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Parasitic Infections in HIV Infected Individuals: Diagnostic & Therapeutic Challenges

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Parasitic Infections in HIV Infected Individuals: Diagnostic & Therapeutic Challenges Review Article Indian J Med Res 134, December 2011, pp 878-897 Parasitic infections in HIV infected individuals: Diagnostic & therapeutic challenges Veeranoot Nissapatorn & Nongyao Sawangjaroen* Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia & *Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, Thailand Received September 13, 2011 After 30 years of the human immunodeficiency virus (HIV) epidemic, parasites have been one of the most common opportunistic infections (OIs) and one of the most frequent causes of morbidity and mortality associated with HIV-infected patients. Due to severe immunosuppression, enteric parasitic pathogens in general are emerging and are OIs capable of causing diarrhoeal disease associated with HIV. Of these, Cryptosporidium parvum and Isospora belli are the two most common intestinal protozoan parasites and pose a public health problem in acquired immunodeficiency syndrome (AIDS) patients. These are the only two enteric protozoan parasites that remain in the case definition of AIDS till today. Leismaniasis, strongyloidiasis and toxoplasmosis are the three main opportunistic causes of systemic involvements reported in HIV-infected patients. Of these, toxoplasmosis is the most important parasitic infection associated with the central nervous system. Due to its complexity in nature, toxoplasmosis is the only parasitic disease capable of not only causing focal but also disseminated forms and it has been included in AIDS-defining illnesses (ADI) ever since. With the introduction of highly active anti-retroviral therapy (HAART), cryptosporidiosis, leishmaniasis, schistosomiasis, strongyloidiasis, and toxoplasmosis are among parasitic diseases reported in association with immune reconstitution inflammatory syndrome (IRIS). This review addresses various aspects of parasitic infections in term of clinical, diagnostic and therapeutic challenges associated with HIV-infection. Key words AIDS - anti-parasitic treatment - diagnosis - HAART - HIV-infected individuals - IRIS - parasitic opportunistic infections Introduction epidemiological surveillances have further shown that there are an estimated 2.6 million (2.3-2.8 million) In 1981, the first patient diagnosed with acquired people newly infected with HIV. About 370,000 immunodeficiency syndrome (AIDS) in the USA was (230,000-510,000) children are newly infected with reported. The growing number of people living with HIV. It is also believed that there are 1.8 million (1.6- HIV has constantly been detected the world over and 2.1 million) annually AIDS-related deaths worldwide1. in particular from the three main continents, Asia, Opportunistic infections (OIs) are one of the existing South America and sub-Saharan Africa. In a global identified causes that aggravate the condition of HIV- report on AIDS epidemic, it is estimated that there are infected patients. Of these, parasites play an important 33.3 million (31.4-35.3 million) adults and children role as OIs and are one of the most common causes living with HIV around the world. The data from of morbidity and mortality in HIV/AIDS patients. The 878 NISSAPATORN & SAWANGJAROEN: PARASITIC INFECTIONS IN HIV-INFECTED INDIVIDUALS 879 spectrum of parasitic opportunistic infections (POIs) been reported in HIV-infected patients. Ascaris affecting HIV-infected individuals is divided into lumbricoides, hookworms, Trichuris trichiura and S. protozoa and helminthes (nematodes, cestodes, and stercoralis are intestinal helminthic infections, which trematodes). These POIs are not only associated with have also been reported in these patients9. These symptomatic HIV-infected patients but also are more enteric parasitic infections usually produce diarrhoeal evident with decreasing immune state (CD4+ cell count disease by infecting the small or large intestine, or < 200 cells/μl), which constitutes an ADI. Among POIs, both. They are also often found in children and adults cryptosporiosis, isosporidiosis and microsporidiosis are in tropical climates. Amoebiasis caused by infection the main enteric/intestinal parasitic infections, while with E. histolytica leads to bloody diarrhoea and leishmaniasis and toxoplasmosis are the main systemic hepatic disease. The other protozoa produce persistent POIs reported in HIV-infected patients. Of these, diarrhoea with or without malnutrition. Severe enteritis cryptosporiosis, isosporidiosis, and most importantly and chronic diarrhoea in HIV infected patients are toxoplasmosis with brain involvement are the three often documented as a consequence of multiple key parasitic diseases which have been included in opportunistic intestinal protozoa infections and can the Centers for Disease Control and prevention (CDC) result in significant morbidity and mortality10. case definitions for AIDS2. This review therefore aims to highlight the important issues pertaining to these Cryptosporidium spp., Isospora belli and POIs in term of clinical, diagnostic and therapeutic Microsporidium spp. challenges in HIV-infected patients. It also provides Cryptosporidiosis and isosporiasis have been a better understanding of clinical scenario and future categorized by CDC as ADI2. These are the two management of these POIs at the time of widely most common intestinal protozoan parasites causing access to the HAART, particularly in resource limited diarrhoea and pose a public health problem in AIDS settings. patients. Recent reports from France indicated the Intestinal or enteric parasites in HIV/AIDS increase of isosporiasis from 0.4 per 1000 patients patients in the pre-HAART era (1995-1996) to 4.4 per 1000 patients in the HAART era (2001-2003)11. The Diarrhoea in patients with AIDS is significantly prevalence of cryptosporidiosis varied according to 2,3 caused by intestinal parasites . The main aetiologic geographical locations. In Southeast Asia, the infective agents are intracellular protozoa, Isospora belli, rate of C. parvum is up to 40 per cent12. In clinical 4 Cryptosporidium parvum, and Cyclospora spp . cryptosporidiosis, chronic diarrhoea with watery stools, However, infection with other extracellular parasites weight loss and dehydration are the prominent features is also related to diarrhoeal disease in AIDS patients. in symptomatic patients13. Cryptosporidiosis occurs Among these parasites, Entamoeba histolytica, Giardia in AIDS patients when the CD4+ cell count is < 200 intestinalis and Strongyloides stercoralis are the most 14 5 cells/μl . Microsporidium is an obligate intracellular important . microorganism that was recently reclassified from Several studies have been carried out to determine protozoa to fungi. It has emerged as the causes of the presence of intestinal parasites in HIV patients. A OIs associated with diarrhoea and wasting in AIDS higher prevalence of intracellular parasites, particularly patients especially in developing countries where Cryptosporidium spp. and S. stercoralis was found in combination antiretroviral therapy (ART) is not HIV positive cases, than extracellular parasites6. Since always accessible15. Interestingly, most studies found cellular immunity is the major defense mechanism that Cryptosporidium spp. was the most common against intestinal parasitic infections7, the association intestinal parasitic co-infection with Microsporidium between intestinal parasites and individuals with spp14,16. Clinical symptoms and disease associated reduced immunity due to CD4+ T-lymphocyte reduction with microsporidiosis vary with the status of the host’s in HIV/AIDS is well predictable, particularly from immune system. Persistent diarrhoea, abdominal pain, cases presented with diarrhoea8. and weight loss are common clinical symptoms15. Intestinal protozoan parasites Higher prevalent rates of these intestinal parasitic infections are found related to CD4+ cell count of <100 C. parvum, E. histolytica, G. intestinalis, I. cells/μl17. With greater awareness and implementation belli and Microsporidium spp. (Fig. 1) are among of better diagnostic methods, it was demonstrated that intestinal protozoan infections which have commonly microsporidia contribute to a wide range of clinical 880 INDIAN J MED RES, DECEMbER 2011 Fig. 1. Microscopic images from clinical samples. (A) Oocysts of Cryptosporidium parvum from a stool sample (Modified acid-fast stain). (B) Trophozoite of Entamoeba histolytica from a fresh stool sample. (C) Trophozoite of Giardia intestinalis from a stool sample (Trichrome stain). (D) Oocyst of Isospora belli from a stool sample. (E) Spores of Microsporidiam spp. from a stool sample (Gram-chromotrope stain). (F) Oval-shaped Leishmania donovani amastigotes from a bone marrow aspirate (Giemsa stain). (G) Ring form of Plasmodium falciparum from a blood smear (Giemsa stain). (H) Trophozoites of Toxoplasma gondii from intra-peritoneal fluid (Giemsa stain). (I) Monomorphic trypomastigotes of Trypanosoma cruzi in a blood smear (Giensa stain). (J) Polymorphic trypomastigotes of Trypanosoma brucei gambiense in a blood smear (Giemsa stain). (K) Rhabditiform larva of Strongyloides stercoralis from a stool sample. (L) Cysticercus cellulosae (Carmine and fastgreen stain). (M) Egg of Schistosoma mansoni from a stool sample. (N) Egg of Schistosoma japonicum from a stool sample. (O) Egg of Schistosoma haematobium from a stool sample. Magnifications: (A-J)=1000 x, (K, L)=100 x, (M-O)=400 x. syndromes in HIV-infected individuals18. Therefore, A high prevalence of E. histolytica infection in primary
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