Tetracycline and sulphonamide residues in farmed fish in Dar es Salaam, Tanzania and human health risk implications.

In Africa, antibiotic residue investigations in animal food have primarily been focused on meat, neglecting farmed fish. This cross-sectional study conducted in Dar es Salaam, Tanzania, aimed to assess sulphonamide and tetracycline residues in farmed fish, comparing levels with Codex Alimentarius Commission's acceptable daily intake (ADI) and maximum residue limits (MRLs). A total of 84 farmed fish were sampled and analysed in the presence of tetracycline and sulphonamide residues. All samples were positive for sulphonamide residues (100%; n = 84), and 2.4% (n = 2) were positive for tetracycline and consequently also positive for both compounds. Tetracycline levels were below ADI and MRL, 28.5% (n = 24) surpassed the ADI, and 6% (n = 5) of the samples exceeded the MRL for sulphonamide. Regular monitoring of antibiotic residues in aquaculture products is crucial to mitigate health risks and expanding assessments to include other commonly used compounds is warranted.

Occurrence of Multi-Drug-Resistant Escherichia coli in Chickens, Humans, Rodents and Household Soil in Karatu, Northern Tanzania.

We investigated antibiotic resistance profiles of Escherichia coli among 960 samples obtained from chickens (236), humans (243), rodents (101) and soil (290). E. coli was isolated from 650 (67.7%) samples. Isolation frequency varied significantly between chickens, humans, rodents and soil samples, being 81.6%, 86.5%, 79.2% and 31.0%, respectively (p < 0.001). Resistance rates were particularly higher against imipenem (79.8%), cefotaxime (79.7%) and tetracycline (73.7%) and moderate against amoxicillin-clavulanate (49.4%). Overall, 78.8% of the isolates were multidrug-resistant (MDR) among which, 38.8%, 25.1%, 12.9% and 2.5% exhibited resistance to three, four, five and six different classes of antibiotics, respectively. Multidrug-resistant E. coli were observed in 27.7%, 30.3%, 10.8% and 10.0% of the isolates from chickens, humans, rodents and soil samples, respectively. Our results show high levels of antimicrobial resistance including MDR in E. coli isolated from chickens, humans, rodents and soil samples in Karatu, Northern Tanzania. Comprehensive interventions using a one-health approach are needed and should include improving (i) awareness of the community on judicious use of antimicrobial agents in humans and animals, (ii) house conditions and waste management and (iii) rodent control measures.

Antimicrobial Resistance Profiles of Escherichia coli Isolated from Broiler and Layer Chickens in Arusha and Mwanza, Tanzania.

The rise in the spread of antibiotic-resistant pathogens such as Escherichia coli is one of the very important dynamics off-putting treatment and prophylaxis possibilities, hence posing a threat to the modern human medicine, veterinary medicine, and food safety. Therefore, the aim of this study was to determine antimicrobial resistance profiles in E. coli isolates obtained from broiler and layer chickens in Mwanza and Arusha regions in Tanzania. A cross-sectional study was carried out from February to March, 2021, in 402 poultry farms in Mwanza (201) and Arusha (201) regions in Tanzania. All samples that tested positive for E. coli were confirmed using MALDI-TOF MS, and two hundred and four (204) E. coli isolates were randomly chosen and subjected to antimicrobial susceptibility testing by disc diffusion method. Data were entered in Microsoft Excel® and analyzed using SPSS version 20. Isolates were tested against seven antimicrobial agents belonging to seven classes of antimicrobials. All the tested isolates (n = 204) were resistant to at least one antimicrobial agent. Overall, the highest resistance was observed in ampicillin (100%), whereas the lowest resistance was recorded for gentamicin (10.3%). Majority of the isolates (86.76%) were multidrug resistant. Antimicrobial resistance of E. coli to four classes of antimicrobial agents was the highest in this study (31.1%). Six of the 177 tested isolates (2.9%) were resistant to the seven classes of antimicrobial agents. 21 of the 204 (10.29%) isolates were ESBL producers where 21/21 (100%) isolates expressed bla TEM genes and only two isolates expressed (2/21) bla CTX-M gene. The isolates obtained in this study displayed high resistance to commonly used antimicrobial agents in veterinary and human medicine. This implies that there is existence of practices that accelerate antimicrobial resistance in the production of the sampled birds and therefore integration of appropriate use of antimicrobial agents and other measures that curb the spread of resistant genes is necessary.

Occurrence of Extended Spectrum Beta Lactamase (ESBL) Producers, Quinolone and Carbapenem Resistant Enterobacteriaceae Isolated from Environmental Samples along Msimbazi River Basin Ecosystem in Tanzania.

We conducted environmental surveillance of antimicrobial resistance (AMR) bacteria in the Msimbazi river basin in Tanzania to determine the occurrence of extended-spectrum ß-lactamase (ESBL)-producing, carbapenem resistant Enterobacteriaceae (CRE) and quinolone resistant Escherichia coli and Klebsiella spp. A total of 213 Enterobacteriaceae isolates were recovered from 219 samples. Out of the recovered isolates, 45.5% (n = 97) were Klebsiella pneumoniae and 29.6% (n = 63) were Escherichia coli. K. pneumoniae isolates were more resistant in effluent (27.9%) compared to the E. coli (26.6%). The E. coli had a higher resistance in river water, sediment and crop soil than the K. pneumoniae (35 versus 25%), respectively. Higher resistance in K. pneumoniae was found in nalidixic acid (54.6%) and ciprofloxacin (33.3%) while the E. coli isolates were highly resistant to ciprofloxacin (39.7%) and trimethoprim/sulfamethoxazole (38%). Resistance increased from 28.3% in Kisarawe, where the river originates, to 59.9% in Jangwani (the middle section) and 66.7% in Upanga West, where the river enters the Indian Ocean. Out of 160 E. coli and K. pneumoniae isolates, 53.2% (n = 85) were resistant to more than three classes of the antibiotic tested, occurrence being higher among ESBL producers, quinolone resistant and carbapenem resistant strains. There is an urgent need to curb environmental contamination with antimicrobial agents in the Msimbazi Basin.

Multidrug-Resistant, Including Extended-Spectrum Beta Lactamase-Producing and Quinolone-Resistant, Escherichia coli Isolated from Poultry and Domestic Pigs in Dar es Salaam, Tanzania.

We determined the phenotypic profile of multidrug-resistant (MDR) Escherichia coli isolated from 698 samples (390 and 308 from poultry and domestic pigs, respectively). In total, 562 Enterobacteria were isolated. About 80.5% of the isolates were E. coli. Occurrence of E. coli was significantly higher among domestic pigs (73.1%) than in poultry (60.5%) (p = 0.000). In both poultry and domestic pigs, E. coli isolates were highly resistant to tetracycline (63.5%), nalidixic acid (53.7%), ampicillin (52.3%), and trimethoprim/sulfamethoxazole (50.9%). About 51.6%, 65.3%, and 53.7% of E. coli were MDR, extended-spectrum beta lactamase-producing enterobacteriaceae (ESBL-PE), and quinolone-resistant, respectively. A total of 68% of the extended-spectrum beta lactamase (ESBL) producers were also resistant to quinolones. For all tested antibiotics, resistance was significantly higher in ESBL-producing and quinolone-resistant isolates than the non-ESBL producers and non-quinolone-resistant E. coli. Eight isolates were resistant to eight classes of antimicrobials. We compared phenotypic with genotypic results of 20 MDR E. coli isolates, ESBL producers, and quinolone-resistant strains and found 80% harbored blaCTX-M, 15% aac(6)-lb-cr, 10% qnrB, and 5% qepA. None harbored TEM, SHV, qnrA, qnrS, qnrC, or qnrD. The observed pattern and level of resistance render this portfolio of antibiotics ineffective for their intended use.

The Governance and Implementation of the National Action Plan on Antimicrobial Resistance in Tanzania: A Qualitative Study.

Tanzania launched its first National Action Plan (NAP) on antimicrobial resistance (AMR) in 2017 to reduce the burden of AMR in the country and contribute to the global response. We aimed to analyze the implementation of the NAP on AMR in Tanzania using the governance framework. In-depth interviews were conducted with human and animal health practitioners and national-level policy actors. We adapted Chua's AMR governance framework to analyze the development and implementation of the NAP in Tanzania. Implementation of the NAP has realized several achievements, including: (i) the establishment of a functioning Multi-Sectoral Coordinating Committee for coordinating the implementation of AMR activities; (ii) existence of governance structure; (iii) establishment of human and animal surveillance sites; (iv) creation of AMR awareness in the community and (v) availability of guidelines at the health facility level to ensure AMR stewardship. However, some dimensions of the governance areas, including reporting and feedback mechanisms, accountability, transparency and sustainability of AMR plans, are not effectively implemented. Addressing these challenges should involve strengthening the collaboration of the different sectors involved at different NAP implementation levels by careful planning and coordination, and provision of adequate resources to ensure sustainability.

Assessment of Drivers of Antimicrobial Use and Resistance in Poultry and Domestic Pig Farming in the Msimbazi River Basin in Tanzania.

Uncontrolled use of drugs both in humans and animals coupled with environmental contamination exacerbate the development and spread of antimicrobial resistance. This paper assessed the drivers of antimicrobial use and resistance in poultry and domestic pig farming and the environment. Questionnaires, in-depth interviews, and focus group discussions (FGDs) were used to collect information regarding demographic characteristics, knowledge, practices, attitudes, and perceptions of the drivers of antimicrobial use and resistance in animal farming and the environment. We found a higher proportion of usage of veterinary antimicrobials for prophylactic purposes (87.6%) in animal farming, than for therapeutic purposes (80.5%). The degree of farming experience was significantly (p < 0.05) related to the knowledge on the source of antimicrobial use, methods used in disease diagnosis, access to veterinary services, stocking of antimicrobials at home, and presence of agriculture activities that involve the use of manure. Uncontrolled disposal of wastes from households, disposal of human and veterinary drugs, and weak implementation of the legal framework was identified as the major contributors to the environment. The high usage of veterinary antimicrobials and the environmental contamination identified requires multisectoral interventions, as well as a review of government strategies, policies, and regulations on antimicrobial use.

Antimicrobial use and resistance in food-producing animals and the environment: an African perspective.

BACKGROUND: The overuse of antimicrobials in food animals and the subsequent contamination of the environment have been associated with development and spread of antimicrobial resistance. This review presents information on antimicrobial use, resistance and status of surveillance systems in food animals and the environment in Africa. METHODS: Information was searched through PubMed, Google Scholar, Web of Science, and African Journal Online databases. Full-length original research and review articles on antimicrobial use, prevalence of AMR from Africa covering a period from 2005 to 2018 were examined. The articles were scrutinized to extract information on the antimicrobial use, resistance and surveillance systems. RESULTS: A total of 200 articles were recovered. Of these, 176 studies were included in the review while 24 articles were excluded because they were not relevant to antimicrobial use and/or resistance in food animals and the environment. The percentage of farms using antimicrobials in animal production ranged from 77.6% in Nigeria to 100% in Tanzania, Cameroon, Zambia, Ghana and Egypt. The most antibiotics used were tetracycline, aminoglycoside and penicillin groups. The percentage of multi drug resistant isolates ranged from 20% in Nigeria to 100% in South Africa, Zimbabwe and Tunisia. In the environment, percentage of multi drug resistant isolates ranged from 33.3% in South Africa to 100% in Algeria. None of the countries documented national antimicrobial use and resistance surveillance system in animals. CONCLUSION: There is high level of antimicrobial use, especially tetracycline, aminoglycoside and penicillin in animal production systems in Africa. This is likely to escalate the already high prevalence of antimicrobial resistance and multi drug resistance in the continent. This, coupled with weak antimicrobial resistance surveillance systems in the region is a great concern to the animals, environment and humans as well.

Clinical characteristics and treatment outcomes of patients with MDR tuberculosis in Dar Es Salaam region, Tanzania.

BACKGROUND: In Tanzania more than 28% of all multi-drug resistant tuberculosis (MDR-TB) cases occur in Dar es Salaam. However, information about management and clinical outcomes of patients with MDR-TB in the region is scarce, and hence the need for this study. METHODS: A 5-year retrospective cohort study was conducted in six centres in Dar es Salaam. Descriptive statistics were used to summarize social demographics and clinical characteristics. Associations between occurrence of adverse events, regimen change and cure were determined using the Chi-square test whereas factors associated with mortality were determined using the Log-ranking test and Cox regression model. RESULTS: Three-hundred patient files were found and reviewed. The majority were male 199 (66.3%), aged 25-44 years [176 (58.7%)] and 89 (30.1%) were HIV co-infected. 186 (62%) completed their treatment, 68 (22.0%) were on treatment and 9 (3.3%) were lost to follow-up. The majority, 152 (51.0%) were managed using long MDR-TB regimens. The overall mortality rate was 5.7 per 1000 MDR-TB patients. A higher mortality rate was associated with being ≥45 years [adjusted hazard ratio (AHR): 10.82, 95% CI: 1.14-102.74, P = 0.038), female (AHR: 5.92, 95% CI: 1.75-20.08, P = 0.004), on a short anti-TB regimen (AHR: 4.34, 95% CI: 1.41-13.35, P = 0.010), HIV co-infected [crude hazard ratio (CHR): 2.56, 95% CI: 1.01-6.50, P = 0.048), on concomitant long-term medication use (CHR: 2.99, 95% CI: 1.17-7.64, P = 0.022) and having other co-morbidities (CHR: 3.45, 95% CI: 1.32-9.02, P = 0.011). CONCLUSIONS: MDR-TB mortality was associated with short anti-TB regimens, sex, age, concomitant long-term medication use and HIV coinfection. In this population, use of long and individualized regimens is recommended.

Performance of Widal test and stool culture in the diagnosis of typhoid fever among suspected patients in Dar es Salaam, Tanzania.

OBJECTIVE: We set an experiment to determine the diagnostic performance of the Widal test and stool culture in typhoid-suspected cases attending tertiary hospitals in Dar es Salaam, Tanzania using blood culture as a golden standard. We also evaluated the agreement between Widal, stool and blood culture. RESULTS: This was a cross-sectional study conducted between June and September 2018, in three Regional Referral Hospitals in Dar es Salaam, Tanzania. A total of 158 typhoid-suspected cases were enrolled, after obtaining an informed consent. Of the 158 patients participated in the study, 128 (81%) tested positive for the Widal test and 17 (11%) patients were stool culture positive. Widal test recorded 81.5% sensitivity, 18.3% specificity, 10.1% positive predictive value and 89.7% negative predictive value. Stool culture showed 31.3% sensitivity, 91.5% specificity, 29% positive predictive value and 91.5% negative predictive value. In conclusion, Widal test is not reliable for diagnosis of typhoid fever since false positive and negative results are common. In addition, Widal test recorded poor agreement with the blood culture (kappa = 0.014, p < 0.05) while stool culture had strong agreement with the blood culture (kappa = 0.22, p < 0.05).

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.

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

BACKGROUND: In 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. METHODS: A 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). RESULTS: Candida 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. CONCLUSION: C. 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.

Seroprevalence of human immunodeficiency virus, hepatitis B and C viruses and syphilis infections among blood donors at the Muhimbili National Hospital in Dar es Salaam, Tanzania.

BACKGROUND: According to the latest Tanzanian National AIDS Control Programme (NACP) report a total of 147,271 individuals donated blood during the year 2002. However, blood safety remains an issue of major concern in transfusion medicine in Tanzania where national blood transfusion services and policies, appropriate infrastructure, trained personnel and financial resources are inadequate. Most of the donated blood is screened for HIV alone. METHODS: We determined among blood donors at Muhimbili National Hospital (MNH), the seroprevalence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) and syphilis by donor type, sex and age and to determine association, if any, in the occurrence of the pathogens. The sample included 1599 consecutive donors, 1424(89.1%) males and 175 (10.9%) females, who donated blood between April 2004 and May, 2005. Most of them 1125 (70.4%) were replacement donors and a few 474 (29.6%) voluntary donors. Their age (in years) ranged from 16 to 69, and most (72.2%) were between 20-39 years. RESULTS: Two hundred and fifty four (15.9%) of the donated blood had serological evidence of infection with at least one pathogen and 28 (1.8%) had multiple infections. The current seroprevalence of HIV, HBsAg, HCV and syphilis among blood donors at MNH in Dar es Salaam was found to be 3.8%, 8.8%, 1.5% and 4.7%, respectively. Respective seroprevalences among HIV seronegative blood donors were 8.7% for HBV, 1.6% for HCV and 4.6% for syphilis. The differences in the prevalence of HIV and syphilis infections between replacement and voluntary donors were statistically significant (P < 0.05). Syphilis was the only infection that occurred more frequently among HIV infected (12.1%) than non-infected (4.6%) blood donors (P < 0.05), and whose prevalence increased with age (X2 = 58.5 df = 5, P < 0.001). There were no significant sex differences in the occurrence of pathogens. Finally, there were significant associations in the occurrence of HBsAg and syphilis (OR = 2.2, 95% CI 1.1.-4.2) and HIV and syphilis (OR = 2.2, 95% CI 1.0-5.3). CONCLUSION: The high (15.9%) seroprevalence of blood-borne infections in blood donated at MNH calls for routine screening of blood donors for HBV, HCV, HIV and syphilis and for strict selection criteria of donors, with emphasis on getting young voluntary donors and for establishment of strict guidelines for blood transfusions.

Surveillance of HIV and syphilis infections among antenatal clinic attendees in Tanzania-2003/2004.

BACKGROUND: This paper presents the prevalence of human immunodeficiency virus (HIV) and syphilis infections among women attending antenatal clinics (ANC) in Tanzania obtained during the 2003/2004 ANC surveillance. METHODS: Ten geographical regions; six of them were involved in a previous survey, while the remaining four were freshly selected on the basis of having the largest population among the remaining 20 regions. For each region, six ANC were selected, two from each of three strata (urban, peri-urban and rural). Three of the sites did not participate, resulting into 57 surveyed clinics. 17,813 women who were attending the chosen clinics for the first time for any pregnancy between October 2003 and January 2004. Patient particulars were obtained by interview and blood specimens were drawn for HIV and syphilis testing. HIV testing was done anonymously and the results were unlinked. RESULTS: Of the 17,813 women screened for HIV, 1,545 (8.7% (95% CI = 8.3-9.1)) tested positive with the highest prevalence in women aged 25-34 years (11%), being higher among single women (9.7%) than married women (8.6%) (p < 0.07), and increased with level of education from 5.2% among women with no education to 9.3% among those at least primary education (p < 0.001). Prevalence ranged from 4.8% (95% CI = 3.8%-9.8%) in Kagera to 15.3% (95% CI = 13.9%-16.8%) in Mbeya and was; 3.7%, 4.7%, 9.1%, 11.2% and 15.3% for rural, semi-urban, road side, urban and 15.3% border clinics, respectively (p < 0.001). Of the 17,323 women screened for syphilis, 1265 (7.3% (95%CI = 6.9-7.7)) were positive, with highest prevalence in the age group 35-49 yrs (10.4%) (p < 0.001), and being higher among women with no education than those with some education (9.8% versus 6.8%) (p < 0.0001), but marital status had no influence. Prevalence ranged from 2.1% (95% CI = 1.4%-3.0%) in Kigoma to 14.9% (95% CI = 13.3%-16.6%) in Kagera and was 16.0% (95% CI = 13.3-18.9), 10.5% (95% CI = 9.5-11.5) and 5.8% (95% CI = 5.4-6.3) for roadside, rural and urban clinics, respectively. Syphilis and HIV co-infection was seen in 130/17813 (0.7%). CONCLUSION: The high HIV prevalence observed among the ANC clinic attendees in Tanzania call for expansion of current voluntary counselling and testing (VCT) services and access to antiretroviral drugs (ARV) in the clinics. There is also a need for modification of obstetric practices and infant feeding options in HIV infection in order to prevent mother to child transmission of HIV. To increase uptake to HIV testing the opt-out strategy in which all clients are offered HIV testing is recommended in order to meet the needs of as many pregnant women as possible.

Estimating and projecting HIV prevalence and AIDS deaths in Tanzania using antenatal surveillance data.

BACKGROUND: The Estimations and Projections Package (EPP 2005) for HIV/AIDS estimates and projects HIV prevalence, number of people living with HIV and new HIV infections and AIDS cases using antenatal clinic (ANC) surveillance data. The prevalence projection produced by EPP can be transferred to SPECTRUM, a demographic projection model, to calculate the number of AIDS deaths. This paper presents estimates and projections of HIV prevalence, new cases of HIV infections and AIDS deaths in Tanzania between 2001 and 2010 using the EPP 2005 and SPECTRUM soft-wares on ANC data. METHODS: For this study we used; the 1985-2004 ANC data set, the 2005 UN population estimates for urban and rural adults, which is based on the 2002 population census, and results of the 2003 Tanzania HIV Indicator Survey. The ANC surveillance sites were categorized into urban and rural areas on the basis of the standard national definitions of urban and rural areas, which led to 40 urban and 35 rural clinic sites. The rural and urban epidemics were run independently by fitting the model to all data and on level fits. RESULTS: The national HIV prevalence increased from 0% in 1981 to a peak of 8.1% in 1995, and gradually decreased to 6.5% in 2004 which stabilized until 2010. The urban HIV epidemic increased from 0% in 1981 peaking at 12.6% in 1992 and leveled to between 10.9% and 11.8% from 2003 to 2010. The rural epidemic peaked in 1995 at 7.0% and gradually declined to 5.2% in 2004, and then stabilized at between 5.1% and 5.3% from 2005 to 2010. New infections are projected to rise steadily, resulting in 250,000 new cases in 2010. Deaths due to AIDS started in 1985 and rose steadily to reach 120,000 deaths in 2010, with more females dying than men. CONCLUSION: The fact that the number of new infections is projected to increase steadily to reach 250,000 per year in 2010 calls for more concerted efforts to combat the spread of HIV infection particularly in the rural areas where the infrastructure needed for prevention programmes such as counseling and testing, condom accessibility and AIDS information is less developed.

Antifungal activity of some Tanzanian plants used traditionally for the treatment of fungal infections.

Using the ethnobotanical approach, some Tanzanian plants reported to be used by traditional healers for the treatment of oral candidiasis and fungal infections of the skin were collected and screened for their antifungal activity against Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei and Cryptococcus neoformans. A total of 65 crude methanol extracts belonging to 56 plant species and 38 families were screened using the broth microdilution method, according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI) (formerly, National Committee for Clinical and Laboratory Standards) [National Committee for Clinical Laboratory Standards, 2002. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Approved Standard-2nd Edition M27-A2, National Committee for Clinical Laboratory Standards, Wayne, PA, USA]. Among the tested plant species, 45% (25 species) showed antifungal activity against one or more of the test fungi. The most susceptible yeasts were Cryptococcus neoformans, followed by Candida krusei, Candida tropicalis, and Candida parapsilosis. The least susceptible were Candida albicans and Candida glabrata. Strong antifungal activity was exhibited by extracts of Clausena anisata Oliv., Sclerocariya birrea Sond, Turraea holstii Gurk, Sterculia africana (Lour) Fiori, Acacia robusta subsp. Usambarensis (Taub) Brenan, Cyphosterma hildebrandti (Gilg), Desc, Elaeodendron buchannanii (Lows), Acacia nilotica (L.) Wild ex Del, Jatropha multifida L., and Pteridium aquilinum (L.) Kuhn.

Screening of Tanzanian medicinal plants for anti-Candida activity.

BACKGROUND: Candida albicans has become resistant to the already limited, toxic and expensive anti-Candida agents available in the market. These factors necessitate the search for new anti-fungal agents. METHODS: Sixty-three plant extracts, from 56 Tanzanian plant species obtained through the literature and interviews with traditional healers, were evaluated for anti-Candida activity. Aqueous methanolic extracts were screened for anti-Candida activity by bioautography agar overlay method, using a standard strain of Candida albicans (ATCC 90028). RESULTS: Twenty- seven (48%) out of the 56 plants were found to be active. Extracts of the root barks of Albizia anthelmintica and Balanites aegyptiaca, and roots of Plectranthus barbatus showed strong activity. CONCLUSION: The extracts that showed strong anti-Candida activity are worth of further investigation in order to isolate and identify the active compounds.

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

BACKGROUND: The 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. METHODS: Participants 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. RESULTS: A 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 (chi2 = 4.31; df = 1; p = 0.03) and parotid enlargement (chi2 = 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 (chi2 = 52.4; df = 2; p = 0.006) and with WHO clinical stage (chi2 = 121; df = 3; p = 0.008). Oral lesions were also associated with tobacco smoking (chi2 = 8.17; df = 2; p = 0.04). CONCLUSION: Adult 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.

Genetic variation of innate immune genes in HIV-infected african patients with or without oropharyngeal candidiasis.

BACKGROUND: The occurrence of oropharyngeal candidiasis (OPC) in combination with HIV disease progression is a very common phenomenon. However, not all HIV-infected patients develop OPC, even when they progress to low CD4 T-cell counts. Because T-cell immunity is defective in AIDS, the innate defence mechanisms are likely to have a central role in antifungal immunity in these patients. We investigated whether genetic variations in the innate immune genes DECTIN-1, TLR2, TLR4, TIRAP, and CASPASE-12 are associated with the presence of OPC in HIV-infected subjects from East Africa. METHODS: A total of 225 HIV patients were genotyped for several single nucleotide polymorphisms (SNPs), and this was correlated with the occurrence of OPC in these patients. In addition, primary immune cells obtained from individuals with different genotypes were stimulated with Candida albicans, and cytokine production was measured. RESULTS: The analysis revealed that no significant differences in the polymorphism frequencies could be observed, although a tendency toward a protective effect on OPC of the DECTIN-1 I223S SNP was apparent. Furthermore, interferon gamma production capacity was markedly lower in cells bearing the DECTIN-1 SNP I223S. It could also be demonstrated that the 223S mutated form of the DECTIN-1 gene exhibits a lower capacity to bind zymosan. CONCLUSIONS: These data demonstrate that common polymorphisms of TLR2, TLR4, TIRAP, and CASPASE-12 do not influence susceptibility to OPC in HIV-infected patients in East Africa but suggest an immunomodulatory effect of the I223S SNP on dectin-1 function and possibly the susceptibility to OPC in HIV patients.

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.