Leishmaniasis and HIV coinfection
One of the major threats to control of visceral leishmaniasis (VL) is its interaction with HIV infection. VL has emerged as an important opportunistic infection associated with HIV. In areas endemic for VL, many people have asymptomatic infection. A concomitant HIV infection increases the risk of developing active VL by between 100 and 2320 times. In southern Europe, up to 70% of cases of visceral leishmaniasis in adults are associated with HIV infection.
VL/HIV co-infection has important clinical, diagnostic and epidemiological implications. The two diseases are mutually reinforcing: HIV-infected people are particularly vulnerable to VL, while VL accelerates HIV replication and progression to AIDS. The risk of treatment failure for VL is high, regardless of the drug used, and all co-infected patients will relapse – and eventually die – unless they are given antiretroviral therapy (ART). Indirect methods of diagnosis such as serological tests for VL frequently fail; direct methods such as aspirations (bone marrow, lymph node or splenic) are reliable but are invasive, require skilled microscopy, and have less value in treated and relapsing patients. Further, co-infected patients can serve as human reservoirs, harbouring numerous parasites in their blood and becoming a source of infection for the insect vector.
To date, as many as 35 countries throughout the world have reported cases of VL/HIV co-infection, although most of the published literature concerns the countries of southern Europe. Under-reporting in most endemic areas is due to a lack of facilities to diagnose one or both of the diseases and to poor reporting systems. The fact that VL is not included in the CDC list of opportunistic infections further undermines reporting.
In a particularly ominous trend, the spread of HIV infection is bringing the severe visceral form of leishmaniasis to new geographical areas and changing the epidemiology of the disease in dangerous ways.
Where leishmaniasis occurs in urban areas, conditions often favour explosive epidemics, thus transforming the disease from a sporadic to an epidemic threat. In persons infected with HIV, leishmaniasis accelerates the onset of AIDS by cumulative immunosuppression and by stimulating replication of the virus. The epidemiological significance of asymptomatic carriers of the parasite has also been amplified by the advent of HIV, as co-infection rapidly activates infection to disease in asymptomatic parasite carriers. Sharing of needles by intravenous drug users contributes to the spread of leishmaniasis in Europe, as well as that of HIV.
In 1991, WHO established a global surveillance network of 28 institutions, named Leishnet, to document the extent of the problem of co-infection and monitor trends. Initially, the sites involved in the network were predominantly European, reflecting the epidemiological situation at the time. A standardized case report form was developed to collect information on demographic, clinical and diagnostic features of the disease. In recent years, the network has expanded to all endemic areas and now includes institutions from Africa, South America and Asia. The network aims not only to monitor epidemiological trends but also to develop guidelines for disease management (Report of the Fifth Consultative Meeting on Leishmania/HIV Coinfection, Addis Ababa, 2007).
The number of reported co-infection cases increased rapidly during the 1990s with the spread of the HIV pandemic, increased awareness among reporting institutions, and the growing geographical overlap between the two diseases. By 2001, a total of 1911 co-infection cases had been reported, with more than 50% (1099) coming from Spain. Analysis using geographical information systems (GIS) showed that most cases were in coastal urban areas with high population densities. The spatial pattern suggested a progressive ruralization of co-infection cases, as HIV infection spread into rural areas and VL became increasingly periurban. The number of reported cases in southern Europe peaked between January 1996 and June 1998, then decreased steadily until 2001, remaining stable at a low level thereafter. The decrease is attributed to the routine use of ART since 1997.
Since 2001, new primary co-infections have been reported from Spain (122), Italy (52), France (52) and Portugal (64). There were no significant differences in the age and sex distribution of the cases diagnosed in the pre-ART (1990–1998) and post-ART (since 2001) eras. The mean age of patients was 38.6 (965 cases) and 38.9 (253 cases), respectively, while men accounted for 83.2% and 88.5% of cases.
Co-infection cases have also been reported recently from institutions in Ethiopia (569 cases), Brazil (91), Gedaref state in Sudan (8) and India (7).
In Ethiopia, 535 cases (>90%) were reported by the Médecins sans Frontières VL treatment centre in Kafta Humera district, in the northwestern region of Tigray. They correspond to all co-infection cases treated between 2003 and 2008. In this highly endemic area for VL, the rate of HIV co-infection among VL patients is 15–30%. The position of the area near the Eritrean and Sudanese borders, and its high agricultural activity, attract a high influx of seasonal male migrant workers each year and make it an important transit point for cross-border trade and traffic. The increase in the male population also attracts a high annual influx of commercial sex workers, which probably contributes to the increasing rates of HIV transmission. As in Europe, most of the co-infection cases reported in Africa were in men (94.8%).
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