Browsing by Author "Antonio, M."
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Item Comparative phylogenomics of Streptococcus pneumoniae isolated from invasive disease and nasopharyngeal carriage from West Africans(2012-10-29) Donkor, E.S.; Stabler, R.A.; Hinds, J.; Adegbola, R.A.; Antonio, M.; Wren, B.WAbstract Background We applied comparative phylogenomics (whole genome comparisons of microbes using DNA microarrays combined with Bayesian-based phylogenies) to investigate S. pneumoniae isolates from West Africa, with the aim of providing insights into the pathogenicity and other features related to the biology of the organism. The strains investigated comprised a well defined collection of 58 invasive and carriage isolates that were sequenced typed and included eight different S. pneumoniae serotypes (1, 3, 5, 6A, 11, 14, 19 F and 23 F) of varying invasive disease potential. Results The core genome of the isolates was estimated to be 38% and was mainly represented by gene functional categories associated with housekeeping functions. Comparison of the gene content of invasive and carriage isolates identified at least eleven potential genes that may be important in virulence including surface proteins, transport proteins, transcription factors and hypothetical proteins. Thirteen accessory regions (ARs) were also identified and did not show any loci association with the eleven virulence genes. Intraclonal diversity (isolates of the same serotype and MLST but expressing different patterns of ARs) was observed among some clones including ST 1233 (serotype 5), ST 3404 (serotype 5) and ST 3321 (serotype 14). A constructed phylogenetic tree of the isolates showed a high level of heterogeneity consistent with the frequent S. pneumoniae recombination. Despite this, a homogeneous clustering of all the serotype 1 strains was observed. Conclusions Comparative phylogenomics of invasive and carriage S. pneumoniae isolates identified a number of putative virulence determinants that may be important in the progression of S. pneumoniae from the carriage phase to invasive disease. Virulence determinants that contribute to S. pneumoniae pathogenicity are likely to be distributed randomly throughout its genome rather than being clustered in dedicated loci or islands. Compared to other S. pneumoniae serotypes, serotype 1 appears most genetically uniform.Item Comparative phylogenomics of Streptococcus pneumoniae isolated from invasive disease and nasopharyngeal carriage from West Africans(2012-10-29) Donkor, E.S.; Stabler, R.A.; Hinds, J.; Adegbola, R.A.; Antonio, M.; Wren, B.W.Background: We applied comparative phylogenomics (whole genome comparisons of microbes using DNA microarrays combined with Bayesian-based phylogenies) to investigate S. pneumoniae isolates from West Africa, with the aim of providing insights into the pathogenicity and other features related to the biology of the organism. The strains investigated comprised a well defined collection of 58 invasive and carriage isolates that were sequenced typed and included eight different S. pneumoniae serotypes (1, 3, 5, 6A, 11, 14, 19 F and 23 F) of varying invasive disease potential.Results: The core genome of the isolates was estimated to be 38% and was mainly represented by gene functional categories associated with housekeeping functions. Comparison of the gene content of invasive and carriage isolates identified at least eleven potential genes that may be important in virulence including surface proteins, transport proteins, transcription factors and hypothetical proteins. Thirteen accessory regions (ARs) were also identified and did not show any loci association with the eleven virulence genes. Intraclonal diversity (isolates of the same serotype and MLST but expressing different patterns of ARs) was observed among some clones including ST 1233 (serotype 5), ST 3404 (serotype 5) and ST 3321 (serotype 14). A constructed phylogenetic tree of the isolates showed a high level of heterogeneity consistent with the frequent S. pneumoniae recombination. Despite this, a homogeneous clustering of all the serotype 1 strains was observed.Conclusions: Comparative phylogenomics of invasive and carriage S. pneumoniae isolates identified a number of putative virulence determinants that may be important in the progression of S. pneumoniae from the carriage phase to invasive disease. Virulence determinants that contribute to S. pneumoniae pathogenicity are likely to be distributed randomly throughout its genome rather than being clustered in dedicated loci or islands. Compared to other S. pneumoniae serotypes, serotype 1 appears most genetically uniform. © 2012 Donkor et al.; licensee BioMed Central Ltd.Item A cross-sectional study of tuberculosis drug resistance among previously treated patients in a tertiary hospital in Accra, Ghana: public health implications of standardized regimens(BMC Infectious Diseases, 2018-04) Forson, A.; Kwara, A.; Kudzawu, S.; Omari, M.; Otu, J.; Gehre, F.; de Jong, B.; Antonio, M.Background Mycobacterium tuberculosis drug resistance is a major challenge to the use of standardized regimens for tuberculosis (TB) therapy, especially among previously treated patients. We aimed to investigate the frequency and pattern of drug resistance among previously treated patients with smear-positive pulmonary tuberculosis at the Korle-Bu Teaching Hospital Chest Clinic, Accra. Methods This was a cross-sectional survey of mycobacterial isolates from previously treated patients referred to the Chest Clinic Laboratory between October 2010 and October 2013. The Bactec MGIT 960 system for mycobactrerial culture and drug sensitivity testing (DST) was used for sputum culture of AFB smear-positive patients with relapse, treatment failure, failure of smear conversion, or default. Descriptive statistics were used to summarize patient characteristics, and frequency and patterns of drug resistance. Results A total of 112 isolates were studied out of 155 from previously treated patients. Twenty contaminated (12.9%) and 23 non-viable isolates (14.8%) were excluded. Of the 112 studied isolates, 53 (47.3%) were pan-sensitive to all first-line drugs tested Any resistance (mono and poly resistance) to isoniazid was found in 44 isolates (39.3%) and any resistance to streptomycin in 43 (38.4%). Thirty-one (27.7%) were MDR-TB. Eleven (35.5%) out of 31 MDR-TB isolates were pre-XDR. MDR-TB isolates were more likely than non-MDR isolates to have streptomycin and ethambutol resistance. Conclusions The main findings of this study were the high prevalence of MDR-TB and streptomycin resistance among previously treated TB patients, as well as a high prevalence of pre-XDR-TB among the MDR-TB patients, which suggest that first-line and second-line DST is essential to aid the design of effective regimens for these groups of patients in Ghana.Item High Levels of Recombination among Streptococcus pneumoniae Isolates from the Gambia(® mbio.asm.org, 2011) Donkor, E.S.; Bishop, C.J.; Antonio, M.; et al.We carried out multilocus sequence typing (MLST) on 148 pneumococcal carriage isolates collected from children <24 months old in the Upper River Division, the Gambia. MLST revealed a diverse population. Seventy-six different sequence types (STs) were found, the most common of which were 802 and 919, associated with 23F and 6A serotypes, respectively. Com parison with the MLST database showed that only 11 of the STs found in the present sample had been reported outside Africa. Six STs showed evidence of capsular switching (172, 802, 847, 1730, 1736, and 1737). Serotype switches were confirmed by mi croarrays that detected capsule genes. Of isolates analyzed by using microarrays, 40/69 (58%) harbored the tetM resistance deter minant. A statistical genetic analysis to detect recombination found that 49/144 (34%) isolates showed significant (P < 0.05) evi dence of admixture, which is greater than that observed in similar samples from the United Kingdom (5%) and Finland (2%). We hypothesize that large amounts of admixture could reflect the high prevalence of multiple carriage in this region, leading to more opportunities for homologous recombination between strains. This could have consequences for the population response to conjugate vaccination. IMPORTANCE The population structure of the pneumococcus in sub-Saharan Africa has barely been studied despite the high lev els of morbidity and mortality due to pneumococcal disease in this region. We report the largest sample to date from carriage in sub-Saharan Africa to be typed by sequencing (multilocus sequence typing [MLST]) and microarray analysis. The results clearly show that the population is highly distinct and divergent from others studied in the United States and Europe. Moreover, in con trast with samples from developed countries, the population contains a high proportion of isolates showing a history of homolo gous recombination, which shuffles genetic information into new combinations and can generate drug-resistant and vaccine escape strains. This is likely to have important consequences for the evolutionary response of the pneumococcal population to conjugate vaccination targeting a subset of pneumococcal serotypes, which is under way in the Gambia and other countries.Item Hospital-based Surveillance for Pediatric Bacterial Meningitis in the Era of the 13-Valent Pneumococcal Conjugate Vaccine in Ghana(Clinical Infectious Diseases, 2019-09-05) Renner, L.A.; Usuf, E.; Mohammed, N.I.; Ansong, D.; Dankwah, T.; Kusah, J.T.; Owusu, S.K.; Awunyo, M.; Arhin, B.; Addo, Y.; Asamoah, J.; Biey, J.N.; Ndow, P.S.; Worwui, A.; Senghore, M.; Ntsama, B.; Mwenda, J.M.; Diamenu, S.K.; Adams, B.K.; Antonio, M.Background Global surveillance for vaccine preventable invasive bacterial diseases has been set up by the World Health Organization to provide disease burden data to support decisions on introducing pneumococcal conjugate vaccine (PCV). We present data from 2010 to 2016 collected at the 2 sentinel sites in Ghana. Methods Data were collected from children <5 years of age presenting at the 2 major teaching hospitals with clinical signs of meningitis. Cerebrospinal fluid specimens were collected and tested first at the sentinel site laboratory with conventional microbiology methods and subsequently with molecular analysis, at the World Health Organization Regional Reference Laboratory housed at the Medical Research Council Unit The Gambia, for identification of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, the 3 most common bacteria causing meningitis. Results There were 4008 suspected cases of meningitis during the surveillance period, of which 31 (0.8%) were laboratory confirmed. Suspected meningitis cases decreased from 923 in 2010 to 219 in 2016. Of 3817 patients with available outcome data, 226 (5.9%) died. S. pneumoniae was the most common bacterial pathogen, accounting for 68.5% of confirmed cases (50 of 73). H. influenzae and N. meningitidis accounted for 6.8% (5 of 73) and 21.9% (16 of 73), respectively. The proportion of pneumococcal vaccine serotypes causing meningitis decreased from 81.3% (13 of 16) before the introduction of 13-valent PCV (2010–2012) to 40.0% (8 of 20) after its introduction (2013–2016). Conclusions Cases of suspected meningitis decreased among children <5 years of age between 2010 and 2016, with declines in the proportion of vaccine-type pneumococcal meningitis after the introduction of 13-valent PCV in Ghana.Item Population Biology of Streptococcus pneumonia in West Africa: Multi-locus Sequence Typing of Stereotypes That Exhibit Different Predisposition to Invasive Disease and Carriage(Public Library of Science, 2013) Donkor, E.S.; Adegbola, R.A.; Wren, B.W.; Antonio, M.Background: Little is known about the population biology of Streptococcus pneumonia in developing countries, although the majority of pneumococcal infections occur in this setting. The aim of the study was to apply MLST to investigate the population biology of S. pneumonia in West Africa. Methods: Seventy three invasive and carriage S. pneumonia isolates from three West African countries including The Gambia, Nigeria and Ghana were investigated. The isolates covered seven stereotypes (1, 3, 5, 6A, 11, 14, 23F) and were subjected to multi-locus sequence typing and antibiotic susceptibility testing. Results: Overall, 50 different sequence types (STs) were identified, of which 38% (29) were novel. The most common ST was a novel clone-ST 4012 (6.5%), and some clones including STs 913, 925, 1737, 2160 and 3310 appeared to be specific to the study region. Two STs including ST 63 and ST 4012 were associated with multiple stereotypes indicating a history of stereotype switching. ST 63 was associated with stereotypes 3 and 23F, while ST 4012 was associated with stereotypes 6A and 23. eBURST analyses using the stringent 6/7 identical loci definition grouped the 50 STs into 5 clonal complexes and 65 singletons, expressing a high level of genetic diversity among the isolates. Compared to the other stereotypes, stereotypes 1 and 5 isolates appeared to be more clonal. Internationally recognized antibiotic resistant clones of S. pneumonia were generally absent in the population investigated and the only multi-drug resistant isolate identified (1/66) belong to the Pneumococcal Epidemiology Network clone ST 63. Conclusions: The pneumococcal population in West Africa is quite divergent, and stereotypes that are common in invasive disease (such as stereotypes 1 and 5) are more likely to be clonal than stereotypes that are common in carriage.Item Population Biology of Streptococcus pneumoniae in West Africa: Multilocus Sequence Typing of Serotypes That Exhibit Different Predisposition to Invasive Disease and Carriage(2013-01-16) Donkor, E.S.; Adegbola, R.A.; Wren, B.W.; Antonio, M.Background: Little is known about the population biology of Streptococcus pneumoniae in developing countries, although the majority of pneumococcal infections occur in this setting. The aim of the study was to apply MLST to investigate the population biology of S. pneumoniae in West Africa. Methods: Seventy three invasive and carriage S. pneumoniae isolates from three West African countries including The Gambia, Nigeria and Ghana were investigated. The isolates covered seven serotypes (1, 3, 5, 6A, 11, 14, 23F) and were subjected to multilocus sequence typing and antibiotic susceptibility testing. Results: Overall, 50 different sequence types (STs) were identified, of which 38% (29) were novel. The most common ST was a novel clone-ST 4012 (6.5%), and some clones including STs 913, 925, 1737, 2160 and 3310 appeared to be specific to the study region. Two STs including ST 63 and ST 4012 were associated with multiple serotypes indicating a history of serotype switching. ST 63 was associated with serotypes 3 and 23F, while ST 4012 was associated with serotypes 6A and 23. eBURST analyses using the stringent 6/7 identical loci definition grouped the 50 STs into 5 clonal complexes and 65 singletons, expressing a high level of genetic diversity among the isolates. Compared to the other serotypes, serotypes 1 and 5 isolates appeared to be more clonal. Internationally recognized antibiotic resistant clones of S. pneumoniae were generally absent in the population investigated and the only multidrug resistant isolate identified (1/66) belong to the Pneumocococcal Epidemiology Network clone ST 63. Conclusions: The pneumococcal population in West Africa is quite divergent, and serotypes that are common in invasive disease (such as serotypes 1 and 5) are more likely to be clonal than serotypes that are common in carriage. © 2013 Donkor et al.Item Population Biology of Streptococcus pneumoniae in West Africa: Multilocus Sequence Typing of Serotypes That Exhibit Different Predisposition to Invasive Disease and Carriage(PLOS ONE, 2013) Donkor, E.S.; Adegbola, R.A.; Wren, B.W.; Antonio, M.Background: Little is known about the population biology of Streptococcus pneumoniae in developing countries, although the majority of pneumococcal infections occur in this setting. The aim of the study was to apply MLST to investigate the population biology of S. pneumoniae in West Africa. Methods: Seventy three invasive and carriage S. pneumoniae isolates from three West African countries including The Gambia, Nigeria and Ghana were investigated. The isolates covered seven serotypes (1, 3, 5, 6A, 11, 14, 23F) and were subjected to multilocus sequence typing and antibiotic susceptibility testing. Results: Overall, 50 different sequence types (STs) were identified, of which 38% (29) were novel. The most common ST was a novel clone-ST 4012 (6.5%), and some clones including STs 913, 925, 1737, 2160 and 3310 appeared to be specific to the study region. Two STs including ST 63 and ST 4012 were associated with multiple serotypes indicating a history of serotype switching. ST 63 was associated with serotypes 3 and 23F, while ST 4012 was associated with serotypes 6A and 23. eBURST analyses using the stringent 6/7 identical loci definition grouped the 50 STs into 5 clonal complexes and 65 singletons, expressing a high level of genetic diversity among the isolates. Compared to the other serotypes, serotypes 1 and 5 isolates appeared to be more clonal. Internationally recognized antibiotic resistant clones of S. pneumoniae were generally absent in the population investigated and the only multidrug resistant isolate identified (1/66) belong to the Pneumocococcal Epidemiology Network clone ST 63. Conclusions: The pneumococcal population in West Africa is quite divergent, and serotypes that are common in invasive disease (such as serotypes 1 and 5) are more likely to be clonal than serotypes that are common in carriage.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.Item Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum(Tuberculosis, 2017-05) Ofori-Anyinam, B.; Dolganov, G.; Van, T.; Davis, J.L.; Walter, N.D.; Garcia, B.J.; Voskuil, M.; Fissette, K.; Diels, M.; Driesen, M.; Meehan, C.J.; Yeboah-Manu, D.; Coscolla, M.; Gagneux, S.; Antonio, M.; Schoolnik, G.; Gehre, F.; de Jong, B.C.Mycobacterium africanum lineage (L) 6 is an important pathogen in West Africa, causing up to 40% of pulmonary tuberculosis (TB). The biology underlying the clinical differences between M. africanum and M. tuberculosis sensu stricto remains poorly understood. We performed ex vivo expression of 2179 genes of the most geographically dispersed cause of human TB, M. tuberculosis L4 and the geographically restricted, M. africanum L6 directly from sputa of 11 HIV-negative TB patients from The Gambia who had not started treatment. The DosR regulon was the most significantly decreased category in L6 relative to L4. Further, we identified nonsynonymous mutations in major DosR regulon genes of 44 L6 genomes of TB patients from The Gambia and Ghana. Using Lebek's test, we assessed differences in oxygen requirements for growth. L4 grew only at the aerobic surface while L6 grew throughout the medium. In the host, the DosR regulon is critical for M. tuberculosis in adaptation to oxygen limitation. However, M. africanum L6 appears to have adapted to growth under hypoxic conditions or to different biological niches. The observed under expression of DosR in L6 fits with the genomic changes in DosR genes, microaerobic growth and the association with extrapulmonary disease. © 2017 The AuthorsItem A Streptococcus pneumoniae lineage usually associated with pneumococcal conjugate vaccine (PCV) serotypes is the most common cause of serotype 35B invasive disease in South Africa, following routine use of PCV(Microbial Genomics, 2022) Ndlangisa, K.M.; du Plessis, M.; Lo, S.; de Gouveia, L.; Chaguza, C.; Antonio, M.; Kwambana- Adams, B.; Cornick, J.; Everett, D.B.; Dagan, R.; Hawkins, P.A.; Beall, B.; Corso, A.; Almeida, S.C.G.; Ochoa, T.J.; Obaro, S.; Shakoor, S.; Donkor, E.S.; Gladstone, R.A.; Ho, P.L.; Paragi, M.; Doiphode, S.; Srifuengfung, S.; Ford, R.; Moïsi, J.; Saha, S.K.; Bigogo, G.; Sigauque, B.; Eser, Ö .K.; Elmdaghri, N.; Titov, L.; Turner, P.; Kumar, K.L.R.; Kandasamy, R.; Egorova, E.; IP, M.; Breiman, R.F.; Klugman, K.P.; McGee, L.; Bentley, S.D.; von Gottberg, A.; The Global Pneumococcal Sequencing ConsortiumPneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emer- gence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in 2005–2014 were characterized by whole-genome sequencing (WGS). Multi-locus sequence types and global pneumococcal sequence clusters (GPSCs) were derived from WGS data of 63 35B isolates obtained in 2005–2014. A total of 262 isolates that belong to GPSC5 (115 isolates from South Africa and 147 from other countries) that were sequenced as part of the global pneumococcal sequencing (GPS) project were included for com- parison. Serotype 35B isolates from South Africa were differentiated into seven GPSCs and GPSC5 was most common (49 %, 31/63). While 35B was the most common serotype among GPSC5/CC172 isolates in South Africa during the PCV13 period (66 %, 29/44), 23F was the most common serotype during both the pre-PCV (80 %, 37/46) and PCV7 period (32 %, 8/25). Serotype 35B represented 15 % (40/262) of GPSC5 isolates within the global GPS database and 75 % (31/40) were from South Africa. The predominance of the GPSC5 lineage within non-vaccine serotype 35B, is possibly unique to South Africa and warrants further molecular surveillance of pneumococci.Item Towards host-directed therapies for tuberculosis(Nature Reviews Drug Discovery, 2015-08) Wejse, C.; Petersen, E.; Kaleebu, P.; Oliver, M.; Craig, G.; Corrah, T.; Tientcheu, L.; Antonio, M.; Rao, M.; McHugh, T.D.; Sheikh, A.; Zumla, A.; Maeurer, M.; Chakaya, J.; Hoelscher, M.; Ntoumi, F.; Rustomjee, R.; Vilaplana, C.; Yeboah-Manu, D.; Rasolofo, V.; Munderi, P.; Singh, N.; Aklillu, E.; Padayatchi, N.; Macete, E.; Kapata, N.; Mulenga, M.; Kibiki, G.; Mfinanga, S.; Nyirenda, T.; Maboko, L.; Garcia-Basteiro, A.; Rakotosamimanana, N.; Bates, M.; Mwaba, P.; Reither, K.; Gagneux, S.; Edwards, S.; Mfinanga, E.; Abdulla, S.; Cardona, P.-J; Russell, J.B.W.; Gant, V.; Noursadeghi, M.; Elkington, P.; Bonnet, M.; Menendez, C.; Dieye, T.N.; Diarra, B.; Maiga, A.; Aseffa, A.; Parida, S.; Ippolito, G.; Ramjee, G.; Kaufmann, S.H.E.; Churchyard, G.; Steyn, A.; Grobusch, M.; Sanne, I.; Martinson, N.; Madansein, R.; Wilkinson, R.J.; Mayosi, B.; Schito, M.; Wallis, R.S.The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies