Dynamics of Cough Frequency in Adults Undergoing Treatment for Pulmonary Tuberculosis.

Background: Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. Methods: We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. Results: The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%). Conclusions: Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission

Proliferative cells in racemose neurocysticercosis have an active MAPK signalling pathway and respond to metformin treatment

Racemose neurocysticercosis is an aggressive infection caused by the aberrant expansion of the cyst form of Taenia solium within the subarachnoid spaces of the human brain and spinal cord, resulting in the displacement of the surrounding host tissue and chronic inflammation. We previously demonstrated that the continued growth of the racemose bladder wall is associated with the presence of mitotically active cells but the nature and control of these proliferative cells are not well understood. Here, we demonstrated by immunofluorescence that the racemose cyst has an active mitogen-activated protein kinases (MAPK) signalling pathway that is inhibited after treatment with metformin, which reduces racemose cell proliferation in vitro, and reduces parasite growth in the murine model of Taenia crassiceps cysticercosis. Our findings indicate the importance of insulin receptor-mediated activation of the MAPK signalling pathway in the proliferation and growth of the bladder wall of the racemose cyst and its susceptibility to metformin action. The antiproliferative action of metformin may provide a new therapeutic approach against racemose neurocysticercosis

Using Systems Thinking Tools to Inform the Implementation of a Cysticercosis Control Program in Rural Peru

Cysticercosis is an infectious disease responsible for 30-40% of acquired epilepsy in endemic areas such as rural Peru. Ring Treatment (RT) is a community-engaged cysticercosis control strategy, shown to be efficacious when delivered by research teams. We applied the Consolidated Framework for Implementation Research with additional constructs compatible with low-resource contexts in the formative evaluation to develop a protocol for implementing RT. We included small, medium, and large municipal districts from northern Peru representing different rural primary health delivery settings. We collected 169 semi-structured and 341 network interviews. We applied Social-Network-Analysis to identify key players, roles, and collaborations to inform the RT implementation. We developed process maps to identify the steps and critical people to deliver RT. In preparation for a subsequent pilot study, our team delivered workshops where participants proposed and presented process maps for implementing RT. Social-Network-Analysis and process mapping tools helped refine the implementation protocol by integrating stakeholder feedback. Districts\u27 network sizes differed among small, medium, and large districts. However, some key players for successful implementation were similar among districts, such as the community health care worker (CHW). The CHW had more nominations in the small district. Proposed process maps created in the workshops identified the importance of integrating other community players in the intervention, such as the mayor, and brought new ideas for community case reporting and incentives. This presentation describes implementation tools that allowed us to integrate health professionals\u27 feedback for better optimization of the protocol which is currently scaled up in multiple health districts

Determining a cost effective intervention response to HIV/AIDS in Peru

BACKGROUND: The HIV epidemic in Peru is still regarded as concentrated -- sentinel surveillance data shows greatest rates of infection in men who have sex with men, while much lower rates are found in female sex workers and still lower in the general population. Without an appropriate set of preventive interventions, continuing infections could present a challenge to the sustainability of the present programme of universal access to treatment. Determining how specific prevention and care strategies would impact on the health of Peruvians should be key in reshaping the national response. METHODS: HIV/AIDS prevalence levels for risk groups with sufficient sentinel survey data were estimated. Unit costs were calculated for a series of interventions against HIV/AIDS which were subsequently inputted into a model to assess their ability to reduce infection transmission rates. Interventions included: mass media, voluntary counselling and testing; peer counselling for female sex workers; peer counselling for men who have sex with men; peer education of youth in-school; condom provision; STI treatment; prevention of mother to child transmission; and highly active antiretroviral therapy. Impact was assessed by the ability to reduce rates of transmission and quantified in terms of cost per DALY averted. RESULTS: Results of the analysis show that in Peru, the highest levels of HIV prevalence are found in men who have sex with men. Cost effectiveness varied greatly between interventions ranging from peer education of female commercial sex workers at $US 55 up to$US 5,928 (per DALY averted) for prevention of mother to child transmission. CONCLUSION: The results of this work add evidence-based clarity as to which interventions warrant greatest consideration when planning an intervention response to HIV in Peru. Cost effectiveness analysis provides a necessary element of transparency when facing choices about priority setting, particularly when the country plans to amplify its response through new interventions partly funded by the GFATM

Association between Arsenic and other heavy metal exposures through drinking water and food with lung function and respiratory symptoms: A cross-sectional study

Impaired lung function is a major health concern, particularly in children, as it increases the risk of chronic respiratory diseases and long-term morbidity. Environmental exposure to heavy metals (HMs) such as arsenic, lead, cadmium, and manganese has been associated with reduced lung function and respiratory symptoms. However, findings vary by exposure context and population, with limited research in pediatric populations and few studies evaluating the combined effects of multiple HMs. These exposures disproportionally affect marginalized rural communities, especially in low and middle-income countries with mining activities. This cross-sectional study investigated the association between exposure to As and other HMs through drinking water and food with lung function and respiratory symptoms in children from Tumbes, Peru—a region where the primary freshwater source, the Puyango-Tumbes River, is polluted with HMs, likely due to upstream mining. We recruited 399 children aged 4-17 years from 14 villages in Tumbes in 2023. Hair samples were analyzed for HM levels using inductively coupled plasma mass spectrometry, and lung function was assessed by spirometry and analyzed as percent predicted forced vital capacity (ppFVC) and categorized into lung function patterns. Respiratory symptoms indicative of asthma and allergic rhinitis were evaluated using the International Study of Asthma and Allergies in Childhood questionnaire. After adjusting for confounders, higher hair arsenic levels were significantly associated with nasal symptoms suggestive of allergic rhinitis (adjusted odds ratio: 1.59; 95% CI 1.32, 1.90). A non-significant inverse association was found between hair arsenic and ppFVC. Quantile-based G-computation assessing HM mixtures also showed a non-significant inverse association with ppFVC, with arsenic contributing the most to the negative effect. These findings suggest that while arsenic exposure may be linked to allergic rhinitis, its impact on lung function in this population remains inconclusive

Validation of a Spatial Agent-Based Model for Taenia Solium Transmission (“cystiagent”) Against a Large Prospective Trial of Control Strategies in Northern Peru

Background: The pork tapeworm (Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. CystiAgent is a spatially-explicit agent based model for T. solium that is unique among T. solium models in its ability to represent key spatial and environmental features of transmission and simulate spatially targeted interventions, such as ring strategy. Methods/Principal findings: We validated CystiAgent against results from the Ring Strategy Trial (RST)–a large cluster-randomized trial conducted in northern Peru that evaluated six unique interventions for T. solium control in 23 villages. For the validation, each intervention strategy was replicated in CystiAgent, and the simulated prevalences of human taeniasis, porcine cysticercosis, and porcine seroincidence were compared against prevalence estimates from the trial. Results showed that CystiAgent produced declines in transmission in response to each of the six intervention strategies, but overestimated the effect of interventions in the majority of villages; simulated prevalences for human taenasis and porcine cysticercosis at the end of the trial were a median of 0.53 and 5.0 percentages points less than prevalence observed at the end of the trial, respectively. Conclusions/Significance: The validation of CystiAgent represented an important step towards developing an accurate and reliable T. solium transmission model that can be deployed to fill critical gaps in our understanding of T. solium transmission and control. To improve model accuracy, future versions would benefit from improved data on pig immunity and resistance, field effectiveness of anti-helminthic treatment, and factors driving spatial clustering of T. solium infections including dispersion and contact with T. solium eggs in the environment. Author summary: Neurocysticercosis, caused by the ingestion of Taenia solium eggs, is a major cause of human epilepsy around the world. A wide spectrum of tools to fight T. solium is are now available and include antiparasitic treatment for pigs and humans, porcine vaccines, and sanitation improvements; however, the ideal combination of interventions applied to populations to maximize effectiveness and feasibility is not known. Transmission models are one tool that can be used to compare and evaluate different intervention strategies, but no currently available T. solium models have been tested for accuracy. In this research, we validated our model (“CystiAgent”) by comparing simulations of the model to the results of a large-scale trial testing a variety of T. solium control interventions. The model was calibrated using observed epidemiological data from these villages and evaluated for its ability to reproduce the effect of T. solium control interventions. The validation showed that the model was able to reproduce the baseline levels of disease, but generally overestimated the effect that each intervention would have on transmission. These results will allow us to identify limitations of the current model to improve future versions, and represent a step forward in the creation of a tool to design and evaluate future programs to control and eliminate T. solium