Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia

In Colombia, pentavalent antimonials and miltefosine are the drugs of choice for the treatment of cutaneous leishmaniasis; however, their toxicity, treatment duration, (treatment adherence problems), cost, and decreased parasite sensitivity make the search for alternative treatments of American cutaneous leishmaniasis necessary. Based on the results found in a controlled, open, randomized, phase III clinical trial, the efficacy and safety of miltefosine was compared to that of thermotherapy for the treatment of cutaneous leishmaniasis in Colombia. Adult patients from the Colombian army participated in the study; they received either 50 mg of miltefosine three times per day for 28 days by the oral route (n = 145) or a thermotherapy (Thermomed®) application of 50 °C for 30 seconds over the lesion and surrounding area (n = 149). Both groups were comparable with respect to their sociodemographic, clinical, and parasitological characteristics. The efficacy of miltefosine by protocol and by intention to treat was 70% (85/122 patients) and 69% (85/145 patients), respectively. The adverse effects were primarily gastrointestinal for miltefosine and pain at the lesion site after treatment for thermotherapy. No statistically significant difference was found in the efficacy analysis (intention to treat and protocol) between the two treatments. ClinicalTrials.gov: NCT00471705.

APPLICABILITY OF kDNA-PCR FOR ROUTINE DIAGNOSIS OF AMERICAN TEGUMENTARY LEISHMANIASIS IN A TERTIARY REFERENCE HOSPITAL

SUMMARYThis study evaluated the applicability of kDNA-PCR as a prospective routine diagnosis method for American tegumentary leishmaniasis (ATL) in patients from the Instituto de Infectologia Emílio Ribas (IIER), a reference center for infectious diseases in São Paulo - SP, Brazil. The kDNA-PCR method detected Leishmania DNA in 87.5% (112/128) of the clinically suspected ATL patients, while the traditional methods demonstrated the following percentages of positivity: 62.8% (49/78) for the Montenegro skin test, 61.8% (47/76) for direct investigation, and 19.3% (22/114) for in vitro culture. The molecular method was able to confirm the disease in samples considered negative or inconclusive by traditional laboratory methods, contributing to the final clinical diagnosis and therapy of ATL in this hospital. Thus, we strongly recommend the inclusion of kDNA-PCR amplification as an alternative diagnostic method for ATL, suggesting a new algorithm routine to be followed to help the diagnosis and treatment of ATL in IIER.

USEFULNESS OF kDNA PCR IN THE DIAGNOSIS OF VISCERAL LEISHMANIASIS REACTIVATION IN CO-INFECTED PATIENTS

SUMMARYIt is important to develop new methods for diagnosing relapses in the co-infection of visceral leishmaniasis (VL) and HIV to enable earlier detection using less invasive methods. We report a case of a co-infected patient who had relapses after VL treatment, where the qualitative kDNA PCR showed a good performance. The kDNA PCR seems to be a useful tool for diagnosing VL and may be a good marker for predicting VL relapses after treatment of co-infected patients with clinical symptoms of the disease.

ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

FIRST CASE OF AUTOCHTHONOUS HUMAN VISCERAL LEISHMANIASIS IN THE URBAN CENTER OF RIO DE JANEIRO: CASE REPORT

Visceral leishmaniasis is an anthropozoonosis that is caused by protozoa of the genus Leishmania, especially Leishmania (Leishmania) infantum, and is transmitted to humans by the bite of sandflies of the genus Lutzomyia, such as Lutzomyia longipalpis. There are many reservoirs, including Canis familiaris. It is a chronic infectious disease with systemic involvement that is characterized by three phases: the initial period, the state period and the final period. The main symptoms are fever, malnutrition, hepatosplenomegaly, and pancytopenia. This article reports a case of a patient diagnosed with visceral leishmaniasis in the final period following autochthonous transmission in the urban area of Rio de Janeiro. The case reported here is considered by the Municipal Civil Defense and Health Surveillance of Rio de Janeiro to be the first instance of autochthonous visceral leishmaniasis in humans in the urban area of this city. The patient was discharged and is undergoing a follow-up at the outpatient clinic, demonstrating clinical improvement.

ASPECTS OF THE ECOLOGY OF PHLEBOTOMINES (Diptera: Psychodidae: Phlebotominae) IN AN AREA OF CUTANEOUS LEISHMANIASIS OCCURRENCE, MUNICIPALITY OF ANGRA DOS REIS, COAST OF RIO DE JANEIRO STATE, BRAZIL

Over a complete two-year period, phlebotomine specimens were caught in an area of cutaneous leishmaniasis occurrence in the municipality of Angra dos Reis. A manual suction tube was used to catch phlebotomines on house walls, and also light traps in domestic and peridomestic settings and in the forest. This yielded 14,170 specimens of 13 species: two in the genus Brumptomyia and eleven in the genus Lutzomyia. L. intermedia predominantly in domestic and peridomestic settings, with little presence in the forest, with the same trend being found in relation to L. migonei, thus proving that these species have adapted to the human environment. L. fischeri appeared to be eclectic regarding location, but was seen to be proportionally more endophilic. L. intermedia and L. migonei were more numerous in peridomestic settings, throughout the year, while L. fischeri was more numerous in domestic settings except in March, April, May and September. From the prevalence of L. intermedia, its proven anthropophily and findings of this species naturally infected with Leishmania(Viannia) braziliensis, it can be incriminated as the main vector for this agent of cutaneous leishmaniasis in the study area, especially in the peridomestic environment. L. fischeri may be a coadjuvant in carrying the parasite.

PRESENCE OF RESPIRATORY VIRUSES IN EQUINES IN BRAZIL

Equines are susceptible to respiratory viruses such as influenza and parainfluenza. Respiratory diseases have adversely impacted economies all over the world. This study was intended to determine the presence of influenza and parainfluenza viruses in unvaccinated horses from some regions of the state of São Paulo, Brazil. Blood serum collected from 72 equines of different towns in this state was tested by hemagglutination inhibition test to detect antibodies for both viruses using the corresponding antigens. About 98.6% (71) and 97.2% (70) of the equines responded with antibody protective titers (≥ 80 HIU/25µL) H7N7 and H3N8 subtypes of influenza A viruses, respectively. All horses (72) also responded with protective titers (≥ 80) HIU/25µL against the parainfluenza virus. The difference between mean antibody titers to H7N7 and H3N8 subtypes of influenza A viruses was not statistically significant (p > 0.05). The mean titers for influenza and parainfluenza viruses, on the other hand, showed a statistically significant difference (p < 0.001). These results indicate a better antibody response from equines to parainfluenza 3 virus than to the equine influenza viruses. No statistically significant differences in the responses against H7N7 and H3N8 subtypes of influenza A and parainfluenza 3 viruses were observed according to the gender (female, male) or the age (≤ 2 to 20 years-old) groups. This study provides evidence of the concomitant presence of two subtypes of the equine influenza A (H7N7 and H3N8) viruses and the parainfluenza 3 virus in equines in Brazil. Thus, it is advisable to vaccinate equines against these respiratory viruses.

EXPANSION OF VISCERAL LEISHMANIASIS IN THE STATE OF RIO DE JANEIRO, BRAZIL: REPORT OF THE FIRST AUTOCHTHONOUS CASE IN THE MUNICIPALITY OF VOLTA REDONDA AND THE DIFFICULTY OF DIAGNOSIS

Visceral Leishmaniasis has been showing remarkable epidemiological changes in recent decades, with marked expansion and an emergence of cases in urban areas of the North, Southeast and Midwest regions of Brazil. The Kala-azar cases reported here, despite being very characteristic, presented a great difficulty of diagnosis, because the disease is not endemic in Volta Redonda. The child underwent two hospitalizations in different hospitals, but got the correct diagnosis only after 11 months of symptom onset. In this report we discuss the main differential diagnoses and call attention to the suspected symptoms of visceral leishmaniasis in patients with prolonged fever, hepatosplenomegaly and pancytopenia, even in areas not traditionally endemic for the disease.

FACTORS ASSOCIATED TO ADHERENCE TO DIFFERENT TREATMENT SCHEMES WITH MEGLUMINE ANTIMONIATE IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS

The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.

PARTICIPATION OF TICKS IN THE INFECTIOUS CYCLE OF CANINE VISCERAL LEISHMANIASIS, IN TERESINA, PIAUÍ, BRAZIL

In this study, we detected Leishmania spp. infection in R. sanguineus collected from dogs that were naturally infected with L. (L.) infantum. We examined 35 dogs of both sexes and unknown ages. The infected dogs were serologically positive by the immunofluorescence antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA), and Quick Test-DPP (Dual Path Platform), as well as parasitological examination of a positive skin biopsy or sternal bone marrow aspiration. Ten negative dogs were included as controls. The ticks that infested these dogs were collected in pools of 10 adult females per animal. The PCR was performed with specific primers for Leishmania spp., which amplified a 720-bp fragment. Of the 35 analyzed samples, a product was observed in eight samples (8/35; 22.9%). We conclude that the presence of parasite DNA suggests that ticks participate in the zoonotic cycle of canine visceral leishmaniasis, in the city of Teresina, Piauí.

MOLECULAR DETECTION OF Leishmania IN PHLEBOTOMINE SAND FLIES IN A CUTANEOUS AND VISCERAL LEISHMANIASIS ENDEMIC AREA IN NORTHEASTERN BRAZIL

Several phlebotomine sand fly species have been regarded as putative or proven vectors of parasites of the genus Leishmania in Brazil, but data for the northeastern region remains incipient. In this study, a total of 600 phlebotomine sand flies were grouped in pools of 10 specimens each and tested by a Leishmania genus-specific PCR and by a PCR targeting Leishmania (Leishmania) infantum. Fourteen out of 60 pools were positive by the genus-specific PCR, being five pools of L. migonei, seven of L. complexa, one of L. sordellii and one of L. naftalekatzi, which correspond to a minimal infection rate of 2.3% (14/600). Our results, associated with their known anthropophily and their abundance, suggest the participation of L. migonei and L. complexa as vectors of Leishmania in northeastern Brazil. Remarkably, this is the first time in this country that the detection of Leishmania DNA in L. sordellii and L. naftalekatzi has been reported, but future studies are necessary to better understand the significance of these findings.

SOUTH AMERICAN COLLABORATION IN SCIENTIFIC PUBLICATIONS ON LEISHMANIASIS: BIBLIOMETRIC ANALYSIS IN SCOPUS (2000-2011)

Objectives: Evaluate the production and the research collaborative network on Leishmaniasis in South America. Methods: A bibliometric research was carried out using SCOPUS database. The analysis unit was original research articles published from 2000 to 2011, that dealt with leishmaniasis and that included at least one South American author. The following items were obtained for each article: journal name, language, year of publication, number of authors, institutions, countries, and others variables. Results: 3,174 articles were published, 2,272 of them were original articles. 1,160 different institutional signatures, 58 different countries and 398 scientific journals were identified. Brazil was the country with more articles (60.7%) and Oswaldo Cruz Foundation (FIOCRUZ) had 18% of Brazilian production, which is the South American nucleus of the major scientific network in Leishmaniasis. Conclusions: South American scientific production on Leishmaniasis published in journals indexed in SCOPUS is focused on Brazilian research activity. It is necessary to strengthen the collaboration networks. The first step is to identify the institutions with higher production, in order to perform collaborative research according to the priorities of each country.

FIRST REPORT ON OTOTOXICITY OF MEGLUMINE ANTIMONIATE

Introduction: Pentavalent antimonials are the first drug of choice in the treatment of tegumentary leishmaniasis. Data on ototoxicity related with such drugs is scarcely available in literature, leading us to develop a study on cochleovestibular functions. Case Report: A case of a tegumentary leishmaniasis patient, a 78-year-old man who presented a substantial increase in auditory threshold with tinnitus and severe rotatory dizziness during the treatment with meglumine antimoniate, is reported. These symptoms worsened in two weeks after treatment was interrupted. Conclusion: Dizziness and tinnitus had already been related to meglumine antimoniate. However, this is the first well documented case of cochlear-vestibular toxicity related to meglumine antimoniate.

Jogos digitais com contos infantis - Uma proposta de brinquedo-jogo para dispositivos móveis

O desenvolvimento e proliferação de equipamentos e produtos multimédia, permitindo a combinação de som, imagem e texto despoletou a emergência de novos estímulos que se associam a sensações, novas formas de interagir, de comunicar e também de brincar e aprender. Jogar e brincar são excelentes fontes de estímulos, principalmente para as crianças, pois potenciam a evolução da lógica, do raciocínio, das associações e da capacidade de escolha. No contexto dos jogos, decorrente da evolução tecnológica, o mercado dos jogos digitais tem vindo a expandir-se consideravelmente, nomeadamente na área dos jogos educativos. Os jogos educativos baseados em contos infantis permitem um enriquecimento de experiências, de capacidades sequenciais de lógica e promovem a apetência da criança para fantasiar num mundo paralelo. No entanto, do nosso ponto de vista, o mercado dos jogos digitais ainda tem um longo caminho a percorrer para fornecer de forma equilibrada este tipo de jogos educativos. Com este trabalho abordam-se as potencialidades que os jogos educativos baseados em contos infantis podem ter no desenvolvimento de algumas competências das crianças, nomeadamente através da análise das suas vantagens e dos seus aspetos negativos. O mercado dos jogos digitais é também analisado para determinar os seus contributos e as ideias principais presentes. A componente prática deste trabalho de mestrado contempla a criação de um jogo educativo baseado em contos infantis que corresponda aos interesses das crianças entre os 3 e os 5 anos de idade, e que fomente o desenvolvimento de algumas das suas competências a nível da linguagem. Os testes feitos com o protótipo do jogo permitem aferir a recetividade por parte das crianças. A simplicidade no manuseamento da aplicação e o facto de integrar histórias do imaginário infantil consideram-se fatores positivos e motivadores à utilização do jogo “Contos Baralhados: Brinca com as Histórias”.

IDENTIFICATION OF Leishmania infantum IN PUERTO IGUAZÚ, MISIONES, ARGENTINA

 The emergence of zoonotic visceral leishmaniasis (ZVL) in Latin America is a growing public health problem. The urbanization of ZVL has been observed in different countries around the world, and there are a growing number of reports drawing attention to the emergence of this infection in new locations, as well as its increase in previously established areas of endemicity. In the city of Posadas, Misiones province, Northeastern Argentina, the transmission of ZVL associated with canines and Lutzomyia longipalpis was first reported in 2006. In the city of Puerto Iguazú, also in Misiones province, the first human case of ZVL was reported in February 2014. From 209 surveyed dogs, 15 (7.17%) were identified as positive by serological and/or parasitological methods. Amplification was observed in 14 samples and in all cases the species implicated was Leishmania infantum. To the authors’ knowledge, this is the first molecular characterization of L. infantum from dogs in this area.