The Syphilis and Candida sections has been updated! For a summary of changes, see the What's New section.
Type your search term(s) in the text box. Users can only search one guideline at a time. To search for an exact phrase, use quotation marks (i.e. "what to start"). To narrow your search, add additional relevant terms. If you are not finding what you need, try searching similar terms (i.e. perinatal OR pregnancy) to broaden your search.
Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents
Geographic Opportunistic Infections of Specific Consideration
(Last updated: May 9, 2014; last reviewed: May 7, 2013)
Leishmaniasis is caused by obligate intracellular protozoa that survive and replicate in intracellular vacuoles within macrophages and other mononuclear cells. The Leishmania genus has traditionally been differentiated into multiple species that cause cutaneous, mucosal, and/or visceral disease.1,2
Leishmaniasis occurs in 98 countries or territories in the tropics, subtropics, and southern Europe with an estimated incidence of 1.5 million new cases annually—as many as 1.2 million cases of cutaneous leishmaniasis and 0.4 million cases of visceral leishmaniasis.3 As of March 2010, HIV-leishmaniasis co-infection has been reported in 35 countries, predominantly as visceral leishmaniasis.3,4 The first cases of HIV-leishmaniasis co-infection were described in Spain in the late 1980s. During the 1980s and 1990s, more than 90% of co-infection cases were reported in southern Europe.3,5 After the introduction of combination antiretroviral therapy (ART), the incidence has decreased substantially in developed countries,6,7 but HIV-leishmaniasis co-infection poses a growing problem in parts of Asia, Africa, and Latin America.3,4,8,9 In one large leishmaniasis specialty hospital in Bihar, India, the prevalence of HIV infection in patients with visceral leishmaniasis has increased from 0.88% in 2000 to 2.18% in 2006.3 In a study in a treatment center in Humera in northwestern Ethiopia, 31% of patients with visceral leishmaniasis were co-infected with HIV.10 Most leishmanial infections in immunocompetent hosts are asymptomatic. In many disease-endemic areas, 30% or more of the population has evidence of latent infection, as demonstrated by a positive leishmanin skin test.11-13 After primary infection, Leishmania remain viable in healthy individuals for long periods, leading to a population at risk of reactivation if immunosuppression occurs. In HIV-infected patients without severe immunosuppression, disease manifestations are similar to those in immunocompetent individuals. In those with advanced immunosuppression (i.e., CD4 T lymphocyte (CD4) cell count <200 cells/mm3), manifestations of leishmaniasis can be both atypical and more severe, and relapse after treatment—especially of visceral leishmaniasis—is common.14,15
In endemic areas, Leishmaniasis is usually spread by infected sand flies of the genera Phlebotomus and Lutzomyia.2 However, in Southern Europe, HIV and Leishmania infantum visceral co-infections were reported in association with injection-drug use, suggesting that Leishmania also may be acquired by needle sharing.16Leishmania parasites were demonstrated in 34% to 52% of used syringes discarded by injection-drug users in Madrid, and, based on molecular characteristics, investigators have described a new, epidemiologically significant leishmaniasis transmission cycle, relying on mechanical transfer of amastigotes via syringe.17,18
The term leishmaniasis encompasses multiple syndromes—most notably, cutaneous and visceral leishmaniasis, but also related syndromes, such as mucosal (or mucocutaneous) leishmaniasis, disseminated cutaneous leishmaniasis, diffuse cutaneous leishmaniasis (an anergic form), and post-kala-azar dermal leishmaniasis. The most common clinical presentation of leishmaniasis in HIV-infected individuals is a systemic visceral disease syndrome, but the distribution varies geographically, reflecting differences in the predominant parasite species. In Europe, visceral disease has been reported in 95% of cases (87% typical visceral, 8% atypical visceral).4,5 In contrast, in Brazil, mucosal, visceral, and cutaneous forms have accounted for 43%, 37%, and 20% of reported cases, respectively.19
In patients with HIV and visceral disease, the most common clinical and laboratory findings are fever (65%–100%), systemic malaise (70%–90%), splenomegaly (usually moderate) (60%–90%), hepatomegaly without splenomegaly (34%–85%), hepatosplenomegaly (68%–73%), lymphadenopathy (12%–57%), and pancytopenia (50%–80%).5,15 Anemia is usually marked, with <10g hemoglobin/dL (49%–100%); leukopenia moderate, with <2400 leukocytes/µL (56%–95%); and thrombocytopenia usually is present (52%–93%). Splenomegaly is less pronounced in HIV-co-infected patients than in immunocompetent patients with visceral leishmaniasis.15 In those with more profound immunosuppression, atypical manifestations have been described, including involvement of the upper and lower gastrointestinal tract, lung, pleural and peritoneal cavities, and skin.4-6,15,20 Esophageal involvement can lead to dysphagia and odynophagia, and must be distinguished from other causes of esophagitis in HIV-infected patients, such as candidiasis.5 Non-ulcerative cutaneous lesions that mimic Kaposi sarcoma (KS), nodular diffuse leishmaniasis, and post-kala-azar dermal leishmaniasis have been described.21-23 However, the presence of Leishmania amastigotes in skin can occur in the absence of lesions or in combination with other pathology, such as KS, and does not prove that the parasite is the cause of the lesions.24,25
Disfiguring mucosal lesions associated with anergy to Leishmania antigens have been observed in Europeans with AIDS, in contrast to mucocutaneous disease in immunocompetent patients, which is associated with strong leishmanin skin-test responses.20,26,27
Demonstration of Leishmania parasites by histopathology, cultures, and smears in tissue specimens (such as scrapings, aspirates, and biopsies) is the standard for diagnosing cutaneous leishmaniasis in HIV-co-infected patients.4,5
Visceral leishmaniasis also can be diagnosed by demonstration of leishmanial parasites in blood smears (approximately 50% sensitivity in expert hands), buffy-coat smear preparations, cultures from the peripheral blood, and smears or cultures from bone marrow or splenic aspirates. Other methods useful for demonstrating Leishmania in the blood or tissue of co-infected patients include detection of Leishmania nucleic acid by PCR amplification (>95% sensitivity).18
Serologic tests to detect antibodies against Leishmania antigens have high sensitivity to diagnose visceral leishmaniasis in immunocompetent patients.28 Serology should not be used as a screening test as positive serology can occur in individuals with asymptomatic infection. It should be used only as a confirmatory test in patients with a compatible clinical picture and exposure history suggestive of visceral leishmaniasis. Serology has a low sensitivity in HIV-infected patients, especially in Europe, such that parasitological diagnosis should be sought when clinical suspicion has been raised.4,5,29
The use of recombinant antigen in ELISA assays may increase sensitivity, but a proportion of co-infected patients remain seronegative.30 Immunoblotting with Leishmania infantum soluble antigen has been successful in detecting specific antileishmanial antibodies in up to 70% of European patients.29 Interestingly, reports suggest that the serology sensitivity may remain fairly high in HIV-co-infected patients in Ethiopia (77%-89% in HIV-visceral leishmaniasis co-infected patients, versus 87%-95% in HIV-negative patients).31 Leishmanial skin tests are nearly always negative in active visceral leishmaniasis, with or without HIV co-infection.2
Prevention of exposure to leishmanial infection relies on reservoir host control in areas with zoonotic transmission and vector control activities, such as indoor residual spraying and/or use of insecticide-treated bed nets. The best way for travelers to leishmaniasis-endemic areas to prevent infection is to protect themselves from sand fly bites. Personal protective measures include minimizing nocturnal outdoor activities, wearing protective clothing, and applying insect repellent to exposed skin.
Measures to decrease transmission of infectious agents in injection-drug users, such as the use of needle exchange programs, are appropriate.
Primary chemoprophylaxis to prevent leishmaniasis is not recommended, and no screening or preemptive therapy is appropriate for HIV-infected patients who may have been exposed to leishmanial infection. No vaccine against leishmaniasis is available.
For HIV-infected patients with visceral leishmaniasis, conventional and lipid formulations of amphotericin B appear to be at least as effective as pentavalent antimonials.4,32-35 Liposomal and lipid complex preparations of amphotericin B are typically better tolerated than conventional amphotericin B (amphotericin B deoxycholate) or pentavalent antimony (sodium stibogluconate).36-38 The equivalent efficacy and better toxicity profile have led most clinicians to regard liposomal amphotericin B as the drug of choice for visceral leishmaniasis in HIV-co-infected patients (AII).4,39 The optimal amphotericin B dosage has not been determined.39,40 Regimens with efficacy include liposomal preparations of 2 to 4 mg/kg body weight administered on consecutive days or in an interrupted schedule (e.g., 4 mg/kg on days 1–5, 10, 17, 24, 31, and 38) to achieve a total cumulative dose of 20 to 60 mg/kg body weight (AII), or amphotericin B deoxycholate, 0.5 to 1.0 mg/kg body weight/day intravenously (IV), to achieve a total dose of 1.5 to 2.0 g (BII).32,35,39,41-43 Pentavalent antimony (sodium stibogluconate), which is available in the United States through the Centers for Disease Control and Prevention (CDC), 20 mg/kg/day IV or intramuscular (IM) for 28 consecutive days, may be considered as an alternative (BII).
Additional treatment options for visceral leishmaniasis in HIV-co-infected patients include oral miltefosine and parenteral paromomycin. Miltefosine is an oral antileishmanial agent currently available outside the United States and may be used under individual investigational new drug protocols in the United States. Consultations and drug requests should be addressed to CDC Parasitic Diseases Inquiries (404-718-4745; firstname.lastname@example.org), the CDC Drug Service (404-639-3670; email@example.com) and; for emergencies after business hours, on weekends, and federal holidays; through the CDC Emergency Operations Center (770-488-7100).
Cure rates for visceral leishmaniasis in HIV-negative patients are reported to be approximately 95%.44 In Ethiopia, HIV-co-infected patients treated with miltefosine had lower initial cure rates, compared with those treated with pentavalent antimony (sodium stibogluconate) (78% vs. 90%), but also lower mortality.45 The adult dose is 100 mg daily for 4 weeks. Data supporting the use of miltefosine in HIV-co-infected patients are limited, but it can be used for treatment of visceral leishmaniasis in Europe under a compassionate use protocol (CIII).46 Gastrointestinal symptoms are common but they rarely limit treatment. Paromomycin, an aminoglycoside which is available outside the United States, has been shown to be used successfully in a small number of HIV-negative visceral leishmaniasis patients in India and is now in use in several countries.40 No efficacy data currently are available for paromomycin in HIV-co-infected patients. A recent trial of combination therapy (liposomal amphotericin plus miltefosine or paromomycin; miltefosine plus paromomycin) produced promising results in patients in India whose visceral leishmaniasis was not severe.47 Further research is needed to validate the efficacy of these regimens in severe disease in visceral leishmaniasis in other geographic regions, and in HIV-co-infected patients.
Few systematic data are available on the efficacy of treatment for cutaneous, mucocutaneous, or diffuse cutaneous leishmaniasis in HIV-co-infected patients. On the basis of data in HIV-negative patients with cutaneous leishmaniasis and case reports in HIV-co-infected patients, HIV-infected patients should be treated with liposomal amphotericin B (BIII), as previously outlined,48 or pentavalent antimony (sodium stibogluconate), depending on the form of the disease and the clinical response (BIII).2,49,50 However, pentavalent antimony can increase viral transcription and HIV replication in cultures of human peripheral blood mononuclear cells, raising concerns about its use in HIV-infected patients.51
Potential alternatives for cutaneous leishmaniasis include miltefosine, topical paromomycin, intralesional pentavalent antimony, and local heat therapy; however, no data exist for co-infected patients and in immunocompetent patients, the effectiveness of these modalities is known to be dependent upon the infecting species of Leishmania.40,52-54
Special Considerations with Regard to Starting ART
ART should be initiated or optimized following standard practice for HIV-infected patients (AIII). There are no leishmaniasis-specific data on when to start ART. Appropriate use of ART has substantially improved the survival of co-infected patients in Europe and decreases the likelihood of relapse after antileishmanial therapy.7,15,55 Therefore, ART should be started as soon as patients are able to tolerate it (AIII).
Monitoring of Response to Therapy and Adverse Events (Including IRIS)
Patients treated with liposomal amphotericin B should be monitored for dose-dependent nephrotoxicity, electrolyte disturbances, and infusion-related adverse reactions (AII). Infusional adverse events are ameliorated by pretreatment with acetaminophen, diphenhydramine, or limited doses of corticosteroids (BII). Infusion of 1 L of saline over an hour before drug infusion can help reduce the risk of glomerular function decline during treatment (BIII). The frequency of nephrotoxicity is lower for liposomal or lipid-associated preparations than for amphotericin B deoxycholate.37 Amphotericin B deoxycholate treatment is also associated with an increased risk of anemia.33
Patients receiving pentavalent antimony (sodium stibogluconate) should be monitored closely for adverse reactions.49 Overall, at a dose of 20 mg/kg of body weight per day, greater than 60% of patients have 1 or more of the following reactions: thrombophlebitis, anorexia, myalgia, arthralgia, abdominal pain, elevation of liver transaminases, amylase or lipase, and (in some patients) clinical pancreatitis. Weekly electrocardiograms are recommended during treatment, with vigilance for changes that may indicate early cardiotoxicity, such as prolonged QT intervals and T-wave inversion (CIII). Rarely, arrhythmias and sudden death have occurred.33,41 Severe adverse reactions to pentavalent antimony (sodium stibogluconate), including acute pancreatitis and leukopenia, appear to be more common in co-infected patients than in those who are not infected with HIV.56
Cases of newly symptomatic visceral and cutaneous leishmaniasis have been reported in association with the immune reconstitution inflammatory syndrome (IRIS) following initiation of ART.57,58 Several of these cases have resembled post-kala-azar dermal leishmaniasis or disseminated cutaneous leishmaniasis.59-62 Existing experience with IRIS-associated leishmaniasis, however, is insufficient to provide data for specific management guidelines.
Managing Treatment Failure
For patients who fail to respond to initial therapy or experience a relapse after initial treatment, a repeat course of the initial regimen, or one of the recommended alternatives for initial therapy should be used, as previously outlined (AIII). The response rate for retreatment appears to be similar to that for initial therapy, although some patients evolve to a chronic disease state with serial relapses despite aggressive acute and maintenance therapies.
Immunotherapy, including interferon-gamma and recombinant human granulocyte macrophage colony stimulating factor (GM-CSF), has been used experimentally as an adjunct to antileishmanial treatment for refractory cases.63,64 However, a clinical trial of pentavalent antimony (sodium stibogluconate) plus interferon-gamma for visceral leishmaniasis in HIV-co-infected patients was suspended when an interim analysis indicated that there was no advantage over pentavalent antimony (sodium stibogluconate) alone.41 In addition, the use of interferon-gamma was reported to be associated with acceleration of KS in two patients with visceral leishmaniasis and HIV co-infection.24
Relapses, particularly of visceral leishmaniasis and disseminated cutaneous leishmaniasis, are common after cessation of anti-leishmanial therapy in HIV-infected patients, and frequency of relapse is inversely related to CD4 cell count. In HIV-co-infected patients with visceral leishmaniasis who were not receiving or responding to ART, the risk of relapse at 6 and 12 months was 60% and 90%, respectively, in the absence of secondary prophylaxis (chronic maintenance therapy).5,65 Therefore, secondary prophylaxis with an effective antileishmanial drug, administered at least every 2 to 4 weeks, is recommended, particularly for patients with visceral leishmaniasis and CD4 cell counts <200 cells/µL (AII).5,15,34,65
The only published, randomized trial of secondary prophylaxis compared amphotericin B lipid complex (3 mg/kg every 21 days) in 8 patients to no prophylaxis in 9 patients; this trial reported relapse rates of 50% versus 78%, respectively, after 1 year of follow-up.34 In retrospective observational studies, monthly pentavalent antimony (sodium stibogluconate) or lipid formulations of amphotericin every 2 to 4 weeks were also associated with decreased relapse rates.15,65 Liposomal amphotericin B (4 mg/kg every 2–4 weeks) or amphotericin B lipid complex (3 mg/kg every 21 days) should be used for secondary prophylaxis (AII). Pentavalent antimony (sodium stibogluconate), 20 mg/kg IV or IM every 4 weeks, is an alternative (BII). Although pentamidine is no longer recommended to treat primary visceral leishmaniasis, it has been suggested as another alternative for secondary prophylaxis in a dosage of 6 mg/kg IV every 2 to 4 weeks (CIII).66 Allopurinol, in a dose of 300 mg orally 3 times daily, used for maintenance therapy is less effective than monthly pentavalent antimony and is not recommended (BII).65 Although no published data on efficacy are available, maintenance therapy may be indicated for immunocompromised patients with cutaneous leishmaniasis who have multiple relapses after adequate treatment (CIII).
When to Stop Secondary Prophylaxis
Some investigators suggest that secondary antileishmanial prophylaxis can be discontinued in patients whose CD4 count is >200 to 350 cells/mm3 in response to ART.67 Others, however, suggest that secondary prophylaxis should be maintained indefinitely. In one study, a positive peripheral blood PCR for leishmania correlated with a high risk of relapse.68 Thus, because there are so little published data or clinical trial experience, no recommendation can be made regarding discontinuation of secondary prophylaxis in HIV-leishmania-co-infected persons.
Special Considerations During Pregnancy
Diagnostic considerations are the same in pregnant women as in women who are not pregnant. One study suggests that lesions of cutaneous leishmaniasis may be larger and more likely to be exophytic in pregnancy, and that untreated cutaneous leishmaniasis may be associated with an increased risk of preterm delivery and stillbirth.69 Labels for pentavalent antimony compounds (sodium stibogluconate, available in the United States through CDC, and meglumine antimoniate) state that these drugs are contraindicated for use in pregnant women, although various antimonial compounds were not teratogenic in chickens, rats, or sheep.70-72 Good clinical and pregnancy outcomes have been reported for small series of pregnant women treated with meglumine antimoniate, amphotericin B deoxycholate, or liposomal amphotericin B.73-76 Retrospective analyses suggest that rates of preterm birth and spontaneous abortion may be increased in women with visceral leishmaniasis during pregnancy, especially in the first trimester and when antimonial drugs are used.77,78 Because visceral leishmaniasis is a potentially lethal disease, postponing treatment until after delivery is not an option. Liposomal amphotericin B is the first choice for therapy of visceral leishmaniasis in pregnancy because of concerns about toxicity and lack of experience with use of pentavalent antimony compounds in human pregnancy (AIII).74 The alternatives are amphotericin B deoxycholate (AIII) or pentavalent antimony (sodium stibogluconate) (AIII). Miltefosine is teratogenic and is contraindicated in pregnancy.40 Perinatal transmission of Leishmania spp. is rare; 13 documented cases have been reported.77,79-81 No data are available on the risk of transmission of Leishmania spp. in HIV-infected pregnant women.
Recommendations for Treating Visceral and Cutaneous Leishmaniasis
Treating Visceral Leishmaniasis
Liposomal amphotericin B 2–4 mg/kg IV daily (AII), or
Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on days 1–5, 10, 17, 24, 31, 38) (AII)
Achieve a total dose of 20–60 mg/kg (AII)
Other amphotericin B lipid complex dosed as above, or
Amphotericin B deoxycholate 0.5–1.0 mg/kg IV daily for total dose of 1.5–2.0 grams (BII), or
Pentavalent antimony (Sodium stibogluconate) 20 mg/kg IV or IM daily for 28 days (BII). (Contact the CDC Drug Service at 404-639-3670; firstname.lastname@example.org; for emergencies, call 770-488-7100)
Miltefosine 100 mg PO daily for 4 weeks (CIII). Requires individual IND; consultation should be addressed to CDC Parasitic Diseases Inquiries (404-718-4745; email@example.com) or the CDC Drug Service (404-7639-3670; firstname.lastname@example.org; for emergencies, call 770-488-7100)
Chronic Maintenance Therapy for Visceral Leishmaniasis
For patients with visceral leishmaniasis and CD4 count <200 cells/mm3 (AII)
Liposomal amphotericin B 4 mg/kg every 2–4 weeks (AII), or
Amphotericin B Lipid Complex 3 mg/kg every 21 days (AII)
Pentavalent antimony (Sodium stibogluconate) 20 mg/kg IV or IM every 4 weeks (BII)
Discontinuation of Chronic Maintenance Therapy
Some investigators suggest that therapy can be discontinued after sustained (>3 to 6 months) increase in CD4 count to >200 to 350 cells/mm3 in response to ART, but others suggest that therapy should be continued indefinitely. Therefore, no recommendation can be made regarding discontinuation of chronic maintenance therapy.
Treating Cutaneous Leishmaniasis
Liposomal amphotericin B 2–4 mg/kg IV daily for 10 days or interrupted schedule (e.g., 4 mg/kg on days 1–5, 10, 17, 24, 31, 38) to achieve total dose of 20–60 mg/kg (BIII), or
Pentavalent antimony (Sodium stibogluconate) 20 mg/kg IV or IM daily for 28 days (BIII)
Other options include oral miltefosine (can be obtained in the United States through a treatment IND), topical paromomycin, intralesional pentavalent antimony (sodium stibogluconate), or local heat therapy
Chronic Maintenance Therapy for Cutaneous Leishmaniasis
May be indicated for immunocompromised patients with multiple relapses (CIII)
Key to Acronyms: ART = antiretroviral therapy; CD4 = CD4 T lymphocyte cell; CDC = the Centers for Disease Control and Prevention; IM = intramuscular; IND = investigational new drug; IV = intravenous
Desjeux P. Leishmaniasis: current situation and new perspectives. Comparative immunology, microbiology and infectious diseases. Sep 2004;27(5):305-318. Available at http://www.ncbi.nlm.nih.gov/pubmed/15225981.
Jeronimo SMB, de Queiroz Sousa A, Pearson RD. Leishmaniasis. In: Guerrant RL, Walker DH, Weller PF, eds. Tropical infectious diseases: principles, pathogens and practice. Edinburgh, Scotland: Churchill Livingstone Elsevier; 2006:1095-1113.
World Health Organization. Leishmaniasis. Available at http://www.who.int/leishmaniasis/burden/en/. Accessed March 21, 2013.
Murray HW. Leishmaniasis in the United States: treatment in 2012. Am J Trop Med Hyg. Mar 2012;86(3):434-440. Available at http://www.ncbi.nlm.nih.gov/pubmed/22403313.
Alvar J, Canavate C, Gutierrez-Solar B, et al. Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin Microbiol Rev. Apr 1997;10(2):298-319. Available at http://www.ncbi.nlm.nih.gov/pubmed/9105756.
Rosenthal E, Marty P, del Giudice P, et al. HIV and Leishmania coinfection: a review of 91 cases with focus on atypical locations of Leishmania. Clin Infect Dis. Oct 2000;31(4):1093-1095. Available at http://www.ncbi.nlm.nih.gov/pubmed/11049794.
Tortajada C, Perez-Cuevas B, Moreno A, et al. Highly active antiretroviral therapy (HAART) modifies the incidence and outcome of visceral leishmaniasis in HIV-infected patients. J Acquir Immune Defic Syndr. Jul 1 2002;30(3):364-366. Available at http://www.ncbi.nlm.nih.gov/pubmed/12131576.
Mathur P, Samantaray JC, Vajpayee M, Samanta P. Visceral leishmaniasis/human immunodeficiency virus co-infection in India: the focus of two epidemics. Journal of medical microbiology. Jul 2006;55(Pt 7):919-922. Available at http://www.ncbi.nlm.nih.gov/pubmed/16772420.
Wolday D, Berhe N, Akuffo H, Desjeux P, Britton S. Emerging Leishmania/HIV co-infection in Africa. Medical microbiology and immunology. Nov 2001;190(1-2):65-67. Available at http://www.ncbi.nlm.nih.gov/pubmed/11770113.
ter Horst R, Collin SM, Ritmeijer K, Bogale A, Davidson RN. Concordant HIV infection and visceral leishmaniasis in Ethiopia: the influence of antiretroviral treatment and other factors on outcome. Clin Infect Dis. Jun 1 2008;46(11):1702-1709. Available at http://www.ncbi.nlm.nih.gov/pubmed/18419422.
Marty P, Le Fichoux Y, Giordana D, Brugnetti A. Leishmanin reaction in the human population of a highly endemic focus of canine leishmaniasis in Alpes-Maritimes, France. Trans R Soc Trop Med Hyg. May-Jun 1992;86(3):249-250. Available at http://www.ncbi.nlm.nih.gov/pubmed/1412644.
Moral L, Rubio EM, Moya M. A leishmanin skin test survey in the human population of l'Alacanti region (Spain): implications for the epidemiology of Leishmania infantum infection in southern Europe. Trans R Soc Trop Med Hyg. Mar-Apr 2002;96(2):129-132. Available at http://www.ncbi.nlm.nih.gov/pubmed/12055798.
Werneck GL, Rodrigues L, Santos MV, et al. The burden of Leishmania chagasi infection during an urban outbreak of visceral leishmaniasis in Brazil. Acta Trop. Jul 2002;83(1):13-18. Available at http://www.ncbi.nlm.nih.gov/pubmed/12062788.
Lopez-Velez R, Perez-Molina JA, Guerrero A, et al. Clinicoepidemiologic characteristics, prognostic factors, and survival analysis of patients coinfected with human immunodeficiency virus and Leishmania in an area of Madrid, Spain. Am J Trop Med Hyg. Apr 1998;58(4):436-443. Available at http://www.ncbi.nlm.nih.gov/pubmed/9574788.
Pintado V, Martin-Rabadan P, Rivera ML, Moreno S, Bouza E. Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study. Medicine (Baltimore). Jan 2001;80(1):54-73. Available at http://www.ncbi.nlm.nih.gov/pubmed/11204503.
Alvar J, Jimenez M. Could infected drug-users be potential Leishmania infantum reservoirs? AIDS. Jun 1994;8(6):854. Available at http://www.ncbi.nlm.nih.gov/pubmed/8086149.
Chicharro C, Morales MA, Serra T, Ares M, Salas A, Alvar J. Molecular epidemiology of Leishmania infantum on the island of Majorca: a comparison of phenotypic and genotypic tools. Trans R Soc Trop Med Hyg. Apr 2002;96 Suppl 1:S93-99. Available at http://www.ncbi.nlm.nih.gov/pubmed/12055859.
Cruz I, Morales MA, Noguer I, Rodriguez A, Alvar J. Leishmania in discarded syringes from intravenous drug users. Lancet. Mar 30 2002;359(9312):1124-1125. Available at http://www.ncbi.nlm.nih.gov/pubmed/11943264.
Rabello A, Orsini M, Disch J. Leishmania/HIV co-infection in Brazil: an appraisal. Ann Trop Med Parasitol. Oct 2003;97 Suppl 1:17-28. Available at http://www.ncbi.nlm.nih.gov/pubmed/14678630.
Mota Sasaki M, Matsumo Carvalho M, Schmitz Ferreira ML, Machado MP. Cutaneous Leishmaniasis Coinfection in AIDS Patients: Case Report and Literature Review. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases. Jun 1997;1(3):142-144. Available at http://www.ncbi.nlm.nih.gov/pubmed/11105130.
Gonzalez-Beato MJ, Moyano B, Sanchez C, et al. Kaposi's sarcoma-like lesions and other nodules as cutaneous involvement in AIDS-related visceral leishmaniasis. The British journal of dermatology. Dec 2000;143(6):1316-1318. Available at http://www.ncbi.nlm.nih.gov/pubmed/11122042.
Carnauba D, Jr., Konishi CT, Petri V, Martinez IC, Shimizu L, Pereira-Chioccola VL. Atypical disseminated leishmaniasis similar to post-kala-azar dermal leishmaniasis in a Brazilian AIDS patient infected with Leishmania (Leishmania) infantum chagasi: a case report. Int J Infect Dis. Nov 2009;13(6):e504-507. Available at http://www.ncbi.nlm.nih.gov/pubmed/19447660.
Lindoso JA, Barbosa RN, Posada-Vergara MP, et al. Unusual manifestations of tegumentary leishmaniasis in AIDS patients from the New World. The British journal of dermatology. Feb 2009;160(2):311-318. Available at http://www.ncbi.nlm.nih.gov/pubmed/19187345.
Albrecht H, Stellbrink HJ, Gross G, Berg B, Helmchen U, Mensing H. Treatment of atypical leishmaniasis with interferon gamma resulting in progression of Kaposi's sarcoma in an AIDS patient. The Clinical investigator. Dec 1994;72(12):1041-1047. Available at http://www.ncbi.nlm.nih.gov/pubmed/7711412.
Bosch RJ, Rodrigo AB, Sanchez P, de Galvez MV, Herrera E. Presence of Leishmania organisms in specific and non-specific skin lesions in HIV-infected individuals with visceral leishmaniasis. International journal of dermatology. Oct 2002;41(10):670-675. Available at http://www.ncbi.nlm.nih.gov/pubmed/12390190.
Canovas DL, Carbonell J, Torres J, Altes J, Buades J. Laryngeal leishmaniasis as initial opportunistic disease in HIV infection. The Journal of laryngology and otology. Dec 1994;108(12):1089-1092. Available at http://www.ncbi.nlm.nih.gov/pubmed/7861090.
Miralles ES, Nunez M, Hilara Y, Harto A, Moreno R, Ledo A. Mucocutaneous leishmaniasis and HIV. Dermatology. 1994;189(3):275-277. Available at http://www.ncbi.nlm.nih.gov/pubmed/7949483.
Sundar S, Rai M. Laboratory diagnosis of visceral leishmaniasis. Clin Diagn Lab Immunol. Sep 2002;9(5):951-958. Available at http://www.ncbi.nlm.nih.gov/pubmed/12204943.
Medrano FJ, Canavate C, Leal M, Rey C, Lissen E, Alvar J. The role of serology in the diagnosis and prognosis of visceral leishmaniasis in patients coinfected with human immunodeficiency virus type-1. Am J Trop Med Hyg. Jul 1998;59(1):155-162. Available at http://www.ncbi.nlm.nih.gov/pubmed/9684645.
Houghton RL, Petrescu M, Benson DR, et al. A cloned antigen (recombinant K39) of Leishmania chagasi diagnostic for visceral leishmaniasis in human immunodeficiency virus type 1 patients and a prognostic indicator for monitoring patients undergoing drug therapy. J Infect Dis. May 1998;177(5):1339-1344. Available at http://www.ncbi.nlm.nih.gov/pubmed/9593022.
ter Horst R, Tefera T, Assefa G, Ebrahim AZ, Davidson RN, Ritmeijer K. Field evaluation of rK39 test and direct agglutination test for diagnosis of visceral leishmaniasis in a population with high prevalence of human immunodeficiency virus in Ethiopia. Am J Trop Med Hyg. Jun 2009;80(6):929-934. Available at http://www.ncbi.nlm.nih.gov/pubmed/19478251.
Davidson RN, Di Martino L, Gradoni L, et al. Liposomal amphotericin B (AmBisome) in Mediterranean visceral leishmaniasis: a multi-centre trial. The Quarterly journal of medicine. Feb 1994;87(2):75-81. Available at http://www.ncbi.nlm.nih.gov/pubmed/8153291.
Laguna F, Lopez-Velez R, Pulido F, et al. Treatment of visceral leishmaniasis in HIV-infected patients: a randomized trial comparing meglumine antimoniate with amphotericin B. Spanish HIV-Leishmania Study Group. AIDS. Jun 18 1999;13(9):1063-1069. Available at http://www.ncbi.nlm.nih.gov/pubmed/10397536.
Lopez-Velez R, Videla S, Marquez M, et al. Amphotericin B lipid complex versus no treatment in the secondary prophylaxis of visceral leishmaniasis in HIV-infected patients. J Antimicrob Chemother. Mar 2004;53(3):540-543. Available at http://www.ncbi.nlm.nih.gov/pubmed/14739148.
Russo R, Nigro LC, Minniti S, et al. Visceral leishmaniasis in HIV infected patients: treatment with high dose liposomal amphotericin B (AmBisome). J Infect. Mar 1996;32(2):133-137. Available at http://www.ncbi.nlm.nih.gov/pubmed/8708370.
Lazanas MC, Tsekes GA, Papandreou S, et al. Liposomal amphotericin B for leishmaniasis treatment of AIDS patients unresponsive to antimonium compounds. AIDS. Jul 1993;7(7):1018-1019. Available at http://www.ncbi.nlm.nih.gov/pubmed/8357549.
Sundar S, Mehta H, Suresh AV, Singh SP, Rai M, Murray HW. Amphotericin B treatment for Indian visceral leishmaniasis: conventional versus lipid formulations. Clin Infect Dis. Feb 1 2004;38(3):377-383. Available at http://www.ncbi.nlm.nih.gov/pubmed/14727208.
Torre-Cisneros J, Villanueva JL, Kindelan JM, Jurado R, Sanchez-Guijo P. Successful treatment of antimony-resistant visceral leishmaniasis with liposomal amphotericin B in patients infected with human immunodeficiency virus. Clin Infect Dis. Oct 1993;17(4):625-627. Available at http://www.ncbi.nlm.nih.gov/pubmed/8268341.
Bern C, Adler-Moore J, Berenguer J, et al. Liposomal amphotericin B for the treatment of visceral leishmaniasis. Clin Infect Dis. Oct 1 2006;43(7):917-924. Available at http://www.ncbi.nlm.nih.gov/pubmed/16941377.
Alvar J, Croft S, Olliaro P. Chemotherapy in the treatment and control of leishmaniasis. Advances in parasitology. 2006;61:223-274. Available at http://www.ncbi.nlm.nih.gov/pubmed/16735166.
Laguna F, Videla S, Jimenez-Mejias ME, et al. Amphotericin B lipid complex versus meglumine antimoniate in the treatment of visceral leishmaniasis in patients infected with HIV: a randomized pilot study. J Antimicrob Chemother. Sep 2003;52(3):464-468. Available at http://www.ncbi.nlm.nih.gov/pubmed/12888588.
Meyerhoff A. U.S. Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis. Clin Infect Dis. Jan 1999;28(1):42-48; discussion 49-51. Available at http://www.ncbi.nlm.nih.gov/pubmed/10028069.
Laguna F, Torre-Cisneros J, Moreno V, Villanueva JL, Valencia E. Efficacy of intermittent liposomal amphotericin B in the treatment of visceral leishmaniasis in patients infected with human immunodeficiency virus. Clin Infect Dis. Sep 1995;21(3):711-712. Available at http://www.ncbi.nlm.nih.gov/pubmed/8527591.
Sundar S, Jha TK, Thakur CP, Bhattacharya SK, Rai M. Oral miltefosine for the treatment of Indian visceral leishmaniasis. Trans R Soc Trop Med Hyg. Dec 2006;100 Suppl 1:S26-33. Available at http://www.ncbi.nlm.nih.gov/pubmed/16730038.
Ritmeijer K, Dejenie A, Assefa Y, et al. A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection. Clin Infect Dis. Aug 1 2006;43(3):357-364. Available at http://www.ncbi.nlm.nih.gov/pubmed/16804852.
Sindermann H, Engel KR, Fischer C, Bommer W, Miltefosine Compassionate Use P. Oral miltefosine for leishmaniasis in immunocompromised patients: compassionate use in 39 patients with HIV infection. Clin Infect Dis. Nov 15 2004;39(10):1520-1523. Available at http://www.ncbi.nlm.nih.gov/pubmed/15546090.
Sundar S, Sinha PK, Rai M, et al. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet. Feb 5 2011;377(9764):477-486. Available at http://www.ncbi.nlm.nih.gov/pubmed/21255828.
Wortmann G, Zapor M, Ressner R, et al. Lipsosomal amphotericin B for treatment of cutaneous leishmaniasis. Am J Trop Med Hyg. Nov 2010;83(5):1028-1033. Available at http://www.ncbi.nlm.nih.gov/pubmed/21036832.
Herwaldt BL, Berman JD. Recommendations for treating leishmaniasis with sodium stibogluconate (Pentostam) and review of pertinent clinical studies. Am J Trop Med Hyg. Mar 1992;46(3):296-306. Available at http://www.ncbi.nlm.nih.gov/pubmed/1313656.
Reithinger R, Dujardin JC, Louzir H, Pirmez C, Alexander B, Brooker S. Cutaneous leishmaniasis. Lancet Infect Dis. Sep 2007;7(9):581-596. Available at http://www.ncbi.nlm.nih.gov/pubmed/17714672.
Barat C, Zhao C, Ouellette M, Tremblay MJ. HIV-1 replication is stimulated by sodium stibogluconate, the therapeutic mainstay in the treatment of leishmaniasis. J Infect Dis. Jan 15 2007;195(2):236-245. Available at http://www.ncbi.nlm.nih.gov/pubmed/17191169.
Belay AD, Asafa Y, Mesure J, Davidson RN. Successful miltefosine treatment of post-kala-azar dermal leishmaniasis occurring during antiretroviral therapy. Ann Trop Med Parasitol. Apr 2006;100(3):223-227. Available at http://www.ncbi.nlm.nih.gov/pubmed/16630379.
Reithinger R, Mohsen M, Wahid M, et al. Efficacy of thermotherapy to treat cutaneous leishmaniasis caused by Leishmania tropica in Kabul, Afghanistan: a randomized, controlled trial. Clin Infect Dis. Apr 15 2005;40(8):1148-1155. Available at http://www.ncbi.nlm.nih.gov/pubmed/15791515.
Soto J, Arana BA, Toledo J, et al. Miltefosine for new world cutaneous leishmaniasis. Clin Infect Dis. May 1 2004;38(9):1266-1272. Available at http://www.ncbi.nlm.nih.gov/pubmed/15127339.
de la Rosa R, Pineda JA, Delgado J, et al. Influence of highly active antiretroviral therapy on the outcome of subclinical visceral leishmaniasis in human immunodeficiency virus-infected patients. Clin Infect Dis. Feb 15 2001;32(4):633-635. Available at http://www.ncbi.nlm.nih.gov/pubmed/11181128.
Delgado J, Macias J, Pineda JA, et al. High frequency of serious side effects from meglumine antimoniate given without an upper limit dose for the treatment of visceral leishmaniasis in human immunodeficiency virus type-1-infected patients. Am J Trop Med Hyg. Nov 1999;61(5):766-769. Available at http://www.ncbi.nlm.nih.gov/pubmed/10586909.
Berry A, Abraham B, Dereure J, Pinzani V, Bastien P, Reynes J. Two case reports of symptomatic visceral leishmaniasis in AIDS patients concomitant with immune reconstitution due to antiretroviral therapy. Scandinavian journal of infectious diseases. 2004;36(3):225-227. Available at http://www.ncbi.nlm.nih.gov/pubmed/15119371.
Posada-Vergara MP, Lindoso JA, Tolezano JE, Pereira-Chioccola VL, Silva MV, Goto H. Tegumentary leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome in 2 patients with AIDS. J Infect Dis. Nov 15 2005;192(10):1819-1822. Available at http://www.ncbi.nlm.nih.gov/pubmed/16235183.
Chrusciak-Talhari A, Ribeiro-Rodrigues R, Talhari C, et al. Tegumentary leishmaniasis as the cause of immune reconstitution inflammatory syndrome in a patient co-infected with human immunodeficiency virus and Leishmania guyanensis. Am J Trop Med Hyg. Oct 2009;81(4):559-564. Available at http://www.ncbi.nlm.nih.gov/pubmed/19815866.
Sinha S, Fernandez G, Kapila R, Lambert WC, Schwartz RA. Diffuse cutaneous leishmaniasis associated with the immune reconstitution inflammatory syndrome. International journal of dermatology. Dec 2008;47(12):1263-1270. Available at http://www.ncbi.nlm.nih.gov/pubmed/19126013.
Tadesse A, Hurissa Z. Leishmaniasis (PKDL) as a case of immune reconstitution inflammatory syndrome (IRIS) in HIV-positive patient after initiation of anti-retroviral therapy (ART). Ethiopian medical journal. Jan 2009;47(1):77-79. Available at http://www.ncbi.nlm.nih.gov/pubmed/19743785.
Antinori S, Longhi E, Bestetti G, et al. Post-kala-azar dermal leishmaniasis as an immune reconstitution inflammatory syndrome in a patient with acquired immune deficiency syndrome. The British journal of dermatology. Nov 2007;157(5):1032-1036. Available at http://www.ncbi.nlm.nih.gov/pubmed/17854365.
Badaro R, Johnson WD, Jr. The role of interferon-gamma in the treatment of visceral and diffuse cutaneous leishmaniasis. J Infect Dis. Mar 1993;167 Suppl 1(Suppl 1):S13-17. Available at http://www.ncbi.nlm.nih.gov/pubmed/8433014.
Badaro R, Nascimento C, Carvalho JS, et al. Granulocyte-macrophage colony-stimulating factor in combination with pentavalent antimony for the treatment of visceral Leishmaniasis. Eur J Clin Microbiol Infect Dis. 1994;13 Suppl 2:S23-28. Available at http://www.ncbi.nlm.nih.gov/pubmed/7875148.
Ribera E, Ocana I, de Otero J, Cortes E, Gasser I, Pahissa A. Prophylaxis of visceral leishmaniasis in human immunodeficiency virus-infected patients. Am J Med. May 1996;100(5):496-501. Available at http://www.ncbi.nlm.nih.gov/pubmed/8644760.
Patel TA, Lockwood DN. Pentamidine as secondary prophylaxis for visceral leishmaniasis in the immunocompromised host: report of four cases. Tropical medicine & international health : TM & IH. Sep 2009;14(9):1064-1070. Available at http://www.ncbi.nlm.nih.gov/pubmed/19552658.
Berenguer J, Cosin J, Miralles P, Lopez JC, Padilla B. Discontinuation of secondary anti-leishmania prophylaxis in HIV-infected patients who have responded to highly active antiretroviral therapy. AIDS. Dec 22 2000;14(18):2946-2948. Available at http://www.ncbi.nlm.nih.gov/pubmed/11153679.
Bourgeois N, Bastien P, Reynes J, Makinson A, Rouanet I, Lachaud L. 'Active chronic visceral leishmaniasis' in HIV-1-infected patients demonstrated by biological and clinical long-term follow-up of 10 patients. HIV Med. Nov 2010;11(10):670-673. Available at http://www.ncbi.nlm.nih.gov/pubmed/20500233.
Morgan DJ, Guimaraes LH, Machado PR, et al. Cutaneous leishmaniasis during pregnancy: exuberant lesions and potential fetal complications. Clin Infect Dis. Aug 15 2007;45(4):478-482. Available at http://www.ncbi.nlm.nih.gov/pubmed/17638198.
James LF, Lazar VA, Binns W. Effects of sublethal doses of certain minerals on pregnant ewes and fetal development. American journal of veterinary research. Jan 1966;27(116):132-135. Available at http://www.ncbi.nlm.nih.gov/pubmed/5913019.
Ridgway LP, Karnofsky DA. The effects of metals on the chick embryo: toxicity and production of abnormalities in development. Annals of the New York Academy of Sciences. Aug 8 1952;55(2):203-215. Available at http://www.ncbi.nlm.nih.gov/pubmed/12977037.
Rossi F, Acampora R, Vacca C, et al. Prenatal and postnatal antimony exposure in rats: effect on vasomotor reactivity development of pups. Teratogenesis, carcinogenesis, and mutagenesis. 1987;7(5):491-496. Available at http://www.ncbi.nlm.nih.gov/pubmed/2893463.
Gradoni L, Gaeta GB, Pellizzer G, Maisto A, Scalone A. Mediterranean visceral leishmaniasis in pregnancy. Scandinavian journal of infectious diseases. 1994;26(5):627-629. Available at http://www.ncbi.nlm.nih.gov/pubmed/7855563.
Pagliano P, Carannante N, Rossi M, et al. Visceral leishmaniasis in pregnancy: a case series and a systematic review of the literature. J Antimicrob Chemother. Feb 2005;55(2):229-233. Available at http://www.ncbi.nlm.nih.gov/pubmed/15649998.
Topno RK, Pandey K, Das VN, et al. Visceral leishmaniasis in pregnancy - the role of amphotericin B. Ann Trop Med Parasitol. Apr 2008;102(3):267-270. Available at http://www.ncbi.nlm.nih.gov/pubmed/18348781.
Utili R, Rambaldi A, Tripodi MF, Andreana A. Visceral leishmaniasis during pregnancy treated with meglumine antimoniate. Infection. May-Jun 1995;23(3):182-183. Available at http://www.ncbi.nlm.nih.gov/pubmed/7499009.
Adam GK, Abdulla MA, Ahmed AA, Adam I. Maternal and perinatal outcomes of visceral leishmaniasis (kala-azar) treated with sodium stibogluconate in eastern Sudan. Int J Gynaecol Obstet. Dec 2009;107(3):208-210. Available at http://www.ncbi.nlm.nih.gov/pubmed/19766208.
Mueller M, Balasegaram M, Koummuki Y, Ritmeijer K, Santana MR, Davidson R. A comparison of liposomal amphotericin B with sodium stibogluconate for the treatment of visceral leishmaniasis in pregnancy in Sudan. J Antimicrob Chemother. Oct 2006;58(4):811-815. Available at http://www.ncbi.nlm.nih.gov/pubmed/16916865.
Boehme CC, Hain U, Novosel A, Eichenlaub S, Fleischmann E, Loscher T. Congenital visceral leishmaniasis. Emerg Infect Dis. Feb 2006;12(2):359-360. Available at http://www.ncbi.nlm.nih.gov/pubmed/17080586.
Meinecke CK, Schottelius J, Oskam L, Fleischer B. Congenital transmission of visceral leishmaniasis (Kala Azar) from an asymptomatic mother to her child. Pediatrics. Nov 1999;104(5):e65. Available at http://www.ncbi.nlm.nih.gov/pubmed/10545591.
Zinchuk A, Nadraga A. Congenital visceral leishmaniasis in Ukraine: case report. Ann Trop Paediatr. 2010;30(2):161-164. Available at http://www.ncbi.nlm.nih.gov/pubmed/20522305.