Leishmaniasis: Path toward elimination from the Indian subcontinent.

Leishmaniases are a group of parasitic diseases endemic in 98 countries, with over 350 million people living at risk across the world and 0.7–1.3 million new cases per year.[1] The disease is prevalent both in the “New” (South and the Central America) and the “Old” world (Southern Europe, Africa, Middle East, Central Asia, and Indian subcontinent). It is considered as a disease complex rather than a single disease entity and is among the least studied and most neglected of tropical diseases.[2] The poor sociopolitical background of the afflicted has largely contributed to the minimal enthusiasm shown in the past toward leishmaniases by the policy makers and even scientists. Its apparent overlap with the spread of AIDS has highlighted the increasing threat of HIV-Leishmania co-infections, particularly in India and East Africa.[3]

The leishmaniases have a wide spectrum of disease manifestations. The three main clinical forms are visceral leishmaniasis (VL) (often referred to as kala-azar), cutaneous leishmaniasis (CL), and mucocutaneous leishmaniasis (MCL). Whereas the VL and MCL are potentially fatal, CL is mostly known for its morbidity rather than mortality.

The causative agent of the leishmaniases is protozoan parasites that belong to the genus Leishmania. There are over twenty species of Leishmania that are transmitted by over ninety sandfly species that cause disease in humans.[1] Transmission occurs through the bite of an infected sandfly (Phlebotomus or Lutzomyia spp.), which introduces the infective stages of Leishmania to a mammalian host. Most Leishmania species are considered as zoonotic parasites with humans acting as accidental hosts.[4] The causative agent of VL in the Indian subcontinent, Leishmania donovani is, however, considered as an exception, with the debatable view that this species is strictly anthroponotic, still widely held.[5]

ELIMINATION OF LEISHMANIASIS FROM THE INDIAN SUBCONTINENT

Majority of the estimated 200,000–400,000 annual VL cases reported worldwide are located in the South Asian region that includes India, Nepal, and Bangladesh.[6] VL is, however, substantially under-reported, with reported coverage varying not only between countries but also even between districts within a given country.[2] In May 2005, a memorandum of understanding was signed during the World Health Assembly and the governments of India, Nepal, and Bangladesh committed themselves to work in mutual cooperation to achieve elimination of VL from these countries by 2015.[7] The objective of the VL elimination initiative as laid down at the outset was to reduce the annual incidence of VL below 1/10,000 population at district, subdistrict, or Upazila level in India, Nepal and Bangladesh, respectively.[8] The strategies adopted were based on case detection and management together with vector control. However, though there has been progress in selected areas, considering the present status of leishmaniasis in the targeted countries, it is unlikely that the expected goal of elimination could be reached within the given time frame.[91011] This failure could be attributed to many reasons, including the increased presence of resistance to the traditional anti-Leishmania drugs based on pentavalent antimonials, limited availability, and the high cost of alternative therapeutic agents and the lack of effectiveness of vector control measures just to name a few. In addition to the obvious factors that may have contributed to the sustained L. donovani transmission, the presence of atypical forms of leishmaniasis induced by L. donovani, the causative agent of VL, is also a matter of grave concern in the region: Situation in Sri Lanka being a case in point.[12] The resultant increased parasite burden, a factor that has not been considered in the equation back in 2005. Is also likely to have implications on the plans for elimination of VL from the South-Asian region.

LEISHMANIASIS IN SRI LANKA

Leishmaniasis used to be considered as an exotic disease in Sri Lanka, linked with foreign travel and was particularly seen among returnees from the Middle East or African region.[13] The first autochthonous case of CL was reported in 1992,[14] and there have been a few isolated cases reported since then.[15] However, leishmaniasis soon became an established disease in Sri Lanka,[161718] with a steady increase in the numbers and distribution across the country.[12] The numbers reported to the health system (http://www.epid.gov.lk/web/images/pdf/wer/2015/vol_42_no_24-english.pdf); however, portray an under-representation and would reflect only a fraction of the true burden of country's disease.

The classical presentations of Sri Lankan leishmaniasis are CL with nontender, nonitchy papules, scaling nodules, or ulcers affecting exposed areas of the body, mainly on the extensor surfaces of limbs and the face.[1216] Laboratory facilities necessary for confirmation of diagnosis are not available in all hospitals and patient clinics across the country. In such instances, clinicians have to resort to treat patients based on clinical diagnosis. Treatment is given in the form of cryotherapy, which is available in most district-level hospitals and intralesional or parenteral sodium stibogluconate injections in hospitals with functional dermatology units. Both these forms of treatment require repeated doses, hence, multiple hospital visits and resultant burden both on the patient and the healthcare system. Newer forms of treatment, for example, thermotherapy are being pursued to enable more effective patient treatment (author's unpublished data).

The causative agent of CL in Sri Lanka is L. donovani, MON-37.[1920] This species is an established agent of human VL, particularly in countries such as India, though dermotropism of L. donovani, as seen in Sri Lanka has indeed been observed only occasionally.[21] This has led to investigations on apparently more attenuated parasite forms in L. donovani[22] and a role for host genetics in determining the disease phenotype[23] but the debate continues. Therefore, the theories on CL-inducing L. donovani being essentially dermotropic of having visceralizing potential still remain inconclusive.

The likely vector of leishmaniasis in Sri Lanka has been identified as Phlebotomus argentipes,[24] the same species, that is, found elsewhere in the region. The studies carried out so far support the anthropophagic nature of the local vector,[2526] and the environmental conditions that exist in most parts of the country favor outdoor breeding, although some studies imply indoor breeding habits of this insect as well.[27] There are only a few entomological studies done so far to elucidate vector behavioral habits and feeding preferences,[28] and there is dearth of information even on operationally important biological properties such as insecticide susceptibility of sandflies.[29] Therefore, many important aspects that would need to be considered in determining strategies for disease control are yet to be addressed.

Information regarding reservoir hosts also remains inconclusive. Though it is traditionally believed that the only reservoirs of infection of L. donovani are affected humans, this view has been challenged on many occasions[30313233] and therefore, further studies are warranted in this area too. Overall, there are many questions that still remain unanswered on leishmaniasis situation in Sri Lanka and in this backdrop no organized efforts are in place for the control of this disease at the national level.

LEISHMANIASIS ELIMINATION PROGRAM IN THE SOUTH ASIAN REGION

There are obviously many advantages of moving toward elimination of leishmaniasis from the South Asian region. However, it might be timely to take stock of the situation on the elimination ongoing drive that was put in place in 2005 and consider the possible reasons for its failure.[9] The lapses thus identified[8] should be addressed with gaps in knowledge bridged using properly designed studies. The elimination program thereafter, could be revamped with the necessary monitoring mechanisms in place and also with due considerations made in to the more recent developments in the region, such as the presence of atypical variants of L. donovani, which might have the potential to act as reservoirs of infection for the region. Such new and improved strategies would no doubt ensure a more successful outcome of the regional drive toward elimination of L. donovani-induced leishmaniasis.