampicillin, streptomycin, co-trimoxazole, chloramphenicol and tetracycline rose from 31% in 1994 to 42% at present, with concomitantly higher MICs of each drug. Resistance is encoded on large self-transferable 100-110 kb plasmids. Pulsed field gel electrophoresis of XbaI and SpeI digested chromosomal DNA revealed three main digest patterns for Salmonella enterica serotype Typhimurium and two main patterns for Salmonella enterica serotype Enteritidis. Although the genotypes of NTS remained fairly stable over the last decade, the large increase in MICs of all commonly used drugs and increased MICs of ciprofloxacin, poses a major challenge for treatment of invasive NTS infection.
Asunto(s)
Bacteriemia/epidemiología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Salmonella/epidemiología , Salmonella/clasificación , Salmonella/efectos de los fármacos , Adulto , Antibacterianos/farmacología , Bacteriemia/microbiología , Electroforesis en Gel de Campo Pulsado , Humanos , Kenia/epidemiología , Pruebas de Sensibilidad Microbiana , Plásmidos , Prevalencia , Salmonella/genética , Infecciones por Salmonella/microbiología , SerotipificaciónRESUMEN
We characterized by antibiotic susceptibility, plasmid analysis, incompatibility grouping, and pulsed-field gel electrophoresis (PFGE) of XbaI- and SpeI-digested DNA 102 Salmonella enterica serovar Typhi (serovar Typhi) isolated from recent outbreaks of typhoid in three different parts of Kenya. Only 13.7% were fully susceptible, whereas another 82.4% were resistant to each of the five commonly available drugs: ampicillin, chloramphenicol, and tetracycline (MICs of >256 microg/ml); streptomycin (MIC, >1,024 microg/ml); and cotrimoxazole (MIC of >32 microg/ml). Resistance to these antibiotics was encoded on a 110-kb self-transferable plasmid of IncHI1 incompatibility group. The MICs of nalidixic acid (MIC, 8 to 16 micro g/ml) and ciprofloxacin (MIC of 0.25 to 0.38 micro g/ml) for 41.7% of the 102 serovar Typhi isolates were 5- and 10-fold higher, respectively, than for sensitive strains. Amplification by PCR and sequencing of the genes coding for gyrase (gyrA and gyrB) and topoisomerase IV (parE and parC) within the quinolone resistance-determining region revealed that the increase in the MICs of the quinolones had not resulted from any significant mutation. Analysis of genomic DNA from both antimicrobial agent-sensitive and multidrug-resistant serovar Typhi by PFGE identified two distinct subtypes that were in circulation in the three different parts of Kenya. As the prevalence of multidrug-resistant serovar Typhi increases, newer, more expensive, and less readily available antimicrobial agents will be required for the treatment of typhoid in Kenya.
Asunto(s)
Brotes de Enfermedades , Farmacorresistencia Bacteriana Múltiple , Salmonella typhi/clasificación , Fiebre Tifoidea/epidemiología , Fiebre Tifoidea/microbiología , Adulto , Antibacterianos/farmacología , Técnicas de Tipificación Bacteriana , Conjugación Genética , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Electroforesis en Gel de Campo Pulsado , Humanos , Kenia/epidemiología , Pruebas de Sensibilidad Microbiana , Plásmidos/genética , Salmonella typhi/efectos de los fármacos , Salmonella typhi/genéticaRESUMEN
The paper looks at the usefulness of the Widal agglutination test in the context of variable normal antibody titres in two different populations in Kenya, and in comparison to the blood culture method of diagnosis. It presents a prospective case-control study. We examined 846 blood cultures and an equal number of serum samples, and 782 stools from adults who presented at two study sites; Kenyatta National Hospital and one hospital and 3 clinics in Embu District, with symptoms similar to typhoid. Examined also were 360 serum samples and stools from adults who were apparently healthy (controls) who sought routine medical examination at the study sites. From blood cultures, isolation rates for typhoid for Embu (3% ) and Nairobi (2.2%) were not significantly different (p>0.01). In addition the control population from the two study sites did not show any significant background O antibody titre levels characteristic of typhoid endemic areas. All the 7 commonly available Widal test kits including Murex, Europath, Biotech, Humatex, Biosystems, Microsystems and Typhex, that were evaluated for efficacy were equally specific in diagnosis of typhoid by Widal agglutination methods. However, there were minor differences in the sensitivities of the kits. The Widal test method gave a lower sensitivity (81.3%) than specificity (93%) when compared to the culture of blood for diagnosis of typhoid. Going by the reports of typhoid outbreaks in Embu and Nairobi (ca. 20-25% reported prevalence) we conclude that there has been over-reporting probably due to poor methodologies of performing the Widal test. We recommend adequate clinical examination in suspected cases of typhoid in addition to proper Widal in order to improve typhoid diagnosis. Newer improved methods that are more specific and sensitive than the Widal test need to be evaluated in improving laboratory diagnosis of typhoid.