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.