Part II
The leishmaniases and Leishmania/HIV co-infections,
continued
Areas of co-infection
Cases of Leishmania/HIV co-infections are being reported more frequently in various parts of the world. It is anticipated that the number of Leishmania/HIV co-infections will continue to rise in the coming years and there are indications that cases are no longer restricted to endemic areas.
The overlapping geographical distribution of VL and AIDS is increasing due to two main factors: the spread of the AIDS pandemic in suburban and rural areas of the world, and the simultaneous spread of VL from rural to suburban areas.
Leishmania/HIV co-infections are considered a real threat, especially in south-western Europe. Of the first 1 700 cases of co-infection which have been reported to the World Health Organization (WHO) from 33 countries worldwide up to 1998, 1 440 cases were from the region: Spain (835); Italy (229); France (259); and Portugal (117). Of 965 cases retrospectively analyzed, 83.2% were males, 85.7% were young adults (20-40 years old) and 71.1% were intravenous drug users.
Most co-infections in the Americas are reported in Brazil, where the incidence of AIDS has risen from 0.8 cases per 100 000 inhabitants in 1986 to 10.5 cases per 100 000 inhabitants in 1997. As HIV transmission has spread into rural areas, VL has simultaneously become more urbanized--especially in north-eastern Brazil--increasing the risk of overlapping infection.
The number of cases of Leishmania/HIV co-infection is expected to rise in Africa owing to the simultaneous spread of the two infectious diseases and their increasingly overlapping geographical distribution, complicated by mass migration, displacement, civil unrest, and war.
In general, the reported cases of Leishmania/HIV co-infection in Africa are a very modest estimation and would substantially increase if active surveillance were implemented throughout the continent. Ethiopia has a well-organized system of detection, management and reporting of co-infection. Kenya and Sudan began surveillance in 1998 and Morocco has also established a surveillance centre.
In East Africa, cases of Leishmania/HIV co-infections have been reported in Djibouti (10), Ethiopia (74), Kenya (15), Malawi (1) and Sudan (3). West Africa has no official surveillance system yet, but several cases have been reported: Cameroon (1), Guinea Bissau (1), Mali (4) and Senegal (2). In North Africa, cases have been reported in Algeria (20) and Morocco (4). *
Specific problems
Leishmania/HIV co-infections impose specific difficulties in terms of diagnosis and treatment. The usual clinical features (fever, weight loss, liver and spleen enlargement, inflammation of the lymph nodes) are not always present. The clinical diagnosis can also be made difficult by associated diseases such as cryptosporidium, disseminated cryptococcosis, cytomegalovirus infection or mycobacterial infection.
The serological diagnosis is falsely negative in 42.6% of co-infected patients. HIV-positive patients have difficulty in producing antibodies against new infectious agents, especially at a late stage or during relapses. Consequently, there is a need to use two or more serological tests and antigens freshly prepared in the laboratory to increase sensitivity.
Although multiple localizations are frequent (blood, skin, digestive tract, lungs, central nervous system), parasitological diagnosis can be difficult and has to be repeated to orient the treatment. Bone marrow aspirate (BMA) remains the safest and most sensitive technique, but spleen aspirate and liver biopsy are also used. When BMA cannot be performed, the search for Leishmania can be conducted in peripheral blood samples.
Treatment for co-infected patients is aimed at clinical and parasitological cures and prevention of relapses. Unfortunately, in such patients treatment failure, relapses due to drug resistance and drug toxicity are very common. In south-western Europe, follow-up studies using pentavalent antimonials, the same first-line drug used to treat classic leishmaniasis, show a positive response in 83% of cases. However, 52% of patients relapse within a period of one month to three years, with the number of relapses ranging from one to four.
The main alternative drugs include pentamidine, amphotericin B and amphotericin B encapsulated in liposomes. This encapsulation reduces the occurrence of side-effects, but relapses still occur and the drug remains extremely expensive.
Epidemiological changes
Leishmania/HIV co-infections can lead to epidemiological changes which modify the traditional patterns of zoonotic VL. Co-infected patients harbour a high number of Leishmania in their blood so there is also a risk of them becoming reservoirs of the disease (that is, infective for the sandfly vector) as in anthroponotic foci in Bangladesh, India, Nepal and East Africa. Consequently, there is an increased risk of future epidemics.
Experimentally, sandflies can be infected through a blood meal containing a very small quantity of blood from co-infected patients. The quantity may be less than the content of a needle. As 71.1% of co-infected patients in south-western Europe are intravenous drug users, transmission of Leishmania has occurred through the sharing of syringes in this population group.
The World Health Organization response
Because of the anticipated substantial increase in Leishmania/HIV co-infections, they are among the priorities for WHO's Department of Communicable Disease Surveillance and Response (CSR).
In 1996, WHO established an initial surveillance system, comprised of 14 institutions in 10 countries. A standardized Case Report Form was elaborated and endorsed by the members of the network, and a Central International Registry was set up within WHO to centralize, process and disseminate information on co-infections.
In 1998, a new WHO/Joint United Nations Programme on HIV/AIDS (UNAIDS) initiative was launched which helped strengthen the surveillance network; it has been expanded to include 28 institutions, especially in East Africa and the Indian subcontinent (India, Nepal). All member institutions of the network report to WHO on an annual basis. A computerized Geographic Information System (GIS) is used to map and monitor co-infections in a way that permits easy visualization and analysis of epidemiological data.
The evolution of Leishmania/HIV co-infection is being closely monitored by extending the geographic coverage of the surveillance network and by improving case reporting. WHO encourages active medical surveillance, especially in south-western Europe, of intravenous drug users, the main population at risk. Finally, because case notification of leishmaniasis is compulsory in only 40 of the 88 endemic countries, WHO strongly suggests the remaining 48 endemic countries follow suit.
*Figures from countries without surveillance systems are based upon random reports only. To properly assess the scale of the problem, there is an urgent need for more accurate information based on specific studies
For more information contact:
WHO Media centre
Telephone: +41 22 791 2222
Email:
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