Neglected tropical diseases (NTDs) primarily affect the poorest populations, often living in remote, rural areas, urban slums or conflict zones. Arboviruses are a significant NTD category spread by ...mosquitoes. Dengue, Chikungunya, and Zika are three arboviruses that affect a large proportion of the population in Latin and South America. The clinical diagnosis of these arboviral diseases is a difficult task due to the concurrent circulation of several arboviruses which present similar symptoms, inaccurate serologic tests resulting from cross-reaction and co-infection with other arboviruses.
The goal of this paper is to present evidence on the state of the art of studies investigating the automatic classification of arboviral diseases to support clinical diagnosis based on Machine Learning (ML) and Deep Learning (DL) models.
We carried out a Systematic Literature Review (SLR) in which Google Scholar was searched to identify key papers on the topic. From an initial 963 records (956 from string-based search and seven from a single backward snowballing procedure), only 15 relevant papers were identified.
Results show that current research is focused on the binary classification of Dengue, primarily using tree-based ML algorithms. Only one paper was identified using DL. Five papers presented solutions for multi-class problems, covering Dengue (and its variants) and Chikungunya. No papers were identified that investigated models to differentiate between Dengue, Chikungunya, and Zika.
The use of an efficient clinical decision support system for arboviral diseases can improve the quality of the entire clinical process, thus increasing the accuracy of the diagnosis and the associated treatment. It should help physicians in their decision-making process and, consequently, improve the use of resources and the patient's quality of life.
There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high ...concentration of the drug.
To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19.
This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon.
Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days).
Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4.
Out of a predefined sample size of 440 patients, 81 were enrolled (41 50.6% to high-dosage group and 40 49.4% to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 75.3%) were men. Older age (mean SD age, 54.7 13.7 years vs 47.4 13.3 years) and more heart disease (5 of 28 17.9% vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 18.9%) compared with the low-dosage group (4 of 36 11.1%). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%).
The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19.
ClinicalTrials.gov Identifier: NCT04323527.
In the Brazilian Amazon, long distances, low healthcare coverage, common use of ineffective or deleterious self-care practices, and resistance to seeking medical assistance have an impact on access ...to antivenom treatment. This study aimed to estimate snakebite underreporting, and analyze barriers that prevent victims from obtaining healthcare in communities located in 15 municipalities on the banks of the Solimões, Juruá and Purus Rivers, in the remote Western Brazilian Amazon. Information on the participants' demographics, previous snakebites, access to healthcare, time taken to reach medical assistance, use of self-care practices, and the reason for not accessing healthcare were collected through semi-structured interviews. In the case of deaths, information was collected by interviewing parents, relatives or acquaintances. A total of 172 participants who reported having suffered snakebites during their lifetime were interviewed. A total of 73 different treatment procedures was reported by 65.1% of the participants. Participants living in different river basins share few self-care procedures that use traditional medicine, and 91 (52.9%) participants reported that they had access to healthcare. Living in communities along the Juruá River OR = 12.6 (95% CI = 3.2-49.7; p<0.001) and the use of traditional medicine OR = 11.6 (95% CI = 3.4-39.8; p<0.001) were variables that were independently associated to the lack of access to healthcare. The main reasons for not accessing healthcare were the pprioritization of traditional treatments (70.4%), and the failure to recognize the situation as being potentially severe (50.6%). Four deaths from complications arising from the snakebite were reported, and three of these were from communities on the banks of the Juruá River. Only one of these received medical assistance. We found an unexpectedly high underreporting of snakebite cases and associated deaths. Snakebite victims utilized three main different healing systems: 1) self-care using miscellaneous techniques; 2) official medical healthcare generally combined with traditional practices; and 3) self-care using traditional practices combined with Western medicines. To mitigate snakebite burden in the Brazilian Amazon, an innovative intervention that would optimize timely delivery of care, including antivenom distribution among existing community healthcare centers, is needed.
In recent years, considerable success in reducing its incidence has been achieved in Brazil, leading to a relative increase in the proportion of cases caused by Plasmodium vivax, considered a ...harder-to-eliminate parasite. This study aim is to describe the transmission dynamics and associated risk factors in a rural settlement area in the Western Brazilian Amazon.
A prospective cohort was established in a rural settlement area for 3 years. Follow-up included continuous passive case detection and monthly active case detection for a period of 6 months. Demographic, clinical and transmission control practices data were collected. Malaria diagnosis was performed through thick blood smear. Univariable and multivariable analyses of factors associated with malaria incidence were performed using negative binomial regression models. Factors associated with recurrence of P. vivax and Plasmodium falciparum malaria within 90 days of a previous episode were analysed using univariable and multivariable Cox-Proportional Hazard models.
Malaria prevalence decreased from 7 % at the study beginning to 0.6 % at month 24, with P. vivax predominating and P. falciparum disappearing after 1 year of follow-up. Malaria incidence was significantly higher in the dry season IRR (95 % CI) 1.4 (1.1-1.6); p < 0.001). Use of ITN was associated to malaria protection in the localities IRR (95 % CI) 0.7 (0.6-0.8); p = 0.001). A recurrent P. vivax episode within 90 days was observed in 29.4 % of individuals after an initial diagnosis. A previous P. vivax IRR (95 % CI) 2.3 (1.3-4.0); p = 0.006) or mixed P. vivax + P. falciparum IRR (95 % CI) 2.9 (1.5-5.7); p = 0.002) infections were significantly associated to a vivax malaria episode within 90 days of follow-up.
In an area of P. falciparum and P. vivax co-endemicity, a virtual disappearance of P. falciparum was observed with P. vivax increasing its relative contribution, with a large proportion of recurring episodes. This finding reinforces the perception of P. falciparum being more responsive to early diagnosis and treatment and ITN use and the contribution of relapsing P. vivax to maintain this species' transmission. In areas of P. vivax endemicity, antihypnozoite treatment effectiveness assessment in different transmission intensity may be a fundamental activity for malaria control and elimination.
Despite significant and successful efforts in Brazil regarding snakebites in the areas of research, antivenom manufacture and quality control, training of health professionals in the diagnosis and ...clinical management of bites, little is known about determinants of snakebites incidence in order to further plan interventions to reduce the impact of this medical condition. Understanding the complexity of ecological interactions in a geographical region is important for prediction, prevention and control measures of snakebites. This investigation aims to describe spatial distribution and identify environmental determinants of human envenoming by lancehead pit vipers (Bothrops genus), in the Brazilian Amazon. Aggregated data by the municipality was used to analyze the spatial distribution of Bothrops bites cases and its relationship with geographic and environmental factors. Eight geo-environmental factors were included in the analysis as independent variables: (1) tree canopy loss increase; (2) area with vegetation cover; (3) area covered by water bodies; (4) altitude; (5) precipitation; (6) air relative humidity; (7) soil moisture; and (8) air temperature. Human envenoming by lancehead pit vipers (Bothrops genus) in the Amazon region is more incident in lowlands Adjusted regression coefficient ARC -0.0007 (IC95%: -0.001; -0.0006), p<0.0001, with high preserved original vegetation cover ARC 0.0065 (IC95%: 0.0071; 0.0060), p<0.0001, with heaviest rainfall ARC 0.0001 (IC95%: 0.00009; 0.0001), p<0.0001 and higher air relative humidity ARC 0.0082 (IC95%: 0.0108; 0.0056), p<0.0001. This association is interpreted as the result of the higher prey availability and further abundance of pit vipers in such landscapes.
To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP).
We conducted a case-control study among HCP who had confirmed symptomatic ...COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up.
Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05-1.39), age (OR, 1.01; 95% CI, 1.00-1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07-1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17-0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30-0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01-0.19) were significantly less likely to develop long COVID.
Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.
SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved ...intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.
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.
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.
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.
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).
Abstract
Background
Reducing mosquito abundance or interfering with its ability to support the parasite cycle can help to interrupt malaria in areas of significant risk of malaria transmission. ...Fluralaner is a safe and effective drug for veterinary use indicated for the treatment against fleas and ticks which acts as an antagonist of chloride ion channels mediated by γ-aminobutyric acid (GABA), preventing the entry of these ions into the postsynaptic neuron, leading to hyperexcitability of the postsynaptic neuron of the central nervous system of arthropods. Fluralaner demonstrated insecticidal activity against different insect species.
Methods
The study aimed to evaluate the effects of fluralaner on the biology, survival, and reproductive fitness of
Anopheles aquasalis
. The following lethal concentrations (LC) were determined for
An. aquasalis
: LC
5
= 0.511 µM; LC
25
= 1.625 µM; LC
50
= 3.237 µM.
Results
A significant decrease (P < 0.001) was evident in the number of eggs, larvae, and pupae in the group exposed to a sublethal dose of fluralaner when compared to a control group (without the drug). Using blood from dogs after administration of fluralaner, it was observed that the drug causes 100% mortality in
An. aquasalis
in less than 24 h after feeding; this effect remains even after 90 days in all samples.
Discussion
Fluralaner showed the same result for up to 60 days, and after that, there was a slight reduction in its effect, evidenced by a decrease in the percentage of dead females; however, still significant when compared to the control group.
Conclusion
Fluralaner affects the biology and reduction of survival in
An. aquasalis
in a lasting and prolonged period, and its fecundity with lower dosages, is a strong candidate for controlling disease vectors.
Objective
To assess the spatial distribution of TB and malaria incidence, as well as their spatial association with each other, regardless of environmental and socio‐economic factors commonly ...reported as determinants of both disease rates among the municipalities of Amazonas State, Brazil between 2012 and 2015.
Methods
Through an ecological approach considering municipalities of Amazonas, Brazil, as unit of analysis, a negative binomial regression model was used to assess association between malaria and TB rates, in which the dependent variable was the average municipal tuberculosis incidence rate.
Results
Positive associations of overall malaria (β = 0.100 CI = 0.032, 0.168, P = 0.004), P. vivax malaria (β = 0.115 CI = 0.036, 0.195, P = 0.005), and P. falciparum malaria (β = 0.389 CI = −0.0124, 0.791, P = 0.057) with TB rates were found, regardless of the sociodemographic factors included in the study.
Conclusion
In the Brazilian Amazon, TB and malaria are spatially associated. Therefore, it is very likely that co‐infections also occur in this region, regardless of the HIV status.
Objectif
Evaluer la distribution spatiale de l'incidence de la tuberculose (TB) et du paludisme, ainsi que leur association spatiale, indépendamment des facteurs environnementaux et socioéconomiques communément rapportés comme déterminants des taux des deux maladie dans les municipalités de l'Etat d'Amazonas, au Brésil, entre 2012 et 2015.
Méthodes
Dans le cadre d'une approche écologique prenant en considération les municipalités d'Amazonas, au Brésil, comme unité d'analyse, un modèle de régression binomiale négatif a été utilisé pour évaluer l'association entre les taux de paludisme et de TB, dans laquelle la variable dépendante était le taux moyen d'incidence municipale de la TB.
Résultats
Des associations positives entre le paludisme en général (β = 0,100 IC= 0,032 à 0,168, p = 0,004), le paludisme à P. vivax (β = 0,115 IC: 0,036 à 0,195, p = 0,005) et le paludisme à P. falciparum (β = 0,389 IC: ‐ 0,0124 à 0,791, p = 0,057) avec des taux de TB ont été retrouvées quels que soient les facteurs sociodémographiques inclus dans l’étude.
Conclusion
En Amazonie brésilienne, la TB et le paludisme sont associés spatialement. Par conséquent, il est très probable que des coinfections se produisent également dans cette région, quel que soit le statut VIH.
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