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Tuberculosis Caused by Mycobacterium africanum, United States, 2004-2013.

ABSTRACT: Mycobacterium africanum is endemic to West Africa and causes tuberculosis (TB). We reviewed reported cases of TB in the United States during 2004-2013 that had lineage assigned by genotype (spoligotype and mycobacterial interspersed repetitive unit variable number tandem repeats). M. africanum caused 315 (0.4%) of 73,290 TB cases with lineage assigned by genotype. TB caused by M. africanum was associated more with persons from West Africa (adjusted odds ratio [aOR] 253.8, 95% CI 59.9-1,076.1) and US-born black persons (aOR 5.7, 95% CI 1.2-25.9) than with US-born white persons. TB caused by M. africanum did not show differences in clinical characteristics when compared with TB caused by M. tuberculosis. Clustered cases defined as >2 cases in a county with identical 24-locus mycobacterial interspersed repetitive unit genotypes, were less likely for M. africanum (aOR 0.1, 95% CI 0.1-0.4), which suggests that M. africanum is not commonly transmitted in the United States.

SUBMITTER: Sharma A

PROVIDER: S-EPMC4766873 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Tuberculosis Caused by Mycobacterium africanum, United States, 2004-2013.

Sharma Aditya A Bloss Emily E Heilig Charles M CM Click Eleanor S ES

Emerging infectious diseases 20160301 3

Mycobacterium africanum is endemic to West Africa and causes tuberculosis (TB). We reviewed reported cases of TB in the United States during 2004-2013 that had lineage assigned by genotype (spoligotype and mycobacterial interspersed repetitive unit variable number tandem repeats). M. africanum caused 315 (0.4%) of 73,290 TB cases with lineage assigned by genotype. TB caused by M. africanum was associated more with persons from West Africa (adjusted odds ratio [aOR] 253.8, 95% CI 59.9-1,076.1) an ...[more]

PMID: 26886258

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Tuberculosis caused by Mycobacterium africanum: Knowns and unknowns.

Project description:Tuberculosis (TB), one of the deadliest threats to human health, is mainly caused by 2 highly related and human-adapted bacteria broadly known as Mycobacterium tuberculosis and Mycobacterium africanum. Whereas M. tuberculosis is widely spread, M. africanum is restricted to West Africa, where it remains a significant cause of tuberculosis. Although several differences have been identified between these 2 pathogens, M. africanum remains a lot less studied than M. tuberculosis. Here, we discuss the genetic, phenotypic, and clinical similarities and differences between strains of M. tuberculosis and M. africanum. We also discuss our current knowledge on the immune response to M. africanum and how it possibly articulates with distinct disease progression and with the geographical restriction attributed to this pathogen. Understanding the functional impact of the diversity existing in TB-causing bacteria, as well as incorporating this diversity in TB research, will contribute to the development of better, more specific approaches to tackle TB.

| S-EPMC9135246 | biostudies-literature

Pyrazinamide-monoresistant Mycobacterium tuberculosis in the United States.

Project description:Mycobacterium bovis is naturally resistant to the antituberculosis drug pyrazinamide (PZA). To determine whether all Mycobacterium tuberculosis complex isolates demonstrating PZA monoresistance were truly M. bovis, we examined the phenotype and genotype of isolates reported as PZA monoresistant in five counties in California from January 1996 through June 1999. Isolates reported by local laboratories to be PZA monoresistant were sent to the state reference laboratory for repeat susceptibility testing using the BACTEC radiometric method and to the Centers for Disease Control and Prevention for pncA sequencing and PCR-restriction fragment length polymorphism (RFLP) analysis of the oxyR gene. Of 1,916 isolates, 14 were reported as PZA monoresistant and 11 were available for retesting. On repeat testing, 6 of the 11 isolates were identified as PZA-susceptible M. tuberculosis, 1 was identified as PZA-monoresistant M. bovis, and 1 was identified as M. bovis BCG. The three remaining isolates were identified as PZA-monoresistant M. tuberculosis. Sequencing of the pncA and oxyR genes genotypically confirmed the two M. bovis and the six susceptible M. tuberculosis species. Each of the three PZA-monoresistant M. tuberculosis isolates had different, previously unreported, pncA gene mutations: a 24-bp deletion in frame after codon 88, a base substitution at codon 104 (Ser104Cys), and a base substitution at codon 90 (Ile90Ser). This study demonstrates that PZA monoresistance is not an absolute marker of M. bovis species but may also occur in M. tuberculosis, associated with a number of different mutational events in the pncA gene. It is the first report of PZA-monoresistant M. tuberculosis in the United States.

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Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains.

Project description:The human immunity-related GTPase M (IRGM) has been shown to be critically involved in regulating autophagy as a means of disposing cytosolic cellular structures and of reducing the growth of intracellular pathogens in vitro. This includes Mycobacterium tuberculosis, which is in agreement with findings indicating that M. tuberculosis translocates from the phagolysosome into the cytosol of infected cells, where it becomes exposed to autophagy. To test whether IRGM plays a role in human infection, we studied IRGM gene variants in 2010 patients with pulmonary tuberculosis (TB) and 2346 unaffected controls. Mycobacterial clades were classified by spoligotyping, IS6110 fingerprinting and genotyping of the pks1/15 deletion. The IRGM genotype -261TT was negatively associated with TB caused by M. tuberculosis (OR 0.66, CI 0.52-0.84, P(nominal) 0.0009, P(corrected) 0.0045) and not with TB caused by M. africanum or M. bovis (OR 0.95, CI 0.70-1.30. P 0.8). Further stratification for mycobacterial clades revealed that the protective effect applied only to M. tuberculosis strains with a damaged pks1/15 gene which is characteristic for the Euro-American (EUAM) subgroup of M. tuberculosis (OR 0.63, CI 0.49-0.81, P(nominal) 0.0004, P(corrected) 0.0019). Our results, including those of luciferase reporter gene assays with the IRGM variants -261C and -261T, suggest a role for IRGM and autophagy in protection of humans against natural infection with M. tuberculosis EUAM clades. Moreover, they support in vitro findings indicating that TB lineages capable of producing a distinct mycobacterial phenolic glycolipid that occurs exclusively in strains with an intact pks1/15 gene inhibit innate immune responses in which IRGM contributes to the control of autophagy. Finally, they raise the possibility that the increased frequency of the IRGM -261TT genotype may have contributed to the establishment of M. africanum as a pathogen in the West African population.

| S-EPMC2735778 | biostudies-literature

Variant G57E of mannose binding lectin associated with protection against tuberculosis caused by Mycobacterium africanum but not by M. tuberculosis.

Project description:Structural variants of the Mannose Binding Lectin (MBL) cause quantitative and qualitative functional deficiencies, which are associated with various patterns of susceptibility to infectious diseases and other disorders. We determined genetic MBL variants in 2010 Ghanaian patients with pulmonary tuberculosis (TB) and 2346 controls and characterized the mycobacterial isolates of the patients. Assuming a recessive mode of inheritance, we found a protective association between TB and the MBL2 G57E variant (odds ratio 0.60, confidence interval 0.4-0.9, P 0.008) and the corresponding LYQC haplotype (P(corrected) 0.007) which applied, however, only to TB caused by M. africanum but not to TB caused by M. tuberculosis. In vitro, M. africanum isolates bound recombinant human MBL more efficiently than did isolates of M. tuberculosis. We conclude that MBL binding may facilitate the uptake of M. africanum by macrophages, thereby promoting infection and that selection by TB may have favoured the spread of functional MBL deficiencies in regions endemic for M. africanum.

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Patients infected with Mycobacterium africanum versus Mycobacterium tuberculosis possess distinct intestinal microbiota.

Project description:BACKGROUND:Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB), is composed of eight subspecies. TB in West Africa, in contrast to other geographical regions, is caused by Mycobacterium africanum (MAF) in addition to M. tuberculosis (MTB), with both infections presenting similar symptoms. Nevertheless, MAF is considered to be hypovirulent in comparison with MTB and less likely to progress to active disease. In this study, we asked whether MAF and MTB infected patients possess distinct intestinal microbiomes and characterized how these microbiota communities are affected by anti-tuberculosis therapy (ATT). Additionally, we assessed if the changes in microbiota composition following infection correlate with pathogen induced alterations in host blood-gene expression. METHODS:A longitudinal, clinical study of MAF infected, MTB infected patients assessed at diagnosis and two months after start of ATT, and healthy, endemic controls was conducted to compare compositions of the fecal microbiome as determined by 16S rRNA sequencing. A blood transcriptome analysis was also performed on a subset of subjects in each group by microarray and the results cross-compared with the same individual's microbiota composition. FINDINGS:MAF participants have distinct microbiomes compared with MTB patients, displaying decreased diversity and increases in Enterobacteriaceae with respect to healthy participants not observed in the latter patient group. Interestingly, this observed elevation in Enterobacteriaceae positively correlated with enhanced inflammatory gene expression in peripheral blood and was reversed after initiation of ATT. INTERPRETATION:Our findings indicate that MAF and MTB have distinct associations with the gut microbiome that may be reflective of the differential susceptibility of West Africans to these two co-endemic infections either as biomarkers or as a contributing determinant.

| S-EPMC7219701 | biostudies-literature

Reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban West Africa.

Project description:OBJECTIVE:Understanding transmission dynamics is useful for tuberculosis (TB) control. A population-based molecular epidemiological study was conducted to determine TB transmission in Ghana. METHODS:Mycobacterium tuberculosis complex (MTBC) isolates obtained from prospectively sampled pulmonary TB patients between July 2012 and December 2015 were characterized using spoligotyping and standard 15-locus mycobacterial interspersed repetitive unit variable number tandem repeat (MIRU-VNTR) typing for transmission studies. RESULTS:Out of 2309 MTBC isolates, 1082 (46.9%) unique cases were identified, with 1227 (53.1%) isolates belonging to one of 276 clusters. The recent TB transmission rate was estimated to be 41.2%. Whereas TB strains of lineage 4 belonging to M. tuberculosis showed a high recent transmission rate (44.9%), reduced recent transmission rates were found for lineages of Mycobacterium africanum (lineage 5, 31.8%; lineage 6, 24.7%). CONCLUSIONS:The study findings indicate high recent TB transmission, suggesting the occurrence of unsuspected outbreaks in Ghana. The observed reduced transmission rate of M. africanum suggests other factor(s) (host/environmental) may be responsible for its continuous presence in West Africa.

| S-EPMC6069673 | biostudies-literature

Estimates of Testing for Latent Tuberculosis Infection and Cost, United States, 2013.

Project description:OBJECTIVES:Tracking trends in the testing of latent tuberculosis infection (LTBI) can help measure tuberculosis elimination efforts in the United States. The objectives of this study were to estimate (1) the annual number of persons tested for LTBI and the number of LTBI tests conducted, by type of test and by public, private, and military sectors, and (2) the cost of LTBI testing in the United States. METHODS:We searched the biomedical literature for published data on private-sector and military LTBI testing in 2013, and we used back-calculation to estimate public-sector LTBI testing. To estimate costs, we applied Medicare-allowable reimbursements in 2013 by test type. RESULTS:We estimated an average (low-high) 13.3 million (11.3-15.4 million) persons tested for LTBI and 15.3 million (12.9-17.7 million) LTBI tests, of which 13.2 million (11.1-15.3 million) were tuberculin skin tests and 2.1 million (1.8-2.4 million) were interferon-? release assays (IGRAs). Eighty percent of persons tested were in the public sector, 18% were in the private sector, and 2% were in the military. Costs of LTBI tests and of chest radiography totaled $314 million (range, $256 million to $403 million). CONCLUSIONS:To achieve tuberculosis elimination, millions more persons will need to be tested in all sectors. By targeting testing to only those at high risk of tuberculosis and by using more specific IGRA tests, the incidence of tuberculosis in the United States can be reduced and resources can be more efficiently used.

| S-EPMC6852068 | biostudies-literature

Comparing Observed with Predicted Weekly Influenza-Like Illness Rates during the Winter Holiday Break, United States, 2004-2013.

Project description:In the United States, influenza season typically begins in October or November, peaks in February, and tapers off in April. During the winter holiday break, from the end of December to the beginning of January, changes in social mixing patterns, healthcare-seeking behaviors, and surveillance reporting could affect influenza-like illness (ILI) rates. We compared predicted with observed weekly ILI to examine trends around the winter break period. We examined weekly rates of ILI by region in the United States from influenza season 2003-2004 to 2012-2013. We compared observed and predicted ILI rates from week 44 to week 8 of each influenza season using the auto-regressive integrated moving average (ARIMA) method. Of 1,530 region, week, and year combinations, 64 observed ILI rates were significantly higher than predicted by the model. Of these, 21 occurred during the typical winter holiday break period (weeks 51-52); 12 occurred during influenza season 2012-2013. There were 46 observed ILI rates that were significantly lower than predicted. Of these, 16 occurred after the typical holiday break during week 1, eight of which occurred during season 2012-2013. Of 90 (10 HHS regions x 9 seasons) predictions during the peak week, 78 predicted ILI rates were lower than observed. Out of 73 predictions for the post-peak week, 62 ILI rates were higher than observed. There were 53 out of 73 models that had lower peak and higher post-peak predicted ILI rates than were actually observed. While most regions had ILI rates higher than predicted during winter holiday break and lower than predicted after the break during the 2012-2013 season, overall there was not a consistent relationship between observed and predicted ILI around the winter holiday break during the other influenza seasons.

| S-EPMC4674102 | biostudies-literature

Mycobacterium africanum (Lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (Lineage 4) in Bamako, Mali.

Project description:ObjectiveAncestral M. tuberculosis complex lineages such as M. africanum are underrepresented among retreatment patients and those with drug resistance. To test the hypothesis that they respond faster to TB treatment, we determined the rate of smear conversion of new pulmonary tuberculosis patients in Bamako, Mali by the main MTBc lineages.MethodsBetween 2015 and 2017, we conducted a prospective cohort study of new smear positive pulmonary tuberculosis patients in Bamako. Confirmed MTBc isolates underwent genotyping by spoligotyping for lineage classification. Patients were followed at 1 month (M), 2M and 5M to measure smear conversion in auramine (AR) and Fluorescein DiAcetate (FDA) vital stain microscopy.ResultAll the first six human MTBc lineages were represented in the population, plus M. bovis in 0.8% of the patients. The most widely represented lineage was the modern Euro-American lineage (L) 4, 57%, predominantly the T family, followed by L6 (M. africanum type 2) in 22.9%. Ancestral lineages 1, 5, 6 and M. bovis combined amounted to 28.8%. Excluding 25 patients with rifampicin resistance, smear conversion, both by AR and FDA, occurred later in L6 compared to L4 (HR 0.80 (95% CI 0.66-0.97) for AR, and HR 0.81 (95%CI 0.68-0.97) for FDA). In addition we found that HIV negative status, higher BMI at day 0, and patients with smear grade at baseline ≤ 1+ were associated with earlier smear conversion.ConclusionThe six major human lineages of the MTBc all circulate in Bamako. Counter to our hypothesis, we found that patients diseased with modern M. tuberculosis complex L4 respond faster to TB treatment than those with M. africanum L6.

| S-EPMC6291124 | biostudies-literature

Mycobacterium africanum--review of an important cause of human tuberculosis in West Africa.

Project description:Mycobacterium africanum consists of two phylogenetically distinct lineages within the Mycobacterium tuberculosis complex, known as M. africanum West African 1 and M. africanum West African 2. These lineages are restricted to West Africa, where they cause up to half of human pulmonary tuberculosis. In this review we discuss the definition of M. africanum, describe the prevalence and restricted geographical distribution of M. africanum West African 1 and 2, review the occurrence of M. africanum in animals, and summarize the phenotypic differences described thus far between M. africanum and M. tuberculosis sensu stricto.

| S-EPMC2946903 | biostudies-literature

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