Azithromycin in the treatment of mucosal leishmaniasis

This report describes three elderly patients with mucosal form of American tegumentary leishmaniasis associated with chronic cardiopathy. Due to the known toxicity of classical drugs with activity against Leishmania sp., the patients received three oral courses of azithromycin therapy in single 500 mg daily dose during ten days, every other month. All lesions healed after the third series. One of the patients relapsed and a new series of azithromycin was prescribed. Azithromycin may be an alternative drug for the treatment of leishmaniasis in special situations due to its optimal mucosal and intraphagocyte concentration, single daily posology, high tolerance and oral administration. The mechanism of this drug on Leishmania sp. is unknown at present.

The histopathology of cutaneous leishmaniasis due to Leishmania (Leishmania) mexicana in the Yucatan peninsula, Mexico

Localized Cutaneous Leishmaniasis (LCL) known as "chiclero's ulcer" in southeast Mexico, was described by SEIDELIN in 1912. Since then the sylvatic region of the Yucatan peninsula has been documented as an endemic focus of LCL. This study of 73 biopsies from parasitological confirmed lesions of LCL cases of Leishmania (Leishmania) mexicana infection was undertaken: 1) to examine host response at tissue level; and 2) to relate manifestations of this response to some characteristics of clinical presentation. Based on Magalhães' classification we found that the most common pattern in our LCL cases caused by L. (L.) mexicana was predominantly characterized by the presence of unorganized granuloma without necrosis, (43.8%). Another important finding to be highlighted is the fact that in 50/73 (68.5%) parasite identification was positive. There was direct relation between the size of the lesion and time of evolution (r s = 0.3079, p = 0.03), and inverse correlation between size of the lesion and abundance of amastigotes (r s = -0.2467, p = 0.03). In view of the complexity of clinical and histopathological findings, cell-mediated immune response of the disease related to clinical and histopathological features, as so genetic background should be studied.

Visceral leishmaniasis in Brazil: revisiting paradigms of epidemiology and control

In the last 20 years, despite the known underestimation of cases, Brazil registered a marked increase in the incidence of visceral leishmaniasis. The main goal of this review is to reflect on some aspects of this zoonosis in Brazil and also to encourage the discussion in order to find more viable, effective and affordable strategies to be implemented by the Brazilian Leishmaniasis Control Program. The current situation of visceral leishmaniasis in Brazil might be seen as a paradox: the most important aspects of the disease are known, but so far the control of this disease has not yet been achieved. The current control strategies have not been able to prevent the geographical expansion, and even a rise in the incidence and lethality of visceral leishmaniasis. There is a need not only for a better definition of priority areas, but also for the implementation of a fieldwork monitoring system to the disease surveillance that could permit a further evaluation of the control program in areas where visceral leishmaniasis is endemic.

Sensitivity of an immunoenzymatic test for detection of ant-L. brasiliensis antibodies compared to other tests used for the diagnosis of American cutaneous leishmaniasis

The diagnosis of American cutaneous leishmaniasis (ACL) is frequently based on clinical and epidemiological data associated with the results of laboratory tests. Some laboratory methods are currently being applied for the diagnosis of ACL, among them the indirect immunofluorescence reaction (IIFR), the Montenegro skin test (MST), histopathological examination, and the polymerase chain reaction (PCR). The performance of these methods varies in a considerable proportion of patients. After the standardization of an immunoenzymatic test (ELISA) for the detection of IgG in the serum of patients with ACL using a crude Leishmania braziliensis antigen, the results obtained were compared to those of other tests routinely used for the diagnosis. The tests revealed the following sensitivity, when analyzed separately: 85% for ELISA IgG, 81% for PCR, 64.4% for MST, 58.1% for IIFR, and 34% for the presence of parasites in the biopsy. ELISA was positive in 75% of patients with ACL presenting a negative MST, in 84.8% of ACL patients with negative skin or mucous biopsies for the presence of the parasite, and in 100% of cases with a negative PCR. Thus, ELISA presented a higher sensitivity than the other tests and was useful as a complementary method for the diagnosis of ACL.

Presence of Leishmania amastigotes in peritoneal fluid of a dog with leishmaniasis from Alagoas, Northeast Brazil

The goal of this short communication is to report the uncommon presence of intracellular amastigotes of Leishmania in peritoneal fluid of a dog with leishmaniasis from Alagoas State, Brazil. Physical examination of an adult male rottweiler suspected to be suffering of leishmaniasis revealed severe loss of weight, ascitis, splenomegaly, moderately enlarged lymph nodes, onychogryphosis, generalized alopecia, skin ulcers on the posterior limbs, and conjunctivitis. Samples of bone marrow, popliteal lymph node, skin ulcer, and peritoneal fluid were collected and smears of each sample were prepared and stained with hematoxylin and eosin. Numerous amastigotes were detected in bone marrow, popliteal lymph node, and skin ulcer smears. Smears of peritoneal fluid revealed the unusual presence of several free and intracellular amastigotes of Leishmania. Future studies are needed to determine whether the cytology of ascitic fluid represents a useful tool for diagnosis Leishmania infection in ascitic dogs, particularly in those living in areas where canine leishmaniasis is enzootic.

Low efficacy of azithromycin to treat cutaneous leishmaniasis in Manaus, AM, Brazil

An open trial to evaluate the azithromycin efficacy in cutaneous leishmaniasis patients was carried out in Manaus (AM), where Leishmania (Viannia) guyanensis is the main etiologic agent. Forty-one patients with skin lesions of less than 12 weeks duration, without specific treatment for the last three months and a positive imprint to Leishmania sp. were included. From these, 31 (75.6%) were male with median age of 30.2. All of them received a daily-single oral dose of 500 mg of azithromycin for ten days. At 25th day, 16 (39%) presented therapeutic failure and received intramuscular pentavalent antimonial, four were considered lost, 21, that had improved or were inaltered received another ten-day series of azithromycin and were monthly followed, but nine (21.9%) of them presented a poor clinical response and switched to intramuscular pentavalent antimonial on day 55. Of the 12 remaining cases evaluated on day 55, despite of clinical improvement, three asked for antimony therapy and 9 (21.9%) continued the follow-up but, only three were cured on 55th, 85th and 115th days, and six did not come back for final evaluation. The intention-treatment overall response rate was 22% and whole cure was seen in three (7.3%) of cases. Thus, azithromycin showed a low efficacy to treat cutaneous leishmaniasis in Manaus.

A comparison of the immune parameters of dogs infected with visceral leishmaniasis using Western blot and neutralization techniques

The Western blot technique was used to demonstrate the presence of antibodies in the blood of dogs that presented canine visceral leishmaniasis. This technique was used against some specific molecules present in the lysate of the promastigote form of Leshmania chagasi.Through the association of the results of the Western blot technique with the morphological alterations seen as a result of the serum neutralization technique performed in McCoy cells (which mimetizes the macrophage) it was possible to observe the role of some molecules of great relevance in determining the disease in symptomatic dogs as well as that of some other molecules associated with asymptomatic infected dogs that may become transmitters as well as differentiating them as asymptomatic resistant dogs. In the sera analyses carried out during the immunobloting a variation of 9 to 27 immunoreacting bands was observed, which were then compared using Dice's similarity coefficient. In the dendrogram constructed on the basis of the coefficient, 50% similarity was observed among the total number of reagent bands with the promastigote lysate, thus creating five groups. The main difference observed related to the clinical condition of the dogs: symptomatic and asymptomatic dogs were found in separate groups. The asymptomatic group of dogs was distributed in two different places in the dendrogram because they presented two different behavior patterns regarding the cellular morphology in the serum neutralization reaction: the presence or absence of cellular lysis. According to this analysis it is possible to evaluate the immune status and associate it with specific markers observed in the reaction found in the Western blot strips.

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

A non-randomized controlled clinical trial was carried outin order to evaluate both azithromycin and antimony efficacy in cutaneous leishmaniasis in Manaus, AM, Brazil. Forty nine patients from both genders, aged 14 to 70, with cutaneous ulcers for less than three months and a positive imprint for Leishmania spp. amastigotes were recruited into two groups. Group I (26 patients) received a daily-single oral dose of 500 mg of azithromycin for 20 days and Group II (23 patients) received a daily-single intramuscular dose of 20 mg/kg of meglumine antimony, also for 20 days. Azithromycin cured three of 24 (12.5%) patients on days 60, 90 and 120 respectively whereas therapeutic failure was considered in 21 of 24 (87.5%) cases. In group II, antimony cured eight of 19 (42.1%) cases as follows: three on day 30, one each on day 60 and day 90, and three on day 120. Therapeutic failure occurred in 11 of 19 (57.9%) individuals. The efficacy of antimony for leishmaniasis was better than azithromycin but analysis for the intention-to-treat response rate did not show statistical difference between them. Although azithromycin was better tolerated, it showed a very low efficacy to treat cutaneous leishmaniasis in Manaus.

American tegumentary leishmaniasis: langerhans cells in montenegro skin test

This work analyzed the histopathology and epidermal Langerhans cells (LC) of Montenegro skin test (MST) in patients with American tegumentary leishmaniasis (ATL) in order to in situ characterize and compare the immunological reaction of the two major clinical forms of ATL, localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). MST histopathology of both LCL and MCL showed superficial and deep perivascular inflammatory infiltrate composed mainly of lymphocytes and histiocytes. Epidermal LC population was higher in MST biopsies taken from LCL patients when compared to MCL group, at 48 and 72 hours after antigen inoculation. Increased number of epidermal LC displayed in MST biopsies of LCL patients represents specific cellular immunity against parasites. The decrease of LC in MST biopsies of MCL patients does not necessarily indicate a worse specific cellular immunity in this clinical form of leishmaniasis.

Cytokine profile in Montenegro skin test of patients with localized cutaneous and mucocutaneous leishmaniasis

American tegumentary leishmaniasis presents as two major clinical forms: localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). The immune response in leishmaniasis is efficiently evaluated by the response to Leishmania antigen through the Montenegro skin test (MST). Both LCL and MCL present positive response to MST, indicating that the patients present cell-mediated immunity against the parasite - Leishmania. In spite of the presence of immunity in MCL, this is not sufficient to stop disease progression and prevent resistance to treatment. In this study we demonstrated interleukin (IL) 2, 4, 5 and interferon (IFN) gamma expression in biopsies of MST of ten patients with American tegumentary leishmaniasis. The obtained results were compared between LCL (n = 5) and MCL (n = 5) patients. The MST of MCL patients displayed a higher expression of IL-2, IL-4 and IL-5, in comparison to LCL. There was no significant difference in IFN-gamma expression between groups. The obtained results suggest the role of IL-4 and IL-5 in the maintenance of the immunopathogenic mechanism of the destructive lesions that characterize MCL.