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1.
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
3.
PLoS Negl Trop Dis ; 13(9): e0007620, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31513580

RESUMO

Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever, a systemic human infection with a burden exceeding 20 million cases each year that occurs disproportionately among children in low and middle income countries. Antimicrobial therapy is the mainstay for treatment, but resistance to multiple agents is common. Here we report genotypes and antimicrobial resistance (AMR) determinants detected from routine whole-genome sequencing (WGS) of 533 S. Typhi isolates referred to Public Health England between April 2014 and March 2017, 488 (92%) of which had accompanying patient travel information obtained via an enhanced surveillance questionnaire. The majority of cases involved S. Typhi 4.3.1 (H58) linked with travel to South Asia (59%). Travel to East and West Africa were associated with genotypes 4.3.1 and 3.3.1, respectively. Point mutations in the quinolone resistance determining region (QRDR), associated with reduced susceptibility to fluoroquinolones, were very common (85% of all cases) but the frequency varied significantly by region of travel: 95% in South Asia, 43% in East Africa, 27% in West Africa. QRDR triple mutants, resistant to ciprofloxacin, were restricted to 4.3.1 lineage II and associated with travel to India, accounting for 23% of cases reporting travel to the country. Overall 24% of isolates were MDR, however the frequency varied significantly by region and country of travel: 27% in West Africa, 52% in East Africa, 55% in Pakistan, 24% in Bangladesh, 3% in India. MDR determinants were plasmid-borne (IncHI1 PST2 plasmids) in S. Typhi 3.1.1 linked to West Africa, but in all other regions MDR was chromosomally integrated in 4.3.1 lineage I. We propose that routine WGS data from travel-associated cases in industrialised countries could serve as informal sentinel AMR genomic surveillance data for countries where WGS is not available or routinely performed.


Assuntos
Farmacorresistência Bacteriana/genética , Salmonella typhi/genética , Febre Tifoide/epidemiologia , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Quinolonas/farmacologia , Inquéritos e Questionários , Doença Relacionada a Viagens , Febre Tifoide/microbiologia , Sequenciamento Completo do Genoma
4.
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
5.
Med. clín (Ed. impr.) ; 153(5): 205-212, sept. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-183997

RESUMO

El incremento de los viajes internacionales, la creciente presencia de vectores transmisores de arbovirus en nuestro país, las alertas de fiebres hemorrágicas, como el actual brote de ébola en la R. D. del Congo y los casos autóctonos de fiebre hemorrágica de Crimea-Congo en nuestro país, ponen de nuevo en primer plano las enfermedades tropicales. El aislamiento de los casos sospechosos de enfermedades de alta transmisibilidad y letalidad ha de ser una prioridad (fiebres hemorrágicas, MERS-CoV). Al valorar al paciente, una cuidadosa historia clínica basada en los aspectos epidemiológicos de la zona de procedencia, las actividades realizadas, el tiempo de estancia en el mismo y el inicio de los síntomas nos ayudarán finalmente, si no al diagnóstico definitivo, sí al menos a descartar las enfermedades que signifiquen una amenaza para él. Por su frecuencia y gravedad la malaria debe ser descartada, sin olvidar las otras causas habituales de fiebre con las que el médico de urgencias debe estar familiarizado también


The increase in international travel, the growing presence of arbovirus vectors in our country, and notifications of haemorrhagic fever such as the current outbreak of Ebola in D.R. Congo and the cases of Crimea-Congo haemorrhagic fever in our country have again cast the spotlight on tropical diseases Isolating suspected cases of highly contagious and lethal diseases must be a priority (Haemorrhagic fever, MERS-CoV). Assessing the patient, taking a careful medical history based on epidemiological aspects of the area of origin, activities they have carried out, their length of stay in the area and the onset of symptoms, will eventually help us, if not to make a definitive diagnosis, at least to exclude diseases that pose a threat to these patients. Malaria should be ruled out because of its frequency, without forgetting other common causes of fever familiar to emergency doctors


Assuntos
Humanos , Controle Sanitário de Viajantes , Doença Relacionada a Viagens , Isolamento de Pacientes/tendências , Saúde do Viajante , Doenças Transmissíveis Importadas/epidemiologia , Febres Hemorrágicas Virais/epidemiologia , Infecções por Arbovirus/epidemiologia , Arbovirus/isolamento & purificação , Meningite/epidemiologia , Febre Tifoide/epidemiologia , Rickettsia/isolamento & purificação , Coronavirus/isolamento & purificação , Esquistossomose/epidemiologia
6.
PLoS Negl Trop Dis ; 13(7): e0007539, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31314752

RESUMO

Typhoid fever is endemic across sub-Saharan Africa. However, estimates of the burden of typhoid are undermined by insufficient blood volumes and lack of sensitivity of blood culture. Here, we aimed to address this limitation by exploiting pre-enrichment culture followed by PCR, alongside routine blood culture to improve typhoid case detection. We carried out a prospective diagnostic cohort study and enrolled children (aged 0-4 years) with non-specific febrile disease admitted to a tertiary hospital in Blantyre, Malawi from August 2014 to July 2016. Blood was collected for culture (BC) and real-time PCR after a pre-enrichment culture in tryptone soy broth and ox-bile. DNA was subjected to PCR for invA (Pan-Salmonella), staG (S. Typhi), and fliC (S. Typhimurium) genes. A positive PCR was defined as invA plus either staG or fliC (CT<29). IgM and IgG ELISA against four S. Typhi antigens was also performed. In total, 643 children (median age 1.3 years) with nonspecific febrile disease were enrolled; 31 (4.8%) were BC positive for Salmonella (n = 13 S. Typhi, n = 16 S. Typhimurium, and n = 2 S. Enteritidis). Pre-enrichment culture of blood followed by PCR identified a further 8 S. Typhi and 15 S. Typhimurium positive children. IgM and IgG titres to the S. Typhi antigen STY1498 (haemolysin) were significantly higher in children that were PCR positive but blood culture negative compared to febrile children with all other non-typhoid illnesses. The addition of pre-enrichment culture and PCR increased the case ascertainment of invasive Salmonella disease in children by 62-94%. These data support recent burden estimates that highlight the insensitivity of blood cultures and support the targeting of pre-school children for typhoid vaccine prevention in Africa. Blood culture with real-time PCR following pre-enrichment should be used to further refine estimates of vaccine effectiveness in typhoid vaccine trials.


Assuntos
Carga Bacteriana , Efeitos Psicossociais da Doença , Febre/microbiologia , Febre Tifoide/epidemiologia , Antígenos de Bactérias/genética , Hemocultura , Pré-Escolar , Feminino , Febre/epidemiologia , Hospitalização , Humanos , Lactente , Recém-Nascido , Malaui/epidemiologia , Masculino , Estudos Prospectivos , Salmonella typhi/genética , Febre Tifoide/sangue , Febre Tifoide/diagnóstico
7.
Emerg Infect Dis ; 25(8): 1501-1510, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31310226

RESUMO

Immigrants traveling to their birth countries to visit friends or relatives are disproportionately affected by travel-related infections, in part because most preventive travel health services are not publicly funded. To help identify cost-effective policies to reduce this disparity, we measured the medical costs (in 2015 Canadian dollars) of 3 reportable travel-related infectious diseases (hepatitis A, malaria, and enteric fever) that accrued during a 3-year period (2012-2014) in an ethnoculturally diverse region of Canada (Peel, Ontario) by linking reportable disease surveillance and health administrative data. In total, 318 case-patients were included, each matched with 2 controls. Most spending accrued in inpatient settings. Direct healthcare spending totaled $2,058,196; the mean attributable cost per case was $6,098 (95% CI $5,328-$6,868) but varied by disease (range $4,558-$7,852). Costs were greatest for enteric fever. Policies that address financial barriers to preventive health services for high-risk groups should be evaluated.


Assuntos
Custos de Cuidados de Saúde , Hepatite A/epidemiologia , Malária/epidemiologia , Doença Relacionada a Viagens , Febre Tifoide/epidemiologia , Estudos de Casos e Controles , Feminino , Hepatite A/história , História do Século XXI , Humanos , Malária/história , Masculino , Ontário/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Vigilância em Saúde Pública , Febre Tifoide/história
8.
Artigo em Inglês | MEDLINE | ID: mdl-31284613

RESUMO

Proximal characteristics and conditions in the residential setting deserve greater attention for their potential to influence typhoid transmission. Using a case-control design in Central Division, Republic of Fiji, we examined bacterial (coliform and Escherichia coli) contamination and chemical composition of water and soil as potential vehicles of exposure to Salmonella Typhi, combining observational analysis of residential living conditions, geospatial analysis of household locations, and factor analysis to explore multivariate associations with the risk of developing typhoid fever. Factors positively associated with typhoid infection related to drainage [phosphate (OR 4.235, p = 0.042) and E. coli concentrations (OR 2.248, p = 0.029) in toilet drainage soil, housing [external condition (OR 3.712, p < 0.001)], drinking water contamination (OR 2.732, p = 0.003) and sanitary condition (OR 1.973, p = 0.031). These five factors explained 42.5% of the cumulative variance and were significant in predicting typhoid infection. Our results support the hypothesis that a combination of spatial and biophysical attributes of the residential setting influence the probability of typhoid transmission; in this study, factors associated with poor drainage, flooding, and sanitary condition increase local exposure to contaminated water and soil, and thereby infection. These findings extend testing of causal assumptions beyond the immediate domestic domain, enhance the scope of traditional case control epidemiology and allow greater specificity of interventions at the scale of the residential setting.


Assuntos
Salmonella typhi , Febre Tifoide/epidemiologia , Microbiologia da Água , Adolescente , Adulto , Estudos de Casos e Controles , Características da Família , Feminino , Fiji/epidemiologia , Humanos , Instituições Residenciais , Água/química , Abastecimento de Água
10.
BMC Infect Dis ; 19(1): 487, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151421

RESUMO

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.


Assuntos
Salmonella typhi/genética , Salmonella typhi/isolamento & purificação , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Cloranfenicol/uso terapêutico , Ciprofloxacino/uso terapêutico , Técnicas de Laboratório Clínico/estatística & dados numéricos , Surtos de Doenças , Resistência Microbiana a Medicamentos/genética , Eletroforese em Gel de Campo Pulsado , Feminino , Haplótipos , Humanos , Laboratórios/estatística & dados numéricos , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Salmonella enterica/classificação , Salmonella enterica/genética , Salmonella enterica/isolamento & purificação , Salmonella typhi/classificação , Sorogrupo , Febre Tifoide/diagnóstico , Febre Tifoide/tratamento farmacológico , Zimbábue/epidemiologia
11.
Epidemiol Mikrobiol Imunol ; 68(1): 47-50, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31181952

RESUMO

Typhoid fever is a disease caused by the highly virulent bacterium Salmonella Typhi. It is transmitted by the oral-faecal route. In the Czech Republic, 53 cases of typhoid fever were reported in 1997-2017. Only seven of these cases were autochthonous. In August 2017, an imported case of typhoid fever was recorded in a 25-year-old unvaccinated woman who participated in the Rainbow Gathering in Italy one week prior to the onset of the disease. During her stay in Italy, she slept in a tent, ate her own food, and drank unboiled water. Presenting with persisting cough, tiredness, muscle and joint pain, and fever up to 40 °C after her return, she was admitted to the Třebíč Hospital where she was diagnosed with S. Typhi. The epidemiological investigation identified six contacts. On discharge from hospital and at follow-up, the patient was tested negative. None of the contacts became ill.


Assuntos
Doença Relacionada a Viagens , Febre Tifoide , Adulto , República Tcheca/epidemiologia , Feminino , Humanos , Itália , Salmonella typhi , Febre Tifoide/diagnóstico , Febre Tifoide/epidemiologia , Febre Tifoide/patologia
12.
Indian J Med Res ; 149(3): 404-411, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31249207

RESUMO

Background & objectives: : Azithromycin has been in use as an alternate treatment option for enteric fever even when the guidelines on the susceptibility testing were not available. There is lack of data on susceptibility and mechanisms of resistance of azithromycin in Salmonella Typhi and S. Paratyphi A. The aim of the present study was to determine the azithromycin susceptibility and resistance mechanisms in typhoidal salmonellae isolates archived in a tertiary care centre in north India for a period of 25 years. Methods: : Azithromycin susceptibility was determined in 602 isolates of S. Typhi (469) and S. Paratyphi A (133) available as archived collection isolated during 1993 to 2016, by disc diffusion and E-test method.PCR was done for ereA, ermA, ermB, ermC, mefA, mphA and msrA genes from plasmid and genomic DNA and sequencing was done to detect mutations in acrR, rplD and rplV genes. Results: : Azithromycin susceptibility was seen in 437/469 [93.2%; 95% confidence interval (CI), 90.5 to 95.1%] isolates of S. Typhi. Amongst 133 isolates of S. Paratyphi A studied, minimum inhibitory concentration (MIC) of ≤16 mg/l was found in 102 (76.7%; 95% CI, 68.8 to 83.0). MIC value ranged between 1.5 and 32 mg/l with an increasing trend in MIC50and MIC90with time. Mutations were found in acrR in one and rplV in two isolates of S. Typhi. No acquired mechanism for macrolide resistance was found. Interpretation & conclusions: : Azithromycin could be considered as a promising agent against typhoid fever on the basis of MIC distribution in India. However, due to emergence of resistance in some parts, there is a need for continuous surveillance of antimicrobial susceptibility and resistance mechanisms. There is also a need to determine the breakpoints for S. Paratyphi A.


Assuntos
Azitromicina/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Febre Tifoide/tratamento farmacológico , Azitromicina/efeitos adversos , Proteínas de Bactérias/classificação , Humanos , Índia/epidemiologia , Mutação/genética , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/genética , Salmonella enterica/patogenicidade , Salmonella paratyphi A/efeitos dos fármacos , Salmonella paratyphi A/genética , Salmonella paratyphi A/patogenicidade , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/genética , Salmonella typhi/patogenicidade , Febre Tifoide/epidemiologia , Febre Tifoide/genética , Febre Tifoide/microbiologia
13.
Indian J Med Res ; 149(2): 263-269, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31219092

RESUMO

Background & objectives: Antimicrobial resistance is a major challenge in the treatment of typhoid fever with limited choices left to empirically treat these patients. The present study was undertaken to determine the current practices of antibiotic use in children attending a tertiary care hospital in north India. Methods: This was a descriptive observational study in children suffering from enteric fever as per the case definition including clinical and laboratory parameters. The antibiotic audit in hospitalized children was measured as days of therapy per 1000 patient days and in outpatient department (OPD) as antibiotic prescription on the treatment card. Results: A total of 128 children with enteric fever were included in the study, of whom, 30 were hospitalized and 98 were treated from OPD. The mean duration of fever was 9.5 days at the time of presentation. Of these, 45 per cent were culture positive with Salmonella Typhi being aetiological agent in 68 per cent followed by S. Paratyphi A in 32 per cent. During hospitalization, the average length of stay was 10 days with mean duration of defervescence 6.4 days. Based on antimicrobial susceptibility ceftriaxone was given to 28 patients with mean duration of treatment being six days. An additional antibiotic was needed in six patients due to clinical non-response. In OPD, 79 patients were prescribed cefixime and additional antibiotic was needed in five during follow up visit. Interpretation & conclusions: Based on our findings, ceftriaxone and cefixime seemed to be the first line of antibiotic treatment for typhoid fever. Despite susceptibility, clinical non-response was seen in around 10 per cent of the patients who needed combinations of antibiotics.


Assuntos
Ceftriaxona/administração & dosagem , Ciprofloxacino/administração & dosagem , Farmacorresistência Bacteriana Múltipla/genética , Febre Tifoide/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Índia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/patogenicidade , Salmonella paratyphi A/efeitos dos fármacos , Salmonella paratyphi A/patogenicidade , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/patogenicidade , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia
14.
PLoS One ; 14(4): e0214650, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31009473

RESUMO

Typhoid fever affects 21 million people globally, 1% of whom succumb to the disease. The social, economic and public health consequences of this disease disproportionately affect people in Africa and Asia. In order to design context specific prevention strategies, we need to holistically characterise outbreaks in these settings. In this study, we used retrospective data (2013-2016) at national and district level to characterise temporal and spatial dynamics of Typhoid fever outbreaks using time series and spatial analysis. We then selected cases matched with controls to investigate household socio-economic drivers using a conditional logistic regression model, and also developed a Typhoid fever outbreak-forecasting framework. The incidence rate of Typhoid fever at national and district level was ~ 160 and 60 cases per 100,000 persons per year, respectively, predominantly in urban areas. In Kasese district, Bwera sub-county registered the highest incidence rate, followed by Kisinga, Kitholhu and Nyakiyumbu sub-counties. The male-female case ratio at district level was at 1.68 and outbreaks occurred between the 20th and 40th week (May and October) each year following by seven weeks of precipitation. Our forecasting framework predicted outbreaks better at the district level rather than national. We identified a temporal window associated with Typhoid fever outbreaks in Kasese district, which is preceded by precipitation, flooding and displacement of people. We also observed that areas with high incidence of Typhoid fever also had high environmental contamination with limited water treatment. Taken together with the forecasting framework, this knowledge can inform the development of specific control and preparedness strategies at district and national level.


Assuntos
Febre Tifoide/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Surtos de Doenças , Características da Família , Feminino , Humanos , Umidade , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Salmonella/isolamento & purificação , Temperatura Ambiente , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Uganda/epidemiologia , Adulto Jovem
15.
BMC Infect Dis ; 19(1): 330, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999894

RESUMO

BACKGROUND: Invasive Salmonella infections result in significant morbidity and mortality in developing countries. In Asia, typhoid and paratyphoid fever are reported to be the major invasive Salmonella infections, while invasive non-typhoidal Salmonella (iNTS) infections are believed to be uncommon. Data from Sarawak, in Malaysian Borneo, are limited. METHODS: A retrospective study identifying all children aged < 15 years with invasive Salmonella infections from 2011 to 2016 was conducted in Bintulu Hospital in Sarawak. Population incidences, clinical and bacterial characteristics were examined. RESULTS: Forty-four patients were identified during the 6-year study period: 43 had iNTS infection and 1 had typhoid fever. The average annual iNTS incidence was 32.4 per 100,000 children aged < 5 years. None of the children had malaria or HIV infection, and only 7% were severely malnourished. Salmonella Enteritidis and Salmonella Java were the commonest NTS serovars identified. Pneumonia was the most common manifestation of iNTS disease, present in 20 (47%) children. Other manifestations included gastroenteritis, fever without a source, septic arthritis and meningitis. Salmonella Enteritidis was identified in 76% of those with pneumonia, significantly more frequently than in children with other manifestations. Over 25% of children with iNTS developed severe disease and nearly 10% suffered long term morbidity or mortality. While 78% of Salmonella Java isolates were multi-drug resistant, nearly all other isolates were susceptible to most antimicrobials, including ampicillin. CONCLUSIONS: Bintulu Division in Sarawak observed a very high incidence of childhood iNTS infections. Enteric fever was uncommon. The epidemiology of invasive Salmonella infections in Malaysian Borneo differs considerably from that of neighbouring countries in Asia.


Assuntos
Infecções por Salmonella/diagnóstico , Adolescente , Anti-Infecciosos/farmacologia , Bornéu/epidemiologia , Criança , Pré-Escolar , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Lactente , Malásia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Estudos Retrospectivos , Salmonella/efeitos dos fármacos , Salmonella/isolamento & purificação , Infecções por Salmonella/epidemiologia , Salmonella enteritidis/efeitos dos fármacos , Salmonella enteritidis/isolamento & purificação , Sorogrupo , Febre Tifoide/diagnóstico , Febre Tifoide/epidemiologia
16.
Int J Infect Dis ; 81: 191-195, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30849581

RESUMO

BACKGROUND: The primary method of molecular subtyping for the identification and investigation of outbreaks has been pulsed-field gel electrophoresis (PFGE). In some cases, this technique has not been able to show discrimination between the unrelated strains that can be achieved by whole genome sequencing (WGS). METHODS: The aim of this study was to determine the strengths and drawbacks of WGS using different analytic approaches compared to traditional typing method, PFGE, for retrospectively typing clusters cases of 28 S. Typhi. RESULTS: We evaluated three analytical approaches on the WGS data set (Nucleotide Difference (ND), (SNPs) and Whole genome multi locus sequence typing (wgMLST) that identically classified the clusters-related strains into two clusters, cluster A (with strains from 2017), and Cluster B (with strains from 2007). CONCLUSIONS: In this study WGS based typing, was able to compete with PFGE for differentiation of the clusters of S. Typhi strains.


Assuntos
Salmonella typhi/genética , Salmonella typhi/isolamento & purificação , Febre Tifoide/microbiologia , Antibacterianos/administração & dosagem , Brasil/epidemiologia , Pré-Escolar , Surtos de Doenças , Eletroforese em Gel de Campo Pulsado , Feminino , Humanos , Masculino , Tipagem de Sequências Multilocus , Estudos Retrospectivos , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/fisiologia , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia , Sequenciamento Completo do Genoma
17.
Microb Genom ; 5(4)2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30920366

RESUMO

The ability to distinguish different circulating pathogen clones from each other is a fundamental requirement to understand the epidemiology of infectious diseases. Phylogenetic analysis of genomic data can provide a powerful platform to identify lineages within bacterial populations, and thus inform outbreak investigation and transmission dynamics. However, resolving differences between pathogens associated with low-variant (LV) populations carrying low median pairwise single nucleotide variant (SNV) distances remains a major challenge. Here we present rPinecone, an R package designed to define sub-lineages within closely related LV populations. rPinecone uses a root-to-tip directional approach to define sub-lineages within a phylogenetic tree according to SNV distance from the ancestral node. The utility of this software was demonstrated using both simulated outbreaks and real genomic data of two LV populations: a hospital outbreak of methicillin-resistant Staphylococcus aureus and endemic Salmonella Typhi from rural Cambodia. rPinecone identified the transmission branches of the hospital outbreak and geographically confined lineages in Cambodia. Sub-lineages identified by rPinecone in both analyses were phylogenetically robust. It is anticipated that rPinecone can be used to discriminate between lineages of bacteria from LV populations where other methods fail, enabling a deeper understanding of infectious disease epidemiology for public health purposes.


Assuntos
Staphylococcus aureus Resistente à Meticilina/genética , Salmonella typhi/genética , Infecções Estafilocócicas , Febre Tifoide , Camboja , Surtos de Doenças , Genoma Bacteriano/genética , Humanos , Filogenia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Software , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia
18.
BMC Infect Dis ; 19(1): 288, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30917795

RESUMO

BACKGROUND: Enteric fever is one of the common infectious diseases of humans. The objectives of this study were to:1) estimate the prevalence of enteric fever among febrile patients visiting Ambo hospital; 2) comparison of Widal test and stool culture;3) evaluation of the antimicrobial susceptibility of isolates; and 4) assess potential risk factors to acquire enteric fever infection. METHODS: Blood and stool samples were collected from 372 febrile patients with symptoms clinically similar to enteric fever. Widal test was used for testing sera while stool culturing and bacterial identification was done using WHO standard methods. Susceptibility testing was done using Kirby-Bauer disc diffusion method. Chi-Square test and Logistic Regression analysis were used to analyze the data. RESULTS: The apparent and true prevalence of enteric fever were 56.2% (95% confidence interval [CI]: 50.97-61.29%) and 57.52% (95% CI: 52.3-62.6%) respectively, while, the culture prevalence was 2.7% (95% CI: 1.30-4.89%). Isolation rates of S. Typhi and S. Paratyphi were 0.8% (95% CI: 0.17-2.34%) and 1.9% (95% CI: 0.76-3.84%) respectively. The isolates showed 100% resistance to amoxicillin, bacitracin, erythromycin, 80%resistance to cefotaxime and streptomycin and 20% for chloramphenicol. The sensitivity, specificity, positive and negative predictive values of Widal test was 80.0, 44.5, 3.8 and 98.8% respectively. Multivariable logistic regression analysis revealed that age (adjusted odds ratio [aOR] = 2.45; 95% CI: 1.38-4.37; P = 0.002), religion (aOR = 15.57, 95% CI: 3.01-80.64; P = 0.001), level of education (aOR = 2.60, 95% CI: 1.27-5.28; P = 0.009), source of water (aOR = 2.20, 95% CI: 1.21-3.98; P = 0.009), raw milk (aOR =2.19, 95% CI:1.16-4.16; P = 0.016) and raw meat consumption (aOR = 1.80, 95% CI: 1.07-3.01; P = 0.026) are the predictors of enteric fever seropositivity. CONCLUSIONS: Patients were wrongly diagnosed and treated for enteric fever by Widal test. Therefore, rapid tests with better sensitivity and specificity are needed for the diagnosis of enteric fever. Provision of safe water and health education are vital to bring behavioral change towards raw food consumption.


Assuntos
Anti-Infecciosos/farmacologia , Técnicas Microbiológicas/métodos , Salmonella typhi/isolamento & purificação , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos Transversais , Testes Diagnósticos de Rotina , Etiópia/epidemiologia , Fezes/microbiologia , Feminino , Hospitais/estatística & dados numéricos , Humanos , Testes Imunológicos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Salmonella typhi/efeitos dos fármacos , Sensibilidade e Especificidade , Adulto Jovem
20.
Pak J Pharm Sci ; 32(1(Supplementary)): 323-326, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30829210

RESUMO

Malaria and typhoid fever are among the major infectious diseases which impose significant health and socioeconomic burden on affected populations. Further, co-infection and resembling symptomatology in both infections, mostly leads to misdiagnosis and mistreatment. So co-infection of malaria and typhoid fever is becoming a major issue in tropical and subtropical countries. The current study was planned to explore the rate of co-infection of malaria and typhoid fever to show the diagnostic challenges and people health implications in the local population of Faisalabad-Pakistan. For this purpose, 144 samples (n=144) were collected from suspected subjects both male (n=74) and female (n=70) (comprises of three age group ranges viz >01-10, 11-20 and above 20 years old) of typhoid fever and malaria from October to December 2017 at Children Hospital, Faisalabad-Pakistan. Thick smear as a gold standard technique for malaria diagnosis and Widal agglutination technique for typhoid diagnosis were used. Results revealed that the prevalence of co-infection in selected subjects was 6.3% (n=9) with higher prevalence in female subjects (7.1%) as compared to males (5.4%). Further, it was also reported that age groups >01-10 years old, 11-20 years old and 21-above years old have6.6 % (n=75), 5.7 % (n=35) and 5.8% (n=34), coinfection prevalence respectively. In the present study, it could be concluded that although the prevalence of co-infection of malaria and typhoid fever in the studied population was possible but sensitivity of diagnostic tools was limited, so more reliable, specific and sensitive diagnostic tools are required to report confidently more precise correlation of these infectious diseases.


Assuntos
Malária/epidemiologia , Febre Tifoide/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Coinfecção/epidemiologia , Feminino , Humanos , Lactente , Masculino , Paquistão/epidemiologia , Prevalência
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