Zika Virus Update

Zika associated with arthrogryposis

A study by The BMJ published 9 August 2016 provides more details of an association between Zika virus infection in the womb and a condition known as arthrogryposis, which causes joint deformities at birth, particularly in the arms and legs.

Microcephaly (a rare birth defect where a baby is born with an abnormally small head) and other severe foetal brain defects are the main features of congenital Zika virus syndrome. However, little is still known about other potential health problems that Zika virus infection during pregnancy may cause.

Until recently there were no reports of an association between congenital viral infection and arthrogryposis. After the outbreak of microcephaly in Brazil associated with Zika virus, two reports suggested an association, but they did not describe the deformities in detail.

So a research team based in Recife, the Brazilian city at the centre of the Zika epidemic, decided to investigate the possible causes of the joint deformities.

They studied detailed brain and joint images of seven children with arthrogryposis and a diagnosis of congenital infection, presumably caused by Zika virus. All children tested negative for the fi ve other main infectious causes of microcephaly – toxoplasmosis, cytomegalovirus, rubella, syphilis, and HIV.

All children showed signs of brain calcifi cation, a condition in which calcium builds up in the brain. The theory is that the Zika virus destroys brain cells, and forms lesions similar to “scars” on which calcium is deposited.

All the children underwent high defi nition scanning of the joints and surrounding tissues, but there was no evidence of joint abnormalities.

This led the researchers to say that the arthrogryposis “did not result from abnormalities of the joints themselves, but was likely to be of neurogenic origin” – a process involving motor neurones (cells that control the contraction or relaxation of muscles) – leading to fi xed postures in the womb and consequently deformities. They point out that further research is needed with a larger number of cases to study the neurological abnormalities behind arthrogryposis, but suggest that children should receive orthopaedic follow-up ... “because they could develop musculoskeletal deformities secondary to neurological impairment”.

Based on these observations, the researchers conclude that “congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis”. Because this is an observational study, no fi rm conclusions can be drawn about the effect of the Zika virus on arthrogryposis. Nevertheless, the authors suggest that this condition might be related to the way motor neurons carry signals to the unborn baby’s muscles, or to problems with arteries and veins (vascular disorders).


Vaccine trial

The US National Institute of Allergy and Infectious Diseases (NIAID) has launched a clinical trial of a vaccine candidate intended to prevent Zika virus infection. The early-stage study will evaluate the experimental vaccine’s safety and ability to generate an immune system response in humans.

The investigational Zika vaccine includes a small, circular piece of DNA – a plasmid – that scientists engineered to contain genes that code for proteins of the Zika virus. When the vaccine is injected into the arm muscle, cells read the genes and make Zika virus proteins, which selfassemble into virus-like particles. The body mounts an immune response to these particles, including neutralizing antibodies and T cells. DNA vaccines do not contain infectious material – so they cannot cause a vaccinated individual to become infected with Zika – and have been shown to be safe in previous clinical trials for other diseases.

The Phase 1 clinical trial, called VRC 319, is led by Julie E. Ledgerwood, D.O., chief of the Vaccine Research Center (VRC) clinical trials program.

Initial safety and immunogenicity data from the VRC 319 trial are expected by the end of 2016. If results show a favourable safety profi le and immune response, NIAID plans to initiate a Phase 2 trial in Zika-endemic countries in early 2017.

NIAID is conducting and supporting research and development of multiple Zika vaccine candidates.

NIAID’s VRC is working with GSK to evaluate a Zika vaccine candidate that uses GSK’s self-amplifying mRNA technology. This research, which will take place at the GSK Vaccine R&D Center in Rockville, Maryland, is still in the pre-clinical stage.

The NIAID Laboratory of Infectious Diseases is developing a live-attenuated investigational Zika vaccine. The vaccine contains a live but weakened virus, so that it cannot cause disease.

NIAID also will be funding Phase 1 trials of a whole-particle inactivated Zika virus vaccine developed by scientists at the Walter Reed Army Institute of Research (WRAIR). WRAIR announced a cooperative research and development agreement with Sanofi Pasteur in June 2016 to advance the vaccine candidate. Two of the Phase 1 trials are set to launch in late 2016 and early 2017.

Date of upload: 15th Sep 2016

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