Spatio-temporal analysis of American Tegumentary Leishmaniasis incidences in the Brazilian state of Amazonas: 2011 to 2022.

This study aimed to conduct a spatio-temporal analysis of tegumentary leishmaniasis occurrences in the Amazonas state, Brazil. An ecological study encompassing time series and spatial analysis was performed, exploring the geographic distribution and temporal trends of American Tegumentary Leishmaniasis (ATL) in Amazonas between 2011 and 2022. Secondary data extracted from the Department of Informatics of the Unified Health System (DATASUS) were utilized for this analysis. The study evaluated the relationship between disease cases and environmental/climatic variables (deforestation, temperature, precipitation, and relative humidity). Over the study period, 19,730 cases of tegumentary leishmaniasis were recorded, averaging an incidence of 41.4/100,000 inhabitants across the 62 municipalities of Amazonas state. Disease intensity varied with seasons. Generally, Amazonas state displayed a declining trend in ATL cases. However, certain municipalities, notably Rio Preto da Eva and Presidente Figueiredo, exhibited high incidence rates, while Canutama, Envira, Eirunepé, and Pauini municipalities demand closer attention due to their demonstrated increasing temporal trend of ATL cases. The analysis indicated a correlation between the number of ATL cases reported and relative humidity as well as precipitation. These findings underscore the significance of tegumentary leishmaniasis as a public health issue in the region and emphasize the necessity for public initiatives aimed at preventing this endemic illness.

Chronic Chagas Cardiomyopathy in the Brazilian Amazon region: clinical characteristics and regional distinctiveness.

Objectives: This study aims to provide a comprehensive analysis of clinical and epidemiological data related to Chronic Chagas Cardiomyopathy (CCC) in the Amazon region of Brazil. Methods: A review of observational, retrospective, and cross-sectional studies related to Chagas Disease in the Amazon region of Brazil was conducted, and a case series addressing CCC in patients treated at the FMT-HVD outpatient clinic, a reference center for Chagas disease in Brazil, was carried out. Results: Clinical characteristics of 55 patients from the Amazon region with CCC were described. The most common electrocardiographic alteration observed was abnormal ventricular repolarization (AVR), present in 40% of cases. The most common echocardiographic finding was left ventricular systolic dysfunction (49%), followed by akinesia or hypokinesia of the inferior and/or inferolateral walls (38.1%) and the presence of an apical aneurysm (32.7%). Conclusions: Overall, this study demonstrates that CCC in the Amazon region presents clinical characteristics and severity that are similar to those observed in other regions. However, certain peculiarities, such as the frequency of right bundle branch block (RBBB) and anterior and septal involvement during the acute phase, require additional investigation to better comprehend the disease in the region. Overall, the study provides crucial clinical insights for the diagnosis and treatment of CCC in the Amazon region.

Temporal patterns of cytokine and injury biomarkers in hospitalized COVID-19 patients treated with methylprednisolone.

Background: The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients. Methods: Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1ß) were quantified using cytometric bead array. Results: At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1ß and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14. Conclusion: These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.

Epidemiological clinical profile and closure of chronic plantar ulcers in patients with leprosy sequelae undergoing orthopedic surgery in a municipality in western Amazon.

INTRODUCTION: Chronic plantar ulcers in leprosy are lesions resulting from motor and sensory alterations caused by Mycobacterium leprae. They are lesions refractory to conventional dressings and present high recurrence rates. OBJECTIVE: To evaluate the epidemiological clinical profile of patients with chronic plantar ulcers associated with bony prominences in the lesion bed and to evaluate the efficacy of orthopedic surgical treatment of these lesions. METHODS: This is a descriptive and analytical retrospective study with the evaluation of medical records of patients undergoing surgical treatment of chronic plantar ulcers from 2008 to 2018. The surgical technique applied consisted of corrective resection of bone prominences and the primary closure of the lesion with bipediculated local flap. RESULTS: 234 patients were submitted to surgery, 55.1% male with an average age of 69.5 years old. Of these, 82.9% were illiterate; and 88.5% with open lesions over 10 years. After surgical treatment, total wound healing occurred in an average time of 12 weeks. The variables that contributed to shorter healing time were: Patients' lower age group; regular use of orthopedic shoes and insoles and dressings performed by nurse aides in health units before surgery. Obesity was the factor that correlated with the delay of healing time. CONCLUSION: A higher incidence was observed in males and male and female illiterate patients. The regular use of shoes and insoles and dressings performed by nurse aides in health units contributed to shorter postoperative healing time. Orthopedic surgical treatment with corrective resection of bony prominences proved to be an efficient therapeutic method for the closure of chronic plantar ulcers. It is a reproducible method, justifying the importance of the orthopedic surgeon in the context of the multidisciplinary team to cope with these complex lesions.

Acute Chagas disease associated with ingestion of contaminated food in Brazilian western Amazon.

OBJECTIVE: To describe clinical, epidemiological and management information on cases of acute Chagas disease (ACD) by oral transmission in the state of Amazonas in western Amazon. METHODS: Manual and electronic medical records of patients diagnosed with ACD at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) were included. RESULTS: There were 147 cases of acute CD registered from 10 outbreaks that occurred in the state of Amazonas between 2004 and 2022. The transmission pathway was through oral route, with probable contaminated palm fruit juice (açaí and/or papatuá), and involved people from the same family, friends or neighbours. Of 147 identified cases, 87 (59%) were males; cases were aged 10 months to 82 years. The most common symptom was the febrile syndrome (123/147; 91.8%); cardiac alterations were present in 33/100 (33%), (2/147; 1.4%) had severe ACD with meningoencephalitis, and 12 (8.2%) were asymptomatic. Most cases were diagnosed through thick blood smear (132/147; 89.8%), a few (14/147; 9.5%) were diagnosed by serology and (1/147; 0.7%) by polymerase chain reaction (PCR) and blood culture. In all these outbreaks, 74.1% of the patients were analysed by PCR, and Trypanosoma cruzi TcIV was detected in all of them. No deaths were recorded. The incidence of these foci coincided with the fruit harvest period in the state of Amazonas. CONCLUSION: The occurrence of ACD outbreaks in the Amazon affected individuals of both sexes, young adults, living in rural and peri-urban areas and related to the consumption of regional foods. Early diagnosis is an important factor in surveillance. There was a low frequency of cardiac alterations. Continuous follow-up of most patients was not carried out due to difficulty in getting to specialised centres; therefore, little is known about post-treatment.

Resisting an invasion: A review of the triatomine vector (Kissing bug) defense strategies against a Trypanosoma sp infection.

Triatomines are an important group of insects in the Americas. They serve as transmission vectors for Trypanosoma cruzi, the etiologic agent responsible for the deadly Chagas disease in humans. The digenetic parasite has a complex life cycle, alternating between mammalian and insect hosts, facing different environments. In the insect vector, the metacyclic trypomastigote (non-replicative) and epimastigote (replicative) stages face a set of insect-mediated environmental changes, such as intestinal pH, body temperature, nutrient availability, and vector immune response. These insects have the ability to differentiate between self and non-self-particles using their innate immune system. This immune system comprises physical barriers, cellular responses (phagocytosis, nodules and encapsulation), humoral factors, including effector mechanisms (antimicrobial peptides and prophenoloxidase cascade) and the intestinal microbiota. Here, we consolidate and synthesize the available literature to describe the defense mechanisms deployed by the triatomine vector against the parasite, as documented in recent years, the possible mechanisms developed by the parasite to protect against the insect's specific microenvironment and innate immune responses, and future perspectives on the Triatomine-Trypanosome interaction.

Metabolomic Profiling of Plasma Reveals Differential Disease Severity Markers in COVID-19 Patients.

The severity, disabilities, and lethality caused by the coronavirus 2019 (COVID-19) disease have dumbfounded the entire world on an unprecedented scale. The multifactorial aspect of the infection has generated interest in understanding the clinical history of COVID-19, particularly the classification of severity and early prediction on prognosis. Metabolomics is a powerful tool for identifying metabolite signatures when profiling parasitic, metabolic, and microbial diseases. This study undertook a metabolomic approach to identify potential metabolic signatures to discriminate severe COVID-19 from non-severe COVID-19. The secondary aim was to determine whether the clinical and laboratory data from the severe and non-severe COVID-19 patients were compatible with the metabolomic findings. Metabolomic analysis of samples revealed that 43 metabolites from 9 classes indicated COVID-19 severity: 29 metabolites for non-severe and 14 metabolites for severe disease. The metabolites from porphyrin and purine pathways were significantly elevated in the severe disease group, suggesting that they could be potential prognostic biomarkers. Elevated levels of the cholesteryl ester CE (18:3) in non-severe patients matched the significantly different blood cholesterol components (total cholesterol and HDL, both p < 0.001) that were detected. Pathway analysis identified 8 metabolomic pathways associated with the 43 discriminating metabolites. Metabolomic pathway analysis revealed that COVID-19 affected glycerophospholipid and porphyrin metabolism but significantly affected the glycerophospholipid and linoleic acid metabolism pathways (p = 0.025 and p = 0.035, respectively). Our results indicate that these metabolomics-based markers could have prognostic and diagnostic potential when managing and understanding the evolution of COVID-19.

Impact of El Niño on the dynamics of American cutaneous leishmaniasis in a municipality in the western Amazon.

Vector-borne diseases are some of the leading public health problems in the tropics, and their association with climatic anomalies is well known. The current study aimed to evaluate the trend of American cutaneous leishmaniasis cases in the municipality of Manaus, Amazonas-Brazil, and its relationship with climatic extremes (ENSO). The study was carried out using a series of secondary data from notifications on the occurrence of several American cutaneous leishmaniasis cases in the municipality of Manaus between 1990 and 2017 obtained through the Sistema de Informação de Agravos de Notificação. Data regarding temperature, relative humidity, and precipitation for this municipality were derived from the Instituto Nacional de Meteorologia (INMET) and the National Oceanic and Atmospheric Administration (NOAA) websites. Coherence and wavelet phase analysis was conducted to measure the degree of relationship of the occurrence of the cases of cutaneous leishmaniasis and the El Niño-Southern Oscillation (ENSO). The results show that during La Niña events, an increase in American cutaneous leishmaniasis (ACL) cases is anticipated after the increase in rainfall from November, resulting in a more significant number of cases in January, February, and March. It was observed that in the municipality of Manaus, the dynamics of ACL cases are directly influenced by ENSO events that affect environmental variables such as precipitation, temperature, and humidity. Therefore, climatic variations consequently change the ACL incidence dynamics, leading to subsequent increases or decreases in the incidence of ACL cases in the area.

Performance of a sensitive haemozoin-based malaria diagnostic test validated for vivax malaria diagnosis in Brazilian Amazon.

BACKGROUND: Vivax malaria diagnosis remains a challenge in malaria elimination, with current point of care rapid diagnostic tests (RDT) missing many clinically significant infections because of usually lower peripheral parasitaemia. Haemozoin-detecting assays have been suggested as an alternative to immunoassay platforms but to date have not reached successful field deployment. Haemozoin is a paramagnetic crystal by-product of haemoglobin digestion by malaria parasites and is present in the food vacuole of malaria parasite-infected erythrocytes. This study aimed to compare the diagnostic capability of a new haemozoin-detecting platform, the Gazelle™ device with optical microscopy, RDT and PCR in a vivax malaria-endemic region. METHODS: A comparative, double-blind study evaluating symptomatic malaria patients seeking medical care was conducted at an infectious diseases reference hospital in the western Brazilian Amazon. Optical microscopy, PCR, RDT, and Gazelle™ were used to analyse blood samples. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa values were calculated. RESULTS: Out of 300 patients, 24 test results were excluded from the final analysis due to protocol violation (6) and inconclusive and/or irretrievable results (18). Gazelle™ sensitivity was 96.1 % (91.3-98.3) and 72.1 % (65.0-78.3) when compared to optical microscopy and PCR, respectively whereas it was 83.9 % and 62.8 % for RDTs. The platform presented specificity of 100 % (97.4-100), and 99.0 % (94.8-99.9) when compared to optical microscopy, and PCR, respectively, which  was the same for RDTs. Its correct classification rate was 98.2 % when compared to optical microscopy and 82.3 % for PCR; the test's accuracy when compared to optical microscopy was 98.1 % (96.4-99.7), when compared to RDT was 95.2 % (93.0-97.5), and when compared to PCR was 85.6 % (82.1-89.1). Kappa (95 % CI) values for Gazelle™ were 96.4 (93.2-99.5), 88.2 (82.6-93.8) and 65.3 (57.0-73.6) for optical microscopy, RDT and PCR, respectively. CONCLUSIONS: The Gazelle™ device was shown to have faster, easier, good sensitivity, specificity, and accuracy when compared to microscopy and was superior to RDT, demonstrating to be an alternative for vivax malaria screening particularly in areas where malaria is concomitant with other febrile infections (including dengue fever, zika, chikungunya, Chagas, yellow fever, babesiosis).

Methylene blue inhibits lumefantrine-resistant Plasmodium berghei.

INTRODUCTION: Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The large-scale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is need to identify drugs that can be used as substitutes to lumefantrine for use in combination therapy. Methylene blue, a synthetic anti-methemoglobinemia drug, has been shown to contain antimalarial properties, making it a candidate for drug repurposing. The present study sought to determine antiplasmodial effects of methylene blue against lumefantrine- and pyrimethamine-resistant strains of P. berghei. METHODOLOGY: Activity of methylene blue was assessed using the classical four-day test on mice infected with lumefantrine-resistant and pyrimethamine-resistant P. berghei. A dose of 45 mg/kg/day was effective for testing ED90. Parasitemia and mice survival was determined. RESULTS: At 45 mg/kg/day, methylene blue sustained significant parasite inhibition, over 99%, for at least 6 days post-treatment against lumefantrine-resistant and pyrimethamine-resistant P. berghei (p = 0.0086 and p = 0.0191, respectively). No serious adverse effects were observed. CONCLUSIONS: Our results indicate that methylene blue at a concentration of 45 mg/kg/day confers over 99% inhibition against lumefantrine- and pyrimethamine-resistant P. berghei for six days. This shows the potential use methylene blue in the development of antimalarials against lumefantrine- and pyrimethamine-resistant parasites.