Clinical severity of enteric viruses detected using a quantitative molecular assay compared to conventional assays in the Global Enteric Multicenter Study.

BACKGROUND: Quantitative molecular assays are increasingly used for detection of enteric viruses. METHODS: We compared the clinical severity using modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIA] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (CT) cutoffs. RESULTS: Using conventional assays, the median (interquartile range) mVS was 10 (8, 11) for rotavirus, 9 (7, 11) for adenovirus 40/41, 8 (6, 10) for astrovirus, sapovirus, and norovirus GII, and 7 (6, 9) for norovirus GI. Compared to rotavirus EIA-positive cases, the median mVS was 2 and 3 points lower for EIA-negative/TAC-positive cases with CT<32.6 and 32.6≤CT<35, respectively (p-value<.0001). Adenovirus 40/41 EIA-positive and EIA-negative/TAC-positive cases were similar, regardless of CT cutoff. CONCLUSIONS: Quantitative molecular assays compared to conventional assays, such as EIA, may influence severity of identified cases, especially for rotavirus. Cutoffs to assign etiology for quantitative assays should be considered in the design and interpretation of enteric virus studies.

Azithromycin for Bacterial Watery Diarrhea: A Reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) Trial Incorporating Molecular Diagnostics.

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.

Prevalence of Colonization With Antibiotic-Resistant Organisms in Hospitalized and Community Individuals in Bangladesh, a Phenotypic Analysis: Findings From the Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance (AMR) but often lack adequate surveillance to inform mitigation efforts. Colonization can be a useful metric to understand AMR burden. We assessed the colonization prevalence of Enterobacterales with resistance to extended-spectrum cephalosporins, carbapenems, colistin, and methicillin-resistant Staphylococcus aureus among hospital and community dwellers. METHODS: Between April and October 2019, we conducted a period prevalence study in Dhaka, Bangladesh. We collected stool and nasal specimens from adults in 3 hospitals and from community dwellers within the hospitals' catchment area. Specimens were plated on selective agar plates. Isolates underwent identification and antibiotic susceptibility testing using Vitek 2. We performed descriptive analysis and determined population prevalence estimates accounting for clustering at the community level. RESULTS: The majority of both community and hospital participants were colonized with Enterobacterales with resistance to extended-spectrum cephalosporins (78%; 95% confidence interval [95% CI], 73-83; and 82%; 95% CI, 79-85, respectively). Thirty-seven percent (95% CI, 34-41) of hospitalized patients were colonized with carbapenems compared with 9% (95% CI, 6-13) of community individuals. Colistin colonization prevalence was 11% (95% CI, 8-14) in the community versus 7% (95% CI, 6-10) in the hospital. Methicillin-resistant Staphylococcus aureus colonization was similar in both community and hospital participants (22%; 95% CI, 19-26 vs 21% (95% CI, 18-24). CONCLUSIONS: The high burden of AMR colonization observed among hospital and community participants may increase the risk for developing AMR infections and facilitating spread of AMR in both the community and hospital.

P-score in preoperative biopsies accurately predicts P-score in final pathology at radical prostatectomy in patients with localized prostate cancer.

BACKGROUND: Prostate cancer (PCa) is a highly heterogeneous, multifocal disease, and identification of clinically significant lesions is challenging, which complicates the choice of adequate treatment. The Prostatype® score (P-score) is intended to guide treatment decisions for newly diagnosed PCa patients based on a three-gene signature (IGFBP3, F3, and VGLL3) and clinicopathological information obtained at diagnosis. This study evaluated association of the P-score measured in preoperative magnetic resonance imaging/transrectal ultrasound fusion-guided core needle biopsies (CNBs) and the P-score measured in radical prostatectomy (RP) specimens of PCa patients. We also evaluated the P-score association with the pathology of RP specimens. Furthermore, concordance of the P-score in paired CNB and RP specimens, as well as in index versus concomitant nonindex tumor foci from the same RP was investigated. METHODS: The study included 100 patients with localized PCa. All patients were diagnosed by CNB and underwent RP between 2015 and 2018. Gene expression was assessed with the Prostatype® real-time quantitative polymerase chain reaction kit and the P-score was calculated. Patients were categorized into three P-score risk groups according to previously defined cutoffs. RESULTS: For 71 patients, sufficient CNB tumor material was available for comparison with the RP specimens. The CNB-based P-score was associated with the pathological T-stage in RP specimens (p = 0.02). Moreover, the CNB-based P-score groups were in substantial agreement with the RP-based P-score groups (weighted κ score: 0.76 [95% confidence interval, 95% CI: 0.60-0.92]; Spearman's rank correlation coefficient r = 0.83 [95% CI: 0.74-0.89]; p < 0.0001). Similarly, the P-score groups based on paired index tumor and concomitant nonindex tumor foci (n = 64) were also in substantial agreement (weighted κ score: 0.74 [95% CI: 0.57-0.91]; r = 0.83 [95% CI: 0.73-0.89], p < 0.0001). CONCLUSIONS: Our findings suggest that the P-score based on preoperative CNB accurately reflects the pathology of the whole tumor, highlighting its value as a decision support tool for newly diagnosed PCa patients.

Urinary arsenic is associated with wasting and underweight status in young children in rural Bangladesh.

BACKGROUND: Deficits in child growth are associated with poor cognitive outcomes and an increased risk for infection and mortality globally. One hundred forty million people are chronically exposed to arsenic from contaminated drinking water worldwide. While arsenic exposure has been associated with cognitive developmental delays in children, there is limited research on the association between arsenic exposure and growth deficits in young children. PURPOSE: The objective of this study was to assess the association between chronic arsenic exposure and deficits in growth among children under 5 years in a rural setting in Bangladesh. METHODS: Urinary arsenic measurements were collected from 465 children between the ages of 28 days-59 months in rural Matlab, Bangladesh, and analyzed by graphite furnace atomic absorption. Height and weight measurements were collected from children according to World Health Organization child growth standards. A z-score cutoff2 standard deviations below the mean was used to define stunting (height-for-age z-score), underweight (weight-for-age z-score), and wasting (weight-for-height z-score). RESULTS: Children under 5 years with urinary arsenic concentrations in the third tertile (greater than 31 µg per liter (µg/L)) had a two times higher odds of being underweight after adjustment for age, creatinine, paternal education, breastfeeding, number of individuals using the same sleeping room, and physician-diagnosed pneumonia (Odds Ratio (OR): 2.29 (95% Confidence Interval (CI): 1.16, 4.52)). Children under 2 years of age had a two times higher odds of being wasted after adjustment for age, creatinine, paternal education, breastfeeding, number of individuals using the same sleeping room, and physician-diagnosed pneumonia (OR: 2.85 (95% CI: 1.18, 6.89)). CONCLUSIONS: These findings suggest that arsenic exposure is associated with an increased odds of being wasted and underweight among young children in rural Bangladesh.

Clostridioides difficile ribotypes isolated from domestic environment and from patients in Bangladesh.

Clostridioides difficile infection (CDI) is an emerging but often understudied infectious disease in developing countries. This study was aimed to isolate and characterize C. difficile from shoe sole swabs and diarrheal patient's stool samples in Bangladesh. We collected 94 shoe sole swabs samples from urban communities in Dhaka and 208 diarrheal stool samples from hospitalized patients over a period of 4 months. Samples were incubated anaerobically for C. difficile growth, confirmed toxigenic, and PCR-ribotyped. Eleven of 94 (11.7%) shoe sole swabs and 4 of 208 (1.9%) stool samples were culture positive of which 9 shoe sole isolates were toxigenic. Six PCR ribotypes from the 9 toxigenic isolates were identified with ribotype F014-020 being the most common (n = 4; 44%). The recently identified ribotype 106 strain was also identified. To the best of our knowledge, this is the first report of C. difficile culture, isolation and characterization from environmental sources in Bangladesh.

Standardization of Laboratory Methods for the PERCH Study.

The Pneumonia Etiology Research for Child Health study was conducted across 7 diverse research sites and relied on standardized clinical and laboratory methods for the accurate and meaningful interpretation of pneumonia etiology data. Blood, respiratory specimens, and urine were collected from children aged 1-59 months hospitalized with severe or very severe pneumonia and community controls of the same age without severe pneumonia and were tested with an extensive array of laboratory diagnostic tests. A standardized testing algorithm and standard operating procedures were applied across all study sites. Site laboratories received uniform training, equipment, and reagents for core testing methods. Standardization was further assured by routine teleconferences, in-person meetings, site monitoring visits, and internal and external quality assurance testing. Targeted confirmatory testing and testing by specialized assays were done at a central reference laboratory.

Microscopic Analysis and Quality Assessment of Induced Sputum From Children With Pneumonia in the PERCH Study.

BACKGROUND.: It is standard practice for laboratories to assess the cellular quality of expectorated sputum specimens to check that they originated from the lower respiratory tract. The presence of low numbers of squamous epithelial cells (SECs) and high numbers of polymorphonuclear (PMN) cells are regarded as indicative of a lower respiratory tract specimen. However, these quality ratings have never been evaluated for induced sputum specimens from children with suspected pneumonia. METHODS.: We evaluated induced sputum Gram stain smears and cultures from hospitalized children aged 1-59 months enrolled in a large study of community-acquired pneumonia. We hypothesized that a specimen representative of the lower respiratory tract will contain smaller quantities of oropharyngeal flora and be more likely to have a predominance of potential pathogens compared to a specimen containing mainly saliva. The prevalence of potential pathogens cultured from induced sputum specimens and quantity of oropharyngeal flora were compared for different quantities of SECs and PMNs. RESULTS.: Of 3772 induced sputum specimens, 2608 (69%) had <10 SECs per low-power field (LPF) and 2350 (62%) had >25 PMNs per LPF, measures traditionally associated with specimens from the lower respiratory tract in adults. Using isolation of low quantities of oropharyngeal flora and higher prevalence of potential pathogens as markers of higher quality, <10 SECs per LPF (but not >25 PMNs per LPF) was the microscopic variable most associated with high quality of induced sputum. CONCLUSIONS.: Quantity of SECs may be a useful quality measure of induced sputum from young children with pneumonia.

The Diagnostic Utility of Induced Sputum Microscopy and Culture in Childhood Pneumonia.

BACKGROUND.: Sputum microscopy and culture are commonly used for diagnosing the cause of pneumonia in adults but are rarely performed in children due to difficulties in obtaining specimens. Induced sputum is occasionally used to investigate lower respiratory infections in children but has not been widely used in pneumonia etiology studies. METHODS.: We evaluated the diagnostic utility of induced sputum microscopy and culture in patients enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study, a large study of community-acquired pneumonia in children aged 1-59 months. Comparisons were made between induced sputum samples from hospitalized children with radiographically confirmed pneumonia and children categorized as nonpneumonia (due to the absence of prespecified clinical and laboratory signs and absence of infiltrate on chest radiograph). RESULTS.: One induced sputum sample was available for analysis from 3772 (89.1%) of 4232 suspected pneumonia cases enrolled in PERCH. Of these, sputum from 2608 (69.1%) met the quality criterion of <10 squamous epithelial cells per low-power field, and 1162 (44.6%) had radiographic pneumonia. Induced sputum microscopy and culture results were not associated with radiographic pneumonia, regardless of prior antibiotic use, stratification by specific bacteria, or interpretative criteria used. CONCLUSIONS.: The findings of this study do not support the culture of induced sputum specimens as a diagnostic tool for pneumonia in young children as part of routine clinical practice.

The Effect of Antibiotic Exposure and Specimen Volume on the Detection of Bacterial Pathogens in Children With Pneumonia.

BACKGROUND.: Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children. METHODS.: PERCH (Pneumonia Etiology Research for Child Health) is a case-control study of pneumonia in children aged 1-59 months investigating pathogens in blood, nasopharyngeal/oropharyngeal (NP/OP) swabs, and induced sputum by culture and PCR. Antibiotic exposure was ascertained by serum bioassay, and for cases, by a record of antibiotic treatment prior to specimen collection. Inoculated blood culture bottles were weighed to estimate volume. RESULTS.: Antibiotic exposure ranged by specimen type from 43.5% to 81.7% in 4223 cases and was detected in 2.3% of 4863 controls. Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture. Reduction in yield of Streptococcus pneumoniae from NP culture was approximately 30% in cases and approximately 32% in controls. Several bacteria had significant but marginal reductions (by 5%-7%) in detection by PCR in NP/OP swabs from both cases and controls, with the exception of S. pneumoniae in exposed controls, which was detected 25% less frequently compared to nonexposed controls. Bacterial detection in induced sputum by PCR decreased 7% for exposed compared to nonexposed cases. For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% (95% confidence interval, 0.47%-0.54%), from 2% when volume was ≤1 mL to approximately 6% for ≥3 mL. CONCLUSIONS.: Antibiotic exposure and blood culture volume affect detection of bacterial pathogens in children with pneumonia and should be accounted for in studies of etiology and in clinical management.

Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.

BACKGROUND.: There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. METHODS.: In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens. RESULTS.: Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)-positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii. CONCLUSIONS.: There is evidence for an association between H. influenzae colonization density and H. influenzae-confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings.

Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries.

BACKGROUND.: We investigated the performance of polymerase chain reaction (PCR) on blood in the diagnosis of pneumococcal pneumonia among children from 7 low- and middle-income countries. METHODS.: We tested blood by PCR for the pneumococcal autolysin gene in children aged 1-59 months in the Pneumonia Etiology Research for Child Health (PERCH) study. Children had World Health Organization-defined severe or very severe pneumonia or were age-frequency-matched community controls. Additionally, we tested blood from general pediatric admissions in Kilifi, Kenya, a PERCH site. The proportion PCR-positive was compared among cases with microbiologically confirmed pneumococcal pneumonia (MCPP), cases without a confirmed bacterial infection (nonconfirmed), cases confirmed for nonpneumococcal bacteria, and controls. RESULTS.: In PERCH, 7.3% (n = 291/3995) of cases and 5.5% (n = 273/4987) of controls were blood pneumococcal PCR-positive (P < .001), compared with 64.3% (n = 36/56) of MCPP cases and 6.3% (n = 243/3832) of nonconfirmed cases (P < .001). Blood pneumococcal PCR positivity was higher in children from the 5 African countries (5.5%-11.5% among cases and 5.3%-10.2% among controls) than from the 2 Asian countries (1.3% and 1.0% among cases and 0.8% and 0.8% among controls). Among Kilifi general pediatric admissions, 3.9% (n = 274/6968) were PCR-positive, including 61.7% (n = 37/60) of those with positive blood cultures for pneumococcus. DISCUSSION.: The utility of pneumococcal PCR on blood for diagnosing childhood pneumococcal pneumonia in the 7 low- and middle-income countries studied is limited by poor specificity and by poor sensitivity among MCPP cases.

Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study.

BACKGROUND.: Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. METHODS.: The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the "optimal threshold" that distinguished MCPP cases from controls. RESULTS.: Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 × 103 vs 0.19 × 103 copies/mL), but overlapped substantially (range, 0.16-989.9 × 103 copies/mL and 0.01-551.9 × 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls. CONCLUSIONS.: Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies.

Sexually Transmitted Infections and Associated Risk Factors Among Street-Based and Residence-Based Female Sex Workers in Dhaka, Bangladesh.

BACKGROUND: Female sex workers (FSWs) in Bangladesh remain at elevated risk of sexually transmitted infections (STIs) although the human immunodeficiency virus (HIV) prevalence among them is low. Recent information on the burden and etiological diagnosis of STIs among them has been lacking. This study examines prevalence and risk behaviors of selected STIs among FSWs in Dhaka in 2014. METHODS: Between August and October 2014, a cross-sectional study was conducted among street-based and residence-based FSWs receiving HIV prevention services at 24 drop in centers in Dhaka. Participants underwent behavioral interview, clinical examination, and laboratory testing for selected STIs using cervical swabs and blood. RESULTS: The sample consisted of 371 streets and 329 residence FSWs. Prevalence of gonorrhea, chlamydia, and active syphilis were 5.1%, 4.6%, 1.3% in street FSWs and were 5.8%, 8.2%, and 0.6% for residence FSWs which are lower compared with the previously reported rates. The following factors were associated with having any STI: being ≤5 years in sex trade (odds ratio, 2.2; 95% confidence interval, 1.2-3.9; P < 0.01), and having a cervical discharge (odds ratio, 2.6, 95% confidence interval, 1.5-4.6; P < 0.01). Resistance to cefixime and azithromycin was observed for 1 and 3 Neisseria gonorrhoeae strains, respectively. CONCLUSIONS: Despite receiving HIV/STI prevention services, bacterial STIs remain prevalent among FSWs suggesting the need for more effective management of STIs. The guidelines for management of STIs need revision in view of the emerging resistance.

Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of Vibrio cholerae.

We evaluated the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MS) for the identification of Vibrio cholerae. MS identified all 42 isolates of V. cholerae O1 and O139 and 7 of 9 non-O1/O139 isolates. MS correctly discriminated between all Aeromonas and V. cholerae isolates. Overall, MS performed as well as or better than biochemical methods.

Arsenic exposure is associated with pediatric pneumonia in rural Bangladesh: a case control study.

BACKGROUND: Pneumonia is the leading cause of death for children under 5 years of age globally, making research on modifiable risk factors for childhood pneumonia important for reducing this disease burden. Millions of children globally are exposed to elevated levels of arsenic in drinking water. However, there is limited data on the association between arsenic exposure and respiratory infections, particularly among pediatric populations. METHODS: This case control study of 153 pneumonia cases and 296 controls 28 days to 59 months of age in rural Bangladesh is the first to assess whether arsenic exposure is a risk factor for pneumonia in a pediatric population. Cases had physician diagnosed World Health Organization defined severe or very severe pneumonia. Urine collected during hospitalization (hospital admission time point) and 30 days later (convalescent time point) from cases and a single specimen from community controls was tested for urinary arsenic by graphite furnace atomic absorption. RESULTS: The odds for pneumonia was nearly double for children with urinary arsenic concentrations higher than the first quartile (≥6 µg/L) at the hospital admission time point (Odd Ratio (OR):1.88 (95% Confidence Interval (CI): 1.01, 3.53)), after adjustment for urinary creatinine, weight for height, breastfeeding, paternal education, age, and number of people in the household. This was consistent with findings at the convalescent time point where the adjusted OR for children with urinary arsenic concentrations greater than the first quartile (≥6 µg/L) was 2.32 (95% CI: 1.33, 4.02). CONCLUSION: We observed a nearly two times higher odds of pneumonia for children with creatinine adjusted urinary arsenic concentrations greater than the first quartile (≥6 µg/L) at the hospital admission time point. This novel finding suggests that low to moderate arsenic exposure may be a risk factor for pneumonia in children under 5 years of age.

Long-term comparison of antibiotic resistance in Vibrio cholerae O1 and Shigella species between urban and rural Bangladesh.

From 2000 to 2012, Vibrio cholerae O1 and Shigella species isolates from urban Dhaka and rural Matlab were tested for resistance to all clinically relevant antibiotics in Bangladesh. Resistances in urban and rural Bangladesh tended to rise and fall together, especially a few years after the introduction of new resistance.

Emergence of the novel sixth Candida auris Clade VI in Bangladesh.

Candida auris, initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of C. auris, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of C. auris from Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. Ten C. auris isolates collected from hospital settings in Bangladesh were initially identified by CHROMagar Candida Plus, followed by VITEK2 system, and later sequenced using Illumina NextSeq 550 system. Reference-based phylogenetic analysis and variant calling pipelines were used to classify the isolates in different clades. All isolates aligned ~90% with the Clade I C. auris B11205 reference genome. Of the 10 isolates, 8 were clustered with Clade I isolates, highlighting a South Asian lineage prevalent in Bangladesh. Remarkably, the remaining two isolates formed a distinct cluster, exhibiting >42,447 single-nucleotide polymorphism differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) of C. auris in Bangladesh, with potential for international transmission. AFST results showed that 80% of the C. auris isolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealed ERG11_Y132F mutation conferring azole resistance while FCY1_S70R mutation found inconsequential in describing 5-flucytosine resistance. Our study underscores the pressing need for comprehensive genomic surveillance in Bangladesh to better understand the emergence, transmission dynamics, and resistance profiles of C. auris infections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.IMPORTANCECandida auris is a nosocomial fungal pathogen that is commonly misidentified as other Candida species. Since its emergence in 2009, this multidrug-resistant fungus has become one of the five urgent antimicrobial threats by 2019. Whole-genome sequencing (WGS) has proven to be the most accurate identification technique of C. auris which also played a crucial role in the initial discovery of this pathogen. WGS analysis of C. auris has revealed five distinct clades where isolates of each clade differ among themselves based on pathogenicity, colonization, infection mechanism, as well as other phenotypic characteristics. In Bangladesh, C. auris was first reported in 2019 from clinical samples of a large hospital in Dhaka city. To understand the origin, transmission dynamics, and antifungal-resistance profile of C. auris isolates circulating in Bangladesh, we conducted a WGS-based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh.

The Enterics for Global Health (EFGH) Shigella Surveillance Study in Bangladesh.

Background: Shigella is an important cause of diarrhea in Bangladeshi children <5 years of age, with an incidence rate of 4.6 per 100 person-years. However, the report was more than a decade old, and data on Shigella consequences are similarly outdated and heterogeneously collected. Methods: Facility-based disease surveillance is planned to be carried out under the Enterics for Global Health (EFGH) Shigella Surveillance Study consortium for 2 years with aims to optimize and standardize laboratory techniques and healthcare utilization and coverage survey, clinical and anthropometric data collection, safety monitoring and responsiveness, and other related activities. The EFGH is a cohesive network of multidisciplinary experts, capable of operating in concert to conduct the study to generate data that will pave the way for potential Shigella vaccine trials in settings with high disease burden. The study will be conducted within 7 country sites in Asia, Africa, and Latin America. Conclusions: We outline the features of the Bangladesh site as part of this multisite surveillance network to determine an updated incidence rate and document the consequences of Shigella diarrhea in children aged 6-35 months, which will help inform policymakers and to implement the future vaccine trials.

Childhood growth during recovery from acute illness in Africa and South Asia: a secondary analysis of the childhood acute illness and nutrition (CHAIN) prospective cohort.

Background: Growth faltering is well-recognized during acute childhood illness and growth acceleration during convalescence, with or without nutritional therapy, may occur. However, there are limited recent data on growth after hospitalization in low- and middle-income countries. Methods: We evaluated growth following hospitalization among children aged 2-23 months in sub-Saharan Africa and South Asia. Between November 2016 and January 2019, children were recruited at hospital admission and classified as: not-wasted (NW), moderately-wasted (MW), severely-wasted (SW), or having nutritional oedema (NO). We describe earlier (discharge to 45-days) and later (45- to 180-days) changes in length-for-age [LAZ], weight-for-age [WAZ], mid-upper arm circumference [MUACZ], weight-for-length [WLZ] z-scores, and clinical, nutritional, and socioeconomic correlates. Findings: We included 2472 children who survived to 180-days post-discharge: NW, 960 (39%); MW, 572 (23%); SW, 682 (28%); and NO, 258 (10%). During 180-days, LAZ decreased in NW (-0.27 [-0.36, -0.19]) and MW (-0.23 [-0.34, -0.11]). However, all groups increased WAZ (NW, 0.21 [95% CI: 0.11, 0.32]; MW, 0.57 [0.44, 0.71]; SW, 1.0 [0.88, 1.1] and NO, 1.3 [1.1, 1.5]) with greatest gains in the first 45-days. Of children underweight (<-2 WAZ) at discharge, 66% remained underweight at 180-days. Lower WAZ post-discharge was associated with age-inappropriate nutrition, adverse caregiver characteristics, small size at birth, severe or moderate anaemia, and chronic conditions, while lower LAZ was additionally associated with household-level exposures but not with chronic medical conditions. Interpretation: Underweight and poor linear growth mostly persisted after an acute illness. Beyond short-term nutritional supplementation, improving linear growth post-discharge may require broader individual and family support. Funding: Bill & Melinda Gates FoundationOPP1131320; National Institute for Health ResearchNIHR201813.