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1.
Folia Med Cracov ; 60(1): 25-32, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658209

RESUMO

Outbreaks of typhoid fever for centuries decimated armies, cities and large hosts of people. Discovery of an agent causing such a grave disease became one of the most important achievements of bacteriology - science, which had experienced rapid development in the last quarter of the 19th century and changed the course of our civilization.The article deals with the discovery of Tadeusz Browicz, Polish anatomopathologist, who in 1874 reported about rod-shaped "parasites" in viscera of typhoid fever victim. His achievement became shaded by the later discoveries of Eberth, Klebs and Gaffky, but as authors stated below, Browicz should be recognized with mentioned scientists as a co-discoverer of the typhoid fever bacillus.


Assuntos
Surtos de Doenças/história , Salmonella typhi/isolamento & purificação , Febre Tifoide/diagnóstico , Febre Tifoide/história , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Achados Incidentais , Polônia/epidemiologia , Febre Tifoide/epidemiologia
2.
BMC Infect Dis ; 20(1): 422, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552753

RESUMO

BACKGROUND: In Kenya, typhoid fever and invasive non-typhoidal salmonellosis present a huge burden of disease, especially in poor-resource settings where clean water supply and sanitation conditions are inadequate. The epidemiology of both diseases is poorly understood in terms of severity and risk factors. The aim of the study was to determine the disease burden and spatial distribution of salmonellosis, as well as socioeconomic and environmental risk factors for these infections, in a large informal settlement near the city of Nairobi, from 2013 to 2017. METHODS: Initially, a house-to-house baseline census of 150,000 population in Mukuru informal settlement was carried out and relevant socioeconomic, demographic, and healthcare utilization information was collected using structured questionnaires. Salmonella bacteria were cultured from the blood and faeces of children < 16 years of age who reported at three outpatient facilities with fever alone or fever and diarrhea. Tests of association between specific Salmonella serotypes and risk factors were conducted using Pearson Chi-Square (χ2) test. RESULTS: A total of 16,236 children were recruited into the study. The prevalence of bloodstream infections by Non-Typhoidal Salmonella (NTS), consisting of Salmonella Typhimurium/ Enteriditis, was 1.3%; Salmonella Typhi was 1.4%, and this was highest among children < 16 years of age. Occurrence of Salmonella Typhimurium/ Enteriditis was not significantly associated with rearing any domestic animals. Rearing chicken was significantly associated with high prevalence of S. Typhi (2.1%; p = 0.011). The proportion of children infected with Salmonella Typhimurium/ Enteriditis was significantly higher in households that used water pots as water storage containers compared to using water directly from the tap (0.6%). Use of pit latrines and open defecation were significant risk factors for S. Typhi infection (1.6%; p = 0.048). The proportion of Salmonella Typhimurium/ Enteriditis among children eating street food 4 or more times per week was higher compared to 1 to 2 times/week on average (1.1%; p = 0.032). CONCLUSION: Typhoidal and NTS are important causes of illness in children in Mukuru informal settlement, especially among children less than 16 years of age. Improving Water, Sanitation and Hygiene (WASH) including boiling water, breastfeeding, hand washing practices, and avoiding animal contact in domestic settings could contribute to reducing the risk of transmission of Salmonella disease from contaminated environments.


Assuntos
Infecções por Salmonella/epidemiologia , Salmonella typhi/imunologia , Salmonella typhimurium/imunologia , Febre Tifoide/epidemiologia , Adolescente , Animais , Galinhas , Criança , Pré-Escolar , Características da Família , Fezes/microbiologia , Feminino , Humanos , Higiene , Lactente , Recém-Nascido , Quênia/epidemiologia , Masculino , Áreas de Pobreza , Prevalência , Fatores de Risco , Infecções por Salmonella/microbiologia , Salmonella typhi/isolamento & purificação , Salmonella typhimurium/isolamento & purificação , Saneamento , Testes Sorológicos , Febre Tifoide/microbiologia
3.
Int J Infect Dis ; 97: 334-336, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32569838

RESUMO

OBJECTIVES: Enteric fever remains an important diagnostic and treatment challenge in febrile children living in the tropics. In the context of a national Salmonella enterica serovar Paratyphi A outbreak, the objective of this retrospective study was to compare features of S. Typhi and S. Paratyphi A infections in Cambodian children. METHODS: Clinical and laboratory features were reviewed for 192 blood culture-confirmed children with S. Typhi and S. Paratyphi A infections presenting to a paediatric referral hospital in Siem Reap, 2012-2016. RESULTS: Children with S. Typhi infections were younger, were more likely to have chills and/or diarrhoea, and were more frequently hospitalized than those with S. Paratyphi A infections. Over three quarters (88.3%) of S. Typhi isolates were multidrug-resistant, compared to none of the S. Paratyphi A. CONCLUSIONS: In this small study of Cambodian children, S. Typhi infections were more severe than S. Paratyphi A infections. Antibiotic resistance limits treatment options for enteric fever in this population.


Assuntos
Febre Paratifoide/microbiologia , Salmonella paratyphi A/fisiologia , Salmonella typhi/fisiologia , Febre Tifoide/microbiologia , Adolescente , Antibacterianos/administração & dosagem , Camboja/epidemiologia , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Masculino , Febre Paratifoide/tratamento farmacológico , Febre Paratifoide/epidemiologia , Estudos Retrospectivos , Salmonella paratyphi A/genética , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/genética , Salmonella typhi/isolamento & purificação , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia
4.
J Med Microbiol ; 69(6): 817-823, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32459614

RESUMO

Introduction. Identification of typhoidal Salmonella (TS) serovars and their discrimination from non-typhoidal Salmonella (NTS) is conventionally performed by seroagglutination. This method is labour-intensive, requires technical experience and can be inconclusive in some cases. Molecular assays may be reliable alternative diagnostic tools.Aim. This study was designed to evaluate the eazyplex TyphiTyper based on loop-mediated isothermal amplification (LAMP) for fast identification of TS and S. Choleraesuis in culture.Methodology. A total of 121 Salmonella strains and 33 isolates of other Enterobacterales species were tested by the eazyplex TyphiTyper. Simulated and clinical blood cultures (BCs) were used to examine the performance of the assay for diagnosis of systemic infection. Sample preparation took about 5 min and the test running time was 20 min. Amplification was measured by real-time fluorescence detection.Results. All TS and S. Choleraesuis strains were correctly identified. The most common NTS S. Typhimurium (n=34) and S. Enteritidis (n=15) were detected as Salmonella species without any false positive result for TS targets. Cross-reactions of NTS with TS were only rarely observed. Direct testing of positive BCs gave correct results. Sensitivities and specificities of the assay were as follows: 100 and 99.3 % for S. Typhi, 100 and 98.7 % for S. Paratyphi A, 100 and 97.3 % for S. Paratyphi B, 100 and 100 % for S. Paratyphi C, 100 and 100 % for S. Choleraesuis, and 100 and 100 % for Salmonella species, respectively.Conclusion. The eazyplex TyphiTyper is very easy to perform and allows the rapid identification of TS and S. Choleraesuis isolates.


Assuntos
Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Salmonella/isolamento & purificação , Humanos , Salmonella/classificação , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação
5.
Appl Environ Microbiol ; 86(13)2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32332133

RESUMO

The "Moore swab" is a classic environmental surveillance tool whereby a gauze pad tied with string is suspended in flowing water or wastewater contaminated with human feces and harboring enteric pathogens that pose a human health threat. In contrast to single volume "grab" samples, Moore swabs act as continuous filters to "trap" microorganisms, which are subsequently isolated and confirmed using appropriate laboratory methods. Continuous filtration is valuable for the isolation of transiently present pathogens such as human-restricted Salmonella enterica serovars Typhi and Paratyphi A and B. The technique was first proposed (1948) to trace Salmonella Paratyphi B systematically through sewers to pinpoint the residence of a chronic carrier responsible for sporadic outbreaks of paratyphoid fever. From 1948 to 1986, Moore swabs proved instrumental to identify long-term human reservoirs (chronic carriers) and long-cycle environmental transmission pathways of S Typhi and Paratyphi, for example, to decipher endemic transmission in Santiago, Chile, during the 1980s. Despite limitations such as intermittent shedding of typhoidal Salmonella by humans and the effects of dilution, S Typhi and S Paratyphi have been recovered from sewers, surface waters, irrigation canals, storm drains, flush toilets, and septic tanks by using Moore swabs. Driven by the emergence of multiple antibiotic-resistant S Typhi and S Paratyphi A strains that limit treatment options, several countries are embarking on accelerated typhoid control programs using vaccines and environmental interventions. Moore swabs, which are regaining appreciation as important components of the public health/environmental microbiology toolbox, can enhance environmental surveillance for typhoidal Salmonella, thereby contributing to the control of typhoid fever.


Assuntos
Monitoramento Ambiental/instrumentação , Salmonella enterica/isolamento & purificação , Esgotos/microbiologia , Águas Residuárias/microbiologia , Filtração , Humanos , Salmonella typhi/isolamento & purificação , Febre Tifoide/epidemiologia
6.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(3): 323-326, 2020 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-32187940

RESUMO

To conduct outbreak identification and transmission factor analysis of typhoid epidemic occurred in Xinqiao town, Jiangyin city from June to September 2016. A total of 14 strains of Salmonella typhi isolated from confirmed cases were collected, and 65 external environment samples and 13 food samples related to the outbreak were taken. Real-time PCR was used to detect specific gene of Salmonella typhi in the samples. Conventional method was used to isolate strains. The strains isolated from both the samples and patients in the epidemic were subjected to antimicrobial susceptibility testing and PFGE molecular characteristics. Salmonella typhi strain was isolated from one external sample (well water of a deli processing plant). The results of drug susceptibility showed that 15 strains were resistant to nalidixic acid. A total of 15 strains of Salmonella typhi were divided into 2 molecular patterns by pulsed field gel electrophoresis. The fingerprints of PFGE from the 13 patients and the environmental isolate were completely consistent, and there was one band difference from the other patient isolate. Combined with the epidemiological investigation and laboratory test results, it was determined that the outbreak was caused by genetic clone of the same Salmonella typhi. Food processing plant should be one of the key links.


Assuntos
DNA Bacteriano/genética , Surtos de Doenças , Epidemias , Salmonella enterica/genética , Salmonella typhi/genética , Febre Tifoide/epidemiologia , Antibacterianos/uso terapêutico , China/epidemiologia , Resistência Microbiana a Medicamentos , Eletroforese em Gel de Campo Pulsado , Humanos , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase em Tempo Real , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/isolamento & purificação , Salmonella typhi/classificação , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Febre Tifoide/diagnóstico , Febre Tifoide/tratamento farmacológico , Febre Tifoide/microbiologia
7.
PLoS Negl Trop Dis ; 14(3): e0008040, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32155148

RESUMO

Salmonella Typhi (S. Typhi) is the causative agent of typhoid fever; a systemic disease affecting ~20 million people per year globally. There are little data regarding the contemporary epidemiology of typhoid in Latin America. Consequently, we aimed to describe some recent epidemiological aspects of typhoid in Colombia using cases reported to the National Public Health Surveillance System (Sivigila) between 2012 and 2015. Over the four-year reporting period there were 836 culture confirmed cases of typhoid in Colombia, with the majority (676/836; 80.1%) of reported cases originated from only seven departments. We further characterized 402 S. Typhi isolates with available corresponding data recovered from various departments of Colombia through antimicrobial susceptibility testing and molecular subtyping. The majority (235/402; 58.5%) of these typhoid cases occurred in males and were most commonly reported in those aged between 10 and 29 years (218/402; 54.2%); there were three (0.74%) reported fatalities. The overwhelming preponderance (339/402; 84.3%) of S. Typhi were susceptible to all tested antimicrobials. The most common antimicrobial to which the organisms exhibited non-susceptibility was ampicillin (30/402;7.5%), followed by nalidixic acid (23/402, 5.7%). Molecular subtyping identified substantial genetic diversity, which was well distributed across the country. Despite the diffuse pattern of S. Typhi genotypes, we identified various geographical hotspots of disease associated with local dominant genotypes. Notably, we found limited overlap of Colombian genotypes with organisms reported in other Latin American countries. Our work highlights a substantial burden of typhoid in Colombia, characterized by sustained transmission in some regions and limited epidemics in other departments. The disease is widely distributed across the country and associated with multiple antimicrobial susceptible genotypes that appear to be restricted to Colombia. This study provides a current perspective for typhoid in Latin America and highlights the importance of pathogen-specific surveillance to add insight into the limited epidemiology of typhoid in this region.


Assuntos
Salmonella typhi/isolamento & purificação , Febre Tifoide/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Colômbia/epidemiologia , Farmacorresistência Bacteriana , Monitoramento Epidemiológico , Feminino , Variação Genética , Genótipo , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Estudos Retrospectivos , Salmonella typhi/classificação , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/genética , Distribuição por Sexo , Adulto Jovem
8.
Z Gastroenterol ; 58(2): 160-170, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32050286

RESUMO

Typhoid fever and paratyphoid fever are systemic infectious diseases of global significance caused by Salmonella enterica subspecies enterica Serovar Typhi (short name: Salmonella Typhi) or Serovar Paratyphi (short name: Salmonella Paratyphi). The course of these fecal-orally transmitted diseases is mainly characterized by a high fever. Left untreated, the course of typhoid fever can be severe and lethal. The infection is almost always acquired outside of Europe (mainly in India) and is notifiable in Germany, Austria and Switzerland. Paratyphoid is an attenuated disease of typhoid fever caused by Salmonella Paratyphi. Available vaccines only protect against Salmonella Typhi. Antibiotic resistance reflects the situation in endemic countries and shows a worrying increase of multi-drug resistant isolates. Currently, third-generation cephalosporins such as ceftriaxone are recommended as first-line therapy; if sensitive to quinolones, fluoroquinolones such as ciprofloxacin may continue to be administered. Crucial preventive measures for travelers to endemic regions include consistent water and food hygiene as well as vaccination, whereby only protection rates of 50-70 % are achieved by currently available vaccines. In the light of increasing multi-drug resistance, a more effective conjugate vaccine against Salmonella Typhi with cross-reactivity against Salmonella Paratyphi is needed more than ever.


Assuntos
Antibacterianos/farmacologia , Febre Paratifoide/tratamento farmacológico , Febre Paratifoide/prevenção & controle , Salmonella paratyphi A/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/tratamento farmacológico , Febre Tifoide/prevenção & controle , Vacinas Conjugadas/administração & dosagem , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Fluoroquinolonas/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Febre Paratifoide/diagnóstico , Febre Paratifoide/microbiologia , Quinolonas/uso terapêutico , Salmonella enterica , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Febre Tifoide/diagnóstico , Febre Tifoide/microbiologia
10.
PLoS Negl Trop Dis ; 14(2): e0008036, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32106221

RESUMO

BACKGROUND: Multi-drug resistant typhoid fever remains an enormous public health threat in low and middle-income countries. However, we still lack a detailed understanding of the epidemiology and genomics of S. Typhi in many regions. Here we have undertaken a detailed genomic analysis of typhoid in urban Dhaka, Bangladesh to unravel the population structure and antimicrobial resistance patterns in S. Typhi isolated between 2004-2016. PRINCIPAL FINDINGS: Whole genome sequencing of 202 S. Typhi isolates obtained from three study locations in urban Dhaka revealed a diverse range of S. Typhi genotypes and AMR profiles. The bacterial population within Dhaka were relatively homogenous with little stratification between different healthcare facilities or age groups. We also observed evidence of exchange of Bangladeshi genotypes with neighboring South Asian countries (India, Pakistan and Nepal) suggesting these are circulating throughout the region. This analysis revealed a decline in H58 (genotype 4.3.1) isolates from 2011 onwards, coinciding with a rise in a diverse range of non-H58 genotypes and a simultaneous rise in isolates with reduced susceptibility to fluoroquinolones, potentially reflecting a change in treatment practices. We identified a novel S. Typhi genotype, subclade 3.3.2 (previously defined only to clade level, 3.3), which formed two localized clusters (3.3.2.Bd1 and 3.3.2.Bd2) associated with different mutations in the Quinolone Resistance Determining Region (QRDR) of gene gyrA. SIGNIFICANCE: Our analysis of S. Typhi isolates from urban Dhaka, Bangladesh isolated over a twelve year period identified a diverse range of AMR profiles and genotypes. The observed increase in non-H58 genotypes associated with reduced fluoroquinolone susceptibility may reflect a change in treatment practice in this region and highlights the importance of continued molecular surveillance to monitor the ongoing evolution of AMR in Dhaka. We have defined new genotypes and lineages of Bangladeshi S. Typhi which will facilitate the identification of these emerging AMR clones in future surveillance efforts.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Salmonella typhi/efeitos dos fármacos , Bangladesh/epidemiologia , DNA Bacteriano/genética , Genoma Bacteriano , Genótipo , Humanos , Internacionalidade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Infecções por Salmonella/transmissão , Salmonella typhi/genética , Salmonella typhi/isolamento & purificação , Fatores de Tempo , Viagem , População Urbana
11.
PLoS Negl Trop Dis ; 14(1): e0007805, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31945052

RESUMO

BACKGROUND: In surveillance for typhoid fever, under-detection of cases occurs when patients with fever do not seek medical care, or seek medical care but do not receive a blood test. Missing data may result in incorrect estimates of disease incidence. METHODS: We used data from an ongoing randomised clinical trial of typhoid conjugate vaccine among children in Nepal to determine if eligible patients attending our fever clinics who did not have blood taken for culture had a lower risk of disease than those who had blood drawn. We assessed clinical and demographic predictors of having blood taken for culture, and predictors of culture-positive results. Missing blood culture data were imputed using multiple imputations. RESULTS: During the first year of surveillance, 2392 fever presentations were recorded and 1615 (68%) of these had blood cultures. Children were more likely to have blood taken for culture if they were older, had fever for longer, a current temperature ≥38 degrees, or if typhoid or a urinary tract infection were suspected. Based on imputation models, those with blood cultures were 1.87 times more likely to have blood culture-positive fever than those with missing data. CONCLUSION: Clinical opinion on the cause of the fever may play a large part in the decision to offer blood culture, regardless of study protocol. Crude typhoid incidence estimates should be adjusted for the proportion of cases that go undetected due to missing blood cultures while adjusting for the lower likelihood of culture-positivity in the group with missing data.


Assuntos
Hemocultura/estatística & dados numéricos , Febre/diagnóstico , Febre Tifoide/diagnóstico , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Diagnóstico Ausente , Nepal/epidemiologia , Febre Paratifoide/sangue , Febre Paratifoide/diagnóstico , Febre Paratifoide/epidemiologia , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Febre Tifoide/sangue , Febre Tifoide/epidemiologia , Infecções Urinárias
12.
BMC Med ; 18(1): 1, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898501

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention. METHODS: We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance. FINDINGS: We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified. INTERPRETATION: Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice. TRIAL REGISTRATION: PROSPERO CRD42018029432.


Assuntos
Salmonella paratyphi A , Salmonella typhi , Febre Tifoide/epidemiologia , Antibacterianos/farmacologia , Azitromicina/farmacologia , Farmacorresistência Bacteriana , Saúde Global , Humanos , Febre Paratifoide/epidemiologia , Prevalência , Salmonella paratyphi A/classificação , Salmonella paratyphi A/efeitos dos fármacos , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/classificação , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Febre Tifoide/tratamento farmacológico
13.
Malawi Med J ; 31(3): 184-192, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31839887

RESUMO

Background: Over-dependence on clinical presentation and/or the Widal agglutination test for the diagnosis of typhoid fever in developing countries can lead to antibiotic abuse. In Nigeria, the antibiotic resistance of typhoid organisms is poorly characterized. In this study, we determined the prevalence of culture positivity among patients suspected of having typhoid fever, evaluated the diagnostic value of the Widal test and the burden created by the multi-drug resistance of typhoid organisms in South-East Nigeria. Methodology: This was a prospective and case-controlled study carried out between 2013 and 2016. We acquired samples of blood/stool/urine cultures, and data relating to the Widal agglutination test and malaria parasites from 810 febrile patients (suspected of having typhoid) and 288 apparently healthy controls. Individuals with a history of antibiotic use within the previous 14 days were excluded. We then carried out antibiotic susceptibility tests on all isolates. Multi-drug resistance was defined as a resistance to ≥3 of the antibiotics tested. We determined the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Widal test for typhoid laboratory diagnosis compared to bacterial culture which is the gold standard. A P-value <0.05 was considered to be statistically significant. Results: The mean age of typhoid suspects was 33.1±6.5 years and 50.7% were women. Of the 810 typhoid suspects tested, 114 (14.1%) had positive cultures for the typhoid organisms Salmonella enterica serovar paratyphi (72) and S. enterica serovar Typhi (42). Sample-specific rates of culture positivity were as follows: stool (72; 8.9%), blood (21; 2.6%) and urine (21; 2.6%), P<0.001. None of the controls had typhoid isolates. The sensitivity, specificity, PPV and NPV of the Widal test were 49.1%, 90.7%, 46.2% and 91.6%, respectively. Malaria parasitaemia was detected in 180 (22.2%) febrile patients, out of whom 115 (63.9%) had a positive Widal test for O/H antigens vs. 1% (6/630) in those with negative malaria parasite test results (P<0.001). The rate of false-positive Widal titres was 48%. Antibiotic multi-drug resistance was detected in 52.6% of patients. The antibiotics with the highest susceptibility were ciprofloxacin, levofloxacin and meropenem (all 100% susceptibility) and ceftriaxone (95.6% susceptibility). Conclusion: Our data showed that while typhoid fever is common in Nigeria, malaria is more prevalent. Our analysis showed that the Widal test performed poorly as a diagnostic test and that the burden created by multi-drug resistance was high. Our data indicate that periodic surveillance of antibiotic susceptibility is critical for optimal typhoid therapy.


Assuntos
Testes de Aglutinação/métodos , Antibacterianos/farmacologia , Anticorpos Antibacterianos/sangue , Febre/etiologia , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Febre Tifoide/diagnóstico , Febre Tifoide/epidemiologia , Adulto , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Farmacorresistência Bacteriana , Feminino , Humanos , Testes de Sensibilidade Microbiana , Nigéria/epidemiologia , Prevalência , Estudos Prospectivos , Sensibilidade e Especificidade , Febre Tifoide/tratamento farmacológico , Febre Tifoide/microbiologia
14.
N Engl J Med ; 381(23): 2209-2218, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31800986

RESUMO

BACKGROUND: Salmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking. METHODS: In this phase 3, randomized, controlled trial in Lalitpur, Nepal, in which both the participants and observers were unaware of the trial-group assignments, we randomly assigned children who were between 9 months and 16 years of age, in a 1:1 ratio, to receive either a TCV or a capsular group A meningococcal conjugate vaccine (MenA) as a control. The primary outcome was typhoid fever confirmed by blood culture. We present the prespecified analysis of the primary and main secondary outcomes (including an immunogenicity subgroup); the 2-year trial follow-up is ongoing. RESULTS: A total of 10,005 participants received the TCV and 10,014 received the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 7 participants who received TCV (79 cases per 100,000 person-years) and in 38 who received MenA vaccine (428 cases per 100,000 person-years) (vaccine efficacy, 81.6%; 95% confidence interval, 58.8 to 91.8; P<0.001). A total of 132 serious adverse events (61 in the TCV group and 71 in the MenA vaccine group) occurred in the first 6 months, and 1 event (pyrexia) was identified as being vaccine-related; the participant remained unaware of the trial-group assignment. Similar rates of adverse events were noted in the two trial groups; fever developed in 5.0% of participants in the TCV group and 5.4% in the MenA vaccine group in the first week after vaccination. In the immunogenicity subgroup, seroconversion (a Vi IgG level that at least quadrupled 28 days after vaccination) was 99% in the TCV group (677 of 683 participants) and 2% in the MenA vaccine group (8 of 380 participants). CONCLUSIONS: A single dose of TCV was immunogenic and effective in reducing S. Typhi bacteremia in children 9 months to 16 years of age. (Funded by the Bill and Melinda Gates Foundation; Current Controlled Trials number, ISRCTN43385161.).


Assuntos
Salmonella typhi/isolamento & purificação , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/imunologia , Vacinas Conjugadas/imunologia , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Doenças Endêmicas/prevenção & controle , Feminino , Humanos , Incidência , Lactente , Estimativa de Kaplan-Meier , Masculino , Vacinas Meningocócicas/efeitos adversos , Vacinas Meningocócicas/imunologia , Nepal/epidemiologia , Febre Tifoide/diagnóstico , Febre Tifoide/epidemiologia , Vacinas Tíficas-Paratíficas/efeitos adversos , Vacinas Conjugadas/efeitos adversos
15.
Biomed Microdevices ; 21(4): 95, 2019 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-31707575

RESUMO

Enteric fever is one of the leading causes of infection and subsequent fatality (greater than 1.8 million) (WHO 2018), especially in the developing countries due to contaminated water and food inter twinned with unhygienic practices. Clinical gold standard technique of culture-based method followed by biochemical tests demand 72+ hours for diagnosis while newly developed techniques (like PCR, RT-PCR, DNA microarray etc.) suffer from high limit of detection or involve high-cost infrastructure or both. In this work, a quick and highly specific method, SMOL was established for simultaneous detection of Salmonella paratyphi A and Salmonella typhi in clinical blood samples. SMOL consists of (i) pre-concentration of S. typhi and S. paratyphi A cells using magnetic nanoparticles followed by (ii) cell lysis and DNA extraction (iii) amplification of select nucleic acids by LAMP technique and (iv) detection of amplified nucleic acids using an affordable portable device (costs less than $70). To identify the viability of target cells at lower concentrations, the samples were processed at two different time periods of t = 0 and t = 4 h. Primers specific for the SPA2539 gene in S. paratyphi A and STY2879 gene in S. typhi were used for LAMP. Within 6 h SMOL was able to detect positive and negative samples from 55 human clinical blood culture samples and detect the viability of the cells. The results were concordant with culture and biochemical tests as well as by qPCR. Statistical power analysis yielded 100%. SMOL results were concordant with culture and biochemical tests as well as by qPCR. The sensitive and affordable system SMOL will be effective for poor resource settings.


Assuntos
Sangue/microbiologia , Custos e Análise de Custo , Limite de Detecção , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Testes Sorológicos/economia , Testes Sorológicos/instrumentação , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Humanos , Técnicas de Amplificação de Ácido Nucleico , Salmonella paratyphi A/genética , Salmonella typhi/genética , Fatores de Tempo , Febre Tifoide/microbiologia
16.
PLoS Negl Trop Dis ; 13(11): e0007868, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31730615

RESUMO

BACKGROUND: With the rise in fluoroquinolone-resistant Salmonella Typhi and the recent emergence of ceftriaxone resistance, azithromycin is one of the last oral drugs available against typhoid for which resistance is uncommon. Its increasing use, specifically in light of the ongoing outbreak of extensively drug-resistant (XDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, cotrimoxazole, streptomycin, fluoroquinolones and third-generation cephalosporins) in Pakistan, places selective pressure for the emergence and spread of azithromycin-resistant isolates. However, little is known about azithromycin resistance in Salmonella, and no molecular data are available on its mechanism. METHODS AND FINDINGS: We conducted typhoid surveillance in the two largest pediatric hospitals of Bangladesh from 2009-2016. All typhoidal Salmonella strains were screened for azithromycin resistance using disc diffusion and resistance was confirmed using E-tests. In total, we identified 1,082 Salmonella Typhi and Paratyphi A strains; among these, 13 strains (12 Typhi, 1 Paratyphi A) were azithromycin-resistant (MIC range: 32-64 µg/ml) with the first case observed in 2013. We sequenced the resistant strains, but no molecular basis of macrolide resistance was identified by the currently available antimicrobial resistance prediction tools. A whole genome SNP tree, made using RAxML, showed that the 12 Typhi resistant strains clustered together within the 4.3.1.1 sub-clade (H58 lineage 1). We found a non-synonymous single-point mutation exclusively in these 12 strains in the gene encoding AcrB, an efflux pump that removes small molecules from bacterial cells. The mutation changed the conserved amino acid arginine (R) at position 717 to a glutamine (Q). To test the role of R717Q present in azithromycin-resistant strains, we cloned acrB from azithromycin-resistant and sensitive strains, expressed them in E. coli, Typhi and Paratyphi A strains and tested their azithromycin susceptibility. Expression of AcrB-R717Q in E. coli and Typhi strains increased the minimum inhibitory concentration (MIC) for azithromycin by 11- and 3-fold respectively. The azithromycin-resistant Paratyphi A strain also contained a mutation at R717 (R717L), whose introduction in E. coli and Paratyphi A strains increased MIC by 7- and 3-fold respectively, confirming the role of R717 mutations in conferring azithromycin resistance. CONCLUSIONS: This report confirms 12 azithromycin-resistant Salmonella Typhi strains and one Paratyphi A strain. The molecular basis of this resistance is one mutation in the AcrB protein at position 717. This is the first report demonstrating the impact of this non-synonymous mutation in conferring macrolide resistance in a clinical setting. With increasing azithromycin use, strains with R717 mutations may spread and be acquired by XDR strains. An azithromycin-resistant XDR strain would shift enteric fever treatment from outpatient departments, where patients are currently treated with oral azithromycin, to inpatient departments to be treated with injectable antibiotics like carbapenems, thereby further burdening already struggling health systems in endemic regions. Moreover, with the dearth of novel antimicrobials in the horizon, we risk losing our primary defense against widespread mortality from typhoid. In addition to rolling out the WHO prequalified typhoid conjugate vaccine in endemic areas to decrease the risk of pan-resistant Salmonella Typhi strains, it is also imperative to implement antimicrobial stewardship and water sanitation and hygiene intervention to decrease the overall burden of enteric fever.


Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Farmacorresistência Bacteriana , Salmonella paratyphi A/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/microbiologia , Proteínas de Bactérias , Bangladesh , DNA Bacteriano/química , DNA Bacteriano/genética , Genótipo , Hospitais Pediátricos , Humanos , Proteínas de Membrana Transportadoras , Testes de Sensibilidade Microbiana , Polimorfismo de Nucleotídeo Único , Salmonella paratyphi A/classificação , Salmonella paratyphi A/genética , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/classificação , Salmonella typhi/genética , Salmonella typhi/isolamento & purificação , Sequenciamento Completo do Genoma
17.
Trop Med Int Health ; 24(12): 1369-1383, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31633858

RESUMO

OBJECTIVES: Hospital-based studies of community-onset bloodstream infections (CO-BSI) are less resource-intensive to carry out than population-based incidence studies. We examined several metrics capturing the potential role of Salmonella Typhi as a cause of CO-BSI for making inferences about incidence. METHODS: We systematically reviewed three databases for hospital-based studies of CO-BSI. We determined, by study, the prevalence and rank order of Salmonella among pathogenic bloodstream isolates, and the prevalence ratio of Salmonella Typhi to Escherichia coli (S:E ratio). We then describe these hospital-based study metrics in relation to population-based typhoid fever incidence data from a separate systematic review. RESULTS: Forty-four studies met the inclusion criteria, of which 23 (52.3%) isolated Salmonella Typhi at least once. Among studies isolating Salmonella Typhi, the median (interquartile range) prevalence and rank order of Salmonella Typhi compared to other pathogens isolated in BSI was 8.3% (3.2-37.9%) and 3 (1-6), respectively. The median (interquartile range) S:E ratio was 1.0 (0.4-3.0). With respect to incidence, in Pemba Island, Tanzania, prevalence, rank order, S:E ratio, and incidence was 64.8%, 1, 9.2 and 110 cases per 100 000, respectively, and in Boulkiemdé, Burkina Faso, was 13.3%, 3, 2.3 and 249 cases per 100 000. CONCLUSIONS: We describe considerable variation in place and time for Salmonella Typhi prevalence, rank order, and S:E ratio among hospital-based studies of CO-BSI. Data from simultaneous typhoid prevalence and incidence studies are limited. We propose that hospital-based study metrics warrant evaluation for making inference about typhoid incidence and as covariates in typhoid incidence models.


Assuntos
Bacteriemia/epidemiologia , Hospitalização , Salmonella typhi/isolamento & purificação , Febre Tifoide/epidemiologia , Bacteriemia/etiologia , Bacteriemia/microbiologia , Burkina Faso/epidemiologia , Feminino , Humanos , Incidência , Masculino , Prevalência , Tanzânia/epidemiologia , Febre Tifoide/etiologia , Febre Tifoide/microbiologia
18.
J Med Case Rep ; 13(1): 303, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31551082

RESUMO

BACKGROUND: Typhoid fever is a human-specific disease caused by a bacterium, Salmonella enterica subspecies enterica serovar Typhi. It is transmitted through ingestion of contaminated food or water. It is mostly diagnosed by blood culture. Salmonella Typhi usually manifests as a febrile illness with bacteremia after initial entry through the gastrointestinal route, but it can occasionally cause significant disease in extraintestinal sites. We report a case of a girl in Fiji with a right ovarian abscess infected by Salmonella Typhi. CASE PRESENTATION: A 14-year-old iTaukei (indigenous Fijian) girl presented to our hospital with abdominal pain of 1 month's duration. Two days prior to her admission, she developed high-grade fever and nausea and had one episode of vomiting. On presentation, she appeared unwell; she was tachycardic (116 beats per minute) and febrile (38.8 °C). Her abdominal examination revealed generalized tenderness. Other examination findings were normal. The provisional diagnosis of abdominal sepsis led to an emergency laparotomy during which an enlarged right ovary was found to be spontaneously discharging pus. The ovary was incised and drained, and the patient was commenced on intravenous ceftriaxone 1 g twice daily, cloxacillin 1 g four times daily, and metronidazole 500 mg three times daily. She recovered promptly and was discharged to home on the sixth postoperative day. The purulent material from the ovary grew Salmonella Typhi. CONCLUSION: Extraintestinal infections caused by Salmonella Typhi are rare but can cause severe and life-threatening disease. Our patient had a prolonged history of abdominal pain and was found to have a ruptured right ovarian abscess due to Salmonella Typhi. Ovarian abscesses in girls who are not sexually active are not associated with pelvic inflammatory disease and suggest local or hematogenous spread. This case report may increase health workers awareness to include common and endemic infections in the differential diagnosis of unusual clinical presentations to help the initiation of appropriate investigation and management as quickly as possible.


Assuntos
Abscesso/microbiologia , Doenças Ovarianas/microbiologia , Salmonella typhi/isolamento & purificação , Febre Tifoide/diagnóstico , Dor Abdominal/etiologia , Adolescente , Feminino , Humanos
20.
BMC Med Genomics ; 12(1): 126, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481113

RESUMO

BACKGROUND: Indigenous typhoid fever was continuing to be identified in Taiwan which has not been endemic for the enteric fever for more than 20 years. The source and transmission by which the local patients acquired typhoid and the population structure of the indigenous typhoid strains remain not well characterized. METHODS: During 2001 and 2014, non-duplicated clinical Salmonella enterica serovar Typhi isolates in a hospital were analyzed by whole-genome sequencing (WGS) and determined for pulsotypes. Maximum likelihood phylogeny was constructed by nucleotide alterations in core genomes and compared to the framework of global typhoid strains. Potential source and transmission were traced by correlating the phylogeny and the temporal relationship between isolates. RESULTS: A total of 43 S. Typhi isolates from indigenous cases were analyzed and a majority (39, 90.7%) of them were belonged to six WGS-defined genotypes prevailing mainly in Southeast Asia. Genotype 3.4.0 and a multidrug-resistant type 4.3.1 (also known as pandemic H58 haplotype) were associated respectively with two solitary small-scale outbreaks, implying a transmission mode of importation followed by outbreak. Twelve isolates with nearly identical core genomes were belonged to genotype 3.2.1 but were categorized into three different pulsotypes. The 3.2.1 isolates were identified across 13 years and involved in three clusters and a sporadic case, indicating sustained local transmission of the same strain. The remaining indigenous isolates belonging to three genotypes (2.1, 3.1.2, and 3.0.0) were of substantial genetic diversity and isolated at different time points, indicating independent event of each case. CONCLUSIONS: Indigenous typhoid in Taiwan occurred mainly with the forms of small-scale outbreaks or sporadic events likely by contracting imported strains which prevailed in Southeast Asia. Sustained local transmission of certain strain was also evident by WGS analysis, but not by conventional pulsotyping, highlighting the importance of continuing molecular surveillance of typhoid fever with adequate tools in the non-endemic region.


Assuntos
Dinâmica Populacional , Febre Tifoide/epidemiologia , Febre Tifoide/transmissão , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Demografia , Surtos de Doenças , Genoma Humano , Humanos , Filogenia , Salmonella typhi/isolamento & purificação , Taiwan/epidemiologia , Febre Tifoide/tratamento farmacológico , Febre Tifoide/microbiologia , Sequenciamento Completo do Genoma
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