Browsing by Author "Bebell, Lisa M."

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    The Bacterial and Viral Complexity of Postinfectious Hydrocephalus in Uganda
    (Science translational medicine, 2020) Paulson, Joseph N.; Williams, Brent L.; Hehnly, Christine; Mishra, Nischay; Sinnar, Shamim A.; Zhang, Lijun; Ssentongo, Paddy; Kabachelor, Edith Mbabazi; Wijetunge, Dona S. S.; Bredow, Benjamin von; Mulondo, Ronnie; Kiwanuka, Julius; Bajunirwe, Francis; Bazira, Joel; Bebell, Lisa M.; Burgoine, Kathy; Couto-Rodriguez, Mara; Ericson, Jessica E.; Erickson, Tim; Ferrari, Matthew; Gladstone, Melissa; Guo, Cheng; Haran, Murali; Hornig, Mady; Isaacs, Albert M.; Kaaya, Brian Nsubuga; Kangere, Sheila M.; Kulkarni, Abhaya V.; Kumbakumba, Elias; Li, Xiaoxiao; Limbrick, David D.; Magombe, Joshua; Morton, Sarah U.; Mugamba, John; Ng, James; Olupot, Peter Olupot; Onen, Justin; Peterson, Mallory R.; Roy, Farrah; Sheldon, Kathryn; Townsend, Reid; Weeks, Andrew D.; Whalen, Andrew J.; Quackenbush, John; Ssenyonga, Peter; Galperin, Michael Y.; Almeida, Mathieu; Atkins, Hannah; Warf, Benjamin C.; Lipkin, W. Ian; Broach, James R.; Schiff, Steven J.
    Postinfectious hydrocephalus (PIH), often following neonatal sepsis, is the most common cause of pediatric hydrocephalus world-wide, yet the microbial pathogens remain uncharacterized. Characterization of the microbial agents causing PIH would lead to an emphasis shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention. We examined blood and CSF from 100 consecutive cases of PIH and control cases of non-postinfectious hydrocephalus (NPIH) in infants in Uganda. Genomic testing was undertaken for bacterial, fungal, and parasitic DNA, DNA and RNA sequencing for viral identification, and extensive bacterial culture recovery. We uncovered a major contribution to PIH from Paenibacillus, upon a background of frequent cytomegalovirus (CMV) infection. CMV was only found in CSF in PIH cases. A facultatively anaerobic isolate was recovered. Assembly of the genome revealed a strain of P. thiaminolyticus. In mice, this isolate designated strain Mbale, was lethal in contrast with the benign reference strain. These findings point to the value of an unbiased pan-microbial approach to characterize PIH in settings where the organisms remain unknown, and enables a pathway towards more optimal treatment and prevention of the proximate neonatal infections.
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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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    Trends in one-year Cumulative Incidence of Death between 2005 and 2013 among Patients initiating Antiretroviral Therapy in Uganda
    (International journal of STD & AIDS, 2017-09-20) Bebell, Lisa M.; Musinguzi, Nicholas; Bwana, Bosco M.; Muyindike, Winnie; Bangsberg, David R.
    Recent ecological data demonstrate improving outcomes for HIV-infected people in sub-Saharan Africa. Recently, Uganda has experienced a resurgence in HIV incidence and prevalence, but trends in HIV-related deaths have not been well described. Data were collected through the Uganda AIDS Rural Treatment Outcomes (UARTO) Study, an observational longitudinal cohort of Ugandan adults initiating antiretroviral therapy (ART) between 2005 and 2013. We calculated cumulative incidence of death within one year of ART initiation, and fit Poisson models with robust variance estimators to estimate the effect enrollment period on one-year risk of death and loss to follow-up. Of 760 persons in UARTO who started ART, 30 deaths occurred within one year of ART initiation (cumulative incidence 3.9%, 95% confidence interval [CI] 2.7–5.6%). Risk of death was highest for those starting ART in 2005 (13.0%, 95% CI 6.0–24.0%), decreased in 2006–2007 to 4% (95% CI 2.0–6.0%), and did not change thereafter (P = 0.61). These results were robust to adjustment for age, sex, CD4 cell count, viral load, asset wealth, baseline depression, and body mass index. Here, we demonstrate that one-year cumulative incidence of death was high just after free ART rollout, decreased the following year, and remained low thereafter. Once established, ART programs in President’s Emergency Fund for AIDS Relief-supported countries can maintain high quality care.