Analysis of testing for COVID-19 in Parnaíba city, state of Piauí, from march to December 2020 / Análise da testagem para COVID-19 na cidade de Parnaíba, estado do Piauí, de março a dezembro de 2020 / Análisis de pruebas de COVID-19 en la ciudad de Parnaíba, estado de Piauí, de marzo a diciembre de 2020

Background and Objectives: it is extremely important and necessary to assess epidemiological events through the analysis of measures adopted at the time of crises, especially those with a health impact as a way of improving the system for future events, with testing being a gold standard to be assessed during an epidemic. This study aimed to analyze tests for COVID-19 diagnosis, with a view to detecting possible false negative results, in Parnaíba, Piauí, from March to December 2020. Methods: a statistical analysis of the data reported and made available by the Municipal Health Department using the IBM SPSS Statistics® 21.0 software, in which the variables type of test, date of symptom onset and date of material collection were crossed to obtain the results. Results: a total of 9,473 tests were negative, of which 11.1% were carried out using the RT-PCR methodology, 6.5% using rapid antigen tests, and 82.3% using a rapid antibody test. The analysis revealed that only 0.47% RT-PCR tests and 1.7% rapid antigen tests had been carried out within the ideal testing interval. On the other hand, the rapid antibody test had 0.14% performed outside the range. Conclusion: the most successful diagnostic test was the rapid antibody test, but it is the least specific and not suitable for determining health crisis management policies, especially for isolation measures for infected people, which suggests improvements in testing systems and development of tests with longer and more accurate testing intervals.(AU)

Justificativa e Objetivos: é de suma importância e necessidade a avaliação dos eventos epidemiológicos por meio da análise das medidas adotadas no momento das crises, em especial aqueles de impacto sanitário como forma de melhor o sistema para eventos futuros, sendo a testagem um padrão-ouro a ser avaliado durante uma epidemia. O objetivo deste estudo foi analisar os testes para o diagnóstico de COVID-19, na perspectiva de detectar possíveis resultados falsos negativos, em Parnaíba, Piauí, de março a dezembro de 2020. Métodos: análise estatística dos dados notificados e disponibilizados pela Secretaria Municipal de Saúde a partir do software IBM SPSS® Statistics 21.0, em que as variáveis tipo de teste, data do início dos sintomas e data da coleta do material foram cruzadas para obtenção dos resultados. Resultados: 9.473 testes resultaram negativo, em que 11,1% foram realizados pela metodologia RT-PCR, 6,5%, pelos testes rápidos de antígeno, e 82,3%, por teste rápido de anticorpo. A análise revelou que apenas 0,47% testes por RT-PCR e 1,7% testes rápidos de antígeno haviam sido realizados dentro do intervalo ideal de testagem. Por outro lado, o teste rápido de anticorpo teve 0,14% realizados fora do intervalo. Conclusão: o teste com maior sucesso de diagnóstico foi o teste rápido de anticorpo, porém é o menos específico e não adequado para determinação de políticas de gerenciamento de crise sanitária, em especial para medidas de isolamento de infectados, o que sugere melhorias em sistemas de testagem e desenvolvimento de testes com intervalos de testagem maior e precisos.(AU)

Justificación y Objetivo: es sumamente importante y necesario evaluar los eventos epidemiológicos a través del análisis de las medidas adoptadas en el momento de las crisis, especialmente aquellas con impacto en la salud, como una forma de mejorar el sistema para eventos futuros, siendo las pruebas un estándar de oro a ser evaluado durante una epidemia. El objetivo de este estudio fue analizar pruebas para el diagnóstico de COVID-19, con miras a detectar posibles resultados falsos negativos, en Parnaíba, Piauí, de marzo a diciembre de 2020. Métodos: análisis estadístico de los datos reportados y puestos a disposición por la Secretaría de Salud Municipal mediante el software IBM SPSS® Statistics 21.0, en el cual se cruzaron las variables tipo de prueba, fecha de inicio de síntomas y fecha de recolección del material para obtener los resultados. Resultados: un total de 9.473 pruebas resultaron negativas, de las cuales el 11,1% se realizaron mediante la metodología RT-PCR, el 6,5% mediante pruebas rápidas de antígenos y el 82,3% mediante prueba rápida de anticuerpos. El análisis reveló que sólo el 0,47% de las pruebas RT-PCR y el 1,7% de las pruebas rápidas de antígenos se habían realizado dentro del intervalo de prueba ideal. Por otro lado, la prueba rápida de anticuerpos tuvo un 0,14% realizado fuera del rango. Conclusión: la prueba diagnóstica más exitosa fue la prueba rápida de anticuerpos, pero es la menos específica y no adecuada para determinar políticas de gestión de crisis sanitarias, especialmente para medidas de aislamiento de personas infectadas, lo que sugiere mejoras en los sistemas de pruebas y desarrollo de pruebas con tiempos más largos y precisos. intervalos de prueba.(AU)

Curzerene antileishmania activity: Effects on Leishmania amazonensis and possible action mechanisms.

Leishmaniasis is a set of infectious diseases with high rates of morbidity and mortality, it affects millions of people around the world. Treatment, mainly with pentavalent antimonials, presents significant toxicity and many cases of resistance. In previous works we have demonstrated the effective and selective antileishmanial activity of Eugenia uniflora L. essential oil, being constituted (47.3%) by the sesquiterpene curzerene. Considering the high rate of parasite inhibition demonstrated for E. uniflora essential oil, and the significant presence of curzerene in the oil, this study aimed to evaluate its antileishmania activity and possible mechanisms of action. Curzerene was effective in inhibiting the growth of promastigotes (IC50 3.09 ± 0.14 µM) and axenic amastigotes (EC50 2.56 ± 0.12 µM), with low cytotoxicity to RAW 264.7 macrophages (CC50 83.87 ± 4.63 µM). It was observed that curzerene has direct effects on the parasite, inducing cell death by apoptosis with secondary necrotic effects (producing pores in the plasma membrane). Curzerene proved to be even more effective against intra-macrophage amastigote forms, with an EC50 of 0.46 ± 0.02 µM. The selectivity index demonstrated by curzerene on these parasite forms was 182.32, being respectively 44.15 and 8.47 times more selective than meglumine antimoniate and amphotericin B. The antiamastigote activity of curzerene was associated with immunomodulatory activity, as it increased TNF-α, IL-12, and NO levels, and lysosomal activity, and decreased IL-10 and IL-6 cytokine levels detected in macrophages infected and treated. In conclusion, our results demonstrate that curzerene is an effective and selective antileishmanial agent, a candidate for in vivo investigation in models of antileishmanial activity.

Prevalence and Influence of the -174 G/C Polymorphism in the Interleukin-6 Gene in Arboviruses Infections.

Dengue virus and Chikungunya virus are arboviruses that affect thousands of people worldwide annually. The mechanisms involved in viral pathogenesis still need to be better understood. Single nucleotide polymorphisms (SNPs) in immune genes may be involved in the protection, susceptibility, and/or progression of these diseases. This study was performed to investigate the SNP -174 G/C in the interleukin-6 (IL-6) gene in patients with dengue or chikungunya from Northeastern Brazil. A total of 581 blood samples were analyzed, of which 244 were part of the negative control group, genomic DNA was extracted, and the SNP was genotyped using real-time polymerase chain reaction (PCR). The data obtained were used to conduct statistical analyses of the genotype and allele frequencies. We suggest that the G/C genotype and C allele of the SNP -174 G/C in the IL-6 gene are related to protection against dengue in the studied population. No significant differences were observed in chikungunya patients. This is the first study that assessed the association of the SNP -174 G/C in patients with chikungunya. We identified the presence of the C allele as a protective factor against dengue in the studied population.

What is the association between the IL6-174 G > C (rs1800795) polymorphism and the risk of dengue? Evidence from a meta-analysis.

The association of polymorphisms in genes responsible for immunological mediators with dengue allows the identification of certain genetic alterations that increase or decrease the development risk of the disease. A few number of studies that correlate the interleukin 6-174 G > C (IL6-174 G > C) polymorphism (rs1800795) with dengue. However, there is an inconsistency on the polymorphism influence on the disease which motivated this meta-analysis. So, this study aimed to evaluate the rs1800795 polymorphism with protection or susceptibility for development of dengue. A search of the literature was performed for studies published before 05 September 2020 in various databases. Calculations of Odds Ratio (OR) with 95% of Confidence Intervals (CI) and heterogeneity (I2) were assessed and publication bias was done by Begg' and Egger's test. The value of P < 0.05 was considered as significant. As results, five case-control studies were identified and included in the results. The analysis showed that the heterozygous genotype has a protective role against dengue without warning signs (DWOS) (OR = 0.57, p = 0.001), as well as the polymorphic C allele (OR = 0.77, p = 0.04). When unifying the data from the included studies, the GG genotype was more prevalent among individuals with dengue with warning signs (DWWS) when compared to the control group (p = 0.0221). GC genotype was more prevalent in the control group than in the DWWS group (p = 0.0119). Therefore, in our study we observed that the GC genotype and the C allele have a protective role against DWOS. Since this polymorphism is associated with low IL-6 expression, thus it is expected that there will be a decreased pro-inflammatory response. However, more studies regarding this thematic are necessary to have a consensus about this polymorphism and dengue.

Eugenia piauhiensis Vellaff. essential oil and γ-elemene its major constituent exhibit antileishmanial activity, promoting cell membrane damage and in vitro immunomodulation.

Leishmaniasis is considered as one of the most Neglected Tropical Diseases (NTDs) in the world, caused by protozoan parasites of the genus Leishmania. Treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. The search for new therapeutic agents from natural sources has been a constant for the treatment of diseases such as leishmaniasis. The objective of this study was to evaluate the biological activity of Eugenia piauhiensis Vellaff. essential oil (EpEO) and its major constituent γ-elemene on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis, its cytotoxicity, and possible mechanisms of action. EpEO was more active (IC50 6.43 ± 0.18 µg/mL) against promastigotes than γ-elemene [9.82 ± 0.15 µg/mL (48.05 ± 0.73 µM)] and the reference drug miltefosine [IC50 17.25 ± 0.26 µg/mL (42.32 ± 0.64 µM)]. EpEO and γ-elemene exhibited low cytotoxicity against J774.A1 macrophages, with CC50 225.8 ± 3.57 µg/mL and 213.21 ± 3.3 µg/mL (1043 ± 16.15 µM), respectively. Additionally, EpEO and γ-elemene present direct activity against the parasite, decreasing plasma membrane integrity. EpEO and γ-elemene also proved to be even more active against intracellular amastigotes of the parasite [IC50 4.59 ± 0.07 µg/mL and 8.06 ± 0.12 µg/mL (39.44 ± 0.59 µM)], respectively), presenting indirect effects through macrophage activity modulation. Anti-amastigote activity was associated with increased TNF-α, IL-12, NO, and ROS levels. In conclusion, our results suggest EpEO and γ-elemene as promising candidates for new drug development against leishmaniasis.

Polymorphisms in the interleukin genes and chronic periodontitis: A field synopsis and revaluation by Bayesian approaches.

Periodontitis is a high prevalent disease into the clinical dentistry. Genetic variations in interleukins (IL) genes were associated with chronic periodontitis (CP) and were focus of several meta-analyses. This study aimed to assess the noteworthiness in the meta-analyses by means of a Bayesian approach to determinate possible false report associations. A systematic search was performed for meta-analyses with associations between gene polymorphisms in interleukins and CP. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-6. As results, eight meta-analyses approaching the IL1A/rs1800587, IL1B/rs1143634, IL1RN/rs2234663, IL4/rs2243250, IL6/rs1800795/rs1800796, IL17A/rs2275913 and IL18/rs1946518/rs187238 polymorphisms have been identified. Twenty-two from 270 calculations (8.15%) were noteworthy. Herein, we have identified the IL1A and IL1B polymorphisms as noteworthy biomarkers for CP susceptibility.

Association of single nucleotide polymorphisms in TNF-α (-308G/A and -238G/A) to dengue: Case-control and meta-analysis study.

Dengue is an acute viral disease whose clinical condition is related to the interaction of factors related to the Dengue virus (DENV), environment and the host, with the immunity of the human host contributing a substantial role in the pathogenesis of DENV infection. Studies have demonstrated that single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes such as tumor necrosis factor (TNF-α) affect transcription and/or expression; and therefore, may influence the pathogenesis of infectious diseases, such as dengue. Consequently, the objective of this study was to assess through a case-control study whether there was an association between the presence of SNPs -308G/A and -238G/A in the TNF-α gene and 158 patients with dengue and 123 controls. No association was found between the SNPs and the dengue cases in the study population. We then performed a meta-analysis, retrieving data from case-control studies in the literature for the same polymorphisms. For SNP-308G/A, the GG genotype was associated with dengue fever (DF) risk (OR = 1.24, 1.00-1.53; p = 0.05; I2 = 0%), while the GA genotype (OR = 0.75, 0.60-0.93; p = 0.01; I2 = 0%) and allele A (OR = 0.75, 0.60-0.93; p = 0.01; I2 = 0%) were associated with protection. The genotype GG population in the Asian continent (OR = 1.81 [1.06, 3.09], p = 0.03, I2 = 0%) and American (OR = 1.29 [1.00, 1.65], p = 0.05, I2 = 0%) was also associated with protection in the comparison between the cases versus the control group. In each comparison, the dominant model AA + GA (p < 0.00001) conferred protection. For SNP-238G/A the GA genotype was associated with risk for dengue hemorrhagic fever (DHF; OR = 2.17, 1.28-3.67; p = 0.004; I2 = 0%)), and the dominant AA + GA model (p < 0.00001) was associated with protection in each comparison. In summary, our results did not associate SNPs in the TNF-α gene to dengue in the Brazilian northeast population. However, combined literature data suggested the effect of the GG and GA genotypes of the SNP-308G/A on risk and protection, respectively, in Asian and American populations.

Circulation of Chikungunya virus East-Central-South Africa genotype during an outbreak in 2016-17 in Piaui State, Northeast Brazil.

Chikungunya virus (CHIKV) is an arbovirus that emerged in the Americas in 2013. Infection with CHIKV is symptomatic in most of the cases and patients can develop chronic arthralgia that lasts from months to years in over 40% of the cases. The East-Central-South Africa (ECSA) genotype was introduced in Brazil in 2014, in Bahia State. Here we report the circulation of the CHIKV ECSA genotype in Piaui State, Northeast Brazil, during the years 2016-2017. The phylogenetic analysis revealed a single introduction of this lineage probably in 2015 and its maintenance at least until 2017. This analysis has also demonstrated the proximity of this genotype with isolates from neighboring States, and its partial nucleotide sequence of the viral E1 gene revealed a synapomorphy synonyms. This finding highlights the spread of the ECSA genotype in Brazil and supports its circulation in the Brazilian Northeast.

High prevalence of dengue antibodies and the arginine variant of the FcγRIIa polymorphism in asymptomatic individuals in a population of Minas Gerais State, Southeast Brazil.

Dengue is the most prevalent arthropod-borne viral illness in humans worldwide. Single-nucleotide polymorphisms (SNPs) in genes involved in the immune response, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), IgG Fc receptor II-A (FcγRIIa), vitamin D receptor (VDR), and tumor necrosis factor alpha (TNF-α), were previously reported to be associated with susceptibility to dengue disease in different human populations. Therefore, due to the relevant association of host immune and genetic status with disease susceptibility/severity of dengue, this work aims to verify the frequency of anti-dengue virus antibodies and some dengue-associated risk SNPs in a population in Minas Gerais State, Southeast Brazil. A total of 1560 individuals were genotyped for polymorphisms in DC-SIGN (rs4804803), FcγRIIa (rs1801274), VDR (rs7975232), and TNF-α (rs1800629). The presence of anti-dengue antibodies (IgM and/or IgG) in these samples was also assayed. Anti-dengue antibodies were detected at an overall frequency of 16.86%, indicating a virus infection in asymptomatic individuals. The genotypic frequencies of all SNPs studied did not differ between the asymptomatic and control groups. Regarding the allelic frequencies of the four SNPs analyzed, a higher frequency was detected of the G allele of FcγRIIa/rs1801274 in the asymptomatic individuals when compared to that in the control group (p = 0.03). Therefore, the results showed a high prevalence of asymptomatic individuals in Minas Gerais State, with a potential association between the presence of the G allele of FcγRIIa/rs1801274 and protection against symptomatic disease.

Antidiarrheal effects of water-soluble proteins from Plumeria pudica latex in mice.

The water-soluble protein fraction obtained from Plumeria pudica (LPPp) latex has previously been demonstrated to have anti-inflammatory and antinociceptive effects. In the present study, LPPp was tested for activity against diarrhea induced by castor oil, prostaglandin E2 (PGE2) or cholera toxin. Different doses of LPPp (10, 20 or 40mg/kg) significantly inhibited the percentage of diarrheal stools (31.18%, 42.97% and 59.70%, respectively) induced by castor oil. This event was followed by significant reduction of both intestinal fluid accumulation (31.42%; LPPp 40mg/kg) and intestinal transit (68.4%; LPPp 40mg/kg). The pretreatment of animals with LPPp (40mg/kg) prevented glutathione and malondialdehyde alterations induced by castor oil. The effects of LPPp against diarrhea induced by castor oil were lost when the fraction was submitted to protein denaturing treatment with heat. LPPp (40mg/kg) also inhibited the average volume of intestinal fluid induced by PGE2 (inhibition of 46.0%). Furthermore, LPPp (40mg/kg) prevented intestinal fluid secretion accumulation (37.7%) and chloride ion concentration (50.2%) induced by cholera toxin. In parallel, colorimetric assays demonstrated that proteinases, chitinases and proteinase inhibitors were found in LPPp. Our data suggest that the antidiarrheal effect of LPPp is due to its protein content and is probably associated with its anti-inflammatory properties.