Options for Active Case Detection of Visceral Leishmaniasis in Endemic Districts of India, Nepal and Bangladesh, Comparing Yield, Feasibility and Costs

For the elimination of any infectious disease (i.e., reduction of the burden of a serious public health problem to a minor problem which can be managed by the general health services) the right mix of public health tools has to be identified for the early detection and successful treatment of new cases as well as effective vector control (in the case of vector borne diseases) at affordable costs. The paper provides a powerful example of evidence building for cost-effective early case detection in the visceral leishmaniasis elimination initiative of Bangladesh, India and Nepal. It compares the camp approach (mobile teams testing in chronic fever camps for spleen enlargement and rapid diagnostic tests) with the index case approach (screening for new cases in the neighbourhood of reported visceral leishmaniasis patients) and the incentive based approach (where basic health workers receive an allowance for detecting a new case) using subsequent house-to-house screening for the identification of the real number of un-detected cases. By applying a mix of different study methods and an itinerate research process to identify the most effective, feasible and affordable case detection method, under different environmental conditions, recommendations could be developed which help governments in shaping their visceral leishmaniasis elimination strategy

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

In vivo evidence that RBM5 is a tumour suppressor in the lung

Abstract Cigarette smoking is undoubtedly a risk factor for lung cancer. Moreover, smokers with genetic mutations on chromosome 3p21.3, a region frequently deleted in cancer and notably in lung cancer, have a dramatically higher risk of aggressive lung cancer. The RNA binding motif 5 (RBM5) is one of the component genes in the 3p21.3 tumour suppressor region. Studies using human cancer specimens and cell lines suggest a role for RBM5 as a tumour suppressor. Here we demonstrate, for the first time, an in vivo role for RBM5 as a tumour suppressor in the mouse lung. We generated Rbm5 loss-of-function mice and exposed them to a tobacco carcinogen NNK. Upon exposure to NNK, Rbm5 loss-of-function mice developed lung cancer at similar rates to wild type mice. As tumourigenesis progressed, however, reduced Rbm5 expression lead to significantly more aggressive lung cancer i.e. increased adenocarcinoma nodule numbers and tumour size. Our data provide in vivo evidence that reduced RBM5 function, as occurs in a large number of patients, coupled with exposure to tobacco carcinogens is a risk factor for an aggressive lung cancer phenotype. These data suggest that RBM5 loss-of-function likely underpins at least part of the pro-tumourigenic consequences of 3p21.3 deletion in humans

Molecular etiopathology of naturally occurring reproductive diseases in female goats

Aim: The aim of the present study was to investigate the molecular etiopathology of occurrence of reproductive diseases in female goats. Reproductive diseases in goats account for major economic losses to goat farmers in terms of valuable loss of offspring and animal productivity. Materials and Methods: A total of 660 female genitalia were examined for pathological conditions (macroscopic and microscopic lesions). The etiopathological study was carried out for the presence of pathogenic organisms such as Brucella, Chlamydia, and Campylobacter in the uterus and ovary. Based on the microscopic lesions, suspected samples were subjected to diagnostic polymerase chain reaction (PCR) for various etiological agents employing 16srRNA genus specific primers for Campylobacter and Chlamydophila and OMP31 gene-based PCR for Brucella melitensis and nested PCR using ITS-1 gene primers for Toxoplasma gondii. For Brucella suspected samples, immunohistochemistry (IHC) was also performed. Results: In studied female genitalia, 108 (16.30%) showed gross abnormalities with overall 23.32% occurrence of pathological conditions (macroscopic and microscopic lesions). Pathological involvement of the uterus was the highest 68 (62.96%), followed by the ovaries 27 (25%) and other organs. Major uterine condition observed was endometritis (5.60%). In uterine infections, 35 (5.30%) samples were found positive for Campylobacter spp., 12 (1.81%) samples for B. melitensis, and 3 (0.45%) samples were positive for Chlamydophila spp. Among the samples positive for B. melitensis by PCR, 3 were found positive by IHC also. Corynebacterium ovis was detected by PCR using specific primers in a case of hydrosalpinx. It was concluded that many pathological lesions in female genitalia of functional significance play a major role in infertility in goats. Conclusion: The present study concluded that many pathological lesions in female genitalia of functional significance play a major role in infertility in goats

The cost-effectiveness of a resilience-based psychosocial intervention for HIV prevention among men who have sex with men in India

MSM in India are at a high risk for HIV infection given psychosocial challenges, sexual orientation stress, and stigma. We examined the cost-effectiveness of a novel resilience-based psychosocial intervention for MSM in India. We parameterized a validated microsimulation model (CEPAC) with India-specific data and results from a randomized trial and examined two strategies for MSM: status quo HIV care (SQ), and a trial-based psychosocial intervention (INT) focused on building resilience to stress, improving mental health, and reducing condomless anal sex (CAS). We projected lifetime clinical and economic outcomes for MSM without HIV initially. Intervention effectiveness, defined as reduction in self-reported CAS, was estimated at 38%; cost was $49.37/participant. We used a willingness-to-pay threshold of US$2100 (2019 Indian per capita GDP) per year of life saved (YLS) to define cost-effectiveness. We also assessed the 5-year budget impact of offering this intervention to 20% of Indian MSM. Model projections showed the intervention would avert 2940 HIV infections among MSM over 10 years. Over a lifetime horizon, the intervention was cost-effective (ICER = $900/YLS). Results were most sensitive to intervention effectiveness and cost; the intervention remained cost-effective under plausible ranges of these parameters. Offering this intervention in the public sector would require an additional US$28 M over 5 years compared with SQ. A resilience-based psychosocial intervention integrated with HIV risk reduction counseling among MSM in India would reduce HIV infections and be cost-effective. Programs using this approach should be expanded as a part of comprehensive HIV prevention in India