Browsing by Author "Boum, Yap"

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    Changes in Immune Activation During Pregnancy and the Postpartum Period in Treated HIV Infection
    (Oxford University Press, 2021) Schnittman, Samuel R.; Byakwaga, Helen; Boum, Yap; Kabakyenga, Jerome; Matthews, Lynn T.; Burdo, Tricia H.; Huang, Yong; Tracy, Russell P.; Haberer, Jessica E.; Kembabazi, Annet; Kaida, Angela; Moisi, Daniela; Lederman, Michael M.; Bangsberg, David R.; Martin, Jeffrey N.; Hunt, Peter W.
    Pregnant women with HIV (PWWH) have high postpartum morbidity and mortality from infections like tuberculosis. Immunologic changes during pregnancy and postpartum periods may contribute to these risks, particularly the immunoregulatory kynurenine pathway of tryptophan catabolism, which contributes to both HIV and tuberculosis pathogenesis and increases in the early postpartum period. Women with HIV initiating antiretroviral therapy (ART) in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort who were pregnant at enrollment or became pregnant during observation were studied (n = 54). Plasma kynurenine/tryptophan (KT) ratio, soluble CD14 (sCD14), sCD163, sCD27, interferon-inducible protein 10 (IP-10), D-dimer, interleukin-6, and intestinal fatty-acid binding protein levels were assessed through the first year of ART and at 3-month intervals throughout pregnancy and 1 year postpartum. Biomarker changes were assessed with linear mixed models adjusted for ART duration. Hemoglobin concentration changes were used to estimate pregnancy-related changes in plasma volume. Results. The median pre-ART CD4 count was 134. D-dimer increased through the third trimester before returning to baseline postpartum, while most other biomarkers declined significantly during pregnancy, beyond what would be expected from pregnancy associated plasma volume expansion. IP-10 and sCD14 remained suppressed for at least 12 months postpartum. KT ratio was the only biomarker that increased above prepregnancy baseline postpartum (mean + 30%; P < .001) and remained higher than baseline for ≥9 months (P ≤ .045 for all time points). Several immune activation markers decline during pregnancy and remain suppressed postpartum, but the kynurenine pathway of tryptophan catabolism increases above baseline for ≥9 months postpartum. The mechanisms underlying postpartum kynurenine pathway activity are incompletely understood but may contribute to increased tuberculosis risk in this setting.
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    Contraceptive use following unintended pregnancy among Ugandan women living with HIV
    (PLoS ONE, 2018) Jarolimova, Jana; Kabakyenga, Jerome; Bennett, Kara; Muyindike, Winnie; Kembabazi, Annet; Martin, Jeffrey N.; Hunt, Peter W.; Boum, Yap; Haberer, Jessica E.; Bangsberg, David R.; Kaida, Angela; Matthews, Lynn T.
    Preventing unintended pregnancy is critical for women living with HIV (WLWH) to safely achieve their reproductive goals. Family planning services should support WLWH at risk of repeat unintended pregnancies. We examined the relationship between unintended pregnancy and subsequent contraception use among WLWH in Uganda. This was a retrospective analysis of data from a longitudinal cohort of individuals initiating antiretroviral therapy (ART), restricted to women with pregnancy (confirmed via urine β-hcg testing) between 2011–2013. The exposure of interest was intended vs unintended pregnancy, and the outcome was self-report of modern contraceptive use (hormonal methods, intrauterine device, sterilization, and/or consistent condom use) at 12 (range 6–18) months post-partum. A log-binomial model was used to estimate relative risks of modern contraceptive use post-partum based on intent of the index pregnancy, adjusted for age, socioeconomic status, education, relationship and HIV status of pregnancy partner, contraceptive use prior to pregnancy, years since HIV diagnosis, ART regimen, and CD4 cell count.
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    Declining Prevalence of Probable Depression Among Patients Presenting for Antiretroviral Therapy in Rural Uganda: The Role of Early Treatment Initiation
    (AIDS and Behavior, 2015) Chan, Brian T.; Weiser, Sheri D.; Boum, Yap; Haberer, Jessica E.; Kembabazi, Annet; Hunt, Peter W.; Martin, Jeffrey N.; Mocello, A. Rain; Bangsberg, David R.; Tsai, Alexander C.
    Little is known about trends in depression at antiretroviral therapy (ART) initiation among people living with HIV (PLHIV) in low- and middle-income countries. We used data from an ongoing cohort of treatment -naı¨ve PLHIV in rural Uganda to estimate secular trends in depression among PLHIV at ART initiation. We fitted linear regression models with depression symptom severity as the outcome variable and year of cohort entry (2005–2012) as the explanatory variable, adjusting for socio-demographic variables and assessing physical health score, body mass index (BMI), and CD4 count as potential mediators of a secular trend in depression symptom severity. There was a statistically significant negative association between year of entry and depression symptom severity, suggesting a 3.1 % relative decline in the mean depression symptom severity score at ART initiation in each year of study recruitment after the first year. This trend remained statistically significant after inclusion of baseline socio demographic characteristics to the model and appeared to be driven by improved physical health scores, but not CD4 count or BMI.
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    Evaluation of the Deki Reader™, an automated RDT reader and data management device, in a household survey setting in low malaria endemic southwestern Uganda
    (Malaria Journal, 2017) Oyet, Caesar; Roh, Michelle E.; Kiwanuka, Gertrude N.; Orikiriza, Patrick; Wade, Martina; Parikh, Sunil; Mwanga‑Amumpaire, Juliet; Boum, Yap
    Early diagnosis of suspected malaria cases with a rapid diagnostic test (RDT) has been shown to be an effective malaria control tool used in many resource-constrained settings. However, poor quality control and quality assurance hinder the accurate reporting of malaria diagnoses. Recent use of a portable, battery operated RDT reader (Deki Reader™, Fio Corporation) has shown to have high agreement with visual inspection across diverse health centre settings, however evidence of its feasibility and usability during cross sectional surveys are limited. This study aimed to evaluate the performance of the Deki Reader™ in a cross-sectional survey of children from southwestern Uganda. Methods: A two-stage, stratified cluster sampling survey was conducted between July and October 2014 in three districts of southwestern Uganda, with varying malaria transmission intensities. A total of 566 children aged 6–59 months were included in the analysis. Blood samples were collected and tested for malaria using: the SD Bioline Malaria Ag Pf/Pan RDT and microscopy. Results were compared between visual inspection of the RDT and by the Deki Reader™. Diagnostic performance of both methods were compared to gold-standard microscopy. Results: The sensitivity and specificity of the Deki Reader™ was 94.1% (95% CI 69.2–99.6%) and 95.6% (95% CI 93.4–97.1%), respectively. The overall percent agreement between the Deki Reader™ and visual RDT inspection was 98.9% (95% CI 93.2–99.8), with kappa statistic of 0.92 (95% CI 0.85–0.98). Conclusions: The findings from this study suggest that the Deki Reader™ is comparable to visual inspection and performs well in detecting microscopy-positive Plasmodium falciparum cases in a household survey setting. However, the reader’s performance was highly dependent on ensuring adequate battery life and a work environment free of dirt particles.
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    Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda
    (Malaria journal, 2011) De Beaudrap, Pierre; Nabasumba, Carolyn; Grandesso, Francesco; Turyakira, Eleanor; Schramm, Birgit; Boum, Yap; Etard, Jean-François
    Malaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection. Methods: Two cross-sectional surveys were conducted in 2004 and in 2010 at the end of the rainy and dry seasons to measure the prevalence of P. falciparum infection among children less than five years of age. Rapid diagnostic tests and blood smears were used to diagnose malaria infection. In 2010, sampling was stratified by urban and rural areas. In each selected household, knowledge of malaria and bed nets, and bed net ownership and use, were assessed. Results: In 2004 and 2010, respectively, a total of 527 and 2,320 (999 in the urban area and 1,321 in rural areas) children less than five years old were enrolled. Prevalence of malaria infection declined from 43% (95% CI: 34-52) in 2004, to 23% (95% CI: 17-30) in rural areas in 2010 and 3% (95% CI: 2-5) in the urban area in 2010. From the rainy to dry season in 2010, prevalence decreased from 23% to 10% (95% CI: 6-14) in rural areas (P = 0.001) and remained stable from 3% to 4% (95% CI: 1-7) in the urban area (P = 0.9). The proportion of households reporting ownership and use of at least one bed net increased from 22.9% in 2004 to 64.7% in the urban area and 44.5% in rural areas in 2010 (P < 0.001). In 2010, the risk of malaria infection was consistently associated with child age and household wealth. In rural areas, malaria infection was also associated with geographic factors. Conclusions: This study reports a significant drop in the prevalence of malaria infection among children below five years of age, paralleled by an uptake in bed-net use. However, prevalence remains unacceptably high in rural areas and is strongly associated with poverty.
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    High incidence of intended partner pregnancy among men living with HIV in rural Uganda: Implications for safer conception services
    (Journal of acquired immune deficiency syndromes, 2019) Kaida, Angela; Kabakyenga, Jerome; Bwana, Mwebesa; Bajunirwe, Francis; Muyindike, Winnie; Bennett, Kara; Kembabazi, Annet; Haberer, Jessica E.; Boum, Yap; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.; Matthews, Lynn T.
    Many men with HIV express fertility intentions and nearly half have HIV-uninfected sexual partners. We measured partner pregnancy among a cohort of men accessing antiretroviral therapy (ART) in Uganda.Self-reported partner pregnancy incidence and bloodwork (CD4, HIV-RNA) were collected quarterly. Interviewer-administered questionnaires assessed men’s sexual and reproductive health annually and repeated at time of reported pregnancy (2011–2015). We measured partner pregnancy incidence overall, by pregnancy intention, and by reported partner HIV-serostatus. We assessed viral suppression (≤400 copies/mL) during the peri-conception period. Cox proportional hazard regression with repeated events identified predictors of partner pregnancy.Among 189 men, baseline median age was 39.9 years [IQR:34.7,47.0], years on ART was 3.9 [IQR:0.0,5.1], and 51% were virally suppressed. Over 530.2 person-years of follow-up, 63 men reported 85 partner pregnancies (incidence=16.0/100 person-years); 45% with HIV-serodifferent partners. By three years of follow-up, 30% of men reported a partner pregnancy, with no difference by partner HIV-serostatus (p=0.75). 69% of pregnancies were intended, 18% wanted but mis-timed, and 8% unwanted. 78% of men were virally suppressed prior to pregnancy report. Men who were younger (aHR:0.94/year;95%CI:0.89–0.99), had incomplete primary education (aHR:2.95;95%CI:1.36–6.40), and reported fertility desires (aHR:2.25;95%CI:1.04–4.85) had higher probability of partner pregnancy.A high incidence of intended partner pregnancy highlights the need to address men’s reproductive goals within HIV care. Nearly half of pregnancy partners were at-risk for HIV and one-quarter of men were not virally suppressed during peri-conception. Safer conception care provides opportunity to support men’s health and reproductive goals, while preventing HIV transmission to women and infants.
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    Immunologic Pathways That Predict Mortality in HIV-Infected Ugandans Initiating Antiretroviral Therapy
    (The Journal of infectious diseases, 2017) Lee, Sulggi; Byakwaga, Helen; Boum, Yap; Burdo, Tricia H.; Williams, Kenneth C.; Lederman, Michael M.; Huang, Yong; Tracy, Russell P.; Cao, Huyen; Haberer, Jessica E.; Kembabazi, Annet; Bangsberg, David R.; Martin, Jeffrey N.; Hunt, Peter W.
    The plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated human immunodeficiency virus (HIV) disease in Ugandans as compared to US-based populations. Here, the KT ratio and T-cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. The month 6 KT ratio (adjusted hazard ratio [aHR], 2.74), soluble CD14 level (aHR, 2.32), interleukin 6 level (aHR, 2.34), and D-dimer level (aHR, 1.95) were associated with mortality occurring ≥6 months after ART initiation. The KT ratio remained significantly predictive of mortality even after adjustment for the additional biomarkers, suggesting an independent contribution to clinical outcomes in resource-limited settings.
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    Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment
    (Malaria journal, 2013) De Beaudrap, Pierre; Turyakira, Eleanor; White, Lisa J.; Nabasumba, Carolyn; Tumwebaze, Benon; Muehlenbachs, Atis; Guérin, Philippe J.; Boum, Yap; McGready, Rose; Piola, Patrice
    Malaria in pregnancy (MiP) is a major public health problem in endemic areas of sub-Saharan Africa and has important consequences on birth outcome. Because MiP is a complex phenomenon and malaria epidemiology is rapidly changing, additional evidence is still required to understand how best to control malaria. This study followed a prospective cohort of pregnant women who had access to intensive malaria screening and prompt treatment to identify factors associated with increased risk of MiP and to analyse how various characteristics of MiP affect delivery outcomes. Methods: Between October 2006 and May 2009, 1,218 pregnant women were enrolled in a prospective cohort. After an initial assessment, they were screened weekly for malaria. At delivery, blood smears were obtained from the mother, placenta, cord and newborn. Multivariate analyses were performed to analyse the association between mothers’ characteristics and malaria risk, as well as between MiP and birth outcome, length and weight at birth. This study is a secondary analysis of a trial registered with ClinicalTrials.gov, number NCT00495508. Results: Overall, 288/1,069 (27%) mothers had 345 peripheral malaria infections. The risk of peripheral malaria was higher in mothers who were younger, infected with HIV, had less education, lived in rural areas or reported no bed net use, whereas the risk of placental infection was associated with more frequent malaria infections and with infection during late pregnancy. The risk of pre-term delivery and of miscarriage was increased in mothers infected with HIV, living in rural areas and with MiP occurring within two weeks of delivery. In adjusted analysis, birth weight but not length was reduced in babies of mothers exposed to MiP (−60g, 95%CI: -120 to 0 for at least one infection and -150 g, 95%CI: -280 to −20 for >1 infections). Conclusions: In this study, the timing, parasitaemia level and number of peripherally-detected malaria infections, but not the presence of fever, were associated with adverse birth outcomes. Hence, prompt malaria detection and treatment should be offered to pregnant women regardless of symptoms or other preventive measures used during pregnancy, and with increased focus on mothers living in remote areas
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    Increasing Prevalence of HIV Pretreatment Drug Resistance in Women But Not Men in Rural Uganda During 2005–2013
    (AIDS patient care and STDs, 2018) McCluskey, Suzanne M.; Lee, Guinevere Q.; Kamelian, Kimia; Kembabazi, Annet; Musinguzi, Nicholas; Bwana, Mwebesa B.; Muzoora, Conrad; Haberer, Jessica E.; Hunt, Peter W.; Martin, Jeffrey N.; Boum, Yap; Bangsberg, David R.; Harrigan, Richard; Siedner, Mark J.
    The prevalence of HIV pretreatment drug resistance (PDR) is increasing in sub-SaharanAfrica.We sought to describe correlates of PDR and evaluate effects of PDR on clinical outcomes in rural Uganda. We analyzed data from the Uganda AIDS Rural Treatment Outcomes study, a cohort of antiretroviral therapy (ART)-naive adults with HIV (2005–2015). We performed resistance testing on pre-ART specimens. We defined PDR as any World Health Organization (WHO) 2009 surveillance drug resistance mutation and classified PDR level using the Stanford algorithm. We fit unadjusted and sex-stratified log binomial regression and Cox proportional hazardmodels to identify correlates of PDR and the impact of PDR on viral suppression, loss to follow-up (LTFU), and death. We analyzed data from 738 participants (median age 33 years, 69% female). Overall, prevalence of PDR was 3.5% (n = 26), owing mostly to resistance to non-nucleoside reverse transcriptase inhibitors. PDR increased over time in women (1.8% in those enrolling in clinic in 2001–2006, vs. 7.0% in 2007–2013; p = 0.006), but not in men (1.15% vs. 0.72%, p = 0.737). Lower pre-ART log10 HIV RNA was also associated with higher prevalence of PDR. We identified longer time to viral suppression among those with PDR compared with without PDR (0.5 and 0.3 years, respectively, p = 0.023), but there was no significant relationship with mortality or LTFU ( p = 0.139). We observed increasing rates of PDR in women in southwestern Uganda. Implications of this trend, particularly to prevention of mother-to-child transmission programs in the region, require attention due to delayed viral suppression among those with PDR.
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    Inhaled Nitric Oxide and Cerebral Malaria: Basis of a Strategy for Buying Time for Pharmacotherapy
    (The Pediatric Infectious Disease Journal, 2012) Bergmark, Brian; Bergmark, Regan; Beaudrap, Pierre De; Boum, Yap; Mwanga-Amumpaire, Juliet; Carroll, Ryan; Zapol, Warren
    There are approximately 225–600 million new malaria infections worldwide annually, with severe and cerebral malaria representing major causes of death internationally. The role of nitric oxide (NO) in the host response in cerebral malaria continues to be elucidated, with numerous known functions relating to the cytokine, endovascular and cellular responses to infection with Plasmodium falciparum. Evidence from diverse modes of inquiry suggests NO to be critical in modulating the immune response and promoting survival in patients with cerebral malaria. This line of investigation has culminated in the approval of 2 phase II randomized prospective clinical trials in Uganda studying the use of inhaled NO as adjuvant therapy in children with severe malaria. The strategy underlying both trials is to use the sytemic antiinflammatory properties of inhaled NO to “buy time” for chemical antiparasite therapy to lower the parasite load. This article reviews the nexus of malaria and NO biology with a primary focus on cerebral malaria in humans.
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    Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children: A Phase II Randomized Open-Label Clinical Trial
    (Oxford University Press, 2015) Mwanga-Amumpaire, Juliet; Carroll, Ryan W.; Baudin, Elisabeth; Kemigisha, Elisabeth; Nampijja, Dorah; Mworozi, Kenneth; Santorino, Data; Nyehangane, Dan; Nathan, Daniel I.; De Beaudrap, Pierre; Etard, Jean-François; Feelisch, Martin; Fernandez, Bernadette O.; Berssenbrugge, Annie; Bangsberg, David; Bloch, Kenneth D.; Boum, Yap; Zapol, Warren M.
    Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate.We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-α, interferon- γ, interleukin [IL]-1β, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels—blood methemoglobin and plasma nitrate—increased in patients treated with NO (both P < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions. Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours.
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    Internalized stigma, depressive symptoms, and the modifying role of antiretroviral therapy: A cohort study in rural Uganda
    (SSM-Mental Health, 2021) Bebell, Lisa M.; Kembabazi, Annet; Musinguzi, Nicholas; Martin, Jeffrey N.; Hunt, Peter W.; Boum, Yap; O'Laughlin, Kelli N.; Muzoora, Conrad; Haberer, Jessica E.; Mwebesa, Bosco Bwana; Bangsberg, David R.; Siedner, Mark J.; Tsai, Alexander C.
    Depression affects over 40% of people with HIV (PHIV) in low- and middle-income countries, and over half of PHIV report HIV related internalized stigma. However, few longitudinal studies of PHIV have examined the relationship between HIV-related stigma and depression. Data were analyzed from the 2007-15 Uganda AIDS Rural Treatment Outcomes (UARTO) Study, a cohort of 454 antiretroviral therapy (ART)-naïve PHIV (68% women) starting ART. Our primary outcome was depression symptom severity over the first two years of ART, measured using a locally adapted version of the Hopkins Symptom Checklist; our primary exposure was the 6-item Internalized AIDS-Related Stigma Scale. Both scores were measured at enrollment and at quarterly follow-up visits. We fit linear generalized estimating equations (GEE) regression models to estimate the association between stigma and depression symptom severity, adjusting for potential confounders. We included a stigma timeproduct term to assess the modifying effect of ART on the association between internalized stigma and depression symptom severity. UARTO participants had a median age of 32 years and median enrollment CD4 count of 217 cells/mm3. Both depression symptom severity and internalized stigma declined on ART, particularly during the first treatment year. In multivariable regression models, depression symptom severity was positively associated with internalized stigma (b ¼ 0.03; 95% confidence interval [CI], 0.02 to 0.04) and negatively associated with ART duration >6 months (b ¼ 0.16; 95% CI, 0.19 to 0.13). The estimated product term coefficient was negative and statistically significant (P ¼ 0.004), suggesting that the association between internalized stigma and depression symptom severity weakened over time on ART. Thus, in this large cohort of PHIV initiating ART in rural Uganda, depression symptom severity was associated with internalized stigma but the association declined with time on ART. These findings underscore the potential value of ART as a stigma reduction intervention for PHIV, particularly during early treatment.
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    The Kynurenine Pathway of Tryptophan Catabolism, CD4+ T-Cell Recovery, and Mortality Among HIV-Infected Ugandans Initiating Antiretroviral Therapy
    (The Journal of infectious diseases, 2014) Byakwaga, Helen; Boum, Yap; Huang, Yong; Muzoora, Conrad; Kembabazi, Annet; Weiser, Sheri D.; Bennett, John; Cao, Huyen; Haberer, Jessica E.; Deeks, Steven G.; Bangsberg, David R.; McCune, Joseph M.; Martin, Jeffrey N.; Hunt, Peter W.
    Human immunodeficiency virus (HIV) infection–induced indoleamine 2,3-dioxygenase-1 (IDO) expression in activated monocytes and dendritic cells catabolizes tryptophan to kynurenine and other downstream catabolites that inhibit T-cell proliferation and interleukin 17 (IL-17) production. The prognostic significance of this pathway in treated HIV disease is unknown. We measured systemic IDO activity (calculated as the ratio of plasma levels of kynurenine to tryptophan; hereafter, the “KT ratio”) in HIV-infected Ugandans before and during antiretroviral therapy (ART)–mediated viral suppression and its association with the rate of subsequent CD4+ T-cell count recovery and mortality. Among 435 participants, a higher pre-ART KT ratio was associated with a higher plasma virus load (P < .001) and lipopolysaccharide level (P = .018), a lower CD4+ T-cell count (P < .001), and female sex (P = .047). Through month 12 of ART-mediated viral suppression, the plasma KT ratio decreased by approximately 50% (P < .001). After adjustment for pre-ART CD4+ T-cell count, virus load, age, and sex, a higher month 12 KT ratio predicted a slower rate of subsequent CD4+ T-cell count recovery (P = .001). Thirty-nine participants died. After adjustment for pre-ART CD4+ T-cell count, virus load, body mass index, sex, and age, a higher pre-ART and month 6 KT ratio predicted increased mortality (P ≤ .016). The kynurenine pathway of tryptophan catabolism independently predicts poor CD4+ T-cell count recovery and increased mortality among HIV-infected Ugandans initiating ART and may be an important target for interventions.
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    Multidistrict Outbreak of Marburg Virus Disease—Uganda, 2012
    (The Journal of infectious diseases, 2015) Knust, Barbara; Schafer, Ilana J.; Wamala, Joseph; Nyakarahuka, Luke; Okot, Charles; Shoemaker, Trevor; Dodd, Kimberly; Gibbons, Aridth; Balinandi, Stephen; Tumusiime, Alex; Campbell, Shelley; Newman, Edmund; Lasry, Estrella; DeClerck, Hilde; Boum, Yap; Makumbi, Issa; Bosa, Henry Kyobe; Mbonye, Anthony; Aceng, Jane Ruth; Nichol, Stuart T.; Ströher, Ute; Rollin, Pierre E.
    In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription–polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection.
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    Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the “PI-POC” Trial
    (JMIR research protocols, 2020) Gaudenzi, Giulia; Kumbakumba, Elias; Rasti, Reza; Nanjebe, Deborah; Réu, Pedro; Nyehangane, Dan; Mårtensson, Andreas; Nassejje, Milly; Karlsson, Jens; Mzee, John; Nilsson, Peter; Businge, Stephen; Loh, Edmund; Boum, Yap; Andersson-Svahn, Helene; Gantelius, Jesper; Mwanga-Amumpaire, Juliet; Alfvén, Tobias
    A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid–based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. Conclusions: The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
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    Prevalence of HI V-related thrombocytopenia among clients at Mbarara Regional Referral Hospital, Mbarara, southwestern Uganda
    (Journal of blood medicine, 2015) Taremwa, Ivan M.; Muyindike, Winnie R.; Muwanguzi, Enoch; Boum, Yap; Natukunda, Bernard
    We aimed to determine the prevalence and correlates of thrombocytopenia among people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and to assess occurrence of antiplatelet antibodies, among thrombocytopenic HIV clients at Mbarara Regional Referral Hospital, southwestern Uganda.This was a retrospective review of hematologic results at enrollment to HIV care from 2005 to 2013.. The prevalence and correlates of thrombocytopenia were estimated based on the Immune Suppressed Syndrome (ISS) Clinic electronic database. A cross-sectional study determined the occurrence of antiplatelet antibodies, using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) technique.We reviewed 15,030 client records. The median age was 35.0 (range 18–78; interquartile range [IQR] 28–42) years, and there were 63.2% (n=9,500) females. The overall prevalence of thrombocytopenia was 17.4% (95% confidence interval [CI]: 16.8%–18.0%). The prevalence of thrombocytopenia was 17.8% (95% CI: 17.1%–18.4%) among antiretroviral therapy (ART)-naïve clients (n=2,675) and was 13.0% (95% CI: 0.3%–21.9%) for clients who were on ART (n=6). The study found a significant association between thrombocytopenia and other cytopenias, CD4 counts, ART, and deteriorating HIV stage (P,0.05). Two of the 40 participants (5.0%) had antiplatelet antibodies.This study has showed a high prevalence of HIV-related thrombocytopenia. Antiplatelet antibodies were found in 5.0% of HIV-infected thrombocytopenic participants. Our study shows a significant association of thrombocytopenia burden in a high-HIV study population (Southwest Uganda); therefore, there is need to monitor platelet counts and initiate platelet transfusion in our blood banking practices, to avert possible risks of bleeding.
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    Relationship Power and Sexual Violence Among HIV-Positive Women in Rural Uganda
    (AIDS and Behavior, 2016) Conroy, Amy A.; Tsai, Alexander C.; Clark, Gina M.; Boum, Yap; Hatcher, Abigail M.; Kawuma, Annet; Hunt, Peter W.; Martin, Jeffrey N.; Bangsberg, David R.; Weiser, Sheri D.
    Gender-based power imbalances place women at significant risk for sexual violence, however, little research has examined this association among women living with HIV/AIDS. We performed a cross-sectional analysis of relationship power and sexual violence among HIV-positive women on anti-retroviral therapy in rural Uganda. Relationship power was measured using the Sexual Relationship Power Scale (SRPS), a validated measure consisting of two subscales: relationship control (RC) and decision-making dominance. We used multivariable logistic regression to test for associations between the SRPS and two dependent variables: recent forced se and transactional sex. Higher relationship power (full SRPS) was associated with reduced odds of forced sex (AOR = 0.24; 95 % CI 0.07–0.80; p = 0.020). The association between higher relationship power and transactional sex was strong and in the expected direction, but not statistically significant (AOR = 0.47; 95 % CI 0.18–1.22; p = 0.119). Higher RC was associated with reduced odds of both forced sex (AOR = 0.18; 95 % CI 0.06–0.59; p\0.01) and transactional sex (AOR = 0.38; 95 % CI 0.15–0.99; p = 0.048). Violence prevention interventions with HIV-positive women should consider approaches that increase women’s power in their relationships.