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Many important questions in infectious disease epidemiology involve associations between covariates (e.g., age or vaccination status) and infectiousness or susceptibility. Because disease transmission produces dependent outcomes, these questions are difficult or impossible to address using standard regression models from biostatistics. Pairwise survival analysis handles dependent outcomes by calculating likelihoods in terms of contact interval distributions in ordered pairs of individuals. The contact interval in the ordered pair i j $$ ij $$ is the time from the onset of infectiousness in i $$ i $$ to infectious contact from i $$ i $$ to j $$ j $$ , where an infectious contact is sufficient to infect j $$ j $$ if they are susceptible. Here, we introduce a pairwise accelerated failure time regression model for infectious disease transmission that allows the rate parameter of the contact interval distribution to depend on individual-level infectiousness covariates for i $$ i $$ , individual-level susceptibility covariates for j $$ j $$ , and pair-level covariates (e.g., type of relationship). This model can simultaneously handle internal infections (caused by transmission between individuals under observation) and external infections (caused by environmental or community sources of infection). We show that this model produces consistent and asymptotically normal parameter estimates. In a simulation study, we evaluate bias and confidence interval coverage probabilities, explore the role of epidemiologic study design, and investigate the effects of model misspecification. We use this regression model to analyze household data from Los Angeles County during the 2009 influenza A (H1N1) pandemic, where we find that the ability to account for external sources of infection increases the statistical power to estimate the effect of antiviral prophylaxis., (© 2024 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd.)

Nipah virus spillovers via consumption of date palm sap in Bangladesh vary substantially between years and have been associated with lower winter temperatures and precipitation. However, the mechanisms driving the interannual variation and the influence of weather remain unexplained. Here we investigated the hypothesis that weather patterns change human sap consumption and explain interannual variation in observed spillovers. We analyzed responses from a nationally representative survey conducted in Bangladesh in 2013-2016 on household date palm sap consumption and weather data for each division of Bangladesh, using logistic regression to examine whether sap consumption is associated with weather variability. We found significant associations of lower minimum temperatures and precipitation with increased household sap consumption during the sap harvesting season. This relationship was largely similar within all months and divisions, and strong associations of temperature (χ2 (1, n = 5,027) = 7.74, p < 0.01) and, independently, precipitation (χ2 = 8.00, p < 0.01) remained strong after accounting for month, location, and annual sap season. Interannual variation in date palm sap consumption in Bangladesh is likely best explained by temperature and precipitation patterns, where colder, drier winter days pose a higher risk for Nipah virus spillover. The knowledge gained in this study may be valuable for targeting timing of future behavioral interventions against consumption of date palm sap in Bangladesh., Competing Interests: No conflicts of interest have been reported for this work., (Copyright: © 2024 Jackson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Endometriosis is a disease among women of reproductive age, which causes several health problems, such as dysmenorrhea, dyspareunia, and subfertility. In addition, it increases psychological stress and often results in marital disharmony. Similarly, migraine is more frequent among this group of women. Several studies have shown an association between endometriosis and migraine among groups of populations completely different from Bangladesh., Objective: This study aimed to identify the association between endometriosis and migraine among the Bangladeshi population., Study Design: This nonrandomized case-control study was conducted with cases of endometriosis and controls without endometriosis who were confirmed by laparoscopy or laparotomy. Among the study participants, cases of migraine in 1 group of respondents who were already diagnosed as patients of migraine were identified, and the others with complaints of headaches were further confirmed by a medicine specialist. Patients were recruited from the Department of Obstetrics and Gynecology at the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders General Hospital and Ibrahim Medical College. The study was approved by the ethical review committee of the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders General Hospital. Multivariate logistic regression was used to identify the association between endometriosis and migraine using odds ratios and 95% confidence intervals., Results: Of 1496 patients who underwent laparoscopy or laparotomy during the study period, the frequency of endometriosis was found to be 12.7%. A total of 190 patients with confirmed endometriosis cases and an equal number of controls without endometriosis were enrolled, maintaining the age distribution of the controls similar to that of the cases. Compared with controls, the distribution of age, body mass index, education, and marital status of the patients with endometriosis were similar. The average ages of respondents were 30.6 years in both the case and control groups. Regarding occupation, cases included more students than controls (12% vs 0%, respectively). The odds of suffering from dysmenorrhea and dyspareunia among the cases were 3.3 (95% confidence interval, 2.66-4.15; P <.001) and 9.5 (95% confidence interval, 5.3-17.9; P <.001) times higher than that of controls, respectively. In addition, the odds of menstrual irregularity was 60% lower among the cases than among controls (odds ratio, 0.4; 95% confidence interval, 0.24-0.64; P <.001). No significant difference was observed in having primary subfertility and secondary subfertility among the 2 groups of respondents. Univariate regression analysis showed that patients with endometriosis have 6.13 times higher odds (95% confidence interval, 2.50-18.40; P <.001) of having a migraine and 2.00 times higher odds (95% confidence interval, 1.2-3.2; P =.01) of having a headache than controls. Furthermore, the age- and body mass index-adjusted multivariate model showed that patients with endometriosis have 5.4 times higher odds of having migraine than patients without endometriosis (95% confidence interval, 2.11-16.4; P <.001). In addition, the higher the age of reproductive-age women, the higher the odds of having migraine. A 1-year increase in age increases the odds of having migraine by 23% (odds ratio, 1.23; 95% confidence interval, 1.13-1.16; P <.001)., Conclusion: Our results support the association between endometriosis and migraine among the Bangladeshi population, which is similar to relevant studies conducted in other geographic locations. The groups of physicians who treat patients suffering from the 2 diseases, endometriosis and migraine, should keep this interrelationship in mind to ensure a better quality of life for the patient., (© 2024 The Authors.)

Background: Congenital heart disease (CHD) remains a significant risk factor for neurologic injury because altered fetal hemodynamics may be unable to support typical brain development during critical periods of growth and maturation., Objectives: The primary objective was to assess differences in the cerebral biochemical profile between healthy fetuses and fetuses with complex CHD and to relate these with infant outcomes., Methods: Pregnant participants underwent fetal magnetic resonance imaging with cerebral proton magnetic resonance spectroscopy acquisitions as part of a prospective observational study. Cerebral metabolites of N-acetyl aspartate, creatine, choline, myo-inositol, scyllo-inositol, lactate, and relevant ratios were quantified using LCModel., Results: We acquired 503 proton magnetic resonance spectroscopy images (controls = 333; CHD = 170) from 333 participants (controls = 221; CHD = 112). Mean choline levels were higher in CHD compared with controls (CHD 2.47 IU [Institutional Units] ± 0.44 and Controls 2.35 IU ± 0.45; P = 0.02), whereas N-acetyl aspartate:choline ratios were lower among CHD fetuses compared with controls (CHD 1.34 ± 0.40 IU vs controls 1.44 ± 0.48 IU; P = 0.001). Cerebral lactate was detected in all cohorts but increased in fetuses with transposition of the great arteries and single-ventricle CHD (median: 1.63 [IQR: 0.56-3.27] in transposition of the great arteries and median: 1.28 [IQR: 0-2.42] in single-ventricle CHD) compared with 2-ventricle CHD (median: 0.79 [IQR: 0-1.45]). Cerebral lactate also was associated with increased odds of death before discharge (OR: 1.75; P = 0.04)., Conclusions: CHD is associated with altered cerebral metabolites in utero, particularly in the third trimester period of pregnancy, which is characterized by exponential brain growth and maturation, and is associated with survival to hospital discharge. The long-term neurodevelopmental consequences of these findings warrant further study., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Institutes of Health Award R01HL116585 by the National Heart, Lung, and Blood Institute (primary investigator: Dr Limperopoulos) and the District of Columbia Intellectual and Developmental Disabilities Research Center Award P50HD105328 by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (primary investigator: Dr Gallo). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: We conducted a clean fuel intervention trial (Bangladesh Global Environmental and Occupational Health (GEOHealth) (NCT02824237) with liquefied petroleum gas (LPG) for 26 months among rural Bangladeshi women chronically exposed to household air pollution (HAP) from biomass fuel (BMF) use. We aimed to evaluate the effect of HAP reduction following LPG intervention on immune response outcome., Methods: We supplied LPG cook stove and refills in cylinder in 200 households for 26 months. We measured personal exposure to HAP [particulate matter 2.5 (PM 2·5 ), black carbon (BC) and carbon monoxide (CO)] in 200 women (main cook) by personal monitors at pre- and post-intervention. Immune function was assessed before and after intervention, in blood collected within 2 weeks of HAP measurements. Primary endpoints included reduction in HAP, lymphocyte proliferation and oxidative stress response, and alterations in T and B cell proportions., Findings: Exclusive LPG use for 26 months resulted in significant reduction in PM 2·5 (43.5%), BC (13%) and CO (48%) exposure in the women. For one unit decrease in BC, Treg cells and memory B cells increased by 7% and 34% respectively, in the peripheral circulation. One unit decrease in CO was significantly associated with increase in early B cells and plasmablasts by 66% and 5% respectively. For one unit decrease in BC, percent-dividing cells, proliferation and expansion indices increased by 2%, 0.4%, and 1%, respectively., Interpretation: Reduced personal exposure to HAP through clean fuel intervention was related to a return towards cellular immune balance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Gamma-aminobutyric acid (GABA) and glutamatergic system perturbations following premature birth may explain neurodevelopmental deficits in the absence of structural brain injury. Using GABA-edited spectroscopy (MEscher-GArwood Point Resolved Spectroscopy [MEGA-PRESS] on 3 T MRI), we have described in-vivo brain GABA+ (+macromolecules) and Glx (glutamate + glutamine) concentrations in term-born infants. We report previously unavailable comparative data on in-vivo GABA+ and Glx concentrations in the cerebellum, the right basal ganglia, and the right frontal lobe of preterm-born infants without structural brain injury. Seventy-five preterm-born (gestational age 27.8 ± 2.9 weeks) and 48 term-born (39.6 ± 0.9 weeks) infants yielded reliable MEGA-PRESS spectra acquired at post-menstrual age (PMA) of 40.2 ± 2.3 and 43.0 ± 2 weeks, respectively. GABA+ (median 2.44 institutional units [i.u.]) concentrations were highest in the cerebellum and Glx higher in the cerebellum (5.73 i.u.) and basal ganglia (5.16 i.u.), with lowest concentrations in the frontal lobe. Metabolite concentrations correlated positively with advancing PMA and postnatal age at MRI (Spearman's rho 0.2-0.6). Basal ganglia Glx and NAA, and frontal GABA+ and NAA concentrations were lower in preterm compared with term infants. Moderate preterm infants had lower metabolite concentrations than term and extreme preterm infants. Our findings emphasize the impact of premature extra-uterine stimuli on GABA-glutamate system development and may serve as early biomarkers of neurodevelopmental deficits., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bats, rodents and monkeys are reservoirs for emerging zoonotic infections. We sought to describe the frequency of human exposure to these animals and the seasonal and geographic variation of these exposures in Bangladesh. During 2013-2016, we conducted a cross-sectional survey in a nationally representative sample of 10,002 households from 1001 randomly selected communities. We interviewed household members about exposures to bats, rodents and monkeys, including a key human-bat interface-raw date palm sap consumption. Respondents reported observing rodents (90%), bats (52%) and monkeys (2%) in or around their households, although fewer reported direct contact. The presence of monkeys around the household was reported more often in Sylhet division (7%) compared to other divisions. Households in Khulna (17%) and Rajshahi (13%) were more likely to report drinking date palm sap than in other divisions (1.5-5.6%). Date palm sap was mostly consumed during winter with higher frequencies in January (16%) and February (12%) than in other months (0-5.6%). There was a decreasing trend in drinking sap over the three years. Overall, we observed substantial geographic and seasonal patterns in human exposure to animals that could be sources of zoonotic disease. These findings could facilitate targeting emerging zoonoses surveillance, research and prevention efforts to areas and seasons with the highest levels of exposure., (© 2023. EcoHealth Alliance.)

Antibiotic resistance is a leading cause of hospitalization and death worldwide. Heavy metals such as arsenic have been shown to drive co-selection of antibiotic resistance, suggesting arsenic-contaminated drinking water is a risk factor for antibiotic resistance carriage. This study aimed to determine the prevalence and abundance of antibiotic-resistant Escherichia coli (AR-Ec) among people and drinking water in high (Hajiganj, >100 μg/L) and low arsenic-contaminated (Matlab, <20 μg/L) areas in Bangladesh. Drinking water and stool from mothers and their children (<1 year) were collected from 50 households per area. AR-Ec was detected via selective culture plating and isolates were tested for antibiotic resistance, arsenic resistance, and diarrheagenic genes by PCR. Whole-genome sequencing (WGS) analysis was done for 30 E. coli isolates from 10 households. Prevalence of AR-Ec was significantly higher in water in Hajiganj (48%) compared to water in Matlab (22%, p <0.05) and among children in Hajiganj (94%) compared to children in Matlab (76%, p <0.05), but not among mothers. A significantly higher proportion of E. coli isolates from Hajiganj were multidrug-resistant (83%) compared to isolates from Matlab (71%, p <0.05). Co-resistance to arsenic and multiple antibiotics (MAR index >0.2) was observed in a higher proportion of water (78%) and child stool (100%) isolates in Hajiganj than in water (57%) and children (89%) in Matlab (p <0.05). The odds of arsenic-resistant bacteria being resistant to third-generation cephalosporin antibiotics were higher compared to arsenic-sensitive bacteria (odds ratios, OR 1.2-7.0, p <0.01). WGS-based phylogenetic analysis of E. coli isolates did not reveal any clustering based on arsenic exposure and no significant difference in resistome was found among the isolates between the two areas. The positive association detected between arsenic exposure and antibiotic resistance carriage among children in arsenic-affected areas in Bangladesh is an important public health concern that warrants redoubling efforts to reduce arsenic exposure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Amin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Medication Regimen Complexity (MRC) refers to the combination of medication classes, dosages, and frequencies. The objective of this study was to examine the relationship between the scores of different MRC tools and the clinical outcomes. Methods: We conducted a retrospective cohort study at Roger William Medical Center, Providence, Rhode Island, which included 317 adult patients admitted to the intensive care unit (ICU) between 1 February 2020 and 30 August 2020. MRC was assessed using the MRC Index (MRCI) and MRC for the Intensive Care Unit (MRC-ICU). A multivariable logistic regression model was used to identify associations among MRC scores, clinical outcomes, and a logistic classifier to predict clinical outcomes. Results: Higher MRC scores were associated with increased mortality, a longer ICU length of stay (LOS), and the need for mechanical ventilation (MV). MRC-ICU scores at 24 h were significantly (p < 0.001) associated with increased ICU mortality, LOS, and MV, with ORs of 1.12 (95% CI: 1.06−1.19), 1.17 (1.1−1.24), and 1.21 (1.14−1.29), respectively. Mortality prediction was similar using both scoring tools (AUC: 0.88 [0.75−0.97] vs. 0.88 [0.76−0.97]. The model with 15 medication classes outperformed others in predicting the ICU LOS and the need for MV with AUCs of 0.82 (0.71−0.93) and 0.87 (0.77−0.96), respectively. Conclusion: Our results demonstrated that both MRC scores were associated with poorer clinical outcomes. The incorporation of MRC scores in real-time therapeutic decision making can aid clinicians to prescribe safer alternatives.

The household secondary attack risk (SAR), often called the secondary attack rate or secondary infection risk, is the probability of infectious contact from an infectious household member A to a given household member B, where we define infectious contact to be a contact sufficient to infect B if he or she is susceptible. Estimation of the SAR is an important part of understanding and controlling the transmission of infectious diseases. In practice, it is most often estimated using binomial models such as logistic regression, which implicitly attribute all secondary infections in a household to the primary case. In the simplest case, the number of secondary infections in a household with m susceptibles and a single primary case is modeled as a binomial(m, p) random variable where p is the SAR. Although it has long been understood that transmission within households is not binomial, it is thought that multiple generations of transmission can be neglected safely when p is small. We use probability generating functions and simulations to show that this is a mistake. The proportion of susceptible household members infected can be substantially larger than the SAR even when p is small. As a result, binomial estimates of the SAR are biased upward and their confidence intervals have poor coverage probabilities even if adjusted for clustering. Accurate point and interval estimates of the SAR can be obtained using longitudinal chain binomial models or pairwise survival analysis, which account for multiple generations of transmission within households, the ongoing risk of infection from outside the household, and incomplete follow-up. We illustrate the practical implications of these results in an analysis of household surveillance data collected by the Los Angeles County Department of Public Health during the 2009 influenza A (H1N1) pandemic., Competing Interests: The authors have declared that no competing interests exist.

Background: Dengue, a febrile illness, is caused by a Flavivirus transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Climate influences the ecology of the vectors. We aimed to identify the influence of climatic variability on the occurrence of clinical dengue requiring hospitalization in Zone-5, a high incidence area of Dhaka City Corporation (DCC), Bangladesh., Methods and Findings: We retrospectively identified clinical dengue cases hospitalized from Zone-5 of DCC between 2005 and 2009. We extracted records of the four major catchment hospitals of the study area. The Bangladesh Meteorological Department (BMD) provided data on temperature, rainfall, and humidity of DCC for the study period. We used autoregressive integrated moving average (ARIMA) models for the number of monthly dengue hospitalizations. We also modeled all the climatic variables using Poisson regression. During our study period, dengue occurred throughout the year in Zone-5 of DCC. The median number of hospitalized dengue cases was 9 per month. Dengue incidence increased sharply from June, and reached its peak in August. One additional rainy day per month increased dengue cases in the succeeding month by 6% (RR = 1.06, 95% CI: 1.04-1.09)., Conclusions: Dengue is transmitted throughout the year in Zone-5 of DCC, with seasonal variation in incidence. The number of rainy days per month is significantly associated with dengue incidence in the subsequent month. Our study suggests the initiation of campaigns in DCC for controlling dengue and other Aedes mosquito borne diseases, including Chikunguniya from the month of May each year. BMD rainfall data may be used to determine campaign timing.

Available measures of handwashing are prone to bias. We tested the feasibility and reliability of weighing soap at repeated visits and subtracting the measured weight from the prior weight to assess daily per capita soap consumption in a low-income community in Dhaka, Bangladesh. Fieldworkers approached 220 households twice weekly over 2 months. They interviewed participants, weighed soap, and assessed hand cleanliness and the presence of a handwashing station. Respondents used bar soap (91% [201]) and laundry detergent cakes (39% [85]) for handwashing as well as for bathing and laundry. Ninety-eight percent of households had bar soap present on at least one visit, although only 50% had bar soap at every visit during the 2-month period. Fieldworkers observed a soap fragment on the wall near the latrine in 27% (470) of visits. Households consumed a mean 1.5 g of bar soap and 3.2 g detergent cake per person per day. Daily per capita soap consumption was similar in households visited by fieldworkers after different intervals (2, 3, 4, or 5 days). Soap consumption was not associated with household wealth, education of the household head, the presence of a handwashing station, the presence of water or soap at a handwashing station, or palm inspections of the mother or child. Soap weight measurements were an objective, reliable measure of soap consumption that provided different information from other handwashing indicators. The frequent use of a soap product for purposes other than handwashing complicates using soap consumption as a handwashing measure.

Introduction: We investigated a cluster of patients with encephalitis in the Manikgonj and Rajbari Districts of Bangladesh in February 2008 to determine the etiology and risk factors for disease., Methods: We classified persons as confirmed Nipah cases by the presence of immunoglobulin M antibodies against Nipah virus (NiV), or by the presence of NiV RNA or by isolation of NiV from cerebrospinal fluid or throat swabs who had onset of symptoms between February 6 and March 10, 2008. We classified persons as probable cases if they reported fever with convulsions or altered mental status, who resided in the outbreak areas during that period, and who died before serum samples were collected. For the case-control study, we compared both confirmed and probable Nipah case-patients to controls, who were free from illness during the reference period. We used motion-sensor-infrared cameras to observe bat's contact of date palm sap., Results: We identified four confirmed and six probable case-patients, nine (90%) of whom died. The median age of the cases was 10 years; eight were males. The outbreak occurred simultaneously in two communities that were 44 km apart and separated by a river. Drinking raw date palm sap 2-12 days before illness onset was the only risk factor most strongly associated with the illness (adjusted odds ratio 25, 95% confidence intervals 3.3-∞, p<0.001). Case-patients reported no history of physical contact with bats, though community members often reported seeing bats. Infrared camera photographs showed that Pteropus bats frequently visited date palm trees in those communities where sap was collected for human consumption., Conclusion: This is the second Nipah outbreak in Bangladesh where date palm sap has been implicated as the vehicle of transmission. Fresh date palm sap should not be drunk, unless effective steps have been taken to prevent bat access to the sap during collection.

In an earlier study in Karachi, Pakistan, households that received free soap and handwashing promotion for 9 months reported 53% less diarrhea than controls. Eighteen months after the intervention ended, these households were enrolled in a follow-up study to assess sustainability of handwashing behavior. Upon re-enrollment, mothers in households originally assigned to the intervention were 1.5 times more likely to have a place with soap and water to wash hands (79% versus 53%, P = 0.001) and when asked to wash hands were 2.2 times more likely to rub their hands together at least three times (50% versus 23%, P = 0.002) compared with controls. In the ensuing 14 months, former intervention households reported a similar proportion of person-days with diarrhea (1.59% versus 1.88%, P = 0.66) as controls. Although intervention households showed better handwashing technique after 2 years without intervention, their soap purchases and diarrhea experience was not significantly different from controls.