This study provides with a first insight on Mycobacterium tuberculosis complex epidemiology and genetic diversity in the Cross River State, Nigeria. Starting with 137 smear positive patients recruited over a period of 12 months (June 2008 to May 2009), we obtained 97 pure mycobacterial isolates out of which 81 (83.5%) were identified as M. tuberculosis complex. Genotyping revealed a total of 27 spoligotypes patterns with 10 clusters (n = 64% or 79% of clustered isolates, 2–32 isolates/cluster), with patients in the age group range 25–34 years being significantly associated with shared-type pattern SIT61 (p = 0.019). Comparison with SITVIT2 database showed that with the exception of a single cluster (SIT727/H1), all other clusters observed were representative of West Africa; the two main lineages involved were LAM10-CAM (n = 42/81% or 51.8%) of M. tuberculosis and AFRI_2 sublineage of Mycobacterium africanum (n = 27/81% or 33.3%). Subsequent 12-loci MIRU typing resulted in a total of 13 SIT/MIT clusters (n = 52 isolates, 2–9 isolates per cluster), with a resulting recent n − 1 transmission rate of 48.1%. Available drug-susceptibility testing (DST) results for 58/81 clinical isolates revealed 6/58% or 10.4% cases of multiple drug-resistance (MDR); 5/6 MDR cases were caused by strains belonging to LAM10-CAM lineage (a specific cluster SIT61/MIT266 in 4/6 cases, and an orphan spoligotype pattern in 1/6 case). Additionally, MIT266 was associated with streptomycin resistance (p = 0.016). All the six MDRTB isolates were concomitantly resistance to streptomycin and ethambutol; however, 4/6 MDR strains with identical MIRU patterns were characterized by consecutive strain numbers hence the possibility of laboratory cross contamination could not be excluded in 3/4 serial cases. The present preliminary study underlines the usefulness of spoligotyping and 12-loci MIRU–VNTRs to establish a baseline of circulating genotypic lineages of M. tuberculosis complex in 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.
Summaryobjective To assess the efficacy of weekly zinc or zinc plus retinol as adjuncts for the treatment of pulmonary tuberculosis.methods Double-blind, randomized, placebo-controlled trial in 350 patients >15 years old with smear-positive tuberculosis in Nigeria (ISRCTN36636609). In addition to antituberculous treatment, patients were randomly allocated to weekly supplements of zinc (90 mg), zinc plus retinol (5000 IU) or placebos for 6 months. Primary outcomes were time to sputum smear conversion and resolution of radiographic abnormalities.results After 8 weeks of treatment, 68% had achieved sputum smear conversion, and the median conversion time was 6.5 weeks. Hazard ratios (HR, 95%CI) for sputum conversion relative to the placebo group were not significant for zinc (1.07, 0.92-1.29) or zinc plus retinol (0.89, 0.76-1.07). Significant predictors of time to sputum conversion were lung abnormality score, sputum smear grade, age and serum C-reactive protein. HIV co-infection and gender were not independent predictors of time to sputum conversion. There were no significant differences between supplement groups in clinical, radiological or laboratory outcomes at 2 months or 6 months. There were 9, 9 and 2 deaths in patients receiving zinc, zinc plus retinol or placebos, respectively. Mortality in those who received zinc (HR 1.71, or zinc plus retinol (HR 1.54, did not differ significantly from those who received placebos. Most deaths occurred in patients co-infected with HIV.conclusions Supplementation with zinc or zinc plus retinol did not lead to better outcomes than placebos, and caution is warranted regarding routine micronutrient supplementation, particularly in patients co-infected with HIV.
Summaryobjectives To determine the levels of resistance to first-line tuberculosis drugs in three cities in three geopolitical zones in Nigeria.methods A total of 527 smear-positive sputum samples from Abuja, Ibadan and Nnewi were cultured on BACTEC-MGIT 960. Drug susceptibility tests (DST) for streptomycin, isoniazid, rifampicin and ethambutol were performed on 428 culture-positive samples on BACTEC-MGIT960.results Eight per cent of the specimens cultured were multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) with varying levels of resistance to individual and multiple first-line drugs. MDR was strongly associated with previous treatment: 5% of new and 19% of previously treated patients had MDR-TB (OR 4.1 (95% CI 1.9-8.8), P = 0.001) and with young adult age: 63% of patients with and 38% without MDR-TB were 25-34 years old (P = 0.01). HIV status was documented in 71%. There was no association between MDR-TB and HIV coinfection (P = 0.9) and gender (P > 0.2 for both).conclusions MDR-TB is an emerging problem in Nigeria. Developing good quality drug susceptibility test facilities, routine monitoring of drug susceptibility and improved health systems for the delivery of and adherence to first-and second-line treatment are imperative to solve this problem.keywords multi-drug-resistant tuberculosis, urban cities, first-line TB drugs, newly diagnosed and previously treated TB, HIV
Tuberculosis (TB) is a global public health problem, with the highest burden occurring in low-income countries. In these countries, the use of more sensitive diagnostics, such as Xpert MTB/RIF (Xpert), is still limited by costs. A cost-saving strategy to diagnose other diseases is to pool samples from various individuals and test them with single tests. The samples in positive pool samples are then retested individually to identify the patients with the disease. We assessed a pooled testing strategy to optimize the affordability of Xpert for the diagnosis of TB. Adults with presumptive TB attending hospitals or identified by canvassing of households in Abuja, Nigeria, were asked to provide sputum for individual and pooled (4 per T uberculosis (TB) is a significant global public health problem (1). Despite the availability of curative treatment, TB sits behind only human immunodeficiency virus (HIV) as the major cause of mortality associated with infectious disease worldwide (1). In 2013 there were an estimated 9 million new cases and 1.5 million deaths from TB, most of which occurred in low-and middle-income countries (LMICs) (1). The highest rates of TB per capita and the highest proportion of cases with HIV coinfection occur in sub-Saharan Africa (1).In most low-income countries, direct sputum smear microscopy is the mainstay of TB diagnostics (2), as this test is inexpensive and highly specific, but it has a low to moderate sensitivity (2). The sensitivity of direct sputum smear microscopy is lower in patients with paucibacillary disease associated with HIV coinfection and in children, due to lower bacillary loads (3), and it cannot provide information on drug susceptibility (4). Conversely, sputum culture, in particular, automated liquid culture, is the most sensitive and specific diagnostic tool available for TB and facilitates drug susceptibility testing (2). However, culture requires a laboratory infrastructure, including biosafety equipment, not widely available in low-resource settings, and results typically take 2 to 6 weeks and, therefore, are rarely helpful for initial treatment decisions (2, 4).The Xpert MTB/RIF (Xpert) assay (Cepheid Inc., Sunnyvale, CA, USA) is a self-contained, fully automated, real-time PCR assay that facilitates rapid semiquantitative detection of Mycobacterium tuberculosis and rifampin (RIF) resistance with minimal laboratory requirements compared to those needed for culture and other manually operated nucleic acid amplification tests (NAATs) (4). Xpert is highly specific (99%) and substantially more sensitive than smear microscopy (4). The assay's turnaround time is less than 2 h, greatly shortening the time to TB diagnosis in locations where the machine is available, and it detects markers of RIF resistance (4). For low-income countries, the single-use cartridges cost $9.98 (FIND, 2013). However, despite this concessionary pricing, the cost involved to purchase and run the tests is still a limiting factor for widespread sustainable adoption of Xpert by TB control programs i...
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