Factors Associated With Discontinuation of Tuberculosis Preventive Treatment: Post Hoc Analysis of 2 Randomized, Controlled Trials.

BACKGROUND: Adherence to tuberculosis preventive treatment (TPT) is an important determinant of clinical benefit. We assessed the association of participant behaviors early in TPT with subsequent discontinuation. METHODS: We used data from a phase 3 randomized trial and the preceding phase 2 trial to compare 4 months of rifampin to 9 months of isoniazid for TPT. We excluded participants whose providers discontinued TPT due to adverse events or tuberculosis disease. We analyzed 4 outcomes: discontinuing TPT within the first month of treatment, discontinuing TPT between the first and second month, discontinuing TPT after the second month, and completing treatment but not per protocol. We analyzed the association of outcomes with regimen and participant characteristics and 4 behavioral predictors of discontinuation recorded at the month 1 and month 2 follow-up visits: reporting symptoms of intolerance, missing >20% of doses, rescheduling appointments, and not bringing their medication bottle. RESULTS: Overall, 6656 participants were included (phase 3, 5848; phase 2, 808), of whom 4318 (64.9%) completed treatment per protocol. Participant characteristics were inconsistently associated with discontinuation. Phase 3 trial participants with 1, 2, or 3-4 behavioral predictors at the month 1 follow-up had 5.0 (95% confidence interval, 3.6-6.7), 18.6 (13.3-26.1), and 79.4 (38.2-165.0), respectively, higher odds of discontinuing before the second month. The corresponding number of predictors at the month 2 follow-up had 1.8 (1.4-2.2), 4.7 (3.6-6.2), and 7.4 (4.6-11.9) higher odds of discontinuing before completing treatment; phase 2 findings were similar. CONCLUSIONS: Four behavioral predictors recorded early in therapy were more strongly associated with subsequent discontinuation than participant characteristics, particularly when more than 1 behavioral predictor was recorded. Clinical Trials Registration. NCT00170209; NCT00931736.

On the Environmental Presence of Burkholderia pseudomallei in South-Central Ghana.

Burkholderia pseudomallei is a Gram-negative soil saprophyte with the potential to cause melioidosis, an opportunistic disease with a high mortality potential. Periodic case reports of melioidosis in or imported from Africa occur in the literature dating back decades. Furthermore, statistical models suggest Western sub-Saharan Africa as a high-risk zone for the presence of B. pseudomallei. A recent case report from the United Kingdom of a returning traveler from Ghana highlights the need for environmental studies in Ghana. We examined 100 soil samples from a rice farm in south-central Ghana. Soil was subjected to selective enrichment culture for B. pseudomallei using threonine-basal salt solution with colistin (TBSS-C50) and erythritol medium, as described in the literature. Bacterial cultures were identified with standard biochemical tests, a rapid antigen detection assay, and real-time PCR specific for B. pseudomallei. Of the 100 soil samples, 55% yielded cultures consistent with B. pseudomallei on Ashdown's agar as well as by capsular polysaccharide antigen production. This is the first confirmatory report of culture-confirmed B. pseudomallei in the environment of Ghana. Our study emphasizes the need for further exploration of the burden of human melioidosis in Ghana. We recommend that local clinicians familiarize themselves with the diagnosis and clinical management of melioidosis, while laboratories develop capacity for the safe isolation and identification of B. pseudomallei. IMPORTANCE We present the first confirmation of the presence of B. pseudomallei in the environment of Ghana. This study will bring attention to a disease with the potential to cause significant morbidity and mortality in Ghana, but which has gone completely unrecognized until this point. Furthermore, this work would encourage local clinicians to familiarize themselves with the diagnosis and clinical management of melioidosis and laboratories to develop capacity for the safe isolation and identification of B. pseudomallei.

Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults.

BACKGROUND: A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects. METHODS: In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels. RESULTS: Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence interval [CI], -0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100 person-years (95% CI, -0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis. The upper boundaries of the 95% confidence interval for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75 percentage points in cumulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7 to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) were -1.1 percentage points (95% CI, -1.9 to -0.4) for all events and -1.2 percentage points (95% CI, -1.7 to -0.7) for hepatotoxic events. CONCLUSIONS: The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety. (Funded by the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council; ClinicalTrials.gov number, NCT00931736 .).

Design considerations for identifying breast cancer risk factors in a population-based study in Africa.

Although breast cancer is becoming more prevalent in Africa, few epidemiologic studies have been undertaken and appropriate methodologic approaches remain uncertain. We therefore conducted a population-based case-control study in Accra and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy (if given), blood, saliva and fecal samples were sought for study subjects. Response rates, risk factor prevalences and odds ratios for established breast cancer risk factors were calculated. A total of 54.5% of the recruited cases were diagnosed with malignancies, 36.0% with benign conditions and 9.5% with indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9% in controls, with the vast majority of interviewed subjects providing saliva (97.9% in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences were unique as compared to women in other countries (e.g., less education, higher parity), cancer risk factors resembled patterns identified elsewhere (elevated risks associated with higher levels of education, familial histories of breast cancer, low parity and larger body sizes). Subjects with benign conditions were younger and exhibited higher socioeconomic profiles (e.g., higher education and lower parity) than those with malignancies, suggesting selective referral influences. While further defining breast cancer risk factors in Africa, this study showed that successful population-based interdisciplinary studies of cancer in Africa are possible but require close attention to diagnostic referral biases and standardized and documented approaches for high-quality data collection, including biospecimens.

Sepsis endotypes identified by host gene expression across global cohorts.

BACKGROUND: Sepsis from infection is a global health priority and clinical trials have failed to deliver effective therapeutic interventions. To address complicating heterogeneity in sepsis pathobiology, and improve outcomes, promising precision medicine approaches are helping identify disease endotypes, however, they require a more complete definition of sepsis subgroups. METHODS: Here, we use RNA sequencing from peripheral blood to interrogate the host response to sepsis from participants in a global observational study carried out in West Africa, Southeast Asia, and North America (N = 494). RESULTS: We identify four sepsis subtypes differentiated by 28-day mortality. A low mortality immunocompetent group is specified by features that describe the adaptive immune system. In contrast, the three high mortality groups show elevated clinical severity consistent with multiple organ dysfunction. The immunosuppressed group members show signs of a dysfunctional immune response, the acute-inflammation group is set apart by molecular features of the innate immune response, while the immunometabolic group is characterized by metabolic pathways such as heme biosynthesis. CONCLUSIONS: Our analysis reveals details of molecular endotypes in sepsis that support immunotherapeutic interventions and identifies biomarkers that predict outcomes in these groups.

Sepsis is a life-threatening multi-organ failure caused by the body's immune response to infection. Clinical symptoms of sepsis vary from one person to another likely due to differences in host factors, infecting pathogen, and comorbidities. This difference in clinical symptoms may contribute to the lack of effective interventions for sepsis. Therefore, approaches tailored to targeting groups of patients who present similarly are of great interest. This study analysed a large group of sepsis patients with diverse symptoms using laboratory markers and mathematical analysis. We report four patient groups that differ by risk of death and immune response profile. Targeting these defined groups with tailored interventions presents an exciting opportunity to improve the health outcomes of patients with sepsis.

Gene expression signatures in blood from a West African sepsis cohort define host response phenotypes.

Our limited understanding of the pathophysiological mechanisms that operate during sepsis is an obstacle to rational treatment and clinical trial design. There is a critical lack of data from low- and middle-income countries where the sepsis burden is increased which inhibits generalized strategies for therapeutic intervention. Here we perform RNA sequencing of whole blood to investigate longitudinal host response to sepsis in a Ghanaian cohort. Data dimensional reduction reveals dynamic gene expression patterns that describe cell type-specific molecular phenotypes including a dysregulated myeloid compartment shared between sepsis and COVID-19. The gene expression signatures reported here define a landscape of host response to sepsis that supports interventions via targeting immunophenotypes to improve outcomes.

Drinking water quality and source reliability in rural Ashanti region, Ghana.

Site-specific information about local water sources is an important part of a community-driven effort to improve environmental conditions. The purpose of this assessment was to gather this information for residents of rural villages in Ghana. Sanitary surveys and bacteriological testing for total coliforms and Escherichia coli (EC) using Colilert(®) were conducted at nearly 80 water sources serving eight villages. A focus group was carried out to assess the desirability and perceived quality of water sources. Standpipes accounted for almost half of the available water sources; however, a third of them were not functioning at the time of the survey. EC bacteria were found in the majority of shallow wells (80%), rivers (67%), and standpipes (61%), as well as 28% of dug wells. Boreholes were free of EC. Residents felt that the standpipes and boreholes produced safe drinking water. Intermittent service and poor water quality from the piped supply has led to limited access to drinking water. The perception of residents, that the water from standpipes is clean and does not need to be treated at home, is particularly troubling in light of the poor bacteriological quality of water from the standpipes.

Prevalence of hypertension and diabetes mellitus in adults from a rural community in Ghana.

OBJECTIVES: The aim of this study was to determine the prevalence of hypertension and diabetes mellitus (DM) in the Adankwame community of Ghana. DESIGN: This was a cross-sectional, observational study. SETTING: This study took place in the rural Adankwame community of Ghana, approximately 12 km from Kumasi, Ghana. PARTICIPANTS: Study subjects were adults (older than aged 18 years). A two-tier random sampling approach was taken to recruit study participants to achieve a sample size of 326 adults, 94 males and 232 females. MAIN OUTCOME MEASURES: The subjects' height, weight, abdominal circumference, demographic and risk factor information, blood pressure measurements, and blood glucose levels were measured and recorded. RESULTS: The mean systolic and diastolic blood pressures in the population were 131 (SD 26.61) and 78 mmHg (SD 15.24), respectively. The prevalence of hypertension was 0.35 (95% CI 0.30-0.40). The prevalence of pre-hypertension, Stage 1 hypertension, and Stage 2 hypertension were approximately 0.248, 0.19, and 0.16, respectively. Mean fasting blood sugar and random blood sugar in the study population were 108 mg/dL (SD 35.33) and 131 mg/dL (SD 41.35), respectively. The overall prevalence of DM in this sample population was 0.077 (95% Cl 0.05-0.11). CONCLUSIONS: Hypertension and diabetes mellitus are rising as diseases of public health importance in the Adankwame community. Research to provide substantial data on the prevalence of these two diseases in Ghana is needed to inform national non-communicable disease policy.

Access to artesunate-amodiaquine, quinine and other anti-malarials: policy and markets in Burundi.

BACKGROUND: Malaria is the leading cause of morbidity and mortality in post-conflict Burundi. To counter the increasing challenge of anti-malarial drug resistance and improve highly effective treatment Burundi adopted artesunate-amodiaquine (AS-AQ) as first-line treatment for uncomplicated Plasmodium falciparum malaria and oral quinine as second-line treatment in its national treatment policy in 2003. Uptake of this policy in the public, private and non-governmental (NGO) retail market sectors of Burundi is relatively unknown. This study was conducted to evaluate access to national policy recommended anti-malarials. METHODS: Adapting a standardized methodology developed by Health Action International/World Health Organization (HAI/WHO), a cross-sectional survey of 70 (24 public, 36 private, and 10 NGO) medicine outlets was conducted in three regions of Burundi, representing different levels of transmission of malaria. The availability on day of the survey, the median prices, and affordability (in terms of number of days' wages to purchase treatment) of AS-AQ, quinine and other anti-malarials were calculated. RESULTS: Anti-malarials were stocked in all outlets surveyed. AS-AQ was available in 87.5%, 33.3%, and 90% of public, private, and NGO retail outlets, respectively. Quinine was the most common anti-malarial found in all outlet types. Non-policy recommended anti-malarials were mainly found in the private outlets (38.9%) compared to public (4.2%) and NGO (0%) outlets. The median price of a course of AS-AQ was US$0.16 (200 Burundi Francs, FBu) for the public and NGO markets, and 3.5-fold higher in the private sector (US$0.56 or 700 FBu). Quinine tablets were similarly priced in the public (US$1.53 or 1,892.50 FBu), private and NGO sectors (both US$1.61 or 2,000 FBu). Non-policy anti-malarials were priced 50-fold higher than the price of AS-AQ in the public sector. A course of AS-AQ was affordable at 0.4 of a day's wage in the public and NGO sectors, whereas, it was equivalent to 1.5 days worth of wages in the private sector. CONCLUSIONS: AS-AQ was widely available and affordable in the public and NGO markets of hard-to-reach post-conflict communities in Burundi. However greater accessibility and affordability of policy recommended anti-malarials in the private market sector is needed to improve country-wide policy uptake.

Family planning in a sub-district near Kumasi, Ghana: side effect fears, unintended pregnancies and misuse of a medication as emergency contraception.

The Barekuma Collaborative Community Development Project (BCCDP) performed a study regarding family planning in communities in the Barekese sub-district near Kumasi, Ghana in July 2010. Eighty-five women, ages 15-49 years, in three communities were interviewed with a modified version of the 2008 Ghana Demographic and Health Survey. While virtually all women recognized at least one family planning method, half of all recent or current pregnancies were unintended and 20 percent of women had a previous abortion. Unexpectedly, 27 percent of women had misused norethisterone tablets (Primolut N or "N-tablets"), a synthetic progesterone, as emergency contraception. Women had a variety of concerns about family planning methods, including one-third having a fear of side effects for hormonal methods (particularly heart palpitations), as well as unfamiliarity with and particular aspects they did not like for most methods. However, women were interested in learning more about side effects as well as modern fertility awareness-based methods. There is an urgent need for interventions aimed at regulating and implementing the correct use of Primolut N tablets, addressing real and perceived side effects of family planning practices through properly trained community health nurses and introducing modern methods of fertility awareness such as Standard Days Method and the Two-day Method in the Barekese sub-district.