Liliane de Fátima Antonio

Evaluation of polymerase chain reaction in the routine diagnosis for tegumentary leishmaniasis in a referral centre.

The present study investigated the diagnostic value of polymerase chain reaction (PCR) performed in parallel to conventional methods at an American tegumentary leishmaniasis (ATL) referral centre for diagnosis. Accuracy parameters for PCR were calculated using 130 patients with confirmed ATL (ATL group), 15 patients established with other diseases and 23 patients with a lesion suggestive of ATL, but without parasitological confirmation (NDEF group). PCR showed 92.3% sensitivity, 93.3% specificity, a 99.2% positive predictive value and a 13.84 positive likelihood ratio. In the NDEF group, PCR confirmed ATL in 13 of the 23 patients, seven of whom responded to leishmaniasis treatment and six who presented spontaneous healing of the lesion. PCR should be included in the routine diagnostic procedures for ATL, especially for cases found to be negative by conventional methods.

Montenegro skin test and age of skin lesion as predictors of treatment failure in cutaneous leishmaniasis.

A case-control study was conducted to examine the association among the Montenegro skin test (MST), age of skin lesion and therapeutic response in patients with cutaneous leishmaniasis (CL) treated at Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. For each treatment failure (case), two controls showing skin lesion healing following treatment, paired by sex and age, were randomly selected. All patients were treated with 5 mg Sb5+/kg/day of intramuscular meglumine antimoniate (Sb5+) for 30 successive days. Patients with CL were approximately five times more likely to fail when lesions were less than two months old at the first appointment. Patients with treatment failure showed less intense MST reactions than patients progressing to clinical cure. For each 10 mm of increase in MST response, there was a 26% reduction in the chance of treatment failure. An early treatment - defined as a treatment applied for skin lesions, which starts when they are less than two months old at the first appointment -, as well as a poor cellular immune response, reflected by lower reactivity in MST, were associated with treatment failure in cutaneous leishmaniasis.

Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature

We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

FIRST REPORT OF CUTANEOUS LEISHMANIASIS CAUSED BY Leishmania (Leishmania) infantum chagasi IN AN URBAN AREA OF RIO DE JANEIRO, BRAZIL.

SUMMARY American tegumentary leishmaniasis (ATL) is an infectious disease caused by protozoa of the genus Leishmania, and transmitted by sandflies. In the state of Rio de Janeiro, almost all of the cases of American tegumentary leishmaniasis (ATL) are caused by Leishmania (Viannia) braziliensis, while cases of visceral leishmaniasis (VL) are caused by Leishmania (Leishmania) infantum chagasi. The resurgence of autochthonous VL cases in Rio de Janeiro is related to the geographic expansion of the vector Lutzomyia longipalpis and its ability to adapt to urban areas. We report the first case of leishmaniasis with exclusively cutaneous manifestations caused by L. (L.) infantum chagasi in an urban area of Rio de Janeiro. An eighty-one-year-old woman presented three pleomorphic skin lesions that were not associated with systemic symptoms or visceromegalies. Multilocus enzyme electrophoresis identified L. (L.) infantum chagasi, but direct smear and PCR of bone narrow were negative for Leishmania sp. (suggesting exclusively cutaneous involvement). We discuss the different dermatological presentations of viscerotropic leishmaniasis of the New and Old World, and the clinical and epidemiological importance of the case. Etiologic diagnosis of ATL based upon exclusive clinical criteria may lead to incorrect conclusions. We should be aware of the constant changes in epidemiological patterns related to leishmaniases.

Comparison between in vivo measurement of the Montenegro skin test and paper recording

Montenegro skin test and paper recording The Montenegro skin test (MST) is the main complementary exam for the diagnosis of American cutaneous leishmaniasis (ACL) and evaluates the delayed hypersensitivity reaction to Leishmania antigens. The antigen is injected intradermally into the forearm and, after 48 hours, the presence of local induration is evaluated. Induration diameters of 5 mm or more are considered to be positive. Sokal observed that some professionals encounter difficulties during the tuberculin test in delimiting the margin of the induration by palpation. Additionally, discordance in the reading was observed between trained professionals. The author therefore developed the ballpoint pen technique, in which a line is drawn with a ballpoint pen from a point about 2 cm away from the indurated area toward its center until noting resistance when the margin of the induration is reached. Reading of the reaction became possible after the introduction of the stamping technique in which paper soaked in 70% alcohol is pressed on the site of the induration.. However, no studies are available in the literature comparing measurements performed in vivo at the site of application of the test and those recorded on paper. A total of 154 patients with a clinical suspicion of ACL seen at Instituto de Pesquisa Clínica Evandro Chagas, Fiocruz, were submitted to the MST. After 48 hours, in vivo reading was performed by the ballpoint pen technique (Fig. 1). In addition, a paper recording was obtained from each reaction and stored for subsequent measurement by another professional. Both the in vivo and paper measurements were performed within the demarcation line with a millimeter-graded ruler. The results of the two measures were compared by the kappa test using the Epi-Info 6 program. A total of 143 results were concordant and 11 were discordant in terms of a positive or negative MST. The kappa index of agreement between the two measurements was 0.83%, with an approximate standard error of 0.048 and P < 0.0001 (Table 1). A difference of 1 mm between readings was observed in 59 patients, and differences of 2–6 mm were observed in 18. However, the paper reading resulted in a negative test (diameter <5 mm) in only 11 patients. These results suggest that the paper recording might be used as an alternative to the direct reading, despite the 11 discordant patients. In addition, the paper with the tracing provides a record and documentation of the exam and may serve as a quality control for the evaluation of services standardizing the technique.

Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil

Background Although high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute. Methods A single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of Leishmania (Viannia) braziliensis transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: NCT01301924. Results Overall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7–29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1–31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony. Conclusions Compared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.

Effect of secondary infection on epithelialisation and total healing of cutaneous leishmaniasis lesions

BACKGROUND Cutaneous leishmaniasis (CL) generally presents with a single or several localised cutaneous ulcers without involvement of mucous membranes. Ulcerated lesions are susceptible to secondary contamination that may slow the healing process. OBJECTIVE This study verified the influence of non-parasitic wound infection on wound closure (epithelialisation) and total healing. METHODS Twenty-five patients with a confirmed diagnosis of CL and ulcerated lesions underwent biopsy of ulcer borders. One direct microbial parameter (germ identification in cultures) and four indirect clinical parameters (secretion, pain, burning sensation, pruritus) were analysed. FINDINGS Biopsies of ten lesions showed secondary infection by one or two microorganisms (Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, Streptococcus pyogenes and Candida parapsilosis). “Secretion” and “burning sensation” influenced epithelialisation time but not total healing time. Positive detection of germs in the ulcer border and “pain” and “pruritus” revealed no influence on wound closure. CONCLUSIONS Our borderline proof of clinical CL ulcer infection inhibiting CL wound healing supports the need to follow antimicrobial stewardship in CL ulcer management, which was recently proposed for all chronic wounds.

Low dose systemic or intralesional meglumine antimoniate treatment for American tegumentary leishmaniasis results in low lethality, low incidence of relapse, and low late mucosal involvement in a referral centre in Rio de Janeiro, Brazil (2001-2013)

BACKGROUND American tegumentary leishmaniasis (ATL) is a non-lethal parasitic disease that presents with cutaneous (CL) and mucosal (ML) clinical forms. ATL treatment aims at healing the lesions and preventing the development of the late mucosal form. Systemic meglumine antimoniate (MA) therapy with 10-20 mg Sb5+/kg/day is the first choice of treatment. However, alternative therapies using 5 mg Sb5+/kg/day or intralesional (IL) MA are the usual regimens at the National Institute of Infectious Diseases (NIID), Rio de Janeiro, Brazil. OBJECTIVES To evaluate lethality and the incidence of relapse and development of late ML in CL patients treated at NIID from 2001 until 2013. METHODS Data were recovered from records of all ATL patients diagnosed during that period. FINDINGS Out of 777 patients, 753 were treated with MA (96.9%). Of those, 89.1% received alternative therapy of 9.9% IL and 79.2% systemic 5 mg Sb5+/kg/day. Some patients required 1-3 additional courses of treatment, thus making a total of 997 courses; 85.2% of them were subjected to alternative therapies. Lethality was 0.1%, relapse incidence 5.8%, and late ML incidence 0.25%. As a final outcome for the 777 patients, 95.9% were cured, 0.1% died and 4.0% were not able to follow-up. MAIN CONCLUSIONS Alternative MA schedules resulted in low lethality without increase of relapse or late ML incidence.

Sporothrix schenckii Sensu Lato identification in fragments of skin lesion cultured in NNN medium for differential diagnosis of cutaneous leishmaniasis

Eighty-nine patients with clinical suspicion of leishmaniasis were referred for differential diagnosis. Sporothrix schenckii sensu lato was isolated in Novy-MacNeal-Nicolle + Schneider media in 98% of 64 patients with final diagnosis of sporotrichosis. This medium may be suitable for diagnosis of sporotrichosis in areas where cutaneous leishmaniasis is also endemic.

Pancreatic toxicity as an adverse effect induced by meglumine antimoniate therapy in a clinical trial for cutaneous leishmaniasis

SUMMARY American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial. In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA). Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit. We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients. Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group. Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL.