Jean-Pierre Dedet

The Relationship between Leishmaniasis and AIDS: the Second 10 Years

SUMMARY 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.

Spread of Vector-borne Diseases and Neglect of Leishmaniasis, Europe

Exotic vector-borne diseases are gaining attention at the expense of leishmaniasis.

Outbreak of Cutaneous Leishmaniasis in Northern Israel

This study describes a new focus of cutaneous leishmaniasis (CL) due to Leishmania tropica, in the Galilee region of northern Israel. Thirty-three cases from 4 villages (northern part) and from the city of Tiberias (southern part) have been clinically diagnosed since 1996. Parasites from 13 patients and from 6 sand flies were characterized by isoenzyme electrophoresis, 2 immunological methods, and 3 polymerase chain reaction (PCR)-based methods. Isolates from the northern part were antigenically similar to Leishmania major and were different from other L. tropica isolates, including those from the southern part of the focus. They belonged to a newly reported zymodeme and were separable from all known Israeli L. tropica isolates, by use of 2 different PCR-based methods. Five (5.2%) of 97 Phlebotomus (Adlerius) arabicus and 2 (1.2%) of 162 Phlebotomus (Paraphlebotomus) sergenti females from the northern part of the focus were found to be infected with L. tropica. Three of 29 hyraxes (Procavia capensis) were positive for Leishmania ribosomal DNA. Thus, the northern part of this emerging focus of CL in Israel is distinct from all known L. tropica foci. P. arabicus is the main vector, and it transmits parasites that are different from other L. tropica isolates, with respect to antigenic, molecular, and biochemical parameters.

Geographical distribution and epidemiological features of Old World cutaneous leishmaniasis foci, based on the isoenzyme analysis of 1048 strains

A series of 1048 Leishmania strains from Old World cutaneous leishmaniasis foci, isolated between 1981 and 2005, were studied by isoenzyme analysis. The strains were obtained from humans, rodents, dogs and sandflies from 33 countries. The four typically dermotropic species, Leishmania major, L. tropica, L. aethiopica and L. killicki, were found. The viscerotropic species L. donovani and L. infantum, which can occasionally be responsible for cutaneous leishmaniasis, are not considered in this paper. Leishmania major was the least polymorphic species (12 zymodemes, 638 strains). Leishmania tropica was characterized by a complex polymorphism varying according to focus (35 zymodemes, 329 strains). Leishmania aethiopica, a species restricted to East Africa, showed a high polymorphism, in spite of a limited number of strains (23 zymodemes, 40 strains). Leishmania killicki, mainly restricted to Tunisia had a single zymodeme for 39 strains. Recently a parasite close to L. killicki (one zymodeme, two strains) was isolated in Algeria, which lead us to revise the taxonomic status of this taxon.

Leishmania infantum and L. major in Algeria

Since 1980, the development of leishmaniasis in Algeria has been marked by a considerable increase in the number of cases of both visceral leishmaniasis (1121 cases recorded) and cutaneous leishmaniasis (more than 2000 cases per year). New Leishmania infantum and L. major foci have appeared in the north and south of the country. During this period, 100 strains of Leishmania isolated from humans, other mammals and sandflies have been identified. The presence of L. major MON-25 in Psammomys obesus and Phlebotomus papatasi had identified these species as the main reservoir and vector, respectively, of zoonotic cutaneous leishmaniasis. Similarly, the presence of L. infantum MON-1 in Ph. perniciosus and dogs has implicated them as the vector and reservoir of visceral leishmaniasis. The isolation of the dermotropic zymodeme MON-24 of L. infantum from Ph. perfiliewi suggested that it was one of the main vectors of cutaneous leishmaniasis in the north of the country; the reservoir has not been identified. In addition, other zymodemes of Leishmania have been identified in visceral leishmaniasis patients, frequently associated with human immunodeficiency virus (MON-24, MON-33, MON-34 and MON-78), in patients with cutaneous leishmaniasis (MON-80), and in dogs with leishmaniasis (MON-34 and MON-77).

Differentiation and Gene Flow among European Populations of Leishmania infantum MON-1

Background Leishmania infantum is the causative agent of visceral and cutaneous leishmaniasis in the Mediterranean region, South America, and China. MON-1 L. infantum is the predominating zymodeme in all endemic regions, both in humans and dogs, the reservoir host. In order to answer important epidemiological questions it is essential to discriminate strains of MON-1. Methodology/Principal Findings We have used a set of 14 microsatellite markers to analyse 141 strains of L. infantum mainly from Spain, Portugal, and Greece of which 107 strains were typed by MLEE as MON-1. The highly variable microsatellites have the potential to discriminate MON-1 strains from other L. infantum zymodemes and even within MON-1 strains. Model- and distance-based analysis detected a considerable amount of structure within European L. infantum. Two major monophyletic groups—MON-1 and non-MON-1—could be distinguished, with non-MON-1 being more polymorphic. Strains of MON-98, 77, and 108 were always part of the MON-1 group. Among MON-1, three geographically determined and genetically differentiated populations could be identified: (1) Greece; (2) Spain islands–Majorca/Ibiza; (3) mainland Portugal/Spain. All four populations showed a predominantly clonal structure; however, there are indications of occasional recombination events and gene flow even between MON-1 and non-MON-1. Sand fly vectors seem to play an important role in sustaining genetic diversity. No correlation was observed between Leishmania genotypes, host specificity, and clinical manifestation. In the case of relapse/re-infection, only re-infections by a strain with a different MLMT profile can be unequivocally identified, since not all strains have individual MLMT profiles. Conclusion In the present study for the first time several key epidemiological questions could be addressed for the MON-1 zymodeme, because of the high discriminatory power of microsatellite markers, thus creating a basis for further epidemiological investigations.

Leishmania donovani leishmaniasis in Cyprus.

1recently discussed the emergence of Leishmania donovani in Cyprus. We would like to provide some additional data regarding possible vector species that might have caused the disease outbreak on this island. The presence of L donovani was reported in the eastern Mediterranean basin about 10 years ago in the vicinity of Kassab, northern Syria, when an isolate taken from Phlebotomus tobbi—a suspected vector of canine leishmaniasis caused by Leishmania infantum at the time of the infected sandfl y’s discovery—was typed as belonging to a zymodeme close to L donovani MON-3. 2

Sudan: the possible original focus of visceral leishmaniasis.

Fifty-two Leishmania strains, obtained from human patients and dogs in a visceral leishmaniasis focus in Sudan, were characterized by isoenzyme electrophoresis (15 enzymes). The phylogenetic analysis showed that the 7 Leishmania zymodemes obtained hold ancestral positions on the phylogenetic tree, supporting the hypothesis of an East African origin of visceral leishmaniasis.

Drug regimens for visceral leishmaniasis in Mediterranean countries

Until the early 1990s, pentavalent antimony was the only documented first‐line drug employed for the treatment of zoonotic visceral leishmaniasis (VL) in the Mediterranean, with reported cure rates exceeding 95% in immunocompetent patients. The emergence of antimony resistance in other endemic settings and the increase in drug options have stimulated re‐evaluation of the current therapeutic approaches and outcomes in Mediterranean countries. A scientific consortium (‘LeishMed’ network) collected updated information from collaborating clinical health centres of 11 endemic countries of Southern Europe, Northern Africa and the Middle East. In contrast with the previous situation, VL is now treated differently in the region, basically through three approaches: (1) In Northern Africa and in part of the Middle East, pentavalent antimony is still the mainstay for therapy, with no alternative drug options for treating relapses; (2) In some European countries and Israel, both pentavalent antimony and lipid‐associated amphotericin B (AmB) formulations are used as first‐line drugs, although in different patients’ categories; (3) In other countries of Europe, mainly liposomal AmB is employed. Importantly, cure rates exhibited by different drugs, including antimonials in areas where they are still in routine use, are similarly high (≥95%) in immunocompetent patients. Our findings show that antimony resistance is not an emerging problem in the Mediterranean. A country’s wealth affects the treatment choice, which represents a balance between drug efficacy, toxicity and cost, and costs associated with patient’s care.

Environmental risk mapping of canine leishmaniasis in France.

BackgroundCanine leishmaniasis (CanL) is a zoonotic disease caused by Leishmania infantum, a Trypanosomatid protozoan transmitted by phlebotomine sandflies. Leishmaniasis is endemic in southern France, but the influences of environmental and climatic factors on its maintenance and emergence remain poorly understood. From a retrospective database, including all the studies reporting prevalence or incidence of CanL in France between 1965 and 2007, we performed a spatial analysis in order to i) map the reported cases in France, and ii) produce an environment-based map of the areas at risk for CanL. We performed a Principal Component Analysis (PCA) followed by a Hierarchical Ascendant Classification (HAC) to assess if the locations of CanL could be grouped according to environmental variables related to climate, forest cover, and human and dog densities. For each group, the potential distribution of CanL in France was mapped using a species niche modelling approach (Maxent model).ResultsResults revealed the existence of two spatial groups of CanL cases. The first group is located in the Cévennes region (southern Massif Central), at altitudes of 200-1000 m above sea level, characterized by relatively low winter temperatures (1.9°C average), 1042 mm average annual rainfall and much forest cover. The second group is located on the Mediterranean coastal plain, characterized by higher temperatures, lower rainfall and less forest cover. These two groups may correspond to the environments favoured by the two sandfly vectors in France, Phlebotomus ariasi and Phlebotomus perniciosus respectively. Our niche modelling of these two eco-epidemiological patterns was based on environmental variables and led to the first risk map for CanL in France.ConclusionResults show how an ecological approach can help to improve our understanding of the spatial distribution of CanL in France.