Intestinal Perforations Associated With a High Mortality and Frequent Complications During an Epidemic of Multidrug-resistant Typhoid Fever in Blantyre, Malawi

Abstract Background Typhoid fever remains a major source of morbidity and mortality in low-income settings. Its most feared complication is intestinal perforation. However, due to the paucity of diagnostic facilities in typhoid-endemic settings, including microbiology, histopathology, and radiology, the etiology of intestinal perforation is frequently assumed but rarely confirmed. This poses a challenge for accurately estimating burden of disease. Methods We recruited a prospective cohort of patients with confirmed intestinal perforation in 2016 and performed enhanced microbiological investigations (blood and tissue culture, plus tissue polymerase chain reaction [PCR] for Salmonella Typhi). In addition, we used a Poisson generalized linear model to estimate excess perforations attributed to the typhoid epidemic, using temporal trends in S. Typhi bloodstream infection and perforated abdominal viscus at Queen Elizabeth Central Hospital from 2008–2017. Results We recruited 23 patients with intraoperative findings consistent with intestinal perforation. 50% (11/22) of patients recruited were culture or PCR positive for S. Typhi. Case fatality rate from typhoid-associated intestinal perforation was substantial at 18% (2/11). Our statistical model estimates that culture-confirmed cases of typhoid fever lead to an excess of 0.046 perforations per clinical typhoid fever case (95% CI, .03–.06). We therefore estimate that typhoid fever accounts for 43% of all bowel perforation during the period of enhanced surveillance. Conclusions The morbidity and mortality associated with typhoid abdominal perforations are high. By placing clinical outcome data from a cohort in the context of longitudinal surgical registers and bacteremia data, we describe a valuable approach to adjusting estimates of the burden of typhoid fever.

Download Full-text

Typhoid Fever Complicated with Bowel Perforation in an HIV Patient

10.21203/rs.3.rs-655331/v1 ◽

2021 ◽

Author(s):

Parackrama Karunathilake ◽

Thilak Jayalath ◽

Shamali Abeygunawardena ◽

Udaya Ralapanawa

Keyword(s):

Hiv Infection ◽

Typhoid Fever ◽

Opportunistic Infections ◽

Epigastric Pain ◽

Bowel Perforation ◽

Delayed Diagnosis ◽

Case Fatality ◽

Severe Pneumonia ◽

Exploratory Laparotomy ◽

Full Blood Count

Abstract Background Patients with HIV infection often develop multiple complications and comorbidities, including malignancies and opportunistic infections. The association of HIV infection with typhoid fever remains unclear, though there is a clear risk of typhoid in HIV infected persons. Therefore, the diagnosis of typhoid should be considered in HIV infected individuals, mainly when they present with severe ulcerative diarrhoea. Case Presentation A 38-year-old gentleman presented with fever with significant weight loss and anorexia for eight months. He had worked abroad in a middle east country and had recently returned to Sri Lanka. On examination, he was thinly built with a BMI of 18 kg/m2. The initial full blood count revealed lymphopenia, anaemia and thrombocytopenia. He also had mild hyponatremia. His HIV Ag/Ab combo assay became positive, and he was found to have a low CD4 count. While on antiretroviral therapy, he developed nausea, vomiting and diarrhoea while continuing the preexisting fever followed by severe dyspnoea and epigastric pain and tenderness associated with tachypnoea, tachycardia and hypotension. The urgent chest X-ray revealed gas under the diaphragm. An urgent exploratory laparotomy was done, and he was found to have distal ileal perforation with a typhoid ulcer which was histologically confirmed later. During the postoperative period, the patient developed severe pneumonia, scummed despite all the resuscitation care given. Conclusion Fever in HIV patients could be due to HIV itself, opportunistic infections or malignancies. The diagnosis of typhoid should be considered in HIV infected individuals, mainly when they present with severe ulcerative diarrhoea, constipation or bowel perforation. Salmonella typhi infection in HIV/AIDS patients may cause life-threatening complications, where the case fatality rate of typhoid significantly increase when present concurrently with HIV, and the mortality further increases with delayed diagnosis.

Download Full-text

Part I. Analysis of data gaps pertaining to Salmonella enterica serotype Typhi infections in low and medium human development index countries, 1984–2005

Epidemiology and Infection ◽

10.1017/s0950268807009338 ◽

2007 ◽

Vol 136 (4) ◽

pp. 436-448 ◽

Cited By ~ 61

Author(s):

J. A. CRUMP ◽

P. K. RAM ◽

S. K. GUPTA ◽

M. A. MILLER ◽

E. D. MINTZ

Keyword(s):

Blood Culture ◽

Typhoid Fever ◽

Human Development ◽

Intestinal Perforation ◽

Human Development Index ◽

Case Fatality ◽

Population Based ◽

Current Understanding ◽

Complication Rates ◽

Development Index

SUMMARYThere are only 10 contemporary, population-based studies of typhoid fever that evaluate disease incidence using blood culture for confirmation of cases. Reported incidence ranged from 13 to 976/100 000 persons per year. These studies are likely to have been done preferentially in high- incidence sites which makes generalization of data difficult. Only five of these studies reported mortality. Of these the median (range) mortality was 0% (0–1·8%). Since study conditions usually involved enhanced clinical management of patients and the studies were not designed to evaluate mortality as an outcome, their usefulness for generalizing case-fatality rates is uncertain. No contemporary population-based studies reported rates of complications. Hospital-based typhoid fever studies reported median (range) complication rates of 2·8% (0·6–4·9%) for intestinal perforation and case-fatality rates of 2·0% (0–14·8%). Rates of complications other than intestinal perforation were not reported in contemporary hospital-based studies. Hospital-based studies capture information on the most severe illnesses among persons who have access to health-care services limiting their generalizability. Only two studies have informed the current understanding of typhoid fever age distribution curves. Extrapolation from population-based studies suggests that most typhoid fever occurs among young children in Asia. To reduce gaps in the current understanding of typhoid fever incidence, complications, and case-fatality rate, large population-based studies using blood culture confirmation of cases are needed in representative sites, especially in low and medium human development index countries outside Asia.

Download Full-text

A retrospective study of patients with blood culture-confirmed typhoid fever in Fiji during 2014–2015: epidemiology, clinical features, treatment and outcome

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/trz075 ◽

2019 ◽

Vol 113 (12) ◽

pp. 764-770 ◽

Cited By ~ 1

Author(s):

Aneley Getahun S ◽

Christopher M Parry ◽

John A Crump ◽

Varanisese Rosa ◽

Adam Jenney ◽

...

Keyword(s):

Blood Culture ◽

Typhoid Fever ◽

Clinical Features ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Case Fatality ◽

Clinical Information ◽

Salmonella Typhi ◽

Fatality Risk ◽

Case Fatality Risk

Abstract Background Typhoid fever is endemic in Fiji. We sought to describe the epidemiology, clinical features and case fatality risk of blood culture-confirmed typhoid fever from January 2014 through December 2015. Methods Blood culture-positive patients were identified from a typhoid surveillance line list. A standardised case investigation form was used to record data from patients’ medical records. Results Of 542 patients, 518 (95.6%) were indigenous Fijians (iTaukei) and 285 (52.6%) were male. The median (IQR) age was 25 (16–38) y. Mean (SD) time from the onset of illness to admission was 11.1 (6.9) d. Of 365 patients with clinical information, 346 (96.9%) had fever, 239 (66.9%) diarrhoea, 113 (33.5%) vomiting, and 72 (30.2%) abdominal pain. There were 40 (11.0%) patients with complications, including 17 (4.7%) with shock, and 11 (3.0%) with hepatitis. Nine patients died for a case fatality risk of 1.7%. Of the 544 Salmonella Typhi isolates tested, none were resistant to first line antimicrobials; 3(0.8%) were resistant to ciprofloxacin and 5(1.4%) to nalidixic acid. Conclusions In Fiji, most blood culture-confirmed typhoid fever cases were in young adults. Common clinical manifestations were fever and gastrointestinal symptoms. Further studies are required to elucidate the factors associated with complications and death.

Download Full-text

Small Intestinal Perforation Secondary to Necrotizing Enteritis—An Under-Recognized Complication of Crohn’s Disease

The American Surgeon ◽

10.1177/00031348211054521 ◽

2022 ◽

pp. 000313482110545

Author(s):

Carlos Theodore Huerta ◽

Antoine J. Ribieras ◽

Karishma Kodia ◽

D. Dante Yeh ◽

David Kerman ◽

...

Keyword(s):

Small Intestine ◽

Crohn’S Disease ◽

Small Bowel ◽

Crohn's Disease ◽

Intestinal Perforation ◽

Bowel Perforation ◽

Case Fatality ◽

Regional Enteritis ◽

Small Bowel Perforation ◽

Small Intestinal

Small bowel perforation is an uncommon but severe event in the natural history of Crohn’s disease with fewer than 100 cases reported. We review Crohn’s disease cases with necrotizing enteritis and share a case of a 26-year-old female who presented with a recurrent episode of small intestinal perforation. A PubMed literature review of case reports and series was conducted using keywords and combinations of “Crohn’s disease,” “small intestine perforation,” “small bowel perforation,” “free perforation,” “regional enteritis,” and “necrotizing enteritis.” Data extracted included demographic data, pre- or postoperative steroid administration, medical or surgical management, and case fatality. Nineteen reports from 1935 to 2021 qualified for inclusion. There were 43 patients: 20 males and 23 females with a mean age of 36 ± 15 years old. 75 total perforations were described: 56 ileal (74.6%), 15 jejunal (20.0%), 2 cecal (2.7%), and 1 small intestine non-specified (2.7%). 38 of 43 patients were managed surgically by primary repair (11), ostomy creation (21), or an anastomosis (11). Of 11 case fatalities, medical management alone was associated with higher mortality (5/5; 100% mortality) compared to those treated surgically (6/38; 15.8% mortality; P < .001). Patient sex, disease history, acute abdomen, and pre- or postoperative steroid use did not significantly correlate with mortality. Jejunal perforation was significantly ( P = .028) associated with event mortality while ileal was not ( P = .45). Although uncommon, necrotizing enteritis should be considered in Crohn’s patients who present with small intestinal perforation. These cases often require urgent surgical intervention and may progress to fulminant sepsis and fatality if not adequately treated.

Download Full-text

Country differences in transmissibility, age distribution and case-fatality of SARS-CoV-2: a global ecological analysis

10.1101/2021.02.17.21251839 ◽

2021 ◽

Author(s):

Caroline Favas ◽

Prudence Jarrett ◽

Ruwan Ratnayake ◽

Oliver J Watson ◽

Francesco Checchi

Keyword(s):

Low Income ◽

Immune Modulation ◽

Age Distribution ◽

Case Fatality ◽

Outcome Data ◽

Low Income Countries ◽

Parasitic Infections ◽

Ecological Design ◽

Country Level ◽

Co Morbidity

AbstractIntroductionSARS-CoV-2 has spread rapidly across the world yet the first pandemic waves in many low-income countries appeared milder than initially forecasted through mathematical models. Hypotheses for this observed difference include under-ascertainment of cases and deaths, country population age structure, and immune modulation secondary to exposure to endemic parasitic infections. We conducted a country-level ecological study to describe patterns in key SARS-CoV-2 outcomes by country and region and to explore possible associations of the potential explanatory factors with these outcomes.MethodsWe collected publicly available data at country level and compared them using standardisation techniques. We then explored the association between exposures and outcomes using alternative approaches: random forest (RF) regression and linear (LM) regression. We adjusted for potential confounders and plausible effect modifications.ResultsAltogether, data on the mean time-varying reproduction number (mean Rt) were available for 153 countries, but standardised averages for the age of cases and deaths and for the case-fatality ratio (CFR) could only be computed for 61, 39 and 31 countries respectively. While mean Rt was highest in the WHO Europe and Americas regions, median age of death was lower in the Africa region even after standardisation, with broadly similar CFR. Population age was strongly associated with mean Rt and the age-standardised median age of observed cases and deaths in both RF and LM models. The models highlighted other plausible roles of population density, testing intensity and co-morbidity prevalence, but yielded uncertain results as regards exposure to common parasitic infections.ConclusionsThe average age of a population seems to be an important country-level factor explaining both transmissibility and the median age of observed cases and deaths, even after age-standardisation. Potential associations between endemic infections and COVID-19 are worthy of further exploration but seem unlikely, from this analysis, to be key drivers of the variation in observed COVID-19 epidemic trends. Our study was limited by the availability of outcome data and its causally uncertain ecological design, with the observed distribution of age amongst reported cases and deaths suggesting key differences in surveillance and testing strategy and capacity by country and the representativeness of case reporting of infection. Research at subnational and individual level is needed to explore hypotheses further.

Download Full-text

Evaluation of Salmonella typhi dipstick for detection of IgM antibodies from suspect Typhoid fever patient

Medical Journal of Indonesia ◽

10.13181/mji.v7isupp1.1127 ◽

1998 ◽

pp. 252

Author(s):

M. Hatta ◽

L. Chairuddin ◽

H.L. Smith

Keyword(s):

Typhoid Fever ◽

Salmonella Typhi ◽

Fever Patient ◽

Igm Antibodies

Download Full-text

#53: High Burden of Serious Bacterial Infections in African Children Treated for Cancer

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa170.019 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

pp. S6-S6

Author(s):

G Naidu ◽

A Izu ◽

R Wainwright ◽

S Poyiadjis ◽

D MacKinnon ◽

...

Keyword(s):

Bacterial Infections ◽

Case Fatality ◽

Morbidity And Mortality ◽

Coagulase Negative Staphylococci ◽

Children With Cancer ◽

Indwelling Catheter ◽

High Burden ◽

African Children ◽

Serious Bacterial Infections ◽

Living With Hiv

Abstract Background Infectious complications in children treated for cancer contribute to their morbidity and mortality. There is a paucity of studies on the incidence, microbiological etiology, risk factors, and outcome of serious bacterial infections in African children treated for cancer. Aim The aim of the study was to delineate the epidemiology of infectious morbidity and mortality in South African children with cancer. Methods This prospective, single-center, longitudinal-cohort study enrolled children one-19 years old hospitalized for cancer treatment at the Paediatric Oncology Unit, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. Children were investigated for infection as part of the standard of care. Results In total, 169 children were enrolled, 82 with hematological malignancy (HM), 87 with a solid tumor (ST), median age was 68.5 months and 10.7% were living with HIV. The incidence (per 100 child-years) of septic episodes (SE) and microbiologically confirmed SE (MSCE) was 101 (138 vs. 70, P < 0.001) and 70.9 (99.1 vs. 47.3; P < 0.001), respectively; higher in children with HM than ST. The incidence of MCSE in children with high-risk HM (137.7) was 4.32-fold greater compared with those with medium-risk HM (30.3; P < 0.001). Children with metastatic ST had a higher incidence (84.4) of MSCE than those with localized ST (33.6; aOR: 2.52; P < 0.001). The presence of an indwelling catheter was 3-fold (P < 0.001) more likely to be associated with MCSE compared with those without. There was no association for age group, nutritional status or HIV-status, and incidence of MCSE. The incidence of gram-positive (GPB) and gram-negative (GNB) SEs was 48.5 and 37.6, respectively, and higher in children with an HM. The most commonly identified GPB were Coagulase-negative Staphylococci, Streptococcus viridans and Enterococcus faecium; while the most common GNB were Escherichia coli, Acinetobacter baumannii, and Pseudomonas species. The median CRP was higher in children with MSCE compared with those with culture-negative SE (CNSE) (116.5 vs. 92; P < 0.001) in both HM (132.5 vs. 117; P < 0.001) and ST (87.5 vs. 46; P < 0.001). The procalcitonin was higher in those with MSCE compared with those with CNSE (2.30 vs. 1.40; P < 0.001) in both HM (2.95 vs. 1.60; P = 0.002) and ST (2.10 vs. 1.20; P < 0.001). The case fatality risk was 40.4%; 80% was attributed to sepsis. Of these, 35 (72.92%) had HM and 34 of the 35 (97.14%) had HR-HM. Children with HM had an overall sepsis CFR of 42.68%. Four (30.77%) of the 13 sepsis-related deaths in STs had metastatic disease and 8 (16.67%) of the total number of sepsis-related deaths were in children living with HIV. There was no association between malnutrition or HIV-positivity and death. The odds of dying from sepsis were higher in children with profound (aOR 3.96; P = 0.004) and prolonged (aOR 3.71; P = 0.011) neutropenia. Pneumonia (58.85% vs. 29.23%; aOR 2.38; P = 0.025) and tuberculosis (70.83% vs. 34.91%; aOR 4.3; P = 0.005) were independently associated with a higher CFR. Conclusion The current study emphasizes the high burden of sepsis in African children treated for cancer, and especially HM, and highlights the association of tuberculosis and pneumonia as independent predictors of death in children with cancer.

Download Full-text