Systemic exposure to rifampicin in patients with tuberculosis and advanced HIV disease during highly active antiretroviral therapy in Burkina Faso.

OBJECTIVES: Low plasma concentrations of rifampicin, an essential antituberculosis drug, have been reported particularly among HIV co-infected persons. In a prospective, longitudinal study we measured rifampicin systemic exposure at different timepoints during highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: From May 2006 to April 2007, 16 tuberculosis (TB)/HIV co-infected patients were enrolled in Ouagadougou, Burkina Faso. All patients received fixed dose combinations of rifampicin, isoniazid, pyrazinamide and ethambutol under direct observation and HAART, consisting of a fixed dose combination of stavudine, lamivudine and nevirapine. Rifampicin concentrations during the dosing interval were determined by HPLC at three different timepoints: (i) after 2 weeks of TB therapy and before starting HIV therapy (T0); (ii) after 4 weeks of combined therapy (T1); and (iii) after 10 weeks of combined therapy (T2). RESULTS: The median values of the area under the curve (AUC(0-24)) of rifampicin increased by 39% at T1 (15.69 µg ·â€Šh/mL; P = 0.01) and by 83% at T2 (20.65 µg ·â€Šh/mL; P = 0.001) compared with T0 (11.28 µg ·â€Šh/mL). Similar variations were observed for the median C(max) at T0 (2.24 µg/mL) compared with T2 (2.83 µg/mL; P = 0.003). However, none of the subjects had C(max) levels >8 µg/mL at either T0 or T2. CONCLUSIONS: Rifampicin systemic exposure increased during combined TB and HIV therapy, possibly due to increased drug absorption or decreased oral clearance, but remained invariably low in this population. Studies to define the C(max) rifampicin concentrations, which are associated with a significantly increased risk of treatment failure, are urgently warranted.

Extensively drug-resistant tuberculosis, Burkina Faso.

Because data from countries in Africa are limited, we measured the proportion of extensively drug-resistant (XDR) tuberculosis (TB) cases among TB patients in Burkina Faso for whom retreatment was failing. Of 34 patients with multidrug-resistant TB, 2 had an XDR TB strain. Second-line TB drugs should be strictly controlled to prevent further XDR TB increase.

Molecular detection of rifampin and isoniazid resistance to guide chronic TB patient management in Burkina Faso.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is considered a real threat to the achievement of TB control. Testing of mycobacterial culture and testing of drug susceptibility (DST) capacity are limited in resource-poor countries, therefore inadequate treatment may occur, favouring resistance development. We evaluated the molecular assay GenoType MTBDRplus (Hain Lifescience, Germany) in order to detect DR-TB directly in clinical specimens as a means of providing a more accurate management of chronic TB patients in Burkina Faso, a country with a high TB-HIV co-infection prevalence. METHODS: Samples were collected in Burkina Faso where culture and DST are not currently available, and where chronic cases are therefore classified and treated based on clinical evaluation and sputum-smear microscopy results. One hundred and eight chronic TB patients (sputum smear-positive, after completing a re-treatment regimen for pulmonary TB under directly observed therapy) were enrolled in the study from December 2006 to October 2008. Two early morning sputum samples were collected from each patient, immediately frozen, and shipped to Italy in dry ice. Samples were decontaminated, processed for smear microscopy and DNA extraction. Culture was attempted on MGIT960 (Becton Dickinson, Cockeysville, USA) and decontaminated specimens were analyzed for the presence of mutations conferring resistance to rifampin and isoniazid by the molecular assay GenoType MTBDRplus. RESULTS: We obtained a valid molecular test result in 60/61 smear-positive and 47/47 smear-negative patients. Among 108 chronic TB cases we identified patients who (i) harboured rifampin- and isoniazid-susceptible strains (n 24), (ii) were negative for MTB complex DNA (n 24), and (iii) had non-tuberculous mycobacteria infections (n 13). The most represented mutation conferring rifampin-resistance was the D516V substitution in the hotspot region of the rpoB gene (43.8% of cases). Other mutations recognized were the H526D (15.6%), the H526Y (15.6%), and the S531L (9.4%). All isoniazid-resistant cases (n 36) identified by the molecular assay were carrying a S315T substitution in the katG gene. In 41.7% of cases, a mutation affecting the promoter region of the inhA gene was also detected. CONCLUSION: The GenoType MTBDRplus assay performed directly on sputum specimens improves the management of chronic TB cases allowing more appropriate anti-TB regimens.

Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis.

BACKGROUND: Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM. METHODS: HIV-1-infected patients with CD4+ T-lymphocyte count

Vaginal colonization with Candida spp. in human immunodeficiency virus-infected women: a cohort study.

We have conducted a longitudinal study on factors associated with candidal vaginal colonization, a precursor of vaginitis, in a cohort of HIV-infected women in Italy. All consecutive women attending a single, tertiary care clinical site were offered free screening for sexually transmitted infections and genital disorders every 6-12 months. Candidal vaginal colonization was defined as a positive culture for Candida spp. in an asymptomatic woman. From January 1998 to July 2002 we analysed 214 women. The baseline prevalence of candidal vaginal colonization was 16.8%. In the logistic regression analysis, the time since HIV infection > or =36 months (odds ratio [OR] = 0.18, 95% confidence interval [CI] 0.016-0.53, P = 0.002) and a plasma viral load > or =10,000 copies/mL (OR = 3.9, 95% CI 1.03-14.9, P = 0.045) were independently associated with candidal colonization. Among 130 women who were followed for a mean period of 24 months, the incidence of vaginal colonization was 10.7/100 women-years. In the Cox regression analysis, a CD4(+) T-lymphocytes count <100 cells/microL during the follow-up was associated with an increased risk of candidal vaginal colonization (OR = 4.45, C.I. = 1.20-16.81, P = 0.03). Risk of candidal vaginal colonization episodes in HIV-infected women significantly increase when CD4(+) T-lymphocytes are less than 100.

Factors predicting uptake of voluntary counselling and testing in a real-life setting in a mother-and-child center in Ouagadougou, Burkina Faso.

OBJECTIVE: To identify factors predicting uptake of voluntary HIV counselling and testing in pregnant women. METHODS: All pregnant women receiving ante-natal group health education at St Camille Medical Center, Ouagadougou, Burkina Faso from 1 May 2002 to 30 April 2004 were offered voluntary HIV counselling and testing. If they consented, the women were pre-test counselled, tested by two rapid tests giving immediate results and post-test counselled. RESULTS: Less than one-fifth of pregnant women [1,216/6,639 (18.3%, CI 17.4-19.3%)] accepted voluntary HIV counselling and testing, mainly at the first ante-natal visit (83.4%) and at early gestational age (73.4% before week 24). The HIV seroprevalence rate was 10.6% (8.8-12.5%). The uptake rate was independently associated with age, the number of previous pregnancies and the number of previous miscarriages. CONCLUSIONS: Our two-step approach of group education followed by voluntary HIV counselling and testing yielded a low uptake rate in this setting. However, the drop-out rate after enrolling in the programme was nearly zero. The timing of programme uptake would permit implementation of earlier prophylactic courses. Effective scaling-up of voluntary HIV counselling and testing outside the clinical trial requires a mass sensibilization campaign pointing out the programme's benefits and addressing the stigma of HIV. The independent value of age and previous obstetrical episodes show how important social factors are in influencing the voluntary HIV counselling and testing uptake rate.

Prevention and treatment of traveler's diarrhea. Focus on antimicrobial agents.

Diarrhea, mostly due to bacterial infection of the gut, is the most frequent health complaint in the international traveler, affecting 20-70% of the traveling population depending on the destination and other factors. It is usually benign and self-limiting in nature, but symptoms may occasionally be distressing causing modifications of normal activities and sometimes confinement to bed or hospitalization. Prevention of traveler's diarrhea should ideally be based on dietary restrictions, but experience shows that this target is extremely difficult to achieve. Antibiotic chemoprophylaxis should be restricted to selected groups of travelers at risk of severe complications of diarrhea or when diarrhea-driven alterations of planned activities are highly undesirable (critical trips). The effectiveness of alternative prophylactic approaches, such as vaccination or the use of probiotics, still awaits confirmation. Treatment of mild diarrheal cases without intestinal symptoms may be limited to rehydration with or without antimotility agents. When antibiotic therapy is considered, non-absorbable antibiotics, such as rifaximin, may be considered a valid alternative to systemic antibiotics to treat uncomplicated cases, leaving fluoroquinolones and/or azithromycin for use in more severe cases or when invasive pathogens are suspected. Indeed, therapeutic use of doxycycline and trimethoprim-sulfamethoxazole (TMP-SMX) is limited by widespread resistance of many enteropathogens. The addition of loperamide or other antimotility agents usually provides symptom relief and further shortens the duration of illness and may be therefore safely adopted in the healthy adult unless dysentery is present.

Imported malaria in an HIV-positive traveler: a case report with a fatal outcome.

We report a fatal case of malaria in an HIV-coinfected nonimmune traveler. The primary cause of death is discussed. The importance of prevention of malaria in nonimmune travelers is stressed. Prevention of malaria in nonimmune travelers should be regarded as a priority area for clinical practice and operational research.

Respiratory syndrome and respiratory tract infections in foreign-born and national travelers hospitalized with fever in Italy.

BACKGROUND: We measured frequency and epidemiologic, clinical, and hematochemical variables associated with respiratory tract infections (RTIs) in foreign-born and national patients hospitalized with fever with a history of international travel, and compared the final diagnosis of RTI with the presence of a respiratory syndrome (RS) at presentation. METHODS: A prospective, multicenter, observational study was conducted at tertiary care hospitals in Northern Italy from September 1998 to December 2000. RESULTS: A final diagnosis of RTI was obtained in 40 cases (7.8%), 27 (67.5%) with lower RTI and 13 (32.5%) with upper RTI. The most common RTIs were pneumonia (35%) and pulmonary tuberculosis (15%). A white blood cell count > or = 10,000 and an erythrocyte sedimentation rate > or = 20 mm/h were independently associated with a final diagnosis of RTI; onset of symptoms at > or = 16 days and > or = 75% neutrophils were independently associated with lower RTI. An RS was identified in 51 (9.9%) of 515 travelers. Sensitivity, specificity, and positive and negative predictive values of a diagnosis of RS for a final diagnosis of RTI were 67.5%, 94.9%, 52.9%, and 97.2%, respectively. CONCLUSIONS: Pneumonia and pulmonary tuberculosis were frequent among foreign-born and national travelers with fever admitted to a tertiary care hospital. Half of the pneumonia cases did not present with an RS at first clinical examination.

Mefloquine versus quinine plus sulphalene-pyrimethamine (metakelfin) for treatment of uncomplicated imported falciparum malaria acquired in Africa.

We conducted a multicenter, randomized, open-label trial to compare mefloquine with a 3-day quinine plus sulphalene-pyrimethamine (SP) regimen for the treatment of imported uncomplicated malaria acquired in Africa. The end points of the study were efficacy, tolerability, and length of hospital stay. From July 1999 to February 2003, 187 patients were enrolled in five centers in Italy, of whom 93 were randomized to receive mefloquine (the M group) and 94 were randomized to receive quinine plus SP (the QSP group). Immigrants and visiting relatives and friends represented 90% of the cases and were mainly from western African countries. A slightly increased proportion of cases in the QSP group had abnormal alanine aminotransferase levels at the baseline. The early cure rate was similar in the two groups: 98.9% (confidence interval [CI] = 97 to 100%) in the M group and 96.8% (CI = 93 to 100%) in the QSP group. The extended follow-up was completed by 135 subjects (72.2%), and no case of recrudescence was detected. There were no differences in the parasite clearance time, but patients in the M group had shorter mean fever clearance time (35.9 h versus 44.4 h for the QSP group; P = 0.05) and a shorter mean hospital stay (3.9 days versus 4.6 days for the QSP group; P = 0.007). The overall proportions of reported side effects were similar in the two groups, but patients in the M group had a significantly higher rate of central nervous system disturbances (29.0% versus 9.6% for the QSP group; P < 0.001).