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Energy metabolism of bloodstream form Trypanosoma theileri
Bloodstream form Trypanosoma theileri degrades glucose to acetate (47%) and succinate (45%) and, therefore, does not solely rely on glycolysis for ATP production. This trypanosomatid does not use amino acids for energy metabolism. These results refute the prevailing hypothesis that substrate availability determines the type of energy metabolism of trypanosomatids
Functional adrenal insufficiency among critically ill patients with human immunodeficiency virus in a resource-limited setting
Background: Functional adrenal insufficiency (FAI) is associated with increased mortality and is defined as subnormal cortisol production during acute severe illness. Methods: After screening 200 adult patients admitted in the medical emergency unit of Mulago Hospital, Kampala, Uganda, 113 critically ill HIV-infected adults not receiving corticosteroids were enrolled after obtaining informed consent to determine the prevalence and factors associated with FAI. Results: Functional adrenal insufficiency, defined in this study as morning total serum cortisol level of = 25 mug/dl, was detected in 21 (19%) of 113 patients (95% CI 11-26%). Eosinophilia (>3%) occurred in 52% (11 of 21) patients with FAI compared to 24% (22 of 92) patients with normal adrenal function (p= 0.01). Factors predicting FAI on multivariate analysis were use of rifampicin and eosinophilia. The mortality rate among patients with FAI (19%) was not significantly different when compared to that among patients with a normal cortisol response (33%) (p=0.221). Hyponatremia, hypoglycemia, hyperkalemia, postural hypotension and the use of ketoconazole were not associated with FAI in this study. Conclusion: The diagnosis of FAI should be considered in severely ill patients with stage IV HIV disease using rifampicin or those found to have unexplained eosinophilia. Further studies to determine benefits of corticosteroids in critically ill HIV patients are needed in this setting
Anti-tuberculosis drug resistance among new and previously treated pulmonary tuberculosis patients in Cotonou, Benin
OBJECTIVES: To assess the current anti-tuberculosis drug resistance situation in Cotonou, at the largest anti-tuberculosis centre of Benin. METHODS: A total of 470 isolates of Mycobacterium tuberculosis complex from pulmonary tuberculosis (TB) patients were analysed: 244 from new cases and 226 from previously treated cases. Drug susceptibility testing of isolates against first-line drugs was performed using the proportion method. RESULTS: Primary multidrug resistance (MDR) depends on the patients' origin: MDR in new cases is relatively high (1.6%) when all patients are considered, but low (0.5%) and comparable to 1994 national survey results when only patients residing in Benin are considered. MDR in previously treated patients (11.1%) remains comparable to the study performed in Benin in 1994. No relation was found between human immunodeficiency virus co-infection and anti-tuberculosis drug resistance. CONCLUSION: This study shows the great importance of correct patient identification in epidemiological surveys, where results may vary according to the population(s) studied
Current hemoglobin levels are more predictive of disease progression than hemoglobin measured at baseline in patients receiving antiretroviral treatment for HIV type 1 infection
The role of hemoglobin levels as an independent prognostic marker of progression to AIDS and/or death in HIV-infected patients starting combination antiretroviral therapy (cART) was investigated. A total of 2,579 patients from the EuroSIDA cohort with hemoglobin, CD4 cell count, and HIV RNA viral load measured 6 months prior to starting cART was included in the analyses. Anemia was defined as mild (<or=14 g/dl males, <or=12 g/dl females) and severe (<8 g/dl both genders). Poisson regression was used to determine factors related to clinical progression (new AIDS/death). Hemoglobin levels increased by a median of +0.48 g/dl (IQR -0.4 to +1.3) in the first year of cART. During 14,272 person years of follow-up (PYFU) there were 505 new AIDS/deaths. Of the patients 304 (11.8%) developed mild and 19 severe anemia (0.7%). In multivariate analysis baseline hemoglobin was significantly associated with progression to AIDS/death after starting cART with an IRR of 1.07 per 1 g/dl lower (95% CI 1.01-1.13; p = 0.023). When hemoglobin was fitted as a time-updated variable the IRR increased to 1.36 per 1 g/dl lower (95% CI 1.30-1.42; p < 0.001). Starting cART was associated with an increase in hemoglobin levels. Lower hemoglobin values, particularly the latest measured, were associated with an increased risk of disease progression
Newly developed primers for comprehensive amplification of the rpoB gene and detection of rifampin resistance in Mycobacterium tuberculosis
New rpoB gene primers for detecting Rif(r) in Mycobacterium tuberculosis complex bacteria achieved 100% specificity and 88% (fresh sputa) and 92% (ethanol-preserved sputa) diagnostic sensitivity and detected up to 4 CFU/sample. Of the 99 Rif(r) isolates examined, 97% had mutations within cluster I, 2% at codon 176, and 1% at codon 497
Results on a national survey on drug resistance among pulmonary tuberculosis patients in Rwanda
BACKGROUND: One of the principal objectives of tuberculosis (TB) control is to minimise the emergence of drug resistance. The first national survey was conducted in Rwanda to determine the prevalence of M. tuberculosis drug resistance. METHODS: Sputum samples were collected from all new and retreatment cases in the health districts from November 2004 to February 2005. Drug susceptibility testing of isolates against first-line drugs was performed by the proportion method. RESULTS: Of 616 strains from new cases, 6.2% were resistant to isoniazid, 3.9% to rifampicin and 3.9% were multidrug-resistant TB. Among 85 strains from previously treated cases, the prevalence of resistance was respectively 10.6%, 10.6% and 9.4% (MDR-TB strains). Eight MDR cases showed additional resistance to ethambutol and streptomycin. CONCLUSION: The level of MDR-TB among TB patients in Rwanda is high. The main reasons of this emergence of MDR-TB can be attributed to the disorganisation of the health system, migration of the population during the 1994 civil war and poor success rates, with a high number of patients transferred out and lost to follow-up. On the other hand, the use of treatment regimens administered twice weekly during the continuation phase could be another important factor and merit further investigations
A dual chamber model of female cervical mucosa for the study of HIV transmission and for the evaluation of candidate HIV microbicides
A dual chamber system was established to model heterosexual HIV transmission. Cell-associated, but not cell-free HIV, added to a confluent layer of cervical epithelial cells in the apical chamber, reproducibly infected monocyte-derived dendritic cells (MO-DC) and CD4(+) T cells in the basal compartment. Only minimal epithelial transmigration of HIV-infected mononuclear cells (HIV-PBMCs) was observed. Most evidence points to transepithelial migration of virus, released from HIV-PBMCs after their activation by epithelial cells. We used this model for evaluation of the therapeutic index of various potentially preventive antiviral compounds, including non-nucleoside reverse transcriptase inhibitors (NNRTIs, including UC781 and various diaryltriazines and diarylpyrimidines), poly-anionic entry inhibitors (including PRO2000, cellulose sulphate, dextrane sulphate 5000 and polystyrene sulphonate) and the fusion inhibitor T-20. The epithelium was pre-treated with compound and incubated with HIV-PBMCs for 24 h. Afterwards the apical chamber was removed and MO-DC/CD4(+) T cell co-cultures were further cultured without compound. NNRTIs, including a TMC120 gel, blocked infection of the sub-epithelial targets at sub-micromolar concentrations. Polyanionic entry inhibitors (up to 100 microg/ml) and T-20 (up to 449 microg/ml) failed to inhibit transmission. Moreover, whereas the NNRTIs used interfered with epithelial integrity with cervical epithelium only at very high concentrations, the evaluated entry inhibitors showed toxicity at concentrations that did not prevent infection