Incidence Of Zika Virus Infection Research Articles

Redox Regulation and Metabolic Dependency of Zika Virus Replication: Inhibition by Nrf2-Antioxidant Response and NAD(H) Antimetabolites.

Viral infections alter host cell metabolism and homeostasis; however, the mechanisms that regulate these processes have only begun to be elucidated. We report here that Zika virus (ZIKV) infection activates the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2), which precedes oxidative stress. Downregulation of Nrf2 or inhibition of glutathione (GSH) synthesis resulted in significantly increased viral replication. Interestingly, 6-amino-nicotinamide (6-AN), a nicotinamide analog commonly used as an inhibitor of the pentose phosphate pathway (PPP), decreased viral replication by over 1,000-fold. This inhibition was neither recapitulated by the knockdown of PPP enzymes, glucose 6-phosphate dehydrogenase (G6PD), or 6-phosphogluconate dehydrogenase (6PGD), nor prevented by supplementation with ribose 5-phosphate. Instead, our metabolomics and metabolic phenotype studies support a mechanism in which 6-AN depletes cells of NAD(H) and impairs NAD(H)-dependent glycolytic steps resulting in inhibition of viral replication. The inhibitory effect of 6-AN was rescued with precursors of the salvage pathway but not with those of other NAD+ biosynthesis pathways. Inhibition of glycolysis reduced viral protein levels, which were recovered transiently. This transient recovery in viral protein synthesis was prevented when oxidative metabolism was inhibited by blockage of the mitochondrial pyruvate carrier, fatty acid oxidation, or glutaminolysis, demonstrating a compensatory role of mitochondrial metabolism in ZIKV replication. These results establish an antagonistic role for the host cell Nrf2/GSH/NADPH-dependent antioxidant response against ZIKV and demonstrate the dependency of ZIKV replication on NAD(H). Importantly, our work suggests the potential use of NAD(H) antimetabolite therapy against the viral infection. IMPORTANCE Zika virus (ZIKV) is a major public health concern of international proportions. While the incidence of ZIKV infections has declined substantially in recent years, the potential for the reemergence or reintroduction remains high. Although viral infection alters host cell metabolism and homeostasis to promote its replication, deciphering the mechanism(s) involved in these processes is important for identifying therapeutic targets. The present work reveals the complexities of host cell redox regulation and metabolic dependency of ZIKV replication. An antagonistic effect of the Nrf2/GSH/NADP(H)-dependent antioxidant response against ZIKV infection and an essential role of NAD(H) metabolism and glycolysis for viral replication are established for the first time. These findings highlight the potential use of NAD(H) antimetabolites to counter ZIKV infection and pathogenesis.

The global trends and regional differences in incidence of Zika virus infection and implications for Zika virus infection prevention.

BackgroundZika virus (ZIKV) infection has potential result in severe birth effects. An improved understanding of global trend and regional differences is needed.MethodsAnnual ZIKV infection episodes and incidence rates were collected from Global Burden of Disease Study 2019. Episodes changes and estimated annual percentage changes (EAPCs) of age-standardized incidence rate (ASR) were calculated. Top passenger airport-pairs were obtained from the International Air Transport Association to understand places susceptible to imported ZIKV cases.ResultsGlobally, the ASR increased by an average of 72.85% (95%CI: 16.47% to 156.53%) per year from 2011 to 2015 and subsequently decreased from 20.25 per 100,000 in 2015 to 3.44 per 100,000 in 2019. Most of ZIKV infections clustered in Latin America. The proportion of episodes in Central and Tropical Latin America decreased in 2019 with sporadic episodes elsewhere. High Socio-Demographic Index (SDI) regions had more episodes in 2019 than in 2015. Additionally, 15–49 years group had the largest proportion of episodes, females had a higher number of episodes, and a higher incidence rate of 70 plus group was observed in males than females. Certain cities in Europe, North America and Latin America/Caribbean had a high population mobility in ZIKV outbreak areas considered a high risk of imported cases.ConclusionsZIKV infection is still a public health threat in Latin America and Caribbean and high SDI regions suffered an increasing trend of ZIKV infection. Interventions such as development of surveillance networks and vector-control should be attached to ZIKV control in these key regions. Reproductive suggestions should be taken to reduce ZIKV-related birth defects for the people of reproductive age who are facing a higher threat of ZIKV infection, especially females. Moreover, surveillance of travellers is needed to reverse the uptrends of travel-related imported ZIKV infection. More studies focusing on ZIKV should be performed to make targeted and effective prevention strategies in the future.

Serological Evidence of Zika Virus Infection in Febrile Patients and Healthy Blood Donors in Sabah, Malaysian Borneo, 2017-2018.

Several Zika virus (ZIKV) seroprevalence studies have been conducted in Africa, Asia, Oceania, the Americas, and the Caribbean. However, studies on ZIKV seroprevalence are limited in Malaysia though several studies have shown that the disease is endemic in the Malaysian state of Sabah. To evaluate the seroprevalence of ZIKV infection, 818 serum samples were collected from febrile patients and healthy blood donors from the Kudat and Kota Kinabalu districts in Sabah from 2017 to 2018. They were screened for ZIKV infection by IgM and IgG ELISA, and positive ZIKV IgM samples were subjected to a 90% neutralization test for confirmation. Twenty-four (6% [95% CI 4 to 8]) confirmed and two (0.5% [95% CI 0.13 to 1.8]) probable ZIKV infections were detected among 400 febrile illness patients. Of 418 healthy blood donor samples, six (1.4% [95% CI 0.65 to 3]) were determined as confirmed ZIKV infections and six (1.4% [95% CI 0.65 to 3]) indicated probable ZIKV infection. This is the first study on the seroprevalence of ZIKV infections among patients and healthy blood donors in Sabah. Compared with previous studies in Malaysia, this study shows that the incidence of ZIKV infection has increased. It also suggests that a sero-surveillance system is essential to determine the circulation of ZIKV in Sabah, Malaysia.

Incidence of Zika Virus Infection from a Dengue Epidemiological Study of Children in Ratchaburi Province, Thailand.

Zika virus (ZIKV) is the mosquito-transmitted virus that the WHO declared a Public Health Emergency of International Concern in 2016 due to the consequence of microcephaly from infected pregnancies. The incidence of Zika infection has been unclear in many countries because most infected people have nonspecific febrile illnesses. This study’s aim is to investigate the incidence of symptomatic Zika virus infections from the archived samples of a dengue cohort study of children in central Thailand from 2006 to 2009. We performed Zika NS1 immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) screening to identify symptomatic Zika infections in paired acute/convalescent serum samples. Symptomatic Zika infections were confirmed by reverse transcription polymerase chain reactions (RT-PCR) of acute serum samples. The comparison of the Zika NS1 IgG ELISA results between acute and convalescent samples showed 290/955 (30.4%) seropositive cases. Zika RT-PCR results were positive in 28 febrile cases (15 females, 13 males). Zika RT-PCR showed that symptomatic Zika infection occurred in children aged 4–11 years in Ratchaburi province, Thailand (2007–2009, first case in April 2007), and the symptomatic Zika:dengue infection ratio was 28 Zika:394 dengue (1:14). Phylogenetic analysis showed that all Zika viruses were of Asian lineage. Zika NS1 IgG ELISA identified Zika-infected patients and showed a low Zika:dengue ratio.

Pregnancy and Zika virus

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the Flaviviridae family. In 1947 and 1948 ZIKV was first isolated from a nonhuman primate as well as from mosquitoes in Africa, respectively. For half a century, ZIKV infections in human were sporadic prior to 2015–2016 pandemic spreading. Transmission of ZIKV from mother to fetus can occur in any trimester of pregnancy, even if mother was an asymptomatic carrier. The clinical signs of ZIKV infection are nonspecific and can be misdiagnosed as some other infectious diseases, especially those caused by arboviruses such as Dengue and Chikungunya. ZIKV infection was solely associated with mild illness prior to the large French Polynesian and Brazil outbreaks, when severe neurological complications, Guillain–Barre syndrome and dramatically increased rate of severe congenital malformations (including microcephaly) were reported. The adaptation of ZIKV to an urban cycle in endemic areas suggests that the incidence of ZIKV infections may be underestimated. The pandemic of novel coronavirus infection (COVID-19) demonstrates that lessons from ZIKV pandemic propagation has not been learned properly.

Zika Virus Infection in Pregnant Women, Yucatan, Mexico.

We report demographic, epidemiologic, and clinical findings for a prospective cohort of pregnant women during the initial phase of Zika virus introduction into Yucatan, Mexico. We monitored 115 pregnant women for signs of active or recent Zika virus infection. The estimated cumulative incidence of Zika virus infection was 0.31 and the ratio of symptomatic to asymptomatic cases was 1.7 (range 1.3-4.0 depending on age group). Exanthema was the most sensitive clinical sign but also the least specific. Conjunctival hyperemia, joint edema, and exanthema were the combination of signs that had the highest specificity but low sensitivity. We did not find evidence of vertical transmission or fetal anomalies, likely because of the low number of pregnant women tested. We also did not find evidence of congenital disease. Our findings emphasize the limited predictive value of clinical features in areas where Zika virus cocirculates with other flaviviruses.

Seroprevalence of Zika and Dengue Virus Antibodies among Migrant Workers, Taiwan, 2017.

A serosurvey of 600 workers newly arrived in Taiwan from 4 Southeast Asia countries showed that 18 (3%) were positive for Zika virus IgM; 6 (1%) fulfilled the World Health Organization criteria for laboratory-confirmed recent Zika virus infection. The incidence of Zika virus infection in Southeast Asia might be underestimated.

Prevalence and Incidence of Zika Virus Infection Among Household Contacts of Patients With Zika Virus Disease, Puerto Rico, 2016–2017

Little is known about the prevalence or incidence of Zika virus (ZIKV) infection in settings affected by the 2015-2016 Zika pandemic and associated risk factors. We assessed these factors among household contacts of patients with ZIKV disease enrolled in a cohort study in Puerto Rico during 2016-2017. Household contacts of index case patients completed a questionnaire and gave specimens for real-time polymerase chain reaction (RT-PCR) and immunoglobulin M enzyme-linked immunosorbent assay testing to detect ZIKV infection. We measured the prevalence of ZIKV infection among contacts and associated individual and household factors, examined sexual transmission using a sexual-networks approach, and assessed incident infection among initially uninfected household contacts 2-4 months later. Of 366 contacts, 34.4% had evidence of ZIKV infection at enrollment, including 11.2% by RT-PCR. Having open doors and windows that were either screened (prevalence ratio [PR], 2.1 [95% confidence interval {CI}, 1.2-3.6]) or unscreened (PR, 2.5 [95% CI, 1.5-4.1]) was associated with increased prevalence. Sexual partners were more likely to both be RT-PCR positive relative to other relationships (odds ratio, 2.2 [95% CI, 1.1-4.5]). At follow-up, 6.1% of contacts had evidence of incident infection. This study identified sexual contact as a risk factor for ZIKV infection. Persons living with ZIKV-infected individuals should be a focus of public health efforts.

Incidence of Zika virus infection in a prospective cohort of Belgian travellers to the Americas in 2016

BackgroundThe incidence rate of Zika virus (ZIKV) infection in travellers from non-endemic areas to the Americas during the ZIKV outbreak in 2016 is unknown. MethodsBelgian adults who planned to travel to South America, Central America, and the Caribbean were recruited prospectively to study the incidence and characteristics of ZIKV. Demographic data and sera were collected at baseline. Participants were trained to collect capillary blood on filter paper (BFP). When ill during travel, the participants completed a questionnaire and they sampled BFP for post-hoc analysis. All symptomatic participants were screened for ZIKV using ZIKV-specific RT-PCR on serum or urine, or BFP, and antibody detection assays (ELISA). Follow-up sera of asymptomatic travellers, obtained at least 20 days post travel, were tested by ZIKV ELISA only. All positive ELISA results were subject to confirmation by virus neutralization testing (VNT). ResultsForty-nine participants completed follow-up: 38 women and 11 men, with a median age of 32 years (range 19–64 years). Travel destinations were countries in South America (n=20), Central America (n=24), and the Caribbean (n=5). The total travel duration was 67.8 person-months. Illness was reported by 24 participants (49.0%). ZIKV infection was confirmed in nine cases, by RT-PCR (n=5) and by VNT (n=4). Only one of nine ZIKV cases (11.1%) was asymptomatic. The ZIKV incidence rate was 17.0% (95% confidence interval 7.8–32.2%) per month of travel. ConclusionsThe ZIKV incidence rate in adult travellers from non-endemic countries to the epidemic territories during the 2016 outbreak was high. Asymptomatic ZIKV infection was rare in this population.

Zika Virus: An Emerging Global Health Threat.

Zika virus (ZIKV) is an emerging healthcare threat. The presence of the mosquito Aedes species across South and Central America in combination with complementary climates have incited an epidemic of locally transmitted cases of ZIKV infection in Brazil. As one of the most significant current public health concerns in the Americas, ZIKV epidemic has been a cause of alarm due to its known and unknown complications. At this point, there has been a clear association between ZIKV infection and severe clinical manifestations in both adults and neonates, including but not limited to neurological deficits such as Guillain-Barré syndrome (GBS) and microcephaly, respectively. The gravity of the fetal anomalies linked to ZIKV vertical transmission from the mother has prompted a discussion on whether to include ZIKV as a formal member of the TORCH [Toxoplasma gondii, other, rubella virus, cytomegalovirus (CMV), and herpes] family of pathogens known to breach placental barriers and cause congenital disease in the fetus. The mechanisms of these complex phenotypes have yet to be fully described. As such, diagnostic tools are limited and no effective modalities are available to treat ZIKV. This article will review the recent advancements in understanding the pathogenesis of ZIKV infection as well as diagnostic tests available to detect the infection. Due to the increase in incidence of ZIKV infections, there is an immediate need to develop new diagnostic tools and novel preventive as well as therapeutic modalities based on understanding the molecular mechanisms underlying the disease.

Transmission of Zika Virus - Haiti, October 12, 2015-September 10, 2016.

Zika virus disease is caused by infection with a flavivirus with broad geographic distribution and is most frequently transmitted by the bite of an infected mosquito. The disease was first identified in the World Health Organization's Region of the Americas in 2015 and was followed by a surge in reported cases of congenital microcephaly in Brazil; Zika virus disease rapidly spread to the rest of the region and the Caribbean (1), including Haiti. Infection with the virus is associated with adverse fetal outcomes (1) and rare neurologic complications in adults. The magnitude of public health issues associated with Zika virus led the World Health Organization to declare the Zika virus outbreak a Public Health Emergency of International Concern on February 1, 2016 (2). Because many persons with mild Zika virus disease are asymptomatic and might not seek care, it is difficult to estimate the actual incidence of Zika virus infection. During October 12, 2015-September 10, 2016, the Haitian Ministry of Public Health and Population (Ministère de la Santé Publique et de la Population [MSPP]) detected 3,036 suspected cases of Zika virus infection in the general population, 22 suspected cases of Zika virus disease among pregnant women, 13 suspected cases of Guillain-Barré syndrome (GBS), and 29 suspected cases of Zika-associated congenital microcephaly. Nineteen (0.6%) patients with suspected Zika virus disease, residing in Ouest (10 patients), Artibonite (six), and Centre (three) administrative departments,* have been confirmed by laboratory testing, including two among pregnant women and 17 in the general population. Ongoing laboratory-enhanced surveillance to monitor Zika virus disease in Haiti is important to understanding the outbreak and ensuring effective response activities.

High incidence of Zika virus infection detected in plasma and cervical cytology specimens from pregnant women in Guayaquil, Ecuador

Zika virus (ZIKV) infection during pregnancy has been linked to severe birth defects, and the epidemiologic situation of the ZIKV epidemic in Ecuador is poorly understood. Guayaquil, Ecuador, has a tropical climate and experiences frequent outbreaks of dengue and chikungunya virus, and in December 2015, ZIKV was identified. Given the well-documented effects of ZIKV in pregnancy, including microcephaly, we tested for the presence of ZIKV in both plasma and cervical cytology of pregnant women. We report the identification of a population of pregnant women with a high incidence of ZIKV infection detected in the plasma and lower reproductive tract. A case-control study was performed to determine the incidence of ZIKV infection among low-income, pregnant women at risk for preterm delivery compared to matched controls. Plasma and cervical cytology specimens were tested for ZIKV by rRT-PCR. Fifty-nine pregnant women were enrolled. The incidence of ZIKV was 54% (32/59) overall: 18/31 (58.1%) in cases and 14/28 (50.0%) in controls. ZIKV detection in plasma and cervical cytology specimens demonstrated good agreement. Overall, outcomes for neonates born to ZIKV-positive and ZIKV-negative mothers were similar. However, two neonates were born with microcephaly to case mothers who were ZIKV positive. We report a high incidence of ZIKV infection (54%) in a distinctive population in Guayaquil, Ecuador. We identify ZIKV in cervical samples that correlates with ZIKV in the plasma. These data raise concerns regarding the breadth of the ZIKV epidemic in Ecuador and demonstrate the utility of cervical cytology specimens for ZIKV testing.

Mapping Zika virus disease incidence in Valle del Cauca.

Geographical information systems (GIS) use for development of epidemiological maps in tropical diseases is increasingly frequently utilized. Here, we apply this technique to map the current Zika virus (ZIKV) outbreak in Colombia. Surveillance cases data of the ongoing epidemic of ZIKV in Valle del Cauca department and its capital, Cali (2015-2016), were used to estimate cumulated incidence rates (cases/100,000 population) to develop the first maps in the department and it municipalities. The GIS software used was Kosmo Desktop 3.0RC1®. Three thematic incidence rate maps were developed. Up to April 2, 2016, 9,825 cases of ZIKV were reported (15.15% of the country cases). The burden of ZIKV infection has been concentrated in the North of the department. Valle del Cauca borders with other departments with incidence of ZIKV infection, such as Quindío (173 cases) and Risaralda (687 cases). Eleven municipalities of Valle del Cauca had cases in the range between 250 and 499 cases/100,000, all in the North and East of the department. Cali, the capital concentrates more than a third of the reported cases of ZIKV in Valle del Cauca. Use of GIS-based epidemiological maps allows to guide decision-making for prevention and control of diseases that constitute significant public health problems in the region and the country, such as exemplified by the emergence of ZIKV infection, particularly in departments such as Valle del Cauca with a high disease incidence.

Times to key events in Zika virus infection and implications for blood donation: a systematic review.

ObjectiveTo estimate the timing of key events in the natural history of Zika virus infection.MethodsIn February 2016, we searched PubMed, Scopus and the Web of Science for publications containing the term Zika. By pooling data, we estimated the incubation period, the time to seroconversion and the duration of viral shedding. We estimated the risk of Zika virus contaminated blood donations.FindingsWe identified 20 articles on 25 patients with Zika virus infection. The median incubation period for the infection was estimated to be 5.9 days (95% credible interval, CrI: 4.4–7.6), with 95% of people who developed symptoms doing so within 11.2 days (95% CrI: 7.6–18.0) after infection. On average, seroconversion occurred 9.1 days (95% CrI: 7.0–11.6) after infection. The virus was detectable in blood for 9.9 days (95% CrI: 6.9–21.4) on average. Without screening, the estimated risk that a blood donation would come from an infected individual increased by approximately 1 in 10 000 for every 1 per 100 000 person–days increase in the incidence of Zika virus infection. Symptom-based screening may reduce this rate by 7% (relative risk, RR: 0.93; 95% CrI: 0.89–0.99) and antibody screening, by 29% (RR: 0.71; 95% CrI: 0.28–0.88).ConclusionNeither symptom- nor antibody-based screening for Zika virus infection substantially reduced the risk that blood donations would be contaminated by the virus. Polymerase chain reaction testing should be considered for identifying blood safe for use in pregnant women in high-incidence areas.