Noncommunicable Respiratory Disease and Air Pollution Exposure in Malawi (CAPS). A Cross-Sectional Study.

RationaleNoncommunicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults.ObjectivesWe set out to explore the prevalence and determinants of noncommunicable respiratory disease among adults living in Chikhwawa District, Malawi.MethodsWe performed a cross-sectional study among adults in communities participating in a randomized controlled trial of a cleaner-burning biomass-fueled cookstove intervention (CAPS [Cooking and Pneumonia Study]) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, and personal exposure to air pollution (particulate matter <2.5 μm in aerodynamic diameter [PM2.5] and carbon monoxide [CO]). Weighted prevalence estimates were calculated; multivariable and intention-to-treat analyses were done.Measurements and main resultsOne thousand four hundred eighty-one participants (mean [SD] age, 43.8 [17.8] yr; 57% female) were recruited. The prevalence of chronic respiratory symptoms, spirometric obstruction, and restriction were 13.6% (95% confidence interval [CI], 11.9-15.4), 8.7% (95% CI, 7.0-10.7), and 34.8% (95% CI, 31.7-38.0), respectively. Median 48-hour personal PM2.5 and CO exposures were 71.0 μg/m3 (interquartile range [IQR], 44.6-119.2) and 1.23 ppm (IQR, 0.79-1.93), respectively. Chronic respiratory symptoms were associated with current/ex-smoking (odds ratio [OR], 1.59; 95% CI, 1.05-2.39), previous tuberculosis (OR, 2.50; 95% CI, 1.04-15.58), and CO exposure (OR, 1.46; 95% CI, 1.04-2.05). Exposure to PM2.5 was not associated with any demographic, clinical, or spirometric characteristics. There was no effect of the CAPS intervention on any of the secondary trial outcomes.ConclusionsThe burden of chronic respiratory symptoms, abnormal spirometry, and air pollution exposures in adults in rural Malawi is of considerable potential public health importance. We found little evidence that air pollution exposures were associated with chronic respiratory symptoms or spirometric abnormalities and no evidence that the CAPS intervention had effects on the secondary trial outcomes. More effective prevention and control strategies for noncommunicable respiratory disease in sub-Saharan Africa are needed. Clinical trial registered with www.isrctn.com (ISRCTN 59448623)

Renal safety of lithium in HIV-infected patients established on tenofovir disoproxil fumarate containing antiretroviral therapy: analysis from a randomized placebo-controlled trial

BACKGROUND: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. OBJECTIVE: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment. METHODS: We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR <60 mL/min and treated with medications predisposing to lithium toxicity. We reviewed participants weekly for the first month for adverse events followed by 4 weekly visits for renal function assessment, adverse event monitoring and adherence. Lithium dose was titrated to achieve the maintenance target plasma concentration of between 0.6 and 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo. RESULTS: We included 23 participants allocated to the lithium arm and 30 participants allocated to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131.0 mL/min in the lithium and placebo arms respectively. There was no statistical significant difference in the reduction in eGFR or increase in potassium between the two arms during the 24 weeks. CONCLUSIONS: We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity. Trial registration The study was registered on the Pan African Clinical Trials Registry (PACTR) with the identifier number PACTR201310000635418. Registered 11 October 2013 before the first participant was enrolled

Host adapted intramammary infections in pregnant heifers which were co-housed and reared on fresh milk as calves

BACKGROUND:Heifers can calve down with intramammary infections (IMI) and udder damage. This will have a negative impact on their longevity, future milk yield and financial return. Co-housed pre-weaned calves that are fed fresh milk have the opportunity to suckle each other's teats and may infect udders of fellow heifer calves with pathogens present in milk. The prevalence of IMI in pregnant heifers in South Africa (SA) which were co-housed and reared on fresh milk as calves, is not known. Quarter secretion samples from both pregnant heifers (n=2065) and dry cows (n=5365) were collected for microbiological analysis from eight SA dairy herds. All heifers tested in this study were co-housed pre-weaning and were fed fresh milk as calves. RESULTS: The prevalence of coagulase negative staphylococci, Staphylococcus aureus, Streptococcus agalactiae, environmental streptococci, coliforms and samples with no bacterial growth in heifers was 26%, 0.9%, 0.08%, 1.4%, 0.4% and 66%, respectively. The overall prevalence ratio between heifers and cows for Staphylococcus aureus IMI was 0.76 (95% CI: 0.59, 0.98). Four of the individual herds had prevalence ratios of less than one (p<0.05), one herd had a prevalence ratio of 3.15 (95% CI: 1.52, 6.32), and the remaining 3 herds had a prevalence ratio not significantly different from 1.0. Marginally significant differences were found between Staphylococcus aureus IMI in pregnant heifers compared to cows in their second and later lactations (p=0.06, p=0.05, respectively) but no significant differences between heifers and cows in their first lactation. CONCLUSIONS: The presence of Streptococcus agalactiae IMI in heifers came as a surprise, especially as herd infection rates were low. The high prevalence ratio of Staphylococcus aureus between heifers and cows in one herd warrants further investigation due to the potential danger of udder damage in a young cow at the start of her productive life. The IMI in heifers with host adapted pathogens can also act as a source of new IMI for lactating dairy cows

A review of simulation models for the long-term management of type 2 diabetes in low-and-middle income countries

Abstract Introduction The burden of type 2 diabetes is steadily increasing in low-and-middle-income countries, thereby posing a major threat from both a treatment, and funding standpoint. Although simulation modelling is generally relied upon for evaluating long-term costs and consequences associated with diabetes interventions, no recent article has reviewed the characteristics and capabilities of available models used in low-and-middle-income countries. We review the use of computer simulation modelling for the management of type 2 diabetes in low-and-middle-income countries. Methods A search for studies reporting computer simulation models of the natural history of individuals with type 2 diabetes and/or decision models to evaluate the impact of treatment strategies on these populations was conducted in PubMed. Data were extracted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed using modelling checklists. Publications before the year 2000, from high-income countries, studies involving animals and analyses that did not use mathematical simulations were excluded. The full text of eligible articles was sourced and information about the intervention and population being modelled, type of modelling approach and the model structure was extracted. Results Of the 79 articles suitable for full text review, 44 studies met the inclusion criteria. All were cost-effectiveness/utility studies with the majority being from the East Asia and Pacific region (n = 29). Of the included studies, 34 (77.3%) evaluated the cost-effectiveness of pharmacological interventions and approximately 75% of all included studies used HbA1c as one of the treatment effects of the intervention. 32 (73%) of the publications were microsimulation models, and 29 (66%) were state-transition models. Most of the studies utilised annual cycles (n = 29, 71%), and accounted for costs and outcomes over 20 years or more (n = 38, 86.4%). Conclusions While the use of simulation modelling in the management of type 2 diabetes has been steadily increasing in low-and-middle-income countries, there is an urgent need to invest in evaluating therapeutic and policy interventions related to type 2 diabetes in low-and-middle-income countries through simulation modelling, especially with local research data. Moreover, it is important to improve transparency and credibility in the reporting of input data underlying model-based economic analyses, and studies

Asthma care in sub-Saharan Africa: Mind the gap!

No abstract

Concentration-dependent antagonism and culture conversion in pulmonary tuberculosis

Background There is scant evidence to support target drug exposures for optimal tuberculosis outcomes. We therefore assessed whether pharmacokinetic/pharmacodynamic (PK/PD) parameters could predict 2-month culture conversion. Methods One hundred patients with pulmonary tuberculosis (65% HIV-co-infected) were intensively sampled to determine rifampicin, isoniazid and pyrazinamide plasma concentrations after 7-8 weeks of therapy, and pharmacokinetic parameters determined using non-linear-mixed-effects models. Detailed clinical data and sputum for culture were collected at baseline, 2 and 5-6 months. Minimum inhibitory concentrations (MIC) were determined on baseline isolates. Multivariate logistic regression and the assumption-free multivariate adaptive regression splines (MARS) were used to identify clinical and PK/PD predictors of 2-month culture conversion. Potential PK/PD predictors included 24-hour-area-under-the-curve (AUC0-24), peak concentration (Cmax), AUC0-24/MIC, Cmax/MIC and % time that concentrations persisted above MIC (%TMIC). Results 26% of patients had Cmax (mg/L) of rifampicin4.6 mg/L, higher isoniazid exposures were associated with improved rates of culture conversion. Conclusions PK/PD analyses using MARS identified isoniazid Cmax and rifampicin Cmax/MIC thresholds below which there is concentration-dependent antagonism that reduces 2-month sputum culture conversion