Introduction

Leishmaniasis is a chronic, neglected tropical disease brought on by flagellate protozoa of the genus Leishmania. Even though it can happen anywhere, most of the cases are in South America, the Mediterranean, and some parts of Asia and Africa. There are three main types of leishmaniasis i.e., cutaneous (the most common), mucocutaneous, and abdominal. It's also called kala-azar when it affects the organs. To identify leishmaniasis, you need to show that Leishmania amastigotes are present in medical samples that are looked at under a microscope or through molecular research.¹ There are several treatments for cutaneous leishmaniasis (CL), but there isn't a lot of evidence to back them. The standard symptoms of leishmaniasis and how we treat it have changed over the last few decades. This is because of acquired immune deficiency, which can be caused by things like human immunodeficiency virus (HIV) or the use of tumour necrosis factor inhibitors.²

Etiology

Leishmania infections generally arise from the bite of sandflies, specifically those of the Phlebotomus species in Europe, North Africa, the Middle East, and Asia, or Lutzomyia species from the southern United States to northern Argentina.³ Non-vector transmission, such as through accidental laboratory infection, is infrequent. Transmission of cutaneous leishmaniasis can be classified as either anthroponotic or zoonotic, contingent upon whether humans serve as the primary reservoir host.

Transmission and pathogenesis

When sandflies bite a person, skin cells take in the Leishmania bugs. They then switch forms and spread inside the cells. How fast the disease moves depends a lot on the body's ability to fight back. A Th1-type defense often makes sores that fix themselves, but a Th2-tilted or slow fight (like in HIV/AIDS or other weak immune cases) might make long-lasting or widely spreading sicknesses.⁴

Parasite virulence and host factors like genetic susceptibility, nutritional state, and other infections that the host has can also affect how the disease shows up. This interaction between multiple factors and the immune system is what makes CL so different from case to case.

Clinical variants of CL

There are many variants of eishmaniasishaving different clinical presentations. In areas like Central and South America, leishmaniasis is known as "New World" leishmaniasis, whereas if presented in the Middle East, Mediterranean, Asia, India and Africa, it is called "Old World" leishmaniasis.⁵

Old-world cutaneous leishmaniasis

It is usually caused by L. major, L. tropica, and L. aethiopica species. CL caused by L. major is found in central Asia, North Africa, Middle east, North Pakistan and India. Some cases of cutaneous leishmaniasis were also reported in Nepal. L. tropica-caused CL results in dry, painless skin ulcers on the face, arms, legs, and feet.

A slowly developing skin lesion on the face is characterised by leishmaniasis recidivans (LR), also known as tuberculoid or lupoid leishmaniasis, which is also caused by L. tropica.

Diffuse CL results from specific deficiency of cell-mediated immunity to Leishmania antigen. It is caused by L. aethiopica and reported from Ethiopia and Kenya. It starts with a single lesion and spreads over the face, extremities, and whole body.

According to reports from Dharan (the eastern region of Nepal), L. tropica and L. major are the causes of CL in that country. Infiltrating erythematous plaque with a vague boundary and thick crusting was the hallmark of Nepalese CL.

New world cutaneous leishmaniasis

In South and Central America, different forms of Leishmania cause a wide range of symptoms. Localised, disseminated, widespread, and atypical cutaneous and mucocutaneous leishmaniasis are the different types of the disease.

Localized cutaneous leishmaniasis 

It is caused by several species in the subgeneras Leishmania and Viannia. On the skin, tumours look like a macule at the infection site, then a papule that breaks open.

Post Kala-Azar Dermal Leishmaniasis (PKDL)

It is caused by L. donovani and is common in East Africa and the Indian region, where up to 50% of people who get Kala-azar also get PKDL. PKDL presents itself in three types i.e., macular and hypopigmented lesions; erythematous patches and clusters; and nodules.⁶

Mucocutaneous leishmaniasis

L. braziliensis and L. panamensis are the parasites that cause this disease. There are two stages: an initial skin lesion and, sometimes, a secondary mucosal involvement.

Diagnostic techniques

CL is diagnosed by looking at symptoms (backed up by epidemiological data) and doing tests in the lab. There are a lot of different diagnostic methods, and their accuracy varies a lot. Some of these methods are direct parasitologic study (microscopy, histopathology, and parasite culture) and/or indirect testing with serology and molecular diagnostics.

Parasitologic diagnosis: Due to its high accuracy, parasitologic diagnosis is still thought to be the best way to diagnose leishmaniasis. This is usually done by looking at the histopathology of frozen tissue or growing parasites in a lab from samples from possible lesions.⁷
Immunological Test: Serologic tests used today to check for CL mostly use indirect fluorescent antibody, enzyme-linked immunosorbent assay (ELISA), western blot, lateral flow assay, and direct agglutination tests.⁸
Skin Test for leishmaniasis: The Montenegro skin test (MST) or Leishmania intradermal skin test (LST) is a way to measure the immune system's reaction to cells.⁹ It is sometimes used to diagnose CL because it is easy to use and has a high sensitivity of 86.4% to 100%.

Diagnostic challenges for cutaneous leishmaniasis

Similarity to other cutaneous diseases: It's hard to diagnose CL because it can look like a lot of different skin diseases. This can lead to wrong diagnoses and longer treatment times. The skin changes caused by CL can look like a number of different skin conditions, from inflammatory ones like impetigo and eczema to granulomatous ones like sarcoidosis and lupus vulgaris to skin tumours like basal cell carcinoma and squamous cell carcinoma.

Akcali et al. and Oetken et al. both published about cases of cutaneous leishmaniasis that looked like squamous cell cancer.^10,11 Akman et al. have seen cases of CL that looked like rosacea, erysipelas, hydroa vacciniform, and eczema.¹²

Problems with microscopy: Conventional means, like microscopy, can give false-negative results, and healthcare providers who aren't aware of the problem make it harder to spot and report. Different numbers of parasites in lesions make it harder to find them, and you need to know what the results mean to avoid getting false positives or rejections.

Culture tests compatibility: Because some parasite types are not compatible with each other, diagnostic tests that use parasite material or depend on the immune system of the host might not work well. Adopting advanced tests is often hard because of a lack of resources.

Delayed Diagnosis: If you wait too long to get a diagnosis, the sickness may get worse and spread to other people. Taking care of these problems is necessary to make it easier to diagnose and treat this type of leishmaniasis.¹³

Innovative diagnostic techniques

In places with few resources, high-frequency ultrasound might be a good way to find out if someone has CL. In 2020, Saavendra et al. did a study in Peru that showed high-frequency ultrasound was a good way to see Leishmania (Viannia) braziliensis-induced CL without hurting the person.¹⁴

Zare et al. created an algorithm for finding Leishmania parasites that uses integral picture representation to make the process go faster.¹⁵ The study was able to find leishmania-infected macrophages with a recall rate of 65% and an accuracy rate of 50%.

A proof-of-concept study done in Sri Lanka using photographic imaging showed that new methods have a lot of promise, especially for figuring out how a lesion will react to anti-leishmanial treatment.¹⁶

Summary

Cutaneous leishmaniasis is still a big health issue all over the world, even though it shows many signs itis tough to spot. To diagnose it right, you need to know about each type, have good lab tools, and be very alert, more so in areas where it happens a lot. Quick finding and firm public health rules are key for handling it well. To make this hard, and often not seen, illness simpler to manage, we must improve our methods of training doctors, make better testing sites, and put more resources into studying it further.