Leishmaniasis is a parasitic infection that is caused by different species of intracellular protozoan parasites that belong to genus Leishmania. This parasite resides inside the digestive tract of certain kinds of female sandflies. These sandflies belong to the Phlebotomus, Lutzomyia, and Psychodopygus species. When these sandflies are infected with Leishmania, they act as perfect carrier/vector for leishmaniasis infection.
Origin of Leishmaniasis
The word leishmaniasis was derived from the name of a Scottish pathologist and British Army medical officer Sir William Boog Leishman (6 November 1865 – 2 June 1926). He has been serving as Director-General of Army Medical Services from 1923 to 1926. The name was given to this condition in ~1905, by Sir Ronald Ross who was a fan of Leishman’s work on Kala Azar (Visceral Leishmaniasis). So “Leishmaniasis” has two words origin. “Leishman” on the name of Sir William B. Leishman, and “-iasis” means “process; morbid condition,” or “A pathological condition characterized or produced by”. So Leishmaniasis is a disease produced by Leishmania.
Epidemiology of Leishmaniasis
Leishmaniasis is prevalent in more than 90 countries. These countries are spanned throughout Asia, Europe, Africa, and North and South America. According to a careful estimate, 12 million cases of leishmaniasis are reported per annum worldwide. Among them, 1.5 to 2 million are new cases. Risks of acquiring leishmaniasis in the Old World are greater than acquiring it in the New World. However, if a U.S. citizen visits Latin America, he/she is prone to have this disease.
Frequency of Leishmaniasis
Each year, Fifty to 100 cases of New World cutaneous Leishmaniasis are reported in the United States. In Latin America, Leishmaniasis is highly contracted, especially in Peru and Brazil. Although the disease is widespread and can be restricted in any country from Mexico to Argentina, except Uruguay and Chile. There also is an endemic focus in Texas. It is interesting that Uruguay’s climate is heaven for Leishmania but the very first case of Human Leishmaniasis is reported in 2018, for the very first time. Before that, Canine Visceral Leishmaniasis was reported in dogs in 2010. Leishmaniasis is a disease directly linked with rural areas, poverty, and low standard life, but it has been migrating to Urban areas as well.
History of Leishmaniasis
Leishmaniasis might have roots in the pre-historic era. Several shreds of evidence have been gathered to establish that Leishmaniasis was present but with different names according to perspective symptoms. The first ever evidence to be found was traced back to tablets from King Ashurbanipal in the 7th century BCE. Some of them are believed to be more ancient records like 1500 to 2500 BCE. In the 10th century, many Persian physicians, especially Avicenna, provided comprehensive information about leishmaniasis kind of disease named “Balkh sore”.
Text from Incan civilization in 15th and 16th and ledgers of Spanish conquistadors claimed the presence of skin lesions in agriculturists and farmers coming from the Andes. Back then, these lesions look like leprosy ulcers and named as ““white leprosy,” “Andean sickness,” or “valley sickness””. Alexander Russell also gave a detailed description of the same disease after examining a Turkish patient in 1756. He named this condition as “Aleppo Boil”.
In the 1st century AD, evidence of Leishmaniasis was found in the Americas (Peru and Ecuador), and it was presented on pre-Incan Pottery with depictions of skin lesions and ugly scars. These depictions are very similar to current leishmaniasis symptoms.
Major contributions were made by the physicians working in the Indian Sub-continent. Leishmaniasis has been called “Kala-Azar” in Hindi and Urdu. “Kala” for black, and “Azar” for fever or discomfort.
History is not sure who discovered Leishmania. David Douglas Cunningham was a Scottish Surgeon who has been working in the British Indian army may have observed it during his tenure in 1985. But He may not be able to relate to disease. Another glimpse was found back to 1898 when a Russian military surgeon named Peter Borovsky worked on how “oriental sore” or “sart sore” was spread. His studies indicated parasite’s relation to host tissues and he was successful in tracing the actual culprit as protozoa. His research could not get enough attention at that time.
William B. Leishman extracted certain organisms from Spleen of a person who has died from “Dum Dum fever”. Those organisms were proved to be trypanosomes. After a few months, Captain Charles Donovan affirmed the presence of some specimens in patients of Madras. These specimens were known later as Leishman Donovan bodies. Later, Ronald Ross named them as “Leishmania donovani” and claimed that these bodies are intermediates of the new parasites. Charles Donovan established a link between Leishmania donovani and Kala-azar. It was confirmed by Charles Bentley who successfully extracted Leishmania donovani from Kala-azar patients
Causes of leishmaniasis
The causative agent of Leishmaniasis is a group of more than 20 species of Leishmania. Leishmania is a protozoan parasite, which is a unicellular, eukaryotic trypanosome. The characteristic feature of its body structure is kinetoplasts (circular DNA inside mitochondria) and flagella.
Transmission of Leishmania/ Vector of Leishmaniasis
Leishmania are transmitted to their hosts through the bites of sand flies. The sandflies are just 2-3 mm long in size.
Approximately 500 species of phlebotomine sandflies have been discovered at the moment. Among them, only 30 species are known to deliver the Leishmania to their hosts. It is interesting that only female phlebotomine sandflies infect their hosts with the Leishmania parasite.
The female sandflies need to feed on host blood for their eggs to develop. When they bite a Leishmania-infected person, parasite transfers to their mouth and resides in the gut for 4- 25 days. When carrier sand fly bites another host for fresh blood, Leishmania is transferred to a new host individual. Hence transmission of Leishmania is completed. So it is clear that the gut of sandflies is not a birthplace for Leishmania, but just a vector/vehicle.
Habitat of Phlebotomine sand flies
Phlebotomine sand flies are found throughout the hot and hot-humid, as well as in moderate areas. Phlebotomus genus is the carrier of Leishmania in the old world (Africa, Asia, and Europe or collectively Afro-Eurasia), while genus Lutzomyia spreads leishmania in the new world (the Americas and Oceania).
The most favorite places for laying eggs are the holes of certain rodents, the bark of old hollow trees, abandoned buildings, uncleansed cracks in the walls, animal shelters, and household garbage. These places provide organic matter, humidity, and heat so that eggs can develop.
Female Sand flies find their hosts for blood from dusk till dawn. They can travel up to hundreds of meters around their habitat.
Development and life cycle of sand flies
The life cycle of Sand flies is completed in four-stages: egg, larva, pupa, and adult. After the eggs are laid, they are hatched after 4‒20 days. This time span is prolonged if the weather is cool or temperature is lower than 16 C. The Larval development stage is comprised of four instars, and is completed between 20 to 30 days. This time span can be fluctuated by multiple factors. These factors are species type, temperature, and nutrient availability. Environmental stresses like heat, cold, or drought can force larvae to cease the developmental stage, delaying the development period for months. Larvae are mainly foragers that feed on organic matter (e.g. fungi, putrefying fallen leaves, animal feces, and dead insects). The pupa takes 6‒13 days before it has emerged into an adult sand fly.
Development and life cycle of Causative agent (Leishmania)
- Leishmania aethiopica
- Leishmania amazonensis
- Leishmania arabica
- Leishmania donovani
- Leishmania gerbilli
- Leishmania hertigi
- Leishmania infantum
- Leishmania killicki
- Leishmania major
- Leishmania mexicana
- Leishmania siamensis
- Leishmania tropica
- Leishmania turanica
- Leishmania braziliensis
- Leishmania peruviana
- Leishmania guyanensis
- Leishmania panamensis
- Leishmania enriettii
- Sauroleishmania tarentolae
All the trypanosomes, especially Leishmania organisms have two distinct structural (also functional) alternates, i.e. promastigotes and amastigotes. Both are residents of different hosts. In order to understand the mode of infection by Leishmania, their morphology must be understood. Mastigote means an organism having one or more flagella.
Since mid-gut of the phlebotomine sand fly is the first rest house of Leishmania, their physical structure is built/modified according to the environment. In the mid-gut of sand flies, Leishmania is structurally referred to as Promastigotes. Promastigotes are characterized as extracellular motile forms. Since mid-gut of sand flies are not having any permeability issue, this structure is usually larger than the other counterpart i.e. amastigote. Promastigotes are usually 15–30 µm long and 5 µm wide. It is boat-shaped (spindle) that is tapered at both ends.
Leishmania promastigotes movement
Since promastigotes need to move and anchor, nature has provided them with a flagellum with equal body length for motion. This flagellum is present outside the body, at the anterior edge. The nucleus is present in the center neighbored by the kinetoplast and the basal body.
When the infected sand fly bites a human host, Leishmania promastigotes are injected into human skin via sand fly proboscis. At this stage, leishmania needs to modify its body because blood vessels and skin pores are not as wide as sand fly’s mid-gut is. Leishmania promastigotes (having one or more flagella) are reduced to another leishmania structural variant called amastigote (without flagella). Amastigote is an intracellular and non-motile form of Leishmania parasite without a distinct external flagellum. Amastigotes enter mononuclear phagocytes and circulatory systems of humans.
Leishmania amastigotes are characterized by their size (i.e. 3–6 µm long and 1–3 µm wide), and the presence of embedded tiny flagellum that is not projected outside the body. The kinetoplast and basal body are present near the anterior end.
Leishmania Infection and Life Cycle
To understand the Leishmaniasis life cycle, we must first understand the life cycle of Leishmania. Leishmania species infect their hosts in different ways, according to the host environment. As we have mentioned above, Leishmania species have two distinct variants for each host. The destiny of Leishmania is the human body. But they cycle their life from sand flies to humans and some canine-like dogs and some rodents. Human is considered as their definitive host.
Leishmania Definitive Host (Human)
When an infected sand fly bites human, it transfers infective promastigotes form of Leishmania to the human through its proboscis. These promastigotes were residing and being nurtured inside sand fly’s hollow gut. After the bite, some of the promastigotes enter into the bloodstream directly through blood vessels. Now, they may face different fates according to the defense mechanism of the host. Some promastigotes are destroyed by the macrophages through the process of macrophagic cytolysis. Those who survive this macrophagic attack are taken up by mononuclear phagocytes in the liver, spleen and bone marrow through the process of phagocytosis. These surviving promastigotes undergo certain transformations inside the phagocytes and are converted into amastigotes. It is very interesting to note that Promastigotes are selectively destroyed by the granulocytes by oxidative destruction. Amastigotes have shown resistance against granulocytes. Another reason for the death of promastigotes and freedom of amastigotes is a differential release of superoxides by macrophages.
Macrophages have been observed to release high levels of superoxide against the infection by promastigotes. On the other hand, they release low levels of superoxide against amastigotes. That’s the reason amastigotes are survived.
Now, Promastigotes are gone for good and only amastigotes are lucky enough to live on under the hiding of Phagocytes. There, these amastigotes are replicated by simple binary fission. When the host cell is full of newly-divided amastigotes, it can no longer hold them and is ruptured. A phagocyte cell can hold only 50-200 amastigotes. Upon release into open cell environment, these amastigotes attack other cells, leading up to entire tissue infection and destruction.
Again, many amastigotes migrate towards the bloodstream and readily picked up by sand flies during a blood meal. Now Leishmania parasites are transferred to sand fly’s mid-gut. Here begins another host life cycle of Leishmania.
Leishmania Intermediate Host (Sandfly)
Only female sand flies are responsible for Leshmaniasis infection. Amastigotes from human bloodstream enter into female sand fly’s digestive tract. Now the process of converting from promastigotes into amastigotes is reversed. Amastigotes become larger in size and remake/enlarge their flagellum. Now amastigotes are converted back to promastigotes. Flagellum helps them to anchor at the epithelial lining of the gut. Here they multiply more through asexual binary fission. They can also multiply by sexual reproduction by fusing their genetic material at the epithelial lining.
Now, promastigotes move toward anterior digestive system as pharynx and buccal cavity. This process belongs to only Leshmania species and is called anterior station development. Infection in the pharynx or buccal cavity occurs after 6-9 days from a blood meal. It is where promastigotes become highly infective, this stage is called the metacyclic stage. The infective promastigotes gather inside the hollow proboscis of sand fly and fill it, blocking the food passage completely. That is why upon the first contact during a blood meal, promastigotes readily enter into the host skin.
Leishmania reservoir host
Reservoir host is usually an organism that is used to harbor and nurture the infecting agent outside the human host. This organism provides all means of multiplication and shelter to the parasite. It may or may not cause infection in the reservoir host.
In the case of Leishmania, the reservoir host is usually canine animals, especially dogs and few fox species (Lycalopex vetulus and Cerdocyon thous). The most common guest inside these reservoirs hosts is Leishmania donovani. When an infection is spread between the animals, this infection is called zoonotic infection. When dogs and foxes become reservoir hosts, Leishmaniasis will be regarded as Zoonotic infection. When human infects some animal, it is called reverse zoonotic or anthroponosis.
Types of Leishmaniasis
There are 2 types of Leishmaniasis: Cutaneous Leishmaniasis and Visceral Leishmaniasis. Modifications and prolonging of these types may convert Cutaneous Leishmaniasis into mucocutaneous Leishmaniasis. On the other hand, Visceral Leishmaniasis may appear as Post Kala-azar Visceral Leishmaniasis. There are 20 different species of Leishmania that can cause disease in humans. Different species are associated with each form of leishmaniasis.
Synonyms: “oriental sore, tropical sore, chiclero ulcer, chiclero’s ulcer, Aleppo boil, Delhi Boil or desert boil”
Cutaneous Leishmaniasis (CL) is primary and the most common type of leishmaniasis affecting the human. Although it is not a life-threatening condition, it leaves many psychological and social effects on the patient even after healing. The skin ulcers left by cutaneous Leishmaniasis are so ugly that they keep the patient embarrassed, stigmatized and finally result in ostracism, impaired education as well as a social and economic failure. Such conditions get worse in societies deprived of resources. When this condition comes where HIV is already present, it can lead to entire organ failure and severe weakness.
The exact occurrence of Cutaneous Leishmaniasis is not known. According to an estimate, 600,000-1,000,000 cases are observed each year. Major victims of Cutaneous Leishmaniasis are children, and not all of them are properly treated. The incubation of Leishmaniasis can take up to two to eight weeks. Delayed incubation periods have also been observed.
Cutaneous Leishmaniasis affects both the Old World and the New World. In the Old World, infection is caused by Leishmania tropica in urban areas. Dry desert areas of the Old World are crawled with Leishmania major. The Latin America (New World) is affected by CL through two subgenera of Leishmaniasis, i.e. Leishmania leishmania (e.g., Leishmania mexicana, Leishmania amazonensis, Leishmania chagasi) and Leishmania viannia (e.g., Leishmania panamensis, Leishmania braziliensis, Leishmania guyanensis).
The area affected by Cutaneous leishmaniasis is quite huge, ranging from the Indian subcontinent, throughout Central and South-Western Asia, the Mediterranean Basin, the northern half of the African continent, and Central and South America.
Types of Cutaneous Leishmaniasis
There are different forms of Cutaneous Leishmaniasis. We have divided CL according to symptoms as well as the mode of transmission.
According to the symptoms, CL has the following types:
Localized cutaneous leishmaniasis (LCL) begins as a red papule that enlarges to form granulomatous, painless ulcers, which may resolve without treatment, leaving a scar.
Causes are Leishmaniasis major and Leishmaniasis tropica in the Old World, and Leishmaniasis braziliensis, Leishmaniasis peruviana, Leishmaniasis guyanensis, Leishmaniasis panamensis, Leishmaniasis amazonensis, and Leishmaniasis mexicana in the New World.
The symptoms of a localized cutaneous leishmaniasis (LCL) infection are started with small erythema on the spot where sand fly bites. Possible affected areas of that bite are those not covered by a cloth or anything. After that, this erythema in matured into a red papule. This papule is increased in size to form a nodule. These nodules produce ulcers on granulation tissues. It must be noted that these ulcers do not have a circling induration and they are usually painless. Lymph nodes or glandular tissues can be swollen (localized adenopathy) on the affected area, especially in the early stages of the infection. LCL lesions are not always the same in harshness and clinical appearance. They can take differential time spans to be cured spontaneously. Most lesions are healed without any treatment, yet their time to heal varies depending upon culprit Leishmania species as well as the host’s immune strength. After spontaneous healing, hypopigmented skin patch may appear that is usually depressed like a burrowed land.
Leishmaniasis recidivans (LR) also called lupoid leishmaniasis is caused by L. tropica in the Middle East and characterized by new papules occurring in areas of prior scar months or sometimes years after the initial infection.
leishmaniasis recidivans (LR) is an unusual clinical form of Leishmaniasis. It is an extended, deteriorating type of cutaneous leishmaniasis that usually looks like tuberculosis of the skin. LR may persist for many years with an enduring and relapsing progression. This unusual divergent is believed to be caused by Leishmania tropica species in the Old World. In New World, this credit goes to Leishmania braziliensis, Leishmania amazonensis, Leishmania panamensis, and Leishmania guyanensis.
Leishmaniasis recidivans normally reappear at the site of an original ulcer, generally within 2 years after the healing of cutaneous leishmaniasis. It may also appear on the edge of the scar, usually on the face, and proceed inward to form a psoriasiform lesion. The reason behind this recurring condition can be the reactivation of dormant leishmania or other infections due to other causative agents. Children are highly susceptible to this form of Leishmaniasis. Treatment of Leishmaniasis recidivans is very difficult that is why it is also named as “chronic relapsing cutaneous leishmaniasis”.
Due to the war in Syria, the epidemiology of leishmaniasis and species distribution of the causative agents are rapidly changing as a result of the migration of refugees from Syria to neighboring Turkey and the other countries. Unusual manifestations of the disease frequently occur, which complicates the diagnosis and treatment. This letter aims to reflect our experience with leishmaniasis recidivans (LR) in pediatric cases, the most prevalent group for cutaneous leishmaniasis (CL).
LR is a rare clinical form that occurs the following years after the resolution of localized CL because of the reactivation of the dormant parasites. In the Old World, LR is usually caused by Leishmania tropica, the main causative agent for CL in Turkey, an endemic country. The scarcity of the parasites in skin biopsy complicates the diagnosis, especially for patients in a nonendemic region. The lesions become destructive and disfiguring after many years because most of the patients may be resistant to regular treatment.
The pathogenesis of LR is still unclear. Receiving an incomplete course of treatment may play a role in resistance and recurrence of the lesions. The host immunologic status, especially defective Th1-type immune response, can also result in the reduction of parasitic clearance.
Diffuse cutaneous leishmaniasis (DCL)
DCL is a rare form of cutaneous leishmaniasis and usually seen in patients with deficient cell-mediated immunity. DCL is usually caused by Leishmaniasis aethiopica in the Old World (Kenya and Ethiopia), and Leishmaniasis mexicana and Leishmaniasis amazonensis in the New World (South and Central America).
When amastigotes of Leishmania species are spread to other areas of skin (especially face and cooler extensor parts of limbs), they form non-ulcerative nodules/plaques. The nodules are progressively converted into loathsome lesions. DCL characteristically follows a long-lasting progressive path spanned over months to years and leads to marked deformity.
Synonyms: Espundia, Uta, chiclero ulcer
Cutaneous Leishmaniasis affects the skin. However, when the disease is advanced to affect mucous membranes, it destroys (partially or completely) the mucous membranes of the nose, mouth and throat area. The destruction is so terrible that the affected person is rejected by the community due to ugly looks. Mucocutaneous Leishmaniasis is the rarest form of Leishmaniasis.
Another way of occurrence of Mucocutaneous Leishmaniasis (MCL) is through metastasis. The destruction path is covered over time until any mucous area comes in range. Yet, the true pathway of MCL is not yet fully understood. Some believe that host genetic buildup plays an important role.
Cutaneous Leishmaniasis may spontaneously heal over time leaving deformed scars on the affected area. But the reappearance of CL is possible on the same spot or any other with a more aggressive approach. After CL occurrence and healing, months or years later, it can reappear as MCL. It has much more severity and damage. MCL has been reported in 5-20% untreated patients of Leshmania viannia triggered Cutaneous Leishmaniasis. This frequency is associated with the area were Leishmaniasis in endemic.
Mucocutaneous Leishmaniasis is, in fact, a complication of Cutaneous Leishmaniasis. When the primary lesions appear, parasites move from primary cutaneous leishmaniasis via lymphatic blood vessels and reach upper respiratory tract mucosa. Species belonging to Leishmania viannia subgenus (previously known as L. braziliensis complex) are usually responsible for such metastatic spread. These species are present in tropical forest lands of central and South America.
Synonyms: kala-azar, black fever, Dumdum fever
Visceral Leishmaniasis is the deadliest form of Leishmaniasis. Viscera means the internal body organs, especially of the abdomen area. So, Visceral Leishmaniasis must be defined as Leishmaniasis of internal body parts. The target organs of VIsceral Leishmaniasis (VL) are spleen, Liver and bone-marrow.
Two Leishmania species are responsible for Visceral Leishmaniasis. Leishmania donovani is responsible for Visceral Leishmaniasis in Old World (East Africa and the Indian subcontinent). Leishmania infantum (L. chagasi) is a major culprit for causing Visceral Leishmaniasis (VL) in New World (Europe, North Africa, and Latin America).
Poor diagnosis of Visceral Leishmaniasis increases the death rate of patients, so does poor or no treatment. If untreated, VL causes 100% mortality rate. The icing on the cake, if VL is co-occurred with AIDS, death is certain. This death may not be directly due to VL, but because of other opportunistic diseases like Pneumonia, tuberculosis, and dysentery.
Visceral Leishmaniasis is characterized by irregular visits of fever, intense weight loss, anorexia (appetite loss), liver and spleen enlargement, pancytopaenia (deficiency of red cells, white cells, and platelets), and anemia. It is because of these symptoms, that untreated patients can die within months.
Leishmania donovani is the causative agent for Visceral Leishmaniasis in Old World. We have mentioned above that this parasite was named after two scientists who worked on it. William B. Leishman and Charles Donovan. Both doctors could not classify the causative agent of Kala-azar. Ronald Ross characterized and classified it and named it in honor of these two doctors.
post–kala azar dermal leishmaniasis
Post-Kala-azar dermal Leishmaniasis is a skin condition (kind of dermatitis) that usually appears after Visceral Leishmaniasis is cured. It can also appear independently but most cases have shown its appearance after many years to VL is cured. It appears as a macular, maculopapular, and nodular rash. The time span when PKDL will appear varies among regions. Sudanese population has a short period i.e. 6 months after Visceral Leishmaniasis is treated. In India, PKDL appears after 2-3 years. Few cases have been reported where PKDL has appeared after 10 years of VL treatment.
Causative agent (parasite) for post-Kala-azar dermal leishmaniasis is the same for Visceral Leishamaniasis i.e. Leishmania donovani. It is suggested that L. donovani has successfully hidden inside the body. When a proper environment is induced, it reappears. PKDL can be regarded as a reservoir for Leishmania infection.
The difference between Visceral Leishmaniasis (VL) and post-kala-azar Dermal Leishmaniasis is the presence of prolonged fever. PKDL is characterized by skin lesions and hypo-pigmentation. Papules and nodules may appear in PKDL. Whereas, Visceral Leishmaniasis comes with random shots of high fever, anemia, anorexia, and weight loss. In PKDL, the rash starts from the mouth and spreads to the entire body. Post-kala-azar dermal Leishmaniasis is specific to two regions i.e. South Asia (Bangladesh, India, and Nepal) as well as East Africa (especially Sudan). PKDL is observed in 50% of patients treated for Visceral Leishmaniasis in Sudan. In India, 5-10% of patients have shown PKDL.
Difference between South Asia PKDL and East African PKDL
In South Asian PKDL, lesions are usually polymorphic i.e. patches/nodules and papulonodules reside together. But in Sudan, PKDL appears as either papules or nodules (not both).
Why post-kala-azar dermal Leishmaniasis occurs?
PKDL is post-traumatic event after the successful treatment of Visceral Leishmaniasis. It is enlisted in Neglected Tropical Diseases. There are five hypotheses about the development of post-kala-azar dermal leishmaniasis.
1.Antimonial drugs interaction
Studies have suggested a strong relationship between antimonial drugs (Sodium Antimony gluconate/SAG) and PKDL. In the Indian population, 73% of patients have shown PKDL who were treated with Sodium Antimony gluconate (SAG) to control Visceral Leishmaniasis. In Sudan, Bangladesh, and Nepal, 100% of patients are treated with SAG. A very small group of patients has shown PKDL that had not been affected with Visceral Leishmaniasis, hence it did not receive any antimonial drugs.
2.Skin damage due to Ultraviolet radiation
PKDL lesions usually appear on exposed body parts like face, arms, ears, etc. This may suggest UV light’s role in the pathogenicity of PKDL. Another hypothesis suggests the immunosuppressive role of UV light.
3.reappearance of infection
All infectious diseases have one property in common, persistence of parasite even after the disease is cured. Sample smears abstracted from PKDL lesions were diagnosed with the presence of Leishmania donovani. So PKDL might be considered as reinfection of L. donovani.
4.memory T-cells failed to respond in the specific organ
T-cells are trained to remember any antigen (parasite) to cope with it in the future. If these memory cells lost their ability, infection is possible reappeared. This might happen due to immunosuppression (again possibly due to UV light-induced immunosuppression).
5.host cell genetic susceptibility
All the factors given above may be dependent on host genetics. This hypothesis is not supported by the amount of scientific research data. Yet, possibilities are there that some genetic weaknesses may harness PKDL. A strong association between interferon γ receptor (IFN-γ R polymorphism) and appearance of PKDL was observed. Inability induced due to IFN- γ polymorphism may have helped the Leishmania parasite to survive and thrive. This also explains reinfection as PKDL.
Symptoms of Leishmaniasis
All types of Leishmaniasis have common symptoms but few of them have different ones. In order to educate our reader, we have tried to symptoms of Leishmaniasis according to the subtype of it. Many patients are confused about what type of Leishmaniasis they have. So, our effort will help them to understand what they are suffering from.
Symptoms of Cutaneous Leishmaniasis
Since Cutaneous Leishmaniasis is further divided into Localized Cutaneous Leishmaniasis, Diffused Cutaneous Leishmaniasis and Leishmaniasis Recidivans, we present their symptoms separately.
Symptoms of Localized Cutaneous Leishmaniasis
- small erythema on the spot of the bite
- erythema in matured into a red papule
- papules develop into nodules
- a single red nodule that develops into a granulomatous ulcer
- single/ solitary nodule in New World
- Single nodule with small satellite nodules with multiple lesions in Old World
- elevated borders and central depression
- mostly without pain, unless other infection takes place
- adenopathy (swollen glandular tissues) may be observed
- swollen lymph nodes (lymphangitis) may be observed
- mostly appear on ears but occasionally appear on all exposed parts of the body
- lesion appear after weeks or month, maybe years after the bite
- may spontaneously heal after several months
- leave a bad looking scar after healing
- that scar looks like hypo pigmented depressed land
Symptoms of Leishmaniasis Recidevans
- new ulcers and papules are developed at the border of old scars after two years of first cutaneous Leishmaniasis
- later these papules travel inward to form psoriasis-like patches
- most affected people are children
- treatment usually do not affect the LR infections
Symptoms of Diffuse cutaneous leishmaniasis (DCL)
- non-ulcerating nodules throughout the body especially face and cooler extensor parts of limbs
- the abundance of parasites in skin lacerations
- no visceral manifestations
- results are negative for Leishmanin skin test
- treatment is not effective
- symptoms come and go time to time
Symptoms of mucocutaneous leishmaniasis
- initial symptoms resemble cutaneous Leishmaniasis
- single or many lesions/ulcers at mucous regions
- partial or complete destruction of the mucous membranes of the nose, mouth and throat area
- bones remain intact
- lesions multiple to propagate the damage
- the affected area is deformed severely that person affected is rejected by society
- The incubation period is 1 month to 24 years
Symptoms of Visceral Leishmaniasis
- most symptoms are like that of malaria
- random periods of High fever
- weight loss
- muscle fatigue
- swelling of liver and spleen
- deadliest when co-infected with HIV
- leave ugly scars after treatment
Symptoms of post–kala-azar dermal leishmaniasis
- sequential event of Visceral Leishmaniasis
- occurs along with VL or especially after recovery from VL
- multiple maculopapular and nodular patches or macular rash on the entire body especially arms and face