Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants during pregnancy. ...Mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied.
Our cohort study screened 1006 pregnant women with a Zika/dengue/CHIKV rapid test at two clinics in Nigeria between 2019 and 2022. Women who tested positive for the rapid test were followed through their pregnancy and their infants were observed for 6 months, with a subset tested by reverse transcription-polymerase chain reaction (RT-PCR) and neutralization, to investigate seropositivity rates and MTCT of CHIKV.
Of the 1006, 119 tested positive for CHIKV immunoglobulin (Ig)M, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with eight normal and four abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis, and jaundice. CHIKV IgM testing identified three possible antepartum transmissions.
In Nigeria, we found significant CHIKV infection in pregnancy and possible CHIKV antepartum transmission associated with birth abnormalities.
Background Chikungunya virus (CHIKV) has caused worldwide epidemics that impose a major burden on health systems. Approximately half of infected individuals develop chronic debilitating arthralgia, ...affecting their quality of life. Here, we identified the relevant clinical and demographic variables in the acute phase of CHIKV infection prospectively linked to chronic arthralgia to elaborate a prognostic scoring system. Methods Acute CHIKV infection cases (n = 134) confirmed by serology or molecular test were examined <10 days of disease onset and followed for one year to evaluate for disease progression. Potential risk factors for chronic arthralgia were evaluated by multivariate analysis to develop a prognostic scoring system, which was subsequently tested in an independent validation cohort consisting of 42 individuals. Results A total of 107 out of 134 (80%) acute CHIKV-confirmed cases from the derivation cohort were re-examined one year after enrollment. Chronic arthralgia post-CHIKV infection was diagnosed in 64 (60%). Five of the 12 parameters evaluated in the acute phase were statistically associated with persistent arthralgia and were further tested by Bayesian analysis. These variables were weighted to yield a prognosis score denominated SHERA (Sex, Hypertension, Edema, Retroocular pain, Age), which exhibited 81.3% accuracy in predicting long-term arthralgia post-CHIKV infection in the derivation cohort, and 76.5% accuracy in the validation cohort. Conclusions The simplified and externally validated prognostic scoring system, SHERA, is a useful method to screen acutely CHIKV-infected patients at elevated risk of chronic arthralgia who will benefit from specific interventions. This tool could guide public health policies, particularly in resource-constrained settings.
parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive
and
mapping of the ...signaling pathways upstream and downstream of antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in cutaneous leishmaniasis (CL), by combining functional assays in human and murine macrophages with a systems biology analysis of
(skin biopsies) CL patient samples. First, we show the PKR pathway controls the expression and activation of Nrf2 in
infection
. Nrf2 activation also required PI3K/Akt signaling and autophagy mechanisms. Nrf2- or PKR/Akt-deficient macrophages exhibited increased levels of ROS/RNS and reduced expression of
Nrf2-dependent gene and reduced parasite load.
counteracted the Nrf2 inhibitor Keap1 through the upregulation of p62
PKR. This Nrf2/Keap1 observation was confirmed
in skin biopsies from
-infected patients. Next, we explored the
transcriptome in CL patients, as compared to healthy controls. We found the antioxidant response element/Nrf2 signaling pathway was significantly upregulated in CL, including downstream target p62.
enrichment analysis confirmed upstream signaling by interferon and PI3K/Akt, and validated our
findings. Our integrated
, and
approach establish Nrf2 as a central player in human cutaneous leishmaniasis and reveal Nrf2/PKR crosstalk and PI3K/Akt pathways as potential therapeutic targets.
The treatment of cutaneous leishmaniasis is a challenge. A better understanding of the in situ mechanisms involved in the evolution and cure of the disease is essential for the development of new ...therapies.
Correlate histopathological and immunological characteristics of cutaneous leishmaniasis lesions with clinical outcome after different treatment regimens.
The authors analyzed cellular infiltration and immunohistochemistry staining for CD4, CD8 and IL-17 in biopsy samples from 33 patients with cutaneous leishmaniasis before treatment. All patients were recruited in a randomized clinical trial at Corte de Pedra (Bahia-Brazil) and assigned to receive Glucantime®, Glucantime® + Oral Tamoxifen or Glucantime® + Topical Tamoxifen. Patients were followed for 2 to 6 months to define disease outcome.
A similar expression of CD4, CD8 and IL-17 was observed in lesion samples regardless of clinical outcome. In general, a higher amount of CD8 cells were observed compared with CD4 cells. An important observation was that all patients whose cellular infiltrate did not contain plasma cells were cured after treatment.
Isolated quantification of TCD8 and IL-17 using immunohistochemistry is insufficient to analyze the role of these molecules in the immunopathogenesis of cutaneous leishmaniasis. In addition, the expansion of the immunohistochemistry panel would allow a more complete analysis of the immune response in situ.
The absence of plasma cells in cutaneous leishmaniasis lesions was related to a favorable therapeutic outcome.
The Americas, particularly Brazil, were greatly impacted by the widespread Zika virus (ZIKV) outbreak in 2015 and 2016. Efforts were made to implement genomic surveillance of ZIKV as part of the ...public health responses. The accuracy of spatiotemporal reconstructions of the epidemic spread relies on the unbiased sampling of the transmission process. In the early stages of the outbreak, we recruited patients exhibiting clinical symptoms of arbovirus-like infection from Salvador and Campo Formoso, Bahia, in Northeast Brazil. Between May 2015 and June 2016, we identified 21 cases of acute ZIKV infection and subsequently recovered 14 near full-length sequences using the amplicon tiling multiplex approach with nanopore sequencing. We performed a time-calibrated discrete phylogeographic analysis to trace the spread and migration history of the ZIKV. Our phylogenetic analysis supports a consistent relationship between ZIKV migration from Northeast to Southeast Brazil and its subsequent dissemination beyond Brazil. Additionally, our analysis provides insights into the migration of ZIKV from Brazil to Haiti and the role Brazil played in the spread of ZIKV to other countries, such as Singapore, the USA, and the Dominican Republic. The data generated by this study enhances our understanding of ZIKV dynamics and supports the existing knowledge, which can aid in future surveillance efforts against the virus.
Serological diagnosis of Zika virus (ZIKV) infection is challenging because of antigenic cross-reactivity with dengue virus (DENV). This study evaluated the accuracy of the Zika IgM antibody capture ...enzyme-linked immunosorbent assay (CDC Zika IgM MAC-ELISA) in differentiating between ZIKV and DENV infections. To determine sensitivity, we used acute- and convalescent-phase sera from 21 patients with RT-PCR-confirmed ZIKV infection. To determine specificity, we used acute- and convalescent-phase sera from 60 RT-PCR-confirmed dengue cases and sera from 23 blood donors. During the acute-phase of the illness, the assay presented a sensitivity of 12.5% (2/16) for samples collected 0–4 days post symptoms onset (DPSO), and of 75.0% (3/4) for samples collected 5–9 DPSO. During the convalescent-phase of the illness, the test sensitivity was 90.9% (10/11), 100% (2/2), and 0% (0/2) for samples obtained 12–102, 258–260, and 722–727 DPSO, respectively. Specificity for acute- and convalescent-phase samples from RT-PCR-confirmed dengue cases was 100% and 93.2%, respectively. Specificity for blood donor samples was 100%. The assay is an accurate method for Zika serological diagnosis and proved to be reliable for use during surveillance and outbreak investigations in settings where ZIKV and DENV cocirculate.
Localized cutaneous leishmaniasis (LCL) is a chronic disease characterized by ulcerated skin lesion(s) and uncontrolled inflammation. The mechanisms underlying the pathogenesis of LCL are not ...completely understood, and little is known about posttranscriptional regulation during LCL. MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression and can be implicated in the pathogenesis of LCL. We investigated the involvement of miRNAs and their targets genes in human LCL using publicly available transcriptome data sets followed by
validation. Initial analysis highlighted that miRNA expression is altered during LCL, as patients clustered separately from controls. Joint analysis identified eight high confidence miRNAs that had altered expression (-1.5 ≤ fold change ≥ 1.5;
< 0.05) between cutaneous ulcers and uninfected skin. We found that the expression of miR-193b and miR-671 are greatly associated with their target genes, CD40 and TNFR, indicating the important role of these miRNAs in the expression of genes related to the inflammatory response observed in LCL. In addition, network analysis revealed that miR-193b, miR-671, and
correlate only in patients who show faster wound healing (up to 59 days) and not in patients who require longer cure times (more than 60 days). Given that these miRNAs are associated with control of inflammation and healing time, our findings reveal that they might influence the pathogenesis and prognosis of LCL.
Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) amplifies the immune response, operating synergistically with Toll-Like Receptors (TLRs) in the production of inflammatory mediators. TREM-1 ...signaling depends on the adapter protein DAP12, which results in the activation of NFkB, the expression of inflammatory genes, and the release of antimicrobial peptides, such as Beta-defensin 2. We evaluated the activation of the TREM-1 signaling pathways in Cutaneous Leishmaniasis (CL) caused by Leishmania braziliensis and linage human keratinocytes exposed to these parasites since the host immune response against Leishmania plays a critical role in promoting parasite killing but also participates in inflammation and tissue damage. We analyzed publicly available transcriptome data from the lesions of CL patients. In the CL biopsies, we found increased expression of the molecules involved in the TREM-1 pathway. We then validated these findings with RT-qPCR and immunohistochemistry in newly obtained biopsies. Surprisingly, we found a strong labeling of TREM-1 in keratinocytes, prompting the hypothesis that increased TREM-1 activation may be the result of tissue damage. However, increased TREM-1 expression was only seen in human lineage keratinocytes following parasite stimulation. Moreover, no up-regulation of TREM-1 expression was observed in the skin lesions caused by other non-infectious inflammatory diseases. Together, these findings indicate that L. braziliensis (Lb) induces the expression of the TREM-1 receptor in tissue keratinocytes regardless of tissue damage, suggesting that non-immune skin cells may play a role in the inflammatory response of CL.
Dengue outbreaks can affect 390 million persons yearly. In a trial involving 16,235 persons in Brazil, the live, attenuated, tetravalent Butantan vaccine was efficacious in all age groups at 2 years.
•Olfactory loss correlates with lower quality of life.•QOD is a reliable tool for olfactory assessment in Brazil.•QOD validation fills a crucial gap in Brazilian olfactory research.
The incidence of ...olfactory disorders has increased in recent years, mainly related to COVID-19 infection. In Brazil, over 37 million cases of COVID-19 have been reported, and approximately 10 % of those cases continue to experience olfactory disorders for more than one month. Despite the significant negative impact on well-being, there is currently no validated instrument to assess how olfactory disorders impact the quality of life in Brazil.
This study aimed to validate the Questionnaire of Olfactory Disorders (QOD) for Brazilian Portuguese.
The authors first performed translation, back-translation, expert review, pre-testing, psychometric evaluation and cultural adaptation of the English version of the questionnaire. To assure linguistic and conceptual equivalence of the translated questionnaire, 126 participants from two Brazilian states and varying degrees of olfactory loss answered the QOD and the World Health Organization Quality of Life bref (WHOQOL-bref) questionnaires. The University of Pennsylvania Smell Identification Test (UPSIT®) was used to quantify the olfactory loss. Furthermore, to evaluate the reliability of the Portuguese version a test-retest was performed on a subgroup of patients. The authors observed a high Cronbach's alpha (α = 0.86) for internal consistency of the quality of Life (QOD-QOL) statements.
As expected, there was a negative correlation between QOD-QOL and UPSIT® (Spearman's ρ = -0.275, p = 0.002), since QOL score increases and UPSIT® score decreases with worsening of olfactory function. Correlations were moderate between QOD-QOL and WHOQOL-bref mean (Spearman's ρ = -0.374, p < 0.001) and weak to moderate between the QOD-QOL and Visual Analog Scale of the QOD regarding professional life, leisure, and private life (Spearman's ρ = -0.316, p = 0.000; Spearman's ρ = -0.293, p = 0.001; Spearman's ρ = -0.261, p = 0.004; respectively).
In conclusion, the authors have demonstrated a high internal consistency and validity of the Brazilian Portuguese version of the QOD for evaluating the quality of life in individuals with olfactory disorders.
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