Research Report on Pathogen Leishmania Donovani Paper

Research Report on Pathogen Leishmania Donovani Paper

Parasites occur in two distinct forms: the multicellular metazoa called worms or helminths and the single-celled protozoa. The major protozoan pathogens are then grouped according to their location in the body and where they cause disease. There are intestinal (Giardia, Entamoeba, and Cryptosporidium), urogenital (Trichomonas vaginalis), and blood and tissue (Pneumocystis carinii, Toxoplasma gondii, Trypanosoma, Plasmodium, and Leishmania species) protozoan pathogens (Levinson, 2020). The Leishmania genus has four major pathogens: Leishmania donovani, Leishmania braziliensis, Leishmania mexicana, and Leishmania tropica. This paper analyzes Leishmania donovani, its molecular mechanism of infection, signs and symptoms of the disease it causes, its relation with other members of its genus, and its most common environments. The paper also discusses spread and prevention strategies, treatment, and the pathogen’s incidence and mechanism of resistance.

Molecular Mechanism of Infection

Leishmania donovani has several important properties that propagate its virulence, transmission, and causing disease. Its life cycle commences when the sandfly injects promastigotes after biting human beings. Macrophages and other mononuclear cells then phagocytize the promastigotes, transforming them into amastigotes (the parasite’s tissue stage) in those cells. They then multiply by simple division, infecting other phagocytic cells (CDC, 2020). At this point, parasitic and host factors determine whether the infection becomes symptomatic and whether visceral or cutaneous leishmaniasis results. A study by Zheng et al. (2020) elicited genetic mutations driven by long-term environmental adaptations serve to cause virulence and resistance of the pathogen. By severely affecting the reticuloendothelial organs, the pathogen causes disease.

Type and Symptoms of Disease

Leishmania donovani cause kala-azar (visceral leishmaniasis). In the disease, organs of the reticuloendothelial system (bone marrow, liver, and spleen) are severely affected. Cellular destruction and reduced bone marrow in the spleen cause thrombocytopenia, anemia, and leukopenia (Levinson, 2020). Consequently, a bleeding tendency and susceptibility to infections ensues. Sequestration of blood cells and proliferating macrophages leads to striking splenomegaly. The clinical findings of leishmaniasis commence with an intermittent fever, weight loss, and weakness (World Health Organization, 2020). There is hyperpigmentation of the skin. Initially, a patient feels reasonably well despite a persisting fever. However, as thrombocytopenia, anemia, and leukopenia become more profound, gastrointestinal bleeding, infections, and weakness occur.

Relationship to Other Members of the Genus

While L. donovani causes visceral leishmaniasis, L. mexicana and L. tropica cause visceral leishmaniasis, the latter being found in the Americas while the former is found in the Old World. On the other hand, L. braziliensis causes mucocutaneous leishmaniasis in South and Central America (Levinson, 2020). While sandflies are the primary vectors for these three organisms as they are for L. donovani, the main reservoirs for the former are the forest rodents, in contrast to the latter, whose main reservoirs are foxes, dogs, and a variety of mammals. While L. donovani can be cultured in the laboratory, the other three members of the genus are unculturable, with their clinical diagnosis being dependent on demonstration of the presence of amastigotes in smears taken from the skin lesions (Levinson, 2020). Lastly, lesions in cutaneous leishmaniasis are confined to the skin and the cartilage, skin, and mucous membranes in mucocutaneous leishmaniasis. Lesions caused by L. donovani are confined to the spleen, liver, and bone marrow.

Most Common Environments

Kala-azar occurs in three distinct epidemiologic patterns. In one area, which includes southern Russia, the Middle East, parts of China, and the Mediterranean basin, reservoir hosts are mainly foxes and dogs. In Sub-Saharan Africa, the main reservoirs are small carnivores (like civets) and rats. The third pattern is seen in India and neighboring countries, where human beings are seemingly the only reservoirs (Levinson, 2020). The Centers for Disease Control and Prevention (CDC) (2019) observe that more than 90% of the world’s cases of visceral leishmaniasis are found in India, Brazil, Nepal, Sudan, and Bangladesh. The World Health Organization (2022) states that leishmaniasis is more endemic in poor socioeconomic settings, with poor housing and domestic sanitary conditions such as open sewerage and improper waste management increasing the breeding and resting sites for breeding and resting sites the sandflies as well as their access to human beings. Sandflies are also attracted more to overcrowded areas.

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Associated Epidemics

Visceral leishmaniasis is still a serious disease affecting people living in developing countries. A review by Mann et al. (2021) elicited that annual cases of visceral leishmaniasis are estimated to be currently below 100,000, with more than 95% of those cases being reported by WHO to be from India, Nepal, Kenya, Brazil, China, Ethiopia, Sudan, and Somalia. Bi et al. (2018) showed that the number of visceral leishmaniasis (VL) cases reported annually has significantly dropped. However, the disease remains a serious threat to public health globally.

Spread and Prevention

There are no drugs or vaccines to prevent infections by Leishmania donovani. Control and prevention strategies are vital in reducing the cases of leishmaniasis. These strategies require various efforts since transmission occurs in a complex biological system involving animal or human reservoirs, the parasite, and the sandfly vector. Some of the key strategies include early diagnosis and prompt treatment to reduce the disease prevalence and prevent disability and death. It also aids in lowering the transmission of the disease (World Health Organization, 2020). Vector control is another crucial strategy that helps interrupt or reduce the transmission of the disease by reducing the number of sandflies. Levinson (2020) asserts that vector control can be achieved through insecticide spraying, insecticide repellants, protective clothing, and sleeping under nets to avoid sandfly bites. Additionally, social mobilization and health education must always be locally adapted for behavior change and incorporation of prevention strategies at the community levels.

Treatment

Effective drug therapy is vital for leishmaniasis, as is supportive care (for instance, treating anemia/bleeding, concurrent infections, malnutrition therapy). Liposomal amphotericin B (given IV) is an FDA-approved drug and is the treatment choice for visceral leishmaniasis in the US (CDC, 2022). While there are various suggested regimens, standard approaches have not been established (the optimal agent, dosage, and dose intervals). Conventional amphotericin B is a highly effective therapy. Still, it is more toxic than liposomal amphotericin B. CDC (2022) states that in 2014, the FDA approved miltefosine, an oral agent, to treat leishmaniasis caused by Leishmania donovani in adolescents and adults who are not pregnant or lactating. Paromomycin (chemically equivalent to aminosidine) is a parenteral agent that has gained merits in treating L. donovani in some settings, although it is not available parenterally in the US (CDC, 2022).

Resistance

            Leishmania has developed strategies for evading host immune mechanisms. Leishmania modifies the complement system and phagocytosis, alters the toll-like receptors pathways, and modifies responses of the T cells. Resistance to drugs has also emerged. Resistance-associated mutations to amphotericin B, miltefosine, and paromomycin have been reported (Capela et al., 2019). Drug resistance increases the cost of managing leishmaniasis.

Conclusion

            Leishmania donovani is an important pathogen causing significant clinical disease that can complicate and cause death without timely interventions. Since there are no vaccines or drugs to prevent infection, prevention strategies should be maximized. Researchers should analyze how the problem can be solved with the observed trends of some resistance to drug therapy. More research should also develop standard treatments and vaccines to prevent leishmaniasis.

References

Bi, K., Chen, Y., Zhao, S., Kuang, Y., & John Wu, C.-H. (2018, July 10). Current Visceral Leishmaniasis Research: A Research Review to Inspire Future Study. BioMed Research International. https://www.hindawi.com/journals/bmri/2018/9872095/

Capela, R., Moreira, R., & Lopes, F. (2019). An Overview of Drug Resistance in Protozoal Diseases. International Journal of Molecular Sciences, 20(22). https://doi.org/10.3390/ijms20225748

CDC. (2020). Parasites – Leishmaniasis. CDC. https://www.cdc.gov/parasites/leishmaniasis/biology.html

CDC. (2022). CDC – Leishmaniasis – Resources for Health Professionals. Centers for Disease Control and Prevention. https://www.cdc.gov/parasites/leishmaniasis/health_professionals/index.html

Centers for Disease Control and Prevention (CDC). (2019). Leishmaniasis. Cdc.org. https://www.cdc.gov/dpdx/leishmaniasis/index.html

Levinson, W. E. (2020). Review Of Medical Microbiology And Immunology. Mcgraw-Hill Education.

Mann, S., Frasca, K., Scherrer, S., Henao-Martínez, A. F., Newman, S., Ramanan, P., & Suarez, J. A. (2021). A Review of Leishmaniasis: Current Knowledge and Future Directions. Current Tropical Medicine Reports, 1–12. https://doi.org/10.1007/s40475-021-00232-7

World Health Organization. (2020, January 8). Leishmaniasis. Who.int; World Health Organization: WHO. https://www.who.int/news-room/fact-sheets/detail/leishmaniasis

World Health Organization. (2022, January 8). Leishmaniasis. Who.int; World Health Organization: WHO. https://www.who.int/news-room/fact-sheets/detail/leishmaniasis

Zheng, Z., Chen, J., Ma, G., Satoskar, A. R., & Li, J. (2020). Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance. Parasites & Vectors, 13(1). https://doi.org/10.1186/s13071-020-04397-4

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The assignment cannot be longer than 5 pages (font 11 or 12; 1.5 or double spaced) not including title page, pictures, or your reference page. The potential subtopics for your assignment are listed below. You can include other information if you think it is warranted. You choose how much space you want to devote to each subtopic – different pathogens will have more information/interest in some areas and not in others. The focus is not identical for every pathogen. Remember – there will be contrasting information – I expect to see this addressed in your report. You should tackle this as though you are preparing to present the most current information associated with your pathogen (disease, use, treatment, etc). Always consider WHY you are writing something and then convey it to the reader.
Part B: Choose a pathogen and use the following as a guide to write your report. ✓ Molecular mechanism of Infection and level of virulence.
✓ Type and symptoms of disease(s) caused by the pathogen
✓ Relation to other members of the genus
✓ Is the pathogen classified as the same level in other countries?

✓ Most common environments. (Hospital? Community? Geography?
✓ Description of any associated Epidemics, pandemics
✓ Spread and prevention
✓ Treatments and their molecular mechanisms. How likely would you be infected while working on patients as a Health Care worker?
✓ Are there current Clinical or Pre-Clinical trials currently being conducted that are testing therapies against your pathogen?
✓ Incidence and mechanism of Resistance. Are there any strategies to overcome the resistant species?
✓ Other topics of interest