NRU :: Browsing by Author "Manabe, Yukari C."

Browsing by Author "Manabe, Yukari C."

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Antibiotic overuse, poor antimicrobial stewardship, and low specificity of syndromic case management in a cross section of men with urethral discharge syndrome in Kampala, Uganda
(PLoS ONE, 2024) Hamill, Matthew M.; Onzia, Annet; Rosalind, M. Parkes-Ratanshi; Kyambadde, Peter; Mande, Emmanuel; Nakate, Vivian; Johan, H. Melendez; Ethan, Gough; Manabe, Yukari C.
Objective High prevalence of sexually transmitted infections (STIs) combined with poor antimicrobial stewardship are drivers of STI antimicrobial resistance (AMR) especially in resource-limited settings where syndromic case management (SCM) is the norm. We characterized patterns of antibiotic use prior to clinic attendance and study enrollment in Ugandan men with urethral discharge syndrome (UDS), evaluated in-clinic prescribing, and the performance characteristics of SCM. Methods Participants were recruited from government clinics participating in an existing gonococcal surveillance program in Kampala, Uganda. Questionnaires including antimicrobial use prior to attendance, prior episodes of UDS, penile swabs, and blood samples were collected. Bivariable and multivariable logistic regression models were used to estimate odds ratios (OR) for preselected factors likely to be associated with antibiotic use. In-clinic antibiotic treatment data were extracted from clinical notes, and the performance of SCM against laboratory-based STI diagnoses was evaluated. Findings Between October 2019 and November 2020, 100(40%) of 250 men with UDS reported taking antibiotics in the 14days prior to attending the clinic. Of these 210(84%) had at least one curable STI and 20% had a reactive point-of-care HIV test. Multivariable analysis demonstrated significant associations between recent antimicrobial use and duration of UDS symptoms <6 days (OR 2.98(95%CI 1.07,8.36), p = 0.038), and sex with women only (OR 0.08(95%CI 0.01,0.82),p = 0.038). The sensitivity of SCM ranged from 80.0% to 94.4%; specificity was low between 5.6% and 33.1%. The positive predictive value of SCM ranged from 2.4(95%CI 0.7,6.0) for trichomoniasis to 63.4(95%CI 56.5,69.9) for gonorrhea. Conclusion Pre-enrollment antibiotic use was common in this population at high risk of STI and HIV. Combined with the poor specificity of SCM for male UDS, extensive antibiotic use is a likely driver of STI-AMR in Ugandan men. Interventions to improve antimicrobial stewardship and deliver affordable diagnostics to augment SCM and decrease overtreatment of STI syndromes are required.
Baseline Xpert MTB/RIF ct values predict sputum conversion during the intensive phase of anti-TB treatment in HIV infected patients in Kampala, Uganda: a retrospective study
(BMC Infectious Diseases, 2021) Namugenyi, Juliet; Musaazi, Joseph; Katamba, Achilles; Kalyango, Joan; Sendaula, Emmanuel; Kambugu, Andrew; Fehr, Jan; Castelnouvo, Barbara; Manabe, Yukari C.; Ssengooba, Willy; Sekaggya-Wiltshire, Christine
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.
Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda
(African Journal of Laboratory Medicine, 2023) Omali, Denis; Buzibye, Allan; Kwizera, Richard; Byakika-Kibwika, Pauline; Namakula, Rhoda; Matovu, Joshua; Mbabazi, Olive; Mande, Emmanuel; Sekaggya-Wiltshire, Christine; Nakanjako, Damalie; Gutteck, Ursula; McAdam, Keith; Easterbrook, Philippa; Kambugu, Andrew; Fehr, Jan; Castelnuovo, Barbara; Manabe, Yukari C.; Lamorde, Mohammed; Mueller, Daniel; Merry, Concepta
Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda. Intervention: Existing laboratory infrastructure was repurposed, and new equipment was acquired. Laboratory personnel were hired and trained to optimise, validate, and develop in-house methods for testing antiretroviral, anti-tuberculosis and other drugs, including 10 high-performance liquid chromatography methods and four mass spectrometry methods. We reviewed all research collaborations and projects for which samples were assayed in the laboratory from January 2006 to November 2020. We assessed laboratory staff mentorship from collaborative relationships and the contribution of research projects towards human resource development, assay development, and equipment and maintenance costs. We further assessed the quality of testing and use of the laboratory for research and clinical care. Lessons learnt: Fourteen years post inception, the clinical pharmacology laboratory had contributed significantly to the overall research output at the institute by supporting 26 pharmacokinetic studies. The laboratory has actively participated in an international external quality assurance programme for the last four years. For clinical care, a therapeutic drug monitoring service is accessible to patients living with HIV at the Adult Infectious Diseases clinic in Kampala, Uganda. Recommendations: Driven primarily by research projects, clinical pharmacology laboratory capacity was successfully established in Uganda, resulting in sustained research output and clinical support. Strategies implemented in building capacity for this laboratory may guide similar processes in other low- and middle-income countries.
Delayed Sputum Culture Conversion in Tuberculosis– Human Immunodeficiency Virus–Coinfected Patients With Low Isoniazid and Rifampicin Concentrations
(Clinical Infectious Diseases, 2018) Sekaggya-Wiltshire, Christine; Braun, Amrei von; Lamorde, Mohammed; Ledergerber, Bruno; Buzibye, Allan; Henning, Lars; Musaazi, Joseph; Gutteck, Ursula; Denti, Paolo; Kock, Miné de; Jetter, Alexander; Byakika-Kibwika, Pauline; Eberhard, Nadia; Matovu, Joshua; Joloba, Moses; Muller, Daniel; Manabe, Yukari C.; Kamya, Moses R.; Corti, Natascia; Kambugu, Andrew; Castelnuovo, Barbara; Fehr2, Jan S.
The relationship between concentrations of antituberculosis drugs, sputum culture conversion, and treatment outcome remains unclear. We sought to determine the association between antituberculosis drug concentrations and sputum conversion among patients coinfected with tuberculosis and human immunodeficiency virus (HIV) and receiving first-line antituberculosis drugs. Methods. We enrolled HIV-infected Ugandans with pulmonary tuberculosis. Estimation of first-line antituberculosis drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of tuberculosis treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion. Results. We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of tuberculosis treatment (hazard ratio, 0.54; 95% confidence interval, .37–.77; P = .001) or by the end of follow-up (0.61; .44–.85; P = .003). Patients in the highest quartile for area under the rifampicin and isoniazid concentration-time curves for were twice as likely to experience sputum conversion than those in the lowest quartile. Rifampicin and isoniazid concentrations below the thresholds and weight <55 kg were both risk factors for unfavorable tuberculosis treatment outcomes. Only 4.4% of the participants had treatment failure. Conclusion. Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission.
Depressive and Anxiety Symptoms Predict Sustained Quality of Life Deficits in HIV-Positive Ugandan Adults Despite Antiretroviral Therapy
(Medicine, 2016) Ezeamama, Amara E.; Woolfork, Makhabele N.; Guwatudde, David; Bagenda, Danstan; Manabe, Yukari C.; Fawzi, Wafaie W.; Fawzi, Mary C. Smith
: The impact of psychosocial status at onset of antiretroviral therapy on changes in quality of life (QOL) and subjectively rated health (SRH) among adults on ART in resource-limited settings is poorly understood. Therefore, we evaluate the association between stigma, anxiety, depression, and social support and change in QOL and SRH in HIV-infected Ugandan adults during an 18-month period. Psychosocial indicators were assessed at enrollment using structured questionnaires. QOL and SRH measures were assessed at months 0, 6, 12, and 18 using the Medical Outcomes Survey-HIV. Linear mixed models determined risk estimated differences in QOL and SRH in relation to quartiles of each psychosocial status indicator. Repeated measures generalized estimating equations modeling was implemented to assess differences inlikelihood ofimproved versus nonimproved SRH during follow-up. QOL scores and SRH improved significantly for all participants over 18 months (P< 0.0001). The gain in QOL increased dose-dependently as baseline depressive symptoms (time depression P< 0.001) and anxiety levels (time anxiety P< 0.001) declined. Lower social support was associated with worse QOL at baseline (P¼ 0.0005) but QOL improvement during follow-up was not dependent on baseline level of social support (time social support P¼ 0.8943) or number of stigmatizing experiences (time stigma P¼ 0.8662). Psychosocial determinants did not predict changes in SRH in this study. High levels of depression and anxiety symptoms at HAART initiation predicts lower gains in QOL for HIV-positive patients for as long as 18 months. Long-term QOL improvements in HIV-infected adults may be enhanced by implementation of psychosocial interventions to reduce depression and anxiety in HIV-infected adults
The effect of standard dose multivitamin supplementation on disease progression in HIV infected adults initiating HAART: a randomized double blind placebo-controlled trial in Uganda
(BMC infectious diseases, 2015) Guwatudde, David; Wang, Molin; Ezeamama, Amara E.; Bagenda, Danstan; Kyeyune, Rachel; Wamani, Henry; Manabe, Yukari C.; Fawzi, Wafaie W.
Efficacy trials investigating the effect of multivitamin (MV) supplementations among patients on Highly Active Antiretroviral Therapy (HAART) have so far been inconclusive. We conducted a randomized, double blind, placebo controlled trial to determine the effect of one recommended daily allowance (RDA) of MV supplementation on disease progression in patients initiating HAART. Methods: Eligible subjects were randomized to receive placebo or MV supplementation including vitamins Bcomplex, C and E. Participants were followed for up to 18 months. Primary endpoints were: change in CD4 cell count, weight and quality of life (QoL). Secondary endpoints were: i) development of a new or recurrent HIV disease progression event, including all-cause mortality; ii) switching from first- to second-line antiretroviral therapy (ART); and iii) occurrence of an adverse event. Intent-to-treat analysis, using linear regression mixed effects models were used to compare changes over time in the primary endpoints between the study arms. Kaplan-Meier time-toevent analysis and the log-rank test was used to compare HIV disease progression events and all-cause mortality. Results: Four hundred participants were randomized, 200 onto MV and 200 onto placebo. By month 18, the average change in CD4 cell count in the MV arm was 141 cells/uL compared to 147 cells/uL in the placebo arm, a mean difference of −6 · 17 [95 % CI −29 · 3, 16 · 9]. The average change in weight in the MV arm was 3 · 9 kg compared to 3 · 3 kg in the placebo arm, a mean difference of 0 · 54 [95 % CI −0 · 40, 1 · 48]; whereas average change in QoL scores in the MV arm was 6 · 8 compared to 8 · 8 in the placebo arm, a mean difference of −2.16 [95 % CI −4 · 59,0 · 27]. No significant differences were observed in these primary endpoints, or in occurrence of adverse events between the trial arms. Conclusions: One RDA of MV supplementation was safe but did not have an effect on indicators of disease progression among HIV infected adults initiating HAART.
Estimating the effect of pretreatment loss to follow up on TB associated mortality at public health facilities in Uganda
(PLoS ONE, 2020) Zawedde-Muyanja, Stella; Musaazi, Joseph; Manabe, Yukari C.; Katamba, Achilles; Nankabirwa, Joaniter I.; Castelnuovo, Barbara; Cattamanchi, Adithya
Tuberculosis (TB) mortality estimates derived only from cohorts of patients initiated on TB treatment do not consider outcomes of patients with pretreatment loss to follow-up (LFU). We aimed to assess the effect of pretreatment LFU on TB-associated mortality in the six months following TB diagnosis at public health facilities in Uganda. Methods At ten public health facilities, we retrospectively reviewed treatment data for all patients with a positive Xpert®MTB/RIF test result from January to June 2018. Pretreatment LFU was defined as not initiating TB treatment within two weeks of a positive test. We traced patients with pretreatment LFU to ascertain their vital status. We performed Kaplan Meier survival analysis to compare the cumulative incidence of mortality, six months after diagnosis among patients who did and did not experience pretreatment LFU. We also determined the health facility level estimates of TB associated mortality before and after incorporating deaths prior to treatment initiation among patients who experienced pretreatment LFU. Results Of 510 patients with positive test, 100 (19.6%) experienced pretreatment LFU. Of these, we ascertained the vital status of 49 patients. In the six months following TB diagnosis, mortality was higher among patients who experienced pretreatment LFU 48.1/1000py vs 22.9/ 1000py. Hazard ratio [HR] 3.18, 95% confidence interval [CI] (1.61–6.30). After incorporating deaths prior to treatment initation among patients who experienced pretreatment LFU, health facility level estimates of TB associated mortality increased from 8.4% (95% CI 6.1%- 11.6%) to 10.2% (95% CI 7.7%-13.4%). Conclusion Patients with confirmed TB who experience pretreatment LFU have high mortality within the first six months. Efforts should be made to prioritise linkage to treatment for this group of patients. Deaths that occur prior to treatment initation should be included when reporting TB mortality in order to more accurately reflect the health impact of TB.
Feasibility of a multifaceted intervention to improve treatment initiation among patients diagnosed with TB using Xpert MTB/RIF testing in Uganda
(PLoS ONE, 2022) Zawedde-Muyanja, Stella; Musaazi, Joseph; Castelnuovo, Barbara; Cattamanchi, Adithya; Katamba, Achilles; Manabe, Yukari C.
One in five patients diagnosed with TB in Uganda are not initiated on TB treatment within two weeks of diagnosis. We evaluated a multifaceted intervention for improving TB treatment initiation among patients diagnosed with TB using Xpert® MTB/RIF testing in Uganda. Methods This was a pre-post interventional study at one tertiary referral hospital. The intervention was informed by the COM-B model and included; i) medical education sessions to improve healthcare worker knowledge about the magnitude and consequences of pretreatment loss to follow-up; ii) modified laboratory request forms to improve recording of patient contact information; and iii) re-designed workflow processes to improve timeliness of sputum testing and results dissemination. TB diagnostic process and outcome data were collected and compared from the period before (June to August 2019) and after (October to December 2019) intervention initiation. Results In September 2019, four CME sessions were held at the hospital and were attended by 58 healthcare workers. During the study period, 1242 patients were evaluated by Xpert® MTB/ RIF testing at the hospital (679 pre and 557 post intervention). Median turnaround time for sputum test results improved from 12 hours (IQR 4–46) in the pre-intervention period to 4 hours (IQR 3–6) in the post-intervention period. The proportion of patients started on treatment within two weeks of diagnosis improved from 59% (40/68) to 89% (49/55) (difference 30%, 95% CI 14%-43%, p<0.01) while the proportion of patients receiving a same-day diagnosis increased from 7.4% (5/68) to 25% (14/55) (difference 17.6%, 95% CI 3.9%- 32.7%, p<0.01). Conclusion The multifaceted intervention was feasible and resulted in a higher proportion of patients initiating TB treatment within two weeks of diagnosis.
High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
(BMC infectious diseases, 2011) Nakanjako, Damalie; Ssewanyana, Isaac; Mayanja-Kizza, Harriet; Kiragga, Agnes; Manabe, Yukari C.; Nabatanzi, Rose; Kamya, Moses R.; Cao, Huyen
Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated.T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30].Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022].T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.
Implementation of Provider-Based Electronic Medical Records and Improvement of the Quality of Data in a Large HIV Program in Sub-Saharan Africa
(PLoS ONE, 2012) Castelnuovo, Barbara; Kiragga, Agnes; Afayo, Victor; Ncube, Malisa; Orama, Richard; Magero, Stephen; Okwi, Peter; Manabe, Yukari C.; Kambugu, Andrew
Starting in June 2010 the Infectious Diseases Institute (IDI) clinic (a large urban HIV out-patient facility) switched to provider-based Electronic Medical Records (EMR) from paper EMR entered in the database by data-entry clerks. Standardized clinics forms were eliminated but providers still fill free text clinical notes in physical patients’ files. The objective of this study was to compare the rate of errors in the database before and after the introduction of the providerbased EMR. Methods and Findings: Data in the database pre and post provider-based EMR was compared with the information in the patients’ files and classified as correct, incorrect, and missing. We calculated the proportion of incorrect, missing and total error for key variables (toxicities, opportunistic infections, reasons for treatment change and interruption). Proportions of total errors were compared using chi-square test. A survey of the users of the EMR was also conducted. We compared data from 2,382 visits (from 100 individuals) of a retrospective validation conducted in 2007 with 34,957 visits (from 10,920 individuals) of a prospective validation conducted in April–August 2011. The total proportion of errors decreased from 66.5% in 2007 to 2.1% in 2011 for opportunistic infections, from 51.9% to 3.5% for ART toxicity, from 82.8% to 12.5% for reasons for ART interruption and from 94.1% to 0.9% for reasons for ART switch (all P,0.0001). The survey showed that 83% of the providers agreed that provider-based EMR led to improvement of clinical care, 80% reported improved access to patients’ records, and 80% appreciated the automation of providers’ tasks. Conclusions: The introduction of provider-based EMR improved the quality of data collected with a significant reduction in missing and incorrect information. The majority of providers and clients expressed satisfaction with the new system. We recommend the use of provider-based EMR in large HIV programs in Sub-Saharan Africa.
Multivitamin supplementation in HIV infected adults initiating antiretroviral therapy in Uganda: the protocol for a randomized double blinded placebo controlled efficacy trial
(BMC Infectious Diseases, 2012) Guwatudde, David; Ezeamama, Amara E.; Bagenda, Danstan; Wabwire-Mangen, Fred; Wamani, Henry; Mugusi, Ferdinand; Spiegelman, Donna; Kyeyune, Rachel; Wang, Molin; Manabe, Yukari C.; Fawzi, Wafaie W.
Use of multivitamin supplements during the pre-HAART era has been found to reduce viral load, enhance immune response, and generally improve clinical outcomes among HIV-infected adults. However, immune reconstitution is incomplete and significant mortality and opportunistic infections occur in spite of HAART. There is insufficient research information on whether multivitamin supplementation may be beneficial as adjunct therapy for HIV-infected individuals taking HAART. We propose to evaluate the efficacy of a single recommended daily allowance (RDA) of micronutrients (including vitamins B-complex, C, and E) in slowing disease progression among HIV-infected adults receiving HAART in Uganda. Methods/Design: We are using a randomized, double-blind, placebo-controlled trial study design. Eligible patients are HIV-positive adults aged at least 18 years, and are randomized to receive either a placebo; or multivitamins that include a single RDA of the following vitamins: 1.4 mg B1, 1.4 mg B2, 1.9 mg B6, 2.6 mcg B12, 18 mg niacin, 70 mg C, 10 mg E, and 0.4 mg folic acid. Participants are followed for up to 18 months with evaluations at baseline, 6, 12 and 18 months. The study is primarily powered to examine the effects on immune reconstitution, weight gain, and quality of life. In addition, we will examine the effects on other secondary outcomes including the risks of development of new or recurrent disease progression event, including all-cause mortality; ARV regimen change from first- to second-line therapy; and other adverse events as indicated by incident peripheral neuropathy, severe anemia, or diarrhea. Discussions: The conduct of this trial provides an opportunity to evaluate the potential benefits of this affordable adjunct therapy (multivitamin supplementation) among HIV-infected adults receiving HAART in a developing country setting.
Optimisation of the Medical Education Partnership Initiative to address African health-care challenges
(The Lancet. Global health, 2014) Manabe, Yukari C.; Campbell, James D.; Ovuga, Emilio; Maling, Samuel; Bollinger, Robert C.; Sewankambo, Nelson
The Medical Education Partnership Initiative (MEPI) is an innovative and potentially transformative 5-year programme, established by the US Government in 2010, to increase the number of doctors to meet crucial human resource needs in sub-Saharan Africa.1 MEPI allows African institutions that are the direct grantees to define and direct programmes to address their own crucial gaps in medical education and workforce shortages in partnership with US academic partners.
Patient and health system factors associated with pretreatment loss to follow up among patients diagnosed with tuberculosis using Xpert® MTB/RIF testing in Uganda
(BMC public health, 2020) Zawedde-Muyanja, Stella; Katamba, Achilles; Cattamanchi, Adithya; Castelnuovo, Barbara; Manabe, Yukari C.
In 2018, Uganda started only 65% of persons with incident tuberculosis on treatment. Pretreatment loss to follow up is an important contributor to suboptimal treatment coverage. We aimed to describe the patient and health facility-level characteristics associated with pretreatment loss to follow up among patients diagnosed with pulmonary tuberculosis at public health facilities in Uganda. Methods: At ten public health facilities, laboratory register data was used to identify patients aged ≥ 15 years who had a positive Xpert®MTB/RIF test. Initiation on TB treatment was ascertained using the clinical register. Factors associated with not being initiated on TB treatment within two weeks of diagnosis were examined using a multilevel logistic regression model accounting for clustering by health facility. Results: From January to June 2018, 510 patients (61.2% male and 31.5% HIV co-infected) were diagnosed with tuberculosis. One hundred (19.6%) were not initiated on TB treatment within 2 weeks of diagnosis. Not having a phone number recorded in the clinic registers (aOR 7.93, 95%CI 3.93–13.05); being HIV-infected (aOR 1.83; 95% CI: 1.09–3.26) and receiving care from a high volume health facility performing more than 12 Xpert tests per day (aOR 4.37, 95%CI 1.69–11.29) and were significantly associated with pretreatment loss to follow up. Conclusion: In public health facilities in Uganda, we found a high rate of pretreatment loss to follow up especially among TBHIV co-infected patients diagnosed at high volume health facilities. Interventions to improve the efficiency of Xpert® MTB/RIF testing, including monitoring of the TB care cascade should be developed and implemented.
Patient and health system level barriers to and facilitators for tuberculosis treatment initiation in Uganda: a qualitative study
(BMC health services research, 2022) Zawedde‑Muyanja, Stella; Manabe, Yukari C.; Cattamanchi, Adithya; Castelnuovo, Barbara; Katamba, Achilles
The WHO END TB strategy targets to place at least 90% of all patients diagnosed with Tuberculosis (TB) on appropriate treatment. In Uganda, approximately 20% of patients diagnosed with TB are not initiated on TB treatment. We sought to identify the patient and health system level barriers to and facilitators for TB treatment initiation in Uganda. Methods: We conducted the study at ten public health facilities (three primary care, four district and three tertiary referral hospitals). We carried out in-depth interviews with patients diagnosed with TB and key informant interviews with health managers. In addition, we held focus group discussions with healthcare workers involved in TB care. Data collection and thematic analysis of transcripts was informed by the Capability, Opportunity, Motivation and Behavior (COM-B) model. We identified relevant intervention functions using the Behavior Change Wheel. Results: We interviewed 79 respondents (31 patients, 10 health managers and 38 healthcare workers). Common barriers at the health facility level included; lack of knowledge about the proportion of patients not initiated on TB treatment (psychological capability); difficulty accessing sputum results from the laboratory as well as difficulty tracing patients due to inadequate recording of patient addresses (physical opportunity). At the patient level, notable barriers included long turnaround time for sputum results and lack of transport funds to return to health facilities (physical opportunity); limited TB knowledge (psychological capability) and stigma (social opportunity). The most important facilitators identified were quick access to sputum test results either on the date of first visit (same-day diagnosis) or on the date of first return and availability of TB treatment (physical opportunity). We identified education, restructuring of the service environment to improve sputum results turnaround time and enablement to improve communication of test results as relevant intervention functions to alleviate these barriers to and enhance facilitators for TB treatment initiation. Conclusion: We found that barriers to treatment initiation existed at both the patient and health facility-level across all levels of the (Capability, Opportunity and Motivation) model. The intervention functions identified here should be tested for feasibility.
Point-of-care testing for HIV and sexually transmitted infections reveals risky behavior among men at gambling centers in Uganda
(International journal of STD & AIDS, 2021) Kiragga, Agnes N.; Bwanika, John M.; Kyenkya, Joshua; Banturaki, Grace; Kigozi, Joanita; Musinguzi, Davis; Namimbi, Florence; Chander, Geetanjali; Reynolds, Steven J.; Manabe, Yukari C.
In sub-Saharan Africa (SSA), men are generally difficult to engage in healthcare programs. However, sports gambling centers in SSA can be used as avenues for male engagement in health programs. We offered point-of-care HIV and syphilis testing for men located at five gambling centers in Uganda and assessed HIV risky sexual behavior. Among 507 men, 0.8% were HIV-positive and 3.8% had syphilis. Risky sexual behavior included condomless sex with partner(s) of unknown HIV status (64.9%), having multiple sexual partners (47.8%), engaging in transactional sex (15.5%), and using illicit drugs (9.3%). The majority at 64.5% were nonalcohol consumers, 22.9% were moderate users, and 12.6% had hazardous consumption patterns. In 12 months of follow-up, the incidence rate of syphilis was 0.95 (95% CI: 0.82-1.06) among 178 men. Thus, men in SSA have a high prevalence of syphilis and risky sexual behavior which should be more effectively addressed to reduce the risk of HIV acquisition.
Predictors and outcomes of mycobacteremia among HIV-infected smear- negative presumptive tuberculosis patients in Uganda
(BMC infectious Diseases, 2015) Nakiyingi, Lydia; Ssengooba, Willy; Nakanjako, Damalie; Armstrong, Derek; Kirenga, Bruce J.; Mayanja-Kizza, Harriet; Joloba, Moses L.; Ellner, Jerrold J.; Dorman, Susan E.; Manabe, Yukari C.
Sputum smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity in HIV-infected symptomatic patients and increases the likelihood that mycobacterial infections particularly disseminated TB will be missed; delays in diagnosis can be fatal. Given the duration for MTB growth in blood culture, clinical predictors of MTB bacteremia may improve early diagnosis of mycobacteremia. We describe the predictors and mortality outcome of mycobacteremia among HIV-infected sputum smear-negative presumptive TB patients in a high prevalence HIV/TB setting.Between January and November 2011, all consenting HIV-infected adults suspected to have TB (presumptive TB) were consecutively enrolled. Diagnostic assessment included sputum smear microscopy, urine Determine TB lipoarabinomannan (LAM) antigen test, mycobacterial sputum and blood cultures, chest X-ray, and CD4 cell counts in addition to clinical and socio-demographic data. Patients were followed for 12 months post-enrolment.Of 394 sputum smear-negative participants [female, 63.7%; median age (IQR) 32 (28–39) years], 41/394 (10.4%) had positive mycobacterial blood cultures (mycobacteremia); all isolates were M. tuberculosis (MTB). The median CD4 cell count was significantly lower among patients with mycobacteremia when compared with those without (CD4 31 versus 122 cells/μL, p < 0.001). In a multivariate analysis, male gender [OR 3.4, 95%CI (1.4-7.6), p = 0.005], CD4 count <100 cells/μL [OR 3.1, 95% CI (1.1-8.6), p = 0.030] and a positive lateral flow urine TB LAM antigen test [OR 15.3, 95%CI (5.7-41.1), p < 0.001] were significantly associated with mycobacteremia. At 12 months of follow-up, a trend towards increased mortality was observed in patients that were MTB blood culture positive (35.3%) compared with those that were MTB blood culture negative (23.3%) (p = 0.065). Mycobacteremia occurred in 10% of smear-negative patients and was associated with higher mortality compared with smear-negative patients without mycobacteremia. Advanced HIV disease (CD4 < 100 cells/mm3), male gender and positive lateral flow urine TB LAM test predicted mycobacteremia in HIV-infected smear-negative presumptive TB patients in this high prevalence TB/HIV setting.
Predictors for MTB Culture-Positivity among HIV-Infected Smear-Negative Presumptive Tuberculosis Patients in Uganda: Application of New Tuberculosis Diagnostic Technology
(PLoS ONE, 2015) Nakiyingi, Lydia; Nonyane, Bareng A. S.; Ssengooba, Willy; Kirenga, Bruce J.; Nakanjako, Damalie; Lubega, Gloria; Byakika-Kibwika, Pauline; Joloba, Moses L.; Ellner, Jerry J.; Dorman, Susan E.; Mayanja-Kizza, Harriet; Manabe, Yukari C.
The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIVinfected smear-negative presumptive TB. We sought to determine predictors for MTB culture- positivity among these patients.
Retrospective Analysis of Ugandan Men with Urethritis Reveals Mycoplasma genitalium and Associated Macrolide Resistance
(Microbiology Spectrum, 2022) Johan, H. Melendez; Justin, Hardick; Onzia, Annet; Tong, Yu; Kyambadde, Peter; Rosalind, Parkes-Ratanshi; Nakku-Joloba, Edith; Kiragga, Agnes; Manabe, Yukari C.; Hamilla, Matthew M.
The rising rates of antimicrobial resistance (AMR) in Mycoplasma genitalium globally and the association of this sexually transmitted infection (STI) with cervicitis, urethritis, and HIV are potentially of great public health concern. Data on the epidemiology of M. genitalium in men in sub-Saharan Africa are limited. We sought to determine the prevalence of M. genitalium and macrolide resistance in men with urethritis in Kampala, Uganda. Self-collected penile-meatal swabs and/or urine samples from men with symptomatic urethritis (n = 250) were retrospectively analyzed for the presence of M. genitalium and macrolide resistance markers with the Aptima M. genitalium and ResistancePlus M. genitalium assays. Additionally, demographic and STI coinfection data were used to investigate associations with M. genitalium infection. M. genitalium was detected in 12.8% (32/250) of individuals; 40.6% (n = 13) had M. genitalium monoinfection. Mutations associated with macrolide resistance were detected in 10.7% (3/28) of participants. Coinfection with Neisseria gonorrhoeae was common (41.0%), but M. genitalium was more prevalent in participants without N. gonorrhoeae coinfection (P = 0.001). M. genitalium is common in Ugandan men with urethritis both as a monoinfection and as a coinfection with other curable STIs. Macrolide resistance was present and warrants further research on treatment outcomes and the association between untreated M. genitalium and subsequent morbidity.
Salmonella Bloodstream Infections in Hospitalized Children with Acute Febrile Illness—Uganda, 2016–2019
(The American Journal of Tropical Medicine and Hygiene, 2021) Appiah, Grace D.; Mpimbaza, Arthur; Lamorde, Mohammed; Freeman, Molly; Kajumbula, Henry; Salah, Zainab; Kugeler, Kiersten; Mikoleit, Matthew; Bumpus White, Porscha; Kapisi, James; Borchert, Jeff; Sserwanga, Asadu; Van Dyne, Susan; Mead, Paul; Kim, Sunkyung; Lauer, Ana C.; Winstead, Alison; Manabe, Yukari C.; Flick, Robert J.; Mintz, Eric
Invasive Salmonella infection is a common cause of acute febrile illness (AFI) among children in sub- Saharan Africa; however, diagnosing Salmonella bacteremia is challenging in settings without blood culture. The Uganda AFI surveillance system includes blood culture-based surveillance for etiologies of bloodstream infection (BSIs) in hospitalized febrile children in Uganda. We analyzed demographic, clinical, blood culture, and antimicrobial resistance data from hospitalized children at six sentinel AFI sites from July 2016 to January 2019. A total of 47,261 children were hospitalized. Median age was 2 years (interquartile range, 1–4) and 26,695 (57%) were male. Of 7,203 blood cultures, 242 (3%) yielded bacterial pathogens including Salmonella (N = 67, 28%), Staphylococcus aureus (N = 40, 17%), Escherichia spp. (N = 25, 10%), Enterococcus spp. (N = 18, 7%), and Klebsiella pneumoniae (N = 17, 7%). Children with BSIs had longer median length of hospitalization (5 days versus 4 days), and a higher case-fatality ratio (13% versus 2%) than children without BSI (all P < 0.001). Children with Salmonella BSIs did not differ significantly in length of hospitalization or mortality from children with BSI resulting from other organisms. Serotype and antimicrobial susceptibility results were available for 49 Salmonella isolates, including 35 (71%) non-typhoidal serotypes and 14 Salmonella serotype Typhi (Typhi). Among Typhi isolates, 10 (71%) were multi-drug resistant and 13 (93%) had decreased ciprofloxacin susceptibility. Salmonella strains, particularly non-typhoidal serotypes and drug-resistant Typhi, were the most common cause of BSI. These data can inform regional Salmonella surveillance in East Africa and guide empiric therapy and prevention in Uganda.
Tuberculosis treatment default among HIV-TB co-infected patients in urban Uganda
(Tropical Medicine & International Health, 2011) Elbireer, Sawsan; Guwatudde, David; Mudiope, Peter; Nabbuye-Sekandi, Juliet; Manabe, Yukari C.
To identify health facility and patient-specific factors associated with TB treatment default in HIV-infected patients, in a TB clinic on the campus of Mulago National Referral Hospital in Kampala, Uganda. methods Unmatched case–control study between March and May 2009. Cases were TB patients known to have defaulted on their anti-TB treatment, defined as a TB patient who had documented discontinuation of TB medication for two or more consecutive months due to reasons other than physician’s advice and who did not access care at another facility. Controls were TB patients who completed 8 months of anti-TB treatment without interruption of two or more months. Data on health facility-specific factors and individual characteristics were collected using semi-structured questionnaires. results Factors associated with defaulting from TB treatment were: distance from home to clinic (OR 2.22; 1.21–4.06); long waiting time at the clinic (OR 4.18; 2.18–8.02); poor drug availability (OR 4.75; 2.29–9.84); conduct of staff (OR 2.72; 1.02–7.25); lack of opportunity to express feelings (OR 3.47; 1.67–7.21). Other patient-related factors were lack of health education, i.e. not being aware of the duration of treatment or the risk of discontinuing it (OR 5.31; 1.94–14.57); not knowing that TB can be cured (OR 44.11; 13.66–142.41); length of TB treatment (OR 10.77; 5.18–22.41), and side effects of treatment OR 5.53 (2.25–13.61). conclusions Defaulting is influenced by health systems, staff factors, and patient misinformation. Health education on TB directed at patients combined with staff sensitization could help to improve adherence to TB treatment.

Browsing by Author "Manabe, Yukari C."

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