Household-level risk factors for secondary influenza-like illness in a rural area of Bangladesh

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objective To describe household‐level risk factors for secondary influenza‐like illness (ILI), an important public health concern in the low‐income population of Bangladesh. Methods Secondary analysis of control participants in a randomised controlled trial evaluating the effect of handwashing to prevent household ILI transmission. We recruited index‐case patients with ILI – fever (<5 years); fever, cough or sore throat (≥5 years) – from health facilities, collected information on household factors and conducted syndromic surveillance among household contacts for 10 days after resolution of index‐case patients’ symptoms. We evaluated the associations between household factors at baseline and secondary ILI among household contacts using negative binomial regression, accounting for clustering by household. Results Our sample was 1491 household contacts of 184 index‐case patients. Seventy‐one percentage reported that smoking occurred in their home, 27% shared a latrine with one other household and 36% shared a latrine with >1 other household. A total of 114 household contacts (7.6%) had symptoms of ILI during follow‐up. Smoking in the home (RRadj 1.9, 95% CI: 1.2, 3.0) and sharing a latrine with one household (RRadj 2.1, 95% CI: 1.2, 3.6) or >1 household (RRadj 3.1, 95% CI: 1.8–5.2) were independently associated with increased risk of secondary ILI. Conclusion Tobacco use in homes could increase respiratory illness in Bangladesh. The mechanism between use of shared latrines and household ILI transmission is not clear. It is possible that respiratory pathogens could be transmitted through faecal contact or contaminated fomites in shared latrines

Evaluating Hospital-Based Surveillance for Outbreak Detection in Bangladesh: Analysis of Healthcare Utilization Data.

BACKGROUND: The International Health Regulations outline core requirements to ensure the detection of public health threats of international concern. Assessing the capacity of surveillance systems to detect these threats is crucial for evaluating a country's ability to meet these requirements. METHODS AND FINDINGS: We propose a framework to evaluate the sensitivity and representativeness of hospital-based surveillance and apply it to severe neurological infectious diseases and fatal respiratory infectious diseases in Bangladesh. We identified cases in selected communities within surveillance hospital catchment areas using key informant and house-to-house surveys and ascertained where cases had sought care. We estimated the probability of surveillance detecting different sized outbreaks by distance from the surveillance hospital and compared characteristics of cases identified in the community and cases attending surveillance hospitals. We estimated that surveillance detected 26% (95% CI 18%-33%) of severe neurological disease cases and 18% (95% CI 16%-21%) of fatal respiratory disease cases residing at 10 km distance from a surveillance hospital. Detection probabilities decreased markedly with distance. The probability of detecting small outbreaks (three cases) dropped below 50% at distances greater than 26 km for severe neurological disease and at distances greater than 7 km for fatal respiratory disease. Characteristics of cases attending surveillance hospitals were largely representative of all cases; however, neurological disease cases aged <5 y or from the lowest socioeconomic group and fatal respiratory disease cases aged ≥60 y were underrepresented. Our estimates of outbreak detection rely on suspected cases that attend a surveillance hospital receiving laboratory confirmation of disease and being reported to the surveillance system. The extent to which this occurs will depend on disease characteristics (e.g., severity and symptom specificity) and surveillance resources. CONCLUSION: We present a new approach to evaluating the sensitivity and representativeness of hospital-based surveillance, making it possible to predict its ability to detect emerging threats

Maternal Exposure to Different Types of Hormonal Compounds from Oral Contraceptives in the First Trimester of Pregnancy and Its Association with Birth Defects

Oral contraceptives (OCs) are the most commonly used prescription medication by women of reproductive age. Prior studies on the association of OCs and birth defects lacked power or assessed all formulations for OCs in aggregate, and in the process overlooked the specific hormonal components contained in the OCs. We examined the association of specific types of hormonal compounds in OCs and 58 structural birth defects. We undertook an analysis of the complete database of the National Birth Defect Prevention Study (NBDPS), 1997-2011. NBDPS is a multi-center, nationwide case-control study conducted by the Centers for Disease Control and Prevention. After exclusions, we analyzed observations from 41,589 mothers in the NBDPS database. We classified OCs reported by the participants in the NBDPS into categories using a priori approaches: i) categorization by the type of progestin, ii) categorization by level of estrogen and iii) categorization by phasic or monophasic formulations. For each of the sub-groups of progestin, estrogen and phasic vs monophasic, we calculated adjusted odds ratios for associations between exposure to these types of OCs during the first trimester and 58 categories of birth defects. For use of any type of OC in the first trimester of pregnancy, we observed elevated adjusted odds ratios (ORs) for hypoplastic left heart syndrome (OR 1.59, [95% CI 1.08-2.35]), cleft palate (OR 1.38, [95% CI 1.05-1.81]), cleft lip with or without cleft palate (OR 1.40, [95% CI 1.14-1.71]) and gastroschisis (OR 1.39, [95% CI 1.08-1.79]). A fourth generation progestin, drospirenone was significantly associated with hydrocephaly (OR 3.63, [95% CI 1.05-12.55]); a third generation of progestin, norgestimate was significantly associated with double outlet right ventricular obstruction-other (OR 2.68, [95% CI 1.05-6.86]) and aortic stenosis (OR 2.10, [95% CI 1.14-3.89]). We observed a significant association of norethindrone containing OCs and cleft lip with or without cleft palate (OR 1.89 [95% CI 1.23-2.92]), desogestrel with cleft palate (OR 3.90, [95% CI 1.30-11.71]) and levonorgestrel with spina bifida (OR 1.95, [95% CI 1.12-3.39]). OCs containing high levels of estrogen and monophasic vs phasic pills were not associated with any birth defect. Our findings indicate a possible risk associated with exposure to any type of OCs during the first trimester and several major structural birth defects. These findings warrant caution in OC use and a need for further studies to look into the possible pathogenesis of specific birth defects and specific progestin compounds

NF-κB signaling and its relevance to the treatment of mantle cell lymphoma

Abstract Mantle cell lymphoma is an aggressive subtype of non-Hodgkin B cell lymphoma that is characterized by a poor prognosis determined by Ki67 and Mantle Cell International Prognostic Index scores, but it is becoming increasingly treatable. The majority of patients, especially if young, achieve a progression-free survival of at least 5 years. Mantle cell lymphoma can initially be treated with an anti-CD20 antibody in combination with a chemotherapy backbone, such as VR-CAP (the anti-CD20 monoclonal antibody rituximab administered with cyclophosphamide, doxorubicin, and prednisone) or R-CHOP (the anti-CD20 monoclonal antibody rituximab administered with cyclophosphamide, doxorubicin, vincristine, and prednisone). While initial treatment can facilitate recovery and complete remission in a few patients, many patients experience relapsed or refractory mantle cell lymphoma within 2 to 3 years after initial treatment. Targeted agents such as ibrutinib, an inhibitor of Bruton’s tyrosine kinase, which has been approved only in the relapsed setting, can be used to treat patients with relapsed or refractory mantle cell lymphoma. However, mantle cell lymphoma cells often acquire resistance to such targeted agents and continue to survive by activating alternate signaling pathways such as the PI3K-Akt pathway or the NF-κB pathways. NF-κB is a transcription factor family that regulates the growth and survival of B cells; mantle cell lymphoma cells depend on NF-κB signaling for continued growth and proliferation. The NF-κB signaling pathways are categorized into canonical and non-canonical types, wherein the canonical pathway prompts inflammatory responses, immune regulation, and cell proliferation, while the non-canonical leads to B cell maturation and lymphoid organogenesis. Since these pathways upregulate survival genes and tumor-promoting cytokines, they can be activated to overcome the inhibitory effects of targeted agents, thereby having profound effects on tumorigenesis. The NF-κB pathways are also highly targetable in that they are interconnected with numerous other pathways, including B cell receptor signaling, PI3K/Akt/mTOR signaling, and toll-like receptor signaling pathways. Additionally, elements of the non-canonical NF- κB pathway, such as NF-κB-inducing kinase, can be targeted to overcome resistance to targeting of the canonical NF- κB pathway. Targeting the molecular mechanisms of the NF-κB pathways can facilitate the development of novel agents to treat malignancies and overcome drug resistance in patients with relapsed or refractory mantle cell lymphoma

Smoldering mantle cell lymphoma

Abstract Background Mantle cell lymphoma (MCL) is an aggressive disease, with poor prognosis and a limited survival. However, some patients with indolent MCL can survive beyond 7~10 years. These patients remain largely asymptomatic and can be in observation for a long time without any treatment. The process of “wait and watch” leaves these patients with the potential risk of evolution to classic, aggressive MCL. On the other hand, early treatment for these patients may not impact overall survival but rather affects the quality of life. Therefore, it is essential to clearly identify this type of indolent MCL at the time of diagnosis. Results Reported findings of indolent presentation of MCL include: lack of B symptoms, normal serum lactic dehydrogenase (LDH) and β2-microglobulin levels (β2M), low MCL-International Prognostic Index (MIPI) score, maximum tumor diameter less than 3 cm, spleen size < 20 cm, positron emission tomography/computerized tomography with the Standard Uptake Value max <6, Ki-67 less than 30%, with some particular immunophenotype, such as CD5 and CD38 negative, markedly increased CD23 positive lymphocytes proportions, high expression of CD200, kappa light chain restriction, without C-myc, TP53 and NOTCH1/2 mutations, non-blastoid/pleomorphic histology, and no tumor growth on reevaluation every 2~3 months (followed for at least 6 months). Imaging evaluation may only be performed in the presence of disease-related symptoms or organ involvement. Meanwhile, if novel nodal or extranodal lesion is found, biopsy is mandatory to exclude lymphoma. Common clinopathological forms of indolent presentations include monoclonal B lymphocytosis with t (11; 14); “indolent leukemic” presentation of MCL with involvement of peripheral blood, bone marrow involvement, splenomegaly, and minimal lymphadenopathies and in situ lymphoma (often found in lymph nodes removed for other reasons, and in gastrointestinal biopsies). Conclusions Considering these distinct indolent clinical presentations with particular features in cytology and gene mutational status, we propose to include these MCL clinical presentations under the umbrella of “Smoldering Mantle Cell Lymphoma”

Incidence of acute diarrhea-associated death among children < 5 years of age in Bangladesh, 2010-12

Although acute diarrheal deaths have declined globally among children = 13.6 km. Diarrhea contributes to childhood death at a higher proportion than when considering it only as the sole underlying cause of death. These data support the use of interventions aimed at preventing acute diarrhea, especially available vaccinations for common etiologies, such as rotavirus

Effectiveness of an educational intervention to improve antibiotic dispensing practices for acute respiratory illness among drug sellers in pharmacies, a pilot study in Bangladesh

Abstract Background Inappropriate dispensing of antibiotics for acute respiratory illness (ARI) is common among drug sellers in Bangladesh. In this study, we evaluated the impact of an educational intervention to promote guidelines for better ARI management among drug sellers. Methods From June 2012 to December 2013, we conducted baseline and post-intervention surveys on dispensing practices in 100 pharmacies within Dhaka city. In these surveys, drug sellers participated in 6 standardized role-playing scenarios led by study staffs acting as caregivers of ARI patients and drug sellers were blinded to these surveys. After the baseline survey, we developed ARI guidelines and facilitated a one-day educational intervention about ARI management for drug sellers. Our guidelines only recommended antibiotics for children with complicated ARI. Finally, we conducted the six month post-intervention survey using the same scenarios to record changes in drug dispensing practices. Results Only 2/3 of participating pharmacies were licensed and few (11%) of drug sellers had pharmacy training. All the drug sellers were male, had a median age of 34 years (IQR 28–41). For children, dispensing of antibiotics for uncomplicated ARI decreased (30% baseline vs. 21% post-intervention; p = 0.04), but drug sellers were equally likely to dispense antibiotics for complicated ARI (15% baseline vs. 17% post-intervention; p = 0.6) and referrals to physicians for complicated ARIs decreased (70% baseline vs. 58% post-intervention; p = 0.03). For adults, antibiotic dispensing remained similar for uncomplicated ARI (48% baseline vs. 40% post-intervention; p = 0.1) but increased among those with complicated ARI (44% baseline vs. 78% post-intervention; p < 0.001). Although our evidence-based guidelines recommended against prescribing antihistamines for children, drug sellers continued to sell similar amounts for uncomplicated ARI (33% baseline vs. 32% post-intervention; p = 0.9). Conclusions Despite the intervention, drug sellers continued to frequently dispense antibiotics for ARI, except for children with uncomplicated ARI. Pairing educational interventions among drug sellers with raising awareness about proper antibiotic use among general population should be further explored. In addition, annual licensing and an reaccreditation system with comprehensive monitoring should be enforced, using penalties for non-compliant pharmacies as possible incentives for appropriate dispensing practices