Using genetic data to identify transmission risk factors: Statistical assessment and application to tuberculosis transmission.

Identifying host factors that influence infectious disease transmission is an important step toward developing interventions to reduce disease incidence. Recent advances in methods for reconstructing infectious disease transmission events using pathogen genomic and epidemiological data open the door for investigation of host factors that affect onward transmission. While most transmission reconstruction methods are designed to work with densely sampled outbreaks, these methods are making their way into surveillance studies, where the fraction of sampled cases with sequenced pathogens could be relatively low. Surveillance studies that use transmission event reconstruction then use the reconstructed events as response variables (i.e., infection source status of each sampled case) and use host characteristics as predictors (e.g., presence of HIV infection) in regression models. We use simulations to study estimation of the effect of a host factor on probability of being an infection source via this multi-step inferential procedure. Using TransPhylo-a widely-used method for Bayesian estimation of infectious disease transmission events-and logistic regression, we find that low sensitivity of identifying infection sources leads to dilution of the signal, biasing logistic regression coefficients toward zero. We show that increasing the proportion of sampled cases improves sensitivity and some, but not all properties of the logistic regression inference. Application of these approaches to real world data from a population-based TB study in Botswana fails to detect an association between HIV infection and probability of being a TB infection source. We conclude that application of a pipeline, where one first uses TransPhylo and sparsely sampled surveillance data to infer transmission events and then estimates effects of host characteristics on probabilities of these events, should be accompanied by a realistic simulation study to better understand biases stemming from imprecise transmission event inference.

Botswana tuberculosis (TB) stakeholders broadly support scaling up next-generation whole genome sequencing: Ethical and practical considerations for Botswana and global health.

Global health agencies are increasingly promoting the scale-up of next-generation whole genome sequencing (NG-WGS) of pathogens into infectious disease control programs, including for tuberculosis (TB). However, little is known about how stakeholders in low-to-middle income countries (LMICs) understand the ethics, benefits, and risks of these proposals. We conducted a qualitative study in Greater Gaborone, Botswana to learn how TB stakeholders there viewed a potential scale-up of NG-WGS into Botswana's TB program. We conducted 30 interviews and four deliberative dialogues with TB stakeholders based in Greater Gaborone, the country's largest city and capital. We created and showed participants an animated video series about a fictional family that experienced TB diagnosis, treatment, contact tracing, and data uses that were informed by NG-WGS. We analyzed transcripts using reflexive thematic analysis. We found broad support for the scale-up of TB NG-WGS in Botswana, owing to perceived benefits. Support was qualified with statements about ensuring adequate planning, resource-allocation, community and stakeholder engagement, capacity-building, and assessing ethical norms around publishing data. Our results suggest that scaling up NG-WGS for TB in Botswana would be supported by stakeholders there, contingent upon the government and other entities adequately investing in the initiative. These findings are relevant to other LMICs considering scale-ups of NG-WGS and related technologies for infectious diseases and suggest the need for sustained research into the acceptability of pathogen sequencing in other contexts.

Cervical Cancer in Botswana: Current State and Future Steps for Screening and Treatment Programs.

Botswana has a high burden of cervical cancer due to a limited screening program and high HIV prevalence. About 60% of the cervical cancer patients are HIV positive; most present with advanced cervical disease. Through initiatives by the Botswana Ministry of Health and various strategic partnerships, strides have been made in treatment of pre-invasive and invasive cancer. The See and Treat program for cervical cancer is expanding throughout the country. Starting in 2015, school-going girls will be vaccinated against HPV. In regards to treatment of invasive cancer, a multidisciplinary clinic has been initiated at the main oncology hospital to streamline care. However, challenges remain such as delays in treatment, lack of trained human personnel, limited follow-up care, and little patient education. Despite improvements in the care of pre-invasive and invasive cervical cancer patients, for declines in cervical cancer-related morbidity and mortality to be achieved, Botswana needs to continue to invest in decreasing the burden of disease and improving patient outcomes of patients with cervical cancer.