F. H. M. Mikx

Oral manifestations of HIV infection in children and adults receiving highly active anti-retroviral therapy [HAART] in Dar es Salaam, Tanzania

BackgroundThe aim of the study was to compare the prevalence and types of HIV-related oral lesions between children and adult Tanzanian patients on HAART with those not on HAART and to relate the occurrence of the lesions with anti-HIV drug regimen, clinical stage of HIV disease and CD4+ cell count.MethodsParticipants were 532 HIV infected patients, 51 children and 481 adults, 165 males and 367 females. Children were aged 2–17 years and adults 18 and 67 years. Participants were recruited consecutively at the Muhimbili National Hospital (MNH) HIV clinic from October 2004 to September 2005. Investigations included; interviews, physical examinations, HIV testing and enumeration of CD4+ T cells.ResultsA total of 237 HIV-associated oral lesions were observed in 210 (39.5%) patients. Oral candidiasis was the commonest (23.5%), followed by mucosal hyperpigmentation (4.7%). There was a significant difference in the occurrence of oral candidiasis (χ2 = 4.31; df = 1; p = 0.03) and parotid enlargement (χ2 = 36.5; df = 1; p = 0.04) between children and adults. Adult patients who were on HAART had a significantly lower risk of; oral lesions (OR = 0.32; 95% CI = 0.22 – 0.47; p = 0.005), oral candidiasis (OR = 0.28; 95% CI = 0.18 – 0.44; p = 0.003) and oral hairy leukoplakia (OR = 0.18; 95% CI = 0.04 – 0.85; p = 0.03). There was no significant reduction in occurrence of oral lesions in children on HAART (OR = 0.35; 95% CI = 0.11–1.14; p = 0.15). There was also a significant association between the presence of oral lesions and CD4+ cell count < 200 cell/mm3 (χ2 = 52.4; df = 2; p = 0.006) and with WHO clinical stage (χ2 = 121; df = 3; p = 0.008). Oral lesions were also associated with tobacco smoking (χ2 = 8.17; df = 2; p = 0.04).ConclusionAdult patients receiving HAART had a significantly lower prevalence of oral lesions, particularly oral candidiasis and oral hairy leukoplakia. There was no significant change in occurrence of oral lesions in children receiving HAART. The occurrence of oral lesions, in both HAART and non-HAART patients, correlated with WHO clinical staging and CD4+ less than 200 cells/mm3.

Mutans Streptococci and Lactobacilli in Breast-Fed Children with Rampant Caries

This study aimed to investigate the prevalence of selected components of the oral microflora in breast-fed children who developed rampant caries (resembling nursing caries) under hitherto unexplained circumstances. Dental plaque and saliva samples were collected from breast-fed children, aged between 1 and 2.5 years, with and without rampant caries. Mutans streptococci and lactobacilli were isolated from dental plaque of all children with rampant caries and from most caries-free children. None of the colonies of mutans streptococci resembled those of Streptococcus sobrinus. The mean counts of the mutans streptococci and lactobacilli were 100-fold higher in plaque samples from children with rampant caries as compared with caries-free children. No difference could be found between the numbers of mutans streptococci in plaque overlaying cavities and that from adjacent sound enamel. In contrast, the counts of lactobacilli in plaque were approximately 100-fold higher from cavities than from sound surfaces. The levels of mutans streptococci in saliva were directly related to the presence of rampant caries. The results show that caries-free and caries-active breast-fed children, aged 1 to 2.5 years, harbour mutans streptococci and lactobacilli on their teeth. Rampant caries in these children can occur in the absence of nursing bottles or any other feeding abuse during weaning and in the presence of an aciduric plaque microflora, as has been reported for children with nursing bottle caries.

Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis

BackgroundIn Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis.MethodsA total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients with oropharyngeal candidiasis at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Identification of the yeasts was performed using standard phenotypic methods. Antifungal susceptibility to fluconazole, itraconazole, miconazole, clotrimazole, amphotericin B and nystatin was assessed using a broth microdilution format according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI; M27-A2).ResultsCandida albicans was the most frequently isolated species from 250 (84.5%) patients followed by C. glabrata from 20 (6.8%) patients, and C. krusei from 10 (3.4%) patients. There was no observed significant difference in species distribution between patients with primary and recurrent oropharyngeal candidiasis, but isolates cultured from patients previously treated were significantly less susceptible to the azole compounds compared to those cultured from antifungal naïve patients.ConclusionC. albicans was the most frequently isolated species from patients with oropharyngeal candidiasis. Oral yeast isolates from Tanzania had high level susceptibility to the antifungal agents tested. Recurrent oropharyngeal candidiasis and previous antifungal therapy significantly correlated with reduced susceptibility to azoles antifungal agents.

Selection of a Micromethod and Its Use in the Estimation of Salivary Streptococcus mutans and Lactobacillus Counts in Relation to Dental Caries in Tanzanian Children

Three micromethods for the estimation of Streptococcus mutans and lactobacilli were compared. A micropipette method was selected because of its ability to detect low levels of the o

Single-Dose Fluconazole versus Standard 2-Week Therapy for Oropharyngeal Candidiasis in HIV-Infected Patients: A Randomized, Double-Blind, Double-Dummy Trial

BACKGROUND Oropharyngeal candidiasis is the most common opportunistic infection affecting patients with human immunodeficiency virus (HIV) infection. Because of convenience, cost, and reluctance to complicate antiretroviral treatment regimens, single-dose fluconazole may be a favorable regimen for treatment of moderate to severe oropharyngeal candidiasis. We conducted a prospective, randomized, double-blind, placebo-controlled trial to compare the clinical and mycological responses, relapse rates, and safety of a single 750-mg dose and a 14-day course of treatment with fluconazole. METHODS A total of 220 HIV-infected patients with clinical and mycological evidence of oropharyngeal candidiasis were randomly assigned in a 1:1 ratio to receive either a 750-mg single dose of orally administered fluconazole (110 patients) or 150 mg of orally administered fluconazole once per day for 2 weeks (110 patients). The primary efficacy analysis was based on clinical and mycological responses at the end of treatment. Secondary parameters were safety and relapse rate. RESULTS Single-dose fluconazole was equivalent to a 14-day course of fluconazole in achieving clinical and mycological cure, with clinical cure rates of 94.5% and 95.5%, respectively (odds ratio, 0.825; 95% confidence interval, 0.244-2.789; P= .99), and mycological cure rates of 84.5% and 75.5%, respectively (odds ratio, 1.780; 95% confidence interval, 0.906-3.496; P= .129). Drug-related adverse events were uncommon and were not different between the treatment groups. CONCLUSION A single dose of 750 mg of fluconazole was safe, well tolerated, and as effective as the standard 14-day fluconazole therapy in patients with HIV infection and acquired immunodeficiency syndrome who had oropharyngeal candidiasis coinfection.

Evaluation of cytotoxic, genotoxic and CYP450 enzymatic competition effects of Tanzanian plant extracts traditionally used for treatment of fungal infections.

HIV-infected patients in sub-Saharan countries highly depend on traditional medicines for the treatment of opportunistic oral infections as candidiasis. Previous investigations on antifungal activity of medicinal plant extracts utilized by traditional healers in Tanzania have revealed 12 extracts with potent antifungal activity. Although the plants may be good candidates for new treatment opportunities, they can be toxic or genotoxic and could cause pharmacokinetic interactions when used concomitantly with antiretroviral agents. Therefore, we investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342, Alamar Blue, calcein-AM, glutathione depletion and O(2)-consumption assays and genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP inhibition screening. Pregnane X receptor (PXR) activation was tested using Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing high human PXR activation were tested for enhanced CYP3A4 mRNA levels with quantitative polymerase chain reaction. Genotoxicity was found for Jatropha multifida, Sterculia africana and Spirostachys africana. All plant extracts showed high cytotoxic effects in almost all tests. Potent competition with CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant activation of human PXR, but only Agaura salicifolia, Turraea holstii and S. africana significantly induced CYP3A4 mRNA levels. These results indicate the possibility of potential medicinal plant-antiretroviral interactions.

Fermentation of carbohydrates in different flours by Streptococcus mutans

The ability of Streptococcus mutans to ferment carbohydrates and to produce acid was investigated in different flours in vitro. The amounts of acid produced suggest a possible ecological role of the tested flours in the occurrence of Strep. mutans in dental plaque.