Browsing by Author "Mayanja-Kizza, Harriet"

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    A 10-year retrospective study of lung cancer in Uganda
    (BioMed Central Ltd, 2022-02) Bogere, Naghib; Bongomin, Felix; Katende, Andrew; Omaido, Blair Andrew; Namukwaya, Elizabeth; Mayanja-Kizza, Harriet; Walusansa, Victoria
    Abstract Background Lung cancer is a leading cause of cancer-related deaths in Uganda. In this study, we aimed to describe the baseline characteristics and survival of patients with lung cancer at the Uganda Cancer Institute (UCI). Methods We retrospectively reviewed medical records of all patients with a histological diagnosis of lung cancer registered at UCI between January 2008 and August 2018. Data on demographic, clinical, and treatment characteristics, and vital status were abstracted and analyzed. Patients with undocumented vital status on the medical records were contacted through phone calls. We determined survival as time from histological diagnosis to death. The Kaplan-Meier survival analysis was performed to estimate the median survival time and the 5-year overall survival rate. Results Of the 207 patients enrolled, 56.5% (n = 117) were female, median age was 60 years (range: 20–94), 78.7% (n = 163) were never-smokers and 18 (8.7%) were living with HIV. Presumptive anti-tuberculosis treatment was given to 23.2% (n = 48). Majority had non-small cell lung cancer (96.6%, n = 200) with 74.5% (n = 149) adenocarcinoma and 19% (n = 38) squamous cell carcinoma. All had advanced (stage III or IV) disease with 96.1% (n = 199) in stage IV. Chemotherapy (44.9%, n = 93) and biological therapy (34.8%, n = 72) were the commonest treatments used. Overall survival at 6 months, 1-, 2- and 5-years was 41.7, 29.7, 11.8, and 1.7%, respectively. The median survival time of 4.4 months was not statistically significantly different between participants with NSCLC or SCLC (4.5 versus 3.9 months, p = .335). Conclusion In Uganda, adenocarcinoma is the predominant histologic subtype of lung cancer and patients are predominantly females, and non-smokers. Patients present late with advanced disease and poor overall survival. Public awareness should be heightened to facilitate early detection and improve outcomes.
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    Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial
    (The Lancet Global Health, 2013) Wanyenze, Rhoda K.; Kamya, Moses R.; Fatch, Robin; Mayanja-Kizza, Harriet; Baveewo, Steven; Szekeres, Gregory; Bangsberg, David; Coates, Thomas; Hahn, Judith A.
    HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its eff ect on HIV risk is uncertain and methods to improve linkage to care have not been studied. We did this factorial randomised controlled study at Mulago Hospital, Uganda. Participants were randomly assigned to abbreviated or traditional HIV counselling and testing; HIV-infected patients were randomly assigned to enhanced linkage to care or standard linkage to care. All study personnel except counsellors and the data offi cer were masked to study group assignment. Participants had structured interviews, given once every 3 months. We compared sexual risk behaviour by counselling strategy with a 6·5% non-inferiority margin. We used Cox proportional hazards analyses to compare HIV outcomes by linkage to care over 1 year and tested for interaction by sex. This trial is registered with ClinicalTrials.gov (NCT00648232). We enrolled 3415 participants; 1707 assigned to abbreviated counselling versus 1708 assigned to traditional. Unprotected sex with an HIV discordant or status unknown partner was similar in each group (232/823 [27·9%] vs 251/890 [28·2%], diff erence –0·3%, one-sided 95% CI 3·2). Loss to follow-up was lower for traditional counselling than for abbreviated counselling (adjusted hazard ratio [HR] 0·61, 95% CI 0·44–0·83). 1003 HIV-positive participants were assigned to enhanced linkage (n=504) or standard linkage to care (n=499). Linkage to care did not have a signifi cant eff ect on mortality or receipt of co-trimoxazole. Time to treatment in men with CD4 cell counts of 250 cells per μL or fewer was lower for enhanced linkage versus standard linkage (adjusted HR 0·60, 95% CI 0·41–0·87) and time to HIV care was decreased among women (0·80, 0·66–0·96).
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    Acceptance of Routine Testing for HIV among Adult Patients at the Medical Emergency Unit at a National Referral Hospital in Kampala, Uganda
    (AIDS and Behavior, 2007) Nakanjako, Damalie; Kamya, Moses; Mayanja-Kizza, Harriet; Freers, Jurgen; Whalen, Christopher; Katabira, Elly
    HIV testing is an entry point to comprehensive HIV/AIDS prevention and care. In Uganda, Routine Testing and Counseling for HIV (RTC) is not widely offered as part of standard medical care in acute care settings. This study determined the acceptance of RTC in a medical emergency setting at Mulago national referral hospital. We interviewed 233 adult patients who were offered HIV testing. Overall, 83% were unaware of their HIV serostatus and 88% of these had been to a health unit in the previous six months. Of the 208 eligible for HIV testing, 95% accepted to test. Half the patients were HIV infected and 77% of these were diagnosed during the study. HIV testing was highly acceptable and detected a significant number of undiagnosed HIV infections. We recommend adoption of RTC as standard of care in the medical emergency unit in order to scale HIV diagnosis and linkage to HIV/AIDS care.
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    Airway microbiome signature accurately discriminates Mycobacterium tuberculosis infection status
    (Elsevier Inc, 2024-06) Kayongo, Alex; Ntayi, Moses Levi; Olweny, Geoffrey; Kyalo, Edward; Ndawula, Josephine; Ssengooba, Willy; Kigozi, Edgar; Kalyesubula, Robert; Munana, Richard; Namaganda, Jesca; Caroline, Musiime; Sekibira, Rogers; Bagaya, Bernard Sentalo; Kateete, David Patrick; Joloba, Moses Lutaakome; Jjingo, Daudi; Sande, Obondo James; Mayanja-Kizza, Harriet
    Abstract Mycobacterium tuberculosis remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for novel therapeutic strategies. Despite advances in understanding the interplay between microbiome and disease in humans, the specific role of the microbiome in predicting disease susceptibility and discriminating infection status in tuberculosis still needs to be fully investigated. We investigated the impact of M.tb infection and M.tb-specific IFNγ immune responses on airway microbiome diversity by performing TB GeneXpert and QuantiFERON-GOLD assays during the follow-up phase of a longitudinal HIV-Lung Microbiome cohort of individuals recruited from two large independent cohorts in rural Uganda. M.tb rather than IFNγ immune response mainly drove a significant reduction in airway microbiome diversity. A microbiome signature comprising Streptococcus, Neisseria, Fusobacterium, Prevotella, Schaalia, Actinomyces, Cutibacterium, Brevibacillus, Microbacterium, and Beijerinckiacea accurately discriminated active TB from Latent TB and M.tb-uninfected individuals. [Display omitted] •M.tb infection drives a significant reduction in airway microbiome diversity•M.tb-specific IFNg does not directly impact airway microbiome diversity•Airway microbiome signature discriminates active TB from LTBI and uninfected states•LTBI and M.tb-uninfected states display similar airway microbiome diversity Microbiology; Bacteriology; Microbiome
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    Analysis of Host Responses to Mycobacterium tuberculosis Antigens in a Multi-Site Study of Subjects with Different TB and HIV Infection States in Sub-Saharan Africa
    (PloS one, 2013) Sutherland, Jayne S.; Lalor, Maeve K.; Mayanja-Kizza, Harriet; Kaufmann, Stefan H. E.; and the GCGH Biomarkers for TB consortium
    Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas.
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    Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals
    (Malaria Research and Treatment, 2011) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Mayanja-Kizza, Harriet; Khoo, Saye; Merry, Concepta; Van geertruyden, Jean-Pierre Van geertruyden4
    Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART) poses significant challenges. Artemetherlumefantrine (AL) is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine aremetabolized by hepatic cytochrome P450 (CYP450) enzymes which metabolize the protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) used forHIV treatment. Coadministration of NNRTIs and PIs with AL could potentially cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4 enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target populations are urgently needed.
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    Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial
    (Tropical medicine & international health, 2015) Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D.; Kamya, Moses R.; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet
    T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery.A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry.Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported.Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa.
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    Burden of tuberculosis disease among adolescents in a rural cohort in Eastern Uganda
    (BMC Infectious Diseases,, 2013) Waako, James; Verver, Suzanne; Wajja, Anne; Ssengooba, Willy; Joloba, Moses L; Colebunders, Robert; Musoke, Philippa; Mayanja-Kizza, Harriet
    Background: The world health organization (WHO) declared tuberculosis (TB) a global emergency, mainly affecting people in sub-Saharan Africa. However there is little data about the burden of TB among adolescents. We estimated the prevalence and incidence of TB and assessed factors associated with TB among adolescents aged 12–18 years in a rural population in Uganda in order to prepare the site for phase III clinical trials with novel TB vaccines among adolescents. Methods: In a prospective cohort study, we recruited 5000 adolescents and followed them actively, every 6 months, for 1–2 years. Participants suspected of having TB were those who had any of; TB signs and symptoms, history of TB contact or a positive tuberculin skin test (TST) of ≥10 mm. Laboratory investigations included sputum smear microscopy and culture. Results: Of the 5000 participants, eight culture confirmed cases of TB were found at baseline: a prevalence of 160/100,000 (95% confidence interval (CI), 69–315). There were 13 incident TB cases detected in an average of 1.1 person years: an incidence of 235/100,000 person years (95% CI, 125–402). None of the confirmed TB cases were HIV infected. Predictors for prevalent TB disease were: a history of TB contact and a cough ≥ 2 weeks at baseline and being out of school, while the only predictor for incident TB was a positive TST during follow-up. Conclusion: The TB incidence among adolescents in this rural part of Uganda seemed too low for a phase III TB vaccine trial. However, the study site demonstrated capability to handle a large number of participants with minimal loss to follow-up and its suitability for future clinical trials. Improved contact tracing in TB program activities is likely to increase TB case detection among adolescents. Future studies should explore possible pockets of higher TB incidence in urban areas and among out of school youth
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    Cardiac Conduction Safety during Coadministration of Artemether-Lumefantrine and Lopinavir/Ritonavir in HIV-Infected Ugandan Adults
    (Chemotherapy research and practice, 2011) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Lwabi, Peter; Nyakoojo, Wilson B.; Okaba-Kayom, Violet; Mayanja-Kizza, Harriet; Boffito, Marta; Katabira, Elly; Back, David; Khoo, Saye; Merry, Concepta
    We aimed to assess cardiac conduction safety of coadministration of the CYP3A4 inhibitor lopinavir/ritonavir (LPV/r) and the CYP3A4 substrate artemether-lumefantrine (AL) in HIV-positive Ugandans. Methods. Open-label safety study of HIV positive adults administered single-dose AL (80/400 mg) alone or with LPV/r (400/100 mg). Cardiac function was monitored using continuous electrocardiograph (ECG). Results. Thirty-two patients were enrolled; 16 taking LPV/r -based ART and 16 ART naıve. All took single dose AL. No serious adverse events were observed. ECG parameters in milliseconds remained within normal limits. QTc measurements did not change significantly over 72 hours although were higher in LPV/r arm at 24 (424 versus 406; P = .02) and 72 hours (424 versus 408; P = .004) after AL intake. Conclusion. Coadministration of single dose of AL with LPV/r was safe; however, safety of six-dose AL regimen with LPV/r should be investigated.
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    CD81 T Cells Provide an Immunologic Signature of Tuberculosis in Young Children
    (American Thoracic Society, 2011) Lancioni, Christina; Nyendak, Mellisa; Sarah Zalwango, Sarah Kiguli; Mori, Tomi; Mayanja-Kizza, Harriet; Balyejusa, Stephen; Null, Megan; Baseke, Joy; Mulindwa, Deo; Byrd, Laura; Swarbrick, Gwendolyn; Scott, Christine; Johnson, Denise F.; Malone, LaShaunda; Mudido-Musoke, Philipa; Boom, Henry; Lewinsohn, David M.; Lewinsohn, Deborah A.
    Mycobacterium tuberculosis (Mtb), the etiology of tuberculosis (TB), causes over 9 million cases of disease and 1.7 million deaths annually (1). The only available vaccine to prevent TB, bacillus Calmette-Gue´ rin, offers little protection against the most common disease manifestations (2) and efforts to develop an improved vaccine are hampered by poor understanding of immunologic events that occur after Mtb exposure. Scientific studies of immunologic responses to initial Mtb infection are difficult because most individuals living in TB-endemic settings have experienced multiple Mtb exposures. Young children, however, suffer disproportionately after exposure to Mtb, because they are at substantial risk for developing TB after primary infection (3–5). Therefore, young children with TB offer a valuable window into the human immune response to primary Mtb infection.
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    Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda
    (BioMed Central, 2014) Ma, Ningning; Zalwango, Sarah; Malone, LaShaunda L; Nsereko, Mary; Wampande, Eddie M; Thiel, Bonnie A; Okware, Brenda; Igo Jr., Robert P; Joloba3, Moses L.; Mupere, Ezekiel; Mayanja-Kizza, Harriet; Boom, Henry; Stein, Catherine M
    Background: Despite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment. Methods: During a TB household contact study in Kampala, Uganda, PTST-, TSTC, and TST + individuals were identified. PTST- individuals maintained a negative TST over a 2 year observation period despite prolonged exposure to an infectious tuberculosis (TB) case. Epidemiological and clinical characteristics were compared, a risk score developed by another group to capture risk for Mtb infection was computed, and an ordinal regression was performed. Results: When analyzed independently, epidemiological risk factors increased in prevalence from PTST- to TSTC to TST+. An ordinal regression model suggested age (p < 0.01), number of windows (p < 0.01) and people (p = 0.07) in the home, and sleeping in the same room (p < 0.01) were associated with PTST- and TSTC. As these factors do not exist in isolation, we examined a risk score, which reflects an accumulation of risk factors. This compound exposure score did not differ significantly between PTST-, TSTC, and TST+, except for the 5–15 age group (p = 0.009). Conclusions: Though many individual factors differed across all three groups, an exposure risk score reflecting a collection of risk factors did not differ for PTST-, TSTC and TST + young children and adults. This is the first study to rigorously characterize the epidemiologic risk profile of individuals with persistently negative TSTs despite close exposure to a person with TB. Additional studies are needed to characterize possible epidemiologic and host factors associated with this phenotype.
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    Comprehensive definition of human immunodominant CD8 antigens in tuberculosis
    (NPJ vaccines, 2017) Lewinsohn, Deborah A.; Swarbrick, Gwendolyn M.; Park, Byung; Cansler, Meghan E.; Null, Megan D.; Toren, Katelynne G.; Baseke, Joy; Zalwango, Sarah; Mayanja-Kizza, Harriet; Malone, LaShaunda L.; Nyendak, Melissa; Wu, Guanming; Guinn, Kristi; McWeeney, Shannon; Mori, Tomi; Chervenak, Keith A.; Sherman, David R.; Boom, W. Henry; Lewinsohn, David M.
    Despite widespread use of the Bacillus Calmette-Guerin vaccine, tuberculosis, caused by infection with Mycobacterium tuberculosis, remains a leading cause of morbidity and mortality worldwide. As CD8+ T cells are critical to tuberculosis host defense and a phase 2b vaccine trial of modified vaccinia Ankara expressing Ag85a that failed to demonstrate efficacy, also failed to induce a CD8+ T cell response, an effective tuberculosis vaccine may need to induce CD8+ T cells. However, little is known about CD8, as compared to CD4, antigens in tuberculosis. Herein, we report the results of the first ever HLA allele independent genome-wide CD8 antigen discovery program. Using CD8+ T cells derived from humans with latent tuberculosis infection or tuberculosis and an interferon-γ ELISPOT assay, we screened a synthetic peptide library representing 10% of the Mycobacterium tuberculosis proteome, selected to be enriched for Mycobacterium tuberculosis antigens. We defined a set of immunodominant CD8 antigens including part or all of 74 Mycobacterium tuberculosis proteins, only 16 of which are previously known CD8 antigens. Immunogenicity was associated with the degree of expression of mRNA and protein. Immunodominant antigens were enriched in cell wall proteins with preferential recognition of Esx protein family members, and within proteins comprising the Mycobacterium tuberculosis secretome. A validation study of immunodominant antigens demonstrated that these antigens were strongly recognized in Mycobacterium tuberculosisinfected individuals from a tuberculosis endemic region in Africa. The tuberculosis vaccine field will likely benefit from this greatly increased known repertoire of CD8 immunodominant antigens and definition of properties of Mycobacterium tuberculosis proteins important for CD8 antigenicity.
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    Concise gene signature for point-of-care classification of tuberculosis
    (EMBO molecular medicine, 2016) Maertzdorf, Jeroen; McEwen, Gayle McEwenGayle; Weine, January; Mayanja-Kizza, Harriet; Kaufmann, Stefan HE
    There is an urgent need for new tools to combat the ongoing tuberculosis (TB) pandemic. Gene expression profiles based on blood signatures have proved useful in identifying genes that enable classification of TB patients, but have thus far been complex. Using real-time PCR analysis, we evaluated the expression profiles from a large panel of genes in TB patients and healthy individuals in an Indian cohort. Classification models were built and validated for their capacity to discriminate samples from TB patients and controls within this cohort and on external independent gene expression datasets. A combination of only four genes distinguished TB patients from healthy individuals in both cross-validations and on separate validation datasets with very high accuracy. An external validation on two distinct cohorts using a real-time PCR setting confirmed the predictive power of this 4-gene tool reaching sensitivity scores of 88% with a specificity of around 75%. Moreover, this gene signature demonstrated good classification power in HIV+ populations and also between TB and several other pulmonary diseases. Here we present proof of concept that our 4-gene signature and the top classifier genes from our models provide excellent candidates for the development of molecular point-of-care TB diagnosis in endemic areas.
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    Contact Investigation for Active Tuberculosis Among Child Contacts in Uganda
    (Oxford University Press, 2013) Jaganath, Devan; Zalwango, Sarah; Okware, Brenda; Nsereko, Mary; Kisingo, Hussein; Malone, LaShaunda; Lancioni, Christina; Okwera, Alphonse; Joloba, Moses; Mayanja-Kizza, Harriet; Boom, Henry; Stein, Catherine; Mupere, Ezekiel
    Background. Tuberculosis is a large source of morbidity and mortality among children. However, limited studies characterize childhood tuberculosis disease, and contact investigation is rarely implemented in high-burden settings. In one of the largest pediatric tuberculosis contact investigation studies in a resource-limited setting, we assessed the yield of contact tracing on childhood tuberculosis and indicators for disease progression in Uganda. Methods. Child contacts aged <15 years in Kampala, Uganda, were enrolled from July 2002 to June 2009 and evaluated for tuberculosis disease via clinical, radiographic, and laboratory methods for up to 24 months. Results. Seven hundred sixty-one child contacts were included in the analysis. Prevalence of tuberculosis in our child population was 10%, of which 71% were culture-confirmed positive. There were no cases of disseminated tuberculosis, and 483 of 490 children (99%) started on isoniazid preventative therapy did not develop disease. Multivariable testing suggested risk factors including human immunodeficiency virus (HIV) status (odds ratio [OR], 7.90; P < .001), and baseline positive tuberculin skin test (OR, 2.21; P = .03); BCG vaccination was particularly protective, especially among children aged ≤5 years (OR, 0.23; P < .001). Adult index characteristics such as sex, HIV status, and extent or severity of disease were not associated with childhood disease. Conclusions. Contact tracing for children in high-burden settings is able to identify a large percentage of culture-confirmed positive tuberculosis cases before dissemination of disease, while suggesting factors for disease progression to identify who may benefit from targeted screening.
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    Determinants of hypertension in a young adult Ugandan population in epidemiological transition—the MEPI-CVD survey
    (BMC public health, 2015) Kayima, James; Nankabirwa, Joaniter; Sinabulya, Isaac; Nakibuuka, Jane; Zhu, Xiaofeng; Rahman, Mahboob; Longenecker, Christopher T.; Katamba, Achilles; Mayanja-Kizza, Harriet; Kamya, Moses R.
    High blood pressure is the principal risk factor for stroke, heart failure and kidney failure in the young population in Africa. Control of hypertension is associated with a larger reduction in morbidity and mortality in younger populations compared with the elderly; however, blood pressure control efforts in the young are hampered by scarcity of data on prevalence and factors influencing awareness, treatment and control of hypertension. We aimed to describe the prevalence of prehypertension and hypertension among young adults in a peri-urban district of Uganda and the factors associated with occurrence of hypertension in this population. Methods: This cross-sectional study was conducted between August, 2012 and May 2013 in Wakiso district, a suburban district that that encircles Kampala, Uganda’s capital city. We collected data on socio-demographic characteristics and hypertension status using a modified STEPs questionnaire from 3685 subjects aged 18–40 years selected by multistage cluster sampling. Blood pressure and anthropometric measurements were performed using standardized protocols. Fasting blood sugar and HIV status were determined using a venous blood sample. Association between hypertension status and various biosocial factors was assessed using logistic regression. Results: The overall prevalence of hypertension was 15 % (95 % CI 14.2 – 19.6) and 40 % were pre-hypertensive. Among the 553 hypertensive participants, 76 (13.7 %) were aware of their diagnosis and all these participants had initiated therapy with target blood pressure control attained in 20 % of treated subjects. Hypertension was significantly associated with the older age-group, male sex and obesity. There was a significantly lower prevalence of hypertension among participants with HIV OR 0.6 (95 % CI 0.4–0.8, P = 0.007). Conclusion: There is a high prevalence of high blood pressure in this young periurban population of Uganda with sub-optimal diagnosis and control. There is previously undocumented high rate of treatment, a unique finding that may be exploited to drive efforts to control hypertension. Specific programs for early diagnosis and treatment of hypertension among the young should be developed to improve control of hypertension. The relationship between HIV infection and blood pressure requires further clarification by longitudinal studies.
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    Diagnostic accuracy of the Cepheid 3-gene host response fingerstick blood test in a prospective, multi-site study: interim results
    (Clinical Infectious Diseases, 2021) Sutherland, Jayne S.; Spuy, Gian van der; Gindeh, Awa; Thuong, Nguyen Thuy; Namuganga, AnnRitah; Owolabi, Olumuyiwa; Mayanja-Kizza, Harriet; Nsereko, Mary; Thwaites, Guy; Winter, Jill; Dockrell, Hazel M.; Scriba, Thomas J.; Geluk, Annemieke; Corstjens, Paul; Stanley, Kim; Richardson, Tracy; Shaw, Jane A.; Smith, Bronwyn; Walzl, Gerhard
    The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert-MTB-Host Response (HR)-Prototype), which generates a ‘TB score’ based on mRNA expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype.
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    Doctoral training in Uganda: evaluation of mentoring best practices at Makerere university college of health sciences
    (BMC Medical Education, 2014) Nakanjako, Damalie; Katamba, Achilles; Kaye, Dan K.; Okello, Elialilia; Kamya, Moses R.; Sewankambo, Nelson; Mayanja-Kizza, Harriet
    Good mentoring is a key variable for determining success in completing a doctoral program. We identified prevailing mentoring practices among doctoral students and their mentors, identified common challenges facing doctoral training, and proposed some solutions to enhance the quality of the doctoral training experience for both candidates and mentors at Makerere University College of Health Sciences (MakCHS). Methods: This cross-sectional qualitative evaluation was part of the monitoring and evaluation program for doctoral training. All doctoral students and their mentors were invited for a half-day workshop through the MakCHS mailing list. Prevailing doctoral supervision and mentoring guidelines were summarised in a one-hour presentation. Participants were split into two homogenous students’ (mentees’) and mentors’ groups to discuss specific issues using a focus group discussion (FGD) guide, that highlighted four main themes in regard to the doctoral training experience; what was going well, what was not going well, proposed solutions to current challenges and perceived high priority areas for improvement. The two groups came together again and the note-takers from each group presented their data and discussions were recorded by a note-taker. Results: Twelve out of 36 invited mentors (33%) and 22 out of 40 invited mentees (55%) attended the workshop. Mentors and mentees noted increasing numbers of doctoral students and mentors, which provided opportunities for peer mentorship. Delays in procurement and research regulatory processes subsequently delayed students’ projects. Similarly, mentees mentioned challenges of limited; 1) infrastructure and mentors to support basic science research projects, 2) physical office space for doctoral students and their mentors, 3) skills in budgeting and finance management and 4) communication skills including conflict resolution. As solutions, the team proposed skills’ training, induction courses for doctoral students-mentor teams, and a Frequently Asked Questions’ document, to better inform mentors’, mentees’ expectations and experiences. Conclusion: Systemic and infrastructural limitations affect the quality of the doctoral training experience at MaKCHS. Clinical and biomedical research infrastructure, in addition to training in research regulatory processes, procurement and finance management, communication skills and information technology, were highlighted as high priority areas for strategic interventions to improve mentoring within doctoral training of clinician scientists.
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    The Effect of a Bidirectional Exchange on Faculty and Institutional Development in a Global Health Collaboration
    (PLoS One, 2015) Bodnar, Benjamin E.; Claassen, Cassidy W.; Solomon, Julie; Mayanja-Kizza, Harriet; Rastegar, Asghar
    The MUYU Collaboration is a partnership between Mulago Hospital-Makerere University College of Health Sciences (M-MakCHS), in Kampala, Uganda, and the Yale University School of Medicine. The program allows Ugandan junior faculty to receive up to 1 year of subspecialty training within the Yale hospital system. The authors performed a qualitative study to assess the effects of this program on participants, as well as on M-MakCHS as an institution.Data was collected via semi-structured interviews with exchange participants. Eight participants (67% of those eligible as of 4/2012) completed interviews. Study authors performed data analysis using standard qualitative data analysis techniques.Analysis revealed themes addressing the benefits, difficulties, and opportunities for improvement of the program. Interviewees described the main benefit of the program as its effect on their fund of knowledge. Participants also described positive effects on their clinical practice and on medical education at M-MakCHS. Most respondents cited financial issues as the primary difficulty of participation. Post-participation difficulties included resource limitations and confronting longstanding institutional and cultural habits. Suggestions for programmatic improvement included expansion of the program, ensuring appropriate management of pre-departure expectations, and refinement of program mentoring structures. Participants also voiced interest in expanding post-exchange programming to ensure both the use of and the maintenance of new capacity.The MUYU Collaboration has benefitted both program participants and M-MakCHS, though these benefits remain difficult to quantify. This study supports the assertion that resource-poor to resource-rich exchanges have the potential to provide significant benefits to the resource-poor partner.
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    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.
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    Evaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease
    (Journal of Infection, 2016) Awoniyi, Dolapo O.; Teuchert, Andrea; Sutherland, Jayne S.; Mayanja-Kizza, Harriet; Howe, Rawleigh; Mihret, Adane; Loxton, Andre G.; Sheehama, Jacob; Kassa, Desta; Crampin, Amelia C.; Dockrell, Hazel M.; Kidd, Martin; Rosenkrands, Ida; Geluk, Annemieke; Ottenhoff, Tom H.M.; Chegou, Novel N.; Walzl, Gerhard
    We investigated the accuracy of host markers detected in Mtb antigenstimulated whole blood culture supernatant in the diagnosis of TB. Methods: Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24 h whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques. Results: 17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients. Conclusions: A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance.