Endemic parasitic infections

Although not at first considered typical HIV-related opportunistic infections, endemic protozoan parasitic infection such as leishmaniasis, trypanosomiasis and malaria have increasingly become recognised as important co-infections in people with HIV infection (32).


 Leishmania spp. are protozoa that can cause a variety of clinical syndromes, including visceral, cutaneous and mucocutaneous forms of disease. Of particular importance is visceral leishmaniasis that been recognised as an important opportunistic infection in patients with HIV infection (33). Although rarely seen in Australia, it is one of the most common protozoan infections seen in people with HIV infection worldwide (34). It is found in almost a hundred countries across the tropics, subtropics and southern Europe. A number of different species exist in different geographic areas,  which result in different clinical manifestations (19).

 In endemic areas, the usual route of transmission is from the bite of an infected female sand fly. In parts of southern Europe, however, transmission has been reported in association with injecting-drug use (19, 35). The best way for travellers to protect themselves is by avoiding sand fly bites by using personal protective measures such as protective clothing and insect repellents.

 Clinical presentation

 Systemic visceral disease is the most common clinical presentation of leishmaniasis in people with HIV infection and is associated with advanced immunodeficiency (CD4+ T cell counts <200/μL). Onset may be in the context or primary infection or reactivation of latent infection. In contrast to immunocompetent individuals, isolated cutaneous disease is rare in HIV-infected individuals, although cutaneous involvement may accompany visceral disease (36). Systemic symptoms, such as fever and malaise are often seen along with lymphadenopathy and hepatosplenomegaly. Pancytopenia is another notable characteristic feature (19, 33).  Commonly involved organs include bone marrow, liver, spleen, lymph nodes, the gastrointestinal tract, and occasionally atypical sites such as the myocardium and adrenals (37, 38). While splenomegaly is often a defining feature in non-HIV infected individuals, it may be less pronounced in the setting of HIV infection (39)


 The standard investigation for diagnosing leishmaniasis in HIV co-infected patients is direct demonstration of parasites in blood smears (up to 50% sensitivity reported) (40), or tissue samples (scrapings, biopsies, bone marrow or splenic aspirates). PCR is also of value in diagnosis (41). Serological assays are commercially available, and while useful in immunocompetent individuals, the false positive rate is high in the context of HIV co-infection (42).


 The management of HIV-associated visceral leishmaniasis is extremely challenging, with high rates of relapse and mortality. Treatment has traditionally been with either pentavalent antimonial salts or amphotericin B, both of which are associated with significant toxicity. Liposomal amphotericin B is better tolerated and has increasingly become the drug of choice in HIV co-infected patients, although the optimal dosage has not been determined (19).  Oral miltefosine and parenteral paromomycin are alternative agents (43, 44), and programs in endemic regions are increasingly moving towards combination therapy (45). Prompt initiation of ART should be standard practice in this setting, although there is no leishmaniasis-specific data on the optimal timing of initiation. IRIS-type reactions have also been described (46).

 In cases of treatment failure or relapse, immunotherapy, including interferon-gamma and recombinant human granulocyte macrophage colony stimulating factor have been used experimentally as an adjunct to anti-leishmanial treatment (47, 48); however, supporting data are limited. Relapses are common and therefore secondary prophylaxis with an antileishmanial drug, administered at regular intervals, is recommended, particularly for patients with CD4+ T cell counts <200/μL (19, 49). The only published randomized control trial of secondary prophylaxis compared amphotericin B lipid complex in 8 patients to no prophylaxis in 9 patients, and reported that relapse rates were 50% versus 78%, respectively, after 1 year of follow up (50). There are limited data to guide the recommended duration of secondary prophylaxis but because of the high risk of disease relapse, some experts recommend indefinite prophylaxis (19).

 Chagas disease

 Chagas disease (American trypanosomiasis) is caused by the protozoa Trypanosoma cruzi, and is transmitted to humans by infected triatomine bugs, small insects that live in crevices of dirt walls and roofs of rural dwellings. They defaecate during or after feeding, usually at night. The parasite is present in the faeces of the infected bugs, and enter through the bite wound, or through mucous membranes. The disease is endemic in the Americas, and historically transmission has occurred largely in rural areas of Latin America. Cases of transmission following blood or organ transplantation, or from mother to infant, have also been described (51, 52). In the Australian context, exposure in a traveller is unlikely unless travel is planned to rural areas in endemic countries, or from receiving blood products in an area where blood screening is not universal (53).

 Clinical presentation

 In the acute phase of infection, patients may present with the characteristic Romana’s sign - unilateral periorbital oedema, sometimes with a non-specific febrile illness. At the end of this phase, as parasitemia levels fall, patients move into the chronic phase (19). Most patients with chronic infection are asymptomatic, and over the course of their lives around a third may progress to clinically evident Chagas disease, typically cardiomyopathy (52).  In the setting of HIV infection and associated immunodeficiency, Trypanosoma cruzi infection can reactivate to cause disease. The most common manifestation of this is meningoencephalitis, with or without brain abscess (chagoma). This presentation may be very similar clinically, and on radiological imaging, to toxoplasmosis and may be difficult to distinguish (54). The second most common manifestation in HIV-infected patients is acute myocarditis, although it is usually associated with concurrent CNS involvement (55, 56).


 Most people infected with Trypanosoma cruzi globally are in the chronic phase of infection and asymptomatic. Hence screening for asymptomatic infection is important in HIV-infected patients who have potentially been exposed because of the risk of reactivation of the infection. Diagnosis of chronic Trypanosoma cruzi infection is made using serological assays; however, there is no gold standard assay and interpretation of results can be challenging. Often, more than one assay may need to be performed based on different antigens and techniques. PCR is generally not useful due to variable primers and methods used, and also because results may be positive in chronic infection, even in the absence of infection reactivation (19).

 In the setting of a HIV-infected patient presenting with a CNS mass lesion, meningoencephalitis, arrythmia or heart failure, Chagas disease should be considered if there are epidemiological risk factors. A definitive diagnosis is made by direct identification of the parasite in tissue (such as brain biopsy), in CSF or in blood (55).


 Treatment of Chagas disease is specialised. Chemotherapy is usually with benznidazole or nifurtimox, which are effective in reducing parasitemia, but have limited efficacy in achieving parasitological cure. The duration of therapy in HIV co-infection is unclear and mortality is high for symptomatic reactivated Trypanosoma cruzi infection. The role of secondary prophylaxis or long-term suppression is also unknown. Timing of ART initiation in opportunistic infections of the CNS in HIV patients is often an important consideration due to the risk of an IRIS; however, no cases of Chagas disease-asociated IRIS have been described in the medical literature (19)


 There is a significant interaction between malaria and HIV infection. An increased frequency (one to two times higher) of both parasitaemia and clinical malaria is observed in HIV-infected adults, with increasing risk associated with worsening immunodeficiency, particularly when CD4+ T cell counts are <200 cells/μL (57-59). Data on the effect of malaria on maternal to child transmission of HIV in the pre-ART era are conflicting (60-62), but there is an increased risk of pre-term deliveries, low birthweight infants, and post-natal mortality.

 Pre-travel advice should be sought with a travel medicine specialist as risk can vary with different geographic locations and travel itineraries. Chemoprophylaxis and personal protective measures are recommended for those who may be exposed, and recommendations are the same as for HIV-negative individuals. Consideration should be given to potential drug interactions with antiretroviral drugs; for example, mefloquine is known to decrease plasma levels of nevirapine, ritonavir and possibly other protease inhibitors, while plasma levels of mefloquine may decrease when it is co-administered with efavirenz.