Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory mediators in malaria by Plasmodium vivax during enteroparasites coinfection.

Malaria is a major health issue with more than 200 million cases occurring annually. Moreover, in Malaria endemic area are frequently observed Malaria-enteroparasite co-infections associated with the modulation of inflammatory response. In this aspect, biomarkers play an important role in the disease prognosis. This study aimed to evaluate inflammatory mediators in malaria during coinfection with enteroparasites. A subset of serum samples already collected was analyzed and divided into four groups: Malaria (n = 34), Co-infected (n = 116), Enteroparasite (n = 120) and Control (n = 95). The serum levels of sTREM-1 and IL-6 were measured by ELISA. TNF-α, and IL-10 levels were previously carried out by flow cytometry. Higher serum levels of sTREM-1 and IL-6 were showed in malaria patients compared to healthy controls. In co-infected malarial patients sTREM-1 serum levels were similar to control group. Interestingly, co-infected malaria patients showed IL-6 serum levels decreased compared to individuals only infected with P. vivax. However, in Malaria patients and co-infected there was a positive correlation between the IL-6 and IL-10 levels (P < 0.0001). This is the first report of sTREM-1 levels in P. vivax infected. Moreover, the results revealing a divergent effect of co-infection with the increased balance between pro-and anti-inflammatory cytokines and reduced IL-6 levels but increases the anemia occurrence. The results also highlight the potential use of IL-6 as a biomarker for P. vivax and enteroparasites coinfection.

Association of toll-like receptors in malaria susceptibility and immunopathogenesis: A meta-analysis.

Toll-like receptors (TLRs) play a key role in the induced immune response in malaria. Although the potential roles of TLRs have been described, it is necessary to elucidate which of these receptors may actually have an impact on the immunopathogenesis of the disease. This article performed a meta-analysis adhered to the PRISMA statement on TLRs studied in malaria by Plasmodium falciparum and Plasmodium vivax and its impact on susceptibility and pathogenesis during malaria. A search of the literature was undertaken in PubMed, LILACS and SciELO published until June 30th, 2020. The risk of bias was calculated using the Joanna Briggs Institute's Critical Review Checklist. Later, based on the inclusion and/or exclusion criteria, 17 out of 296 articles were harvested for this systematic review, the meta-analysis included studies incorporating 6,747 cases and 8,983 controls. The results showed that only TLR1, TLR9 and TLR4 receptors were associated with parasitemia, TLR2 and TLR6 were related with severity and none TLR was correlated with susceptibility. The data described here should be taken with caution, since the current evidence is limited and inconsistent. More studies are needed given that the results may change depending on the region and genetic background of the populations.

Family COVID-19 cluster analysis of an infant without respiratory symptoms.

Diagnosing cases of coronavirus disease (COVID-19) with only non-respiratory symptoms has been challenging. We reported the diagnosis of a child who tested positive for COVID-19 with abdominal pain/diarrhea and tracked his family cluster. One member of the family tested positive for COVID-19 on real-time reverse-transcription polymerase chain reaction assay and three other family members had anti-SARS-CoV-2 antibodies.

Polymorphism in the IL-1ß promoter is associated with IgG antibody response to circumsporozoite protein repeats of Plasmodium vivax.

BACKGROUND: It is well established that infection by Plasmodium vivax is a result of host-parasite interactions. In the present study, association with the IL1/IL2 cytokine profiles, anticircumsporozoite protein antibody levels and parasitic loads was evaluated in individuals naturally infected with P. vivax in an endemic area of the Brazilian Amazon. METHODS: Molecular diagnosis of P. vivax and variants was performed using the PCR-RFLP method and IL1B -511C>T, IL2 -330T>G and IL2+114T>G polymorphisms were identified using PCR-RFLP and allele-specific PCR. IL-1ß and IL-2 cytokine levels were detected by flow cytometry and circumsporozoite protein (CSP) antibodies were measured by ELISA. RESULTS: Three variants of P. vivax CSP were identified and VK247 was found to be the most frequent. However, the prevalence and magnitude of IgG antibodies were higher for the VK210 variant. Furthermore, the antibody response to the CSP variants was not associated with the presence of the variant in the infection. Significant differences were observed between the single nucleotide polymorphism (SNP) -511T>C in the IL1B gene and levels of antibodies to the VK247 and P. vivax-like variants, but there were no associations between SNPs in IL1 and IL2 genes and their plasma products. CONCLUSIONS: Individuals with the rs16944 CC genotype in the IL1ß gene have higher antibody levels to the CSP of P. vivax of VK247 and P. vivax-like variants.

Impact of a twelve-year rotavirus vaccine program on acute diarrhea mortality and hospitalization in Brazil: 2006-2018.

BACKGROUND: Monitoring the impact of vaccine programs is necessary to identify changes in vaccine efficacy. We report the impact of the 12-year rotavirus vaccine program on diarrhea mortality and hospitalizations and their correlation to socioeconomic indicators. METHODS: this ecological study describes diarrhea hospitalizations and deaths from 2006 to 2018 in Brazil and correlates rotavirus vaccine coverage, hospitalizations and deaths to socioeconomic indicators and social vulnerability index (SVI) by state and region. Hospitalizations, deaths, and vaccine coverage trends were analyzed using Joinpoint regression models. Associations between hospitalizations, mortality and rotavirus vaccination coverage and socioeconomic and SVI indicators were established using Ordinary Least Square regressions. RESULTS: Rotavirus vaccine coverage remained stable between 2006 and 2018 (annual percentage changes (APC) [95%CI]: 4.4% [-0.3%, 9.2%]). Diarrhea hospitalization rates decreased 52.5% (-5.7% [-7.5%, -3.8%]), from 68.4 to 32.5 hospitalizations per 10,000 children <5 years-old between 2006 and 2018, with significant decreases in diarrhea mortality (-9.8% [-11.2%, -8.5%]). The Northeast region experienced the largest reductions (-13.9% [-15.7%, -12.2%]). Vaccination coverage and diarrhea-mortality were inversely correlated with the SVI. CONCLUSION: The burden of childhood diarrhea has decreased over an extended period. States with high SVI, but high vaccination coverage had the largest reductions in hospitalizations and deaths.

Family COVID-19 cluster analysis of an infant without respiratory symptoms

Abstract Diagnosing cases of coronavirus disease (COVID-19) with only non-respiratory symptoms has been challenging. We reported the diagnosis of a child who tested positive for COVID-19 with abdominal pain/diarrhea and tracked his family cluster. One member of the family tested positive for COVID-19 on real-time reverse-transcription polymerase chain reaction assay and three other family members had anti-SARS-CoV-2 antibodies.

Chloroquine and mefloquine resistance profiles are not related to the circumsporozoite protein (CSP) VK210 subtypes in field isolates of Plasmodium vivax from Manaus, Brazilian Amazon.

BACKGROUND: The central repetitive region (CRR) of the Plasmodium vivax circumsporozoite surface protein (CSP) is composed of a repetitive sequence that is characterised by three variants: VK210, VK247 and P. vivax-like. The most important challenge in the treatment of P. vivax infection is the possibility of differential response based on the parasite genotype. OBJECTIVES: To characterise the CSP variants in P. vivax isolates from individuals residing in a malaria-endemic region in Brazil and to profile these variants based on sensitivity to chloroquine and mefloquine. METHODS: The CSP variants were determined by sequencing and the sensitivity of the P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. FINDINGS: Although five different allele sizes were amplified, the sequencing results showed that all of the isolates belonged to the VK210 variant. However, we observed substantial genetic diversity in the CRR, resulting in the identification of 10 different VK210 subtypes. The frequency of isolates that were resistant to chloroquine and mefloquine was 11.8 and 23.8%, respectively. However, we did not observe any difference in the frequency of the resistant isolates belonging to the VK210 subtypes. MAIN CONCLUSION: The VK210 variant is the most frequently observed in the studied region and there is significant genetic variability in the CRR of the P. vivax CSP. Moreover, the antimalarial drug sensitivity profiles of the isolates does not seem to be related to the VK210 subtypes.

Chloroquine and mefloquine resistance profiles are not related to the circumsporozoite protein (CSP) VK210 subtypes in field isolates of Plasmodium vivax from Manaus, Brazilian Amazon

BACKGROUND The central repetitive region (CRR) of the Plasmodium vivax circumsporozoite surface protein (CSP) is composed of a repetitive sequence that is characterised by three variants: VK210, VK247 and P. vivax-like. The most important challenge in the treatment of P. vivax infection is the possibility of differential response based on the parasite genotype. OBJECTIVES To characterise the CSP variants in P. vivax isolates from individuals residing in a malaria-endemic region in Brazil and to profile these variants based on sensitivity to chloroquine and mefloquine. METHODS The CSP variants were determined by sequencing and the sensitivity of the P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. FINDINGS Although five different allele sizes were amplified, the sequencing results showed that all of the isolates belonged to the VK210 variant. However, we observed substantial genetic diversity in the CRR, resulting in the identification of 10 different VK210 subtypes. The frequency of isolates that were resistant to chloroquine and mefloquine was 11.8 and 23.8%, respectively. However, we did not observe any difference in the frequency of the resistant isolates belonging to the VK210 subtypes. MAIN CONCLUSION The VK210 variant is the most frequently observed in the studied region and there is significant genetic variability in the CRR of the P. vivax CSP. Moreover, the antimalarial drug sensitivity profiles of the isolates does not seem to be related to the VK210 subtypes.

Impact of population admixture on the distribution of immune response co-stimulatory genes polymorphisms in a Brazilian population.

Co-stimulatory molecules are essential in the orchestration of immune response and polymorphisms in their genes are associated with various diseases. However, in the case of variable allele frequencies among continental populations, this variation can lead to biases in genetic studies conducted in admixed populations such as those from Brazil. The aim of this study was to evaluate the influence of genomic ancestry on distributions of co-stimulatory genes polymorphisms in an admixed Brazilian population. A total of 273 individuals from the north of Brazil participated in this study. Nine single nucleotide polymorphisms in 7 genes (CD28, CTLA4, ICOS, CD86, CD40, CD40L and BLYS) were determined by polymerase chain reaction-restriction fragment length polymorphism. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. The analysis showed that the main contribution was European (43.9%) but also a significant contribution of African (31.6%) and Amerindian (24.5%) ancestry. ICOS, CD40L and CD86 polymorphisms were associated with genomic ancestry. However there were no significant differences in the proportions of ancestry for the other SNPs and haplotypes studied. Our findings reinforce the need to apply AIMs in genetic association studies involving these polymorphisms in the Brazilian population.

Influence of HLA-DRB-1 alleles on the production of antibody against CSP, MSP-1, AMA-1, and DBP in Brazilian individuals naturally infected with Plasmodium vivax.

We evaluated the influence of allelic frequency of the human leukocyte antigen (HLA) -DRB1 on the acquisition of antibody response against malaria sporozoite and merozoite peptides in patients with Plasmodium vivax malaria acquired in endemic areas of Brazil. IgG antibodies were detected by enzyme-linked immunosorbent assay against four peptides of circumsporozoite protein (CSP) (amino, carboxyl, and VK210 and VK247 repeats) and peptides of merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and Duffy-binding protein (DBP). We found an association between HLA-DR3 and HLA-DR5 alleles and lack of antibody response to CSP amino terminal, as well as an association between HLA-DR3 and the highest antibody response to MSP1 (Pv200L). In conclusion, we suggest a potential regulatory role of the HLA-DRB1 alleles in the production of antibodies to a conserved region of P. vivax CSP and MSP1 in Brazilian population exposed to malaria.

Giardiasis as zoonosis: between proof of principle and paradigm in the Northwestern region of São Paulo State, Brazil.

OBJECTIVE: In order to evaluate the potential zoonotic transmission of Giardia duodenalis, isolates from humans and dogs in the Northwestern region of the São Paulo State, Brazil were characterized based on the ß-giardin gene. METHODS: The samples were analyzed by sequencing of the Nested-PCR products. RESULTS: The A1 and A2 subgenotypes were detected in human and dogs. Cysts of assemblage B, C and D have not been found in any isolates studied. CONCLUSIONS: These results are consistent with the view that giardiasis in the largest endemic region of the Brazil should not be seen as a single entity.

Giardiasis as zoonosis: between proof of principle and paradigm in the Northwestern region of São Paulo State, Brazil

OBJECTIVE: In order to evaluate the potential zoonotic transmission of Giardia duodenalis, isolates from humans and dogs in the Northwestern region of the São Paulo State, Brazil were characterized based on the β-giardin gene. METHODS: The samples were analyzed by sequencing of the Nested-PCR products. RESULTS: The A1 and A2 subgenotypes were detected in human and dogs. Cysts of assemblage B, C and D have not been found in any isolates studied. CONCLUSIONS: These results are consistent with the view that giardiasis in the largest endemic region of the Brazil should not be seen as a single entity.

Development of PCR-RFLP assay for the discrimination of Plasmodium species and variants of P. vivax (VK210, VK247 and P. vivax-like) in Anopheles mosquitoes.

The identification of Plasmodium species in Anopheles mosquitoes is an integral component of malaria control programs. We developed a new assay to identify Plasmodium falciparum, Plasmodium malariae, and Plasmodium vivax variants. Specific primers were designed to hybridize to CS gene-specific regions. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to distinguish the P. vivax variants VK210, VK247, and P. vivax-like. The new PCR-RFLP assay revealed good agreement when compared with a nested PCR using artificially infected Anopheles mosquitoes. This sensitive PCR-RFLP method can be useful when detection of Plasmodium species and P. vivax variants is required and may be employed to improve the understanding of malaria transmission dynamics by Anopheles species.

The frequency of HLA-DRB1 polymorphisms in Brazilian Plasmodium vivax malaria patients and in blood donors from the Amazon Region / Frequência de polimorfismos HLA-DRB1 em pacientes brasileiros com malária por Plasmodium vivaxe em doadores de sangue da Região Amazônica

We evaluated the frequency of different HLA-DRB1 alleles in Plasmodium vivax-infected individuals and in healthy blood donors from malaria endemic areas of Brazil. Low-resolution human leukocyte antigen-DRBl genotyping was performed for 73 malaria patients and 29 healthy blood donors. The most frequent alleles in individuals from northern Brazil were human leukocyte antigen-DRB1*04, *08, *07 and *13. The frequency of human leukocyte antigen-DRB1*07 was higher in malaria-infected individuals than in the control group, which reinforces the theory that this allele plays an important role in susceptibility to malaria. This study offers new information about a potential susceptibility factor for P. vivax malaria in a Brazilian population that is naturally exposed to malaria.

Este estudo avaliou a frequência de diferentes alelos HLA-DRB1 em indivíduos infectados por Plasmodium vivax e em doadores de sangue saudáveis provenientes de áreas endêmicas de malária do Brasil. Foi realizada uma genotipagem de baixa resolução dos alelos HLA-DRB1 em 73 pacientes com malária e em 29 doadores de sangue saudáveis. Os alelos mais frequentes em indivíduos do norte do Brasil foram HLA-DRB1 *04, *08, *07 e *13. A frequência de HLA-DRB1 *07 foi maior nos indivíduos infectados com malária do que no grupo controle, o que reforça a hipótese de que esse alelo desempenha um papel importante na suscetibilidade à malária. Esta pesquisa fornece novas informações sobre um fator potencial de suscetibilidade à malária por P. vivax em uma população brasileira naturalmente exposta à doença.