EDCTP Alumni Network

RIA2018D-2511

Source of funding:

European and Developing Countries Clinical Trials Partnership (EDCTP)

2999989.25

Co-Applicant

2020-01-01

2024-01-01

Ssengooba, W.
Kirenga, B.
Muwonge, C.
Kyaligonza, S.
Kasozi, S.
Mugabe, F.
Boeree, M.
Joloba, M.
Okwera, A.

2016-01-01

African Health Sciences

DOI: 10.4314/ahs.v16i4.28
EID: 2-s2.0-85014796386

Asiimwe BB , author
Bagyenzi GB , author
Ssengooba W , author
Mumbowa F , author
Mboowa G , author
Wajja A , author
Mayanja-Kiiza H , author
Musoke PM , author
Wobudeya E , author
Kallenius G , author
Joloba ML , author

2013-01-01

DOI: 10.1186/1471-2334-13-88
PMID: 23413873
PMC: PMC3599115

Willy Ssengooba , author
Lydia Nakiyingi , author
Edgar Kigozi , author
Yukari C. Manabe , author
Moses L. Joloba , author

2019-04-29

DOI: 10.21203/rs.2.9331/v1

2022-01-12

Microbiology spectrum

Not all patients produce sputum, yet most available TB tests use sputum. We investigated the utility of a novel RNA-based quantitative test, the tuberculosis molecular bacterial load assay (TB-MBLA), for the detection and quantification of Mycobacterium tuberculosis in stool. Stools from 100 adult individuals were treated with OMNIgene-sputum reagent and tested using Xpert MTB/RIF ultra (Xpert ultra), auramine O smear microscopy (smear), mycobacterial growth indicator tube (MGIT), and Lowenstein-Jensen (LJ) cultures. The remaining portions were frozen at -20°C and later tested by TB-MBLA. MGIT sputum culture was used as a TB confirmatory test and reference for stool tests. Sixty-one of 100 participants were already confirmed TB positive by MGIT sputum culture, 20 (33%) of whom were HIV coinfected. TB-MBLA detected M. tuberculosis in 57/100 stool samples, including 49 already confirmed for TB. The mean bacterial load measured by stool TB-MBLA was 5.67 ± 1.7 log₁₀ estimated CFU (eCFU) per mL in HIV-coinfected participants, which was higher than the 4.83 ± 1.59 log₁₀ eCFU per mL among the HIV-negative participants (P = 0.04). The sensitivities (95% confidence intervals [CI]) of stool assays were 80% (68 to 89) and 90% (79 to 98) for TB-MBLA and Xpert ultra, which were both higher than the 44% (32 to 58), 64% (51 to 76), and 62% (45 to 77) for smear, MGIT, and Lowenstein-Jensen (LJ) stool cultures, respectively. The specificity (95% CI) of stool assays was highest for smear, at 97% (87 to 100), followed by Xpert ultra at 91% (76 to 98), TB-MBLA at 79% (63 to 90), LJ at 80% (64 to 91), and MGIT at 62% (45 to 77). Twenty-six percent of MGIT and 21% of LJ stool cultures were indeterminate due to contamination. Detection and quantification of viable M. tuberculosis bacilli in stool raises its utility as an alternative to sputum as a sample type for TB diagnosis. IMPORTANCE This paper highlights the value of stool as a sample type for diagnosis of tuberculosis. While other studies have used DNA-based assays like the Xpert MTB/RIF and culture to detect Mycobacterium tuberculosis in stool, this is the first study that has applied TB-MBLA, an RNA-based assay, to quantify TB bacteria in stool. The high microbial density and diversity in stool compromises the specificity and sensitivity of culture-based tests due to overgrowth of non-M. tuberculosis flora. Consequently, TB-MBLA becomes the most sensitive and specific test for the detection and quantification of viable TB bacteria in stool. Most crucially, this study raises the possibility of a nonsputum alternative sample type for diagnosis of TB among people who have difficulty in producing sputum.

PMID: 35019686
DOI: 10.1128/spectrum.02100-21

2021-02-23

Journal of medical microbiology

Introduction. Drug resistant tuberculosis remains a worldwide problem that requires prompt diagnosis.Hypothesis/Gap statement. The WHO recommended direct, rapid Xpert MTB/RIF is prohibitively costly, therefore, there is a need to validate a rapid, affordable DST for use in low- and middle-income settings.Aim. The technical performance and time to results of a simple, direct microscopy-based slide DST (SDST) assay for diagnosis of rifampicin-resistant TB was evaluated in Uganda.Methodology. Sputum samples from 122 smear-positive re-treatment TB patients presenting to the TB treatment centre at Uganda's National Referral Hospital, Mulago, Kampala, Uganda were examined. The sputum samples were tested by the direct SDST which was compared to the indirect Lowenstein Jensen Proportion Method (LJDST) method as the gold standard. The time to results was defined as the time from DST setting to results interpretation. The results were further analysed for sensitivity and specificity as well as agreement between LJDST and SDST for rifampicin resistance determination.Results. A total of 117 smear positive sputum samples with valid results for both tests were compared. The median time to results for SDST was 14 days with an interquartile range (IQR) of 10-14 days compared to 60 days with IQR of 60-75 days for LJDST. The number for rifampicin resistance by the gold standard LJDST was 26. The SDST had a sensitivity of 96 % (95 %; CI 81-99 %) and a specificity of 97.8 % (95 %; CI 93-100 %). The Positive Predictive and Negative Predictive values for SDST were 92.3 % (95 %; CI 76.8-99 %) and 98.9 % (95 %; CI 94-100 %), respectively. The kappa agreement between SDST and LJDST was 92.3 %.Conclusion. The SDST was found to be a rapid and accurate direct test for the detection of rifampicin resistance among retreatment TB cases in low-income settings.

PMID: 33625351
DOI: 10.1099/jmm.0.001331

Muttamba W , author
Ssengooba W , author
Sekibira R , author
Kirenga B , author
Katamba A , author
Joloba M , author

2018-01-01

PloS one

PMID: 29566056
PMC: PMC5864038
DOI: 10.1371/journal.pone.0194741

2021-08-01

Natural Product Communications

DOI: 10.1177/1934578x211035851
Part of ISSN: 1934-578X
Part of ISSN: 1555-9475

Dharan, N.J.
Amisano, D.
Mboowa, G.
Ssengooba, W.
Blakemore, R.
Kubiak, R.W.
Armstrong, D.T.
Jones, M.
Manabe, Y.C.
Joloba, M.L.
Ellner, J.J.
Dorman, S.E.
Alland, D.

2015-01-01

Journal of Clinical Microbiology

DOI: 10.1128/JCM.03619-14
EID: 2-s2.0-84925249889

Ssengooba, W.
Lukoye, D.
Meehan, C.J.
Kateete, D.P.
Joloba, M.L.
De Jong, B.C.
Cobelens, F.G.
Van Leth, F.

2017-01-01

International Journal of Tuberculosis and Lung Disease

DOI: 10.5588/ijtld.16.0544
EID: 2-s2.0-85018599860

Nakiyingi, L.
Nonyane, B.A.S.
Ssengooba, W.
Kirenga, B.J.
Nakanjako, D.
Lubega, G.
Byakika-Kibwika, P.
Joloba, M.L.
Ellner, J.J.
Dorman, S.E.
Mayanja-Kizza, H.
Manabe, Y.C.

2015-01-01

PLoS ONE

DOI: 10.1371/journal.pone.0133756
EID: 2-s2.0-84941687000

2020-12-01

Nature Communications

DOI: 10.1038/s41467-020-16626-6
Part of ISSN: 2041-1723

2019-12-01

Scientific Reports

DOI: 10.1038/s41598-019-48401-z
Part of ISSN: 2045-2322

2021-12-01

Journal of Clinical Tuberculosis and Other Mycobacterial Diseases

DOI: 10.1016/j.jctube.2021.100286
Part of ISSN: 2405-5794

Ssengooba, W.
de Jong, B.C.
Joloba, M.L.
Cobelens, F.G.
Meehan, C.J.

2016-01-01

BMC Infectious Diseases

DOI: 10.1186/s12879-016-1737-2
EID: 2-s2.0-84982793419

Nantongo, J.M.
Wobudeya, E.
Mupere, E.
Joloba, M.
Ssengooba, W.
Kisembo, H.N.
Lubega, I.R.
Musoke, P.M.

2013-01-01

BMC Pediatrics

DOI: 10.1186/1471-2431-13-16
EID: 2-s2.0-84873035111

Manson, A.L.
Cohen, K.A.
Abeel, T.
Desjardins, C.A.
Armstrong, D.T.
Barry, C.E.
Brand, J.
Chapman, S.B.
Cho, S.-N.
Gabrielian, A.
Gomez, J.
Jodals, A.M.
Joloba, M.
Jureen, P.
Lee, J.S.
Malinga, L.
Maiga, M.
Nordenberg, D.
Noroc, E.
Romancenco, E.
Salazar, A.
Ssengooba, W.
Velayati, A.A.
Winglee, K.
Zalutskaya, A.
Via, L.E.
Cassell, G.H.
Dorman, S.E.
Ellner, J.
Farnia, P.
Galagan, J.E.
Rosenthal, A.
Crudu, V.
Homorodean, D.
Hsueh, P.-R.
Narayanan, S.
Pym, A.S.
Skrahina, A.
Swaminathan, S.
Van Der Walt, M.
Alland, D.
Bishai, W.R.
Cohen, T.
Hoffner, S.
Birren, B.W.
Earl, A.M.

2017-01-01

Nature Genetics

DOI: 10.1038/ng.3767
EID: 2-s2.0-85009773526

Muttamba W , author
Kirenga B , author
Ssengooba W , author
Sekibira R , author
Katamba A , author
Joloba ML , author

2018-12-01

The American journal of tropical medicine and hygiene

PMID: 30594259
DOI: 10.4269/ajtmh.18-0281

Willy Ssengooba , author
Jean de Dieu Iragena , author
Lydia Nakiyingi , author
Serestine Mujumbi , author
Eric Wobudeya , author
Robert Mboizi , author
David Boulware , author
David B. Meya , author
Louise Choo , author
Angela M. Crook , author
Kristen Lebeau , author
Moses Joloba , author
Anne-Marie Demers , author
Fiona V. Cresswell , author
Diana M. Gibb , author
Melissa B. Miller , editor

2020-08-24

Journal of Clinical Microbiology

DOI: 10.1128/JCM.00410-20

Gerald Mboowa , author
Carolyn Namaganda , author
Willy Ssengooba , author

2014-01-01

BMC Infectious Diseases

DOI: 10.1186/1471-2334-14-481

Shah M , author
Ssengooba W , author
Armstrong D , author
Nakiyingi L , author
Holshouser M , author
Ellner JJ , author
Joloba M , author
Manabe YC , author
Dorman SE , author

2014-03-01

DOI: 10.1097/QAD.0000000000000264
PMID: 24637544

Waako J , author
Verver S , author
Wajja A , author
Ssengooba W , author
Joloba ML , author
Colebunders R , author
Musoke P , author
Mayanja-Kizza H , author

2013-07-01

DOI: 10.1186/1471-2334-13-349
PMID: 23890464
PMC: PMC3735406

2019-04-01

DOI: 10.1136/bmjgh-2019-edc.107
Part of ISSN: 2059-7908

2021-05-13

PloS one

Introduction

Despite the limited evidence for its effectiveness, thermal screening at points of entry has increasingly become a standard protocol in numerous parts of the globe in response to the COVID-19 pandemic. We sought to determine the effectiveness of thermal screening as a key step in diagnosing COVID-19 in a resource-limited setting.

Materials and methods

This was a retrospective cross-sectional study based on a review of body temperature and Xpert Xpress SARS CoV-2 test results records for truck drivers entering Uganda through Mutukula between 15th May and 30th July 2020. All records missing information for body temperature, age, gender, and Xpert Xpress SARS CoV-2 status were excluded from the data set. A data set of 7,181 entries was used to compare thermal screening and Xpert Xpress SARS CoV-2 assay test results using the diagnostic statistical test in STATAv15 software. The prevalence of COVID-19 amongst the truck drivers based on Xpert Xpress SARS CoV-2 assay results was determined. The sensitivity, specificity, positive predictive value, negative predictive value, positive and negative Likelihood ratios were obtained using Xpert Xpress SARS CoV-2 assay as the gold standard.

Results

Based on our gold standard test, the proportion of persons that tested positive for COVID-19 was 6.7% (95% CI: 6.1-7.3). Of the 7,181 persons that were thermally screened, 6,844 (95.3%) were male. The sample median age was 38 years (interquartile range, IQR: 31-45 years). The median body temperature was 36.5°C (IQR: 36.3-36.7) and only n (1.2%) had a body temperature above 37.5°C. The sensitivity and specificity of thermal screening were 9.9% (95% CI: 7.4-13.0) and 99.5% (95% CI: 99.3-99.6) respectively. The positive and negative predictive values were 57.8 (95% CI: 46.5-68.6) and 93.9 (95% CI: 93.3-94.4) respectively. The positive and negative Likelihood Ratios (LRs) were 19 (95% CI: 12.4-29.1) and 0.9 (95% CI: 0.88-0.93) respectively.

Conclusion

In this study population, the use of Thermal screening alone is ineffective in the detection of potential COVID-19 cases at point of entry. We recommend a combination of screening tests or additional testing using highly sensitive molecular diagnostics such as Polymerase Chain Reaction.

PMID: 33983997
PMC: PMC8118319
DOI: 10.1371/journal.pone.0251150

2020-05-15

PloS one

INTRODUCTION:Susceptibility testing for pyrazinamide (PZA), a cornerstone anti-TB drug is not commonly done in Uganda because it is expensive and characterized with technical difficulties thus resistance to this drug is less studied. Resistance is commonly associated with mutations in the pncA gene and its promoter region. However, these mutations vary geographically and those conferring phenotypic resistance are unknown in Uganda. This study determined the prevalence of PZA resistance and its association with pncA mutations. MATERIALS AND METHODS:Using a cross-sectional design, archived isolates collected during the Uganda national drug resistance survey between 2008-2011 were sub-cultured. PZA resistance was tested by BACTEC Mycobacterial Growth Indicator Tube (MGIT) 960 system. Sequence reads were downloaded from the NCBI Library and bioinformatics pipelines were used to screen for PZA resistance-conferring mutations. RESULTS:The prevalence of phenotypic PZA resistance was found to be 21%. The sensitivity and specificity of pncA sequencing were 24% (95% CI, 9.36-45.13%) and 100% (73.54% - 100.0%) respectively. We identified four mutations associated with PZA phenotypic resistance in Uganda; K96R, T142R, R154G and V180F. CONCLUSION:There is a high prevalence of phenotypic PZA resistance among TB patients in Uganda. The low sensitivity of pncA gene sequencing confirms the already documented discordances suggesting other mechanisms of PZA resistance in Mycobacterium tuberculosis.

PMID: 32413052
DOI: 10.1371/journal.pone.0232543

Shah M , author
Dowdy D , author
Joloba M , author
Ssengooba W , author
Manabe YC , author
Ellner J , author
Dorman SE , author

2013-11-01

PMID: 25119690
PMC: PMC4133735
DOI: 10.1097/QAD.0000000000000008

2022-03-01

The New England journal of medicine

Background

Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen.

Methods

We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment.

Results

From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups).

Conclusions

Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.).

PMID: 35263517
DOI: 10.1056/nejmoa2104535

Lee J , author
Armstrong DT , author
Ssengooba W , author
Park JA , author
Yu Y , author
Mumbowa F , author
Namaganda C , author
Mboowa G , author
Nakayita G , author
Armakovitch S , author
Chien G , author
Cho SN , author
Via LE , author
Barry CE 3rd , author
Ellner JJ , author
Alland D , author
Dorman SE , author
Joloba ML , author

2014-01-01

DOI: 10.1128/AAC.01209-13
PMID: 24100497

2021-09-15

Expert Review of Anti-infective Therapy

DOI: 10.1080/14787210.2021.1967145
Part of ISSN: 1478-7210
Part of ISSN: 1744-8336

Nakiyingi L , author
Nakanwagi P , author
Briggs J , author
Agaba T , author
Mubiru F , author
Mugenyi M , author
Ssengooba W , author
Joloba ML , author
Manabe YC , author

2018-02-01

BMC infectious diseases

PMID: 29466946
PMC: PMC5822669
DOI: 10.1186/s12879-018-2992-1

2021-06-01

Open Forum Infectious Diseases

Ssengooba, W.
Meehan, C.J.
Lukoye, D.
Kasule, G.W.
Musisi, K.
Joloba, M.L.
Cobelens, F.G.
de Jong, B.C.

2016-01-01

Infection, Genetics and Evolution

DOI: 10.1016/j.meegid.2016.02.019
EID: 2-s2.0-84959352626

Muwonge, A.
Malama, S.
Johansen, T.B.
Kankya, C.
Biffa, D.
Ssengooba, W.
Godfroid, J.
Djønne, B.
Skjerve, E.

2013-01-01

PLoS ONE

DOI: 10.1371/journal.pone.0064745
EID: 2-s2.0-84878608813

Ssengooba W , author
Respeito D , author
Mambuque E , author
Blanco S , author
Bulo H , author
Mandomando I , author
de Jong BC , author
Cobelens FG , author
García-Basteiro AL , author

2016-01-01

PMID: 27611466
PMC: PMC5017620
DOI: 10.1371/journal.pone.0162833

Willy Ssengooba , author
Seyed Ehtesham Hasnain , editor
Germine Nakayita , author
Carolyn C. Namaganda , author
Moses L. Joloba , author

2018-06-28

PLOS ONE

DOI: 10.1371/journal.pone.0199638

2022-04-11

BMC infectious diseases

Background

Second-line drug resistance (SLD) among tuberculosis (TB) patients is a serious emerging challenge towards global control of the disease. We characterized SLD-resistance conferring-mutations among TB patients with rifampicin and/or isoniazid (RIF and/or INH) drug-resistance tested at the Uganda National TB Reference Laboratory (NTRL) between June 2017 and December 2019.

Methods

This was a descriptive cross-sectional secondary data analysis of 20,508 M. tuberculosis isolates of new and previously treated patients' resistant to RIF and/or INH. DNA strips with valid results to characterise the SLD resistance using the commercial Line Probe Assay Genotype MTBDRsl Version 2.0 Assay (Hain Life Science, Nehren, Germany) were reviewed. Data were analysed with STATAv15 using cross-tabulation for frequency and proportions of known resistance-conferring mutations to injectable agents (IA) and fluoroquinolones (FQ).

Results

Among the eligible participants, 12,993/20,508 (63.4%) were male and median (IQR) age 32 (24-43). A total of 576/20,508 (2.8%) of the M. tuberculosis isolates from participants had resistance to RIF and/or INH. These included; 102/576 (17.7%) single drug-resistant and 474/576 (82.3%) multidrug-resistant (MDR) strains. Only 102 patients had test results for FQ of whom 70/102 (68.6%) and 01/102 (0.98%) had resistance-conferring mutations in the gyrA locus and gyrB locus respectively. Among patients with FQ resistance, gyrAD94G 42.6% (30.0-55.9) and gyrA A90V 41.1% (28.6-54.3) mutations were most observed. Only one mutation, E540D was detected in the gyrB locus. A total of 26 patients had resistance-conferring mutations to IA in whom, 20/26 77.0% (56.4-91.0) had A1401G mutation in the rrs gene locus.

Conclusions

Our study reveals a high proportion of mutations known to confer high-level fluoroquinolone drug-resistance among patients with rifampicin and/or isoniazid drug resistance. Utilizing routinely generated laboratory data from existing molecular diagnostic methods may aid real-time surveillance of emerging tuberculosis drug-resistance in resource-limited settings.

PMID: 35410160
DOI: 10.1186/s12879-022-07339-w

2019-04-03

Journal of clinical microbiology

Tuberculous meningitis (TBM) is the most lethal manifestation of tuberculosis and requires rapid diagnosis and initiation of treatment to prevent death and serious neurological disability.….

PMID: 30944199
DOI: 10.1128/jcm.00249-19

Ssengooba W , author
Kateete DP , author
Wajja A , author
Bugumirwa E , author
Mboowa G , author
Namaganda C , author
Nakayita G , author
Nassolo M , author
Mumbowa F , author
Asiimwe BB , author
Waako J , author
Verver S , author
Musoke P , author
Mayanja-Kizza H , author
Joloba ML , author

2012-01-01

DOI: 10.1155/2012/970203
PMID: 23304491
PMC: PMC3529437

Ssengooba, W.
Cobelens, F.G.
Nakiyingi, L.
Mboowa, G.
Armstrong, D.T.
Manabe, Y.C.
Joloba, M.L.
De Jong, B.C.

2015-01-01

PLoS ONE

DOI: 10.1371/journal.pone.0132581
EID: 2-s2.0-84941351104

Naghib Bogere , author
Felix Bongomin , author
Andrew Katende , author
Kenneth Ssebambulidde , author
Willy Ssengooba , author
Henry Ssenfuka , author
Edgar Kigozi , author
Samuel Biraro , author
David P. Kateete , author
Irene Andia-Biraro , author

2021-12-01

International Journal of Infectious Diseases

DOI: 10.1016/j.ijid.2021.10.038

2019-05-15

PloS one

BACKGROUND:Determining mycobacterial burden is important in assessing severity of disease, evaluating infectiousness and predicting patient treatment outcomes. Mycobacterial burden assessed by smear microscopy grade and time to culture positivity is clearly interpretable by most physicians. GeneXpert (Xpert) has been recommended by WHO as a first line tuberculosis (TB) diagnostic test as an alternative to smear microscopy. Xpert gives cycle threshold (Ct) values as a potential measure for mycobacterial burden. For physicians to clearly interpret Ct values as measures of mycobacterial burden, this study compared the Xpert quantification capabilities with those of smear microscopy and culture. The study also determined a linear relationship between Xpert Ct values and MGIT culture time to positivity (MGIT-TTP) and associated factors. A cut off Ct value which best predicts smear positivity was also determined using the Receiver Operator Curve analysis method. RESULTS:Excluding missing results and rifampicin resistant TB cases, a moderately strong correlation of 0.55 between Xpert Ct value and smear grade was obtained. A weak correlation of 0.37 was obtained between Xpert Ct values and MGIT time to positivity while that between Xpert Ct values and LJ culture was 0.34. The Xpert Ct values were found to increase by 2.57 for every unit increase in days to positive and HIV status was significantly associated with this relationship. A cut off Ct value of 23.62 was found to best predict smear positivity regardless of HIV status. CONCLUSION:Our study findings show that GeneXpert Ct values are comparable to smear microscopy as a measure of M. tuberculosis burden and can be used to replace smear microscopy. However, given the low correlation between Xpert Ct value and culture positivity, Xpert Ct values cannot replace culture as a measure of M. tuberculosis burden among TB patients.

PMID: 31091275
DOI: 10.1371/journal.pone.0216901

Thomas Clarke , author
Lauren Brinkac , author
Joanna Manoranjan , author
Alberto García-Basteiro , author
Harleen Grewal , author
Anthony Kiyimba , author
Elisa Lopez , author
Ragini Macaden , author
Durval Respeito , author
Willy Ssengooba , author
Michele Tameris , author
Granger Sutton , author

2020-05-28

DOI: 10.12688/f1000research.22620.2
Part of ISSN: 2046-1402

2021-06-01

MicrobiologyOpen

Tuberculosis (TB) is the leading cause of death in humans by a single infectious agent worldwide with approximately two billion humans latently infected with the bacterium Mycobacterium tuberculosis. Currently, the accepted method for controlling the disease is Tuberculosis Directly Observed Treatment Shortcourse (TB-DOTS). This program is not preventative and individuals may transmit disease before diagnosis, thus better understanding of disease transmission is essential. Using whole-genome sequencing and single nucleotide polymorphism analysis, we analyzed genomes of 145 M. tuberculosis clinical isolates from active TB cases from the Rubaga Division of Kampala, Uganda. We established that these isolates grouped into M. tuberculosis complex (MTBC) lineages 1, 2, 3, and 4, with the most isolates grouping into lineage 4. Possible transmission pairs containing ≤12 SNPs were identified in lineages 1, 3, and 4 with the prevailing transmission in lineages 3 and 4. Furthermore, investigating DNA codon changes as a result of specific SNPs in prominent virulence genes including plcA and plcB could indicate potentially important modifications in protein function. Incorporating this analysis with corresponding epidemiological data may provide a blueprint for the integration of public health interventions to decrease TB transmission in a region.

PMID: 34180596
DOI: 10.1002/mbo3.1211

Bruce J Kirenga , author
Willy Ssengooba , author
Catherine Muwonge , author
Lydia Nakiyingi , author
Stephen Kyaligonza , author
Samuel Kasozi , author
Frank Mugabe , author
Martin Boeree , author
Moses Joloba , author
Alphonse Okwera , author

2015-01-01

BMC Public Health

DOI: 10.1186/s12889-015-1376-3

2021-06-01

BMC infectious diseases

Background

In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB.

Methods

A subset of 138 PLHIV from the 'SOUTH' study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity.

Results

A total of 81 patients (58.7%) were males, median age 34 (IQR 29  ̶ 40) years, median CD4 cell count of 180 (IQR 68  ̶ 345) cells/μL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0  ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04  ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03  ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient's colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74  ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79  ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8.

Conclusion

Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.

PMID: 34074248
PMC: PMC8170957
DOI: 10.1186/s12879-021-06220-6

2021-01-13

BMC infectious diseases

Background

Chest X-ray (CXR) interpretation remains a central component of the current World Health Organization recommendations as an adjuvant test in diagnosis of smear-negative tuberculosis (TB). With its low specificity, high maintenance and operational costs, utility of CXR in diagnosis of smear-negative TB in high HIV/TB burden settings in the Xpert MTB/RIF era remains unpredictable. We evaluated accuracy and additive value of CXR to Xpert MTB/RIF in the diagnosis of TB among HIV-positive smear-negative presumptive TB patients.

Methods

HIV co-infected presumptive TB patients were recruited from the Infectious Diseases Institute outpatient clinic and in-patient medical wards of Mulago Hospital, Uganda. CXR films were reviewed by two independent radiologists using a standardized evaluation form. CXR interpretation with regard to TB was either positive (consistent with TB) or negative (normal or unlikely TB). Sensitivity, specificity and predictive values of CXR and CXR combined with Xpert MTB/RIF for diagnosis of smear-negative TB in HIV-positive patients were calculated using sputum and/or blood mycobacterial culture as reference standard.

Results

Three hundred sixty-six HIV co-infected smear-negative participants (female, 63.4%; hospitalized, 68.3%) had technically interpretable CXR. Median (IQR) age was 32 (28-39) years and CD4 count 112 (23-308) cells/mm³. Overall, 22% (81/366) were positive for Mycobacterium tuberculosis (Mtb) on culture; 187/366 (51.1%) had CXR interpreted as consistent with TB, of which 55 (29.4%) had culture-confirmed TB. Sensitivity and specificity of CXR interpretation in diagnosis of culture-positive TB were 67.9% (95%CI 56.6-77.8) and 53.7% (95%CI 47.7-59.6) respectively, while Xpert MTB/RIF sensitivity and specificity were 65.4% (95%CI 54.0-75.7) and 95.8% (95%CI 92.8-97.8) respectively. Addition of CXR to Xpert MTB/RIF had overall sensitivity and specificity of 87.7% (95%CI 78.5-93.9) and 51.6% (95%CI 45.6-57.5) respectively; 86.2% (95%CI 75.3-93.5) and 48.1% (95%CI 40.7-55.6) among inpatients and 93.8% (95%CI 69.8-99.8) and 58.0% (95%CI 47.7-67.8) among outpatients respectively.

Conclusion

In this high prevalence TB/HIV setting, CXR interpretation added sensitivity to Xpert MTB/RIF test at the expense of specificity in the diagnosis of culture-positive TB in HIV-positive individuals presenting with TB symptoms and negative smear. CXR interpretation may not add diagnostic value in settings where Xpert MTB/RIF is available as a TB diagnostic tool.

PMID: 33435896
PMC: PMC7805204
DOI: 10.1186/s12879-020-05752-7

Stucki, D.
Brites, D.
Jeljeli, L.
Coscolla, M.
Liu, Q.
Trauner, A.
Fenner, L.
Rutaihwa, L.
Borrell, S.
Luo, T.
Gao, Q.
Kato-Maeda, M.
Ballif, M.
Egger, M.
Macedo, R.
Mardassi, H.
Moreno, M.
Vilanova, G.T.
Fyfe, J.
Globan, M.
Thomas, J.
Jamieson, F.
Guthrie, J.L.
Asante-Poku, A.
Yeboah-Manu, D.
Wampande, E.
Ssengooba, W.
Joloba, M.
Boom, W.H.
Basu, I.
Bower, J.
Saraiva, M.
Vasconcellos, S.E.G.
Suffys, P.
Koch, A.
Wilkinson, R.
Gail-Bekker, L.
Malla, B.
Ley, S.D.
Beck, H.-P.
De Jong, B.C.
Toit, K.
Sanchez-Padilla, E.
Bonnet, M.
Gil-Brusola, A.
Frank, M.
Penlap Beng, V.N.
Eisenach, K.
Alani, I.
Ndung'U, P.W.
Revathi, G.
Gehre, F.
Akter, S.
Ntoumi, F.
Stewart-Isherwood, L.
Ntinginya, N.E.
Rachow, A.
Hoelscher, M.
Cirillo, D.M.
Skenders, G.
Hoffner, S.
Bakonyte, D.
Stakenas, P.
Diel, R.
Crudu, V.
Moldovan, O.
Al-Hajoj, S.
Otero, L.
Barletta, F.
Carter, E.J.
Diero, L.
Supply, P.
Comas, I.
Niemann, S.
Gagneux, S.

2016-01-01

Nature Genetics

DOI: 10.1038/ng.3704
EID: 2-s2.0-84992759009

Jerome H. Chin , author
Willy Ssengooba , author
Scott Grossman , author
Jacob Pellinen , author
Vincent Wadda , author

2019-02-01

Journal of Clinical Tuberculosis and Other Mycobacterial Diseases

DOI: 10.1016/j.jctube.2019.01.002

2021-03-01

Journal of Medical Microbiology

2021-12-29

Scientific reports

Information on microbiota dynamics in pulmonary tuberculosis (TB) in Africa is scarce. Here, we sequenced sputa from 120 treatment-naïve TB patients in Uganda, and investigated changes in microbiota of 30 patients with treatment-response follow-up samples. Overall, HIV-status and anti-TB treatment were associated with microbial structural and abundance changes. The predominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria and Actinobacteria, accounting for nearly 95% of the sputum microbiota composition; the predominant genera across time were Prevotella, Streptococcus, Veillonella, Haemophilus, Neisseria, Alloprevotella, Porphyromonas, Fusobacterium, Gemella, and Rothia. Treatment-response follow-up at month 2 was characterized by a reduction in abundance of Mycobacterium and Fretibacterium, and an increase in Ruminococcus and Peptococcus; month 5 was characterized by a reduction in Tannerella and Fusobacterium, and an increase in members of the family Neisseriaceae. The microbiota core comprised of 44 genera that were stable during treatment. Hierarchical clustering of this core's abundance distinctly separated baseline (month 0) samples from treatment follow-up samples (months 2/5). We also observed a reduction in microbial diversity with 9.1% (CI 6-14%) of the structural variation attributed to HIV-status and anti-TB treatment. Our findings show discernible microbiota signals associated with treatment with potential to inform anti-TB treatment response monitoring.

PMID: 34966183
DOI: 10.1038/s41598-021-04271-y

Muttamba, W.
Ssengooba, W.
Kirenga, B.
Sekibira, R.
Walusimbi, S.
Katamba, A.
Joloba, M.

2019-01-01

PLoS ONE

DOI: 10.1371/journal.pone.0217900
EID: 2-s2.0-85066756204
Part of ISBN: 19326203

Jones-López E , author
Manabe YC , author
Palaci M , author
Kayiza C , author
Armstrong D , author
Nakiyingi L , author
Ssengooba W , author
Gaeddert M , author
Kubiak R , author
Almeida Júnior P , author
Alland D , author
Dietze R , author
Joloba M , author
Ellner JJ , author
Dorman SE , author

2014-07-01

PMID: 24808236
PMC: PMC4097702
DOI: 10.1128/JCM.00642-14

Sekadde, M.P.
Wobudeya, E.
Joloba, M.L.
Ssengooba, W.
Kisembo, H.
Bakeera-Kitaka, S.
Musoke, P.

2013-01-01

BMC Infectious Diseases

DOI: 10.1186/1471-2334-13-133
EID: 2-s2.0-84874766224

Thomas Clarke , author
Lauren Brinkac , author
Joanna Manoranjan , author
Alberto García-Basteiro , author
Harleen Grewal , author
Anthony Kiyimba , author
Elisa Lopez , author
Ragini Macaden , author
Durval Respeito , author
Willy Ssengooba , author
Michele Tameris , author
Granger Sutton , author

2020-04-09

F1000Research

DOI: 10.12688/f1000research.22620.1

Adrian Muwonge , author
Sydney Malama , author
Barend M. de C. Bronsvoort , author
Demelash Biffa , author
Willy Ssengooba , author
Eystein Skjerve , author
D. William Cameron , editor

2014-06-01

PLoS ONE

DOI: 10.1371/journal.pone.0100720

Willy Ssengooba , author
Lydia Nakiyingi , author
Derek T. Armstrong , author
Frank G. Cobelens , author
David Alland , author
Yukari C. Manabe , author
Susan E. Dorman , author
Jerrold J. Ellner , author
Moses L. Joloba , author
Yoshihiko Hoshino , editor

2014-09-01

PLoS ONE

DOI: 10.1371/journal.pone.0107595

2021-06-01

MicrobiologyOpen

Ssengooba W , author
Gelderbloem SJ , author
Mboowa G , author
Wajja A , author
Namaganda C , author
Musoke P , author
Mayanja-Kizza H , author
Joloba ML , author

2015-01-01

PMID: 25589057
PMC: PMC4326287
DOI: 10.1186/1478-4505-13-4

Lydia Nakiyingi , author
Willy Ssengooba , author
Damalie Nakanjako , author
Derek Armstrong , author
Molly Holshouser , author
Bruce J Kirenga , author
Maunank Shah , author
Harriet Mayanja-Kizza , author
Moses L Joloba , author
Jerrold J Ellner , author
Susan E Dorman , author
Yukari C Manabe , author

2015-02-01

BMC Infect Dis

DOI: 10.1186/s12879-015-0812-4

Deus Lukoye , author
Willy Ssengooba , author
Kenneth Musisi , author
George W Kasule , author
Frank G J Cobelens , author
Moses Joloba , author
Gabriela B Gomez , author

2015-03-01

BMC Public Health

DOI: 10.1186/s12889-015-1614-8

2017-01-01

BMJ global health

PMID: 28589036
PMC: PMC5418676
DOI: 10.1136/bmjgh-2016-000260

John K. Lusiba , author
Lydia Nakiyingi , author
Bruce J. Kirenga , author
Agnes Kiragga , author
Robert Lukande , author
Maria Nsereko , author
Willy Ssengooba , author
Achilles Katamba , author
William Worodria , author
Moses L. Joloba , author
Harriet Mayanja-Kizza , author
Keertan Dheda , editor

2014-07-01

PLoS ONE

DOI: 10.1371/journal.pone.0102702

Muwonge A , author
Kankya C , author
Olea-Popelka F , author
Biffa D , author
Ssengooba W , author
Berit D , author
Skjerve E , author
Johansen TB , author

2013-07-01

DOI: 10.1016/j.meegid.2013.03.039
PMID: 23548804

Ssengooba, W.
Kiwanuka, N.
Kateete, D.P.
Katamba, A.
Joloba, M.L.

2012-01-01

PLoS ONE

DOI: 10.1371/journal.pone.0037650
EID: 2-s2.0-84861325263

Mumpe-Mwanja, D.
Verver, S.
Yeka, A.
Etwom, A.
Waako, J.
Ssengooba, W.
Matovu, J.K.B.
Wanyenze, R.K.
Musoke, P.
Mayanja-Kizza, H.

2015-01-01

African Health Sciences

DOI: 10.4314/ahs.v15i3.20
EID: 2-s2.0-84941361611

2021-11-01

The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

PMID: 34686228
DOI: 10.5588/ijtld.21.0564

Ngabonziza, J.C.S.
Ssengooba, W.
Mutua, F.
Torrea, G.
Dushime, A.
Gasana, M.
Andre, E.
Uwamungu, S.
Nyaruhirira, A.U.
Mwaengo, D.
Muvunyi, C.M.

2016-01-01

BMC Infectious Diseases

DOI: 10.1186/s12879-016-2009-x
EID: 2-s2.0-84994544505

2021-04-02

Open forum infectious diseases

Background

The Global Laboratory Initiative (GLI) guidelines recommend repeat for GeneXpertMTB/RIF (XpertMTB/RIF) in patients with a low pretest probability of rifampicin resistance (RR).

Methods

This was a cross-sectional study using results of sputum specimens collected from participants screened for the STREAM 2 trial. We recruited all patients with XpertMTB/RIF RR-TB detected who were referred for RR/multidrug-resistant (MDR) TB treatment initiation at Mulago National Referral Hospital, Kampala, between September 2017 and October 2019. At baseline, smear microscopy, repeat XpertMTB/RIF, Xpert Ultra, and MTBDRplus assays were done on sputum specimens. Culture-based drug susceptibility testing (DST) was performed on discordant specimens. We analyzed the prevalence and factors associated with discordance between initial and repeat XpertMTB/RIF RR and false XpertMTB/RIF RR. False XpertMTB/RIF RR was defined as no RR detected by any of Xpert Ultra, LPA, or culture DST (reference comparator).

Results

A total of 126/130 patients had repeat XpertMTB/RIF results, of whom 97 (77.0%) had M. tuberculosis detected, 81 (83.5%) had RR detected, and 1 (1.0%) had RR indeterminate. The prevalence of discordant XpertMTB/RIF RR was 15/96 (15.6%), whereas false XpertMTB/RIF RR prevalence was 10/96 (10.4%).Low-bacillary load sputum specimens were more likely to have discordant XpertMTB/RIF RR and false XpertMTB/RIF RR results (adjusted odds ratio [aOR], 0.04; 95% CI, 0.00-0.37; P = .01; aOR, 0.02; 95% CI, 0.01-0.35; P = .01, respectively).

Conclusions

Our findings show a high false-positive rifampicin resistance rate in low-TB burden patients, which calls for repeat testing in order to prevent unnecessary prescription of anti-MDR-TB therapy.

PMID: 34189166
DOI: 10.1093/ofid/ofab173