Luiz Carlos de Lima Ferreira

Paracoccidioidomicose enzoótica em tatus (Dasypus novemcinctus) no estado do Pará

Paracoccidioides brasiliensis foi encontrado, por inoculacao de triturado de figado e baco em hamsters, em 4 de 20 tatus (Dasypus novemcinctus) examinados na regiao de Tucurui, Para. Hamsters inoculados por via intradermica e peritoneal com o parasito desenvolveram infeccoes generalizadas e morreram em 1½ a 13 meses. A diagnose do fungo foi confirmada por histopatologia e cultura. Nao se observaram sinais macroscopios de doencas nos tatus. A distribuicao geografica de D. novemcinctus abrange a area endemica de paracoccidioidomicose humana, sugerindo-se que o tatu tenha algum papel na ecologia do fungo.

Mucosal Leishmaniasis Caused by Leishmania (Viannia) braziliensis and Leishmania (Viannia) guyanensis in the Brazilian Amazon

Background Leishmania (Viannia) braziliensis is a parasite recognized as the most important etiologic agent of mucosal leishmaniasis (ML) in the New World. In Amazonia, seven different species of Leishmania, etiologic agents of human Cutaneous Leishmaniasis, have been described. Isolated cases of ML have been described for several different species of Leishmania: L. (V.) panamensis, L. (V.) guyanensis and L. (L.) amazonensis. Methodology Leishmania species were characterized by polymerase chain reaction (PCR) of tissues taken from mucosal biopsies of Amazonian patients who were diagnosed with ML and treated at the Tropical Medicine Foundation of Amazonas (FMTAM) in Manaus, Amazonas state, Brazil. Samples were obtained retrospectively from the pathology laboratory and prospectively from patients attending the aforementioned tertiary care unit. Results This study reports 46 cases of ML along with their geographical origin, 30 cases caused by L. (V.) braziliensis and 16 cases by L. (V.) guyanensis. This is the first record of ML cases in 16 different municipalities in the state of Amazonas and of simultaneous detection of both species in 4 municipalities of this state. It is also the first record of ML caused by L. (V.) guyanensis in the states of Pará, Acre, and Rondônia and cases of ML caused by L. (V.) braziliensis in the state of Rondônia. Conclusions/Significance L. (V.) braziliensis is the predominant species that causes ML in the Amazon region. However, contrary to previous studies, L. (V.) guyanensis is also a significant causative agent of ML within the region. The clinical and epidemiological expression of ML in the Manaus region is similar to the rest of the country, although the majority of ML cases are found south of the Amazon River.

Estudo clínico randomizado comparando antimoniato de meglumina, pentamidina e anfotericina B para o tratamento da leishmaniose cutânea ocasionada por Leishmania guyanensis

FUNDAMENTALS American tegumentary leishmaniasis (ATL) treatment remains a challenge, since most available drugs are injectable and only a small number of comparative, randomized clinical trials have been performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania. OBJECTIVES To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia) guyanensis. METHODS 185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-examined one, two and six months after completion of treatment. RESULTS No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT) analysis showed efficacy of 58.1% for pentamidine and 55.5% for meglumine (p=0.857). The amphotericin B group was analyzed separately, since 28 patients (75.7%) in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40%) patients, especially arthralgia (20.3%) in the meglumine group, and pain (35.1%) or induration (10.8%) at the site of injection in the pentamidine group. CONCLUSION Pentamidine and meglumine show similar efficacy in the treatment of ATL caused by L. guyanensis. Given the low efficacy of both drugs, there is an urgent need for new therapeutical approaches.

Leprosy and HIV Coinfection: A Clinical, Pathological, Immunological, and Therapeutic Study of a Cohort from a Brazilian Referral Center for Infectious Diseases

BACKGROUND Although awareness of the relevance of leprosy and human immunodeficiency virus (HIV) coinfection is increasing worldwide, several aspects of this co-occurrence are not fully understood. METHODS We describe clinical, pathological, immunological, and therapeutic long-term follow-up of a cohort of 25 individuals with leprosy and HIV infection from Manaus, Amazonas. RESULTS Careful description of our cohort indicates a higher prevalence of leprosy in an HIV-positive population than that in the general population. We also observed upgrading shifting of leprosy clinical forms after initiation of highly active antiretroviral therapy and multidrug therapy and an impact of HIV infection on leprosy granuloma formation, among other features. CONCLUSION Taken together, these new insights allow the proposition of a classification system that includes (1) leprosy and HIV true coinfection, (2) opportunistic leprosy disease, and (3) leprosy related to highly active antiretroviral therapy.

The value of high-resolution anoscopy in the diagnosis of anal cancer precursor lesions in hiv-positive patients

CONTEXT Anal cancer, although a still rare disease, is being observed in ascending rates among some population segments known to be at risk for the development of the disease. Human papillomavirus (HPV) infection, immunodepression and anal intercourse are some factors associated with the development of the malignancy. Its similarities to cervical cancer have led to many studies aiming to establish guidelines for detecting and treating precursor lesions of anal cancer, with the goal of prevention. High-resolution anoscopy is routinely used for the diagnosis of anal cancer precursor lesions in many centers but the medical literature is still deficient concerning the role of this diagnostic modality. OBJECTIVES To evaluate diagnostic validation and precision measures of high-resolution anoscopy in comparison to histopathological results of anal biopsies performed in HIV-positive patients treated at the Tropical Medicine Foundation of Amazonas, AM, Brazil. To observe any possible association between some risk factors for the development of anal cancer and the presence of anal squamous intraepithelial lesions. METHODS A hundred and twenty-eight HIV-positive patients were submitted to anal canal cytological sampling for the detection of HPV infection by a PCR based method. High-resolution anoscopy was then performed after topical application of acetic acid 3% in the anal canal for 2 minutes. Eventual acetowhite lesions that were detected were recorded in respect to location, and classified by their tinctorial pattern, distribution aspect, relief, surface and vascular pattern. Biopsies of acetowhite lesions were performed under local anesthesia and the specimens sent to histopathological analysis. The patients were interviewed for the presence of anal cancer risk factors. RESULTS The prevalences of anal HPV infection and of anal squamous intraepithelial lesions in the studied population were, respectively, 79% and 39.1%. High-resolution anoscopy showed sensibility of 90%, specificity of 19.23%, positive predictive value of 41.67%, negative predictive value of 75%, and a kappa coefficient of 0.076. From the analyzed lesions, high-grade squamous intraepithelial lesions was more frequently observed in association to dense (68%), flat (61%), smooth (61%), non-papillary (83%) and normal vascular pattern (70%) acetowhite lesions, while low-grade squamous intraepithelial lesions tended to be associated to dense (66%), flat-raised or raised (68%), granular (59%), non-papillary (62%) and normal vascular pattern (53%) acetowhite lesions. No statistical significance was observed as to the association of epidemiological characteristics and of most of the investigated anal cancer risk factors and presence of acetowhite lesions or anal squamous intraepithelial lesions. However, anal receptive sex and anal HPV infection were significantly associated to anal squamous intraepithelial lesions (P = 0.0493 and P = 0.006, respectively). CONCLUSION High-resolution anoscopy demonstrated to be a sensitive, but not specific test for the detection of anal squamous intraepithelial lesions. Risk factors anal receptive sex and anal HPV infection were significantly associated to the presence of anal squamous intraepithelial lesions. Based on high-resolution anoscopy image data, acetowhite lesions relief and surface pattern were prone to distinguish between low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions.

High-Resolution Anoscopy in the Diagnosis of Anal Cancer Precursor Lesions in Renal Graft Recipients

BackgroundRenal graft recipients are one of the population groups known to be at high risk of developing anal cancer. This study investigated the presence of subclinical anal squamous intraepithelial lesions and the diagnostic ability of high-resolution anoscopy in detecting these lesions in renal graft recipients followed-up in Manaus.MethodsIn a cross-sectional study, 50 renal graft recipients were interviewed and submitted to high-resolution anoscopy with biopsies of acetowhite lesions or of the anal transition zone mucosa when acetowhitening was absent. Considering the histopathological reports of the examined anal specimens as the gold standard, the diagnostic validation and precision measures of high-resolution anoscopy were calculated as well as the prevalence of anal squamous intraepithelial lesions in the studied population.ResultsIn 42 renal graft recipients with satisfactory histopathological readings, prevalence of anal squamous intraepithelial lesions or condyloma acuminatum (ASIL-ACU) was 23.81%. Sensitivity of high-resolution anoscopy was 100%; specificity, 65.63%; positive predictive value, 47.62%; negative predictive value, 100%; and kappa coefficient, 0.48.ConclusionsWith a prevalence of 23.81% of subclinical ASIL-ACU lesions, the studied renal graft recipients had all these lesions detected by high-resolution anoscopy, notwithstanding most anal transition zone acetowhitened biopsied areas did not reveal histopathological aspects of anal cancer precursor lesions or condyloma acuminatum. Therefore, greater experience with the diagnostic tool was felt necessary to enhance its positive predictive value, specificity and diagnostic precision.Renal graft recipients are one of the population groups known to be at high risk of developing anal cancer. This study investigated the presence of subclinical anal squamous intraepithelial lesions and the diagnostic ability of high-resolution anoscopy in detecting these lesions in renal graft recipients followed-up in Manaus. In a cross-sectional study, 50 renal graft recipients were interviewed and submitted to high-resolution anoscopy with biopsies of acetowhite lesions or of the anal transition zone mucosa when acetowhitening was absent. Considering the histopathological reports of the examined anal specimens as the gold standard, the diagnostic validation and precision measures of high-resolution anoscopy were calculated as well as the prevalence of anal squamous intraepithelial lesions in the studied population. In 42 renal graft recipients with satisfactory histopathological readings, prevalence of anal squamous intraepithelial lesions or condyloma acuminatum (ASIL-ACU) was 23.81%. Sensitivity of high-resolution anoscopy was 100%; specificity, 65.63%; positive predictive value, 47.62%; negative predictive value, 100%; and kappa coefficient, 0.48. With a prevalence of 23.81% of subclinical ASIL-ACU lesions, the studied renal graft recipients had all these lesions detected by high-resolution anoscopy, notwithstanding most anal transition zone acetowhitened biopsied areas did not reveal histopathological aspects of anal cancer precursor lesions or condyloma acuminatum. Therefore, greater experience with the diagnostic tool was felt necessary to enhance its positive predictive value, specificity and diagnostic precision.

Snakebites and Scorpion Stings in the Brazilian Amazon: Identifying Research Priorities for a Largely Neglected Problem

Envenomings by snakebites and scorpion stings impose a high burden worldwide and result in considerable social and economic impact [1]. It is estimated that snakebite rates are as high as over 1.8 million cases per year, with associated deaths reaching more than 90,000 cases annually [2]. However, snakebites are a neglected condition with no associated WHO programmes for control and prevention. The countries most affected by snakebites are located in the intertropical zone in areas with high rates of field use for agriculture where the main affected populations are adult men working in agricultural activities [1]. Approximately two billion people are living in areas at risk for scorpion stings, with over one million accidents occurring annually worldwide [3]. However, the true burden of snakebites and scorpion stings is probably higher and difficult to estimate since only a few countries have a reliable system for epidemiological surveillance of these events. In Brazil, the Ministry of Health implemented the National Program for Snakebites Control in 1986, extended to other poisonous animals in 1988. Since then, antivenom (AV) production has been standardized and all the AV production from the three national laboratories (Instituto Butantan, Fundacao Ezequiel Dias, and Instituto Vital Brazil) was acquired by the Ministry of Health for distribution free of charge to patients. Five types of snake AVs are currently available: Bothrops AV (main one), Crotalus AV, Bothrops-Crotalus AV, Bothrops-Lachesis AV, and Micrurus AV. For scorpion stings, there are two types of AVs available in Brazil: Tityus scorpion AV and a polyvalent AV against Loxosceles and Phoneutria spiders and the Tityus scorpion. Table 1 summarizes information on snake and scorpion AVs produced in Brazil. Table 1 Venom pools used for snake and scorpion AVs production in Brazil. In 2013, 27,181 and 78,091 cases of snakebites and scorpion stings were reported by the Brazilian Ministry of Health, respectively [4]. The highest incidence was in the North region (52.6 cases/100,000 inhabitants) followed by the Midwest (16.4/100,000). These values, expected to be higher in remote areas of the Brazilian Amazon [5], may be underestimated due to considerable underreporting. Fig 1 presents the spatial distribution of snakebites and scorpion stings in the Brazilian Amazon. Fig 1 Spatial distribution of snakebites and scorpion stings in the Brazilian Amazon in 2013.

Older Age and Time to Medical Assistance Are Associated with Severity and Mortality of Snakebites in the Brazilian Amazon: A Case-Control Study

The Amazon region reports the highest incidence of snakebite envenomings in Brazil. We aimed to describe the epidemiology of snakebites in the state of Amazonas and to investigate factors associated with disease severity and lethality. We used a nested case-control study, in order to identify factors associated with snakebite severity and mortality using official Brazilian reporting systems, from 2007 to 2012. Patients evolving to severity or death were considered cases and those with non-severe bites were included in the control group. During the study period, 9,191 snakebites were recorded, resulting in an incidence rate of 52.8 cases per 100,000 person/years. Snakebites mostly occurred in males (79.0%) and in rural areas (70.2%). The most affected age group was between 16 and 45 years old (54.6%). Fifty five percent of the snakebites were related to work activities. Age ≤15 years [OR=1.26 (95% CI=1.03-1.52); (p=0.018)], age ≥65 years [OR=1.53 (95% CI=1.09-2.13); (p=0.012)], work related bites [OR=1.39 (95% CI=1.17-1.63); (p<0.001)] and time to medical assistance >6 hours [OR=1.73 (95% CI=1.45-2.07); (p<0.001)] were independently associated with the risk of severity. Age ≥65 years [OR=3.19 (95% CI=1.40-7.25); (p=0.006)] and time to medical assistance >6 hours [OR=2.01 (95% CI=1.15-3.50); (p=0.013)] were independently associated with the risk of death. Snakebites represent an occupational health problem for rural populations in the Brazilian Amazon with a wide distribution. These results highlight the need for public health strategies aiming to reduce occupational injuries. Most cases of severe disease occurred in the extremes of age, in those with delays in medical attention and those caused by Micrurus bites. These features of victims of snakebite demand adequate management according to well-defined protocols, including prompt referral to tertiary centres when necessary, as well as an effective response from surveillance systems and policy makers for these vulnerable groups.

Borrelia burgdorferi "sensu lato" in Brazil: occurrence confirmed by immunohistochemistry and focus floating microscopy.

In the present study, we report the occurrence of Lymes borreliosis in patients from the Brazilian Amazon Region. Borreliosis was investigated by immunohistochemistry and focus floating microscopy for Borrelia burgdorferi in skin biopsy samples from 22 patients with both clinical and histopathology evidences compatible with Erythema Migrans. Spirochetes were detected by specific immunohistochemistry and focus floating microscopy for B. burgdorferi in samples from five patients. Clinical cure of the cutaneous lesions was observed in all the patients after treatment with doxycycline regimen as proposed by the Center Disease Control guidelines. A limitation of our study was the fact that we were not able to isolate and culture these organisms. These are the first known Brazilian cases of borreliosis to have Focus Floating Microscopy confirmation.

Causas de óbito em pacientes com síndrome da imunodeficiência adquirida, necropsiados na Fundação de Medicina Tropical do Amazonas

The aim of this study was to investigate the causes of death among 129 AIDS patients that were autopsied at the Tropical Medicine Foundation of Amazonas between 1996 and 2003. The degree of concordance between the autopsy diagnoses and the clinical diagnoses was observed. The disease that most frequently caused death was tuberculosis (28%), followed by bacterial pneumonia (17%), histoplasmosis (13%), toxoplasmosis (10%), pneumocystosis (8%), cryptococcosis (5%), bacterial sepsis (4%) and other causes (15%). The concordance between the clinical diagnosis before death and the autopsy was 51.9%. The main organ involved was the lungs (82.2%). The length of survival from the time of the laboratory diagnosis to death ranged from one month to 120 months. The mean length of survival was 15 days and 56% died less than one month after the diagnosis, while 15 patients died on the same day that they were diagnosed. These results show the importance of autopsies in elucidating the causes of death among AIDS patients.