An Overview of Leishmaniasis: Historic to Future Perspectives

*Mümtaz Güran*

### **Abstract**

Human leishmaniasis is a major public health problem with a wide clinical spectrum. Despite there is an epidemiological diversity of the disease, cases mostly occur in the developing countries around the subtropical region, and the incidence is significantly rising. The disease is usually classified into three groups: cutaneous leishmaniasis, mucosal leishmaniasis, and visceral leishmaniasis. But to ensure their survival in different conditions, *Leishmania* spp. have developed many adaptation mechanisms and can be seen in different clinical forms as well. Herein, an overview of the characteristics of the disease and the parasite, interactions with the host, clinical aspects, and latest developments in the diagnosis and treatment is presented.

**Keywords:** leishmaniasis, kala-azar, vector borne diseases

## **1. Introduction**

Human leishmaniasis is a sandfly-mediated parasitic disease that can lead to severe conditions in individuals especially with underdeveloped immune system. It usually affects people living in developing tropical countries and has high mortality rates [1]. Transmission of the parasite starts with an infected sandfly bite. After getting bit by a female sandfly vector carrying the promastigote form of the *Leishmania* protozoan, the promastigotes transform into amastigote form in mammalian hosts [2]. Once amastigotes enter the cells, immune system starts reacting to it. Phagocytes absorb the parasite, and destructive mechanism is initiated in order to kill the parasite. However, parasite has different ways of preventing or lowering the activity of immune system, and three distinct forms of leishmaniasis can be observed as a result which are cutaneous leishmaniasis (CL), visceral leishmaniasis (VL), and mucocutaneous leishmaniasis (ML). CL usually occurs around the uncovered sites such as face, neck, and extremities which are susceptible to sandfly bite and often can result in the formation of ulcers or nodules around exposed areas. In certain conditions, macrophages infected by the parasites at the initial bite site spread among the reticuloendothelial system causing VL. Abnormal growth of internal organs such as the spleen and liver is common in VL, and it can cause death if necessary treatment methods are not applied. Another form of leishmaniasis is the ML in which parasites enter the mucocutaneous tissue, and its effects are usually seen around the oral and upper respiratory tract [3].

Leishmaniasis is considered to be an endemic disease effecting more than 98 countries with a global prevalence of 12 million people. Among different types of disease, CL makes up great percentage of the total amount of cases compared to other two. East Africa, Brazil, and Indian subcontinent are hot spots for VL cases, whereas

CL cases are high in the Middle East, Mediterranean region, Central Asia, and Latin American countries [4]. In European countries where leishmaniasis is not endemic, people traveling to endemic regions for various reasons such as military duty, tourism work, and vacation are the major cause of leishmaniasis occurrence [5].

There are more than 20 *Leishmania* species responsible from leishmaniasis [3]. In general, *Leishmania* major causes CL, *Leishmania donovani* causes VL, and *Leishmania infantum* results in both CL and VL [3]. These species can be further classified into subgenera depending on anatomical varieties of infection sites. Old World sandfly species are common in desert and semidry areas, whereas New World sandfly species transmit the disease to human near forest habitation [6]. *Leishmania* parasite has promastigote form in sandfly and amastigote form in mammalians. It can be transmitted by the vectors from an animal carrying this parasite or humans affected by VL. Amastigotes develop within the phagocytes and spread to other macrophages as a result of cell lysis. Once a sandfly bites an infected host, amastigotes then transform into promastigote form inside the sandfly restarting the transmission process for the next host that will be infected.

Leishmaniasis is ranked second in mortality right after malaria and ranked fourth in terms of morbidity among other communicable diseases [2]. HIV outbreak in the 1990s resulting in HIV/VL coinfection and general global warming of the world increasing the possible habitat for the sandfly led to doubling the amount of cases from 1987 to 2014 despite developing medical technologies [6]. It is estimated that each year around 400,000 people are having VL with a mortality rate of 10% going up to 20% in some areas [2, 3]. The Mediterranean region, Western Asia, and the Americas make up the 90% of 1 million CL cases, whereas ML is represented by 35,000 cases in these regions [3]. Among the other common forms of the disease, CL has the highest amount of cases reported each year. On the other hand, VL is the most fatal one where death usually occurs 2 years after the first transmission.

There are 98 countries and territories with *Leishmania* cases recorded each year [7]. It affects around 12 million people worldwide, and 1.5–2 million new cases are reported each year. Being an ignored tropical disease, leishmaniasis has the highest prevalence in poor countries such as India, Brazil, Ethiopia, and Afghanistan. Notably, there has been an increase in the CL case reports for Syria in the Middle East, Algeria in the Mediterranean, and India [6]. Poor housing, insufficient sanitary conditions, poor waste management, poverty, malnutrition, and change in climate conditions such as temperature, rainfall, and humidity are common features of these countries. Children living in these countries are considered the main reason of parasite transmission as they are the most vulnerable population group to sandfly bite.

Among species, *L. major* shows the biggest geographical distribution in the Middle East region compared to *Leishmania tropica* and *Leishmania infantum* [8]. *L. infantum* caused zoonotic and *L. tropica* caused anthroponotic transmissions to occur. Domestic dogs, rodents, and wild animals in endemic regions hold epidemiological importance as they take part in transmission of the parasite by serving as reservoirs.

Parasites can only reach infective stages in certain species of sandfly which as a result limits its transmission [9]. In addition, parasite-vector contact is rare for great majority of the sandfly species [10]. Epidemiological concerns about the leishmaniasis have increased greatly in the last 30 years. HIV/*Leishmania* coinfection, sandflies becoming more apparent in areas that they were less present such as the United States and Canada, and great risk of *Leishmania* gaining resistance to drugs over time make it a high-risk factor globally [11]. Another major concern for leishmaniasis is the increased resistance gain by parasite to current treatment methods which makes it even more dangerous considering there is an ongoing effort to develop a human vaccine against the disease [12].

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**Figure 1.**

*from [16].*

*An Overview of Leishmaniasis: Historic to Future Perspectives*

Here, we aim to provide a general conceptualization of leishmaniasis by summarizing the historical development of the disease to provide a better understanding

In 1885, after observing *Leishmania* organism for the first time, Cunningham stated that the organism was not a bacteria. Thirteen years later, a Russian military surgeon Peter Borovsky further found out that the organism was a protozoan which was also confirmed by Wright in 1903. During that time, William Leishman

and Charles Donovan described the agent responsible from VL. Leishman conducting his study in India observed enlargement of the spleen and fever in patients which he further observed the samples he took from the patients under the microscope using Romanowsky method for staining and stated that it was not like anything he had seen before [13]. Finally, in 1942, female phlebotomine sandflies had enough evidence to be accepted as the main vector for CL and VL due to the fact that clinical conditions observed following a sandfly bite described as histiocytoses [14]. In terms of changing face of diagnosis of leishmaniasis, starting from the microscopical identification of the agents, medical technologies have progressed in time further into PCR-based DNA sequencing methods for

*L. donovani* was the first identified *Leishmania* species taking its name from William Leishman and Charles Donovan which was given by Ross in order to give

Despite being a neglected tropical disease, our knowledge about the disease has been increasing continuously. Case reports involving uncommon laryngeal leishmaniasis- and HIV-infected individuals showing leishmaniasis effects such as skin lesions and nodules have shown that leishmaniasis can occur again even after

*A rare case of treated laryngeal ML which originated from a previous CL of hands and feet. Isolated agent is L. infantum in this 81-year-old male patient resident in Adana, Turkey, a subtropical area. (a) CL lesions on a patients hand on his first application to clinic. (b) CL lesions on patients foot on his first application to clinic. (c) BT of neck showing papillomatous push elongating into ventricles. (d) Histological examination of laryngeal biopsy specimen (May-Grunwald-Giemsa staining; original magnification, ×1000) showing intracellular amastigotes of Leishmania species and histiocytes with vacuolated cytoplasm and corpuscles inside. (e) Laryngoscopic examination showing lesions with edema and erythema due to ML. Reprinted* 

treatment hinting to the incubation period of parasite (**Figure 1**) [16, 17].

*DOI: http://dx.doi.org/10.5772/intechopen.81643*

for possible future approaches.

**2. History of the disease**

determination of specific species.

credit to their studies [15].

Here, we aim to provide a general conceptualization of leishmaniasis by summarizing the historical development of the disease to provide a better understanding for possible future approaches.
