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1.
Front Public Health ; 9: 706651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368069

RESUMO

Tuberculosis (TB), an airborne infectious disease caused by Mycobacterium tuberculosis complex (MTBC), remains a global health problem. West Africa has a unique epidemiology of TB that is characterized by medium- to high-prevalence. Moreover, the geographical restriction of M. africanum to the sub-region makes West Africa have an extra burden to deal with a two-in-one pathogen. The region is also burdened with low case detection, late reporting, poor treatment adherence leading to development of drug resistance and relapse. Sporadic studies conducted within the subregion report higher burden of drug resistant TB (DRTB) than previously thought. The need for more sensitive and robust tools for routine surveillance as well as to understand the mechanisms of DRTB and transmission dynamics for the design of effective control tools, cannot be overemphasized. The advancement in molecular biology tools including traditional fingerprinting and next generation sequencing (NGS) technologies offer reliable tools for genomic epidemiology. Genomic epidemiology provides in-depth insight of the nature of pathogens, circulating strains and their spread as well as prompt detection of the emergence of new strains. It also offers the opportunity to monitor treatment and evaluate interventions. Furthermore, genomic epidemiology can be used to understand potential emergence and spread of drug resistant strains and resistance mechanisms allowing the design of simple but rapid tools. In this review, we will describe the local epidemiology of MTBC, highlight past and current investigations toward understanding their biology and spread as well as discuss the relevance of genomic epidemiology studies to TB control in West Africa.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , África Ocidental/epidemiologia , Genômica , Humanos , Mycobacterium tuberculosis/genética , Tuberculose/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
2.
PLoS One ; 16(8): e0255433, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34437584

RESUMO

Findings from previous comparative genomics studies of the Mycobacterium tuberculosis complex (MTBC) suggest genomic variation among the genotypes may have phenotypic implications. We investigated the diversity in the phenotypic profiles of the main prevalent MTBC genotypes in West Africa. Thirty-six whole genome sequenced drug susceptible MTBC isolates belonging to lineages 4, 5 and 6 were included in this study. The isolates were phenotypically characterized for urease activity, tween hydrolysis, Thiophen-2-Carboxylic Acid Hydrazide (TCH) susceptibility, nitric oxide production, and growth rate in both liquid (7H9) and solid media (7H11 and Löwenstein-Jensen (L-J)). Lineage 4 isolates showed the highest growth rate in both liquid (p = 0.0003) and on solid (L-J) media supplemented with glycerol (p<0.001) or pyruvate (p = 0.005). L6 isolates optimally utilized pyruvate compared to glycerol (p<0.001), whereas L5 isolates grew similarly on both media (p = 0.05). Lineage 4 isolates showed the lowest average time to positivity (TTP) (p = 0.01; Average TTP: L4 = 15days, L5 = 16.7days, L6 = 29.7days) and the highest logCFU/mL (p = 0.04; average logCFU/mL L4 = 5.9, L5 = 5.0, L6 = 4.4) on 7H11 supplemented with glycerol, but there was no significant difference in growth on 7H11 supplemented with pyruvate (p = 0.23). The highest release of nitrite was recorded for L5 isolates, followed by L4 and L6 isolates. However, the reverse was observed in the urease activity for the lineages. All isolates tested were resistant to TCH except for one L6 isolate. Comparative genomic analyses revealed several mutations that might explain the diverse phenotypic profiles of these isolates. Our findings showed significant phenotypic diversity among the MTBC lineages used for this study.

3.
Int J Infect Dis ; 109: 294-303, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34273514

RESUMO

OBJECTIVE: We conducted a cross-sectional study in the five administrative regions of Northern Ghana to determine the diversity of Mycobacterium tuberculosis complex (MTBC) sub/lineages and their susceptibility to isoniazid (INH) and rifampicin (RIF). METHODS: Sputum specimens were collected and cultured from 566 pulmonary tuberculosis patients reporting to 17 health facilities from 2015 to 2019. Mycobacterial isolates obtained from solid cultures were confirmed as members of the MTBC by PCR amplification of IS6110 and rpoß and assigned lineages and sub-lineages using spoligotyping. RESULTS: Of 294 mycobacterial isolates recovered, MTBC species identified were: M. tuberculosis sensu stricto (Mtbss) 241 (82.0%), M. africanum 41 (13.9%) and M. bovis four (1.4%) with eight (2.7%) unidentified. The human-adapted lineages (L) identified (N=279) were L1 (8/279, 2.9%), L2 (15/279, 5.4%), L3 (7/279, 2.5%), L4 (208/279, 74.5%), L5 (13/279, 4.7%) and L6 (28/279, 10.0%) with three unidentified lineages. Among the 208 L4, the dominant sub-lineages in the region were the Cameroon 120/208 (57.7%) and Ghana 50/208 (24.0%). We found 4.4% (13/294) and 0.7% (2/294) of the patients infected with MTBC isolates resistant to INH only and RIF only, respectively, with 2.4% (7/294) being infected with MDR strains. Whereas L6 was associated with the elderly, we identified that the Ghana sub-lineage of L4 was associated with both INH and MDR (p<0.05), making them important TB pathogens in Northern Ghana and a growing public health concern.


Assuntos
Mycobacterium tuberculosis , Preparações Farmacêuticas , Tuberculose Resistente a Múltiplos Medicamentos , Idoso , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Estudos Transversais , Genótipo , Gana/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
4.
PLoS One ; 16(3): e0238898, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730036

RESUMO

CONTEXT: Available molecular epidemiological data from recent studies suggest significant genetic variation between the different lineages of Mycobacterium tuberculosis complex (MTBC) and the MTBC lineages might have adapted to different human populations. AIM: This study sought to determine the population structure of clinical MTBC isolates from the Volta Region of Ghana. METHODS: The MTBC isolates obtained from collected sputum samples were identified by PCR detecting of IS6110 and genotyped using spoligotyping. Non-tuberculous mycobacterial isolates were characterized by amplification of the heat shock protein 65 (hsp65) gene and sequencing. The drug susceptibility profiles of the MTBCs determined using GenoType MTBDRplus. RESULTS: One hundred and seventeen (117, 93.6%) out of 125 mycobacterial positive isolates were characterized as members of the MTBC of which M. tuberculosis sensu stricto (MTBss) and M. africanum (MAF) were respectively 94 (80.3%) and 23 (19.7%). In all, 39 distinct spoligotype patterns were obtained; 26 for MTBss and 13 for MAF lineages. Spoligotyping identified 89 (76%) Lineage 4, 16 (13.6%) Lineage 5, 7 (6.0%) Lineage 6, 3 (2.6%) Lineage 2, 1(0.9%) Lineage 3 and 1 (0.9%) Lineage 1. Among the Lineage 4 isolates, 62/89 (69.7%) belonged to Cameroon sub-lineage, 13 (14.7%) Ghana, 8 (9.0%) Haarlem, 2 (2.2%) LAM, 1 (1.1%) Uganda I, 1 (1.1%) X and the remaining two (2.2%) were orphan. Significant localization of MAF was found within the Ho municipality (n = 13, 29.5%) compared to the more cosmopolitan Ketu-South/Aflao (n = 3, 8.3%) (p-value = 0.017). Eight (8) non-tuberculous mycobacteria were characterized as M. abscessus (7) and M. fortuitum (1). CONCLUSION: We confirmed the importance of M. africanum lineages as a cause of TB in the Volta region of Ghana.


Assuntos
Mycobacterium/genética , Tuberculose/epidemiologia , Adulto , Antituberculosos/farmacologia , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Feminino , Genótipo , Gana/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium/efeitos dos fármacos , Mycobacterium/isolamento & purificação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Micobactérias não Tuberculosas/genética , Micobactérias não Tuberculosas/isolamento & purificação , Prevalência , Escarro/microbiologia , Tuberculose/microbiologia , Tuberculose/patologia
5.
Int J Infect Dis ; 106: 13-22, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33667696

RESUMO

OBJECTIVE: To retrospectively investigate the cause of recurring tuberculosis (rcTB) among participants with pulmonary TB recruited from a prospective population-based study conducted between July 2012 and December 2015. METHODS: Mycobacterium tuberculosis complex isolates obtained from rcTB cases were characterized by standard mycobacterial genotyping tools, whole-genome sequencing, and phylogenetic analysis carried out to assess strain relatedness. RESULTS: The majority (58.3%, 21/36) of study participants with rcTB episodes had TB recurrence within 12 months post treatment. TB strains with isoniazid (INH) resistance were found in 19.4% (7/36) of participants at the primary episode, of which 29% (2/7) were also rifampicin-resistant. On TB recurrence, an INH-resistant strain was found in a larger proportion of participants, 27.8% (10/36), of which 40% (4/10) were MDR-TB strains. rcTB was attributed to relapse (same strain) in 75.0% (27/36) of participants and 25.0% (9/36) to re-infection. CONCLUSION: Our findings indicate that previous unresolved infectiondue to inadequate treatment, may be the major cause of rcTB.


Assuntos
Genômica , Habitação , Mycobacterium tuberculosis/genética , Tuberculose/epidemiologia , Tuberculose/transmissão , Adulto , Antituberculosos/uso terapêutico , Feminino , Gana/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Mycobacterium tuberculosis/fisiologia , Filogenia , Recidiva , Estudos Retrospectivos , Tuberculose/tratamento farmacológico , Sequenciamento Completo do Genoma
6.
Microb Genom ; 7(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33555243

RESUMO

Human tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC). The MTBC comprises several human-adapted lineages known as M. tuberculosis sensu stricto, as well as two lineages (L5 and L6) traditionally referred to as Mycobacterium africanum. Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known of their genomic diversity, phylogeography and evolution. Here, we analysed the genomes of 350 L5 and 320 L6 strains, isolated from patients from 21 African countries, plus 5 related genomes that had not been classified into any of the known MTBC lineages. Our population genomic and phylogeographical analyses showed that the unclassified genomes belonged to a new group that we propose to name MTBC lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences between L5 and L6 strains with respect to their phylogeographical substructure and genetic diversity. Finally, we could not confirm the previous association of drug-resistance markers with lineage and sublineages. Instead, our results indicate that the association of drug resistance with lineage is most likely driven by sample bias or geography. In conclusion, our study sheds new light onto the genomic diversity and evolutionary history of M. africanum, and highlights the need to consider the particularities of each MTBC lineage for understanding the ecology and epidemiology of TB in Africa and globally.


Assuntos
Farmacorresistência Bacteriana , Mycobacterium tuberculosis/classificação , Tuberculose/microbiologia , Sequenciamento Completo do Genoma/métodos , África Oriental , África Ocidental , Evolução Molecular , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Filogeografia
7.
PLoS One ; 15(7): e0236016, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649692

RESUMO

Cholera remains a major global public health threat and continuous emergence of new Vibrio cholerae strains is of major concern. We conducted a molecular epidemiological study to detect virulence markers and antimicrobial resistance patterns of V. cholerae isolates obtained from the 2012-2015 cholera outbreaks in Ghana. Archived clinical isolates obtained from the 2012, 2014 and 2015 cholera outbreaks in Ghana were revived by culture and subjected to microscopy, biochemical identification, serotyping, antibiotic susceptibility testing, molecular detection of distinct virulence factors and Multi-Locus Variable-Number of Tandem-Repeat Analysis (MLVA). Of 277 isolates analysed, 168 (60.6%) were confirmed to be V. cholerae and 109 (39.4%) isolates constituted other bacteria (Escherichia coli, Aeromonas sobria, Pseudomonas aeruginosa, Enterobacter cloacae and Enterococci faecalis). Serotyping the V. cholerae isolates identified 151 (89.9%) as Ogawa, 3 (1.8%) as Inaba and 14 (8.3%) as non-O1/O139 serogroup. The O1 serogroup isolates (154/168, 91.7%) carried the cholera toxin ctxB gene as detected by PCR. Additional virulence genes detected include zot, tcpA, ace, rtxC, toxR, rtxA, tcpP, hlyA and tagA. The most common and rare virulence factors detected among the isolates were rtxC (165 isolates) and tcpP (50 isolates) respectively. All isolates from 2014 and 2015 were multidrug resistant against the selected antibiotics. MLVA differentiated the isolates into 2 large unique clones A and B, with each predominating in a particular year. Spatial analysis showed clustering of most isolates at Ablekuma sub-district. Identification of several virulence genes among the two different genotypes of V. cholerae isolates and resistance to first- and second-line antibiotics, calls for scaleup of preventive strategies to reduce transmission, and strengthening of public health laboratories for rapid antimicrobial susceptibility testing to guide accurate treatment. Our findings support the current WHO licensed cholera vaccines which include both O1 Inaba and Ogawa serotypes.


Assuntos
Cólera/epidemiologia , Vibrio cholerae/metabolismo , Antibacterianos/farmacologia , Cólera/diagnóstico , Cólera/microbiologia , Toxina da Cólera/genética , Toxina da Cólera/metabolismo , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla/genética , Gana/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Filogenia , Sorogrupo , Sequências de Repetição em Tandem/genética , Vibrio cholerae/classificação , Vibrio cholerae/isolamento & purificação , Vibrio cholerae/patogenicidade , Virulência/genética
8.
Front Med (Lausanne) ; 7: 161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509791

RESUMO

Whole genome sequencing (WGS) is progressively being used to investigate the transmission dynamics of Mycobacterium tuberculosis complex (MTBC). We used WGS analysis to resolve traditional genotype clusters and explored the spatial distribution of confirmed recent transmission clusters. Bacterial genomes from a total of 452 MTBC isolates belonging to large traditional clusters from a population-based study spanning July 2012 and December 2015 were obtained through short read next-generation sequencing using the illumina HiSeq2500 platform. We performed clustering and spatial analysis using specified R packages and ArcGIS. Of the 452 traditional genotype clustered genomes, 314 (69.5%) were confirmed clusters with a median cluster size of 7.5 genomes and an interquartile range of 4-12. Recent tuberculosis (TB) transmission was estimated as 24.7%. We confirmed the wide spread of a Cameroon sub-lineage clone with a cluster size of 78 genomes predominantly from the Ablekuma sub-district of Accra metropolis. More importantly, we identified a recent transmission cluster associated with isoniazid resistance belonging to the Ghana sub-lineage of lineage 4. WGS was useful in detecting unsuspected outbreaks; hence, we recommend its use not only as a research tool but as a surveillance tool to aid in providing the necessary guided steps to track, monitor, and control TB.

9.
PLoS One ; 14(3): e0209395, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30830912

RESUMO

BACKGROUND: Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in both livestock and humans. The association of some M. bovis strains with hyper-virulence, MDR-TB and disseminated disease makes it imperative to understand the biology of the pathogen. METHODS: Mycobacterium bovis (15) among 1755 M. tuberculosis complex (MTBC) isolated between 2012 and 2014 were characterized and analyzed for associated patient demography and other risk factors. Five of the M. bovis isolates were whole-genome sequenced and comparatively analyzed against a global collection of published M. bovis genomes. RESULTS: Mycobacterium bovis was isolated from 3/560(0.5%) females and 12/1195(1.0%) males with pulmonary TB. The average age of M. bovis infected cases was 46.8 years (7-72years). TB patients from the Northern region of Ghana (1.9%;4/212) had a higher rate of infection with M. bovis (OR = 2.7,p = 0.0968) compared to those from the Greater Accra region (0.7%;11/1543). Among TB patients with available HIV status, the odds of isolating M. bovis from HIV patients (2/119) was 3.3 higher relative to non-HIV patients (4/774). Direct contact with livestock or their unpasteurized products was significantly associated with bTB (p<0.0001, OR = 124.4,95% CI = 30.1-508.3). Two (13.3%) of the M. bovis isolates were INH resistant due to the S315T mutation in katG whereas one (6.7%) was RIF resistant with Q432P and I1491S mutations in rpoB. M. bovis from Ghana resolved as mono-phyletic branch among mostly M. bovis from Africa irrespective of the host and were closest to the root of the global M. bovis phylogeny. M. bovis-specific amino acid mutations were detected among MTBC core genes such as mce1A, mmpL1, pks6, phoT, pstB, glgP and Rv2955c. Additional mutations P6T in chaA, G187E in mgtC, T35A in Rv1979c, S387A in narK1, L400F in fas and A563T in eccA1 were restricted to the 5 clinical M. bovis from Ghana. CONCLUSION: Our data indicate potential zoonotic transmission of bTB in Ghana and hence calls for intensified public education on bTB, especially among risk groups.


Assuntos
Infecções por HIV/epidemiologia , Mycobacterium bovis/genética , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Sequenciamento Completo do Genoma/métodos , Adolescente , Adulto , Idoso , Animais , Bovinos , Criança , Comorbidade , DNA Bacteriano/genética , Farmacorresistência Bacteriana , Feminino , Gana , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Mutação , Mycobacterium bovis/classificação , Mycobacterium bovis/isolamento & purificação , Filogenia , Tuberculose Bovina/epidemiologia , Tuberculose Bovina/transmissão , Adulto Jovem
10.
PLoS One ; 14(2): e0211822, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730937

RESUMO

BACKGROUND: Diabetes Mellitus (DM) is a known risk factor for tuberculosis (TB) but little is known on TB-Diabetes Mellitus (TBDM) co-morbidity in Sub-Saharan Africa. METHODS: Consecutive TB cases registered at a tertiary facility in Ghana were recruited from September 2012 to April 2016 and screened for DM using random blood glucose and glycated hemoglobin (HbA1c) level. TB patients were tested for other clinical parameters including HIV co-infection and TB lesion location. Mycobacterial isolates obtained from collected sputum samples were characterized by standard methods. Associations between TBDM patients' epidemiological as well as microbiological variables were assessed. RESULTS: The prevalence of DM at time of diagnosis among 2990 enrolled TB cases was 9.4% (282/2990). TBDM cases were significantly associated with weight loss, poor appetite, night sweat and fatigue (p<0.001) and were more likely (p<0.001) to have lower lung cavitation 85.8% (242/282) compared to TB Non-Diabetic (TBNDM) patients 3.3% (90/2708). We observed 22.3% (63/282) treatment failures among TBDM patients compared to 3.8% (102/2708) among TBNDM patients (p<0.001). We found no significant difference in the TBDM burden attributed by M. tuberculosis sensu stricto (Mtbss) and Mycobacterium africanum (Maf) and (Mtbss; 176/1836, 9.6% and Maf; 53/468, 11.3%, p = 0.2612). We found that diabetic individuals were suggestively likely to present with TB caused by M. africanum Lineage 6 as opposed to Mtbss (odds ratio (OR) = 1.52; 95% confidence interval (CI): 0.92-2.42, p = 0.072). CONCLUSION: Our findings confirms the importance of screening for diabetes during TB diagnosis and highlights the association between genetic diversity and diabetes. in Ghana.


Assuntos
Coinfecção , Complicações do Diabetes , Infecções por HIV , HIV-1 , Mycobacterium tuberculosis , Tuberculose , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Coinfecção/microbiologia , Coinfecção/virologia , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/microbiologia , Complicações do Diabetes/virologia , Feminino , Gana/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/microbiologia , Tuberculose/virologia
11.
Int J Mycobacteriol ; 7(3): 222-227, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30198500

RESUMO

Background: Sputum culture is limited to centralized facilities. Thus, samples require transportation from peripheral laboratories to these facilities, compromising specimen quality since it is difficult to maintain cold chain. We evaluated OMNIgene SPUTUM Reagent (OMS) for transporting sputum samples for tuberculosis (TB) testing. The study was carried out at Noguchi Memorial Institute for Medical Research using sputa from Korle Bu Teaching Hospital and La General Hospital in Ghana. Methods: In a laboratory-based controlled experiment (CE), sputum contaminants were determined on blood agar before treatment with OMS and N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH). TB testing included smear microscopy, culture, and Xpert MTB/RIF. Afterward, two peripheral laboratories were trained to transport sputum samples with OMS without cold chain. Positivity, negativity, and contamination rates were compared between both methods using Chi-square and Fisher's exact tests. Cohen's Kappa was also used to determine agreements. Results: Among 104 sputum samples analyzed in the CE, 93 (89.4%) had bacterial growth on blood agar before decontamination, while 6 (5.8%) and 5 (4.8%) contaminated after NALC-NaOH and OMS treatment, respectively. Contamination was high with NALC-NaOH (12.8%) than OMS (4.3%) on Lowenstein-Jensen media (P < 0.001), but mycobacterial positivity was comparable: NALC-NaOH of 74.5% and OMS of 78.7%. Smear positivity after NALC-NaOH treatment was 89.4% and OMS was 75.9% (P = 0.491). All except one of the samples tested positive by Xpert MTB/RIF after both treatment. Sixteen samples were evaluated in the field experiment and 81.3% yielded positive culture, and no contamination on LJ was observed. Conclusion: Our findings indicate that OMS works well as a transport and decontaminating reagent of samples for TB testing.


Assuntos
Descontaminação/métodos , Indicadores e Reagentes/química , Mycobacterium tuberculosis/isolamento & purificação , Manejo de Espécimes/métodos , Escarro/microbiologia , Técnicas Bacteriológicas/métodos , Gana , Humanos , Laboratórios Hospitalares , Refrigeração , Sensibilidade e Especificidade , Transportes , Tuberculose/diagnóstico
12.
Sci Rep ; 8(1): 11269, 2018 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-30050166

RESUMO

Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some countries of West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including N = 175 Lineage 5 (L5) and N = 78 Lineage 6 (L6). We found that the genomic diversity of L6 was higher than in L5 despite the smaller sample size. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Even though over 90% of the human T cell epitopes were conserved in both lineages, L6 showed a higher ratio of non-synonymous to synonymous single nucleotide variation in these epitopes overall compared to L5. Of the 10% human T cell epitopes that were variable, most carried mutations that were lineage-specific. Our findings indicate that Maf L5 and L6 differ in some of their population genomic characteristics, possibly reflecting different selection pressures linked to distinct ecological niches.


Assuntos
Variação Genética , Genoma Bacteriano , Genômica , Genótipo , Mycobacterium/genética , Tuberculose/microbiologia , Gana , Humanos , Mycobacterium/classificação , Mycobacterium/isolamento & purificação
13.
PLoS Negl Trop Dis ; 12(6): e0006560, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29870529

RESUMO

BACKGROUND: Buruli ulcer (BU), a necrotizing skin infection caused by Mycobacterium ulcerans is the third most important mycobacterial disease globally after tuberculosis and leprosy in immune competent individuals. This study reports on the retrospective analyses of microbiologically confirmed Buruli ulcer (BU) cases in seventy-five health facilities in Ghana. METHOD/PRINCIPAL FINDINGS: Pathological samples were collected from BU lesions and transported either through courier services or by car directly to the laboratory. Samples were processed and analysed by IS2404 PCR, culture and Ziehl-Neelsen staining for detection of acid-fast bacilli. From 2008 to 2016, we analysed by PCR, 2,287 samples of 2,203 cases from seventy-five health facilities in seven regions of Ghana (Ashanti, Brong Ahafo, Central, Eastern, Greater Accra, Northern and Volta). The mean annual positivity rate was 46.2% and ranged between 14.6% and 76.2%. The yearly positivity rates from 2008 to 2016 were 52.3%, 76.2%, 56.7%, 53.8%, 41.2%, 41.5%, 22.9%, 28.5% and 14.6% respectively. Of the 1,020 confirmed cases, the ratio of female to male was 518 and 502 respectively. Patients who were 15 years of age and below accounted for 39.8% of all cases. The median age was 20 years (IQR = 10-43). Ulcerative lesions were 69.2%, nodule (9.6%), plaque (2.9%), oedema (2.5%), osteomyelitis (1.1%), ulcer/oedema (9.5%) and ulcer/plaque (5.2%). Lesions frequently occurred on the lower limbs (57%) followed by the upper limbs (38%), the neck and head (3%) and the least found on the abdomen (2%). CONCLUSIONS/SIGNIFICANCE: Our findings show a decline in microbiological confirmed rates over the years and therefore call for intensive education on case recognition to prevent over-diagnosis as BU cases decline.


Assuntos
Úlcera de Buruli/diagnóstico , Mycobacterium ulcerans/isolamento & purificação , Adolescente , Adulto , Úlcera de Buruli/complicações , Úlcera de Buruli/epidemiologia , Úlcera de Buruli/microbiologia , Criança , Pré-Escolar , Técnicas de Laboratório Clínico , Feminino , Gana/epidemiologia , Instalações de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mycobacterium ulcerans/genética , Osteomielite/microbiologia , Reação em Cadeia da Polimerase/métodos , Estudos Retrospectivos , Adulto Jovem
14.
Int J Infect Dis ; 73: 30-42, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29879521

RESUMO

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.


Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Gana/epidemiologia , Humanos , Pessoa de Meia-Idade , Repetições Minissatélites , Epidemiologia Molecular , Mycobacterium tuberculosis/genética , Estudos Prospectivos , Tuberculose/microbiologia , Adulto Jovem
15.
Infect Drug Resist ; 11: 239-246, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29503573

RESUMO

Background: Drug resistance surveillance is crucial for tuberculosis (TB) control. Therefore, our goal was to determine the prevalence of second-line anti-TB drug resistance among diverse primary drug-resistant Mycobacterium tuberculosis complex (MTBC) isolates in Ghana. Materials and methods: One hundred and seventeen MTBC isolates with varying first-line drug resistance were analyzed. Additional resistance to second-line anti-TB drugs (streptomycin [STR], amikacin [AMK] and moxifloxacin [MOX]) was profiled using the Etest and GenoType MTBDRsl version 2.0. Genes associated with resistance to AMK and MOX (gyrA, gyrB, eis, rrs, tap, whiB7 and tlyA) were then analyzed for mutation. Results: Thirty-seven (31.9%) isolates had minimum inhibitory concentration (MIC) values ≥2 µg/mL against STR while 12 (10.3%) isolates had MIC values ≥1 µg/mL for AMK. Only one multidrug-resistant (MDR) isolate (Isolate ID: TB/Nm 919) had an MIC value of ≥0.125 µg/mL for MOX (MIC = 3 µg/mL). This isolate also had the highest MIC value for AMK (MIC = 16 µg/mL) and was confirmed as resistant to AMK and MOX by the line probe assay GenoType MTBDRsl version 2.0. Mutations associated with the resistance were: gyrA (G88C) and rrs (A514C and A1401G). Conclusion: Our findings suggest the need to include routine second-line anti-TB drug susceptibility testing of MDR/rifampicin-resistant isolates in our diagnostic algorithm.

16.
Am J Trop Med Hyg ; 96(5): 1076-1083, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28500810

RESUMO

AbstractThe exact route of transmission of Mycobacterium ulcerans (MU) (causative agent of Buruli ulcer [BU]), risk factors, and reservoir hosts are not clearly known, although it has been identified as an environmental pathogen. This study assessed potential environmental and behavioral risk factors that influence BU infections. We conducted a case-control study where cases were matched by their demographic characteristics and place of residence. A structured questionnaire was administered to solicit information on the environmental and behavioral factors of participants that may expose them to infection. A total of 176 cases and 176 controls were enrolled into the study. Multivariate conditional logistic regression analysis identified farming in swampy areas (odds ratio [OR] = 4.10, 95% confidence interval [CI] = 3.82-7.18), farming while wearing short clothing (OR = 1,734.1, 95% CI = 68.1-44,120.9), insect bite (OR = 988.3, 95% CI = 31.4-31,115.6), and application of leaves on wounds (OR = 6.23, 95% CI = 4.74-18.11) as potential risk factors. Farming in long clothing (OR = 0.000, 95% CI = 0.00-0.14), washing wound with water and soap (OR = 0.37, 95% CI = 0.29-0.98), and application of adhesive bandage on wounds (OR = 0.31, 95% CI = 0.15-0.82) were found to be protective against BU infection. In the absence of the exact MU transmission mechanisms, education of public in BU-endemic zones on the use of protective clothing during farming activities to limit exposure of the skin and proper wound care management would be essential in the fight against BU.


Assuntos
Úlcera de Buruli/diagnóstico , Úlcera de Buruli/prevenção & controle , Mordeduras e Picadas de Insetos/prevenção & controle , Mycobacterium ulcerans/isolamento & purificação , Roupa de Proteção , Adolescente , Adulto , Agricultura , Úlcera de Buruli/microbiologia , Úlcera de Buruli/transmissão , Estudos de Casos e Controles , Criança , Feminino , Gana , Humanos , Mordeduras e Picadas de Insetos/microbiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Rios , Inquéritos e Questionários , Áreas Alagadas
17.
Microb Ecol ; 74(2): 350-361, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28238016

RESUMO

This study aimed to contribute to the understanding of Mycobacterium ulcerans (MU) ecology by analysing both clinical and environmental samples collected from ten communities along two major river basins (Offin and Densu) associated with Buruli ulcer (BU) at different seasons. We collected clinical samples from presumptive BU cases and environmental samples from ten communities. Following DNA extraction, clinical samples were confirmed by IS2404 PCR and environmental samples were confirmed by targeting MU-specific genes, IS2404, IS2606 and the ketoreductase (KR) using real-time PCR. Environmental samples were first analysed for IS2404; after which, IS2404-positive samples were multiplexed for the IS2606 and KR gene. Our findings indicate an overall decline in BU incidence along both river basins, although incidence at Densu outweighs that of Offin. Overall, 1600 environmental samples were screened along Densu (434, 27 %) and Offin (1166, 73 %) and MU was detected in 139 (9 %) of the combined samples. The positivity of MU along the Densu River basin was 89/434 (20.5 %), whilst that of the Offin River basin was 50/1166 (4.3 %). The DNA was detected mainly in snails (5/6, 83 %), moss (8/40, 20 %), soil (55/586, 9 %) and vegetation (55/675, 8 %). The proportion of MU positive samples recorded was higher during the months with higher rainfall levels (126/1175, 11 %) than during the dry season months (13/425, 3 %). This study indicates for the first time that there is a seasonal pattern in the presence of MU in the environment, which may be related to recent rainfall or water in the soil.


Assuntos
Úlcera de Buruli/microbiologia , Mycobacterium ulcerans/isolamento & purificação , Estações do Ano , Animais , Briófitas/microbiologia , Gana , Humanos , Chuva , Reação em Cadeia da Polimerase em Tempo Real , Caramujos/microbiologia , Microbiologia do Solo , Água
18.
PLoS Negl Trop Dis ; 10(7): e0004856, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27434064

RESUMO

In recent years, comparative genome sequence analysis of African Mycobacterium ulcerans strains isolated from Buruli ulcer (BU) lesion specimen has revealed a very limited genetic diversity of closely related isolates and a striking association between genotype and geographical origin of the patients. Here, we compared whole genome sequences of five M. ulcerans strains isolated in 2004 or 2013 from BU lesions of four residents of the Offin river valley with 48 strains isolated between 2002 and 2005 from BU lesions of individuals residing in the Densu river valley of Ghana. While all M. ulcerans isolates from the Densu river valley belonged to the same clonal complex, members of two distinct clonal complexes were found in the Offin river valley over space and time. The Offin strains were closely related to genotypes from either the Densu region or from the Asante Akim North district of Ghana. These results point towards an occasional involvement of a mobile reservoir in the transmission of M. ulcerans, enabling the spread of bacteria across different regions.


Assuntos
Úlcera de Buruli/microbiologia , Mycobacterium ulcerans/isolamento & purificação , Rios/microbiologia , Variação Genética , Genoma Bacteriano , Genótipo , Gana , Humanos , Mycobacterium ulcerans/classificação , Mycobacterium ulcerans/genética , Filogenia
19.
PLoS One ; 11(6): e0156864, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27271290

RESUMO

Hepatitis B virus (HBV) infections account for approximately 780,000 deaths per year, most of which occur in the developing world. Co-infection with HBV and hepatitis delta virus (HDV) may lead to the most severe form of viral hepatitis. In Ghana, knowledge on the prevalence of HBV and HDV in the general population is scanty and the few genetic analyses of the prevailing HBV genotypes are dating back more than a decade. In the present study, 1,323 serum samples from individuals living in a rural area (Offin river valley) of Ghana were analyzed for the presence of the hepatitis B surface antigen (HBsAg). Positive sera were subsequently tested for the presence of anti-HDV antibodies. A total of 107 (8%) sera were HBsAg positive with an 8.4% prevalence of anti-HDV antibodies among the HBsAg positives. Phylogenetic analysis based on HBV pre-S/S sequences, attributed all 52 typable samples to genotype E. All belonged to serotype ayw4. While 19 sequences clustered with those from a number of African countries, the other 33 formed a separate cluster distinguished by an intergroup mean distance of 1.5% from the pan-African HBV/E cluster. Successful implementation of HBV vaccination in the region was reflected by the low HBsAg carrier rate of 1.8% among children ≤11 years.


Assuntos
Variação Genética , Vírus da Hepatite B/genética , Hepatite B/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Portador Sadio , Criança , Pré-Escolar , DNA Viral/análise , DNA Viral/genética , Feminino , Gana/epidemiologia , Anticorpos Anti-Hepatite/sangue , Hepatite B/sangue , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , Rios , Análise de Sequência de DNA , Estudos Soroepidemiológicos , Adulto Jovem
20.
Appl Environ Microbiol ; 82(14): 4320-4329, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27208141

RESUMO

UNLABELLED: This study aimed to isolate nontuberculous mycobacterial species from environmental samples obtained from some selected communities in Ghana. To optimize decontamination, spiked environmental samples were used to evaluate four decontamination solutions and supplemented media, after which the best decontamination solution and media were used for the actual analysis. The isolates obtained were identified on the basis of specific genetic sequences, including heat shock protein 65, IS2404, IS2606, rpoB, and the ketoreductase gene, as needed. Among the methods evaluated, decontamination with 1 M NaOH followed by 5% oxalic acid gave the highest rate of recovery of mycobacteria (50.0%) and the lowest rate of contamination (15.6%). The cultivation medium that supported the highest rate of recovery of mycobacteria was polymyxin B-amphotericin B-nalidixic acid-trimethoprim-azlocillin-supplemented medium (34.4%), followed by isoniazid-supplemented medium (28.1%). Among the 139 samples cultivated in the main analysis, 58 (41.7%) yielded mycobacterial growth, 70 (50.4%) had no growth, and 11 (7.9%) had all inoculated tubes contaminated. A total of 25 different mycobacterial species were identified. Fifteen species (60%) were slowly growing (e.g., Mycobacterium ulcerans, Mycobacterium avium, Mycobacterium mantenii, and Mycobacterium malmoense), and 10 (40%) were rapidly growing (e.g., Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium abscessus). The occurrence of mycobacterial species in the various environmental samples analyzed was as follows: soil, 16 species (43.2%); vegetation, 14 species (38.0%); water, 3 species (8.0%); moss, 2 species (5.4%); snail, 1 species (2.7%); fungi, 1 species (2.7%). This study is the first to report on the isolation of M. ulcerans and other medically relevant nontuberculous mycobacteria from different environmental sources in Ghana. IMPORTANCE: Diseases caused by mycobacterial species other than those that cause tuberculosis and leprosy are increasing. Control is difficult because the current understanding of how the organisms are spread and where they live in the environment is limited, although this information is needed to design preventive measures. Growing these organisms from the environment is also difficult, because the culture medium becomes overgrown with other bacteria that also live in the environment, such as in soil and water. We aimed to improve the methods for growing these organisms from environmental sources, such as soil and water samples, for better understanding of important mycobacterial ecology.


Assuntos
Úlcera de Buruli/epidemiologia , Doenças Endêmicas , Microbiologia Ambiental , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/isolamento & purificação , Proteínas de Bactérias/genética , Técnicas Bacteriológicas/métodos , Meios de Cultura/química , Elementos de DNA Transponíveis , Descontaminação/métodos , Gana/epidemiologia , Humanos , Micobactérias não Tuberculosas/genética , Manejo de Espécimes/métodos
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