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BACKGROUND: Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera. METHODS: AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2-23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies. RESULTS: Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, -11.6 [95% confidence interval {CI}, -15.6 to -7.6]) and possible bacterial etiology (RDpossible, -8.7 [95% CI, -13.0 to -4.4]) but not in other children (RDunlikely, -0.3% [95% CI, -2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, -3.1 [95% CI, -5.3 to -1.0]; RDpossible, -2.3 [95% CI, -4.5 to -.01]; RDunlikely, -0.6 [95% CI, -1.9 to .6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella. CONCLUSIONS: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment. CLINICAL TRIALS REGISTRATION: NCT03130114.
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Infecciones Bacterianas , Criptosporidiosis , Cryptosporidium , Disentería , Shigella , Niño , Humanos , Lactante , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Criptosporidiosis/tratamiento farmacológico , Patología Molecular , Diarrea/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Bacterias , Disentería/complicaciones , Disentería/tratamiento farmacológicoRESUMEN
BACKGROUND: The rise of Multidrug-resistant organisms (MDROs) poses a considerable burden on the healthcare systems, particularly in low-middle income countries like Pakistan. There is a scarcity of data on the carriage of MDRO particularly in the pediatrics population therefore, we aimed to determine MDRO carriage in pediatric patients at the time of admission to a tertiary care hospital in Karachi, Pakistan, and to identify the risk factors associated with it. METHODS: A cross-sectional study conducted at the pediatric department of Aga Khan University Hospital (AKUH) from May to September 2019 on 347 children aged 1-18 years. For identification of MDRO (i.e., Extended Spectrum Beta-Lactamase (ESBL) producers, Carbapenem Resistant Enterobacteriaceae (CRE), Vancomycin Resistant Enterococci (VRE), Methicillin Resistant Staphylococcus aureus (MRSA), Multidrug-resistant (MDR) Acinetobacter species and MDR Pseudomonas aeruginosa), nasal swabs and rectal swabs or stool samples were cultured on specific media within 72 h of hospitalization. Data was collected on a predesigned structured questionnaire on demographics, prior use of antibiotics for > 48 h in the last 6 months, history of vaccination in last 6 months, exposure to health care facility regardless of the time of exposure, ICU stay for > 72 h, and about the prior use of medical devices (urinary catheter, central venous lines etc.) in last 1 year. Statistical analysis was performed by Standard statistical software. RESULTS: Out of 347 participants, 237 (68.3%) were found to be MDRO carriers. Forty nine nasal swabs from 346 children (14.2%) showed growth of MRSA. The majority of the stool/rectal swabs (n = 222 of 322; 69%) collected were positive for MDRO. The most isolated species were ESBL Escherichia coli 174/222 (78.3%) followed by ESBL Enterobacter species 37/222 (16.7%) and ESBL Klebsiella pneumoniae 35/222 (15.8%). On univariate analysis, none of the risk factors showed statistically significant association with MDRO carriage. CONCLUSION: Overall, a high prevalence of MDRO carriage was identified among admitted pediatric patients. Implementation of systematic screening may help to identify true burden of MDROs carriage in the health care settings.
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Farmacorresistencia Bacteriana Múltiple , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Hospitalización , Humanos , Lactante , Masculino , Pakistán/epidemiología , Admisión del Paciente , Pediatría , Prevalencia , Factores de Riesgo , Centros de Atención TerciariaRESUMEN
We aimed to detect typhoid carriers by performing duodenal fluid culture in patients in a tertiary care hospital in Pakistan. A cross-sectional study was conducted during 2017 at the Aga Khan University Hospital, Karachi. Patients who underwent upper gastrointestinal endoscopy were included. Participants were interviewed, and duodenal fluid samples were taken for culture to detect Salmonella typhi (S. typhi) and paratyphi. A polymerase chain reaction on 100 randomly selected sub-samples was also conducted. A total of 477 participants were enrolled. The mean age was 42.4±15.5 years. History of typhoid fever was present in 73 (15.3%) participants. Out of the 477 duodenal fluid cultures tested for various micro-organisms, 250 (52.4%) were positive. Neither S. typhi nor paratyphi were isolated. S. typhi was also not detected by PCR. To better detect S. typhi carriage in general population, future studies should target people with gall bladder diseases and screen them using culture and PCR based methods.
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Fiebre Tifoidea , Adulto , Portador Sano/diagnóstico , Portador Sano/epidemiología , Estudios Transversales , Humanos , Persona de Mediana Edad , Salmonella typhi , Centros de Atención Terciaria , Fiebre Tifoidea/diagnóstico , Fiebre Tifoidea/epidemiologíaRESUMEN
BACKGROUND: Typhoid fever is endemic in the urban Kathmandu Valley of Nepal; however, there have been no population-based studies of typhoid outside of this community in the past 3 decades. Whether typhoid immunization should be prioritized in periurban and rural communities has been unclear. METHODS: We performed population-based surveillance for enteric fever in 1 urban catchment (Kathmandu) and 1 periurban and rural catchment (Kavrepalanchok) as part of the Surveillance for Enteric Fever in Asia Project (SEAP). We recruited individuals presenting to outpatient and emergency departments at 2 study hospitals with suspected enteric fever and performed blood cultures. Additionally, we conducted a household survey in each catchment area to characterize care seeking for febrile illness. We evaluated spatial heterogeneity in febrile illness, care seeking, and enteric fever incidence. RESULTS: Between September 2016 and September 2019, we enrolled 5736 participants with suspected enteric fever at 2 study hospitals. Among these, 304 (5.3%) were culture positive for Salmonella Typhi (249 [81.9%]) or Paratyphi A (55 [18.1%]). Adjusted typhoid incidence in Kathmandu was 484 per 100 000 person-years and in Kavrepalanchok was 615 per 100 000 person-years. While all geographic areas for which estimates could be made had incidence >200 per 100 000 person-years, we observed spatial heterogeneity with up to 10-fold variation in incidence between communities. CONCLUSIONS: In urban, periurban, and rural communities in and around Kathmandu, we measured a high but heterogenous incidence of typhoid. These findings provide some support for the introduction of conjugate vaccines in Nepal, including outside urban areas, alongside other measures to prevent enteric fever.
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Fiebre Tifoidea , Vacunas Tifoides-Paratifoides , Asia , Humanos , Nepal/epidemiología , Salmonella paratyphi A , Salmonella typhi , Fiebre Tifoidea/epidemiologíaRESUMEN
BACKGROUND: The Aga Khan University clinical microbiology laboratory identified an outbreak of ceftriaxone-resistant Salmonella Typhi in Hyderabad, Pakistan, through antimicrobial resistance surveillance. An outbreak investigation was carried out to identify the risk factors and institute control measures. Here we report the preliminary findings of this outbreak investigation, using data collected from 30 November 2016 to 28 March 2017. METHODS: The design for the investigation was a case-control study that included identification of culture-proven ceftriaxone-resistant S. Typhi cases, suspected cases from the households or neighborhood of the confirmed cases, and enrollment of controls matched by age to identify the risk factors. Data were collected through face-to-face interviews using a structured questionnaire. Blood cultures were obtained from all suspected cases. Drinking water samples from each household of cases and controls were obtained for microbiological testing. Geographic Information System coordinates were obtained for all cases and controls. RESULTS: Only 2 subdistricts of Hyderabad (Latifabad and Qasimabad) were affected. A total of 101 confirmed cases of ceftriaxone-resistant S. Typhi had been reported in 4 months with the first case reported on 30 November 2016. Median age was 48 (interquartile range, 29-84) months. The majority (60% [61/101]) of the cases were 6-60 months old. More than half (56% [57/101]) of the cases were male. About 60% of the cases were admitted to hospital and treated as inpatient. More than half (57/101) of the patients developed complications related to typhoid. CONCLUSIONS: Community awareness was raised regarding chlorination of drinking water and sanitation measures in Hyderabad. These efforts were coordinated with the municipal water and sewage authority established to improve chlorination at processing plants and operationalize fecal sludge treatment plants. Outbreak investigation and control efforts have continued. Immunization of children with typhoid conjugate vaccine within Hyderabad city is planned.
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Ceftriaxona/farmacología , Brotes de Enfermedades , Salmonella typhi/efectos de los fármacos , Fiebre Tifoidea/epidemiología , Fiebre Tifoidea/microbiología , Vacunas Tifoides-Paratifoides/inmunología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Pakistán/epidemiología , Saneamiento , Fiebre Tifoidea/prevención & control , Microbiología del Agua , Calidad del Agua , Abastecimiento de Agua , Adulto JovenRESUMEN
Autosomal Recessive Agammaglobulinemia (ARA) is an uncommon type of primary immunodeficiency characterized by mutations in genes responsible for early B cell differentiation and function. One such gene is the TCF3 gene, which encodes a transcription factor important for immunoglobulin gene expression. We present the case of a 9â¯year old girl with history of diarrhea and recurrent pneumonias. Laboratory investigation showed significantly reduced levels of immunoglobulins along with a significant fall in the number of CD19+ cells. Genetic analysis identified a TCF3 gene base deletion covering exons 5-11.
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Agammaglobulinemia/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Mutación , Niño , Femenino , HumanosRESUMEN
OBJECTIVE: To evaluate the sensitivity, specificity, positive predictive and negative predictive values of Xpert mycobacterium tuberculosis and resistance to rifampicin by comparing it with acid-fast bacilli smear and culture in suspected tuberculosis patients. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised patient data from January 2013 to December 2016. Data related to children with clinical suspicion of pulmonary and extra-pulmonary tuberculosis based on Modified Kenneth Jones criteria, aged 1 month to 18 years whose samples (respiratory or non-respiratory) were sent for Xpert mycobacterium tuberculosis and resistance to rifampicin and acid-fast bacilli smear and culture con currently. Analysis was carried out by STATA 12 and Med Calc softwares . RESULTS: Of the 91 cases, 50(54.9%) related to females. The overall median age of the patients was 12.5 years (interquartile range: 8 years). Overall, 42(46.2%) cases had extra-pulmonary tuberculosis. The Xpert test had 66.7% sensitivity compared to smear microscopy 47.6%. Overall sensitivity, specificity, positive predictive value and negative predictive value were 95.7%, 72%, 51.2% and 98.3% respectively when the two tests were compared. CONCLUSIONS: Xpert mycobacterium tuberculosis was found to be more sensitive than acid-fast bacilli smear and culture in both pulmonary and extra-pulmonar y tuberculosis in children.
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Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis/diagnóstico , Adolescente , Antibióticos Antituberculosos , Niño , Preescolar , Técnicas de Cultivo , Farmacorresistencia Bacteriana/genética , Femenino , Humanos , Lactante , Masculino , Mycobacterium tuberculosis/crecimiento & desarrollo , Técnicas de Amplificación de Ácido Nucleico , Pakistán , Estudios Retrospectivos , Rifampin , Sensibilidad y Especificidad , Centros de Atención Terciaria , Tuberculosis/microbiología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiologíaRESUMEN
Introduction: The Surveillance for Enteric Fever in Asia Project (SEAP) is a multisite surveillance study designed to capture morbidity and mortality burden of enteric fever (typhoid and paratyphoid) in Bangladesh, Nepal, and Pakistan. We aim to describe enteric fever disease burden, severity of illness, and antimicrobial resistance trends in Pakistan. Methods: In this retrospective, cross-sectional study, laboratory records of hospitalized patients who received a blood culture in any of 3 Aga Khan University hospitals in Karachi and Hyderabad, Pakistan, from 2012 to 2014 were reviewed. A case was defined as having a positive blood culture for Salmonella Typhi (S. Typhi) or Salmonella Paratyphi (S. Paratyphi). Antimicrobial sensitivity patterns were characterized for all S. Typhi and S. Paratyphi isolates. Medical records were available for abstraction (demographics, clinical features, complications) only among hospitalized cases. Results: Of the 133017 blood cultures completed during the study period, 2872 (2%) were positive-1979 (69%) for S. Typhi and 893 (31%) for S. Paratyphi. Fluoroquinolone resistance was present in >90% of both the S. Typhi and the S. Paratyphi isolates; almost none of the isolates were resistant to cephalosporins. Multidrug resistance (resistance to ampicillin, chloramphenicol, and cotrimoxazole) was observed in 1035 (52%) S. Typhi isolates and 14 (2%) S. Paratyphi isolates. Among S. Typhi and S. Paratyphi isolates, 666 (23%) were linked to hospitalized patients with medical records. Of the 537 hospitalized S. Typhi cases, 280 (52%) were aged 5-15 years, 133 (25%) were aged 2-4 years, 114 (21%) were aged >15 years, and 10 (2%) were aged 0-1 years. Among the 129 hospitalized S. Paratyphi cases, 73 (57%) were aged >15 years, 41 (32%) were aged 5-15 years, 13 (10%) were aged 2-4 years, and 2 (2%) were aged 0-1 years. Significant differences in symptomology between S. Typhi and S. Paratyphi cases were observed for nausea/vomiting, diarrhea, loss of appetite, and headache. Leukopenia, thrombocytopenia, and encephalopathy were the most commonly reported complications among enteric fever cases. No deaths were reported. Conclusion: Evidence of high antimicrobial resistance levels and disease severity support the need for continued surveillance and improved diagnostics for typhoid. Further prospective studies on vaccination as a tool for prevention of enteric fever in Pakistan are needed to inform disease intervention strategies.
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Laboratorios , Vigilancia de la Población , Fiebre Tifoidea/epidemiología , Fiebre Tifoidea/microbiología , Adolescente , Antibacterianos/farmacología , Niño , Preescolar , Estudios Transversales , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Lactante , Masculino , Pakistán/epidemiología , Estudios Retrospectivos , Salmonella paratyphi A/efectos de los fármacos , Salmonella paratyphi A/aislamiento & purificación , Salmonella typhi/efectos de los fármacos , Salmonella typhi/aislamiento & purificaciónRESUMEN
Objective: The objective of Phase I of the Surveillance for Enteric Fever in Asia Project (SEAP), a multiphase surveillance study characterizing the burden of disease in South Asia, was to inform data collection for prospective surveillance and to capture clinical aspects of disease. Methods: Through a retrospective record review conducted at hospitals in Bangladesh, India, Nepal, and Pakistan, we examined laboratory and clinical records to assess the culture positivity rate for Salmonella Typhi and Salmonella Paratyphi, age and sex distribution, and antimicrobial susceptability in each country. Results: Of all blood cultures performed in Bangladesh, India, Nepal, and Pakistan, 1.5%, 0.43%, 2%, and 1.49%, respectively, were positive for S. Typhi and 0.24%, 0.1%, 0.5%, and 0.67%, respectively, were positive for S. Paratyphi. A higher proportion of laboratory-confirmed infections in Bangladesh and Pakistan were aged ≤5 years, while India and Nepal had a higher proportion of participants aged 15-25 years. In all countries, the sex of the majority of participants was male. The majority of isolates in all countries were resistant to fluoroquinolones, with a high proportion also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Discussion: Enteric fever remains endemic in South Asia. Data generated by this study can help inform strategies for implementation and evaluation of prevention and control measures.
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Vigilancia de Guardia , Fiebre Tifoidea/epidemiología , Asia Occidental/epidemiología , Humanos , Proyectos de Investigación , Estudios RetrospectivosRESUMEN
In order to make and sustain changes in the curriculum, needs assessment is the key. We conducted a need assessment survey using a questionnaire based on a 7 point Likert Scale by residents and alumni. Over all response rate in the study was 77.5%. Fifty eight percent participants were females. Highest level of agreement (mean score 5.7) was found between the alumni and residents regarding the need to revise the content, teaching and assessment strategies in the programme. Twenty seven alumni (n= 38, 71%) had cleared their FCPS exams. The alumni thought that the existing teaching and assessment strategies do not facilitate in passing professional certificate exams (mean score 3.6). The mean attempts required by the alumni for clearing this exam was 3.3, and 84.2% considered their weak clinical skills as the reason for their recurrent failure.
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Éxito Académico , Curriculum/normas , Pediatría/educación , Adulto , Competencia Clínica , Educación Médica Continua/métodos , Educación Médica Continua/normas , Femenino , Hospitales Universitarios , Humanos , Masculino , Evaluación de Necesidades , Pakistán , Mejoramiento de la CalidadRESUMEN
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency with more than 600 mutations in Bruton tyrosine kinase (Bkt) gene which are responsible for early-onset agammaglobulinemia and repeated infections. Herein we present a case of a 3-year-old boy with history of repeated diarrhoea and an episode of meningoencephalitis with hemiplegia. The workup showed extremely low levels of immunoglobulin with low CD+19 cells. Genetic analysis showed Btk mutation 18 c.1883delCp.T628fs. To the best of our knowledge this is the first report of a case of XLA confirmed by molecular technique from Pakistan.
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Agammaglobulinemia Tirosina Quinasa/genética , Agammaglobulinemia , Enfermedades Genéticas Ligadas al Cromosoma X , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/tratamiento farmacológico , Agammaglobulinemia/genética , Agammaglobulinemia/fisiopatología , Preescolar , Análisis Mutacional de ADN , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/tratamiento farmacológico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Mutación/genética , PakistánRESUMEN
OBJECTIVES: To report reduction in transmission of multidrug resistant organisms from the neonatal intensive care unit after the implementation of simple risk-reduction strategies. METHODS: Using a pre-and-post design, the study was carried out from June 2010 to December 2011 at the neonatal intensive care unit of Aga Khan University Hospital, Karachi, which is 12-bed, level III facility. The intervention comprised hand washing certification for all staff, use of chlorhexidine instead of povodine iodine for skin preparation, use of non-sterile gloves for diaper change, implementation of barrier nursing for clinically-suspected and culture-proven infections, provision of separate intubation and central line trolley for each room and limiting the use of umbilical catheters to 7 days. Data is reported for 3-month pre-intervention period, one-month implementation phase, and for 3-month post-intervention phase. Data for 12 months post-implementation is reported to show sustainability. RESULTS: The average pre intervention rates of bloodstream infections due to extended spectrurm 3 lactamase, Acinetobacter, Pseudomonas and methicillin resistant staphylococcus aureus were 4.7, 3.3, 1.2 and zero respectively. The average number of admissions during the 3 phases was almost similar (49, 46 and 53 respectively). There was sustained reduction in rates for all organisms 12 months after the intervention period. CONCLUSION: Nosocomial transmission of multi drug resistant organisms within the neonatal intensive care unit can be effectively reduced by adopting simple strategies.
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Bacteriemia/prevención & control , Infección Hospitalaria/prevención & control , Control de Infecciones/métodos , Unidades de Cuidado Intensivo Neonatal , Bacteriemia/microbiología , Clorhexidina/administración & dosificación , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Resistencia a Múltiples Medicamentos , Contaminación de Equipos/prevención & control , Femenino , Guantes Protectores , Desinfección de las Manos , Humanos , Recién Nacido , Masculino , Pakistán , Atención Terciaria de SaludRESUMEN
BACKGROUND: Patients in pediatric intensive care Units (PICU) are susceptible to infections with antibiotic resistant organisms which increase the morbidity, mortality and cost of care. To describe the clinical characteristics and mortality in patients with Multi-Drug Resistant (MDR) gram negative organisms. We also report safety of Polymyxin B use in these patients. METHODS: Files of patients admitted in PICU of Aga Khan University Hospital, from January 2010 to December 2011, one month to 15 years of age were reviewed. Demographic and clinical features of patients with MDR gram negative infections, antibiotic susceptibility pattern of isolates, discharge disposition and adverse effects of Polymyxin B were recorded. RESULTS: A total of 44.8/1000(36/803) admitted patients developed MDR gram negative infections, of which 47.2%(17/36) were male, with mean age of 3.4 yrs(+/-4.16). Acinetobacter Species (25.5%) was the most frequently isolated MDR organisms followed by Klebsiella Pneumoniae (17%). Sensitivity of isolates was 100% to Polymyxin B, followed by Imipenem (50%), and piperacillin/tazobactem (45%). The crude mortality rate of patients with MDR gram negative infections was 44.4% (16/36). Fourteen of 36 patients received Polymyxin B and 57.1%; (8/14) of them were cured. Nephrotoxicity was observed in 21.4% (3/14) cases, none of the patients showed signs of neuropathy. CONCLUSION: Our study highlights high rates of Carbapenem resistant gram negative isolates, leading to increasing use of Polymyxin B as the only drug to combat against these critically ill children. Therefore, we emphasizeon Stewardship of Antibiotics and continuous surveillance system as strategies in overall management of these critically ill children.
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Acinetobacter/efectos de los fármacos , Antibacterianos/uso terapéutico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , Polimixina B/uso terapéutico , Adolescente , Antibacterianos/farmacología , Niño , Preescolar , Estudios de Cohortes , Enfermedades Transmisibles , Enfermedad Crítica , Países en Desarrollo/estadística & datos numéricos , Farmacorresistencia Bacteriana Múltiple , Femenino , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , Masculino , Polimixina B/farmacología , Estudios RetrospectivosRESUMEN
BACKGROUND: Typhoid is a serious public health threat in many low-income and middle-income countries. Several vaccines for typhoid have been recommended by WHO for typhoid prevention in endemic countries. This study aimed to review the efficacy of typhoid vaccines against culture-confirmed Salmonella enterica serovar Typhi. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for studies published in English between Jan 1, 1986 and Nov 2, 2023. We included randomised controlled trials (RCTs) comparing typhoid vaccines with a placebo or another vaccine. This meta-analysis evaluated the efficacy and safety of several typhoid vaccines, including live attenuated oral Ty21a vaccine, Vi capsular polysaccharide (Vi-PS), Vi polysaccharide conjugated to recombinant Pseudomonas aeruginosa exotoxin A vaccine (Vi-rEPA), and Vi-tetanus toxoid conjugate vaccine (TCV). The certainty of evidence for key outcomes was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. The outcome of interest was typhoid fever confirmed by the isolation of Salmonella enterica serovar Typhi in blood and adverse events following immunisation. This study is registered with PROSPERO (CRD42021241043). FINDINGS: We included 14 RCTs assessing four different vaccines (Ty21a: four trials; Vi-PS: five trials; Vi-rEPA: one trial; TCV: four trials) involving 585â253 participants. All trials were conducted in typhoid endemic countries and the age of participants ranged from 6 months to 50 years. The pooled efficacy against typhoid fever was 45% (95% CI 33-55%; four trials; 247â649 participants; I2 59%; moderate certainty) for Ty21a and 58% (44-69%; five trials; 214â456 participants; I2 34%; moderate certainty) for polysaccharide Vi-PS. The cumulative efficacy of two doses of Vi-rEPA vaccine at 2 years was 91% (88-96%; one trial; 12â008 participants; moderate certainty). The pooled efficacy of a single shot of TCV at 2 years post-immunisation was 83% (77-87%; four trials; 111â130 participants; I2 0%; moderate certainty). All vaccines were safe, with no serious adverse effects reported in the trials. INTERPRETATION: The existing data from included trials provide promising results regarding the efficacy and safety of the four recommended typhoid vaccines. TCV and Vi-rEPA were found to have the highest efficacy at 2 years post-immunisation. However, follow-up data for Vi-rEPA are scarce and only TCV is pre-qualified by WHO. Therefore, roll-out of TCV into routine immunisation programmes in typhoid endemic settings is highly recommended. FUNDING: There was no funding source for this study.
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Salmonella typhi , Fiebre Tifoidea , Vacunas Tifoides-Paratifoides , Humanos , Vacunas Tifoides-Paratifoides/administración & dosificación , Vacunas Tifoides-Paratifoides/inmunología , Salmonella typhi/inmunología , Fiebre Tifoidea/prevención & control , Fiebre Tifoidea/epidemiología , Enfermedades Endémicas/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Eficacia de las VacunasRESUMEN
BACKGROUND: This study aimed to assess the longevity of serologic response and seroconversion rates at several time points following TCV vaccination among children living with HIV aged 6 months to 15 years in Pakistan. METHODS: From November 20, 2020, to January 2, 2021; 336 children were enrolled and followed up prospectively for 12 months. Blood samples were collected before the administration of TCV and at 4-6 weeks, 6 months, and 1 year after administration of a single dose (0.5 ml) of intramuscular Typbar TCV®. Samples were analyzed for anti-Vi-IgG antibodies using ELISA. Geometric mean titers (GMTs), seroconversion rates (fourfold rise in anti-Vi-IgG from baseline), and factors associated with sustained seroconversion at 1 year were evaluated using generalized linear mixed models. FINDINGS: The seroconversion rates were significantly lower in children aged 6 months to 5 years compared to children > 5 years; (127/216 (58·8%)) versus (81/111 (73·0%)) at 6 months and (110/217 (50·7%)) versus (78/109 (71·6%)) at 1 year, only two-third; 188/326 (57·7%) remained seroconverted at 1 year. The GMTs (95 % CI) were significantly lower in children aged 6 months to 5 years compared to children > 5 years, 9·6 (7·6, 12·0) versus 28·9 (20·2, 41·4) at 6 months, and 6·6 (5·4, 8·0) versus 23·1 (16·4, 32·5) at 1 year time point. The odds of sustained seroconversion significantly decreased with time (adjusted odds ratio (aOR): 0·232; 95 % CI: 0·136,0·396). The odds of sustained seroconversion following 1 year of TCV vaccination were significantly higher among children with non-severe HIV clinical disease (aOR: 10·6; 95 % CI: 1·5, 73·9) and children in elder age group (aOR: 7·45; 95 % CI: 11·2, 47·0). CONCLUSIONS: There was a decline in seroconversion after one year of TCV in children living with HIV. The decline was significant in children with severe or advanced HIV disease. A significant decrease in seroconversion rates was observed among children living with HIV following one year of TCV administration.
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OBJECTIVES: Typhoid remains a persistent contributor to childhood morbidity in communities lacking sanitation infrastructure. Typhoid conjugate vaccine (TCV) is effective in reducing disease risk in vaccinees; however, the duration of protection is unknown. This study measured the longevity of immune response to TCV in children aged under 10 years in Hyderabad, Pakistan, where an outbreak of extensively drug-resistant typhoid has been ongoing. METHODS: A subset of children who received the TCV as part of the outbreak response were enrolled purposively from March 2018 to February 2019. The participants were followed up until January 2023. Blood samples were taken at baseline, 4-6 weeks, 6 months, and annually 1-4 years after vaccination to measure anti-Vi immunoglobulin (Ig) G levels using enzyme-linked immunosorbent assay. Active phone-based surveillance was performed to identify breakthrough infections. Blood culture was offered to any child with a history of fever ≥3 days within the last 7 days. A total of 81 children received a second dose of TCV in November 2019 during a catch-up campaign organized by the Sindh government. RESULTS: Nearly all participants seroconverted (802 of 837; 95.8%) at 4-6 weeks after vaccination. A total of 4 years after vaccination, 438 of 579 (75.6%) participants remained above the seroconversion threshold. The geometric mean titer (U/mL) of anti-Vi IgG at 4-6 weeks was 832.6 (95% confidence interval [CI]: 768.0-902.6); at 4 years after vaccination, the geometric mean titers in children aged 6 months to 2 years (12.6, [95% CI: 9.8-16.3]) and >2-5 years (40.1, [95% CI: 34.4-46.6]) were lower than in children aged >5-10 years (71.1, [95% CI: 59.5-85.0]). During 4 years of follow-up, nine children had culture-confirmed Salmonella Typhi infection; these infections occurred after a median duration of 3.4 years. All enteric fever cases seroconverted at 4-6 weeks after vaccination and seven (70.0%) remained seroconverted 4 years after vaccination. CONCLUSIONS: We observed 95.8% seroconversion after a single dose of TCV. There was a decay in anti-Vi IgG titers, and, at 4 years, approximately 75.6% remained seroconverted. There was a faster decay in children aged ≤2 years. Breakthrough infections were documented after a median 3.4 years after vaccination.
RESUMEN
Aeromonas spp. are associated with a number of infectious syndromes in humans including gastroenteritis and dysentery. Our understanding of the genetic diversity, population structure, virulence determinants and antimicrobial resistance of the genus has been limited by a lack of sequenced genomes linked to metadata. We performed a comprehensive analysis of the whole genome sequences of 447 Aeromonas isolates from children in Karachi, Pakistan, with moderate-to-severe diarrhoea (MSD) and from matched controls without diarrhoea that were collected as part of the Global Enteric Multicenter Study (GEMS). Human-associated Aeromonas isolates exhibited high species diversity and extensive antimicrobial and virulence gene content. Aeromonas caviae, A. dhankensis, A. veronii and A. enteropelogenes were all significantly associated with MSD in at least one cohort group. The maf2 and lafT genes that encode components of polar and lateral flagella, respectively, exhibited a weak association with isolates originating from cases of gastroenteritis.
Asunto(s)
Aeromonas , Antiinfecciosos , Gastroenteritis , Niño , Humanos , Aeromonas/genética , Genómica , Diarrea , Variación GenéticaRESUMEN
BACKGROUND: Enteric fever is caused by Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi A, B, and C. It continues to be a significant cause of morbidity and mortality worldwide. In highly endemic areas, children are disproportionately affected, and antimicrobial resistance reduces therapeutic options. It is estimated that 2-5% of enteric fever patients develop chronic asymptomatic infection. These carriers may act as reservoirs of infection; therefore, the prospective identification and treatment of carriers are critical for long-term disease control. We aimed to find the frequency of Salmonella Typhi carriers in patients undergoing cholecystectomy. We also compared the detection limit of culturing versus qPCR in detecting S. Typhi, performed a geospatial analysis of the carriers identified using this study, and evaluated the accuracy of anti-Vi and anti-YncE in identifying chronic typhoid carriage. METHODS: We performed a cross-sectional study in two centers in Pakistan. Gallbladder specimens were subjected to quantitative PCR (qPCR) and serum samples were analyzed for IgG against YncE and Vi by ELISA. We also mapped the residential location of those with a positive qPCR result. FINDINGS: Out of 988 participants, 3.4% had qPCR-positive gallbladder samples (23 S. Typhi and 11 S. Paratyphi). Gallstones were more likely to be qPCR positive than bile and gallbladder tissue. Anti-Vi and YncE were significantly correlated (r = 0.78 p<0.0001) and elevated among carriers as compared to qPCR negative controls, except for anti-Vi response in Paratyphi A. But the discriminatory values of these antigens in identifying carriers from qPCR negative controls were low. CONCLUSION: The high prevalence of typhoid carriers observed in this study suggests that further studies are required to gain information that will help in controlling future typhoid outbreaks in a superior manner than they are currently being managed.
Asunto(s)
Portador Sano , Colecistectomía , Salmonella typhi , Fiebre Tifoidea , Humanos , Estudios Transversales , Fiebre Tifoidea/epidemiología , Fiebre Tifoidea/microbiología , Femenino , Masculino , Portador Sano/microbiología , Portador Sano/epidemiología , Salmonella typhi/aislamiento & purificación , Salmonella typhi/genética , Adulto , Pakistán/epidemiología , Adulto Joven , Persona de Mediana Edad , Adolescente , Enfermedades de la Vesícula Biliar/microbiología , Enfermedades de la Vesícula Biliar/epidemiología , Anticuerpos Antibacterianos/sangre , Vesícula Biliar/microbiología , Niño , Inmunoglobulina G/sangreRESUMEN
Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study-a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella--associated diarrhea in children 6 to 35 months old. Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study. Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis. Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data.