Research Articles

Permanent URI for this communityhttp://197.255.125.131:4000/handle/123456789/22010

A research article reports the results of original research, assesses its contribution to the body of knowledge in a given area, and is published in a peer-reviewed scholarly journal. The faculty publications through published and on-going articles/researches are captured in this community

Browse

Search Results

Now showing 1 - 10 of 20
  • Thumbnail Image
    Item
    TB-Diabetes Co-Morbidity in Ghana: The Importance of Mycobacterium Africanum Infection
    (PLOS, 2019) Asante-Poku, A.; Asare, P.; Yeboah-Manu, D.; et al.
    Background Diabetes Mellitus (DM) is a known risk factor for tuberculosis (TB) but little is known on TBDiabetes 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 byM. 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.
  • Thumbnail Image
    Item
    A Molecular and Epidemiological Study of Vibrio Cholerae Isolates from Cholera Outbreaks in Southern Ghana
    (PLOS, 2020) Danso, E.K.; Asare, P.; Yeboah-Manu, D.; et al.
    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
  • Thumbnail Image
    Item
    The Relevance of Genomic Epidemiology for Control of Tuberculosis in West Africa
    (Frontiers, 2021) Asare, P.; Asante-Poku, A.; Osei-Wusu, S.; Otchere, I.D.; Yeboah-Manu, D.
    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 tocmonitor 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.
  • Thumbnail Image
    Item
    Molecular epidemiology of bovine tuberculosis in Northern Ghana identifies several uncharacterized bovine spoligotypes and suggests possible zoonotic transmission
    (PLOS NEGLECTED TROPICAL DISEASES, 2022) Acquah, S.E.K.; Asare, P.; Danso, E.K; Tetteh, P.; Tetteh, A.Y.; Boateng, D.; Osei-Wusu, S.; Afum, T.; Ayamdooh, Y.I.; Akugre, E.A.; Samad, O.A.; Quaye, L.; Obiri-Danso, K.; Kock, R.; Asante-Poku, A.; Yeboah-Manu, D.
    Objective We conducted an abattoir-based cross-sectional study in the five administrative regions of Northern Ghana to determine the distribution of bovine tuberculosis (BTB) among slaughtered carcasses and identify the possibility of zoonotic transmission. Methods Direct smear microscopy was done on 438 tuberculosis-like lesions from selected cattle organs and cultured on Lowenstein-Jensen media. Acid-fast bacilli (AFB) isolates were confirmed as members of the Mycobacterium tuberculosis complex (MTBC) by PCR amplification of IS6110 and rpoß. Characterization and assignment into MTBC lineage and sublineage were done by spoligotyping, with the aid of the SITVIT2, miruvntrplus and mbovis. org databases. Spoligotype data was compared to that of clinical M. bovis isolates from the same regions to identify similarities. Results A total of 319/438 (72.8%) lesion homogenates were smear positive out of which, 84.6% (270/319) had microscopic grade of at least 1+ for AFB. Two hundred and sixty-five samples (265/438; 60.5%) were culture positive, of which 212 (80.0%) were MTBC. Approximately 16.7% (34/203) of the isolates with correctly defined spoligotypes were negative for IS6110 PCR but were confirmed by rpoß. Spoligotyping characterized 203 isolates as M. bovis (198, 97.5%), M. caprae (3, 1.5%), M. tuberculosis (Mtbss) lineage (L) 4 Cameroon sub-lineage, (1, 0.5%), and M. africanum (Maf) L6 (1, 0.5%). A total of 53 unique spoligotype patterns were identified across the five administrative regions (33 and 28 were identified as orphan respectively by the SITVIT2 and mbovis.org databases), with the most dominant spoligotype being SIT1037/ SB0944 (77/203, 37.93%). Analysis of the bovine and human M. bovis isolates showed 75% (3/4) human M. bovis isolates sharing the same spoligotype pattern with the bovine isolates. Conclusion Our study identified that approximately 29% of M. bovis strains causing BTB in Northern Ghana are caused by uncharacterized spoligotypes. Our findings suggest possible zoonotic transmission and highlight the need for BTB disease control in Northern Ghana.
  • Item
    Relevance of genomic diversity of Mycobacterium tuberculosis complex in Africa
    (Elsevier, 2022) Osei-Wusu, S.; Otchere, I.D.; Asare, P.; Ntoumi, F.; Zumla, A.; Asante-Poku, A.; Yeboah-Manu, D.
    Background: The diversity in the lineages of Mycobacterium tuberculosis complex (MTBC) was initially considered insignificant. However, comparative genomics analysis of MTBC have found genomic variation among the genotypes with potential phenotypic implications. Objective: Therefore, this viewpoint seeks to discuss the impact of the identified genotypic diversity on the physiology of MTBC and the potential implications on TB control. Results: Studies conducted in West Africa and other parts of Africa have unravelled the implications of the genomic diversity on phenotypes such as disease outcome, transmission dynamics and host immune response. The understanding of the phenotypic diversity among the different lineages of MTBC may be an important key to the fight against TB. Conclusion: The relevance of these differences has been observed in the design of new control tools such as diagnostics and anti-TB drugs/vaccines. This only points to the fact that the diversity in MTBC cannot be ignored in future studies especially clinical trials for new vaccines and new anti-TB drugs.
  • Item
    Genetic Analysis of TB Susceptibility Variants in Ghana Reveals Candidate Protective Loci in SORBS2 and SCL11A1 Genes
    (Frontier, 2022) Asante-Poku, A.; Morgan, P.; Osei-Wusu, S.; Aboagye, S.Y.; Asare, P.; Otchere, I.D.; Adadey, S.W.; Mnika, K.; Esoh, K.; Mawuta, K.H.; Arthur, N.; Forson, A.; Mazandu, G.K.; Wonkam, A.; Yeboah-Manu, D.
    Despite advancements made toward diagnostics, tuberculosis caused by Mycobacterium africanum (Maf) and Mycobacterium tuberculosis sensu stricto (Mtbss) remains a major public health issue. Human host factors are key players in tuberculosis (TB) outcomes and treatment. Research is required to probe the interplay between host and bacterial genomes. Here, we explored the association between selected human/host genomic variants and TB disease in Ghana. Paired host genotype datum and infecting bacterial isolate information were analyzed for associations using a multinomial logistic regression. Mycobacterium tuberculosis complex (MTBC) isolates were obtained from 191 TB patients and genotyped into different phylogenetic lineages by standard methods. Two hundred and thirty-five (235) nondisease participants were used as healthy controls. A selection of 29 SNPs from TB disease-associated genes with high frequency among African populations was assayed using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Using 26 high-quality SNPs across 326 case-control samples in an association analysis, we found a protective variant, rs955263, in the SORBS2 gene against both Maf and Mtb infections (PBH = 0.05; OR = 0.33; 95% CI = 0.32–0.34). A relatively uncommon variant, rs17235409 in the SLC11A1 gene was observed with an even stronger protective effect against Mtb infection (MAF = 0.06; PBH = 0.04; OR = 0.05; 95% CI = 0.04–0.05). These findings suggest SLC11A1 and SORBS2 as a potential protective gene of substantial interest for TB, which is an important pathogen in West Africa, and highlight the need for in-depth host-pathogen studies in West Africa.
  • Thumbnail Image
    Item
    Molecular epidemiology of Mycobacterium tuberculosis complex in the Volta Region of Ghana
    (PlOS ONE, 2021) Ameke, S.; Asare, P.; Aboagye, S.Y.; Otchere, I.D.; Osei-Wusu, S.; Yeboah-Manu, D.; Asante-Poku, A.
    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 spoligo type 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). We confirmed the importance of M. africanum lineages as a cause of TB in the Volta region of Ghana.
  • Thumbnail Image
    Item
    Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa
    (PLOS ONE, 2021) Osei-Wusu, S.; Otchere, I.D.; Morgan, P.; Musah, A.B.; Siam, I.M.; Asandem, D.; Afum, T.; Asare, P.; Asante-Poku, A.; Kusi, K.A.; Gagneux, S.; Yeboah-Manu, D.
    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 Lo¨wenstein–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.
  • Thumbnail Image
    Item
    Whole Genome Sequencing and Spatial Analysis Identifies Recent Tuberculosis Transmission Hotspots in Ghana
    (Frontiers in Medicine, 2020-05-19) Asare, P.; Otchere, I.D.; Bedeley, E.; Brites, D.; Loiseau, C.; Baddoo, N.A.; Asante-Poku, A.; Osei-Wusu, S.; Prah, D.A.; Borrell, S.; Reinhard, M.; Forson, A.; Koram, K.A.; Gagneux, S.; Yeboah-Manu, D.
    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.
  • Thumbnail Image
    Item
    Second-line anti-tuberculosis drug resistance testing in Ghana identifies the first extensively drug-resistant tuberculosis case
    (Infection and Drug Resistance, 2018-02) Osei-Wusu, S.; Omari, M.A.; Asante-Poku, A.; Otchere, I.D.; Asare, P.; Forson, A.; Otu, J.; Antonio, M.; Yeboah-Manu, D.
    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.