Reuben Kiggundu's research while affiliated with Makerere University and other places

... We conducted a prospective cohort study of Ugandan adults diagnosed with HIV-associated cryptococcal meningitis, nested within the ASTRO-CM (Adjunctive Sertraline for the Treatment of Cryptococcal Meningitis) randomized clinical trial [18,19]. ASTRO-CM participants were living with HIV, age ≥18 years, with confirmed index cryptococcal meningitis defined by a positive cerebrospinal fluid (CSF) cryptococcal antigen (CrAg). ...

... In this study, 75% (n = 12) of HIV-positive patients who were serum cryptococcal antigen positive had a CD4 count less than 100 and 25% (n = 4) had a CD4 count between 101 and 200, which is not statistically significant. According to Pujari et al., [9] 33.33% of positive cases had a CD4 count less than 100 [15] the study from sub-Saharan Africa indicates that individuals with CD4 + T-cell counts >100 cells/µL also develop cryptococcal meningitis associated with HIV infection. According to their study, 10% of cryptococcosis occurs among patients with CD4 counts between 100 and 200 cells/µL. ...

... Acute bacterial meningitis was diagnosed via Gram's stain, culture and/or by multiplex PCR using the FilmArray Meningitis-Encephalitis panel (BioFire, Salt Lake City, UT, USA). All CSF CrAg-negative patients were systematically evaluated for TBM, including those with symptomatic cryptococcal antigenemia 18 . In patients with confirmed cryptococcal meningitis, TBM co-infection was investigated at physician discretion. ...

... An estimated 50% of fungal blood cultures will be positive and 80% of fungal CSF cultures will be positive [8,11]. Finally, it is important to test serum the CrAg assay in an immunocompromised individual with symptoms of CM, as the presence of cryptococcus may not be identified in the CSF in the early stages of infection [12]. ...

... Several new biomarkers are currently under investigation. Bahr et al. introduced delta-like 1 protein (DLL1), vitamin D binding protein (VDBP), and fetuin as possible host biomarkers that provided sensitivities of 32%, 86%, and 36%, respectively, against CSF Xpert MTB/RIF or culture results in TBM patients [62,74]. Several metabolites identified using H Nuclear Magnetic Resonance from CSF sample; lactate, glutamate, alanine, arginine, 2-hydroxyisobutyrate, format, and cis-aconitate were upregulated in TBM patients when compared with a control group [75]. ...

... The copyright holder for this preprint this version posted June 14, 2024. ; https://doi.org/10.1101/2024.06.12.598760 doi: bioRxiv preprint AIDS-associated cryptococcosis had a prior history of being engaged in HIV care including 278 receipt of antiretroviral drugs (46,47). Similarly, cda1∆2∆3∆ vaccination could be offered to 279 patients on transplant waiting lists in anticipation of their future need for immunosuppressive 280 antirejection drugs (3). ...

... Other CrAg LFA available in the market include Dynamiker [14], CryptoPS (Biosynex) [15], StrongStep (Liming Bio) [16], and FungiXpert cryptococcal capsular polysaccharide K-Set (Genobio) [17]. Scientists have reported extensively on the properties of these CrAg LFA tests and their comparison with IMMY or CALAS [15,16,[18][19][20]. ...

... Ten-week mortality among adults diagnosed with HIV-associated cryptococcal meningitis is 24-40% even in the context of clinical trials [2,3]. Risk factors for mortality are well described and include: Glasgow Coma Scale score <15 [4], anemia [5], acute kidney injury [6], hyponatremia [7], tuberculosis (TB) co-infection [8,9], and cytomegalovirus (CMV) viremia [10]. The lack of cryptococcal antigen screening and late presentation to care are also contributors to cryptococcal meningitis mortality [11]. ...

... Additionally, 50% of CM patients have positive blood cultures [41]. Multiplex PCR tests in CSF and quantitative lateral flow assays are currently being developed and implemented for rapid diagnosis [50][51][52]. ...

... [38,39] In a recent study in Uganda, there was perfect agreement between finger-stick whole blood, serum, and plasma CrAg LFA suggesting that testing from finger-stick whole blood is a viable option for detecting antigen CrAg, particularly in settings where phlebotomy is not available, or in patients with difficult venous access. [40] The CrAg LFA has also been evaluated in both urine and saliva, but agreement with serum LFA was not sufficient to recommend routing screening using these fluids. [41,42] The use of semiquantitative CrAg LFA titers has been shown to correlate with pretreatment quantitative cultures but has not been found to be useful for monitoring treatment response. ...