Classification of cutaneous leishmaniasis patients based on its risk factors using latent class analysis.

Cutaneous leishmaniasis is one of the main health-economic problems around the world. Data were collected from all patients with cutaneous leishmaniasis referred to the health centres of Kermanshah province between 2013 and 2019. Latent class analysis was conducted by PROC LCA in SAS 9.2 and a significant level was set at 0.05. Four latent classes were identified: low (33.8%), moderate (9.8%), high (22.4%) and very high risk (34.0%). The probability of having a travel history was high in the third class. Our study indicated that having history of an eschar has no role in the classification of patients. On the other hand, a positive smear test is important in classifying subjects. Our results indicate that more than half of all patients fell under high risk or very high-risk class. This emphasises the importance of planning preventive intervention by considering different risk factors of cutaneous leishmaniasis simultaneously.

Ability of real-time PCR for differential diagnosis of various forms of cutaneous leishmaniasis: a comparative study with histopathology.

OBJECTIVE: Histopathological studies suggest that parasite load is different between acute and chronic forms of cutaneous leishmaniasis (CL). However, highly sensitive detection methods are still needed to distinguish different forms of leishmaniasis. In the present study, we developed a quantitative real-time polymerase chain reaction (PCR) to detect and quantify Leishmania tropica parasites in paraffin-embedded tissue samples. RESULTS: The ability of real-time PCR for leishmania detection was higher than histopathological evaluation. The quantitative real-time PCR (qPCR) quantified parasite loads were highly correlated with microscopic results (r = 0.598; P < 0.001). Among patients, the parasite load was inversely correlated with disease duration (acute CL lesions had very higher parasite load than chronic CL lesions), but there was no difference in the parasite load according to the patients' age and sex as well as location of the lesions. In contrast to Ridley scoring system (P < 0.001), there were no statistically significant differences in the relative number of parasites among the lupoid and non-lupoid forms of chronic lesions in real-time PCR (P = 0.549), which indicates the superiority of histopathological evaluation for chronic forms differentiation.

[Cutaneous leishmaniasis]. / Leishmanioses cutanées.

Cutaneous leishmaniasis is a parasitic infection caused by a flagellated parasite belonging to the genus Leishmania. In most cases, it is a zoonotic disease transmitted via a bite by bloodsucking sand-flies of the genus Phlebotomus. The disease reservoirs consist of wild or semi-domesticated animals, generally rodents or dogs. The disease itself is distributed extensively worldwide in the Americas, Asia, Europe and Africa. Epidemiology is affected by environmental, migratory and climatic factors. Identification of the different types of leishmaniasis is based chiefly on the biochemical characteristics (isoenzymes) on which their classification is based. The offending parasites are dimorphic intracellular organisms within the phagosome of the host's immune cells, and a single-cell flagellated protozoan with a kinetoplast contained in the gut of the vector and in culture. Three major clinical forms are seen: cutaneous leishmaniasis, mucosal leishmaniasis and visceral leishmaniasis. The clinical presentation depends on factors associated with the virulence of the parasite, with individual immune response and with the site of lesions. Although each type of leishmaniasis may have its own specific cutaneous signs and endemic regions, the most common presentations are crusted, ulcerated nodules and plaques. The natural history of leishmaniasis must also be considered when formulating therapeutic strategies. Cutaneous leishmaniasis resolves spontaneously within between one month and six years. While numerous therapeutic options have been considered in recent decades, very few have shown proven efficacy and safety. Antimony compounds administered either directly to the lesion or parenterally remain the standard treatment and their toxicity calls for vigilance and monitoring of therapy.

Detection of Leishmania DNA and Blood Meal Identification in Sand Flies (Diptera: Psychodidae) From Lençois Maranhenses National Park Region, Brazil.

To elucidate portions of the transmission cycles of American tegumentary leishmaniasis (TL) and visceral leishmaniasis (VL) occurring in the region surrounding the Lençóis Maranhenses National Park, an important tourist center in Brazil, the present study objectives were to determine the rate of natural infection by Leishmania spp. and the blood meal in caught sand flies species in the region. Sand flies were captured over 36 mo in 62 locations of the municipality of Barreirinhas, Maranhão with notifications of disease incidence. Species identification of parasites was performed with internal transcribed spacer 1 (ITS1) PCR-RFLP using HaeIII enzyme. Blood meal identification was performed with cytochrome b (cytb) gene PCR-RFLP using HaeIII and MboI enzyme. The species Lutzomyia longipalpis (Lutz and Neiva 1912) presented a positivity rate of 3.7% for Leishmania infantum. Species not considered vectors of this parasite such as Lu. lenti (Mangabeira 1938) and Lu. whitmani (Antunes & Coutinho 1939) showed infection rates of 0.6% and 0.9%, respectively. Among the vectors of Leishmania spp. was Lu. whitmani with detection rate of 0.3% for Le. braziliensis and Lu. flaviscutellata (Mangabeira 1942) with a detection rate of 8% for Le. amazonensis. After restriction of amplification product encoding a 359bp sequence of the cytb recognized in as follows: pigs (37.9%); dogs (27.4%); chickens (20.9%); horses (9%), rodents (3.3%), and humans (1.4%). The presence of Leishmania DNA in sand flies fed with human blood and domestic animals in villages with transmission of VL and TL suggests that transmission could be occurring in the locations of the infected patients.

Leishmaniasis in the major endemic region of Plurinational State of Bolivia: Species identification, phylogeography and drug susceptibility implications.

The Plurinational State of Bolivia is one of the Latin American countries with the highest prevalence of leishmaniasis, highlighting the lowlands of the Department of La Paz where about 50% of the total cases were reported. The control of the disease can be seriously compromised by the intrinsic variability of the circulating species that may limit the efficacy of treatment while favoring the emergence of resistance. Fifty-five isolates of Leishmania from cutaneous and mucocutaneous lesions from patients living in different provinces of the Department of La Paz were tested. Molecular characterization of isolates was carried out by 3 classical markers: the rRNA internal transcribed spacer 1 (ITS-1), the heat shock protein 70 (HSP70) and the mitochondrial cytochrome b (Cyt-b). These markers were amplified by PCR and their products digested by the restriction endonuclease enzymes AseI and HaeIII followed by subsequent sequencing of Cyt-b gene and ITS-1 region for subsequent phylogenetic analysis. The combined use of these 3 markers allowed us to assign 36 isolates (65.5%) to the complex Leishmania (Viannia) braziliensis, 4 isolates (7, 27%) to L. (Viannia) lainsoni. and the remaining 15 isolates (23.7%) to a local variant of L. (Leishmania) mexicana. Concerning in vitro drug susceptibility the amastigotes from all isolates where highly sensitive to Fungizone® (mean IC50 between 0.23 and 0.5µg/mL) whereas against Glucantime® the sensitivity was moderate (mean IC50 ranging from 50.84µg/mL for L. (V.) braziliensis to 18.23µg/mL for L. (L.) mexicana. L. (V.) lainsoni was not sensitive to Glucantime®. The susceptibility to miltefosine was highly variable among species isolates, being L. (L.) mexicana the most sensitive, followed by L. (V.) braziliensis and L. (V.) lainsoni (mean IC50 of 8.24µg/mL, 17.85µg/mL and 23.28µg/mL, respectively).

Clinical, laboratory, and therapeutic characteristics of American tegumentary leishmaniasis in the 15 th State Health Division, Northwest Paraná State, Southern Brazil.

INTRODUCTION: American tegumentary leishmaniasis (ATL) is an endemic disease in many regions of Brazil; however, only few reports on the actual epidemiological conditions are available. Here, we aimed to assess the clinical, epidemiological, and laboratory characteristics of ATL patients and their treatment in the 15th Regional Health Division of Paraná State, Maringá, Brazil. METHODS: This epidemiological study included patients diagnosed with ATL from January 2010 to September 2014, from the 15th Regional Health Division database. RESULTS: A total of 220 cases aged 3-84 years (85% male and 60.9% with up to 8 years of schooling) were included. The cases were classified as having the cutaneous form (n=183; 83.2%), mucosal form (n=26; 11.8%), mucocutaneous form (n=11; 5%), and relapses (n=21; 9.6%). Diagnosis was made via laboratory test results in 197 (89.5%) patients, and 172 (78.2%) completed the treatment within the study period. With regard to patients with the cutaneous form, 134 (95%) were cured, 131 (97.8%) were treated with Glucantime(r), and 47 (36.7%) received dosage of >15 and <20mg Sb5+/kg/day. Among the cases with mucosal involvement, 87.1% were cured and most were treated with <20mg Sb5+/kg/day. Thus, the cure rate was 93.6%. CONCLUSIONS: During the study period in the 15th Regional Health Division of Paraná State, ATL cases had a good response to treatment with a low rate of relapse or treatment failure, although a high percentage of mucosal or mucocutaneous form cases was also noted.

Clinical, laboratory, and therapeutic characteristics of American tegumentary leishmaniasis in the 15 th state health division, northwest Paraná State, Southern Brazil

Abstract INTRODUCTION American tegumentary leishmaniasis (ATL) is an endemic disease in many regions of Brazil; however, only few reports on the actual epidemiological conditions are available. Here, we aimed to assess the clinical, epidemiological, and laboratory characteristics of ATL patients and their treatment in the 15th Regional Health Division of Paraná State, Maringá, Brazil. METHODS This epidemiological study included patients diagnosed with ATL from January 2010 to September 2014, from the 15th Regional Health Division database. RESULTS A total of 220 cases aged 3-84 years (85% male and 60.9% with up to 8 years of schooling) were included. The cases were classified as having the cutaneous form (n=183; 83.2%), mucosal form (n=26; 11.8%), mucocutaneous form (n=11; 5%), and relapses (n=21; 9.6%). Diagnosis was made via laboratory test results in 197 (89.5%) patients, and 172 (78.2%) completed the treatment within the study period. With regard to patients with the cutaneous form, 134 (95%) were cured, 131 (97.8%) were treated with Glucantime(r), and 47 (36.7%) received dosage of >15 and <20mg Sb5+/kg/day. Among the cases with mucosal involvement, 87.1% were cured and most were treated with <20mg Sb5+/kg/day. Thus, the cure rate was 93.6%. CONCLUSIONS During the study period in the 15th Regional Health Division of Paraná State, ATL cases had a good response to treatment with a low rate of relapse or treatment failure, although a high percentage of mucosal or mucocutaneous form cases was also noted.

Lupoid leishmaniasis among the known cases of cutaneous leishmaniasis in Herat Province, western Afghanistan.

Lupoid cutaneous leishmaniasis (LCL) is an uncommon form of chronic cutaneous leishmaniasis, which is mostly caused by Leishmania tropica in the Old World and has a high incidence throughout early life. Between 2012 and 2013, patients with active lesions suspected to be cutaneous leishmaniasis (CL) were examined. Diagnosis was performed through a combination of methods, i.e., clinical examination, direct smears and kDNA polymerase chain reaction (PCR). Overall, 162(4.2%) subjects, through clinical examination and PCR confirmation alone, were diagnosed as having LCL, with the duration of the lesions varying from 2 to 5 years. Most (85.8%) of the subjects with LCL were <20 years of age. No amastigote was found in direct smears. Moreover, direct PCR on the negative smears for identifying Leishmania provided a specificity of 100%, and the species was identified as Leishmania tropica using specific kDNA PCR. Performing PCR on skin smears appears to offer a valuable method for the diagnosis of LCL because it is highly specific and sensitive, especially for clinical correlative studies.

The Jordanian Mid Jordan Valley is a classic focus of Leishmania major as revealed by RFLP of 56 isolates and 173 ITS-1-PCR-positive clinical samples.

The identity of the causative species of cutaneous leishmaniasis (CL) in the endemic Jordanian Mid Jordan Valley (JMidJV) was investigated using the polymerase chain reaction (PCR) amplifying the ribosomal internal transcribed spacer 1 (ITS-1) followed by the restriction fragment length polymorphism (RFLP). The geographical distribution of CL and the usefulness of ITS1 PCR in diagnosis of suspected CL in the study area were also addressed. Over the period from 2004 to 2009, 56 clinical isolates of Leishmania promastigotes and 185 lesion scrapings spotted on filter papers were obtained from suspected CL patients living in the JMidJV, which is divided into northern and southern districts. The majority (67.1%) of patients occurred in the populated eastern part of the southern district. Of the 185 suspected CL patients, 173 (93.5%) were confirmed positive using PCR. Leishmanial DNA was detected in 27 (90%) of 30 patients having clinically atypical lesions of CL and in 60 (92%) of 65 smear- and culture-negative cases having typical lesions of CL. The parasites in all of the 56 isolates and the 173 PCR-positive scrapings were classified as Leishmania major. In conclusion, PCR is useful in diagnosis of CL especially when smear and culture are negative. It is also recommended as a differential diagnostic tool of atypical lesions when CL is endemic. The identification of L. major as the causative species in such a considerable number of CL cases, representative of all mini foci of CL in the study area, shows that the JMidJV is a classic focus of L. major.

Leishmanioses do continente americano / Leishmaniasis in the Americas

No Brasil, ela já foi responsável por epidemias em diferentes cidades. Nos últimos dez anos, sua letalidade aumentou em diversas regiões do país. Em várias partes do mundo ela vem se expandindo, inclusive em lugares onde, anteriormente, não havia registro de transmissão. A infecção por parasitos do gênero Leishmania causa uma das doenças tropicais mais negligenciadas da atualidade. Estima-se que existam 350 milhões de pessoas em risco de contrair a infecção, sobretudo nas áreas mais pobres do planeta, e que dois milhões de novos casos de leishmanioses ocorram a cada ano. Esse grave cenário justifica o esforço empreendido pelos organizadores e demais pesquisadores do Instituto Oswaldo Cruz (IOC/Fiocruz) especialistas no assunto, assim como por profissionais de outras unidades da Fiocruz e instituições brasileiras: eles prepararam uma coletânea que compila o conhecimento já existente sobre o assunto, identifica os principais desafios e discute estratégias para enfrentá-los...

Intermediate/borderline disseminated cutaneous leishmaniasis.

Leishmaniasis is a diverse group of vector-borne diseases caused by a subset of predominantly intracellular protozoal species of the genus Leishmania. Cutaneous disease may be subdivided into localized, intermediate, and diffuse forms. Intermediate cutaneous leishmaniasis is distributed widely in Latin America and is characterized by cutaneous lesions, which may be accompanied by mucosal disease and demonstrate a tendency toward chronicity and relapse as well as resistance to standard treatment regimens. Leishmania parasites of the subgenus Viannia have been identified as the major etiologic agent of this subset of infections. The present review provides a brief perspective on leishmaniasis followed by a review of classification, transmission, clinical presentation, and evolution of disease, immunology, and current treatment approaches for the intermediate/borderline disseminated subset of cutaneous leishmaniasis.

Influência do estado nutricional na evolução clínica e terapêutica de adultos e idosos com leishmaniose tegumentar americana / Influence of the nutritional status in the clinical and therapeutical evolution in adults and elderly with american tegumentary leishmaniasis

O objetivo deste estudo foi descrever o estado nutricional de pacientes adultos e idosos com leishmaniose tegumentar americana (LTA). Foi realizado um estudo longitudinal em 68 pacientes adultos e idosos com LTA atendidos no Laboratório de Vigilância em Leishmanioses – Instituto de Pesquisa Clínica Evandro Chagas – Fiocruz, no período de 2009 a 2012. A avaliação nutricional foi realizada através do peso, altura, Índice de Massa Corporal e albumina sérica. A evolução clínica(epitelização e cicatrização das lesões) foi avaliada até dois anos após o tratamento de LTA. A maioria da amostra era composta por homens (71%), adultos (73%), com renda familiar de 1 a 5salários mínimos (79%) e com grau de instrução fundamental incompleto (48,5%). A forma predominante da LTA foi a cutânea (72%) e 39% apresentaram comorbidades, sendo a hipertensão arterial a mais frequente (30,8%). As intercorrências clínicas e nutricionais mais prevalentes foram:redução recente na ingestão de alimentos (23,9%), obstrução nasal (22,1%), úlcera oral (14,7%),anorexia + disfagia (13,2% cada) e odinofagia (10,3%). O tempo de cicatrização foi de 145,50 ±87,84 dias para lesões cutâneas e 172,89 ± 123 dias para lesões mucosas. Foram observados baixo peso em 10% e hipoalbuminemia em 12% dos pacientes...

The objective of this study is to describe the nutritional status of adult and elderly patients with American Tegumentary Leishmaniasis (ATL). It was conducted a longitudinal study in 68 adult andelderly patients with ATL treating at the Laboratório de Vigilância em Leishmanioses (Surveillance Leishmaniasis Laboratory) at the Instituto de Pesquisa Clínica Evandro Chagas (Evandro Chagas Clinical Research Institute)-Fiocruz, from 2009 to 2012. The nutritional assessment was performedusing weight, height, the Body Mass Index (BMI) and blood albumin levels. The clinical evolution(epithelialization, and wound healing) was measured up to two years after ATL treatment. Most ofthe sample was composed of men (71%), adults (73%), with household income of 1-5 minimumwages (79%), and incomplete basic education (48.5%). The predominant ATL form was cutaneous(72%), and 39% presented comorbidities, the most frequent was hypertension (30.8%). The most prevalent clinical and nutritional events were: recent reduction in food intake (23.9%); nasal obstruction (22.1%); oral ulcer (14.7%), anorexia + dysphagia (13.2% each) and odynophagia(10.3%). The healing time was 145.50 ± 87.84 days for skin lesions, and 172.89 ± 123 days formucous membrane lesions. Low weight in 10%, and hypoalbuminemia in 12% of the patients havebeen observed...

Leishmania (Viannia) braziliensis identification by PCR in the state of Para, Brazil.

The incidence of cutaneous leishmaniasis (CL) is increasing and there is limited surveillance of Leishmania species throughout the world. We identified the species associated with CL in a region of Amazonia, an area recognized for its Leishmania species variability. Clinical findings were analyzed and correlated with the species identified in 93 patients. PCR assays were based on small subunit ribosomal DNA (SSU-rDNA) and G6PD, and were performed in a laboratory located 3,500km away. Leishmania (V.) braziliensis was identified in 53 patients (57%). The other 40 patients (43%) carried a different species (including six cases of L. (L.) amazonensis). Molecular methods can be employed, using special media, to allow transport to distant laboratories. L. (V.) braziliensis is the most common species in the area of Para. The location of ulcers can suggest CL species.

Characterization of Leishmania spp. causing cutaneous leishmaniasis in Manaus, Amazonas, Brazil.

In the State of Amazonas, American tegumentary leishmaniasis is endemic and presents a wide spectrum of clinical variability due to the large diversity of circulating species in the region. Isolates from patients in Manaus and its metropolitan region were characterized using monoclonal antibodies and isoenzymes belonging to four species of the parasite: Leishmania (Viannia) guyanensis, 73% (153/209); Leishmania (Viannia) braziliensis, 14% (30/209); Leishmania (Leishmania) amazonensis, 8% (17/209); and Leishmania (Viannia) naiffii, 4% (9/209). The most prevalent species was L. (V.) guyanensis. The principal finding of this study was the important quantity of infections involving more than one parasite species, representing 14% (29/209) of the total. The findings obtained in this work regarding the parasite are further highlighted by the fact that these isolates were obtained from clinical samples collected from single lesions.

Fissure leishmaniasis: A new variant of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) may appear at unusual sites or present with atypical morphologies. The lip is considered one of the unusual sites and a fissure of the lower lip is an atypical morphology that has not been described in CL. We report two cases of CL who presented as cutaneous fissures (on lower lip in one patient and dorsum of finger in another). They were diagnosed by demonstrating leishmania parasites in skin smear preparations and were treated accordingly.

Survival, Population Size, and Gonotrophic Cycle Duration of Nyssomyia neivai (Diptera: Psychodidae) at an Endemic Area of American Cutaneous Leishmaniasis in Southeastern Brazil

The survival, absolute population size, gonotrophic cycle duration, and temporal and spatial abundance of Nyssomyia neivai (Pinto) were studied in a rural area endemic for American cutaneous leishmaniasis (ACL) in Conchal, Sõo Paulo State, southeastern Brazil, using mark-release-recapture techniques and by monitoring population fluctuation. The monthly abundance exhibited a unimodal pattern, with forest and domicile habitats having the highest relative abundances. A total of 1,873 males and 3,557 females were marked and released during the six experiments, of which 4.1–13.0% of males and 4.1–11.8% of females were recaptured. Daily survivorship estimated from the decline in recaptures per day was 0.681 for males and 0.667 for females. Gonotrophic cycle duration was estimated to be 4.0 d. Absolute population size was calculated using the Lincoln Index and ranged from 861 to 4,612 males and from 2,187 to 19,739 females. The low proportion of females that reach the age when they are potentially infective suggests that N. neivai has a low biological capacity to serve as a vector and that factors such as high biting rates and opportunistic feeding behavior would be needed to enable Leishmania (Viannia) braziliensis Vianna transmission. This agreed with the epidemiological pattern of ACL in southeastern Brazil that is characterized by low incidence, with isolated cases acquired principally within domiciliary habitats...

Espécies de Lutzomyia França (Diptera: Psychodidae, Phlebotominae) em área de Leishmaniose Tegumentar no município de Carmo, RJ / Species of Lutzomyia França (Diptera: Psychodidae, Phlebotominae) in area with Cutaneous Leishmaniasis case of Carmo County, Rio de Janeiro State, Brazil

Com o objetivo de conhecer a diversidade de flebotomíneos da fazenda São José, município de Carmo, Rio de Janeiro, foram realizadas capturas no intra, peridomicílio e na floresta, tendo em vista o registro do primeiro caso autóctone de leishmaniose tegumentar americana. Foram capturados 4595 flebotomíneos de seis espécies do gênero Lutzomyia: L. intermedia (Lutz & Neiva), L. lenti (Mangabeira), L. whitmani (Antunes & Coutinho), L. migonei (França), L. ayrozai (Barretto & Coutinho) e L. quinquefer (Dyar). L. intermedia foi predominante (99,1 por cento); com alta freqüência entre 18:00h e 20:00h.

Captures of sand flies were carried out in peridomiciliary, domiciliary and forest environments on São José farm, located in Carmo county where an autochthonous case of American Cutaneous Leishmaniasis occurred to investigate the probable vector of the disease. A total of 4.595 sand flies belonging to six species of the genus Lutzomyia were captured: L. intermedia (Lutz & Neiva), L. lenti (Mangabeira), L. whitmani (Antunes & Coutinho) L. migonei (França), L. ayrozai (Barretto & Coutinho) andL. quinquefer (Dyar). L. intermedia was the predominant species (99.1 percent), its highest frequencies occurring between 6 p.m. and 8 p.m.