Pregnant women's perceptions on Information Sources on Zika Virus: a qualitative study.

The Zika virus (ZIKV) epidemic had a sanitary, psychosocial, and economic impact on individuals of reproductive age. The primary concern revolved around infection during pregnancy due to possible vertical transmission and its association with adverse fetal and infant outcomes, known as Congenital Zika Syndrome (CZS). This qualitative study employs phenomenology and grounded theory. This study includes interviews with 98 women, some pregnant during the ZIKV epidemic in Brazil, Colombia, and Puerto Rico, who had children with CZS or without diagnosed neurological impairment. Additionally, the study included a group of women who were pregnant during the COVID-19 pandemic in these same countries. In both groups, interviewees had varying levels of knowledge about ZIKV. The study found that messages conveyed through the media tended to be alarmist, in contrast to the information provided by healthcare professionals, which was considered more trustworthy. Pregnant women during the ZIKV epidemic reported receiving their ZIKV and CSZ infection diagnoses late, either during or after childbirth. The study underscores the needs of pregnant women in high-risk scenarios, the importance of health education processes, and the necessity to reinforce communication and continuing education.

A epidemia do vírus Zika (ZIKV) teve impacto sanitário, psicossocial e econômico sobre pessoas em idade reprodutiva. A principal preocupação foi a infecção durante a gravidez devido a possível transmissão vertical e sua associação com resultados fetais e infantis adversos, conhecida como síndrome congênita associada à infecção pelo Vírus Zika (SCZ). Este estudo qualitativo utiliza a fenomenologia e a teoria fundamentada. O estudo inclui entrevistas com 98 mulheres, parte grávida durante a epidemia de ZIKV no Brasil, Colômbia e Porto Rico e que tiveram filhos com SCZ ou sem comprometimento neurológico diagnosticado. Além disso, o estudo inclui um grupo de mulheres grávidas durante a pandemia de COVID-19 nos mesmos países. Em ambos os grupos, as entrevistadas tinham diferentes níveis de conhecimento sobre ZIKV. O estudo constatou que as mensagens veiculadas por meio da mídia eram alarmistas; em contraste com as informações fornecidas por profissionais de saúde, consideradas mais confiáveis. Mulheres gestantes durante a epidemia do ZIKV relataram ter recebido seu diagnóstico de infecção por ZIKV e SCZ tardiamente ou após o parto. O estudo destaca as necessidades das mulheres grávidas em cenários de alto risco, a importância de processos de educação em saúde e a necessidade de reforçar a comunicação e a educação continuada.

Urban arbovirus exposure in blood donations from an endemic area of Brazil.

BACKGROUND AND OBJECTIVES: In Brazil, urban arboviruses, such as dengue virus (DENV), Zika virus (ZIKV) and chikungunya virus (CHIKV), constitute a major public health problem, and due to their endemicity and asymptomatic cases, they pose a potential threat to blood donations. Rio de Janeiro (RJ), Brazil, has been impacted by extensive DENV epidemics over the last 30 years and, after 2015, by CHIKV and ZIKV. MATERIALS AND METHODS: Urban arboviruses DENV, ZIKV and CHIKV were investigated in blood donations (n = 778) at the State Institute of Hematology, HEMORIO (RJ) from 2019 to 2022 by serological and molecular methods. RESULTS: An overall arbovirus exposure was observed in 26.1% of the blood donations. Anti-DENV IgM was detected in 4.0% of samples and two donations were DENV NS1 positive. Positive anti-CHIKV IgM was observed in 4.7% of the donations. Co-detection of anti-CHIKV IgM and anti-DENV IgM was observed in 1.0% of donors, and CHIKV prevalence was 21.3%. All blood donations tested were negative for the DENV, ZIKV and CHIKV RNA. CONCLUSION: IgM seroprevalence to the arboviruses analyzed here is an indicator of recent infection in asymptomatic donors, showing that the population of blood donors can be a vehicle for new infections, especially during epidemic periods.

[The viral protein NS1: a major player in the pathogenesis of orthoflaviviruses]. / La protéine virale NS1 : un acteur majeur de la pathogenèse des orthoflavivirus.

Orthoflaviviruses are enveloped positive-sense RNA viruses comprising numerous human pathogens transmitted by hematophagous arthropods. This includes viruses such as dengue virus, Zika virus, and yellow fever virus. The viral nonstructural protein NS1 plays a central role in the pathogenesis and cycle of these viruses by acting in two different forms: associated with the plasma membrane (NS1m) or secreted outside the cell (NS1s). The versatility of NS1 is evident in its ability to modulate various aspects of the infectious process, from immune evasion to pathogenesis. As an intracellular protein, it disrupts many processes, interfering with signaling pathways and facilitating viral replication in concert with other viral proteins. As a secreted protein, NS1 actively participates in immune evasion, interfering with the host immune system, inhibiting the complement system, facilitating viral dissemination, and disrupting the integrity of endothelial barriers. This review primarily aims to address the role of NS1 in viral pathogenesis associated with orthoflaviviruses.

Serious Concern of Congenital Zika Syndrome (CZS) in India: A Narrative Review.

Congenital Zika syndrome (CZS) is a major concern in India and highlights the multifaceted challenges posed by the Zika virus (ZIKV). The alarming increase in CZS cases in India, a condition that has serious effects on both public health and newborns, has raised concerns. This review highlights the importance of raising concern and awareness and taking preventive measures by studying the epidemiology, clinical symptoms, and potential long-term consequences of CZS. The review also contributes to worldwide research and information sharing to improve the understanding and prevention of CZS. As India deals with the changing nature of CZS, this thorough review is an important tool for policymakers, health workers, and researchers to understand what is happening now, plan for what to do in the future, and work together as a team, using medical knowledge, community involvement, and study projects to protect newborns' health and reduce the public health impact of these syndromes.

Immunological and Safety Considerations When Selecting the Dose Formulation of a Purified Inactivated Zika Virus Vaccine (PIZV).

We previously reported the first-in-human assessment of three doses (2, 5, and 10 µg) of purified inactivated Zika virus vaccine (PIZV or TAK-426) in the Phase 1 ZIK-101 study (NCT03343626). Here, we report dose selection based on extended safety and immunogenicity data (6 months post-vaccination) and discuss considerations (e.g., immunological, historic, flavivirus immunological cross-reactions) for selecting a Zika virus (ZIKV) vaccine dose formulation. TAK-426 dose selection was conducted at the first interim analysis, and was based on cumulative safety data from both flavivirus-naïve (up to ≥28 days post-dose PD2) and flavivirus-primed participants (up to ≥28 days PD1), and on immunogenicity data from flavivirus-naïve participants only (at 28 days PD1 and 28 days PD2). The safety profile from TAK-426 recipients was compared to placebo recipients. Immunogenicity was assessed by geometric mean titer ratios of neutralizing anti-ZIKV antibodies and differences in seroconversion rates. There was no significant difference in safety between the three TAK-426 doses. The 10 µg dose provided the earliest and strongest immune response (with close to 100% seroconversion and higher antibody titers PD1 in flavivirus-naïve participants), and was well tolerated with acceptable safety profiles in both flavivirus-naïve and flavivirus-primed participants; this dose was selected for further development.

Transcriptomic Signatures of Zika Virus Infection in Patients and a Cell Culture Model.

Zika virus (ZIKV), a re-emerging flavivirus, is associated with devasting developmental and neurological disease outcomes particularly in infants infected in utero. Towards understanding the molecular underpinnings of the unique ZIKV disease pathologies, numerous transcriptome-wide studies have been undertaken. Notably, these studies have overlooked the assimilation of RNA-seq analysis from ZIKV-infected patients with cell culture model systems. In this study we find that ZIKV-infection of human lung adenocarcinoma A549 cells, mirrored both the transcriptional and alternative splicing profiles from previously published RNA-seq data of peripheral blood mononuclear cells collected from pediatric patients during early acute, late acute, and convalescent phases of ZIKV infection. Our analyses show that ZIKV infection in cultured cells correlates with transcriptional changes in patients, while the overlap in alternative splicing profiles was not as extensive. Overall, our data indicate that cell culture model systems support dissection of select molecular changes detected in patients and establishes the groundwork for future studies elucidating the biological implications of alternative splicing during ZIKV infection.

Development and validation of Mayaro virus with luciferase reporter genes as a tool for antiviral assays.

Arboviruses are etiological agents in an extensive group of emerging diseases with great clinical relevance in Brazil, due to the wide distribution of their vectors and the favorable environmental conditions. Among them, the Mayaro virus (MAYV) has drawn attention since its emergence as the etiologic agent of Mayaro fever, a highly debilitating disease. To study viral replication and identify new drug candidates, traditional antiviral assays based on viral antigens and/or plaque assays have been demonstrating low throughput, making it difficult to carry out larger-scale assays. Therefore, we developed and characterized two DNA-launched infectious clones reporter viruses based on the MAYV strain BeAr 20290 containing the reporter genes of firefly luciferase (FLuc) and nanoluciferase (NLuc), designated as MAYV-firefly and MAYV-nanoluc, respectively. The viruses replicated efficiently with similar properties to the parental wild-type MAYV, and luminescence expression levels reflected viral replication. Reporter genes were also preserved during passage in cell culture, remaining stably expressed for one round of passage for MAYV-firefly and three rounds for MAYV-nanoluc. Employing the infectious clone, we described the effect of Rimantadine, an FDA-approved Alzheimer's drug, as a repurposing agent for MAYV but with a broad-spectrum activity against Zika virus infection. Additionally, we validated MAYV-nanoluc as a tool for antiviral drug screening using the compound EIDD-2749 (4'-Fluorouridine), which acts as an inhibitor of alphavirus RNA-dependent RNA polymerase.

Epidemiological, virological and clinical characterization of a Dengue/Zika outbreak in the Caribbean region of Costa Rica 2017-2018.

The increase in incidence and geographical expansion of viruses transmitted by the Aedes mosquitoes, such as dengue (DENV) and zika (ZIKV) in the Americas, represents a burden for healthcare systems in tropical and subtropical regions. These and other under-detected arboviruses co-circulate in Costa Rica, adding additional complexity to their management due to their shared epidemiological behavior and similarity of symptoms in early stages. Since diagnostics of febrile illness is mostly based on clinical symptoms alone, we gathered acute-phase serum and urine from 399 samples of acute dengue-like cases from two healthcare facilities of Costa Rica, during an outbreak of arboviruses from July 2017 to May 2018, and tested them using molecular and serological methods. The analyses showed that of the clinically presumptive arbovirus cases that were reported, only 39.4% (n=153) of the samples were confirmed positive by RT-PCR to be DENV (DENV (10.3%), CHIKV (0.2%), ZIKV (27.3%), or mixed infections (1.5%). RT-PCR for other alphaviruses and flaviviruses, and PCR for Leptospira sp were negative. Furthermore, to assess flavivirus positivity in post-acute patients, the negative sera were tested against Dengue-IgM. 20% of sera were found positive, confounding even more the definitive number of cases, and emphasizing the need of several distinct diagnostic tools for accurate diagnostics. Molecular characterization of the prM and E genes from isolated viruses revealed that the American/Asian genotype of DENV-2 and the Asian lineage of ZIKV were circulating during this outbreak. Two different clades of DENV-2 American/Asian genotype were identified to co-circulate in the same region and a difference in the platelet and leukocyte count was noted between people infected with each clade, suggesting a putative distinct virulence. Our study sheds light on the necessity for healthcare strategies in managing arbovirus outbreaks, emphasizing the importance of comprehensive molecular and serological diagnostic approaches, as well as molecular characterization. This approach aids in enhancing our understanding of the clinical and epidemiological aspects of arboviral diseases during outbreaks. Our research highlights the need to strengthen training programs for health professionals and the need to increase research-based on laboratory evidence for diagnostic accuracy, guidance, development and implementation of public health interventions and epidemiological surveillance.

A novel vaccine construct against Zika virus fever: insights from epitope-based vaccine discovery through molecular modeling and immunoinformatics approaches.

The Zika virus (ZIKV) is an emerging virus associated with the Flaviviridae family that mainly causes infection in pregnant women and leads to several abnormalities during pregnancy. This virus has unique properties that may lead to pathological diseases. As the virus has the ability to evade immune response, a crucial effort is required to deal with ZIKV. Vaccines are a safe means to control different pathogenic infectious diseases. In the current research, a multi-epitope-based vaccination against ZIKV is being designed using in silico methods. For the epitope prediction and prioritization phase, ZIKV polyprotein (YP_002790881.1) and flavivirus polyprotein (>YP_009428568.1) were targeted. The predicted B-cell epitopes were used for MHC-I and MHC-II epitope prediction. Afterward, several immunoinformatics filters were applied and nine (REDLWCGSL, MQDLWLLRR, YKKSGITEV, TYTDRRWCF, RDAFPDSNS, KPSLGLINR, ELIGRARVS, AITQGKREE, and EARRSRRAV) epitopes were found to be probably antigenic in nature, non-allergenic, non-toxic, and water soluble without any toxins. Selected epitopes were joined using a particular GPGPG linker to create the base vaccination for epitopes, and an extra EAAAK linker was used to link the adjuvant. A total of 312 amino acids with a molecular weight (MW) of 31.62762 and an instability value of 34.06 were computed in the physicochemical characteristic analysis, indicating that the vaccine design is stable. The molecular docking analysis predicted a binding energy of -329.46 (kcal/mol) for TLR-3 and -358.54 (kcal/mol) for TLR-2. Moreover, the molecular dynamics simulation analysis predicted that the vaccine and receptor molecules have stable binding interactions in a dynamic environment. The C-immune simulation analysis predicted that the vaccine has the ability to generate both humoral and cellular immune responses. Based on the design, the vaccine construct has the best efficacy to evoke immune response in theory, but experimental analysis is required to validate the in silico base approach and ensure its safety.

Simultaneous detection of arboviruses by a multiplex RT-qPCR assay in Tocantins, a northern state of Brazil.

In Brazil, Dengue, Zika and Chikungunya viruses constitute a major threat to the public health system. Simultaneous circulation of these arboviruses occurs in many regions of the world due to the expansion of transmission vectors. The infection by these arboviruses triggers similar symptoms during their acute phase. However, in some cases, severe symptoms may occur, leading to different types of disabilities and even death. In this context, considering the similarity of the symptoms, the problems caused by the infection of these arboviruses, and the increasing risk of coinfection in humans, the differential diagnosis of these infections is essential for clinical management and epidemiological investigation. Thus, this study aimed to identify, through diagnosis via Quantitative Polymerase Chain Reaction with Reverse Transcription, arbovirus coinfection in patients from the Tocantins state (Northern Brazil). A total of 495 samples were analyzed, three from which were determined to be a coinfection of Dengue and Chikungunya viruses. The data obtained here indicate the co-circulation and coinfection by Dengue and Chikungunya viruses in the Tocantins state. These results highlight the importance of monitoring the circulation of these arboviruses for the development of health actions that aim their prevention and combat, as well as their clinical and therapeutic management.

In vitro and in vivo inhibition of the host TRPC4 channel attenuates Zika virus infection.

Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death.

The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection.

BACKGROUND: Peptide drugs are advantageous because they are subject to rational design and exhibit highly diverse structures and broad biological activities. The NS2B-NS3 protein is a particularly promising flavivirus therapeutic target, with extensive research on the development of inhibitors as therapeutic candidates, and was used as a model in this work to determine the mechanism by which GA-Hecate inhibits ZIKV replication. OBJECTIVE: The present study aimed to evaluate the potential of GA-Hecate, a new antiviral developed by our group, against the Brazilian Zika virus and to evaluate the mechanism of action of this compound on the flavivirus NS2B-NS3 protein. METHODS: Solid-phase peptide Synthesis, High-Performance Liquid Chromatography, and Mass Spectrometry were used to obtain, purify, and characterize the synthesized compound. Real-time and enzymatic assays were used to determine the antiviral potential of GA-Hecate against ZIKV. RESULTS: The RT-qPCR results showed that GA-Hecate decreased the number of ZIKV RNA copies in the virucidal, pre-treatment, and post-entry assays, with 5- to 6-fold fewer RNA copies at the higher nontoxic concentration in Vero cells (HNTC: 10 µM) than in the control cells. Enzymatic and kinetic assays indicated that GA-Hecate acts as a competitive ZIKV NS2B-NS3 protease inhibitor with an IC50 of 32 nM and has activity against the yellow fever virus protease. CONCLUSION: The results highlight the antiviral potential of the GA-Hecate bioconjugate and open the door for the development of new antivirals.

Pooled Cohort Profile: ReCoDID Consortium's Harmonized Acute Febrile Illness Arbovirus Meta-Cohort.

Infectious disease (ID) cohorts are key to advancing public health surveillance, public policies, and pandemic responses. Unfortunately, ID cohorts often lack funding to store and share clinical-epidemiological (CE) data and high-dimensional laboratory (HDL) data long term, which is evident when the link between these data elements is not kept up to date. This becomes particularly apparent when smaller cohorts fail to successfully address the initial scientific objectives due to limited case numbers, which also limits the potential to pool these studies to monitor long-term cross-disease interactions within and across populations. CE data from 9 arbovirus (arthropod-borne viruses) cohorts in Latin America were retrospectively harmonized using the Maelstrom Research methodology and standardized to Clinical Data Interchange Standards Consortium (CDISC). We created a harmonized and standardized meta-cohort that contains CE and HDL data from 9 arbovirus studies from Latin America. To facilitate advancements in cross-population inference and reuse of cohort data, the Reconciliation of Cohort Data for Infectious Diseases (ReCoDID) Consortium harmonized and standardized CE and HDL from 9 arbovirus cohorts into 1 meta-cohort. Interested parties will be able to access data dictionaries that include information on variables across the data sets via Bio Studies. After consultation with each cohort, linked harmonized and curated human cohort data (CE and HDL) will be made accessible through the European Genome-phenome Archive platform to data users after their requests are evaluated by the ReCoDID Data Access Committee. This meta-cohort can facilitate various joint research projects (eg, on immunological interactions between sequential flavivirus infections and for the evaluation of potential biomarkers for severe arboviral disease).

Underdiagnosis of arbovirus infections in returned travelers in an area with growing circulation of Aedes albopictus in North-Eastern France.

BACKGROUND: Vector-borne diseases such as malaria and arboviruses are common etiologies of post-travel fever. METHODS: After excluding malaria, we retrospectively analyzed the diagnosis of dengue virus (DENV), chikungunya virus (CHIKV), and zika virus (ZIKV) infections following recent travel by patients treated at the Strasbourg University Hospital between 2014 and 2023. Available serums (n = 35) sampled in 2023 were retrospectively tested for DENV, CHIKV, and ZIKV infections. RESULTS: Our results showed that 78% of the 915 malaria-negative patients without changes over the course of ten years had not undergone arbovirus infection testing. Retrospective testing revealed missing arbovirus infections: two DENV infections and one CHIKV infection, representing 8.6% (3/35) of patients for whom no mandatory declaration or vector control could be undertaken. CONCLUSION: Our results highlight the need for early case detection, particularly in the context of the upcoming 2024 Olympic Games.

Infection by zika virus increase angiotensin I-converting enzyme activity in mouse brain.

Congenital zika virus syndrome (CZS) has become a significant worldwide concern since the sudden rise of microcephaly related to zika virus (ZIKV) in Brazil. Primarily transmitted by Aedes mosquitoes, ZIKV shares serologic similarities with dengue virus (DENV), complicating the diagnosis and/or clinical management. The Angiotensin I-Converting Enzyme (ACE) was associated with either neuroprotective or anti-inflammatory properties in the central nervous system (CNS). The possible role(s) of ACE in these two flaviviruses infection remain largely unexplored. In this study, we evaluate ACE activity in the brain of ZIKV- or DENV-infected mice, both compared to MOCK, showing about 30 % increased ACE activity only in ZIKV-infected mice (p = 0.024), while no change was noticed in brain from DENV-infected animals (p = 0.888). In addition, the treatment with interferon beta (IFNß), under conditions previously demonstrated to rescue the normal size of microcephalic brains determined by ZIKV infection, also restored ACE activity in ZIKV-infected animals to levels close to that of the MOCK control group. Although inflammatory responses expected for either ZIKV or DENV infections, only ZIKV was associated with microcephaly, as well as with increased ACE activity and reversion by treatment with IFNß. Furthermore, this increase in ACE activity was observed only after intracerebroventricular (ICV) injection (F (2, 16) = 7.907, p = 0.004), but not for intraperitoneal (IP) administration of ZIKV (F (2, 26) = 1.996, p = 0.156), suggesting that the observed central ACE activity modulation may be associated with the presence of this specific flavivirus in the brain.

Cytoskeleton-associated gelsolin responds to the midgut distention process in saline meal-fed Aedes aegypti and affects arbovirus dissemination from the midgut.

The mosquito, Aedes aegypti, is the principal vector for several arboviruses. The mosquito midgut is the initial tissue that gets infected with an arbovirus acquired along with a blood meal from a vertebrate host. Blood meal ingestion leads to midgut tissue distention thereby increasing the pore size of the surrounding basal lamina. This allows newly synthesized virions to exit the midgut by traversing the distended basal lamina to infect secondary tissues of the mosquito. We conducted a quantitative label-free proteomic time course analysis with saline meal-fed Ae. aegypti females to identify host factors involved in midgut tissue distention. Around 2000 proteins were detected during each of the seven sampling time points and 164 of those were uniquely expressed. Forty-five of 97 differentially expressed proteins were upregulated during the 96-h time course and most of those were involved in cytoskeleton modulation, metabolic activity, and vesicle/vacuole formation. The F-actin-modulating Ae. aegypti (Aa)-gelsolin was selected for further functional studies. Stable knockout of Aa-gelsolin resulted in a mosquito line, which showed distorted actin filaments in midgut-associated tissues likely due to diminished F-actin processing by gelsolin. Zika virus dissemination from the midgut of these mosquitoes was diminished and delayed. The loss of Aa-gelsolin function was associated with an increased induction of apoptosis in midgut tissue indicating an involvement of Aa-gelsolin in apoptotic signaling in mosquitoes. Here, we used proteomics to discover a novel host factor, Aa-gelsolin, which affects the midgut escape barrier for arboviruses in mosquitoes and apoptotic signaling in the midgut.

Association between Sleep and Language Development in Children with Congenital Zika Syndrome.

AIM: Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. METHOD: We studied cross-sectionally 135 children with CZS aged 0 to 48 months, investigating sleep using the BISQ Questionnaire. Language development was assessed using the Early Language Milestone Scale, while motor development and cognitive and social ability were assessed using the Bayley Scales of Infant and Young Child Development 3rd edition. We also studied longitudinally a cohort of 16 children (initially aged 0 to 12 months) whom we followed for four years, assessing at one-year intervals. RESULTS: Sleep disturbances and language deficits were highly frequent in this population. In the 0-12 months group, a late bedtime and frequent nighttime awakenings were associated with poorer auditory expressive skills. At 13-24 months, nighttime awakenings were associated with poorer auditory expressive skills, while among 25-36-month-olds decreased auditory receptive skills were associated with longer sleep onset latency and reduced nighttime sleep duration. CONCLUSION: The brain alterations caused by Zika virus infection affect both sleep disturbances and delays in language development. It is possible that sleep disturbance may be a mediating factor in the pathway between CZS and delayed language development, as the three analyzed language skills showed a correlation with sleep parameters.

Serological Evidence of Zika Virus Infections in Sudan.

Little is known about the frequency of Zika virus (ZIKV) infections in Sudan. The aim of this study was to obtain data on the prevalence of ZIKV infections and the immunity of the population in the country. To this end, 198 sera obtained between December 2012 and January 2013 in different regions in Sudan were examined for neutralizing antibodies against ZIKV, dengue virus (DENV), and yellow fever virus (YFV). The sera were non-randomly selected. The neutralization titers were compared with each other and with the WHO 1st International Standard for anti-Asian lineage Zika virus antibody. Twenty-six sera neutralized ZIKV. One-third of these sera had higher neutralization titers against ZIKV than against DENV-2 and -3. Two sera showed higher neutralization titers than the WHO standard for ZIKV antibodies. These data suggest occasional ZIKV infections in Sudan. The low percentage of sera in this cohort that neutralized ZIKV indicates that, in the study period, the population was susceptible to ZIKV infection.

Comparative Evaluation of Select Serological Assays for Zika Virus Using Blinded Reference Panels.

In response to the 2015 Zika virus (ZIKV) epidemic that occurred in Brazil, numerous commercial serological assays have been developed for clinical and research applications. Diagnosis of recent infection in pregnant women remains challenging. Having standardized, comparative studies of ZIKV tests is important for implementing optimal diagnostic testing and disease surveillance. This is especially important for serology tests used to detect ZIKV infection given that antibodies against ZIKV can cross-react with other arboviruses in the same virus family, such as dengue virus (DENV), yellow fever virus (YFV) and West Nile virus (WNV). We looked at the sensitivity and specificity of tests detecting ZIKV antibodies (IgM, IgG) from multiple manufacturers using panels of samples previously collected with known exposure to ZIKV and other arboviruses. We found that performance of the IgM tests was highly variable, with only one test (Inbios 2.0 IgM capture ELISA) having both high sensitivity and specificity. All IgG tests showed good sensitivity; however, specificity was highly variable, with some assays giving false-positive results on samples infected by another flavivirus. Overall, the results confirmed that accurate ZIKV antibody testing is challenging, especially in specimens from regions endemic for multiple other flaviviruses, and highlight the importance of available and suitable reference samples to evaluate ZIKV diagnostics.

Methodology for the Differential Classification of Dengue and Chikungunya According to the PAHO 2022 Diagnostic Guide.

Arboviruses such as dengue, Zika, and chikungunya present similar symptoms in the early stages, which complicates their differential and timely diagnosis. In 2022, the PAHO published a guide to address this challenge. This study proposes a methodological framework that transforms qualitative information into quantitative information, establishing differential weights in relation to symptoms according to the medical evidence and the GRADE scale based on recommendation 1 of the said guide. To achieve this, common variables from the dataset were identified using the PAHO guide, and quality rules were established. A linear interpolation function was then parameterised to assign weights to the symptoms according to the evidence. Machine learning was used to compare the different models, achieving 99% accuracy compared with 79% without the methodology. This proposal represents a significant advancement, allowing the direct application of the PAHO recommendations to the dataset and improving the differential classification of arboviruses.