Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations.

Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omic signatures of asthma focusing on populations of African ancestry. RNASeq and DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) and controls (never-asthma, N = 283) from 7 different geographic sites to identify differentially expressed genes (DEGs) and gene networks. We identify 389 DEGs; the top DEG, FN1, was downregulated in cases (q = 3.26 × 10-9) and encodes fibronectin which plays a role in wound healing. The top three gene expression modules implicate networks related to immune response (CEACAM5; p = 9.62 × 10-16 and CPA3; p = 2.39 × 10-14) and wound healing (FN1; p = 7.63 × 10-9). Multi-omic analysis identifies FKBP5, a co-chaperone of glucocorticoid receptor signaling known to be involved in drug response in asthma, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. This work reveals molecular dysregulation on three axes - increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response - that may play a critical role in asthma within the African Diaspora.

Comparison of Mycobacterium tuberculosis drug susceptibility using solid and liquid culture in Nigeria.

BACKGROUND: This study compares Mycobacterium tuberculosis culture isolation and drug sensitivity testing (DST) using solid (LJ) and liquid (BACTEC-MGIT-960) media in Nigeria. METHODS: This was a cross sectional survey of adults attending reference centres in Abuja, Ibadan and Nnewi with a new diagnosis of pulmonary tuberculosis (TB) or having failed the first-line TB treatment. Patients were requested to provide three sputum specimens for smear-microscopy and culture on LJ and BACTEC-MGIT-960. Positive cultures underwent DST for streptomycin, isoniazid, rifampicin and ethambutol. RESULTS: 527 specimens were cultured. 428 (81%) were positive with BACTEC-MGIT-960, 59 (11%) negative, 36 (7%) contaminated and 4 (1%) had non-tuberculosis mycobacteria (NTM). 411 (78%) LJ cultures were positive, 89 (17%) negative, 22 (4%) contaminated and 5 (1%) had NTM. The mean (SD) detection time was 11 (6) and 30 (11) days for BACTEC-MGIT-960 and LJ. DST patterns were compared in the 389 concordant positive BACTEC-MGIT-960 and LJ cultures. Rifampicin and isoniazid DST patterns were similar. Streptomycin resistance was detected more frequently with LJ than BACTEC-MGIT-960 and ethambutol resistance was detected more frequently with BACTEC-MGIT-960 than LJ, but differences were not statistically significant. MDR-TB was detected in 27 cases by LJ and 25 by BACTEC-MGIT-960 and using both methods detected 29 cases. CONCLUSIONS: There was a substantial degree of agreement between the two methods. However using the two in tandem increased the number of culture-positive patients and those with MDR-TB. The choice of culture method should depend on local availability, cost and test performance characteristics.

Drug prescription pattern for asthma among nigerian doctors in general practice: A cross-sectional survey.

BACKGROUND: A wide range of medications are now available for the treatment of asthma and selection of the optimal treatment combination of agents is essential. OBJECTIVES: This study was designed to evaluate a self-reported drug prescribing pattern for asthma among Nigerian doctors in general practice. METHODS: It was a cross-sectional survey conducted among general practitioners in six states of Nigeria. RESULTS: For acute severe asthma, 75.9% of the doctors prescribed intravenous methylxanthines, which was combined with oral or inhaled short-acting ß(2) agonists (SABA) by 56.3% of them. Systemic steroids were prescribed mainly via the intravenous route by 58.8% of them. Aberrant drugs such as antibiotics, antihistamines, and mucolytics were prescribed by 25.6% of them. For long-term, follow-up treatment of asthma, oral steroids, and oral SABA were commonly prescribed, while inhaled corticosteroids (ICS) and ICS/LABA (long acting beta agonists) were infrequently prescribed. Aberrant drugs such as analgesics, antimalaria, and antihistamines were prescribed by 22.8% of them. About 48% of the doctors had never attended any form of update training on asthma management, whereas, only 16.3% attended update training on asthma within the last year preceding this study. Awareness of international guidelines on asthma treatment was poor among them with only 16.4% being able to mention any correct guideline on asthma management. CONCLUSION: The poor anti-asthma prescribing behavior among these doctors is associated with a low level of participation at update training on asthma management and poor awareness of asthma guidelines. The Nigerian Medical Association and the Nigerian Thoracic Society should urgently address these problems.

A molecular epidemiological and genetic diversity study of tuberculosis in Ibadan, Nnewi and Abuja, Nigeria.

BACKGROUND: Nigeria has the tenth highest burden of tuberculosis (TB) among the 22 TB high-burden countries in the world. This study describes the biodiversity and epidemiology of drug-susceptible and drug-resistant TB in Ibadan, Nnewi and Abuja, using 409 DNAs extracted from culture positive TB isolates. METHODOLOGY/PRINCIPAL FINDINGS: DNAs extracted from clinical isolates of Mycobacterium tuberculosis complex were studied by spoligotyping and 24 VNTR typing. The Cameroon clade (CAM) was predominant followed by the M. africanum (West African 1) and T (mainly T2) clades. By using a smooth definition of clusters, 32 likely epi-linked clusters related to the Cameroon genotype family and 15 likely epi-linked clusters related to other "modern" genotypes were detected. Eight clusters concerned M. africanum West African 1. The recent transmission rate of TB was 38%. This large study shows that the recent transmission of TB in Nigeria is high, without major regional differences, with MDR-TB clusters. Improvement in the TB control programme is imperative to address the TB control problem in Nigeria.