As the coronavirus outbreak quickly surges worldwide, many countries are adopting non-therapeutic preventive measures, which include travel bans, remote office activities, country lockdown, and most importantly, social distancing. However, these measures face challenges in Bangladesh, a lower-middle-income economy with one of the world's densest populations. Social distancing is difficult in many areas of the country, and with the minimal resources the country has, it would be extremely challenging to implement the mitigation measures. Mobile sanitization facilities and temporary quarantine sites and healthcare facilities could help mitigate the impact of the pandemic at a local level. A prompt, supportive, and empathic collaboration between the Government, citizens, and health experts, along with international assistance, can enable the country to minimize the impact of the pandemic.

SummaryBackgroundPakistan faces huge challenges in eradicating polio due to widespread poliovirus transmission and security challenges. Innovative interventions are urgently needed to strengthen community buy-in, to increase the coverage of oral polio vaccine (OPV) and other routine immunisations, and to enhance immunity through the introduction of inactivated polio vaccine (IPV) in combination with OPV. We aimed to evaluate the acceptability and effect on immunisation coverage of an integrated strategy for community engagement and maternal and child health immunisation campaigns in insecure and conflict-affected polio-endemic districts of Pakistan.MethodsWe did a community-based three-arm cluster randomised trial in healthy children aged 1 month to 5 years that resided within the study sites in three districts of Pakistan at high risk of polio. Clusters were randomly assigned by a computer algorithm using restricted randomisation in blocks of 20 by an external statistician (1:1:1) to receive routine polio programme activities (control, arm A), additional interventions with community outreach and mobilisation using an enhanced communication package and provision of short-term preventive maternal and child health services and routine immunisation (health camps), including OPV (arm B), or all interventions of arm B with additional provision of IPV delivered at the maternal and child health camps (arm C). An independent team conducted surveys at baseline, endline, and after each round of supplementary immunisation activity for acceptability and effect. The primary outcome measures for the study were coverage of OPV, IPV, and routine extended programme on immunisation vaccines and changes in the proportion of unvaccinated and fully vaccinated children. This trial is registered with ClinicalTrials.gov, number NCT01908114.FindingsBetween June 4, 2013, and May 31, 2014, 387 clusters were randomised (131 to arm A, 127 to arm B, and 129 to arm C). At baseline, 28 760 children younger than 5 years were recorded in arm A, 30 098 in arm B, and 29 126 in arm C. 359 clusters remained in the trial until the end (116 in arm A, 120 in arm B, and 123 in arm C; with 23 334 children younger than 5 years in arm A, 26 110 in arm B, and 25 745 in arm C). The estimated OPV coverage was 75% in arm A compared with 82% in arm B (difference vs arm A 6·6%; 95% CI 4·8–8·3) and 84% in arm C (8·5%, 6·8–10·1; overall p<0·0001). The mean proportion of routine vaccine doses received by children younger than 24 months of age was 43% in arm A, 52% in arm B (9%, 7–11) and 54% in arm C (11%, 9–13; overall p<0·0001). No serious adverse events requiring hospitalisation were reported after immunisation.InterpretationDespite the challenges associated with the polio end-game in high-risk, conflict-affected areas of Pakistan, a strategy of community mobilisation and targeted community-based health and immunisation camps during polio immunisation campaigns was successful in increasing vaccine coverage, including polio vaccine coverage.FundingBill & Melinda G...

A family of anion exchangers (AEs) including AE1, AE2 and AE3 has been described. AE3 gene has been shown to encode two alternatively spliced isoforms termed as bAE3 (brain subtype) and cAE3 (cardiac subtype). The identity of the AE(s) involved in the human intestinal NaCl absorption is not fully understood. Current studies were undertaken to identify the AE isoforms expressed in the human intestine, to define their regional and vertical axis (crypt vs. surface cells) distribution, and to elucidate their membrane localization in the epithelial cells along the entire length of the human intestine. Our studies utilizing reverse transcription (RT)-PCR with total RNA extracted from pinch biopsies from various regions of the human intestine demonstrate that AE2 and bAE3 but not AE1 or cAE3 were expressed in all the regions of the human intestine. Utilizing in situ RT-PCR, we demonstrated that the message of AE2 was expressed throughout the vertical surface--crypt axis of the colon. Our Western blotting studies demonstrated that AE2 and bAE3 are localized to the basolateral but not the apical membranes of the intestinal epithelial cells from the human ileum and colon. In conclusion, our results demonstrated that in the human intestine, AE2 and bAE3, but not AE1 or cAE3, are expressed throughout the tract with the highest expression in the colon compared to the ileum and jejunum. Both the isoforms were found to be localized to the basolateral but not the apical membranes of the epithelial cells. We speculate that, in the human intestine, AE2 and bAE3 may be the 'housekeeping' isoforms, and the apical AE, the potential candidate for chloride absorption, remains to be identified.

Introduction This study aimed to assess the prevalence, sociodemographic factors, reproductive consequences, and heritable disease burdens associated with consanguineous marriage (CM) in Bangladesh. Methods A total of 7,312 families, including 3,694 CM-families, were recruited from 102 locales of 58 districts of Bangladesh. Using a standard questionnaire, we collected medical history and background sociodemographic data of these families. Family history was assessed by pedigree analysis. Fertility, mortality, secondary sex ratio, selection intensity, lethal equivalents were measured using standard methods. Results The mean prevalence of CM in our studied population was 6.64%. Gross fertility was higher among CM families, as compared to the non-CM families (p < 0.05). The rate of under-5 child (U5) mortality was significantly higher among CM families (16.6%) in comparison with the non-CM families (5.8%) (p < 0.01). We observed a persuasive rise of abortion/miscarriage and U5 mortality rates with the increasing level of inbreeding. The value of lethal equivalents per gamete found elevated for autosomal inheritances as compared to sex-linked inheritance. CM was associated with the incidence of several single-gene and multifactorial diseases, and congenital malformations, including bronchial asthma, hearing defect, heart diseases, sickle cell anemia (p < 0.05). The general attitude and perception toward CM were rather indifferent, and very few people were concerned about its genetic burden. Conclusion This study highlights the harmful consequences of CM on reproductive behavior and the incidence of hereditary conditions. It essences the need for genetic counseling from premarital to postnatal levels in Bangladesh.

Pakistan and Afghanistan remain the only countries where polio is endemic, and Pakistan reports the most cases in the world. Although the rate is lower than in previous years, the situation remains alarming. We conducted a mixed methods study in high-risk areas of Pakistan to identify knowledge, attitudes, and practices of target populations about polio vaccine and its eradication, and to estimate coverage of routine immunization and oral polio vaccine. We surveyed 10,685 households in Karachi, 2522 in Pishin, and 2005 in Bajaur. Some knowledge of polio is universal, but important misconceptions persist. The findings of this study carry strategic importance for program direction and implementation.

The coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has become a global public health concern after being first reported in China and has subsequently spread worldwide. It causes mild to severe respiratory illness with some flu-like symptoms. The causal virus behind this disease, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), conceivably attacks the receptors of the respiratory system of the human body but has no strict evidence of attacking the blood cells yet. However, patients with hemoglobin disorders (e.g., sickle cell anemia, thalassemia) are vulnerable to this global health situation due to their clinical complications. Such patients are generally more prone to viral and bacterial infections, which can worsen their physical condition. Some of these patients present immunocompromised conditions, e.g., splenectomized or post-transplant patients. Therefore, they should follow some preventive steps such as shielding as well as the general guidelines for the COVID-19 pandemic. Transfusion dependent patients require regular monitoring for iron overload, and iron chelation therapy may be stopped by the physician depending on the situation. This article reviews the management strategies and provides some crucial recommendations for people in the corner with hemoglobin disorders.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has disrupted every aspect of our life. The need to provide high-level care for an enormous number of patients with COVID-19 infection during this pandemic has impacted resourcing for and restricted the routine care of all non-COVID-19 conditions. Since the beginning of the pandemic, the people living with rare disorders, who represent a marginalized group of the population even in a normal world, have not received enough attention that they deserve. Due to the pandemic situation, they have experienced (and experiencing) an extreme inadequacy of regular clinical services, counseling, and therapies they need, which have made their life more vulnerable and feel more marginalized. Besides, the clinicians, researchers, and scientists working on rare genetic diseases face extra challenges due to the pandemic. Many ongoing research projects and clinical trials for rare and genetic diseases were stalled to avoid patients' and research staff's transmission to COVID-19. Still, with all the odds, telehealth and virtual consultations for rare disease patients have shown hope. The clinical, organizational, and economic challenges faced by institutions, patients, their families, and the caregivers during the pandemic indicate the importance of ensuring continuity of care in managing rare diseases, including adequate diagnostics and priority management strategies for emergencies. In this review, we endeavored to shed light on the issues the rare disease community faces during the pandemic and the adaptations that could help the rare disease community to better sustain in the coming days.

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