Background Cryptococcus is the most common cause of adult meningitis in Africa. We assessed the s... more Background Cryptococcus is the most common cause of adult meningitis in Africa. We assessed the safety and microbiological efficacy of adjunctive sertraline, previously shown to have in-vitro and in-vivo activity against cryptococcus.
Soil transmitted helminths influence host type 2 T helper cell and anti-inflammatory immune respo... more Soil transmitted helminths influence host type 2 T helper cell and anti-inflammatory immune responses. Certain helminths are also associated with markers of microbial translocation, which has been linked to T-cell activation and HIV disease progression. Previous attempts to quantify relationships between helminths and HIV have primarily measured parasitic infection via microscopy, which has low sensitivity relative to PCR, resulting in exposure misclassification. This cross-sectional study utilized quantitative PCR to establish parasitic co-infection, and examine associations with HIV immunologic outcomes. We enrolled rural HIV-infected Ugandans with previous CD4+ counts <500 cells/mcL from August to September 2013. Single stool and blood samples were taken at enrollment. PCR was used to quantify Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium parvum, Entamoeba histolytica, and Giardia lamblia. Clini...
Réseau Africain de l’Éducation pour la Santé (RAES) developed and implemented a health communicat... more Réseau Africain de l’Éducation pour la Santé (RAES) developed and implemented a health communications pilot project targeting secondary school students throughout Dakar, Senegal, in the summer of 2008. The program focused on the development of a scholastic, Internet-based community dedicated to health information, education, and dissemination, created by and for Senegalese youth. This article focuses on the summer pilot aspect of this program. Forty five students from three local high schools in Dakar were recruited during their summer break to participate in a 10-week pilot project conducted at RAES. This summer project developed students’ communication and technical skills; youth leaders formulated health messages communicating HIV/AIDS issues to their peers by producing their own digital content. Youth designed, wrote, and produced content using web-based applications, audio/visual equipment, and traditional journalistic approaches. The program was designed to positively impact h...
Journal of the Academy of Nutrition and Dietetics, 2015
Habitual intake of black tea has been associated with relatively lower serum cholesterol concentr... more Habitual intake of black tea has been associated with relatively lower serum cholesterol concentrations in observational studies. However, clinical trial results evaluating the effects of black tea on serum cholesterol have been inconsistent. Several factors could explain these mixed results, in particular, uncontrolled confounding caused by lifestyle factors (eg, diet). This diet-controlled clinical trial estimates the effect of black tea flavonoid consumption on cholesterol concentrations in 57 borderline hypercholesterolemic individuals (total cholesterol concentrations between 190 and 260 mg/dL [4.9 and 6.7 mmol/L]). A double-blind, randomized crossover trial was conducted in Minneapolis, MN, from April 2002 through April 2004 in which key conditions were tightly controlled to minimize possible confounding. Participants consumed a controlled low-flavonoid diet plus 5 cups per day of black tea or tea-like placebo during two 4-week treatment periods. The flavonoid-free caffeinated...
ABSTRACT Background: (1-3)-β-D-glucan (BDG) is a helpful diagnostic marker for many invasive fung... more ABSTRACT Background: (1-3)-β-D-glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of cerebrospinal fluid (CSF) and serum BDG as an adjunct diagnostic tool for HIV-infected cryptococcal meningitis patients. Methods: BDG concentrations were measured on cryopreserved CSF (n=177) and serum (n=109) of HIV-infected patients with suspected meningitis in Uganda and South Africa using the Fungitell® assay. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses evaluated BDG’s relationship with mortality. Results: The Fungitell® BDG assay provided 90% sensitivity (69/77) and 85% specificity (34/40) in CSF when compared to cryptococcal meningitis diagnosed by CSF culture or cryptococcal antigen at diagnosis (n=117, 66% with Cryptococcus neoformans). Sensitivity in CSF improved to 98% (57/58) when initial fungal burdens were ≥10,000 CFU/mL. Median (IQR) CSF BDG concentrations at diagnosis were 346 (202-597) pg/mL in cryptococcal patients and 37 (20-46) pg/mL in patients without cryptococcosis. Baseline BDG concentrations correlated with CSF fungal burden (rho=0.820, P&lt;.001) and CRAG LFA titers (rho=0.780, P&lt;.001). BDG normalized rapidly after initiating antifungal therapy [-0.25 (95%CI: -0.31, -0.20) average change in log2BDG level per day of follow-up]. Baseline BDG concentrations correlated with MIP-1β and MCP-1 levels in CSF. Among cryptococcal meningitis patients, a BDG concentration ≥500 pg/mL was associated with increased 10-week mortality. The diagnostic performance of the BDG assay for cryptococcal meningitis was not as good in serum, where we observed 79% (37/47) sensitivity and 61% (38/62) specificity. Conclusion: BDG is detectable in the CSF of HIV-infected patients with Cryptococcus, and may provide useful diagnostic and prognostic information. Further research is needed to clarify the role of BDG in the immunology and management of cryptococcal disease.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2015
The effect of tenofovir and amphotericin co-administration on kidney function is poorly character... more The effect of tenofovir and amphotericin co-administration on kidney function is poorly characterized. We measured creatinine during induction therapy and at 4-weeks post-diagnosis in Ugandans undergoing cryptococcal meningitis therapy, and classified as not receiving antiretroviral therapy (ART), receiving non-tenofovir ART, or receiving tenofovir-based ART. Longitudinal creatinine changes and Grade 2-4 creatinine adverse events were evaluated across groups. Creatinine concentrations were similar across ART groups. At 4 weeks post-diagnosis, creatinine was 0.25mg/dL higher than at diagnosis, but similar across groups. Adverse event incidence was also similar across ART groups. Tenofovir and amphotericin co-administration did not increase the risk of kidney dysfunction.
Background Cryptococcus is the most common cause of adult meningitis in Africa. We assessed the s... more Background Cryptococcus is the most common cause of adult meningitis in Africa. We assessed the safety and microbiological efficacy of adjunctive sertraline, previously shown to have in-vitro and in-vivo activity against cryptococcus.
Soil transmitted helminths influence host type 2 T helper cell and anti-inflammatory immune respo... more Soil transmitted helminths influence host type 2 T helper cell and anti-inflammatory immune responses. Certain helminths are also associated with markers of microbial translocation, which has been linked to T-cell activation and HIV disease progression. Previous attempts to quantify relationships between helminths and HIV have primarily measured parasitic infection via microscopy, which has low sensitivity relative to PCR, resulting in exposure misclassification. This cross-sectional study utilized quantitative PCR to establish parasitic co-infection, and examine associations with HIV immunologic outcomes. We enrolled rural HIV-infected Ugandans with previous CD4+ counts <500 cells/mcL from August to September 2013. Single stool and blood samples were taken at enrollment. PCR was used to quantify Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium parvum, Entamoeba histolytica, and Giardia lamblia. Clini...
Réseau Africain de l’Éducation pour la Santé (RAES) developed and implemented a health communicat... more Réseau Africain de l’Éducation pour la Santé (RAES) developed and implemented a health communications pilot project targeting secondary school students throughout Dakar, Senegal, in the summer of 2008. The program focused on the development of a scholastic, Internet-based community dedicated to health information, education, and dissemination, created by and for Senegalese youth. This article focuses on the summer pilot aspect of this program. Forty five students from three local high schools in Dakar were recruited during their summer break to participate in a 10-week pilot project conducted at RAES. This summer project developed students’ communication and technical skills; youth leaders formulated health messages communicating HIV/AIDS issues to their peers by producing their own digital content. Youth designed, wrote, and produced content using web-based applications, audio/visual equipment, and traditional journalistic approaches. The program was designed to positively impact h...
Journal of the Academy of Nutrition and Dietetics, 2015
Habitual intake of black tea has been associated with relatively lower serum cholesterol concentr... more Habitual intake of black tea has been associated with relatively lower serum cholesterol concentrations in observational studies. However, clinical trial results evaluating the effects of black tea on serum cholesterol have been inconsistent. Several factors could explain these mixed results, in particular, uncontrolled confounding caused by lifestyle factors (eg, diet). This diet-controlled clinical trial estimates the effect of black tea flavonoid consumption on cholesterol concentrations in 57 borderline hypercholesterolemic individuals (total cholesterol concentrations between 190 and 260 mg/dL [4.9 and 6.7 mmol/L]). A double-blind, randomized crossover trial was conducted in Minneapolis, MN, from April 2002 through April 2004 in which key conditions were tightly controlled to minimize possible confounding. Participants consumed a controlled low-flavonoid diet plus 5 cups per day of black tea or tea-like placebo during two 4-week treatment periods. The flavonoid-free caffeinated...
ABSTRACT Background: (1-3)-β-D-glucan (BDG) is a helpful diagnostic marker for many invasive fung... more ABSTRACT Background: (1-3)-β-D-glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of cerebrospinal fluid (CSF) and serum BDG as an adjunct diagnostic tool for HIV-infected cryptococcal meningitis patients. Methods: BDG concentrations were measured on cryopreserved CSF (n=177) and serum (n=109) of HIV-infected patients with suspected meningitis in Uganda and South Africa using the Fungitell® assay. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses evaluated BDG’s relationship with mortality. Results: The Fungitell® BDG assay provided 90% sensitivity (69/77) and 85% specificity (34/40) in CSF when compared to cryptococcal meningitis diagnosed by CSF culture or cryptococcal antigen at diagnosis (n=117, 66% with Cryptococcus neoformans). Sensitivity in CSF improved to 98% (57/58) when initial fungal burdens were ≥10,000 CFU/mL. Median (IQR) CSF BDG concentrations at diagnosis were 346 (202-597) pg/mL in cryptococcal patients and 37 (20-46) pg/mL in patients without cryptococcosis. Baseline BDG concentrations correlated with CSF fungal burden (rho=0.820, P&lt;.001) and CRAG LFA titers (rho=0.780, P&lt;.001). BDG normalized rapidly after initiating antifungal therapy [-0.25 (95%CI: -0.31, -0.20) average change in log2BDG level per day of follow-up]. Baseline BDG concentrations correlated with MIP-1β and MCP-1 levels in CSF. Among cryptococcal meningitis patients, a BDG concentration ≥500 pg/mL was associated with increased 10-week mortality. The diagnostic performance of the BDG assay for cryptococcal meningitis was not as good in serum, where we observed 79% (37/47) sensitivity and 61% (38/62) specificity. Conclusion: BDG is detectable in the CSF of HIV-infected patients with Cryptococcus, and may provide useful diagnostic and prognostic information. Further research is needed to clarify the role of BDG in the immunology and management of cryptococcal disease.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2015
The effect of tenofovir and amphotericin co-administration on kidney function is poorly character... more The effect of tenofovir and amphotericin co-administration on kidney function is poorly characterized. We measured creatinine during induction therapy and at 4-weeks post-diagnosis in Ugandans undergoing cryptococcal meningitis therapy, and classified as not receiving antiretroviral therapy (ART), receiving non-tenofovir ART, or receiving tenofovir-based ART. Longitudinal creatinine changes and Grade 2-4 creatinine adverse events were evaluated across groups. Creatinine concentrations were similar across ART groups. At 4 weeks post-diagnosis, creatinine was 0.25mg/dL higher than at diagnosis, but similar across groups. Adverse event incidence was also similar across ART groups. Tenofovir and amphotericin co-administration did not increase the risk of kidney dysfunction.
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