17th June 2024

Other protozoal infections

Leishmaniasis

Leishmaniasis is a protozoal infection endemic within many tropical and subtropical countries, with an annual incidence of up to 1,000,000 cases worldwide. Transmitted by the phlebotomine sand-fly, various forms of the disease exist, including visceral (kala-azar), cutaneous, mucocutaneous, and post-kala-azar. Visceral leishmaniasis presents with symptoms that include fever, weight loss, lymphadenopathy, and hepatosplenomegaly. Thrombocytopenia, leukopenia, and anaemia are often found on a full blood count. The untreated mortality is close to 100%. There are a variety of ways to make the diagnosis, including antigen-based point of care tests, serology, polymerase chain reaction (PCR), and direct detection of amastigotes through splenic, lymph node, or bone marrow aspiration. It is important to test patients for HIV as this often co-exists with visceral leishmaniasis, with the latter occurring as an opportunistic infection. When HIV co-infection is present, leishmaniasis serology is less sensitive. Treatment of visceral leishmaniasis normally requires intensive parenteral therapy over several weeks. Agents of choice include sodium stibogluconate, amphotericin B, paromomycin and pentamidine. Miltefosine is the only oral agent currently in use. It is beneficial in that it can be administered in the community; however, this may lead to poor compliance, especially due to gastrointestinal side-effects. Teratogenicity is another potential issue with this medication. Post-kala-azar leishmaniasis presents with diffuse maculopapular or nodular lesions, which start at the mouth before potentially spreading to the rest of the body. Again, this is associated with HIV co-infection. Lesions can be biopsied for diagnosis. The natural history of post-kala-azar leishmaniasis varies between regions. It often resolves spontaneously in Sudan, whereas it normally requires treatment in India, using the same medications as for visceral leishmaniasis.

Cutaneous leishmaniasis presents with one or more skin lesions, which can vary in appearance. They are classically said to resemble volcanoes, with a raised outer edge and depressed ulcerated centre. Cutaneous leishmaniasis is generally self-limiting and resolves over several months. The lesions can be biopsied for diagnosis, with PCR used to identify the subgenus. This can be important as the subgenus Viannia can cause mucocutaneous leishmaniasis, which involves disfiguring spread of lesions to the mucosa of the mouth and nose, often months to years after apparent healing of the primary lesions. Whether to treat cutaneous leishmaniasis with anything more than topical therapy (or at all) generally depends on whether it is classified as simple or complex. Cutaneous leishmaniasis may be deemed complex if there are several lesions involved, if the lesions are large, if the lesions are having a significant cosmetic impact, or if they involve the lymphatics. Simple lesions can be left to heal over time or treated with topical or oral therapy. Complex lesions require parenteral treatment, such as intravenous or intramuscular sodium stibogluconate. If there is suspicion that the causative subgenus is Viannia, either by local endemicity or by formal PCR analysis, then parenteral therapy would be used to reduce the risk of subsequent mucosal spread.

African Trypanosomiasis

African trypanosomiasis, or African sleeping sickness, is caused by the protozoal species Trypanosoma brucei. West African trypanosomiasis is caused by the subspecies Trypanosoma brucei gambiense, with the rarer East African trypanosomiasis being caused by the subspecies Trypanosoma brucei rhodesiense. Spread by the tsetse fly, these diseases are fatal unless treated. T. gambiense infection presents with an early stage consisting of low-grade fever, joint pain, and lymphadenopathy. Posterior cervical lymphadenopathy may be present. This is known as Winterbottom’s sign, after the physician and abolitionist who noted its prognostic use by slave traders. The latter stage involves central nervous system (CNS) infection, with personality change, disturbance of circadian rhythm, and death within months if left untreated. T. rhodesiense infection follows a more acute course. The initial stage is more severe and more likely to result in death, with pericarditis, myocarditis, and severe anaemia common. The CNS stage also appears more quickly and follows a rapid course to fatality if left untreated. Blood films, bone marrow biopsies and lymph node biopsies can be useful in diagnosis. Suramin can be used to treat both early-stage variants, though pentamidine is often used for T. gambiense disease. Neither drug penetrates the CNS and therefore, a lumbar puncture is necessary to diagnose late-stage disease. Melarsoprol, which can be used for the late stage of both diseases, carries a significant risk of encephalopathy and death. Eflornithine, which is safer, can only be used for late-stage T. gambiense disease.

Chagas’ disease

South American trypanosomiasis, or Chagas’ disease, is caused by the protozoa Trypanosoma cruzi. It is excreted in the faeces of the triatomine bugs and gains entry to the individual via the site of the triatomine bite. An iatrogenic spread has also been reported via organ and blood transfusions. As with African trypanosomiasis, there is an acute phase and a late phase. However, the acute early phase is often asymptomatic and there is a latency period of years between acute infection and chronic manifestations. Acute infection may cause fever, lymphadenopathy, and splenomegaly. A chagoma is a swelling of the skin related to parasite entry. Romaña’s sign involves periorbital swelling and conjunctivitis after ophthalmic parasite entry. Rarely, the acute phase can cause pericarditis and meningoencephalitis. This is more common in young children and immunosuppressed patients. Chronic disease leads to gastrointestinal tract pathology – megaoeseophagus and megacolon – and cardiac pathology – cardiomegaly and associated conduction abnormalities. The acute phase can generally be diagnosed using a blood film or serology. Early treatment with nifurtimox and benznidazole can prevent acute complications and reduce the risk of chronic infection. Chronic infection is more difficult to diagnose due to low level parasitaemia. The mainstay of treatment for chronic chagas disease involves managing complications. For example, the insertion of a pacemaker for a complete heart block. Xenodiagnosis is a valid method of establishing the diagnosis with low-level parasitaemia. Uninfected triatomine bugs are fed blood from suspected patients and then examined for evidence of parasites. This is not commonly used due to several factors, such as the incubation time needed for low-level parasite replication and the need for a supply of uninfected triatomine bugs.

References

• CDC leishmaniasis factsheet [Internet]. Cdc.gov [cited April 2022]. Available from: https://www.cdc.gov/dpdx/leishmaniasis/
• Mukhopadhyay D, Dalton J, Kaye P, Chatterjee M. Post kala-azar dermal leishmaniasis: an unresolved mystery. Trends Parasitol. 2014;30(2):65-74. doi:10.1016/j.pt.2013.12.004
• O’Dempsey T. Visceral leishmaniasis. In: Beeching N, Gill G, ed. by. Tropical Medicine Lecture Notes. 7th ed. West Sussex: Wiley Blackwell; 2014. p. 70-76
• CDC African trypanosomiasis factsheet [Internet]. Cdc.gov [cited April 2022]. Available from: https://www.cdc.gov/parasites/sleepingsickness/
• Lalloo D. African trypanosomiasis. In: Beeching N, Gill G, ed. by. Tropical Medicine Lecture Notes. 7th ed. West Sussex: Wiley Blackwell; 2014. p. 141-147
• Büscher P, Cecchi G, Jamonneau V, Priotto G. Human African trypanosomiasis. Lancet. 2017;390(10110):2397-2409. doi: 10.1016/S0140-6736(17)31510-6. Epub 2017 Jun 30
• CDC Chagas’ factsheet [Internet]. Cdc.gov [cited April 2022]. Available from: https://www.cdc.gov/parasites/chagas’/
• Echeverria L, Morillo C. American Trypanosomiasis (Chagas’ Disease). Infect Dis Clin North Am. 2019;33(1):119-134. doi: 10.1016/j.idc.2018.10.015
• Lalloo D. South American trypanosomiasis (Chagas’ disease). In: Beeching N, Gill G, ed. by. Tropical Medicine Lecture Notes. 7ᵗʰ ed. West Sussex: Wiley Blackwell; 2014. p. 148-150