Biology subjects

Faruque, A. S. G.

Publications and source records attributed to Faruque, A. S. G..

6 recordsLinked to original sources

bioRxiv2020

Megasphaera in the stool microbiota is negatively associated with diarrheal cryptosporidiosis

BackgroundThe protozoan parasites in the Cryptosporidium genus cause both acute diarrheal disease and subclinical (i.e. non-diarrheal) disease. It is unclear if the microbiota can influence the manifestation of diarrhea during a Cryptosporidium infection. MethodsTo characterize the role of the gut microbiota in diarrheal cryptosporidiosis, the microbiome composition of both diarrheal and surveillance Cryptosporidium-positive fecal samples was evaluated using 16S rRNA gene sequencing. Additionally, the microbiome composition prior to infection was examined to test whether a preexisting microbiome profile could influence the Cryptosporidium infection phenotype. ResultsFecal microbiome composition was associated with diarrheal symptoms at two timepoints. Megasphaera was significantly less abundant in diarrheal samples when compared to subclinical samples at the time of Cryptosporidium detection (log2(fold change) = -4.3, p=10-10) and prior to infection (log2(fold change) = -2.0, p=10-4). Random forest classification also identified Megasphaera abundance in the pre- and post-exposure microbiota.as predictive of a subclinical infection. ConclusionsMicrobiome composition broadly, and specifically low Megasphaera abundance, was associated with diarrheal symptoms prior to and at the time of Cryptosporidium detection. This observation suggests that the gut microenvironment may play a role in determining the severity of a Cryptosporidium infection. SummaryMegasphaera abundance in the stool of Bangladeshi infants is associated with the development of diarrhea upon infection with the Cryptosporidium parasite.

microbiology↗

bioRxiv2019

Evaluation of the impact of Shigella virulence genes on the basis of clinical features observed in patients with shigellosis

Shigella is still attributable to nearly 164,300 deaths annually, mostly in sub-Saharan Africa and South Asian young children, remaining as a major public health threat, especially in the developing countries. Our goal was to study the association between Shigella virulence genes and clinical features observed in shigellosis. Therefore, 61 S. flexneri strains were investigated, isolated from patients from a tertiary level facility in Bangladesh between 2009 to 2013. Subsequently, the presence of 140 MDa large virulence plasmid (p140), virulence (ipaH, ial), toxin (set, sen) and T3SS related genes (virB, ipaBCD, ipgC, ipgB1, ipgA, icsB, ipgD, ipgE, ipgF, mxiH, mxiI, mxiK, mxiE, mxiC, spa15, spa47, spa32 and spa24) were evaluated. p140 was found in 79% (n=48) cases. ipaBCD was found in 90% (n=55) strains, while seven of them were missing p140. However, ial was found in 89% isolates, and ipgC and ipgE in 85% cases. The prevalence of the rest of the genes was less than 85%. These findings were then compared against the clinical features of each of the corresponding pathogens, and several statistically significant correlations were observed (all p<0.05). Briefly, the enterotoxin genes (set, sen) and another virulence gene (ial) were found significantly associated with several clinical features of shigellosis, including bloody mucoid stool, rectal straining, fever, and abdominal pain. Our findings reiterate that the diarrheal disease severity is significantly associated with the enterotoxin producing Shigella infection, also suggesting that the T3SS related virulence genes might be translocated elsewhere other than the 140 MDa large virulence plasmid.

microbiology↗

bioRxiv2019

Genome-wide association study of cryptosporidiosis in infants implicates PRKCA

Diarrhea is a major cause of both morbidity and mortality worldwide, especially among young children. Cryptosporidiosis is a leading cause of diarrhea in children, particularly in South Asia and Sub-Saharan Africa where it is responsible for over 200,000 deaths per year. Beyond the initial clinical presentation of diarrhea, it is associated with long term sequelae such as malnutrition and neurocognitive developmental deficits. Risk factors include poverty and overcrowding, yet not all children with these risk factors and exposure are infected, nor do all infected children develop symptomatic disease. One potential risk factor to explain these differences is their human genome. To identify genetic variants associated with symptomatic cryptosporidiosis, we conducted a genome-wide association study (GWAS) examining 6.5 million single nucleotide polymorphisms (SNPs) in 873 children from three independent cohorts in Dhaka, Bangladesh: the Dhaka Birth Cohort (DBC), the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries (PROVIDE) study, and the Cryptosporidiosis Birth Cohort (CBC). Associations were estimated separately for each cohort under an additive model, adjusting for height-for-age Z-score at 12 months of age, the first two principal components to account for population substructure, and genotyping batch. The strongest meta-analytic association was with rs58296998 (P=3.73x10-8), an intronic SNP and eQTL of PRKCA. Each additional risk allele conferred 2.4 times the odds of cryptosporidiosis in the first year of life. This genetic association suggests a role for protein kinase C alpha in pediatric cryptosporidiosis and warrants further investigation. This article was submitted to an online preprint archive.(1)\n\nImportanceGlobally, one of the major causes of pediatric morbidity and mortality remains diarrhea. The initial symptoms of diarrhea can often lead to long term consequences for the health of young children, such as malnutrition and neurocognitive developmental deficits. Despite many children having similar exposures to infectious causes of diarrhea, not all develop symptomatic disease, indicating a possible role for human genetic variation. Here we conducted a genetic study of susceptibility to symptomatic disease associated with Cryptosporidium infection (a leading cause of diarrhea) in three independent cohorts of infants from Dhaka, Bangladesh. We identified a genetic variant within protein kinase c alpha (PRKCA) associated with higher risk of cryptosporidiosis in the first year of life. These results indicate a role for human genetics in susceptibility to cryptosporidiosis and warrant further research to elucidate the mechanism.

genetics↗

bioRxiv2019

Tubewell use protects against rotavirus infection during the monsoons in an urban setting

Rotavirus, a diarrheal pathogen spread via fecal-oral transmission, is typically characterized by a winter incidence peak in most countries. Unlike for cholera and other water-borne infections, the role of environmental and socioeconomic factors on the spatial variation of rotavirus seasonality remains unclear. Here, we analyze their association with rotavirus seasonality, specifically the odds of monsoon cases, across 46 locations from 2001 to 2012 in Dhaka. Drinking water from tubewells, compared to other sources, has a clear protective effect against cases during the monsoon, when flooding and water contamination are more likely. This finding supports a significant environmental component of transmission.

epidemiology↗

bioRxiv2018

Different features of cholera in malnourished and non-malnourised children: analysis of 10-year surveillance data from a large diarrheal disease hospital in urban Bangladesh

Background: Malnourished children are more prone to infectious diseases including severe diarrhea compared to non-malnourished children. Understanding of the differences in the presentation of severe diarrhea such as cholera in children with varying nutritional status may help in the early identification and management these children. However, data are scarce on differences in the presentation in such children. Thus, we aimed to identify the clinical differentials among children with cholera with or without malnutrition.\n\nMethods: Data were extracted from diarrheal disease surveillance system (DDSS) of the Dhaka Hospital of icddr,b for the period, January 2008 to December 2017. Among under-five children, cholera positive (culture confirmed) and malnourished children (weight-for-age, weight-for-length or height-for-age Z score (WAZ, WHZ or HAZ) <-2) were considered as the cases (n=305) and children with cholera but non-malnourished (WAZ, HAZ, and WHZ [≥]-2.00 to [≤]+2.00) were the controls (n=276).\n\nResults: A total of 14,403 under-five children were enrolled in the surveillance system during the study period. After adjusting for potential covariates such as maternal illiteracy and slum dwelling, it was revealed that under-five malnourished children with cholera significantly more often presented to the hospital during evening hours (6 pm to 12 mid-night) (OR=1.64, 95% CI=1.16-2.31, P<0.05), had fathers who were illiterate (OR=1.70, 95% CI=1.11-2.62, P<0.05), presented with history of cough within last 7 days (OR=1.64, 95% CI=1.10-2.43, P<0.05), dehydrating diarrhea (OR=1.70, 95% CI=1.15-2.53, P<0.05), and had longer hospitalization (OR=1.50, 95% CI=1.05-2.14, P<0.05).\n\nConclusions: The study results underscore the importance of understanding of the basic differences in the presentation of severe cholera in malnourished children for prompt identification and the subsequent management of these children. These observations may help policy makers in formulating better case management strategy.\n\nAuthor SummaryMalnourished children are more vulnerable to infectious diseases including cholera in comparison to the non-malnourished children. They often have suboptimal immune function, though there is no precise information on whether there is any difference in associated factor(s) or clinical course of cholera in under-five children with varying nutritional status. Therefore, this study was conducted to elucidate these insights by using the surveillance data of the Dhaka hospital of icddr,b. Among all the under-five children with cholera, 305 malnourished (WAZ or WLZ or HAZ <-2) children constituted as the cases (malnourished), and another 276 non-malnourished (WAZ, HAZ, and WHZ [≥]-2.00GtoG[≤]+2.00) cholera children formed the comparison group.\n\nIn this study we revealed that care seeking at evening time was more common in the malnourished children with cholera compared to those without malnutrition. Dehydrating diarrhea was about two folds higher and prolonged hospitalization was frequent in malnourished children with cholera than their counterparts. These key findings may help policy makers in formulating better case management strategy in the near future.

microbiology↗

bioRxiv2018

Household Transmission Study of Cryptosporidiosis in Bangladesh

BackgroundCryptosporidium, an apicomplexan protozoa, is a leading contributor to diarrheal morbidity and mortality in children under five years old worldwide. As there is no vaccine and no approved drug for Cryptosporidium spp. in young children, preventing parasite transmission is crucial. We undertook a pilot case-control study to define the extent of person-to-person transmission of cryptosporidiosis within families in an urban and rural community in Bangladesh.\n\nMethodsWe enrolled 48 case families with a Cryptosporidium-infected child aged 6-18 months. Controls were age-sex matched Cryptosporidium-negative children (n=12). Once children were identified, we enrolled all household members. We then followed these individuals for 8 weeks, with weekly surveillance stools and testing with qPCR for Cryptosporidium spp.\n\nFindingsIn the 48 case families, the rate of secondary infections with Cryptosporidium was 18.6% (22/118) compared to 0 new infections (0/35) in the 12 control families. In the 22 urban Mirpur households, the secondary attack rate was 30% (18/60) in cases compared to 0% (0/14) in controls (chi-square p = 0.018). In contrast, in the 21 rural Mirzapur households, the secondary attack rate was 6.9% (4/58) in case households compared to 0% (0/21) in controls (chi-square p = 0.22). Genotyping by gp60 demonstrated infection with the same subspecies in five of six families. Serologic response to Cryptosporidium infection was associated with younger age, longer duration of infection, and C hominis gp60_IbA9G3R2 infection.\n\nInterpretationThe high rate of secondary infection in Mirpur suggests that person-to-person transmission is likely a major source of Cryptosporidium infection for young children living in this region. GP 60 genotyping demonstrated direction of infection in 2 households, and concurrent infection in five households. Further work is needed to understand the differences in parasite transmissibility and immunity to different genotypes.

microbiology↗