Nuccia Saleri

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.

Paradoxical Reaction during Tuberculosis Treatment in HIV-Seronegative Patients

1. Cook PP. Rifampin and pyrazinamide for treatment of latent tuberculosis infection. Clin Infect Dis 2006; 42:892 (in this issue). 2. McElroy PD, Ijaz K, Lambert LA, et al. National survey to measure rates of liver injury, hospitalization, and death associated with rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis 2005; 41: 1125–33. 3. National Institutes of Health. Division of AIDS table for grading the severity of adult and pediatric adverse events, version 1. December 2004. Available at: http://rcc.tech-res -intl.com/tox_tables.htm. Accessed 28 November 2005. 4. Centers for Disease Control and Prevention. Update: adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infectionUnited States, 2003. MMWR Morb Mortal Wkly Rep 2003; 52:735–9. 5. McNeill L, Allen M, Estrada C, Cook P. Pyrazinamide and rifampin vs isoniazid for the treatment of latent tuberculosis. Chest 2003; 123:102–6. 6. Priest DH, Vossel LF, Sherfy EA, Hoy DP, Haley CA. Use of intermittent rifampin and pyrazinamide therapy for latent tuberculosis infection in a targeted tuberculin testing program. Clin Infect Dis 2004; 39:1764–71. 7. Gordin F, Chaisson RE, Matts JP, et al. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons. JAMA 2000; 283:1445–50. 8. Halsey NA, Coberly JS, Desormeaux J, et al. Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection. Lancet 1998; 351:786–92. 9. Mwiga A, Hosp M, Godfrey-Faussett P, et al. Twice weekly tuberculosis preventive therapy in HIV infection in Zambia. AIDS 1998; 12: 2447–57. 10. Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic. JAMA 1999; 281:1014–8.

Outcome and Predictive Factors of Mortality in Hospitalized HIV-Patients in Burkina Faso

Background:The aim of this study was to describe the clinical presentation and predictors of death in a HIV population hospitalized in Ouagadougou, Burkina Faso.Materials and Methods:Baseline demographics, viro-immunological status, clinical presentations, and outcome have been analyzed by univariate analysis and a multivariate model.Results:A total of 1,071 hospitalizations of HIV-positive patients was recorded between 1 January, 2004 and 31 August, 2006, the majority of whom were female (64.1%). The baseline CD4 cell count/μl was higher in the female patients than in the male ones (166.1 vs 110.9). Gastroenteric symptoms were the first cause of hospitalization (61.7%). The crude mortality rate was higher in males than females (38% vs 25.3%). Baseline World Health Organization clinical stage IV (OR 9.22), neurological syndrome (OR 3.04) or wasting syndrome at admission (OR 2.9), positive malaria film (OR 2.17), and an older age independently predicted death. Weight at admission > 40 kg and a higher platelet count at admission were independently associated with a better outcome.Conclusions:Females are admitted to hospital earlier than males, probably as an indirect result of the Prevention of Mother-to-Child Transmission (PMTCT) public health initiative. An active search of HIV status in other members of the family (PMTCT-plus) may result in the detection of asymptomatic HIV-infected patients as well. A Plasmodium falciparum-positive smear during admission significantly impacted on outcome as well as low platelet count.

Prevention and Treatment of Traveler’s Diarrhea

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 (crit- ical 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.

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 ≥36 months (odds ratio [OR] = 0.18, 95% confidence interval [CI] 0.016–0.53, P = 0.002) and a plasma viral load ≥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/μL 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.

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 ≤100 cells per microliter and TB diagnosis received standard anti-TB therapy and a fixed-dose combination of stavudine, lamivudine, and NVP. Full NVP pharmacokinetic curves were calculated at 4 (T1) and 10 weeks (T2) of combined therapy and at 4 (T3) and 26 weeks after termination of anti-TB therapy. Results:In 16 enrolled subjects, the median value of the area under the curve of NVP was reduced by 25.6% at T1 compared with NVP alone (43.7 vs. 58.7 μg·mL−1·h−1; P = 0.02). The reduction was only 7.5% at T2 (54.3 vs. 58.7 μg·mL−1·h−1; P = 0.17). The median Ctrough was reduced of 19.5% at T1 compared with T3 (3.3 vs. 4.2 μg/mL; P = 0.02) and of 7.1% at T2 compared with T3 (3.9 vs. 4.2 μg/mL; P = 0.17). The proportion of subjects with Ctrough values ≤3 μg/mL was 31.2% (5 of 16), 40.0% (6 of 15), and 7.7% (1 of 13) at T1, T2, and T3, respectively. Conclusions:The reduction of the area under the curve of NVP during concomitant RFM treatment substantially decreases over time.

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.

Mefloquine versus Quinine plus Sulphalene-Pyrimethamine (Metakelfin) for Treatment of Uncomplicated Imported Falciparum Malaria Acquired in Africa

ABSTRACT 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).

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 · h/mL; P = 0.01) and by 83% at T2 (20.65 μg · h/mL; P = 0.001) compared with T0 (11.28 μg · h/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.

Failing a re-treatment regimen does not predict MDR/XDR tuberculosis: is “blind” treatment dangerous?

To the Editors: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) represent an emerging public health threat worldwide 1. The Stop TB Strategy has been revised to provide universal access to diagnosis and treatment for all patients with MDR-TB by 2015 2–4. This plan calls for accelerated access to culture for mycobacteria, species identification and drug susceptibility testing (DST) of Mycobacterium tuberculosis . However, in several countries, appropriate TB laboratory facilities are still largely unavailable. In the absence of culture and DST, TB patients failing a re-treatment regimen have been considered eligible for treatment regimens with second-line drugs, under the assumption that ≥80% of them would harbour MDR M. tuberculosis strains 5. In Burkina Faso, as in most low- and some middle-income settings, pulmonary TB cases failing a standard category II regimen are only identified by positive sputum smear microscopy at the end of the fifth month of treatment and are defined as “chronic” TB patients. The diagnosis of chronic TB has significant implications. National guidelines for the management of chronic TB cases in Burkina Faso recommend hospital admission and in-patient treatment for ≥6 months with a standardised category IV treatment regimen 6. Although the diagnosis of chronic TB is taken as a surrogate marker for the identification of MDR-TB, little evidence is available from the literature on its positive predictive value for MDR-TB diagnosis. We systematically performed microbiological investigations, which included both phenotypic and genotypic techniques, on all newly identified chronic TB cases diagnosed over a 2-yr period in Burkina Faso. Here, we report the results and discuss the implications that “blind” treatment with second-line drugs have at programmatic level. A prospective, country-wide investigation was performed to microbiologically characterise all consecutively registered chronic TB cases in Burkina Faso, defined on the basis of …