Papers by Armando Schubach

Memórias do Instituto Oswaldo Cruz, 2015
In human cutaneous leishmaniasis (CL), the immune response is mainly mediated by T-cells. The rol... more In human cutaneous leishmaniasis (CL), the immune response is mainly mediated by T-cells. The role of CD8+ T-lymphocytes, which are related to healing or deleterious functions, in affecting clinical outcome is controversial. The aim of this study was to evaluate T-cell receptor diversity in late-differentiated effector (LDE) and memory CD8+ T-cell subsets in order to create a profile of specific clones engaged in deleterious or protective CL immune responses. Healthy subjects, patients with active disease (PAD) and clinically cured patients were enrolled in the study. Total CD8+ T-lymphocytes showed a disturbance in the expression of the Vβ2, Vβ9, Vβ13.2, Vβ18 and Vβ23 families. The analyses of CD8+ T-lymphocyte subsets showed high frequencies of LDE CD8+ T-lymphocytes expressing Vβ12 and Vβ22 in PAD, as well as effector-memory CD8+ T-cells expressing Vβ22. We also observed low frequencies of effector and central-memory CD8+ T-cells expressing Vβ2 in PAD, which correlated with a greater lesion size. Particular Vβ expansions point to CD8+ T-cell clones that are selected during CL immune responses, suggesting that CD8+ T-lymphocytes expressing Vβ12 or Vβ22 are involved in a LDE response and that Vβ2 contractions in memory CD8+ T-cells are associated with larger lesions.

Mycopathologia, 2002
A total of 148 cats with a clinical and mycologic diagnosis of sporotrichosis and 84 apparently h... more A total of 148 cats with a clinical and mycologic diagnosis of sporotrichosis and 84 apparently healthy cats with domiciliary contact with the affected animals were studied. Sporothrix schenckii was isolated from 148 (n = 148; 100%) clinical samples of cutaneous lesion (biopsy, swab or aspiration of purulent secretion), 47 (n = 71; 66.2%) nasal cavities, 33 (n = 79; 41.8%) oral cavities, and 15 (n = 38; 39.5%) nails of cats with sporotrichosis. Histopathological examination revealed yeast-like structures in 50 (n = 70; 71.4%) of the biopsies studied. S. schenckii was isolated from the blood culture of one cat (n = 5, 20%) with the disseminated cutaneous form of the disease. On another occasion, the fungus was isolated from the testis of one (n = 7; 14.3%) of the animals submitted to sterilization. In the group of cats with domiciliary contacts, 3 (n = 84; 3.57%) oral swabs showed positive cultures. Isolation of S. schenckii from different clinical specimens during both the clinical ...

Since 2006 the monitoring of costs and expenditures in the Evandro Chagas Clinical Research Insti... more Since 2006 the monitoring of costs and expenditures in the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC / FIOCRUZ), uses the estimates generated by the Assessment and Monitoring - Management Indicators Project of IPEC (PAA-IGs). The aim of this paper is to highlight the contribution of the PAA-IGs' model to improve results-oriented management adopted at FIOCRUZ and IPEC from the 90s onward. The research method is a comparative case study that deals with decision making regarding health care support activities resulting from signals provided by three different classes of evidence, namely, the values of the executed budget of IPEC, the budget forecasts in the Annual Plan of IPEC and the estimates of costs and expenditures generated by the Project PAA-IGs. The result is that expenditures calculated by the PAA-IGs' model improve the result of cost drivers computation at IPEC. The conclusion is that the paper points to the requirements of the results-...

Revista brasileira de parasitologia veterinária = Brazilian journal of veterinary parasitology : Órgão Oficial do Colégio Brasileiro de Parasitologia Veterinária
The objective of the present study was to investigate the dynamics and profile of American Cutane... more The objective of the present study was to investigate the dynamics and profile of American Cutaneous Leishmaniasis (ACL) in an old colonization area in the State of Rio de Janeiro. Health departments of municipalities in the Central-Southern region that had notified cases to the Ministry of Health's Notifable Diseases Information System between 1997 and 2002 were contacted to obtain data. Out of the 119 cases recorded, 51 patients were visited for an interview and inspection of the environment. The cases of ACL exhibited a profile similar to that observed in other Brazilian cities, affecting individuals of both genders, all age groups and different occupational categories, especially students. Risk activities were reported by 56.9% of the interviewees and 84.3% had never left their homeland. Water courses, chicken coops, bamboo plantations and different fruit trees including banana plants and mango trees were frequently observed in the surrounding environment. Most of the interv...
International Journal of Dermatology, 2002
Case 1 A 34-year-old woman had ulcerated lesion 2 cm in diameter on the right leg of 2 months&... more Case 1 A 34-year-old woman had ulcerated lesion 2 cm in diameter on the right leg of 2 months' evolution. She also presented painful erythematous nodules on lower limbs accompanied by arthralgia appearing 1 month after the initial lesion (Figure 1a). The patient reported ...
Revista do Instituto de Medicina Tropical de São Paulo, 2009

Revista do Instituto de Medicina Tropical de São Paulo, 2005
A total of 24 patients with syphilis and HIV infection were treated from January 1997 to March 20... more A total of 24 patients with syphilis and HIV infection were treated from January 1997 to March 2003 at the Infectious Dermatology Outpatient Clinic of the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. The caseload consisted of 20 males (83.3%) and four females (16.7%), with a mean age of 38.04 years and mean T CD4+ count of 389.5 cells/mL. Syphilis was diagnosed as secondary in 16 (62.5%) patients, late latent in eight (33.3%), and tertiary in one (4.2%). Manifestations of secondary syphilis were palmar and plantar erythematopapulous cutaneous lesions in nine (37.5%), papulous exanthema in four (16.7%), patchy alopecia in 3 (12.5%) and osteochondritis in one patient (4.2%). Tertiary syphilis was characterized by verrucous lesions. Neurosyphilis was diagnosed in four patients (16.7%), with headache as the only manifestation in two patients. Drugs used in treatment included benzathine penicillin, ceftriaxone, erythromycin, and crystalline penicillin. Cure was achieved in 18 patients (75%). Five patients (20.8%) were retreated, three of whom presented a history of re-exposure. This study confirms the importance of establishing the diagnosis of neurosyphilis in patients with HIV infection, in addition to performing follow-up on treatment for syphilis.
Revista do Instituto de Medicina Tropical de São Paulo, 2014
-Lesion's follow up: A -Ulcerated lesion, before the first intralesional infiltration, measuring ... more -Lesion's follow up: A -Ulcerated lesion, before the first intralesional infiltration, measuring 20 x 10 mm, with infiltrated erythematous borders, partially covered by crusts and with an epithelialized center of about 5 mm. B -Edema of the forearm and hand, after the second intralesional infiltration of the lesion with meglumine antimoniate. Infiltration, erythema and coalescing vesicles, turning into larger bubbles of up to 35 mm. C -Atrophic scar, with erythema, residual hyperpigmentation on the spot where the biggest bubble was located (49 days after the second intralesional meglumine antimoniate).
Revista da Sociedade Brasileira de Medicina Tropical, 2011
This is a case report of a Brazilian soldier with cutaneous leishmaniasis. The lesion relapsed fo... more This is a case report of a Brazilian soldier with cutaneous leishmaniasis. The lesion relapsed following two systemic treatments with meglumine antimoniate. The patient was treated with amphotericin B, which was interrupted due to poor tolerance. Following isolation of Leishmania sp., six intralesional infiltrations of meglumine antimoniate resulted in no response. Leishmania sp promastigotes were again isolated. The patient was submitted to intramuscular 4 mg/kg pentamidine. Parasites from the first and second biopsies were identified as Leishmania (Viannia) braziliensis; those isolated from the first biopsy were more sensitive to meglumine antimoniate in vitro than those isolated from the second biopsy. No relapse was observed.

Disease Markers, 2015
This study evaluated the in vitro sensitivity of paired Leishmania braziliensis samples isolated ... more This study evaluated the in vitro sensitivity of paired Leishmania braziliensis samples isolated from the same patient before pentavalent antimonial treatment (Sample A) and after treatment failure or cutaneous leishmaniasis reactivation (Sample B) in patients undergoing intralesional administration or injections (5 mgSb(V)/kg/d) of meglumine antimoniate. Fourteen samples from 7 patients were studied. After 24 h of drug exposure, 50% lethal dose (LD50) values for promastigotes ranged from 0.37 mg/mL to 5.86 mg/mL for samples obtained before treatment (A) and 0.89 mg/mL to 7.80 mg/mL for samples obtained after treatment (B). After 48 h, LD50 values ranged from 0.37 mg/mL to 5.75 mg/mL and 0.70 mg/mL to 7.68 mg/mL for A and B samples, respectively. After 48 h, LD50 values for amastigotes ranged from 11.7 to 44.3 μg/mL for A samples and 13.7 to 52.7 μg/mL for B samples. Of 7 patients, 1 discontinued treatment and 6 were cured after retreatment with amphotericin B (4 cases) or meglumine antimoniate (2 cases). Overall the B samples had higher LD50 values than A samples; however the difference was not significant. These results do not support the hypothesis that low-dose and intralesional treatments induce selection of resistant parasites in vitro and suggest that other factors may influence therapeutic outcome in patients with poor response to initial treatment.
Revista da Sociedade Brasileira de Medicina Tropical, 2014
Nine cases of visceral leishmaniasis occurred recently in Barra Mansa, State of Rio de Janeiro, w... more Nine cases of visceral leishmaniasis occurred recently in Barra Mansa, State of Rio de Janeiro, with a high mortality rate. We reviewed the medical records of the patients. Eight were male; 7 were adults. Patients who died progressed to death quickly and presented with aggravating factors: systemic steroid therapy before diagnosis, bleeding, severe liver involvement, infection, and/or refusal to receive transfusion. We warn clinicians to be aware of the emergence of visceral leishmaniasis in new areas and to keep in mind the possibility of atypical clinical pictures and aggravating factors, so timely diagnosis can be made and prompt and adequate treatment can be initiated.

Revista do Instituto de Medicina Tropical de São Paulo, 2014
The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Ou... more 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.
Emerging Infectious Diseases, 2005

Revista do Instituto de Medicina Tropical de São Paulo, 2014
A case-control study was conducted to examine the association among the Montenegro skin test (MST... more 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 Sb 5+ /kg/day of intramuscular meglumine antimoniate (Sb 5+ ) 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.
Revista do Instituto de Medicina Tropical de São Paulo, 2014

PLoS ONE, 2014
American tegumentary leishmaniasis (ATL) can affect the skin or mucosa (mucocutaneous leishmanias... more American tegumentary leishmaniasis (ATL) can affect the skin or mucosa (mucocutaneous leishmaniasis - MCL) including the oral cavity. MCL oral lesions are often confused with other oral diseases, delaying diagnosis and specific treatment, and increasing the likelihood of sequelae. Thus, increasing the knowledge of the evolution of ATL oral lesions can facilitate its early diagnosis improving the prognosis of healing. Evaluate the frequency of ATL oral lesion and describe its clinical, laboratory and therapeutic peculiarities. A descriptive transversal study was carried out, using data from medical records of 206 patients with MCL examined at the outpatient clinics-IPEC-Fiocruz between 1989 and 2013. Proportions were calculated for the categorical variables and the association among them was assessed by the Pearson's chi-square test. Measures of central tendency and dispersion were used for the continuous variables and their differences were assessed by both parametric (t test) and non parametric (Mann-Whitney) tests. P-values <0.05 were considered as significant. The most affected site was the nose, followed by the mouth, pharynx and larynx. Seventy eight (37.9%) have oral lesions and the disease presented a lower median of the evolution time than in other mucous sites as well as an increased time to heal. The presence of oral lesion was associated with: the presence of lesions in the other three…

International Journal of Dermatology, 1997
The drug of choice for leishmaniasis is pentavalent antimony and different regimens are under con... more The drug of choice for leishmaniasis is pentavalent antimony and different regimens are under continuous evaluation. The ideal therapy should be simple, effective, and with no or minor side-effects. In this paper we have studied the efficacy of intralesionally applied antimony in New World cutaneous leishmaniasis. Seventy-four patients from Rio de Janeiro state, Brazil, and presenting with single ulcerative cutaneous lesions mainly located on the trunk or extremities were enrolled in the study. The drug employed was N-methyl glucamine (425 mg of Sbv in each 5 ml ampoule). Each lesion was infiltrated with the drug at the four cardinal points in order to achieve complete blanching. Of the 74 patients, 59 (80%) were healed after a 12-week interval. Extensive follow-up (up to 10 years) disclosed no relapses or the development of mucosal lesions. The aim of therapy in New World cutaneous leishmaniasis is the healing of the cutaneous lesion and the prevention of late mucosal damage. Both conditions were achieved with the treatment employed with no side-effects and a considerable decrease in costs. In addition, the method is easy to apply in the field.

Veterinary Parasitology, 2007
American tegumentary leishmaniasis (ATL) shows a reduced humoral response in dogs and levels of s... more American tegumentary leishmaniasis (ATL) shows a reduced humoral response in dogs and levels of specific antibodies may therefore not be detected by indirect immunofluorescence. Although the sensitivity of enzyme-linked immunosorbent assay (ELISA) is higher than that of indirect immunofluorescence, the best antigen for the diagnosis of ATL in dogs has not been defined. The detection of IgG subclasses represents an alternative to increase the efficiency of the serological diagnosis. In Rio de Janeiro, sporotrichosis is the main differential diagnosis of ATL in dogs, and a sensitive, specific and little invasive method that permits the discrimination of the two diseases is desired. In the present study, 69 serum samples, 34 obtained from dogs with ATL and 35 from dogs with sporotrichosis, all of them with a confirmed etiological diagnosis, were tested. The samples were analyzed by ELISA using Leishmania (Viannia) braziliensis and L. (L.) chagasi antigens for the detection of anti-Leishmania IgG, IgG1 and IgG2. The use of L. (V.) braziliensis antigens for the detection of IgG and IgG2 yielded the best results. Using L. (L.) chagasi antigen, the sensitivity and specificity for the detection of IgG were 82.4% and 100%, respectively, whereas both sensitivity and specificity were 97.1% with the L. (V.) braziliensis antigen. No improvement in the performance of the test was observed when IgG2 was analyzed separately. The IgG1 assays presented low accuracy, irrespective of the antigen used: sensitivity and specificity of 58.8% and 60% for L. (V.) braziliensis and of 64.7% and 77.1% for L. (L.) chagasi, respectively. The present results suggest that IgG ELISA using the L. (V.) braziliensis shows the best performance for the diagnosis of ATL, permitting the discrimination between cases of ATL and sporotrichosis in dogs. #

Brazilian Journal of Infectious Diseases, 2004
Euthanasia of seropositive dogs has been one of the principal measures adopted by the Program for... more Euthanasia of seropositive dogs has been one of the principal measures adopted by the Program for the Control of Leishmaniasis in Brazil for many years. However, its efficacy is currently being questioned. We obtained intact skin samples from 20 Leishmania-reactive dogs from the municipality of Rio de Janeiro that had been referred for euthanasia. The promastigote forms of Leishmania were isolated in culture from 18 of these animals. Fourteen of these isolates were identified as Leishmania (Leishmania) chagasi by isoenzyme electrophoresis; seven of these were from asymptomatic dogs and seven were from symptomatic animals with visceral leishmaniasis. In conclusion, cutaneous parasitism is found in the intact skin of dogs naturally infected with L. (L.) chagasi, irrespective of the presence or absence of clinical signs suggestive of visceral leishmaniasis.
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Papers by Armando Schubach