Sentinel Surveillance of Cutaneous Leishmaniasis in Sub-Saharan Africa Based on Non-invasive Molecular Diagnostics: Mapping of Human Cases, Description of Leishamania Species Involved
Sentinel Surveillance of Cutaneous Leishmaniasis in Sub-Saharan Africa Based on Non-invasive Molecular Diagnostics: Mapping of Human Cases, Description of Leishamania Species Involved
Cutaneous leishmaniasis is a neglected tropical disease caused by parasites belonging to the genus Leishmania. This infection can cause skin and sometimes mucous membrane lesions with significant damage. LC has been little studied in sub-Saharan Africa where its incidence is probably underestimated, especially in West Africa. Leishmania major is almost the only isolated species in this region, although recent data suggest the existence of other species, such as L. enrietti. It is said that CL is only present in the arid areas of Africa, but recent outbreaks in wetlands and forests tend to contradict this theory. Due to the lack of availability of the PCR method, the diagnosis of LC in West Africa, especially in Mali, is rarely confirmed. Treatment options are also scarce and their effectiveness is poorly documented. The objectives of this study are to map the occurrence of LC cases with molecular biology confirmation in Niger, Mali and Togo; to determine the different species involved in human cases; evaluate the different treatment options available.
Leishmaniasis is a parasitosis common to humans and animals (anthropozoonosis), caused by flagellated protozoa called Leishmanias, transmitted by the infective bite of the blood-sucking female of a dipteran insect called sandfly. The parasite reservoirs are wild rodents, humans, dogs. Many species of leishmania can infect humans with a multiplicity of clinical pictures that include visceral, localized, diffuse cutaneous forms and mucocutaneous forms.
Cutaneous leishmaniasis (CL) is a neglected tropical disease whose transmission to humans is based on the bite of sandflies previously contaminated on mammalian reservoirs. Worldwide, more than 200,000 new cases are reported annually. While the Americas and the Near or Middle East are the most important areas, sub-Saharan Africa is also concerned. In a systematic review of the literature published in 2018, Sunyoto et al. identified 54 clinical and epidemiological studies on LC in sub-Saharan Africa. Publications were found in 13 of the 48 countries in sub-Saharan Africa. This review highlighted inconsistent case reporting, clear under-publication and data gaps regarding the exact incidence of CL and its transmission factors, particularly in West Africa.
Indeed, cutaneous leishmaniasis is widely described in East Africa, where many studies have been carried out in Ethiopia, Kenya and Sudan. The presence of Leishmania major and Leishmania aethiopica is well documented, and the dynamics of the infection and its risk factors are studied. In West Africa, on the other hand, the data are more fragmented. The disease is historically reported in the "Cutaneous Leishmaniasis Belt", a Sahelian strip of semi-arid zones extending from Senegal to Sudan. WHO nevertheless estimates that the real number of LC contaminations in the sub-region is 5 to 10 times higher than reported.
Thus, no cases were reported between 2015 and 2017 in the sub-region, which is not very credible in view of the dynamics of declarations during the previous or following years. Over the period 2004-2008, only 155 cases per year were reported, across the following countries: Ghana, Mali, Cameroon, Nigeria, Senegal, DRC and Ivory Coast. No data were available for neighbouring countries with similar ecological contexts, such as Niger, Benin, Guinea or Burkina Faso. The latter is probably the country reporting cases on the most regular basis, with between 500 and 1500 cases/year between 1995 and 2015. Nevertheless, no case was reported between 2007 and 2010, which seems difficult to explain scientifically and again testifies to a lack of diagnosis or reporting.
WHO establishes " country profiles " on the epidemiology of LC for each endemic country and designs regional programmes to control the disease. It should be noted that while East African countries such as Kenya or Ethiopia have a well-documented profile, no profile is available for West African countries. In addition, no regional programme has been set up for sub-Saharan Africa, unlike the Americas, South-East Asia, the Eastern Mediterranean or Europe regions. These absences show how neglected this public health problem is in the African region.
Ghana was considered non-endemic to CL until a major outbreak in 2002-2003. More than 2000 cases were then diagnosed, and this after an active screening, following an initial epidemic signal of only about fifteen cases. It is therefore possible that other epidemics, or even a sporadic presence, have remained undetected in some areas of the country. It should be noted that the region of the epidemic (Ho district, Volta region) was bordered by neighbouring Togo, and the testimonies collected in the affected communities suggested an imported pathology. Moreover, it should be noted that this epidemic area in Ghana was located in a forest region, therefore ou tside the LC Belt classically described and the semi-arid areas generally incriminated. This example illustrates the need to explore the epidemiology of LC in areas that are considered non-endemic by their climate.
In a later study carried out in 2015 in 15 villages affected by this epidemic, samples were taken to isolate strains belonging to the Leishmania enriettii complex from three crops. This rarely described species was not generally considered pathogenic to humans. This example illustrates the need for better species diagnosis in some areas where Leishmania major is considered to be the only species involved, although recent data do not support this statement with certainty. The diagnosis of cutaneous leishmaniasis in West Africa is too often based on a simple clinical diagnosis, sometimes supported by a parasitological smear. However, this does not allow the diagnosis of the offending Leishmania species. The lack of molecular biology in isolated areas or populations with limited resources prevents precise knowledge of the species involved.
As for the treatment, it is often inaccessible due to its price or the logistical constraints related to transport. Meglumine antimoniate is the first-line treatment in Senegal but rarely available, while metronidazole is used in Niger. However, its effectiveness has not been strongly demonstrated. In Mali, dermatologists use cryotherapy and thermotherapy, and more rarely meglumine antimoniate. Cyclin-based ointments are also used to treat bacterial superinfection.
Across the subregion, patients are frequently lost to follow-up, due to the high cost of transport for populations in rural areas, which are mainly at risk. The lack of follow-up consultations does not make it possible to reliably assess the proportion of patients who recover spontaneously, those requiring active treatment, the effectiveness of the various treatments offered as well as the possible sequelae (disfiguring scars, etc.) in the absence of active treatment. A prospective cohort with active patient follow-up would provide valuable data to assess whether or not new treatment options are needed.
Overall, it therefore seems relevant to map more precisely the incidence of LC in West Africa, to identify in molecular biology the Leishmania species responsible, to deepen knowledge on the vectors and reservoirs involved and to evaluate the effectiveness and usefulness of current therapeutic options.
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Bamako, Mali BP 1805, Mali