Cryptococcal disease and the burden of other fungal diseases in Uganda; Where are the knowledge gaps and how can we fill them?

The HIV epidemic in Uganda has highlighted Cryptococcus and Candida infections as important opportunistic fungal infections. However, the burden of other fungal diseases is not well described. We aimed to estimate the burden of fungal infections in Uganda. All epidemiological papers of fungal diseases in Uganda were reviewed. Where there is no Ugandan data, global or East African data were used. Recurrent vaginal candidiasis is estimated to occur in 375 540 Uganda women per year; Candida in pregnant women affects up to 651,600 women per year. There are around 45,000 HIV-related oral and oesophageal candidosis cases per year. There are up to 3000 cases per year of post-TB chronic pulmonary aspergillosis. There are an estimated 40,392 people with asthma-related fungal conditions. An estimated 1,300,000 cases of tinea capitis occur in school children yearly in Uganda. There are approximately 800 HIV-positive adults with Pneumocystis jirovecii pneumonia (PJP) annually and up to 42 000 children with PJP per year. There are an estimated 4000 cryptococcal cases annually. There are an estimated 2.5 million fungal infections per year in Uganda. Cryptococcus and PJP cause around 28,000 deaths in adults and children per year. We propose replicating the model of research around cryptococcal disease to investigate and development management strategies for other fungal diseases in Uganda.

Prevalence and type of drug-drug interactions involving ART in patients attending a specialist HIV outpatient clinic in Kampala, Uganda.

OBJECTIVES: Scale-up of HIV services in sub-Saharan Africa has rapidly increased, necessitating evaluation of medication safety in these settings. Drug-drug interactions (DDIs) involving antiretrovirals (ARVs) in sub-Saharan Africa are poorly characterized. We evaluated the prevalence and type of ARV DDIs in Ugandan outpatients and identified the patients most at risk. METHODS: A total of 2000 consecutive patients receiving ARVs at the Infectious Diseases Institute, Kampala were studied. The most recent prescription for each patient was screened for clinically significant DDIs using www.hiv-druginteractions.org. Univariable and multivariable logistic regression were used to identify risk factors for DDIs. A screening tool was developed using significant risk factors and tested in a further 500 patients. RESULTS: Clinically significant DDIs were observed in 374 (18.7%) patients, with a total of 514 DDIs observed. Only 0.2% of DDIs involved a contraindicated combination. Comedications commonly associated with DDIs were antibiotics (4.8% of 2000 patients), anthelmintics (2.2%) and antifungals (3.5%). Patient age, gender, CD4 count and weight did not affect risk of DDIs. In multivariable analysis, the patient factors that independently increased risk of DDIs were two or more comedications (P < 0.0001), a PI-containing ARV regimen (P < 0.0001), use of an anti-infective (P < 0.0001) and WHO clinical stage 3-4 (P = 0.04). A scoring system based on having at least two of these risk factors identified between 75% and 90% of DDIs in a validation cohort. CONCLUSIONS: Significant ARV DDIs occur at similar rates in resource-limited settings and developed countries; however, the comedications frequently causing DDIs differ. Development of tools that are relevant to particular settings should be a priority to assist with prevention and management of DDIs.

Use of nail and oral pigmentation to determine ART eligibility among HIV-infected Ugandan adults.

OBJECTIVES: To evaluate the use of grey/distal banded nails as an indicator of advanced immunosuppression, and thus eligibility for ART, in resource poor settings. METHODS: We tested whether grey/distal banded nails and/or oral pigmentation could be used to identify patients with low CD4 cell counts at two cut-offs: <200 and <350 cells/microl in ART naive adults. RESULTS: Four hundred and three nail and oral cavities were photographed and assessed. Grey/distal banded nails and/or oral pigmentation were significantly associated with a CD4 cell count <200 cells/microl (P < 0.001), with a sensitivity of 66%, a specificity of 50% and a negative predictive value of 77%. However, there was no association when a CD4 cell count cut-off of <350 cells/microl was used. Inter-observer agreement (k 0.46) was fair/moderate. CONCLUSIONS: While grey/distal banded nails and/or oral pigmentation are associated with low CD4 counts, the sensitivity and kappa score are too low for this method to be recommended as a tool to guide ART initiation; large number of individuals eligible for ART would be missed.