NRU :: Browsing by Author "Worodria, William"

Browsing by Author "Worodria, William"

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Access to affordable medicines and diagnostic tests for asthma and COPD in sub Saharan Africa: the Ugandan perspective
(BMC pulmonary medicine, 2017) Kibirige, Davis; Kampiire, Leaticia; Atuhe, David; Mwebaze, Raymond; Katagira, Winceslaus; Muttamba, Winters; Nantanda, Rebecca; Worodria, William; Kirenga, Bruce
Equitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management.
Accuracy of GenoQuick MTB Test in Detection of Mycobacterium tuberculosis in Sputum from TB
(SAGE Open Medicine, 2022) Kaswabuli, Sylvia; Musisi, Emmanuel; Byanyima, Patrick; Sessolo, Abdul; Sanyu, Ingvar; Zawedde, Josephine; Worodria, William; Okeng, Alfred; Bwanga, Freddie
The objective of the study was to determine the diagnostic performance of the GenoQuick MTB test on heated sputum against the conventional Lowenstein–Jensen Mycobacterium tuberculosis culture as the reference method for tuberculosis diagnosis. Fast, reliable, and easy-to-use tests for tuberculosis diagnosis are essential to achieving the Sustainable Development Goal of diagnosing and treating 90% of tuberculosis patients by 2030. We evaluated the diagnostic performance of the GenoQuick MTB, a polymerase chain reaction–lateral flow test, in Uganda, a resource-constrained, high tuberculosisand HIV-burden setting. Fresh sputum samples from presumptive tuberculosis patients at Mulago Hospital were tested for M. tuberculosis using smear microscopy, GenoQuick MTB test, and Lowenstein–Jensen culture. For the GenoQuick MTB test, mycobacterial DNA was extracted by heating sputum at 95°C for 30min while DNA amplification and detection were done following the manufacturer’s protocol (Hain Lifescience, Nehren, Germany). Sensitivity, specificity, and kappa agreements were calculated against Lowenstein–Jensen M. tuberculosis culture as a reference test using STATA V12. Of the 86 tested samples, 30.2% had culture-confirmed pulmonary tuberculosis. Overall, sensitivity was higher for GenoQuick MTB (81%, 95% confidence interval: 60%−93%) than for smear microscopy (69%, 95% confidence interval: 48%−86%). Among people living with HIV, sensitivity was identical for GenoQuick MTB and smear tests (75%, 95% confidence interval: 42%−95%). Contrastingly, smear had a higher overall specificity (98%, 95% confidence interval: 91%−100%) than for GenoQuick MTB (92%, 95% confidence interval: 81%−97%). A similar trend of specificity was observed among the people living with HIV for smear microscopy (100%, 95% CI: 87%−100%) and for GenoQuick MTB (96%, 95% confidence interval: 81%−100%). The GenoQuick MTB test could be a potential tuberculosis diagnostic test given its higher sensitivity. Evaluation of this test in larger studies is recommended.
Accuracy of the tuberculosis molecular bacterial load assay to diagnose and monitor response to anti-tuberculosis therapy: a longitudinal comparative study with standard-of-care smear microscopy, Xpert MTB/RIF Ultra, and culture in Uganda
(Elsevier Ltd, 2024-03) Musisi, Emmanuel; Wamutu, Samuel; Ssengooba, Willy; Kasiinga, Sharifah; Sessolo, Abdulwahab; Sanyu, Ingvar; Kaswabuli, Sylvia; Zawedde, Josephine; Byanyima, Patrick; Kia, Praiscillia; Muwambi, William; Toskin, Divine Tracy; Kigozi, Edgar; Walbaum, Natasha; Dombay, Evelin; Legrady, Mate Bonifac; Ssemambo, Kizza David-Martin; Joloba, Moses; Kuchaka, Davis; Worodria, William; Huang, Laurence; Gillespie, Stephen H; Sabiiti, Wilber
Abstract In 2018, the tuberculosis molecular bacterial load assay (TB-MBLA), a ribosomal RNA-based test, was acknowledged by WHO as a molecular assay that could replace smear microscopy and culture for monitoring tuberculosis treatment response. In this study, we evaluated the accuracy of TB-MBLA for diagnosis and monitoring of treatment response in comparison with standard-of-care tests. For this longitudinal prospective study, patients aged 18 years or older with presumptive tuberculosis (coughing for at least 2 weeks, night sweats, and weight loss) were enrolled at China-Uganda Friendship Hospital Naguru (Kampala, Uganda). Participants were evaluated for tuberculosis by TB-MBLA in comparison with Xpert MTB/RIF Ultra (Xpert-Ultra) and smear microscopy, with Mycobacteria Growth Indicator Tube (MGIT) culture as a reference test. Participants who were positive on Xpert-Ultra were enrolled on a standard 6-month anti-tuberculosis regimen, and monitored for treatment response at weeks 2, 8, 17, and 26 after initiation of treatment and then 3 months after treatment. Between Nov 15, 2019, and June 15, 2022, 210 participants (median age 35 years [IQR 27–44]) were enrolled. 135 (64%) participants were male and 72 (34%) were HIV positive. The pretreatment diagnostic sensitivities of TB-MBLA and Xpert-Ultra were similar (both 99% [95% CI 95–100]) but the specificity was higher for TB-MBLA (90% [83–96]) than for Xpert-Ultra (78% [68–86]). Ten participants were Xpert-Ultra trace positive, eight (80%) of whom were negative by TB-MBLA and MGIT culture. Smear microscopy had lower diagnostic sensitivity (75% [65–83]) but higher specificity (98% [93–100]) than TB-MBLA and Xpert-Ultra. Among participants who were smear microscopy negative, the sensitivity of TB-MBLA was 96% (95 CI 80–100) and was 100% (95% CI 86–100) in those who were HIV positive. 129 (61%) participants were identified as tuberculosis positive by Xpert-Ultra and these individuals were enrolled in the treatment group and monitored for treatment response. According to TB-MBLA, 19 of these patients cleared bacillary load to zero by week 2 of treatment and remained negative throughout the 6-month treatment follow-up. Positivity for tuberculosis decreased with treatment as measured by all tests, but the rate was slower with Xpert-Ultra. Consequently, 31 (33%) of 95 participants were still Xpert-Ultra positive at the end of treatment but were clinically well and negative on TB-MBLA and culture at 6 months of treatment. Two patients were still Xpert-Ultra positive with a further 3 months of post-treatment follow-up. The rate of conversion to negative of the DNA-based Xpert-Ultra was 3·3-times slower than that of the rRNA-based TB-MBLA. Consequently for the same patient, it would take 13 weeks and 52 weeks to reach complete tuberculosis negativity by TB-MBLA and Xpert-Ultra, respectively. Participants who were positive on smear microscopy at 8 weeks, who received an extra month of intensive treatment, had a similar TB-MBLA-measured bacillary load at 8 weeks to those who were smear microscopy negative. TB-MBLA has a similar performance to Xpert-Ultra for pretreatment diagnosis of tuberculosis, but is more accurate at detecting and characterising the response to treatment than Xpert-Ultra and standard-of-care smear microscopy. European and Developing Countries Clinical Trials Partnership, Makerere University Research and Innovation Fund, US National Institutes of Health.
Algorithm-Aided Diagnosis of Chronic Pulmonary Aspergillosis in Low- And Middle-Income Countries by Use of a Lateral Flow Device
(European Journal of Clinical Microbiology & Infectious Diseases, 2020) Kwizera, Richard; Katende, Andrew; Teu, Anneth; Apolot, Denise; Worodria, William; Kirenga, Bruce J.; Bongomin, Felix
Chronic pulmonary aspergillosis (CPA) is a slowly progressive parenchymal lung disease typically caused by Aspergillus fumigatus. CPA affects immunocompetent or subtly immunocompromised patients with underlying structural lung diseases and is estimated to affect approximately three million people per year worldwide. It can co-exist with pulmonary tuberculosis (PTB), has both pulmonary and systemic symptoms that are clinically indistinguishable from that of PTB, and is often misdiagnosed and managed as smear-negative PTB. According to the Infectious Diseases Society of America (IDSA), the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Confederation of Medical Mycology (ECMM), and the European Respiratory Society (ERS) Guidelines, the diagnosis of CPA should be based on characteristic symptoms and radiologic features present or presumed to have been present for at least 3 months in a patient with no or minimal immunosuppression and a prior or current lung condition with microbiological or immunological evidence of Aspergillus spp. infection. This definition is consistent with the original definition of CPA proposed by Denning and colleagues . Still, CPA is under- and mis-diagnosed in resource-constrained settings where adequate diagnostics are unavailable. Previously treated PTB is the most common risk factor for the development of CPA even in the developed world . The global burden of CPA attributed to healed TB lesions alone has been estimated to over 1.2 million cases annually globally. On the other hand, active PTB is the number one differential diagnosis for CPA and CPA is the number one differential diagnosis for patients previously treated for microbiologically confirmed PTB who are currently sputum smear-negative. Recent evidence has shown that the annual rate of new CPA development following completion of PTB treatment is about 6.5% in those with chest radiography cavitation and 0.2% in those without.
Association of circulating serum free bioavailable and total vitamin D with cathelicidin levels among active TB patients and household contacts
(Research Square, 2022) Acen, Ester Lilian; Worodria, William; Kateete, David Patrick; Olum, Ronald; Joloba, Moses L.; Akintola, Ashraf; Bbuye, Mudarshiru; Biraro Andia, Irene
The free hormone hypothesis postulates that the estimation of free circulating 25(OH)D may be a better marker of vitamin D status and is of clinical importance compared to total vitamin D levels because it is the fraction involved in biological activities. Studies have shown that cathelicidin inhibits the growth of Mycobacterium Tuberculosis in a vitamin D-dependent manner and therefore adequate vitamin D is required for its expression. The aim of the study was to determine the association between serum-free and bioavailable and total vitamin D with LL-37 levels in ATB patients, LTBI and individuals with no TB infection. This was a cross sectional study and free and bioavailable vitamin D and LL-37 levels were measured. 95 specimens were further selected to estimate total vitamin D levels. The median free and bioavailable vitamin D levels of study participants were 3.8 ng/mL. The median LL-37 levels were 318.8 ng/mL. The mean total vitamin D levels were 18.9 ng/mL. Significantly weak inverse associations were found and vitamin D is involved in the regulation of LL-37 expression and low vitamin D levels can alter this relationship. Background Vitamin D deficiency is a prominent risk factor for TB disease worldwide (1–5). Vitamin D can be obtained in two forms, D2 is obtained through diet and D3 is obtained through skin biosynthesis (6). Its main circulating active metabolite 1, 25(OH)D is involved in regulation of antimicrobial activity and therefore important in TB therapy (7). So far, total vitamin D or 25(OH)D has been considered a better index for determining vitamin D status due to its longer half-life (6, 8–11). However, the free hormone hypothesis postulates that the estimation of free circulating 25(OH)D may be a better marker of vitamin D status and is of clinical importance compared to total vitamin D levels because it is the fraction involved in biological activities (10, 12–14). Bioavailable 25(OH)D is used to represent free vitamin D and the 10–15% fraction is loosely bound to albumin (8, 15). About 85–90% of total 25(OH)D is bound to VDBP and 10–15% is loosely bound to albumin and a small fraction remains unbound (13, 16). Free 25(OH)D is increased and readily available to cells when DBP levels are at low concentrations Previous studies report that changes in DBP levels and 25(OH)D binding affinity can lead to higher levels of free 25(OH)D, even in the absence of total vitamin D levels (17, 18). According to the Endocrine Society, total vitamin D status is classified into three groups: <20 ng/mL deficient, 21–29 ng/mL deficient, and > 30 ng/mL optimal; or sufficient amounts (19). In vitro and in vivo studies have shown that LL-37 inhibits the growth of MTB in a vitamin D-dependent manner (20, 21). Accordingly, studies have reported that adequate levels of 25(OH)D are required for expression of LL-37(22, 23). According to our systematic review, six studies reported that vitamin D regulates LL-37 expression and that vitamin D deficiency alters this function (24). Because the free fraction of vitamin D, which enters cells to cause biological effects, has not been studied with the LL-37 molecule, we hypothesize that there is no relationship between free and bioavailable vitamin D and total vitamin D with the LL-37 levels among the ATB patients, LTBI and individuals with no TB infection. This study aimed to determine the association between serum-free and bioavailable and total vitamin D with LL-37 levels in ATB patients, LTBI and individuals with no TB infection.
Biobanking: Strengthening Uganda’s Rapid Response to COVID-19 and Other Epidemics
(Biopreservation and Biobanking, 2021) Kamulegeya, Rogers; Kateete, David Patrick; Bagaya, Bernard S.; Nasinghe, Emmanuel; Muttamba, Winters; Nsubuga, Gideon; Kigozi, Edgar; Ashaba Katabazi, Fred; Nakwagala, Fred; Kalungi, Sam; Byamugisha, Josaphat; Worodria, William; Magala, Rose; Kirenga, Bruce; Joloba, Moses L.
SARS-CoV-2 is a fatal disease of global public health concern. Measures to reduce its spread critically depend on timely and accurate diagnosis of virus-infected individuals. Biobanks can have a pivotal role in elucidating disease etiology, translation, and advancing public health. In this article, we show how a biobank has been a critical resource in the rapid response to coronavirus disease of 2019 (COVID-19) in Uganda. Materials and Methods: The Integrated Biorepository of H3Africa Uganda established a COVID-19 biobank. Standard Operating Procedures for sample and data collection, sample processing, and storage were developed. An e-questionnaire data tool was used to collect sociodemographic factors. Samples were collected at 7-day intervals from patients, analyzed for key parameters, processed, annotated, characterized, and stored at appropriate temperatures. Results: Stored samples have been used in validation of 17 diagnostic kits, the Cepheid Xpert Xpress SARSCoV- 2 assay, as well as a sample pooling technique for mass screening and polymerase chain reaction assay validation. Kits that passed validation were deployed for mass screening boosting early detection, isolation, and treatment of COVID-19 cases. Also, 10 applications from researchers and biotech companies have been received and approved and 4 grants have been awarded Conclusion: The CoV-Bank has proven to be an invaluable resource in the fight against the COVID-19 pandemic in Uganda, as samples have been resources in the validation and development of COVID-19 diagnostic tools, which are important in tracing and isolation of infected cases to confront, delay, and stop the spread of the SARS-CoV-2 virus.
The burden of drug resistant tuberculosis in a predominantly nomadic population in Uganda: a mixed methods study
(BMC Infectious Diseases, 2021) Nakafeero Simbwa, Brenda; Katamba, Achilles; Katana, Elizabeth B.; Laker, Eva A. O.; Nabatanzi, Sandra; Sendaula, Emmanuel; Opio, Denis; Ictho, Jerry; Lochoro, Peter; Karamagi, Charles A.; Kalyango, Joan N.; Worodria, William
Emergence of drug resistant tuberculosis (DR-TB) has aggravated the tuberculosis (TB) public health burden worldwide and especially in low income settings. We present findings from a predominantly nomadic population in Karamoja, Uganda with a high-TB burden (3500 new cases annually) and sought to determine the prevalence, patterns, factors associated with DR-TB. Methods: We used mixed methods of data collection. We enrolled 6890 participants who were treated for tuberculosis in a programmatic setting between January 2015 and April 2018. A cross sectional study and a matched case control study with conditional logistic regression and robust standard errors respectively were used to the determine prevalence and factors associated with DR-TB. The qualitative methods included focus group discussions, in-depth interviews and key informant interviews. Results: The overall prevalence of DR-TB was 41/6890 (0.6%) with 4/64,197 (0.1%) among the new and 37/2693 (1.4%) among the previously treated TB patients respectively. The drug resistance patterns observed in the region were mainly rifampicin mono resistant (68.3%) and Multi Drug-Resistant Tuberculosis (31.7%). Factors independently associated with DR-TB were previous TB treatment, adjusted odds ratio (aOR) 13.070 (95%CI 1.552–110.135) and drug stock-outs aOR 0.027 (95%CI 0.002–0.364). The nomadic lifestyle, substance use, congested homesteads and poor health worker attitudes were a great challenge to effective treatment of TB. Conclusion: Despite having the highest national TB incidence, Karamoja still has a low DR-TB prevalence. Previous TB treatment and drug stock outs were associated with DR-TB. Regular supply of anti TB medications and health education may help to stem the burden of TB disease in this nomadic population.
Burden of Fungal Asthma in Africa: A Systematic Review and Meta-Analysis
(PloS one, 2019) Kwizera, Richard; Musaazi, Joseph; Meya, David B.; Worodria, William; Bwanga, Freddie; Kajumbula, Henry; Fowler, Stephen J.; Kirenga, Bruce J.; Gore, Robin; Denning, David W.
Asthma is one of the neglected diseases in Africa with a high prevalence. Allergic fungal diseases have been reported to complicate asthma progression and treatment outcomes. However, data about fungal asthma and its associated complications are limited in Africa. We aimed to estimate the burden of fungal asthma among adults and children in Africa using a systematic review.We first engaged the Institute for Health Metrics and Evaluation (IHME) to highlight the trend in morbidity and mortality attributed to asthma in Africa. We then searched PubMed, HINARI and Google Scholar for all studies of any design focusing on fungal asthma in any African country. Languages were restricted to English and French, but not year of publication. We estimated the weighted prevalence of allergic fungal infections among asthmatics with a 95% CI and pooled the results using a random effects model. This study is registered with PROSPERO, number CRD42019117319.The IHME data showed that there has been a gradual increase in morbidity and mortality due to asthma in African adults with a prevalence of 4%. Our search retrieved 5233 citations. We retained 20 studies that met our selection criteria. These were from 13 African countries published between 1967 and 2018. There were eight cross-sectional studies and twelve review articles. The average asthma prevalence in Africa was 6% from these studies. The prevalence of fungal sensitisation was relatively high (3–52%) in the asthmatic population with an average of 28% and a pooled estimate of 23.3%, mostly due to Aspergillus species. Prevalence of Allergic bronchopulmonary apsergillosis was estimated at 1.6–21.2%. Diagnosis of fungal allergy was mostly made by skin prick tests. There was no data on the use of medication to manage fungal asthma. None of the studies evaluated the association between fungal allergy and asthma severity. Data were lacking in children.There is a high prevalence of fungal sensitization among Africans with asthma. Fungal asthma is a significant problem in Africa but there remains a paucity of data on the epidemiology and associated complications. There is urgent need for national epidemiological studies to estimate the actual burden of fungal asthma in Africa.
The burden of severe asthma in sub-Saharan Africa: Findings from the African Severe Asthma Project
(Elsevier Inc, 2024-01-09) Kirenga, Bruce J; Chakaya, Jeremiah; Yimer, Getnet; Nyale, George; Haile, Tewodros; Muttamba, Winters; Mugenyi, Levicatus; Katagira, Winceslaus; Worodria, William; Aanyu-Tukamuhebwa, Hellen; Lugogo, Njira; Joloba, Moses; Mersha, Tesfaye B.; Bekele, Amsalu; Makumbi, Fred; Mekasha, Amha; Green, Cynthia L.; de Jong, Corina; Kamya, Moses; van der Molen, Thys
Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.
C-Reactive Protein Testing for Active Tuberculosis among Inpatients without HIV in Uganda: a Diagnostic Accuracy Study
(Journal of Clinical Microbiology, 2020) Meyer, Amanda J.; Ochom, Emmanuel; Turimumahoro, Patricia; Byanyima, Patrick; Sanyu, Ingvar; Lalitha, Rejani; Kaswabuli, Sylvia; Andama, Alfred; Walter, Nicholas D.; Katamba, Achilles; Cattamanchi, Adithya; Worodria, William; Huang, Laurence; Yoon, Christina; Davis, Lucian
The objective of this prospective cross-sectional study, conducted at a national referral hospital in Kampala, Uganda, was to determine diagnostic performance of serum C-reactive protein (CRP) as a triage test for tuberculosis (TB) among HIV-seronegative inpatients. We calculated the sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values to determine the diagnostic performance of a CRP enzyme-linked immunosorbent assay (ELISA) (Eurolyser) in comparison to that of a reference standard of Mycobacterium tuberculosis culture on two sputum samples. We constructed receiver operating curves and reported performance in reference to the manufacturer’s cutoff and also to a threshold chosen to achieve sensitivity of 90%, in accordance with the WHO’s targetproduct profile for a triage test. Among 119 HIV-seronegative inpatients, 46 (39%) had culture-positive pulmonary TB. In reference to M. tuberculosis culture, CRP had a sensitivity of 78% (95% confidence interval [CI], 64 to 89%) and a specificity of 52% (95% CI, 40 to 64%) at the manufacturer’s threshold of 10 mg/liter. At a threshold of 1.5 mg/liter, the sensitivity was 91% (95% CI, 79 to 98%) but the specificity was only 21% (95% CI, 12 to 32%). Performance did not differ when stratified by illness severity at either threshold. In conclusion, among HIV-seronegative inpatients, CRP testing performed substantially below targets for a TB triage test. Additional studies among HIV-seronegative individuals in clinics and community settings are needed to assess the utility of CRP for TB screening.
Cardiovascular risk factors among people with drug-resistant tuberculosis in Uganda
(BMC Cardiovascular Disorders, 2022) Baruch Baluku, Joseph; Nabwana, Martin; Nalunjogi, Joanitah; Muttamba, Winters; Mubangizi, Ivan; Nakiyingi, Lydia; Ssengooba, Willy; Olum, Ronald; Bongomin, Felix; Andia-Biraro, Irene; Worodria, William
Tuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda. Methods In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021. The studied CVD risk factors were any history of cigarette smoking, diabetes mellitus (DM) hypertension, high body mass index (BMI), central obesity and dyslipidaemia. We used modified Poisson regression models with robust standard errors to determine factors independently associated with each of dyslipidaemia, hypertension, and central obesity. Results Among 212 participants, 118 (55.7%) had HIV. Overall, 196 (92.5%, 95% confidence interval (CI) 88.0-95.3) had ≥ 1 CVD risk factor. The prevalence; 95% CI of individual CVD risk factors was: dyslipidaemia (62.5%; 55.4–69.1), hypertension (40.6%; 33.8–47.9), central obesity (39.3%; 32.9–46.1), smoking (36.3%; 30.1–43.1), high BMI (8.0%; 5.0–12.8) and DM (6.5%; 3.7–11.1). Dyslipidaemia was associated with an increase in glycated haemoglobin (adjusted prevalence ratio (aPR) 1.14, 95%CI 1.06–1.22). Hypertension was associated with rural residence (aPR 1.89, 95% CI 1.14– 3.14) and previous history of smoking (aPR 0.46, 95% CI 0.21–0.98). Central obesity was associated with increasing age (aPR 1.02, 95%CI 1.00–1.03), and elevated diastolic blood pressure (aPR 1.03 95%CI 1.00–1.06). Conclusion There is a high prevalence of CVD risk factors among people with DRTB in Uganda, of which dyslipidaemia is the commonest. We recommend integrated services for identification and management of CVD risk factors in DRTB.
Characterization of Asthma and Its Determinants in Ethiopia: Part of the African Severe Asthma Project (ASAP)
(Ethiopian Medical Journal, 2021) Bekel, Amsalu; Haile, Tewodros; Mekekasha, Amha; Fuad, Oumer; Muttamba, Winters; Mugenyi, Levi; Katagira, Wincey; Nyale, George; Lugogo, Njira; Worodria, William; Aanyu, Hellen T.; Joloba, Moses; Jong, Corina de; Makumbi, Fred; Molen, Thys van der; Chakaya, Jeremiah; Kirenga, Bruce J; Yimer, Getenet
Asthma is a major public health problem globally affecting 339 million people with 300,000 annual death. African Severe Asthma Program was a multi-country prospective cohort study designed to characterize severe asthma in three African countries, Ethiopia, Uganda and Kenya. In this study, we describe the baseline characteristics and disease severity among asthmatics enrolled in the Ethiopia site of African Severe Asthma Program. Asthmatics seen at Tikur Anbessa Specialized Hospital from August 2016 to May 2018 were studied. Asthma was diagnosed based on symptoms and spirometry. Baseline demographic and clinical data were collected using a structured questionnaire. Standardized research tools were used to assess asthma severity, asthma control and asthma quality of life. A total of 419 asthmatic patients were enrolled in the study; the mean age for the group was 52 ± 8 years and 58.2 % were female. The majority of the participants, 365 (87.2%), had a prior diagnosis of asthma with a median (IQR) age at first diagnosis of 29 (IQR: 22 - 36) years. A family history of asthma was present in 149 (35.6%) subjects. Current or previous cigarette smoking was reported in 8.6% of the participants. Overall, 93.8% of the participants reported uncontrolled asthma symptoms (ACQ >1.5). More than half of the patients, had severe persistent asthma and 35% presented with one or more comorbidities. Conclusions: In Ethiopia, asthmatics presenting to a tertiary care hospital were characterized as predominantly female with late onset disease, poor control, and associated comorbidities. Key Words: Asthma, Characteristics, determinants and Severe
Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
(PLoS ONE, 2018) Farr, Katherine; Ravindran, Resmi; Strnad, Luke; Chang, Emily; Chaisson, Lelia H.; Yoon, Christina; Worodria, William; Andama, Alfred; Ayakaka, Irene; Bbosa Nalwanga, Priscilla; Byanyima, Patrick; Kalema, Nelson; Kaswabuli, Sylvia; Katagira, Winceslaus; Denise Aman, Kyomugisha; Musisi, Emmanuel; Tumwine, Nuwagaba Wallen; Sanyu, Ingvar; Ssebunya, Robert; Davis, J. Lucian; Huang, Laurence; Khan, Imran H.; Cattamanchi, Adithya
Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy. Methods Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough � 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB. Concentrations of 43 cytokines/chemokines were measured at the same time point as C-reactive protein (CRP) in banked plasma samples using commercially-available multiplex kits. Advanced classification algorithms were used to rank cytokines/chemokines for their ability to identify TB, and to model the specificity of the top-ranked cytokines/chemokines individually and in combination with sensitivity constrained to � 90% as recommended for TB screening. Results The median plasma level of 5 biomarkers (IL-6, INF-γ, MIG, CRP, IL-18) was significantly different between patients with and without TB. With sensitivity constrained to 90%, all had low specificity with IL-6 showing the highest specificity (44%; 95% CI 37.4–49.5). Biomarker panels were found to be more valuable than any biomarker alone. A panel combining IFN-γ and IL-6 had the highest specificity (50%; 95% CI 46.7–53.3). Sensitivity remained high (>85%) for all panels among sputum smear-negative TB patients. Conclusions Direct measurement of unstimulated plasma cytokines/chemokines in peripheral blood is a promising approach to TB screening. Cytokine/chemokine panels retained high sensitivity for smear-negative TB and achieved improved specificity compared to individual cytokines/ chemokines. These markers should be further evaluated in outpatient settings where most TB screening occurs and where other illnesses associated with systematic inflammation are less common.
Evaluation of Cepheid’s Xpert MTB/RIF Test on Pleural Fluid in the Diagnosis of Pleural Tuberculosis in a High Prevalence HIV/TB Setting
(PLoS ONE, 2014) Lusiba, John K.; Nakiyingi, Lydia; Kirenga, Bruce J.; Kiragga, Agnes; Lukande, Robert; Nsereko, Maria; Ssengooba, Willy; Katamba, Achilles; Worodria, William; Joloba, Moses L.; Mayanja-Kizza, Harriet
Diagnosis of pleural tuberculosis (TB) using routinely available diagnostic methods is challenging due to the paucibacillary nature of the disease. Histopathology and pleural tissue TB culture involves an invasive procedure which requires expertise and appropriate equipment, both often unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in sputum specimens but data on its performance in pleural TB is scarce. We evaluated the accuracy of Cepheid’s Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural TB in Uganda. Methods: Consenting adult patients with exudative pleural effusions underwent pleural biopsy and the tissue obtained subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also collected. Data on socio-demographic characteristics, clinical symptoms, HIV status and CD4 count were also collected. Sensitivity, specificity, positive and negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB diagnosis were calculated using pleural tissue MTB culture and/or histopathology as the reference standard. Results: Of the 116 participants [female 50%, mean age 34 (SD 613], 87/116 (75%) had pleural TB confirmed on pleural tissue culture and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87 confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test were 28.7% and 96.6% respectively while the positive and negative predictive values were 96.1% and 31.1% respectively. Conclusion: Xpert MTB/Rif test on pleural fluid does not accurately diagnose pleural TB and therefore cannot be used as an initial evaluation test in patients with suspected pleural TB. New, rapid and accurate tests for the diagnosis of pleural TB are still warranted.
Evaluation of circulating serum cathelicidin levels as a potential biomarker to discriminate between active and latent tuberculosis in Uganda
(PloS one, 2022) Acen, Ester Lilian; Kateete, David Patrick; Worodria, William; Olum, Ronald; Joloba, Moses L.; Bbuye, Mudarshiru; Biraro, Irene Andia
Tuberculosis remains a major public health problem worldwide accounting for 1.4 million deaths annually. LL-37 is an effector molecule involved in immunity with both antimicrobial and immunomodulatory properties. The purpose of this study was to compare LL-37 circulatory levels among participants with active and latent tuberculosis and to determine its ability to discriminate between the two infectious states. Methods A cross-sectional study was performed among 56 active tuberculosis patients, 49 latent tuberculosis individuals, and 43 individuals without tuberculosis infection. The enzymelinked immunosorbent assay was used to assess LL-37 levels. Data analysis was performed using STATA software and Graph pad Prism version 8. Mann-Whitney U test was used for correlation between variables with two categories and the Kruskal-Wallis test for three or more categories. Results The study had more female participants than males, with similar median ages across the three groups, 29.5, 25.0, and 23.0 years respectively. Active tuberculosis patients had significantly higher LL-37 levels compared to those with latent tuberculosis and without tuberculosis. The median/interquartile ranges were 318.8 ng/ml (157.9–547.1), 242.2 ng/ml (136.2–579.3), 170.9 ng/ml (129.3–228.3); p = 0.002 respectively. Higher LL-37 was found in the male participant with median/interquartile range, 424.8 ng/ml (226.2–666.8) compared to the females 237.7 ng/ml (129.6–466.6); p = 0.045. LL-37 had better discriminatory potential between active tuberculosis and no tuberculosis (AUC = 0.71, sensitivity 71.4% specificity = 69.8%) than with latent tuberculosis (AUC = 0.55, sensitivity = 71.4%, specificity = 44.9%). There was moderate differentiation between latent tuberculosis and no tuberculosis (AUC = 0.63, sensitivity = 44.9% specificity = 90.7%). Conclusion Significantly higher LL-37 levels were observed among active tuberculosis patients than those without tuberculosis infection and were, therefore able to discriminate between active tuberculosis and other tuberculosis infectious states, especially with no tuberculosis. Further assessment of this biomarker as a screening tool to exclude tuberculosis is required.
Evaluation of in-house PCR for diagnosis of smear-negative pulmonary tuberculosis in Kampala, Uganda
(BMC Research Notes, 2012) Nakiyingi, Lydia; Kateete, David P.; Ocama, Ponsiano; Worodria, William; Sempa, Joseph B.; Asiimwe, Benon B.; Katabazi, Fred A.; Katamba, Achilles; Huang, Laurence; Joloba, Moses L.; Mayanja-Kizza, Harriet
Nucleic acid amplification tests (NAATs) have offered hope for rapid diagnosis of tuberculosis (TB). However, their efficiency with smear-negative samples has not been widely studied in low income settings. Here, we evaluated in-house PCR assay for diagnosis of smear-negative TB using Lowenstein-Jensen (LJ) culture as the baseline test. Two hundred and five pulmonary TB (PTB) suspects with smear-negative sputum samples, admitted on a short stay emergency ward at Mulago Hospital in Kampala, Uganda, were enrolled. Two smear-negative sputum samples were obtained from each PTB suspect and processed simultaneously for identification of MTBC using in-house PCR and LJ culture. Results: Seventy two PTB suspects (35%, 72/205) were LJ culture positive while 128 (62.4%, 128/205) were PCR-positive. The sensitivity and specificity of in-house PCR for diagnosis of smear-negative PTB were 75% (95% CI 62.6-85.0) and 35.9% (95% CI 27.2-45.3), respectively. The positive and negative predictive values were 39% (95% CI 30.4-48.2) and 72.4% (95% CI 59.1-83.3), respectively, while the positive and negative likelihood ratios were 1.17 (95% CI 0.96-1.42) and 0.70 (95% CI 0.43-1.14), respectively. One hundred and seventeen LJ culturenegative suspects (75 PCR-positive and 42 PCR-negative) were enrolled for follow-up at 2 months. Of the PCR-positive suspects, 45 (60%, 45/75) were still alive, of whom 29 (64.4%, 29/45) returned for the follow-up visit; 15 (20%, 15/75) suspects died while another 15 (20%, 15/75) were lost to follow-up. Of the 42 PCR-negative suspects, 22 (52.4%, 22/42) were still alive, of whom 16 (72.7%, 16/22) returned for follow-up; 11 (26.2%, 11/42) died while nine (21.4%, 9/42) were lost to follow-up. Overall, more PCR-positive suspects were diagnosed with PTB during follow-up visits but the difference was not statistically significant (27.6%, 8/29 vs. 25%, 4/16, p = 0.9239). Furthermore, mortality was higher for the PCR-negative suspects but the difference was also not statistically significant (26.2% vs. 20% p = 0.7094). Conclusion: In-house PCR correlates poorly with LJ culture for diagnosis of smear-negative PTB. Therefore, in-house PCR may not be adopted as an alternative to LJ culture.
High Mortality Associated with Retreatment of Tuberculosis in a Clinic in Kampala, Uganda: A Retrospective Study
(The American Journal of Tropical Medicine and Hygiene, 2015) Acuna-Villaorduna, Carlos; Ayakaka, Irene; Dryden-Peterson, Scott; Nakubulwa, Susan; Worodria, William; Reilly, Nancy; Hosford, Jennifer; Fennelly, Kevin P.; Okwera, Alphonse; Jones-Lopez, Edward C.
The World Health Organization recommends for tuberculosis retreatment a regimen of isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and streptomycin (S) for 2 months, followed by H, R, E, and Z for 1 month and H, R, and E for 5 months. Using data from the National Tuberculosis and Leprosy Program registry, this study determined the long-term outcome under programmatic conditions of patients who were prescribed the retreatment regimen in Kampala, Uganda, between 1997 and 2003. Patients were traced to determine their vital status; 62% (234/377) patients were found dead. Having £ 2 treatment courses and not completing retreatment were associated with mortality in adjusted analyses.
Incidence and Predictors of Mortality and the Effect of Tuberculosis Immune Reconstitution Inflammatory Syndrome in a Cohort of TB/HIV Patients Commencing Antiretroviral Therapy
(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2011) Worodria, William; Massinga-Loembe, Marguerite; Mazakpwe, Doreen; Luzinda, Kenneth; Mayanja-Kizza, Harriet; Mugerwa, Roy D.; Reiss, Peter; Colebunders, Robert; For the TB-IRIS Study Group
Tuberculosis-HIV (TB-HIV) coinfection remains an important cause of mortality in antiretroviral therapy (ART) programs. In a cohort of TB-HIV-coinfected patients starting ART, we examined the incidence and predictors of early mortality.Consecutive TB-HIV-coinfected patients eligible for ART were enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Program clinic in Kampala, Uganda. Predictors of mortality were assessed using Cox proportional hazards analysis. Three hundred and two patients [median CD4 count 53 cells/μL (interquartile range, 20-134)] were enrolled. Fifty-three patients died, 36 (68%) of these died within the first 6 months of TB diagnosis. Male sex [hazard (HR): 2.19; 95% confidence interval (CI): 1.19 to 4.03; P = 0.011], anergy to tuberculin skin test [HR: 2.59 (1.10 to 6.12); P = 0.030], a positive serum cryptococcal antigen result at enrollment (HR: 4.27; 95% CI: 1.50 to 12.13; P = 0.006) and no ART use (HR: 4.63; 95% CI: 2. 37 to 9.03; P < 0.001) were independent predictors of mortality by multivariate analysis. Six (10%) patients with TB immune reconstitution inflammatory syndrome died, and in most, an alternative contributing cause of death was identified.Mortality among these TB-HIV-coinfected patients was high particularly when presenting with advanced HIV disease and not starting ART, reinforcing the need for timely and joint treatment for both infections. Screening for a concomitant cryptococcal infection and antifungal treatment for patients with cryptococcal antigenemia may further improve clinical outcome.
New Manual Quantitative Polymerase Chain Reaction Assay Validated on Tongue Swabs Collected and Processed in Uganda Shows Sensitivity That Rivals Sputum-based Molecular Tuberculosis Diagnostics
(Clinical Infectious Diseases, 2024-02-02) Steadman, Amy; Andama, Alfred; Ball, Alexey; Mukwatamundu, Job; Khimani, Khushboo;; Mochizuki, Tessa; Asege, Lucy; Bukirwa, Alice; Kato, John Baptist; Katumba, David; Kisakye, Esther; Mangeni, Wilson; Mwebe, Sandra; Nakaye, Martha; Nassuna, Irene; Nyawere, Justine; Nakaweesa, Annet; Cook, Catherine; Phillips, Patrick; Nalugwa, Talemwa; Bachman, Christine M; Semitala, Fred Collins; Weigl, Bernhard H; Connelly, John; Worodria, William; Cattamanchi, Adithya
BACKGROUNDSputum-based testing is a barrier to increasing access to molecular diagnostics for tuberculosis (TB). Many people with TB are unable to produce sputum, and sputum processing increases assay complexity and cost. Tongue swabs are emerging as an alternative to sputum, but performance limits are uncertain.METHODSFrom June 2022 to July 2023, we enrolled 397 consecutive adults with cough >2 weeks at 2 health centers in Kampala, Uganda. We collected demographic and clinical information, sputum for TB testing (Xpert MTB/RIF Ultra and 2 liquid cultures), and tongue swabs for same-day quantitative polymerase chain reaction (qPCR) testing. We evaluated tongue swab qPCR diagnostic accuracy versus sputum TB test results, quantified TB targets per swab, assessed the impact of serial swabbing, and compared 2 swab types (Copan FLOQSWAB and Steripack spun polyester).RESULTSAmong 397 participants, 43.1% were female, median age was 33 years, 23.5% were diagnosed with human immunodeficiency virus, and 32.0% had confirmed TB. Sputum Xpert Ultra and tongue swab qPCR results were concordant for 98.2% (95% confidence interval [CI]: 96.2-99.1) of participants. Tongue swab qPCR sensitivity was 92.6% (95% CI: 86.5 to 96.0) and specificity was 99.1% (95% CI: 96.9 to 99.8) versus microbiological reference standard. A single tongue swab recovered a 7-log range of TB copies, with a decreasing recovery trend among 4 serial swabs. Swab types performed equivalently.CONCLUSIONSTongue swabs are a promising alternative to sputum for molecular diagnosis of TB, with sensitivity approaching sputum-based molecular tests. Our results provide valuable insights for developing successful tongue swab-based TB diagnostics. MEDLINE - Academic
Performance of Frontloading for Smear Microscopy in the Diagnosis of Pulmonary Tuberculosis: A Cross- Sectional Study at a Referral Hospital in Uganda
(PLoS ONE, 2012) Miremba, Penelope; Kalyango, Joan N.; Worodria, William; Mugerwa, Henry; Nakakawa, Ethel; Asiimwe, Benon B.
To compare the performance of frontloading and the standard WHO method for diagnosis of pulmonary TB at Mulago Hospital in order to validate the technique in this setting. Methods: This was a cross-sectional study in which 229 adult ($18 years) TB suspects were consecutively enrolled. Suspects submitted three sputum samples as follows: at initial presentation, one hour after the first sample, and the next morning. The first and next morning samples formed the standard WHO method, while the first and the one hour later samples formed the frontloading method. Sample processing was by the standard N-acetyl L-cystein (NALC)-NaOH method, and fluorescent microscopy was done for both methods, while cultures of the first sample on Lowenstein-Jensen slants acted as a gold standard. The sensitivity, specificity and predictive values for the WHO standard and frontloading methods were compared. Results: The sensitivity of both the frontloading and standard schemes was 91.1% while their specificities were 86.2% and 91.7% respectively. There was excellent agreement between the diagnostic capacity of the two methods (kappa statistic = 0.87, P,0.0001). The positive predictive value for the frontloading scheme was 87.2% and that for the standard approach was 91.9%, while the negative predictive values were 90.4% and 90.9%, respectively. Among the HIV positive patients, frontloading identified 59/79 (74.7%) culture positive samples while the standard approach identified 55/79 (69.6%). In the HIV sero-negative category, on the other hand, front-loading identified 48/110 (43.6%) culture positive samples compared to 45/110 (40.9%) by the standard approach. Conclusion: Frontloading based on smear examination of two same-day sputum samples has a similar performance to the current standard method and would not be associated with any significant missed diagnosis. It may therefore be advocated for use in our setting so as to reduce time to completion of diagnosis and patient loss to follow-up.

Browsing by Author "Worodria, William"

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