Multiple etiologies of infectious diarrhea and concurrent infections in a pediatric outpatient-based screening study in Odisha, India.
ABSTRACT: There are multiple etiologies responsible for infectious gastroenteritis causing acute diarrhea which are often under diagnosed. Also acute diarrhea is one of the major causes of morbidity and mortality among children less than 5 years of age.In our study, fecal samples (n = 130) were collected from children (<5 years) presenting with symptoms of acute diarrhea. Samples were screened for viral, bacterial, and parasitic etiologies. Rotavirus and Adenovirus were screened by immunochromatographic tests. Diarrheagenic Escherichia coli (EPEC, EHEC, STEC, EAEC, O157, O111), Shigella spp., Salmonella spp., Vibrio cholera, Cryptosporidium spp., and Giardia spp. were detected by gene-specific polymerase chain reaction.Escherichia coli was detected to be the major etiological agent (30.07%) followed by Rotavirus (26.15%), Shigella (23.84%), Adenovirus (4.61%), Cryptosporidium (3.07%), and Giardia (0.77%). Concurrent infections with two or more pathogens were observed in 44 of 130 (33.84%) cases with a predominant incidence particularly in <2-year-old children (65.90%) compared to children of 2-5 years age group (34.09%). An overall result showed significantly higher detection rates among children with diarrhea in both combinations of two as well as three infections concurrently (p = 0.004915 and 0.03917, respectively).Suspecting possible multiple infectious etiologies and diagnosis of the right causative agent(s) can aid in a better pharmacological management of acute childhood diarrhea. It is hypothesized that in cases with concurrent infections the etiological agents might be complementing each other's strategies of pathogenesis resulting in severe diarrhea that could be studied better in experimental infections.
Project description:INTRODUCTION:Diarrheal diseases are among the most frequent causes of morbidity and mortality in children worldwide, especially in resource-poor areas. This case-control study assessed the associations between gastrointestinal infections and diarrhea in children from rural Ghana. METHODS:Stool samples were collected from 548 children with diarrhea and from 686 without gastrointestinal symptoms visiting a hospital from 2007-2008. Samples were analyzed by microscopy and molecular methods. RESULTS:The organisms most frequently detected in symptomatic cases were Giardia lamblia, Shigella spp./ enteroinvasive Escherichia coli (EIEC), and Campylobacter jejuni. Infections with rotavirus (adjusted odds ratio [aOR] = 8.4; 95% confidence interval [CI]: 4.3-16.6), C. parvum/hominis (aOR = 2.7; 95% CI: 1.4-5.2) and norovirus (aOR = 2.0; 95%CI: 1.3-3.0) showed the strongest association with diarrhea. The highest attributable fractions (AF) for diarrhea were estimated for rotavirus (AF = 14.3%; 95% CI: 10.9-17.5%), Shigella spp./EIEC (AF = 10.5%; 95% CI: 3.5-17.1%), and norovirus (AF = 8.2%; 95% CI 3.2-12.9%). Co-infections occurred frequently and most infections presented themselves independently of other infections. However, infections with E. dispar, C. jejuni, and norovirus were observed more often in the presence of G. lamblia. CONCLUSIONS:Diarrheal diseases in children from a rural area in sub-Saharan Africa are mainly due to infections with rotavirus, Shigella spp./EIEC, and norovirus. These associations are strongly age-dependent, which should be considered when diagnosing causes of diarrhea. The presented results are informative for both clinicians treating gastrointestinal infections as well as public health experts designing control programs against diarrheal diseases.
Project description:BACKGROUND:Despite substantial global effort and updated clinical management guidelines, diarrhea continues to be among leading worldwide causes of morbidity and mortality in children. Infectious diarrhea, the most common form of diarrhea causes substantial morbidity and mortality among children in developing countries, and the muddled use of antibiotics needs caution due to potential problems of drug-resistance. The aim of this study is to identify etiologies of diarrhea and drug susceptibility patterns of bacterial isolates in under-five children in refugee camps in Gambella Region, Ethiopia. METHODS:An institution- based matched case control study was conducted using a questionnaire-based interview from June to December 2017 in Pugnido and Teirkidi refugee camps. Stool samples were collected and parasites causing diarrhea were identified by wet mount microscopy. Conventional culture supplemented with API 20E identification kit was used to identify Salmonella and Shigella species. Antibiotic susceptibility of bacterial isolates was investigated by using the disk diffusion method. The association between etiologies and diarrhea was analyzed using McNemar test or Fisher exact test with 95% confidence interval at a level of significance of P?<?0.05. RESULTS:The overall prevalence of enteric pathogens were 55 (41.0%) in diarrhea cases and 18 (13.4%) in healthy controls. The detected etiologies include Giardia lambia (28), Shigella spp. (16), E. hystolyotica/dispar (13), Ascaris lumbricoides (10), Salmonella spp. (6), Cryptosporidium parvum (6), Hymenolepis nana (4) and Isospora belli (3). All isolates were sensitive to kanamycine and ceftazidime. The high resistance rate was observed against ampicillin (100%), amoxicillin (100%), erythromycin (52%), chloramphenicol (47.5%), tetracycline (40.5%), cotrimoxazole (34.8%) and amoxicillin-clavulanic acid (33%). The majorities of the isolates had a low rate of resistance to ciprofloxacin (8.7%), naldxic acid (8.7%) and amikacin (13%). CONCLUSIONS:Giardia lamblia, E. Hystolytica/dispar, and Shigella spp are the common etiologies of diarrhea in children in the studied refugee camps. The study also showed that significant numbers of bacterial isolates were resistant to the commonly used antimicrobial drugs. Therefore, improving clinical laboratory services and promoting evidence-based drug prescription may reinforce proper use of antibiotics and reduce the emergence of microbial resistance.
Project description:Acute diarrheal disease (ADD) can be caused by a range of pathogens, including bacteria, viruses, and parasites. Conventional diagnostic methods, such as culture, microscopy, biochemical assays, and enzyme-linked immunosorbent assays (ELISA), are laborious and time-consuming and lack sensitivity. Combined, the array of tests performed on a single specimen can increase the turnaround time (TAT) significantly. We validated a 19plex laboratory-developed gastrointestinal pathogen panel (GPP) using Luminex xTAG analyte-specific reagents (ASRs) to simultaneously screen directly in fecal specimens for diarrhea-causing pathogens, including bacteria (Campylobacter jejuni, Salmonella spp., Shigella spp., enterotoxigenic Escherichia coli [ETEC], Shiga toxin-producing E. coli [STEC], E. coli O157:H7, Vibrio cholerae, Yersinia enterocolitica, and toxigenic Clostridium difficile), parasites (Giardia lamblia, Cryptosporidium spp., and Entamoeba histolytica), and viruses (norovirus GI and GII, adenovirus 40/41, and rotavirus A). Performance characteristics of GPP ASRs were determined using 48 reference isolates and 254 clinical specimens. Stool specimens from individuals with diarrhea were tested for pathogens using conventional and molecular methods. Using the predictive methods as standards, the sensitivities of the GPP ASRs were 100% for adenovirus 40/41, norovirus, rotavirus A, Vibrio cholerae, Yersinia enterocolitica, Entamoeba histolytica, Cryptosporidium spp., and E. coli O157:H7; 95% for Giardia lamblia; 94% for ETEC and STEC; 93% for Shigella spp.; 92% for Salmonella spp.; 91% for C. difficile A/B toxins; and 90% for Campylobacter jejuni. The overall comparative performance of the GPP ASRs with conventional methods in clinical samples was 94.5% (range, 90% to 97%), with 99% (99.0% to 99.9%) specificity. Implementation of the GPP ASRs enables our public health laboratory to offer highly sensitive and specific screening and identification of the major ADD-causing pathogens.
Project description:We collected clinical and morphologic data from children with diarrhea attending 3 diverse hospitals/clinics in Accra. Stool samples were tested for rotavirus and Cryptosporidium spp. In all, 58% of the children with diarrhea had rotavirus infections, 25% of which were of the G3 sero/genotype. The most common strains were G3P  (18.8%) and G2P  (12.5%). Cryptosporidium spp. infections were uncommon (3/143, 2.0%).
Project description:BACKGROUND:Diarrhea is a major cause of morbidity and mortality, yet incidence and etiology data are limited. We conducted laboratory-based diarrhea surveillance in Guatemala. METHODS:A diarrhea case was defined as ≥3 loose stools in a 24-h period in a person presenting to the surveillance facilities. Epidemiologic data and stool specimens were collected. Specimens were tested for bacterial, parasitic, and viral pathogens. Yearly incidence was adjusted for healthcare seeking behaviors determined from a household survey conducted in the surveillance catchment area. RESULTS:From November 2008 to December 2012, the surveillance system captured 5331 diarrhea cases; among these 1381 (26%) had specimens tested for all enteric pathogens of interest. The adjusted incidence averaged 659 diarrhea cases per 10,000 persons per year, and was highest among children aged < 5 years, averaging 1584 cases per 10,000 children per year. Among 1381 (26%) specimens tested for all the pathogens of interest, 235 (17%) had a viral etiology, 275 (20%) had a bacterial, 50 (4%) had parasites, and 86 (6%) had co-infections. Among 827 (60%) specimens from children aged < 5 years, a virus was identified in 196 (23%) patients; 165 (20%) had norovirus and 99 (12%) rotavirus, including co-infections. Among 554 patients aged ≥5 years, 103 (19%) had a bacterial etiology, including diarrheagenic Escherichia coli in 94 (17%) cases, Shigella spp. in 31 (6%), Campylobacter spp. in 5 (1%), and Salmonella spp. in 4 (1%) cases. Detection of Giardia and Cryptosporidium was infrequent (73 cases; 5%). CONCLUSIONS:There was a substantial burden of viral and bacterial diarrheal diseases in Guatemala, highlighting the importance of strengthening laboratory capacity for rapid detection and control and for evaluation of public health interventions.
Project description:Diarrhea is a leading cause of antibiotic consumption among children in low- and middle-income countries. While vaccines may prevent diarrhea infections for which children often receive antibiotics, the contribution of individual enteropathogens to antibiotic use is minimally understood. We used data from the Global Enteric Multicenter Study (GEMS) to estimate pathogen-specific incidence of antibiotic-treated diarrhea among children under five years old residing in six countries of sub-Saharan Africa and South Asia before rotavirus vaccine implementation. GEMS was an age-stratified, individually-matched case-control study. Stool specimens were obtained from children presenting to sentinel health clinics with newly-onset, acute diarrhea (including moderate-to-severe and less-severe diarrhea) as well as matched community controls without diarrhea. We used data from conventional and quantitative molecular diagnostic assays applied to stool specimens to estimate the proportion of antibiotic-treated diarrhea cases attributable to each pathogen. Antibiotics were administered or prescribed to 9,606 of 12,109 moderate-to-severe cases and 1,844 of 3,174 less-severe cases. Across all sites, incidence rates of clinically-attended, antibiotic-treated diarrhea were 12.2 (95% confidence interval: 9.0-17.8), 10.2 (7.4-13.9) and 1.9 (1.3-3.0) episodes per 100 child-years at risk at ages 6 weeks to 11 months, 12-23 months, and 24-59 months, respectively. Based on the recommendation for antibiotic treatment to be reserved for cases with dysentery, we estimated a ratio of 12.6 (8.6-20.8) inappropriately-treated diarrhea cases for each appropriately-treated case. Rotavirus, adenovirus serotypes 40/41, Shigella, sapovirus, Shiga toxin-producing Escherichia coli, and Cryptosporidium were the leading antibiotic-treated diarrhea etiologies. Rotavirus caused 29.2% (24.5-35.2%) of antibiotic-treated cases, including the largest share in both the first and second years of life. Shigella caused 14.9% (11.4-18.9%) of antibiotic-treated cases, and was the leading etiology at ages 24-59 months. Our findings should inform the prioritization of vaccines with the greatest potential to reduce antibiotic exposure among children.
Project description:BACKGROUND:In Sub-Saharan Africa, infectious diarrhea is a major cause of morbidity and mortality. A case-control study was conducted to identify the etiology of diarrhea and to describe its main epidemiologic risk factors among hospitalized children under five years old in Bangui, Central African Republic. METHODS:All consecutive children under five years old hospitalized for diarrhea in the Pediatric Complex of Bangui for whom a parent's written consent was provided were included. Controls matched by age, sex and neighborhood of residence of each case were included. For both cases and controls, demographic, socio-economic and anthropometric data were recorded. Stool samples were collected to identify enteropathogens at enrollment. Clinical examination data and blood samples were collected only for cases. RESULTS:A total of 333 cases and 333 controls was recruited between December 2011 and November 2013. The mean age of cases was 12.9 months, and 56% were male. The mean delay between the onset of first symptoms and hospital admission was 3.7 days. Blood was detected in 5% of stool samples from cases. Cases were significantly more severely or moderately malnourished than controls. One of the sought-for pathogens was identified in 78% and 40% of cases and controls, respectively. Most attributable cases of hospitalized diarrhea were due to rotavirus, with an attributable fraction of 39%. Four other pathogens were associated with hospitalized diarrhea: Shigella/EIEC, Cryptosporidium parvum/hominis, astrovirus and norovirus with attributable fraction of 9%, 10%, 7% and 7% respectively. Giardia intestinalis was found in more controls than cases, with a protective fraction of 6%. CONCLUSIONS:Rotavirus, norovirus, astrovirus, Shigella/EIEC, Cryptosporidium parvum/hominis were found to be positively associated with severe diarrhea: while Giardia intestinalis was found negatively associated. Most attributable episodes of severe diarrhea were associated with rotavirus, highlighting the urgent need to introduce the rotavirus vaccine within the CAR's Expanded Program on Immunization. The development of new medicines, vaccines and rapid diagnostic tests that can be conducted at the bedside should be high priority for low-resource countries.
Project description:BACKGROUND:Rotavirus vaccine efficacy (VE) estimates in low-resource settings are lower than in developed countries. We detected coinfections in cases of severe rotavirus diarrhea in a rotavirus VE trial to determine whether these negatively impacted rotavirus VE estimates. METHODS:We performed TaqMan Array Card assays for enteropathogens on stools from rotavirus enzyme immunoassay-positive diarrhea episodes and all severe episodes (Vesikari score ≥11), from a phase 3 VE trial of Rotavac, a monovalent human-bovine (116E) rotavirus vaccine, carried out across 3 sites in India. We estimated pathogen-specific etiologies of diarrhea, described associated clinical characteristics, and estimated the impact of coinfections on rotavirus VE using a test-negative design. RESULTS:A total of 1507 specimens from 1169 infants were tested for the presence of coinfections. Rotavirus was the leading cause of severe diarrhea even among vaccinated children, followed by adenovirus 40/41, Shigella/enteroinvasive Escherichia coli, norovirus GII, sapovirus, and Cryptosporidium species. Bacterial coinfections in rotavirus-positive diarrhea were associated with a longer duration of diarrhea and protozoal coinfections with increased odds of hospitalization. Using the test-negative design, rotavirus VE against severe rotavirus gastroenteritis increased from 49.3% to 60.6% in the absence of coinfections (difference, 11.3%; 95% confidence interval, -10.3% to 30.2%). CONCLUSIONS:While rotavirus was the dominant etiology of severe diarrhea even in vaccinated children, a broad range of other etiologies was identified. Accounting for coinfections led to an 11.3% increase in the VE estimate. Although not statistically significant, an 11.3% decrease in VE due to presence of coinfections would explain an important fraction of the low rotavirus VE in this setting.
Project description:Pediatric diarrhea is a common cause of death among children under 5 years of age. In the current study, we investigated the frequency of intestinal parasites among 580 pediatric patients with chronic diarrhea. Parasitic protozoa (all species combined) were detected by molecular tools in 22.9% of the children and the most common parasite was Cryptosporidium spp. (15.1%). Blastocystis hominis was detected in 4.7%, Dientamoeba fragilis in 4%, Giardia duodenalis in 1.7%, and Entamoeba histolytica in 0.17%. Protozoan infections were observed among all regional groups, but prevalence was highest among Qatari subjects and during the winter season. Typing of Cryptosporidium spp. revealed a predominance of Cryptosporidium parvum in 92% of cases with mostly the IIdA20G1 subtype. Subtypes IIdA19G2, IIdA18G2, IIdA18G1, IIdA17G1, IIdA16G1, and IIdA14G1 were also detected. For Cryptosporidium hominis, IbA10G2 and IbA9G3 subtypes were identified. This study provides supplementary information for implementing prevention and control strategies to reduce the burden of these pediatric protozoan infections. Further analyses are required to better understand the local epidemiology and transmission of Cryptosporidium spp. in Qatar.
Project description:BACKGROUND:Intestinal parasites such as Cryptosporidium spp., Giardia lamblia and Entamoeba histolytica can cause severe diarrhea, especially among children in developing countries. This study aims to determine the frequency of Cryptosporidium spp., Giardia lamblia and Entamoeba histolytica in children with diarrhea and identify risk factors for infection. METHODOLOGY:We conducted a cross-sectional study in children aged 0-168 months hospitalized with diarrhea in three regions of Mozambique, from June 2014 to January 2018. Following consent, caretakers were interviewed and a single stool specimen was collected from each child to diagnose Cryptosporidium spp., G. lamblia and E. histolytica using commercial immune-enzymatic assay (TechLab, Inc, Blacksburg, VA, USA). Anthropometric data were collected from the clinical reports. Multivariable logistic regression models were built to identify risk factors for Cryptosporidium spp. and G. lamblia infection. RESULTS:Twenty-one percent of all specimens (212/1008) presented at least one parasitic infection. Cryptosporidium spp. infection was the most common 12.0% (118/985), followed by G. lamblia 9.7% (95/983) and E. histolytica 2.0% (20/1004). Risk factors for infection by Cryptosporidium spp. were: provenience (children from Nampula province showed the highest risk, OR: 8.176; CI: 1.916-34.894; p-value < 0.01); animal contact (children with animal contact had a protective effect OR: 0.627; CI: 0.398-0.986; p-value < 0.05); underweight (children severely underweight showed a risk of 2.309; CI: 1.310-4.069; p-value < 0.05). Risk factors for infection by G. lamblia were: age (group with highest risk, 60-168 months (OR: 2.322; CI: 1.000-5.393, p-value > 0.05)); and living in a household with five or more members (OR: 2.141; CI: 1.286-3.565, p-value < 0.01). CONCLUSIONS:Parasitic infection is common among children with diarrhea. Routine testing, standard treatment, and assessment for risk exposure of children with diarrhea should be implemented at health facilities in Mozambique.