**2. Epidemiology**

The disease classification is complex and can be characterized by either its *clinical presentation* into cutaneous (localized or disseminated), mucocutaneous, and visceral or *geographic location* into *Old World leishmaniasis* mainly including Africa, Asia, the Middle East, the Mediterranean, and India or *New World leishmaniasis* including Central and South America (**Table 1**) [4–6].

More than 90% of the cases of visceral leishmaniasis (VL) cases worldwide were reported from 7 countries in 2015 including Brazil, Ethiopia, Kenya, India, Somalia, Sudan, and South Sudan; however, the disease remains endemic in more than 60 countries [1]. The Indian subcontinent accounts for almost 70% of the world's anthroponotic visceral leishmaniasis cases, India having the highest incidence

followed by Nepal and Bangladesh. In immunocompromised patients, *Leishmania* parasites can persist for decades after management and may reappear exhibiting fulminant reactivation when immunity is compromised. Between 5 and 50% of

Leishmania *taxonomy showing most of the clinically significant Leishmania species [1, 5, 6, 14].*

**Table 1**.

*Leishmaniasis*

*DOI: http://dx.doi.org/10.5772/intechopen.90680*

**299**


#### **Table 1**.

public health problem that requires elimination by developing effective therapeutic

*This photograph depicts a right lateral view of a* Phlebotomus papatasi *sand fly which had landed atop the skin surface of a human volunteer. This specimen had just completed its ingestion of its blood meal, which is visible through its distended transparent abdomen. Sand flies like this* P. papatasi *are responsible for the spread of the vector-borne, parasitic disease, leishmaniasis (courtesy of Centers for Disease Control and Prevention/ prof. Frank Hadley Collins and James Gathany) (https://phil.cdc.gov/Details.aspx?pid=10276).*

The disease classification is complex and can be characterized by either its *clinical presentation* into cutaneous (localized or disseminated), mucocutaneous, and visceral or *geographic location* into *Old World leishmaniasis* mainly including Africa, Asia, the Middle East, the Mediterranean, and India or *New World leish-*

More than 90% of the cases of visceral leishmaniasis (VL) cases worldwide were reported from 7 countries in 2015 including Brazil, Ethiopia, Kenya, India, Somalia, Sudan, and South Sudan; however, the disease remains endemic in more than 60 countries [1]. The Indian subcontinent accounts for almost 70% of the world's anthroponotic visceral leishmaniasis cases, India having the highest incidence

*maniasis* including Central and South America (**Table 1**) [4–6].

regimens and prevention/control plans.

*Parasitology and Microbiology Research*

**2. Epidemiology**

**Figure 1.**

**298**

Leishmania *taxonomy showing most of the clinically significant Leishmania species [1, 5, 6, 14].*

followed by Nepal and Bangladesh. In immunocompromised patients, *Leishmania* parasites can persist for decades after management and may reappear exhibiting fulminant reactivation when immunity is compromised. Between 5 and 50% of

treated VL cases may develop post-kala-azar dermal leishmaniasis (PKDL), depending on geographic location, secondary to the interferon gamma-driven immune response against dermal parasite [7–9].

More than 90% of cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (ML) cases are reported from Pakistan, Afghanistan, Syria, Saudi Arabia, Iran, Brazil, Algeria, and Peru. The number of reported VL cases has decreased substantially in the past decade most likely due to early diagnosis and better access to treatment. In East Africa, however, the fatal disease case number continues to be sustained. However there is a surge in endemic CL across the world predominantly due to increased conflicts with forced displacement of population and living in poor sanitary conditions. In addition, there is also an increase in the number of overall *Leishmania* cases reported worldwide and increased new cases reported from nonendemic areas [10–12]. A renaissance of CL is seen in conflict areas of Middle East in particular Syria mainly due to collapse of public health systems, exposure of nonimmune population, and poor living conditions.

#### **2.1 Risk factors**

Population migration of susceptible individuals in endemic areas as well as into nonendemic areas, malnutrition, poverty, and immune status of the host play a major role. Temperature is another important factor as *Leishmania* species for cutaneous disease grow best at lower temperature, while species causing VL grow better at core temperatures.

reticuloendothelial system. The flagella of the organisms are lost, and amastigotes are formed that continue to multiply until the infected host cells get filled with organisms and rupture releasing free amastigotes that invade new cells, thus continuing the vicious cycle of *Leishmania* infection (**Figure 2**). The incubation period depends on the individual parasite species. In certain geographic areas, the transmission cycle can be maintained by the infected animals and does not require infected humans. In other areas where disease transmission has the anthroponotic cycle via humans, the disease transmission can be controlled by effective treatment

The disease is mainly transmitted by the bite of a 2–3 mm in size female "*Phlebotomus* sand fly" in Old World leishmaniasis and *Lutzomyia* in the New World disease. There are approximately 20 pathogenic *Leishmania* species and up to 500 known phlebotomine sand fly species identified as vectors of disease [17, 18]. The disease is mostly zoonotic with humans being incidental hosts infected by

In addition to the known classic disease spectrum and clinical presentations, new

unusual and atypical forms are emerging which is adding to the complexity of

CL causing *Leishmania* parasites are divided into New world and Old world species. The New World species affect mainly Central and South America and include *L. amazonensis*, *L. braziliensis*, *L. mexicana,* and *L. guyaensis*, among others. The Old World species examples include *L. tropica, L. major,* and *L. aethiopica* that are common in the Indian subcontinent, the Middle East, the Mediterranean basin, and East

achieving control and disease eradication goal [19].

of infected patients [16].

**3.1 Mode of transmission**

**4. Clinical presentation**

**4.1 Cutaneous leishmaniasis**

sand fly bite.

**301**

**Figure 2.**

*Leishmaniasis*

*DOI: http://dx.doi.org/10.5772/intechopen.90680*

*Leishmania life cycle.*

The pathogenesis appears related to T-cell cytotoxicity. The promastigotes activate complement system through alternate pathway with suppression of cellmediated immunity against the organism. In self-resolving and asymptomatic patients, T helper type 1 cells (Th1) predominate with interleukin-2 (IL-2), interferon gamma, and IL-12 as important cytokines helping with disease resolution. In visceral and diffuse cutaneous forms, T helper type 2 cells (TH2) predominate with patients exhibiting anergy to the organism. These cells secrete IL-4, IL-5, IL-9, IL-13, and IL-17E/IL-25.

A susceptibility gene in band 22q12 is identified in parts of Sudan with high prevalence of VL [13].

Coinfection of VL with HIV is a major challenge. Both infections share a common immunopathologic mechanism involving macrophages and dendritic cells of reticuloendothelial system, therefore leading to an accelerated progression of both diseases in coinfection.

#### **3. Life cycle**

*Leishmania* is scientifically classified as a "genus" that belongs to the "order" of Trypanosomatidae family, under the "class" of Kinetoplastea, under the "phylum" of Euglenozoa. The parasite *Leishmania* exists in two forms: flagellated promastigote form in sandflies and cultures and nonflagellated amastigote form in animals and humans (**Figure 2**) [14, 15]. The sandflies acquire infection when they bite an animal or human host. The parasite develops over 4–25 days in the sandflies and transforms into a promastigote form where they multiply by binary fission in the midgut and move upwards to the pharynx. Infection is transmitted mainly during days 6–9 after ingestion when there is heavy pharyngeal infection and promastigotes are regurgitated via a bite to the host. The sand fly can regurgitate more than 1000 parasites per bite. In the host some of the flagellates are destroyed, whereas others enter intracellular lysosomal organelles of macrophages of

## *Leishmaniasis DOI: http://dx.doi.org/10.5772/intechopen.90680*

#### **Figure 2.** *Leishmania life cycle.*

treated VL cases may develop post-kala-azar dermal leishmaniasis (PKDL), depending on geographic location, secondary to the interferon gamma-driven

More than 90% of cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (ML) cases are reported from Pakistan, Afghanistan, Syria, Saudi Arabia, Iran, Brazil, Algeria, and Peru. The number of reported VL cases has decreased substantially in the past decade most likely due to early diagnosis and better access to treatment. In East Africa, however, the fatal disease case number continues to be sustained. However there is a surge in endemic CL across the world predominantly due to increased conflicts with forced displacement of population and living in poor sanitary conditions. In addition, there is also an increase in the number of overall *Leishmania* cases reported worldwide and increased new cases reported from nonendemic areas [10–12]. A renaissance of CL is seen in conflict areas of Middle East in particular Syria mainly due to collapse of public health systems, exposure of

Population migration of susceptible individuals in endemic areas as well as into nonendemic areas, malnutrition, poverty, and immune status of the host play a major role. Temperature is another important factor as *Leishmania* species for cutaneous disease grow best at lower temperature, while species causing VL grow

The pathogenesis appears related to T-cell cytotoxicity. The promastigotes acti-

vate complement system through alternate pathway with suppression of cellmediated immunity against the organism. In self-resolving and asymptomatic patients, T helper type 1 cells (Th1) predominate with interleukin-2 (IL-2), interferon gamma, and IL-12 as important cytokines helping with disease resolution. In visceral and diffuse cutaneous forms, T helper type 2 cells (TH2) predominate with patients exhibiting anergy to the organism. These cells secrete IL-4, IL-5, IL-9, IL-

A susceptibility gene in band 22q12 is identified in parts of Sudan with high

Coinfection of VL with HIV is a major challenge. Both infections share a common immunopathologic mechanism involving macrophages and dendritic cells of reticuloendothelial system, therefore leading to an accelerated progression of both

*Leishmania* is scientifically classified as a "genus" that belongs to the "order" of Trypanosomatidae family, under the "class" of Kinetoplastea, under the "phylum" of Euglenozoa. The parasite *Leishmania* exists in two forms: flagellated promastigote form in sandflies and cultures and nonflagellated amastigote form in animals and humans (**Figure 2**) [14, 15]. The sandflies acquire infection when they bite an animal or human host. The parasite develops over 4–25 days in the sandflies and transforms into a promastigote form where they multiply by binary fission in the midgut and move upwards to the pharynx. Infection is transmitted mainly during days 6–9 after ingestion when there is heavy pharyngeal infection and promastigotes are regurgitated via a bite to the host. The sand fly can regurgitate more than 1000 parasites per bite. In the host some of the flagellates are destroyed,

whereas others enter intracellular lysosomal organelles of macrophages of

immune response against dermal parasite [7–9].

*Parasitology and Microbiology Research*

nonimmune population, and poor living conditions.

**2.1 Risk factors**

better at core temperatures.

13, and IL-17E/IL-25.

prevalence of VL [13].

diseases in coinfection.

**3. Life cycle**

**300**

reticuloendothelial system. The flagella of the organisms are lost, and amastigotes are formed that continue to multiply until the infected host cells get filled with organisms and rupture releasing free amastigotes that invade new cells, thus continuing the vicious cycle of *Leishmania* infection (**Figure 2**). The incubation period depends on the individual parasite species. In certain geographic areas, the transmission cycle can be maintained by the infected animals and does not require infected humans. In other areas where disease transmission has the anthroponotic cycle via humans, the disease transmission can be controlled by effective treatment of infected patients [16].
