A spatially resolved single-cell lung atlas integrated with clinical and blood signatures distinguishes COVID-19 disease trajectories.

COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian patients hospitalized with COVID-19. We identified core clinical and peripheral blood signatures differentiating disease progression between patients who recovered from severe disease compared with those who succumbed to the disease. Signatures were heterogeneous among fatal cases yet clustered into two patient groups: "early death" (<15 days until death) and "late death" (>15 days). Progression to early death was characterized systemically and in lung histopathological samples by rapid endothelial and myeloid activation and the presence of thrombi associated with SARS-CoV-2+ macrophages. In contrast, progression to late death was associated with fibrosis, apoptosis, and SARS-CoV-2+ epithelial cells in postmortem lung tissue. In late death cases, cytotoxicity, interferon, and T helper 17 (TH17) signatures were only detectable in the peripheral blood after 2 weeks of hospitalization. Progression to recovery was associated with higher lymphocyte counts, TH2 responses, and anti-inflammatory-mediated responses. By integrating antemortem longitudinal blood signatures and spatial single-cell lung signatures from postmortem lung samples, we defined clinical parameters that could be used to help predict COVID-19 outcomes.

Standardization of DNA extraction from paraffinized spleen samples: molecular diagnosis of human malaria.

BACKGROUND: Plasmodium vivax is the main species responsible for human malaria in Brazil, and one of its manifestations is splenic malaria, though there are still challenges in its diagnosis. The present study aimed to standardize Plasmodium sp. DNA extraction from histological slices of spleen and diagnosis using real-time qPCR. METHODS: This study performed a microtomy of a paraffin-embedded spleen as a positive control for P. vivax from a patient who had been previously diagnosed with the parasite. The sample was deparaffinized with xylol and ethanol, then DNA extraction was performed with two commercial kits. qPCR was carried out with the Taqman system for detection of Plasmodium sp. and was made species-specific using PvmtCOX1 gene. From 2015 to 2019, 200 spleen samples were obtained from trauma patients subjected to splenectomy in Manaus, Amazonas. All the samples were tested for cell-free human DNA (cfDNA). RESULTS: The deparaffinization and the Plasmodium vivax DNA extraction method was successfully standardized, and the control sample was positive for P. vivax. Of the 200 samples, all qPCRs were negative, but they were positive for human PCR. CONCLUSION: Paraffinization is practical and efficient for the preservation of samples, but the formation of bonds between proteins and DNA makes extraction difficult. Despite this, in this study, it was possible to standardize a method of DNA extraction for detecting P. vivax.

Pediatric central nervous system infections in the Amazon: clinical and laboratory profiles.

Background: Central nervous system (CNS) infections are important causes of mortality and morbidity in children, and they are related to severe problems such as hearing loss, neurological sequelae, and death. The objective was to describe clinical and laboratory exam profiles of children who were diagnosed with CNS infections. Methods: We conducted a cross-sectional study based on medical records, which included pediatric patients aged from 3 months to 15 years, with a clinical suspicion of CNS infection between January 2014 to December 2019. The pathogens were confirmed in cerebrospinal fluid (CSF) samples using Gram staining, cell culture, molecular diagnostics (PCR and qPCR), and serology. Results: Out of the 689 enrolled patients, 108 (15.6%) had laboratory-confirmed infections in CSF. The most common bacterial pathogens isolated from the culture were Neisseria meningitidis serogroup C in 19, Streptococcus pneumoniae in 11, and Haemophilus influenzae in seven samples. The viruses identified were Enterovirus, Cytomegalovirus, Varicella-zoster virus, Epstein-Barr virus, and arbovirus. No patient was found to be positive for Herpes simplex virus 1 and 2. Patients with viral infections showed altered levels of consciousness (p = 0.001) when compared to bacterial infections. Conclusion: This study shows the presence of important vaccine-preventable pathogens, and different families of viruses causing CNS infections in the pediatric patients of Manaus.

CCL-2 and CXCL-8: Potential Prognostic Biomarkers of Acute Kidney Injury after a Bothrops atrox Snakebite.

In the Brazilian Amazon, the snake Bothrops atrox is the primary cause of snakebites. B. atrox (BaV) venom can cause systemic pathophysiological changes such as acute kidney injury (AKI), which leads to the production of chemokines and cytokines in response to the envenomation. These soluble immunological molecules act by modulating the inflammatory response; however, the mechanisms associated with the development of AKI are still poorly understood. Here, we characterize the profile of these soluble immunological molecules as possible predictive biomarkers of the development of AKI. The study involved 34 patients who had been victims of snakebites by Bothrops sp. These were categorized into two groups according to the development of AKI (AKI(-)/AKI(+)), using healthy donors as the control (HD). Peripheral blood samples were collected at three-time points: before antivenom administration (T0) and at 24 and 48 hours after antivenom (T1 and T2, respectively). The soluble immunological molecules (CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-γ, IL-4, and IL-17A) were quantified using cytometric bead array. Our results demonstrated an increase in CXCL-9, CXCL-10, IL-6, IL-2, IL-10, and IL-17A molecules in the groups of patients who suffered Bothrops snakebites (AKI(-) and AKI(+)) before antivenom administration, when compared to HD. In the AKI(+) group, levels of CXCL-8 and CCL-2 molecules were elevated on admission and progressively decreased during the clinical evolution of patients after antivenom administration. In addition, in the signature analysis, these were produced exclusively by the group AKI(+) at T0. Thus, these chemokines may be related to the initiation and extension of AKI after envenomation by Bothrops and present themselves as two potential biomarkers of AKI at T0.

A prenylated dsRNA sensor protects against severe COVID-19.

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that 2'-5'-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that a common splice-acceptor single-nucleotide polymorphism (Rs10774671) governs whether patients express prenylated OAS1 isoforms that are membrane-associated and sense-specific regions of SARS-CoV-2 RNAs or if they only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. In hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting that this antiviral defense is a major component of a protective antiviral response.

The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox).

Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.

Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy.

Introduction:Bothrops atrox snakebites are a major public health problem in the Amazon region and also cause hemostatic disorders. In this study, we assessed the recovery from hemostatic disorders in Bothrops snakebite patients after being given antivenom therapy.Methods: This is a prospective study of Bothrops snakebite patients (n = 100) treated at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazilian Amazon, between January 2016 and December 2017. Blood samples were taken for the measurement of venom concentrations, platelets, clotting time and factors of patients on admission, 12, 24 and 48 h after antivenom therapy, and taken again on discharge. The presence of systemic bleeding was recorded during the follow-up.Results: On admission, systemic bleeding was observed in 14% of the patients. Thrombocytopenia was noted in 10% of the patients. A total of 54% of the patients presented unclottable blood with low levels of fibrinogen and alpha 2-antiplasmin, and high levels of fibrin/fibrinogen degradation product (FDP) and D-dimers. Unclottable blood and systemic bleeding were overcome in most patients 12 h after the antivenom therapy. Three patients developed systemic bleeding 48 h after antivenom therapy. Levels of fibrinogen and alpha 2-antiplasmin, FDP and D-dimer returned to normal around 48 h after the treatment or on discharge. The frequency of thrombocytopenia with high mean platelet volume increased in the first 24 h after antivenom therapy, and decreased on discharge. Bothrops venom levels in patients decreased 12 h after antivenom therapy and were not correlated with coagulation and fibrinolytic parameters. There were no deaths.Conclusion: Laboratorial parameters of coagulopathy returned to normal values within 48 h after the antivenom therapy until discharge. A few patients still presented bleeding signs within 48 h after beginning antivenom therapy. However, the Brazilian antivenom was able to overcome the hemostatic disorders in these cases of envenomation.

Snakebites as cause of deaths in the Western Brazilian Amazon: Why and who dies? Deaths from snakebites in the Amazon.

Snake envenoming represents a major burden for public health worldwide. In the Amazon, the official number of cases and deaths detected is probably underestimated because of the difficulty riverine and indigenous populations have reaching health centers in order to receive medical assistance. Thus, integrated analysis of health information systems must be used in order to improve adequate health policies. The aim of this work is to describe a series of deaths and identify risk factors for lethality from snakebites in the state of Amazonas, Brazil. All deaths from snakebites reported to the Brazilian Notifiable Diseases Surveillance System (SINAN) and to the Mortality Information System (SIM; ICD10-10th revision, X.29), from 2007 to 2015, were included. Variables were assessed by blocks with distal (ecological variables), intermediate (demographics) and proximal (clinical variables) components to identify predictors of case fatality. A total of 127 deaths from snakebites were recorded, with 58 pairs found through linkage of the SINAN and SIM databases (45.7%), 37 (29.1%) deaths found only in SINAN and 32 (25.2%) found only in the SIM. Deaths occurred mostly in males (95 cases; 74.8%) living in rural areas (78.6%). The most affected age group was the ≥61 years old (36 cases; 28.4%). Snakebites were presumably due to Bothrops snakes in 68.5% of the cases and Lachesis in 29.5% based on clinico-epidemiological diagnosis. A proportion of 26.2% of the cases received treatment over 24 h after the bite ocurred. On admission, cases were mostly classified as severe (65.6%). Overall, 28 patients (22.0%). Deceased without any medical assistance Antivenom was given to 53.5%. In the multivariate analysis, a distance from Manaus >300 km [OR = 3.40 (95%CI = 1.99-5.79); (p < 0.001)]; age ≥61 years [OR = 4.31 (95%CI = 1.22-15.21); (p = 0.023)] and Indigenous status [OR = 5.47 (95%CI = 2.37-12.66); (p < 0.001)] were independently associated with case fatality from snakebites. Severe snakebites [OR = 16.24 (95%CI = 4.37-60.39); (p < 0.001)] and a lack of antivenom administration [OR = 4.21 (95%CI = 1.30-13.19); (p = 0.014)] were also independently associated with case fatality. Respiratory failure/dyspnea, systemic bleeding, sepsis and shock were recorded only among fatal cases. In conclusion, i) death from snakebites was underreported in the mortality surveillance system; ii) older age groups living in remote municipalities and indigenous peoples were the population groups most prone to death; iii) lack or underdosage of antivenom resulted in higher case fatality and iv) systemic bleeding, circulatory shock, sepsis and acute respiratory failure were strongly associated to fatal outcome.

Predicting acute renal failure in Bothrops snakebite patients in a tertiary reference center, Western Brazilian Amazon

Acute Kidney Injury (AKI) is the main systemic complication and cause of death in viperid envenomation. Although there are hypotheses for the development of AKI, the mechanisms involved are still not established. The aim of this study was to evaluate the clinical-laboratorial-epidemiological factors associated with AKI in victims of Bothrops sp envenomation. This is an observational study carried out at the Fundac¸ão de Medicina Tropical Dr. Heitor Vieira Dourado. AKI was defined according to the guidelines of the Acute Kidney Injury Network (AKIN). Among the 186 patients evaluated, AKI was observed in 24 (12.9%) after 48 hours of admission. Stage I was present in 17 (70.8%) patients, II in 3 (12.5%) and III in 4 (16.7%). Epidemiological characterization showed predominance of men, occurrence in rural areas, aged between 16–60 years, feet as the most affected anatomical region, and time to medical assistance less than 3 hours. Hypertension and diabetes were the comorbidities identified. Most of the accidents were classified as moderate, and clinical manifestations included severe pain, mild edema, local bleeding and headache. Laboratory results showed blood uncoagulability, hypofibrinogenemia, leukocytosis, increase of creatine kinase, and high lactate dehydrogenase levels. Multivariate analysis showed an association with high LDH levels [AOR = 1.01 (95% CI = 1.01–1.01, p<0.002)], local bleeding [AOR = 0.13 (95%CI = 0.027–0.59, p<0.009)], and the presence of comorbidities [AOR = 60.96 (95%CI = 9.69–383.30; p<0.000)]. Herein, laboratory markers such as high LDH levels along with local bleeding and comorbidities may aid in the diagnosis of AKI.

Snakebites as cause of deaths in the Western Brazilian Amazon: Why and who dies? Deaths from snakebites in the Amazon

Snake envenoming represents a major burden for public health worldwide. In the Amazon, the official number of cases and deaths detected is probably underestimated because of the difficulty riverine and indigenous populations have reaching health centers in order to receive medical assistance. Thus, integrated analysis of health information systems must be used in order to improve adequate health policies. The aim of this work is to describe a series of deaths and identify risk factors for lethality from snakebites in the state of Amazonas, Brazil. All deaths from snakebites reported to the Brazilian Notifiable Diseases Surveillance System (SINAN) and to the Mortality Information System (SIM; ICD10-10th revision, X.29), from 2007 to 2015, were included. Variables were assessed by blocks with distal (ecological variables), intermediate (demographics) and proximal (clinical variables) components to identify predictors of case fatality. A total of 127 deaths from snakebites were recorded, with 58 pairs found through linkage of the SINAN and SIM databases (45.7%), 37 (29.1%) deaths found only in SINAN and 32 (25.2%) found only in the SIM. Deaths occurred mostly in males (95 cases; 74.8%) living in rural areas (78.6%). The most affected age group was the >= 61 years old (36 cases; 28.4%). Snakebites were presumably due to Bothrops snakes in 68.5% of the cases and Lachesis in 29.5% based on clinico-epidemiological diagnosis. A proportion of 26.2% of the cases received treatment over 24 h after the bite ocurred. On admission, cases were mostly classified as severe (65.6%). Overall, 28 patients (22.0%). Deceased without any medical assistance Antivenom was given to 53.5%. In the multivariate analysis, a distance from Manaus >300 km [OR = 3.40 (95%Cl = 1.99-5.79); (p < 0.001)1; age >= 61 years [OR = 431 (95%Cl = 1.22-1521); (p = 0.023)] and Indigenous status [OR = 5.47 (95%Cl = 237-12.66); (p < 0.001)1 were independently associated with case fatality from snakebites. Severe snakebites [OR = 16.24 (95%Cl = 4.37-6039); (p < 0.001)] and a lack of antivenom administration [OR = 4.21 (95%Cl = 1.30-13.19); (p = 0.014)] were also independently associated with case fatality. Respiratory failureklyspnea, systemic bleeding, sepsis and shock were recorded only among fatal cases. In conclusion, i) death from snakebites was under-reported in the mortality surveillance system; ii) older age groups living in remote municipalities and indigenous peoples were the population groups most prone to death; iii) lack or underdosage of anti venom resulted in higher case fatality and iv) systemic bleeding, circulatory shock, sepsis and acute respiratory failure were strongly associated to fatal outcome.

Fatal stroke after Bothrops snakebite in the Amazonas state, Brazil: A case report.

Bothrops atrox is the snake responsible for the majority of snakebites in the Brazilian Amazon. Patients generally evolve to local manifestations such as edema, pain and ecchymoses. Systemic effects of B. atrox venom are usually restricted to blood incoagulability and spontaneous bleeding. However, in a few cases, bleeding in the central nervous system may occur, which can lead to sequels and deaths. Here, we report a case of a 59 year-old woman who presented edema, pain and ecchymoses on the right foot, headache, nausea, diarrhea, hypertension and blood incoagulability after the bite by Bothrops snake in the Brazilian Amazon. This case evolved with stroke resulting in death despite the antivenom and conservative therapy employed. In addition, we were able to identify the presence of venom in the patient's brain tissue after death. Direct action of toxins present in the snake's venom in the induction of systemic hemorrhage allied to blood incoagulability and hypertension presented by the patient could be involved in the mechanism of stroke in this case.

Sustained Presence of Cutaneous Leishmaniasis in Urban Manaus, the Largest Human Settlement in the Amazon.

The Amazon is responsible for approximately 40% of the American tegumentary leishmaniasis (ATL) in Brazil. Herein the sustained presence of ATL in Manaus, the largest settlement in the Amazon, was investigated. Records of notification of historic cases, and data from cases prospectively enrolled in the Tropical Medicine Foundation of the Amazonas State were used. Geographic coordinates of prospective patients' living sites were used to detect inner-city clusters of ATL. Infecting Leishmania species was determined by polymerase chain reaction. Among prospectively enrolled subjects, 94.8% were infected with Leishmania (Viannia) guyanensis, 76.7% were male, 30.2% were 0-20 years old, and 69.8% had an urban residence. Historic cases showed a profile similar to that of prospectively enrolled subjects. Several clusters of ATL, widely distributed within the city of Manaus, could be detected. In conclusion, there was a high frequency of disease in young age groups and cases clustered in urban neighborhoods. It cannot be determined from these data whether transmission of these cases occurred within or outside the city of Manaus.

Systematic review of the cost-effectiveness of the vaccination against HPV in Brazil.

In Brazil, almost 16,000 new cases of cervical cancer (CC), the type of neoplasia that claims the more lives of young women than any other, are expected in 2014. Although the vaccine against HPV has been developed, the application of this strategies to large populations is costly, and its use in Brazil is limited. Studies of the economic implications of new preventive technologies for CC may support rational and evidence-based decisions in public health. A systematic search of articles published between 2000 and 2014 was conducted using MEDLINE, EMBASE, the Cochrane Collaboration of Systematic Reviews, and LILACS. The aim of this search was the identification of original articles that evaluated the cost-effectiveness of vaccination against HPV in Brazil. A total of 6 articles are included in this review, evaluating the addition of a vaccine against HPV in comparison to population screening. Although the vaccine against HPV increases the cost of preventing cervical cancer, this new preventive technology presents favorable cost-effectiveness profiles in the case of Brazil. Failure to utilize the newly available preventative technologies against CC can lead to misguided and perverse consequences in a country in which programs based on the Papanicolaou test have been only partially successful.

Chlamydia trachomatis in human immunodeficiency virus-infected men treated at a referral hospital for sexually transmitted diseases in the Amazonas, Brazil.

OBJECTIVES: The aim of the present study was to determine the Chlamydia trachomatis prevalence and to identify the demographic, behavioural and clinical factors associated with C. trachomatis in human immunodeficiency virus infected men. STUDY: This was a cross-sectional study of C. trachomatis prevalence among human immunodeficiency virus-infected men enrolled at the Outpatient clinic of acquired immunodeficiency syndrome of the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado in Manaus, Amazonas, Brazil. C. trachomatis deoxyribonucleic acid from urethral samples was purified and submitted to real time polymerase chain reaction to identify the presence of C. trachomatis. RESULTS: A total of 276 human immunodeficiency virus-infected men were included in the study. The prevalence of C. trachomatis infection was 12% (95% confidence interval 8.1%-15.7%). The mean age of the participants was 34.63 (standard deviation 10.80) years. Of the 276 human immunodeficiency virus-infected men, 93 (56.2%) had more than one sexual partner in the past year and 105 (38.0%) reported having their first sexual intercourse under the age of 15 years. Men having sex with men and bisexuals amounted to 61.2% of the studied population. A total of 71.7% had received human immunodeficiency virus diagnosis in the last three years and 55.1% were using antiretroviral therapy. Factors associated with C. trachomatis infection in the logistic model were being single (p<0.034), men having sex with men (p<0.021), and having previous sexually transmitted diseases (p<0.001). CONCLUSION: The high prevalence of C. trachomatis infection among human immunodeficiency virus-infected men highlights that screening human immunodeficiency virus-infected men for C. trachomatis, especially among men having sex with men, is paramount to control the spread of C. trachomatis infection.

Performance of p16INK4a immunocytochemistry as a marker of anal squamous intraepithelial lesions.

BACKGROUND: Protein p16(INK4a) immunocytochemistry (ICCp16) has the potential to reveal lesions at risk of progression to anal cancer. This study examined measures of diagnostic validity of ICCp16 in HIV-positive patients treated at the Tropical Medicine Foundation of Amazonas in the coloproctology outpatient clinic. METHODS: One hundred ninety HIV-positive patients were consecutively enrolled in 2007 and 2008. All patients underwent anal cytologic sampling to perform ICCp16 in conventional and GluCyte (Synermed International, Westfield, Indiana and S¸ao Paulo, Brazil) smears and also for genotyping of human papillomavirus (HPV). Patients were then subjected to anal biopsies monitored by high-resolution anoscopy. Hematoxylin-eosin and immunoperoxidase p16 (clone 6H12) stains were performed in slides with biopsied and cytological specimens, respectively. HPV genotyping on anal scrapings was performed by a polymerase-chain reaction (PCR)-based method. The immunochemical findings were compared with histopathological and PCR results in contingency tables and analyzed by nonparametric tests. Measures of diagnostic validity of ICCp16 were calculated. Statistical significance was set at P ≤ .5. RESULTS: There was no statistically significant association between the immunochemical results (conventional or GluCyte smears) and histopathological or HPV genotyping findings (P > .05). In the best scenario, ICCp16 presented 31% sensitivity and 81% specificity for the diagnosis of anal squamous intraepithelial lesion (ASIL) and 30% and 66%, respectively, for the diagnosis of infection with high-risk HPV. CONCLUSIONS: There was no association between ICCp16 results and histopathological findings nor between ICCp16 and HPV genotyping. ICCp16 showed poor sensitivity and moderate specificity for the diagnosis of ASIL or high-risk HPV.

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.

Borrelia Burgdorferi "sensu lato" in Brazil: Occurrence confirmed by immunohistochemistry and focus floating microscopy.

In the present study, we report the occurrence of Lyme's 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.

High-resolution anoscopy in the diagnosis of anal cancer precursor lesions in renal graft recipients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.