Introductory Article on Global Burden and Epidemiology of Typhoid Fever

Radhakrishnan, Amruta; Als, Daina; Mintz, Eric D.; Crump, John A.; Stanaway, Jeffrey D; Breiman, Robert F.; Bhutta, Zulfiqar A

doi:10.4269/ajtmh.18-0032

Cited by 76 publications

(63 citation statements)

References 29 publications

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“…Typhi and S . Paratyphi result in typhoid fever causing an estimated 190, 000 deaths per year and is typically observed in nations lacking adequate sanitation and clean drinking water programs [2, 3]. Symptoms of typhoid include fever, abdominal pain and general malaise [4].…”

Section: Introductionmentioning

confidence: 99%

A loss-of-function mutation inItgalcontributes to the high susceptibility of Collaborative Cross strain CC042 toSalmonellainfections

Zhang

Teh

et al. 2019

Preprint

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25Salmonella are intracellular bacteria that are found in the gastrointestinal tract of mammalian, 26 avian, and reptilian hosts. They are one of the leading causes of foodborne infections and a major 27 threat for human populations worldwide. Mouse models have been extensively used to model 28 distinct aspects of the human Salmonella infections in vivo and have led to the identification of 29 several host susceptibility genes. We have investigated the susceptibility of Collaborative Cross 30 strains to intravenous infection with Salmonella Typhimurium as a model of human systemic 31 invasive infection. In this model, strain CC042 displayed extreme susceptibility with very high 32 bacterial loads and mortality. CC042 mice showed lower spleen weight and decreased splenocyte 33 numbers before and after infection, affecting mostly CD8 + T cells, B cells, and all myeloid 34 populations. Uninfected mice also had lower thymus weight with reduced total number of 35 thymocytes and double negative and (CD4 + , CD8 + ) double positive thymocytes. Analysis of 36 bone marrow resident hematopoietic progenitors showed a strong bias against lymphoid primed 37 multipotent progenitors, which are the precursors of T, B and NK cells. An F2 cross between 38 CC042 and C57BL/6N identified two significant QTLs on chromosome 7 (Stsl6 and Stsl7) with 39 WSB-derived susceptible alleles. A private variant in the integrin alpha L (Itgal) gene is carried 40 by CC042 in the Stsl7 QTL region. A quantitative complementation test confirmed the impact of 41 Itgal loss of function in a (C57BL/6JxCC042)F1 background, but not in a C57BL/6J inbred 42 background. These results further emphasize the utility of the Collaborative Cross to identify 43 new host genetic variants controlling susceptibility to infections and improve our understanding 44 of the function of the Itgal gene. 45 46 3 47 Author summary 48 Salmonella are one of the leading causes of foodborne infections and a major threat for human 49 populations worldwide. Not all humans are equally susceptible to Salmonella infection. Some 50 individuals will develop minor symptoms and recover while others develop severe illness and 51 might die. Mouse models are used to study distinct aspects of human Salmonella infection in 52vivo. We used a new genetically diverse mouse population to investigate host susceptibility 53 differences to Salmonella infection. We identified one mouse strain with an extreme 54 susceptibility to infection characterized by very high bacterial loads and mortality. Mice of this 55 strain had small thymus and spleen, two organs which are very important for producing a fully 56 mature immune system. We showed that the strain's immune response is impaired and that its 57 extreme susceptibility to Salmonella infection is due to multiple genes defects. We identified a 58 loss-of-function mutation in the Itgal gene (Integrin Subunit Alpha L) that plays a central role in 59 the immune response to infection. This gene explains part of the susceptibility and other gene(s) 60 in...

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Section: Introductionmentioning

confidence: 99%

A loss-of-function mutation inItgalcontributes to the high susceptibility of Collaborative Cross strain CC042 toSalmonellainfections

Zhang

Teh

et al. 2019

Preprint

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“…Enteric fever caused by S. Typhi continues to pose as a health burden globally, with the incidence being highest in low to middle income countries (LMIC), due to poor infrastructure of public health (11). According to World Health Organization (12), Pakistan faced the largest outbreak of XDR enteric fever, in Hyderabad in November 2016 followed by a similar outbreak in Karachi.…”

Section: Discussionmentioning

confidence: 99%

A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug resistant (XDR) Salmonella Typhi isolates in children in Karachi.

Shahid

Mahesar

Ghouri

et al. 2020

Preprint

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Background: Enteric fever is a systemic infection, which can be caused by Salmonella enterica; Typhi and Paratyphi A. Over a period of time Salmonella Typhi has developed resistance to many antibiotics which has resulted in emergence of extensively drug resistant (XDR) enteric fever. WHO estimated 5274 cases of XDR Enteric fever in Karachi from November 2016 to December 2019.This study aims to determine clinical course, complications and outcomes of XDR enteric fever among the pediatric population coming to Indus HospitalMethods: A retrospective chart review of pediatric patients (aged 1 month–15 years) seen in Indus Hospital between July 2017 to December 2018 was conducted. A pre-designed data abstraction form was used to record detailed information about seasonality and distribution of cases, demographic details, signs and symptoms, clinical course, treatment, complications and final outcomes of the cases treated for XDR Enteric feverResults: Six hundred and eighty children were included in the study. The median (IQR) age of the patients was 5 (2-8) years. More than half (n=391, 57.5%) of the patients were males. Most common clinical manifestations included fever vomiting and diarrhea which were noted in 680 (100%), 242 (35%) and 174 patients (25%) Final outcomes of 270 (39.7%) patients have been recorded; 351 (51.6%) were lost to follow up, 52 (7.6%) were referred out and 7 (1%) left without medical advice. 266 (39.1%) patients were cured and 4 children (0.6%) expired. Seventy eight patients (82%) and 15 patients (16.3%) got cured on Azithromycin and Meropenum alone while 157 patients got cured on combination of drugs.Conclusion: Our review indicated that children under 5 years of age were affected more with XDR Enteric fever. Meropenum and Azithromycin, either alone or in combination were the most effective antibiotics for treating XDR Enteric fever in children coming to Indus hospital

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“…Enteric fever caused by S. Typhi continues to pose as a health burden globally, with the incidence being highest in low to middle-income countries (LMIC), due to poor infrastructure of public health (11).…”

Section: Discussionmentioning

confidence: 99%

A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug-resistant (XDR) Salmonella Typhi isolates in children in Karachi.

Shahid

Mahesar

Ghouri

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Enteric fever is a systemic infection, which can be caused by Salmonella enterica; Typhi and Paratyphi A. Over time, Salmonella Typhi has developed resistance to antibiotics resulting in the emergence of extensively drug-resistant (XDR) enteric fever. WHO estimated 5274 cases of XDR Enteric fever in Karachi from November 2016 to December 2019. This study aims to determine clinical course, complications and outcomes of XDR enteric fever among the pediatric population coming to Indus HospitalMethods: A retrospective chart review of pediatric patients (aged one month to 15 years) seen in Indus Hospital between July 2017 to December 2018 was conducted. A pre-designed data abstraction form was used to record detailed information about seasonality and distribution of cases, demographic details, signs and symptoms, clinical course, treatment, complications and outcomes of the cases treated for XDR Enteric feverResults: Six hundred and eighty children were included in the study. The median (IQR) age of the patients was 5 (2-8) years. More than half (n=391, 57.5%) of the patients were males. Most common clinical manifestations included fever, vomiting and diarrhea, noted in 680 (100%), 242 (35%) and 174 (25%) patients. Outcomes of 270 (39.7%) patients were recorded. Others were lost to follow up [351 (51.6%)], referred out [52 (7.6%)] or left against medical advice [7 (1%)]. 266 (39.1%) patients were cured, and four children (0.6%) expired. Seventy-eight patients (82%) and 15 patients (16.3%) got cured on Azithromycin and Meropenem alone while 157 on a combination of drugs.Conclusion: Our review indicated that children under five years of age were affected more with XDR Enteric fever. Meropenem and Azithromycin, either alone or in combination were the most effective antibiotics for treating XDR Enteric fever in children coming to Indus hospital

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Introductory Article on Global Burden and Epidemiology of Typhoid Fever

Cited by 76 publications

References 29 publications

A loss-of-function mutation inItgalcontributes to the high susceptibility of Collaborative Cross strain CC042 toSalmonellainfections

A loss-of-function mutation inItgalcontributes to the high susceptibility of Collaborative Cross strain CC042 toSalmonellainfections

A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug resistant (XDR) Salmonella Typhi isolates in children in Karachi.

A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug-resistant (XDR) Salmonella Typhi isolates in children in Karachi.

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