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15/08/2018

Rare case of zika is associated with Guillain-Barré and abortion


Lucas Rocha (IOC/Fiocruz)

Since the health emergency related to zika virus in Latin America between 2015 and 2016, scientists investigate possible correlations between virus infection and the development of neurological manifestations such as Guillain-Barré syndrome and congenital zika syndrome, which includes various disorders such as microcephaly.

Researchers from the Oswaldo Cruz Institute (IOC/Fiocruz), Rio de Janeiro State University (Uerj) and from the Reference Center for Immune Infectious Disease in Campos de Goytacazes investigated a rare case of zika simultaneously associated with Guillain-Barré syndrome and the occurrence of abortion. The study published in the scientific journal Frontiers in Microbiology contributes to the understanding of pathological processes and immunity related to the virus.

The researchers investigated the impacts of zika virus infection on a 28-year-old pregnant woman in the state of Rio de Janeiro. During the gestation period, the patient began to experience weakness of the legs and persistent inability to walk - characteristic symptoms of Guillain-Barré syndrome. The clinical manifestation also included skin eruptions, itching and vomiting. After obstetric examination, the death of the fetus with about 15 weeks of gestation was verified. 

At first, samples of the patient's blood and brain-spinal fluid were subjected to serological tests to identify antibodies. The results were negative for zika, dengue, chikungunya, Epstein Barr and cytomegalovirus - microorganisms already identified as possible causes of Guillain-Barré signs and symptoms. Therefore, complementary analyses were necessary.

Using the technique of immunohistochemistry, which allows the detection of viral antigen in cells of these tissues, the researchers were able to identify the presence of zika virus in the placenta and in different fetal organs, including brain, lungs, kidneys, skin and liver. Analysis of placental tissue indicated severe infections and inflammations, with signs of hemorrhage, swelling and necrosis due to viral action. 

Zika versus maternal immunity

One of the authors of the study, researcher Marciano Viana Paes, from IOC Interdisciplinary Laboratory for Medical Research, explains that placental dysfunction is related to the failure of activation of maternal immune response to infection. According to him, the virus was able to affect cells that make up the immune system of the placenta, known as 'Hofbauer cells'. " Infection of the maternal-fetal organ by zika was evidenced by the exacerbated production of cytokines and mediators related to the alteration in vascular permeability such as VEGFR2 and RANTES, and lymphocyte response such as TCD8+ lymphocytes, which although important for the fight against infection, contributed to exacerbate inflammation," Paes explains. Although it is an important immune response of the organism to the invasion by the most varied microorganisms, when exacerbated the inflammatory reaction can have harmful effects as those pointed out in the study. 

The results further added another piece to the evidence described in other studies: the existence of a mechanism, still unknown, that provides zika virus with a unique ability to bypass maternal immune activation (MIA). When it invaded the placenta, the virus caused several changes in the development of the fetus that led to abortion. The analyses revealed damage to brain tissue structures, including diffuse areas of edema, disorganization in cerebral cortex, and degeneration of nerve fibers. Cell degeneration has had an impact on other organs in formation such as the liver, lungs and kidneys. 

The study suggests that the multiple effects were a result of the persistence of high viremia, that is, a large amount of virus in the patient's blood, and a viral response exacerbated by neurological manifestations resulting from Guillain-Barré syndrome. "Guillain-Barré syndrome potentiated the infection by zika. The involvement of the placenta associated with the damage suffered by the fetus underscores the importance of deepening the investigation on the influence of maternal immunity against an infection by zika in relation to the development of the fetus," Paes pointed out. 

Clinical follow-up showed that a little more than one month after discharge, the patient still needed walking aid and had pain in the lower limbs. After five months, there were still residual sequelae and difficulty locomotion. A little more than a year later, the patient returned to her daily activities.

The study, which is part of a research project of Network 4 - Dengue, Zika and Chikungunya, funded by Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (Faperj), also had the collaboration of experts Luiz José de Souza from the  Reference Center for Immunological Infectious Diseases in Campos dos Goytacazes, Fernando Rosman from Jesus Municipal Hospital and Federal University of Rio de Janeiro (UFRJ), and Carlos Basílio-de-Oliveira and Rodrigo Basílio-de-Oliveira from the Federal University of the State of Rio de Janeiro (Unirio).

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