H5N1

Cross-protection of dengue virus infection against congenital Zika syndrome, northeastern Brazil

Via Emerging Infectious Diseases: Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil. The abstract:

The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)–mediated immune enhancement may promote CZS development. 

In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case–control framework in northeastern Brazil among 29 Zika virus–seropositive mothers of neonates with CZS and 108 Zika virus–seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. 

Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.

Preparing for emerging infections means expecting new syndemics

A letter in The Lancet: Preparing for emerging infections means expecting new syndemics.

When several sources of morbidity come together to produce interlinked and worse health outcomes, they are sometimes called a syndemic. Research on syndemics explores how two or more diseases cluster together; how social, political, economic, and ecological factors drive those clusters; and how clustered conditions interact via biological, psychological, or social pathways. Syndemic interventions target underlying patterns of multidirectional causality to achieve better overall health in susceptible and often dispossessed populations. 

So far, syndemic theory has found limited traction in fields such as ecoepidemiology that dominate emerging infectious disease research, despite a natural fit for three major challenges: proliferation of closely-related emerging viruses; co-occurence with endemic infections; and broader interactions with other aspects of health, including non-communicable diseases, mental health, and stigma. We show the relevance of syndemics for ecoepidemiology by showing how each of these complicates our understanding of the Zika virus epidemic in Latin America and the Caribbean. 

First, the idea of a syndemic formalises existing knowledge about co-occurrence of Aedes mosquito-borne viruses. Dengue and chikungunya viruses have had substantial comorbidity and co-infection with the Zika virus, including at least one case of triple coinfection. Many studies implicitly examine the three viruses as syndemic but do not refer to this linkage using the term. All three viruses are linked through Aedes mosquitoes to urbanisation, driving a broad spatial correlation between poverty, chikungunya, and Zika congenital syndrome (ZCS) in Brazil. Thinking syndemically could lead to mosquito control and public health education that targets several Aedes-borne viruses at once. 

Second, syndemic thinking has the potential to broaden conversations about co-occurring morbidities without adding confusion about causality. After scientific consensus resolved that ZCS was responsible for Brazil's microcephaly epidemic, conversations about other possible drivers were mostly sidelined. However, Brazil is a global hotspot of congenital toxoplasmosis, and microcephaly cases attributable to toxoplasmosis were observed during the Zika virus outbreak. 

Zika, toxoplasmosis, and microcephaly could create a syndemic, even without links between toxoplasmosis and the 2015–16 ZCS epidemic; poverty and environmental degradation connect them, as could fear and stigma. Syndromic surveillance for emerging pathogens like Zika the virus might be weakened by syndemic clustering between endemic and emerging infections of similar pathology or etiology, especially in poor and undersurveilled populations. 

Third, sexual transmission of the virus and fetal effects of ZCS introduced two new topics—safe sex and abortion access—that had never before been extensively discussed in an arboviral outbreak. Already, work focused on the syndemic of Zika virus, HIV, and unintended pregnancy, has identified marital and cultural risk factors that can help target interventions such as condom use and social policy, emphasising the promise of syndemic thinking, and the need for social scientists' involvement in outbreak prevention and management. 

The long-term effects of Zika virus might also be syndemic, as surviving babies become adults with a range of disabilities and sequelae. Although virologists work tirelessly to understand ZCS, this basic medical research remains disconnected from broader anthropological inquiries about the ongoing social effects of Zika. Bridging this gap is imperative to understand and improve quality of life in affected communities. 

The Zika virus outbreak in Latin America and the Caribbean will not be the last major outbreak; several new outbreaks have been reported across India. Other diseases will also raise complicated issues regarding safe sex or access to safe and legal abortions, and virologists have begun to anticipate sexual transmission and teratogenic effects of other emerging viruses. Increased knowledge of these select pathogens can help emerging disease researchers plan for syndemics of the future.

The next Zika virus outbreak will affect young women of reproductive age disproportionately

Via bioRxiv: The next Zika virus outbreak will affect young women of reproductive age disproportionately: mathematical modeling study.

Zika virus (ZIKV) is a mosquito-borne flavivirus. In 2016, Managua, the capital city of Nicaragua experienced a Zika virus outbreak. Amongst confirmed cases, seropositivity increased with age and >50% of the adult population had ZIKV antibodies. 

The duration of immunity to ZIKV remains unclear. We used an agent-based model in a Bayesian framework to describe the dynamics of immunity to ZIKV, and predict the future age-specific risk of ZIKV infection in the population of Managua. We also investigated the potential impact of a ZIKV vaccine under different assumptions about the persistence of immunity. 

Assuming lifelong immunity, the risk of a ZIKV outbreak will remain low until 2035 and rise above 50% in 2047. Young women of reproductive age will be at highest risk of infection during the next ZIKV outbreak. 

ZIKV vaccine development and licensure are urgent, to attain the maximum benefit in reducing the population-level risk of infection and the risk of adverse congenital outcomes.

Emergence of the Zika virus Asian lineage in Angola

Via bioRxiv: Emergence of the Zika virus Asian lineage in Angola. The abstract:

Background: 

Zika virus (ZIKV) infections and suspected microcephaly cases have been recently reported in Angola, but no data are available on the origins, epidemiology, and diversity of the virus. 

Methods: 

Serum samples from 54 suspected ZIKV cases, 76 suspected microcephaly cases, and 24 mothers of infants with suspected microcephaly were received by the Angolan Ministry of Health. Computed tomographic brain imaging and serological assays (PRNT) were conducted on one microcephalic infant. All sera were tested for ZIKV by RT-qPCR. 349 samples from HIV+ patients and 336 samples from patients suspected of chikungunya virus or dengue virus infection were also tested. Portable sequencing was used to generate Angolan ZIKV genome sequences, including from a ZIKV+ neonate with microcephaly born in Portugal to an Angolan resident. Genetic and mobility data were analysed to investigate the date of introduction and geographic origin of ZIKV in Angola. 

Findings: 

Four autochthonous cases were ZIKV positive via RT-qPCR, with all positive samples collected between December 2016 and June 2017. Viral genomes were generated for two of these cases, and from the neonate with microcephaly identified in Portugal. Genetic analyses and other data indicate that ZIKV was introduced to Angola from Brazil between July 2015 and June 2016. This introduction likely initiated local ZIKV circulation in Angola that continued until June 2017. The scanned microcephaly case showed brain abnormalities consistent with congenital Zika syndrome and serological evidence for maternal ZIKV infection. 

Interpretation: 

Our analyses confirm the autochthonous transmission of the ZIKV Asian lineage in continental Africa. Conducting ZIKV surveillance throughout Africa is critical in the light of presented evidence for autochthonous ZIKV transmission in Angola, and associated microcephaly cases.

Congenital brain abnormalities during a Zika virus epidemic in Salvador, Brazil, April 2015 to July 2016

Via Eurosurveillance: Congenital brain abnormalities during a Zika virus epidemic in Salvador, Brazil, April 2015 to July 2016. Excerpt from the discussion section, with my bolding:

In this study, we described a high prevalence of confirmed CBAs in Salvador, as high as 2.2% of the live births in December 2015. The prevalence of image-confirmed CBA estimated for the study period adjusted for one year was 52 times higher than the estimated baseline prevalence of microcephaly in the north-east region (average of 5 cases per 100,000 live births per year, between 2000 and 2014). Unfortunately, we did not have information on serological or virological ZIKV testing, which would allow ascertaining the aetiology of such an outbreak. 

However, the peak of births of babies with microcephaly occurred 30–33 weeks after the peak of ZIKV epidemic in Salvador, and this is consistent with the growing body of evidence suggesting that the first trimester of pregnancy is the period when ZIKV infections pose the highest risk of adverse fetal outcome. Taken together, it is reasonable to assume that most of the imaging-confirmed cases in this study were due to congenital ZIKV infection. 

As we only considered cases with specific neuroimaging findings as confirmed cases, we certainly underestimated cases of congenital ZIKV infection. Several suspected cases had not been investigated by the time we analysed the data and the imaging modality most commonly used was prenatal or postnatal intracranial ultrasound, which is not an optimal modality to detect abnormalities of the corpus callosum and cerebral cortex. 

In addition, suspected microcephaly cases were reported based on birth head circumference, which could be well within normal limits in some cases of congenital ZIKV infection. Although reporting of spontaneous abortions, stillbirths and fetuses presenting alterations in the central nervous system was also encouraged, allowing us to confirm a few cases with normal or large head circumference at birth, we could not evaluate whether there was an increase in abortions and stillbirths in Salvador during the study period. 

On the other hand, some cases counted as confirmed could be due to other causes such as congenital cytomegalovirus infection or genetic disorders, but the number of these cases is expected to be small, considering the baseline rate of microcephaly before the epidemic. In addition, in north-east Brazil (a region in which Salvador was one of the epicenters for the ZIKV outbreak), only 1.3% of confirmed cases of infection-related microcephaly during the 2015–16 period had laboratory evidence of syphilis, toxoplasmosis, cytomegalovirus, or herpes simplex.  

A similar increase in microcephaly cases was reported in other locations where ZIKV epidemics have occurred, such as Colombia, where the prevalence of microcephaly also increased around 6 months after the peak of ZIKV transmission in July 2016. However, the microcephaly prevalence reported in Colombia peaked at 17.7 cases per 10,000 live births, much lower than observed in Salvador. Potential reasons for this difference may include, variable intensity levels of ZIKV transmission, differences in circulating ZIKV strains and different case definitions and surveillance criteria. Further, co-circulation of other arboviruses (dengue and chikungunya, for example), differences in mosquito control measures, and prior exposure to yellow fever vaccination could be contributing factors. 

Additionally, Brazil was the first country in the Americas to experience a large outbreak of ZIKV and to detect an increase in microcephaly cases, and this allowed other countries as Colombia to issue recommendations for delaying pregnancies, which might have resulted in decreased risk of congenital abnormalities associated with ZIKV infection during pregnancy.

Epilepsy profile in infants with congenital Zika virus infection

Via NEJM: Epilepsy Profile in Infants with Congenital Zika Virus Infection. Excerpt:

Congenital Zika virus (ZIKV) infection may have severe clinical consequences, including dysmorphic features, orthopedic abnormalities, ophthalmologic and auditory lesions, microcephaly, and hydrocephalus. When ZIKV infection is acquired in utero, it may be associated with epilepsy, and we characterized aspects of this complication in a study performed at our referral center. 

Patients who were referred to our center had congenital or acquired microcephaly, were asymptomatic or symptomatic newborns who were born to mothers who had confirmed or suspected ZIKV infection during pregnancy, had calcifications (not related to other in utero infections) that were detected by means of neuroimaging studies, or had an unexplained developmental delay and lived in geographic regions where ZIKV infection was epidemic (see Table S2 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). 

Our study included 141 infants, 54.6% of whom were girls, who had congenital ZIKV infection that was confirmed by laboratory analysis. The mean age of the patients was 9 months (range, 1 to 14). Serum samples obtained from the infants and their mothers and samples of cerebrospinal fluid obtained from the infants were tested by means of quantitative reverse-transcriptase–polymerase-chain-reaction assay for the detection of the ZIKV genome and by an IgM antibody capture determined by enzyme-linked immunosorbent assay. In all the infants, structural brain abnormalities were detected by means of neuroimaging studies. The study was approved by the institutional review board of our referral center, and written informed consent was obtained from the parents of the infants.  

The study protocol included a clinical evaluation every other month and immediate assessment in case of the development of unexpected clinical complications. The parents were interviewed with the use of a questionnaire that addressed clinical variables associated with epilepsy. Medical records, electroencephalography (EEG), video EEG, and videos from the families of the patients that documented seizures corroborated this information. Seizures were classified according to the guidelines of the International League against Epilepsy. 

The prevalence of epilepsy in this cohort was 67%, and the mean age of the infants at the onset of epilepsy was 4.9 months. Data from the parents of the infants indicated that the seizures occurred during the first 6 months of life in 74% of the infants. At the onset of epilepsy and during follow-up, the main seizure types were epileptic spasms (in 72% of the infants), focal motor seizures (in 21%), and tonic seizures (in 4%) (Table 1). A single seizure type was documented in 77% of the infants.

First case of confirmed congenital Zika syndrome in continental Africa

Thanks to Gert van der Hoek at FluTrackers for posting this report from the Transactions of the Royal Society for Tropical Medicine: First case of confirmed congenital Zika syndrome in continental Africa. The abstract:

BACKGROUND: Zika virus has been responsible for recent outbreaks in the western hemisphere with known neurological complications such as microcephaly. This complication has not been previously documented in continental Africa.  

METHODS: Neurological evaluation of the newborn was performed after birth, at one and two months of age. The mother and the newborn sera samples were tested by immunofluorescent assay (IFA; immunoglobulin G [IgG] and IgM) for Zika virus and the presence of Zika virus ribonucleic acid (RNA) was checked by qualitative real-time reverse transcription polymerase chain reaction (RT-PCR) in placenta, blood and urine samples. 

RESULTS: We report on a newborn, born in Portugal, with microcephaly with confirmed congenital Zika virus infection (Asian lineage) imported from Angola with typical clinical and imaging findings. 

CONCLUSIONS: To our knowledge this is the first report that shows the circulation of the Asian lineage in Angola and the first report of a congenital Zika syndrome in continental Africa.

Zika virus in French Polynesia 2013–14: Anatomy of a completed outbreak

Via The Lancet Infectious Diseases: Zika virus in French Polynesia 2013–14: anatomy of a completed outbreak. The summary:

The Zika virus crisis exemplified the risk associated with emerging pathogens and was a reminder that preparedness for the worst-case scenario, although challenging, is needed. 

Herein, we review all data reported during the unexpected emergence of Zika virus in French Polynesia in late 2013. We focus on the new findings reported during this outbreak, especially the first description of severe neurological complications in adults and the retrospective description of CNS malformations in neonates, the isolation of Zika virus in semen, the potential for blood-transfusion transmission, mother-to-child transmission, and the development of new diagnostic assays. 

We describe the effect of this outbreak on health systems, the implementation of vector-borne control strategies, and the line of communication used to alert the international community of the new risk associated with Zika virus. 

This outbreak highlighted the need for careful monitoring of all unexpected events that occur during an emergence, to implement surveillance and research programmes in parallel to management of cases, and to be prepared to the worst-case scenario.

Two infants with presumed congenital Zika syndrome, Brownsville, Texas, USA, 2016–2017

Via EID: Ahead of Print -Two Infants with Presumed Congenital Zika Syndrome, Brownsville, Texas, USA, 2016–2017. The abstract:

Since 2007, Zika virus has spread through the Pacific Islands and the Americas. Beginning in 2016, women in Brownsville, Texas, USA, were identified as possibly being exposed to Zika virus during pregnancy. 

We identified 18 pregnant women during 2016–2017 who had supportive serologic or molecular test results indicating Zika virus or flavivirus infection. Two infants were evaluated for congenital Zika syndrome after identification of prenatal microcephaly. Despite standard of care testing of mothers and neonates, comparative results were unreliable for mothers and infants, which highlights need for clinical and epidemiologic evidence for an accurate diagnosis. 

A high index of suspicion for congenital Zika syndrome for at-risk populations is useful because of current limitations of testing.

Zika virus testing and outcomes during pregnancy, Florida, USA, 2016

Via Emerging Infectious Diseases: Zika Virus Testing and Outcomes during Pregnancy, Florida, USA, 2016. The abstract:

Zika virus infection during pregnancy can lead to congenital Zika syndrome. Implementation of screening programs and interpretation of test results can be particularly challenging during ongoing local mosquitoborne transmission. 

We conducted a retrospective chart review of 2,327 pregnant women screened for Zika virus in Miami–Dade County, Florida, USA, during 2016. Of these, 86 had laboratory evidence of Zika virus infection; we describe 2 infants with probable congenital Zika syndrome. Delays in receipt of laboratory test results (median 42 days) occurred during the first month of local transmission. Odds of screening positive for Zika virus were higher for women without health insurance or who did not speak English. 

Our findings indicate the increase in screening for Zika virus can overwhelm hospital and public health systems, resulting in delayed receipt of results of screening and confirmatory tests and the potential to miss cases or delay diagnoses.