{"id":250606,"date":"2017-12-19T18:09:28","date_gmt":"2017-12-19T20:09:28","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/?p=250606\/"},"modified":"2017-12-19T18:09:28","modified_gmt":"2017-12-19T20:09:28","slug":"dengue-may-attenuate-zika","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/dengue-may-attenuate-zika\/","title":{"rendered":"Dengue may attenuate Zika"},"content":{"rendered":"
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Photo Montage James Gathany \/ CDC and L\u00e9o Ramos Chaves<\/span><\/a> Aedes aegypti<\/em>, transmitter of the Zika and dengue viruses: different reactions in primates and micePhoto Montage James Gathany \/ CDC and L\u00e9o Ramos Chaves<\/span><\/p><\/div>\n

If you have had dengue and are then infected by the Zika virus (ZIKV), it appears you will not develop a more severe form of the disease than someone who has not had prior contact with dengue\u2014contrary to what was previously thought. Your case of Zika may even be milder and fleeting. The notion that prior dengue infection may have the effect of moderating Zika emerged from two recent studies, one published June 20, 2017, in the journal Clinical Infectious Diseases<\/em> and the other June 23, 2017, in Nature Communications<\/em>.<\/p>\n

Both studies\u2014the former conducted in Brazil on humans and the latter on monkeys in Puerto Rico\u2014present the first evidence that dengue infection followed by Zika triggers an immune response in primates unlike the response observed in experiments with mice or cells cultured in the laboratory. Prior to the studies published in June, experimental models that used cells in vitro <\/em>or mice with weakened immune systems had indicated that after a dengue infection, ZIKV could more easily evade the body\u2019s defenses and proliferate more, resulting in a more severe case of Zika. Some research groups have used this hypothesis in an attempt to explain why so many more cases of microcephaly have been linked to Zika in Brazil, where dengue is endemic, than elsewhere in the world.<\/p>\n

\u201cOur findings indicate that no such exacerbation occurs or, if it does, it\u2019s quite rare and can\u2019t be detected in a study like the one we did,\u201d says virologist Maur\u00edcio Lacerda Nogueira, a professor at the S\u00e3o Jos\u00e9 do Rio Preto School of Medicine (FAMERP). Nogueira led the study published in Clinical Infectious Diseases<\/em>, the first to signal that prior dengue infection in humans does not necessarily lead to a more severe case of Zika. Both viruses are transmitted by the Aedes aegypti<\/em> mosquito.<\/p>\n

Nogueira\u2019s group collected blood from 65 residents of S\u00e3o Jos\u00e9 do Rio Preto who sought medical treatment between January and July 2016\u2014the height of the Zika epidemic\u2014and who presented symptoms resembling those of dengue or Zika, that is, fever, muscle pain, headache, and body rash. Located in northern S\u00e3o Paulo State, 450 kilometers from the capital, S\u00e3o Jos\u00e9 do Rio Preto lies in a region of endemic dengue that was swept by Zika in 2016.<\/p>\n

Analyses of participants\u2019 blood showed that 45 of them had ZIKV infection at the time, while 20 had dengue. Tests also revealed that 78% of those with Zika (35 individuals) and 70% of those with dengue (14) had been previously infected by the dengue virus.<\/p>\n

\"\"<\/a>Similar severity <\/strong>
\nIn this study, conducted in partnership with researchers from two U.S. institutions and three institutions in S\u00e3o Paulo\u2014the University of S\u00e3o Paulo (USP), S\u00e3o Paulo State University (Unesp), and the Butantan Institute\u2014Nogueira and his team also examined the number of copies of ZIKV in the blood of individuals previously infected with dengue and compared the figure with the quantity found in the blood of those never exposed to the virus. If prior dengue infection facilitated replication of ZIKV, the quantity of the latter should be much higher in the first group of patients. That is not what researchers observed. Instead, the viral load was similar in both cases.<\/p>\n

\u201cOur study was powerful enough statistically to detect a very small difference\u2014of only 10 times\u2014in the concentration of the virus,\u201d says Nogueira, who is a member of the FAPESP-funded Zika Virus Research Network in S\u00e3o Paulo (Rede Zika). It would be expected to find tens of thousands more copies of ZIKV in the blood of someone with prior exposure to dengue if the phenomenon observed in mice and cells in vitro <\/em>also occurred in humans.<\/p>\n

Shortly after Zika began spreading through Brazil\u2014the Ministry of Health recorded nearly 310,000 cases in 2015 and 2016, according to a study published in June 2017 in the journal The <\/em>Lancet<\/em>\u2014the suspicion grew that prior dengue infection could produce more severe cases of Zika, much as what happens with dengue hemorrhagic fever (DHF). Characterized by bleeding and, in more severe cases, by a sharp drop in blood pressure, DHF usually strikes people who have already had the disease and are then infected by a different virus subtype, four of which exist in Brazil. The problem is that the antibodies produced by the immune system to fight one infection do not always efficiently neutralize the other, resulting in partial immunity.<\/p>\n

According to the antibody-dependent enhancement (ADE) hypothesis, incomplete immunity may facilitate the virus\u2019s entry into cells of the defense system where it manages to reproduce, increasing the number of its copies in the body and also the severity of the infection. Since the dengue and Zika viruses are quite similar evolutionally\u2014both belong to the flavivirus family\u2014it was previously thought that partial immunity, which enhances dengue disease, might also result in more severe Zika disease.<\/p>\n

This suspicion gained strength in mid-2016 when the first research came out showing that the antibodies that protect against dengue also act against ZIKV, but do not neutralize it completely. In March 2017, researchers in the United States found that this partial immunity enhanced replication of ZIKV in mice with weakened immune systems. The findings recently presented in Clinical Infectious Diseases<\/em> indicate that what happens with cells in vitro<\/em> and with mice does not necessarily happen with humans.<\/p>\n

\u201cThese findings do not completely exclude the possibility that ADE occurs, but they are an important indication that first having dengue doesn\u2019t lead to more severe Zika infection,\u201d says immunologist Jorge Kalil, USP professor and co-author of the study. \u201cIn fact, there are unpublished reports that people who already had dengue presented a milder form of infection when they contracted Zika.\u201d<\/p>\n

The hypothesis that prior dengue infection can result in a milder form of Zika recently received a significant boost. In the article published in Nature Communications<\/em> on June 23, 2017, the group led by virologist Carlos Sariol of the University of Puerto Rico presented indications that developing immunity to the dengue virus might moderate ZIKV infection in monkeys, an animal whose defense system is more similar to that of the human\u2019s. Researchers at the Caribbean Primate Research Center infected eight rhesus monkeys with Zika and then followed their immune response for 60 days. Half of the monkeys had been infected with dengue about three years earlier, while the other half had never had contact with the virus.<\/p>\n

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L\u00e9o Ramos Chaves<\/span><\/a> Computer screen shows detection of Zika virus (ascending curve<\/em>), using the polymerase chain reaction (PCR) techniqueL\u00e9o Ramos Chaves<\/span><\/p><\/div>\n

Milder infection<\/strong>
\nIn tests of animal blood in vitro<\/em>, dengue antibodies had provided only partial immunity against ZIKV, facilitating replication and corroborating the findings of research with mice. But it was different with the monkeys. Instead of worsening the cases, the dengue antibodies helped reduce the concentration of ZIKV in the blood faster, shortening the infection. \u201cWe urge caution in using immune deficient mouse models to understand the pathogenesis of ZIKV in people,\u201d the researchers wrote in the article in Nature Communications<\/em>.<\/p>\n

Based on these findings, the group led by Sariol raised the hypothesis that pregnant women previously exposed to ZIKV might display a lower probability of transmitting the virus to their fetus, reducing the risk of central nervous system damage in the child. Transmission of ZIKV from mother-to-be to baby seems to require a longer-lasting infection and the presence of greater quantities of the virus.<\/p>\n

\u201cIf enhancement caused by dengue antibodies led to microcephaly, we should have identified hundreds of cases in Rio Preto and Ribeir\u00e3o Preto,\u201d Nogueira explains. \u201cWe didn\u2019t find any.\u201d The virologist\u2019s team also followed 55 women in Rio Preto who had Zika during pregnancy. All of them gave birth to children with no microcephaly. While some of the children did suffer neurological damage, it was much milder than what has been reported in the Northeast.<\/p>\n

\u201cMost certainly, this article [in Clinical Infectious Diseases<\/em>] has broad implications, both epidemiologically and in terms of vaccine development,\u201d says researcher and study co-author Nikos Vasilakis, of the University of Texas. \u201cThese data suggest that other factors may be responsible for Zika congenital syndrome.\u201d<\/p>\n

The evidence that dengue infection might lead to more severe Zika disease has raised concerns regarding vaccine development, especially the dengue vaccine, now being tested in Brazil. \u201cThere was a fear that vaccinating the population against dengue might lead to more severe cases of Zika,\u201d says Kalil. \u201cThese findings indicate that this shouldn\u2019t be a problem.\u201d<\/p>\n

Project<\/strong>
\nEpidemiological study of dengue (serotypes 1-4) in a cohort of S\u00e3o Jos\u00e9 do Rio Preto, S\u00e3o Paulo, Brazil, during 2014-2018 (No. 13\/21719-3<\/a>);\u00a0Grant Mechanism\u00a0<\/strong>Thematic project; Principal Investigator\u00a0<\/strong>Maur\u00edcio Lacerda Nogueira (FAMERP); Investment\u00a0<\/strong>R$2,306,387.68<\/p>\n

Scientific articles<\/em>
\nTERZIAN, A. C. B. et al.<\/em> Viral load and cytokine response profile does not support antibody-dependent enhancement in dengue-primed Zika-infected patients<\/a>. Clinical Infectious Diseases<\/strong>. June 20, 2017.
\nPANTOJA, P. et al.<\/em> Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus<\/a>. Nature Communications<\/strong>. June 23, 2017.<\/p>\n","protected":false},"excerpt":{"rendered":"Dengue infection may moderate cases of Zika","protected":false},"author":16,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[159],"tags":[229,242,260],"coauthors":[105],"class_list":["post-250606","post","type-post","status-publish","format-standard","hentry","category-science","tag-epidemiology","tag-immunology","tag-public-health"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/250606","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/16"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=250606"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/250606\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=250606"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=250606"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=250606"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=250606"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}