Limited effectiveness of high-dose liposomal amphotericin B (AmBisome) for treatment of visceral leishmaniasis in an Ethiopian population with high HIV prevalence.

BACKGROUND: Due to unacceptably high mortality with pentavalent antimonials, Médecins Sans Frontières in 2006 began using liposomal amphotericin B (AmBisome) for visceral leishmaniasis (VL) patients in Ethiopia who were severely ill or positive for human immunodeficiency virus (HIV). METHODS: We used clinical data obtained from January 2007 to January 2009 to compare outcomes by HIV status and VL episode (primary vs relapse) and to identify risk factors for treatment failure among patients treated with AmBisome monotherapy at a total dose of 30 mg/kg in 6 doses on alternate days, a higher dose than recommended by the World Health Organization (20 mg/kg). RESULTS: Among 94 HIV-negative severely ill VL patients, 93% had initial cure and 6% died. Among 195 HIV-positive patients (116 primary, 79 relapse VL), 60% had initial cure, 7% died, and 32% were parasitological failures. AmBisome was less effective in the 79 HIV-positive VL relapse patients (38% initial cure, 5% mortality, 56% parasitological failure) than in the 116 HIV-positive primary VL patients (74% initial cure, 8% mortality, 16% parasitological failure). Sodium stibogluconate (SSG) rescue treatment increased the overall cure rate among all HIV-positive VL patients from 60% to 83%, but 16% (9 of 59) of rescue treatment patients died, mainly due to SSG toxicity. CONCLUSIONS: High-dose AmBisome for VL is safe and effective in severely ill HIV-negative patients, and safe but less effective in HIV-positive patients. Combining AmBisome with another drug may enhance its effectiveness in HIV-positive VL patients. SSG should be avoided for treatment of VL in HIV-positive patients.

The relationship between leishmaniasis and AIDS: the second 10 years.

To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic.

Concordant HIV infection and visceral leishmaniasis in Ethiopia: the influence of antiretroviral treatment and other factors on outcome.

BACKGROUND: Coinfection with human immunodeficiency virus (HIV) and Leishmania donovani visceral leishmaniasis (VL) in Africa is an emerging, poorly understood disease. METHODS: We evaluated 356 consecutive patients coinfected with HIV and VL treated in Humera, northwest Ethiopia, from February 2003 to October 2006, for risk factors for VL relapse and death and the effect of antiretroviral therapy (ART). RESULTS: During 2928 patient-months of follow-up, 256 VL episodes and 39 deaths occurred. Among 195 patients receiving ART, 31.3% had > or = 1 VL episode, and 14.4% died. Among 161 patients who did not receive ART, 26.1% had > or = 1 VL episodes, and 6.8% died. A total of 54 patients who received ART and 58 patients who did not receive ART had > or = 1 VL relapse. VL relapse among patients receiving ART was associated with a baseline CD4 cell count < 100 cells/microL (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.21-5.15) and > or = 2 previous VL episodes (HR, 3.74; 95% CI, 1.40-10.02). Failure to clear parasites after VL treatment was usually followed by symptomatic VL relapse. Patients who relapsed showed poor CD4 cell count recovery while receiving ART. ART was partially protective against VL relapse (HR, 0.46; 95% CI, 0.26-0.82). However, 28% of first VL relapses while receiving ART occurred despite a CD4 cell count > 200 cells/microL; in 5% of VL relapses, the CD4 cell count had been > 200 cells/microL for > 6 months. Factors associated with all-cause mortality among patients receiving ART were baseline CD4 cell count < 100 cells/microL (HR, 3.20; 95% CI, 1.30-7.87) and VL episodes during follow-up (HR for 1 episode, 4.97 [95% CI, 2.09-11.86]; HR for > 2 episodes, 3.22 [95% CI, 1.01-10.23]). CONCLUSIONS: Concordant HIV infection and VL is a major, acquired immunodeficiency syndrome-defining illness with high relapse and mortality rates; ART reduces relapses; and secondary antileishmanial prophylaxis may benefit patients at risk of relapse.

Field evaluation of rK39 test and direct agglutination test for diagnosis of visceral leishmaniasis in a population with high prevalence of human immunodeficiency virus in Ethiopia.

Accuracy of an rK39 rapid diagnostic test (DiaMed-IT-Leish ) for visceral leishmaniasis (VL) was compared with splenic aspiration and the direct agglutination test (DAT) in a population with a high prevalence of infection with human immunodeficiency virus (HIV) in Ethiopia. There were 699 patients clinically suspected of having VL (153 parasitologically confirmed, 482 DAT confirmed, and 130 DAT negative), and 97 DAT-negative controls. A total of 84% were tested for HIV and 34% were HIV positive. Sensitivity of the rK39 test in parasitologically confirmed VL patients was 84% (77% in HIV positive and 87% in HIV negative; P = 0.25). Sensitivity of the DAT was higher (94%; P = 0.01), 89% in HIV-positive patients and 95% in HIV-negative patients; P = 0.27). Specificity of the rK39 test was 99% in DAT-negative controls and 92% in DAT-negative patients clinically suspected of having VL. A diagnostic algorithm combining DAT and the rK39 test had a sensitivity of 98% in HIV-positive VL patients and 99% in HIV-negative VL patients. Despite the lower sensitivity in a population with a high prevalence of HIV, the DiaMed-IT-Leish rK39 test enables decentralization of diagnosis. Patients clinically suspected of having VL who show negative results on the rK39 antigen test should undergo follow-up DAT testing, especially if they are HIV positive.