October 3rd 2016; updated on January 9th 2017
Early September, Minister of Health in Colombia declared end of Zika outbreak. With 78.000 suspected /7166 confirmed cases ; 21 microcephalies and 398 Guillain Barré Syndrome (GBS). It means prevalence for microcephaly estimated in a range of 2.7/10.000 to 29/10.000 at the time being. As of today we have 42 microcephalies recorded leading from 2.7/10.000 to 5.9/10.000 for the confirmed cases.
According to data, 7.9% microcephaly cases are linked/caused by Zika virus so far.
According to evidence based medecine, taking into account tested ZIKV + microcephaly cases, we get 17% of the entire microcephaly tested for ZIKV.
Question: if we all agree to say that Zika virus is involved in the immunological process leading to neural defect and microcephaly, we have to cope with other causes (83%) responsible for microcephalies. On a Global Health issue, it appears more and more obvious that studies are required to build a full picture of the root causes tree regarding microcephaly outbreak in South Americas. By comparing Brazil with Colombia, we might discover different paths to follow, especially by studying what happened in NE Brazil.
Colombia recorded a lot of GBS (>398) compared with microcephaly (>21). A interesting paper is just released in J.Autoimmun 2017 by Colombian researchers pointing out the role of Dengue antibodies. Socio-economics factors are also interfering in the process leading to neurological defects.
“All GBS patients were positive for IgG antibodies against both ZIKV and Dengue virus, and 69% were positive for Chikungunya virus.”
Some time ago, CDC and WHO have posted a statement on microcephaly caused by Zika virus. May be they jump the gun?
May 17th 2016
We were speculating on Colombia as a control group for microcephaly caused by Zika virus. 7 months later, we do not observe the same occurrence/prevalence for microcephaly than declared (without evidence) in NE Brazil. As of today less than 10 microcephalies has been recorded in Colombia. How explaining such a huge discrepancy between Brazil and Colombia?
- Lack of accurate reporting in Brazil leading to overestimation
- Possible non identified co-factors:
- Poverty, poor hygiene, Vitamin deficit/malnutrition
- Timeline of outbreaks: Dengue,Zika
During Zika summit hold in Paris, Institut Pasteur, there were some debate on the role and responsibility of immune system and microcephaly or Guillain-Barré Syndrome (GBS); We see emerging evidence for an autoimmune process as the main cause of central nervous system defects observed during Zika.
Brazil and Colombia have both naive population with regards immunization for Zika. It looks as if Dengue antibodies might react with Zika virus as an enhancement of the immune response on the CNS of fetus during the first quarter of pregnancy, affecting neural cells.
The immune response to the previous infection of dengue is potentially one of the mechanisms that can make you more susceptible to Zika. It’s definitely not been 100% proven yet, but there’s a lot of work going on to investigate it.
Dr Abigail Culsh, Research Associate at Imperial College London
Recently, studies in mice are demonstrating that Zika virus is able to cross placenta barrier and to replicate, damaging the placenta by the way; same for the brain barrier.
These three reports provide conclusive evidence that Zika virus can cross the placenta and cause fetal defects in mice, and provide models to understand the biology and pathogenesis of infection.
But also more and more evidence to support the key role of immunity interacting with Zika virus like Dengue antibodies, leading to neural damages and explaining microcephaly acquired during Q1 of pregnancy.
Better knowledge of Zika virus and its interactions with other substances, antibodies or environments are key elements helping to understand the gaps between Colombia and Brazil. As said before, not sure Brazil will get the capability and willingness to review and validate the entire non tested cases recorded as Zika causing microcephalies. Home State Politics and Olympics Games will now take the lead…
Lucky attendee of the zika summmit in Paris hosted by Institut Pasteur, fully committed in Zika study and on the way for producing a new vaccine; but first starting by discovering Zika virus, its environment, its vector and its morbidity. Nice opening then scientific Lectures followed by some good news by presenting previews of scientific works and studies. At the end of the first day on Public Health and epidemiology of Zika, no speaker declared Zika as causative microcephaly but Zika as involved in the process of microcephaly; that makes a huge difference…
Historical then clinical review of Zika virus discovered in 1947 in Uganda then traveling worldwide, first west then moving back to east before reaching South America in 2015. A timeline of Zika in Americas compared with other outbreaks occurring at the same time or/and at the same location, like Dengue, Chikungunya.
A good reminder on the neurological damages due to CMV and feedbacks.
What are the lessons learned (from French Polynesia) and new trends about Zika virus and microcephaly or Guillain-Barré Syndrome (GBS)?
- Ecosystem:Possible several Vectors for Zika virus
- Zika virus among Flavivirus family including Dengue
- Role and responsibility of immunity:
- Ab, IgM, IgG and autoimmune system
- enhancement of Zika virus by acquired immunity
- Co-infection with Dengue or Chikungunya
- Specs and conditions related to Zika in Americas:
- naive population
- several waves of outbreaks:
- to be at the wrong place at the wrong time
- Neurotropism of Zika
- Co-factors, aggravating factors suspected
- Timeline for pregnancy impacting fetus
- Zika virus crossing placental and blood brain barriers
No more but no less to be happy by attending this meeting entirely dedicated to Zika by gathering scientists working in both Research Lab or Public Health departments, what is called now Global Health and by sharing in real time critical previews of new studies and preliminary results.
No doubt, PHEIC was declared by WHO on February 1st 2016 in order to cope with microcephaly, not Zika virus, as the emergence of an unexplained neurological complications related to a Neglected Tropical Disease (NTD) like Zika. Knowing that almost 80% of Zika cases are unknown due to lack of clinical symptoms, it is a great importance for improving knowledge of pathogenicity and physiopathology. How immune system, autoimmune reaction are connected and if there are cause related to co-infection.
Far from the “politically correct” speaking but always based on evidence, the panel of speakers gave us an optimistic orientated overview with new vision and perspectives for the on coming future. Instead of focusing on what we know, it was effectively more interesting to address the questions about what we don’t know about Zika and microcephaly + GBS. If you see what I mean…
On Feb.1st 2016, WHO declared PHEIC with regards Zika virus threats and its potential health impacts worldwide; since, we are observing a surprising crisis management of Zika disease overwhelmed by an international political crisis.
- Starting with WHO and the funds raising in order to sponsoring both studies on Zika virus in Vitro and epidemiology surveys in Vivo. More questions raised than answered so far since the arrival of the virus in South America, mid April 2015. The emergence of new neurological diseases in link with the virus like GBS, Myelitis or microcephaly which seem to be related to an autoimmune disease are responsible for fears leading to threats for Public Health/Global Health. Pictures of microcephaly posted in Newspapers and social medias are indecent but attracting to People. “Unfortunately”, Zika is responsible for less fatalities than Ebola and is less bankable, despite a urge need to fight the disease.
- Looking at Brazil, we are focusing on the huge amount of microcephaly cases occurring since April 2015 when the Zika virus arrived for the first time in South America. In a way, Zika is a “good opportunity” to hide some of critical points with regards Politics in Brazil including but not limited to corruption scandal with Petrobras, Impeachment procedure of Mrs President. But here are other corps in the cupboard, I mean socio-economics or environmental issues: lack of potable/drinkable water pipe system, sanitation, waste management, vector control by using toxic pesticide/larvicide, poverty leading to malnutrition. It is surprising noticing that the country where started in 1992 in Rio, The precautionary principle applied to Sustainable Development, poor Public Health policy is implemented in some areas like in NE Brazil for testing and monitoring whenever an infectious disease outbreak is emerging. No doubt that budgets have been absorbed by the Olympics Games this summer.
- What is going on in US Capitol and White House? Congress is rejecting to vote funds for fighting mosquitoes and preventing vector borne diseases including Zika, Dengue and Chikungunya. President Obama has decided to move Funds allocated for Ebola to Zika (600 M$). May be a political way to push Congress to feel more responsible and liable just in case of an outbreak of Zika or an increase of microcephaly and especially at the time where Republicans and its representative Donald Trump, are not in the best shape. How avoiding to think about the TV fiction House of Cards and how politicians manipulate each others to achieve their goals. But today is no longer a fiction but true real life.
We are far from Public/Global Health issues and PHEIC despite the need for sponsoring in Vitro Laboratory studies or in Vivo Epidemiology surveys in order to bring on the table some seeds to grind for a better understanding of the pathogenesis and neurotropism of Zika virus.
On one hand, we have the WHO Statement on April 1st:
“The diagnosis of microcephaly was made at 22 weeks and one day of pregnancy on 10 March. On 17 March, the foetus’s samples were collected and tested at the Centre Hospitalier Universitaire of Martinique in Fort-de-France: both amniotic fluid and foetal blood samples resulted positive for Zika virus infection by polymerase chain reaction (PCR). On 22 March, the National Reference Center for arboviruses confirmed the infection with Zika virus.”
Timeline pregnancy/microcephaly during Zika outbreak in Martinique 2016
“On 7 December, the patient’s mother was sampled and a serology test confirmed infection with Flavivirus and alphavirus. A second serology test, which was conducted on 7 January, showed IgG antibodies against flavivirus and chikungunya virus as well as IgM antibodies against Zika virus. A third serology test, which was conducted on 11 February, confirmed once again the presence of IgG antibodies against flavivirus and chikungunya virus. These tests provide evidence that the mother was positive for Zika virus infection. A medical termination of the pregnancy was recommended to the mother.”
This statement is more focusing on clues which refer to Zika virus as causing microcephaly during the first quarterly than other critical information reported such as:
- Other viral infections tested positive in December 7th 2015:
- Flavivirus: might be Dengue (not named)
- Alphavirus: might be Chikungunya (not named)
- Date of arrival of Zika virus in Martinique: first cases reported early January 2016
- Tested positive for Zika virus on January 7th
On the other hand, we observe first:
- co-infection by both Dengue and Chikungunya,
- followed a couple of weeks later by Zika virus infection during the Q1 and just at the beginning of the Zika virus outbreak on going in Martinique.
- Zika virus found in amniotic fluid and foetus blood;
- Foetus diagnosed with microcephaly on March 10th 2016.
“It shows that a foetus can be PCR-positive for Zika virus months after the initial infection of the mother. Furthermore, this report provides additional evidence that infection with Zika virus early in pregnancy could be associated with an increased risk of microcephaly.”
At the end of the day, do we gather enough evidence to declare that this microcephaly is linked to Zika virus or may we address the key role of co-infection with Dengue and/or Chikungunya?
Yes Zika virus is involved in microcephaly but does it play alone or by co-acting with other risk factors?
Here are some lessons learned from the Martinique microcephaly case.
While we are observing an after-peak of Zika cases in Colombia and expecting no longer to reach 600.000 despite stats predictions, what is going on in Brazil and what do we know as of today about Zika virus and its pathogenesis?
What has been confirmed from In vitro studies?
- Zika virus crosses placenta barriers;
- Zika virus crosses blood-brain barrier;
- Zika virus can infect fetus;
- Zika virus has neurotropism;
- Zika virus is responsible for:
- Guillain-Barré Syndrome (GBS)
- Zika virus is linked with microcephaly during the Q1 of pregnancy.
When comparing Brazil/Colombia at the time being, meaning with some delay in the observance of microcephaly due to later spread of Zika virus in Colombia, on 61.393 suspected cases, 11.239 pregnant, zero microcephaly recorded so far in this cohorte but Colombia has identified 50 microcephalies, under investigation, of which only 7 under review for Zika virus while waiting for 25 (half of the cohorte) final results. We would be close to 2/10.000 prevalence or less with regards microcephaly related to Zika virus…more or less the historical prevalence of microcephaly in Brazil (26 times above in 2016).
Questions remaining without answer:
- Has Zika virus mutated since arrival in Americas/Brazil?
- Is there possible co-infection:
- with Dengue?
- with CMV, Rubella?
- Is there possible dual cause:
- with a chemical?
- with larvicide, pesticide?
- with Global Health issues (environment,Socio-economics)?
In a previous blog, we pointed out the choice of Colombia as a control group for the prevalence of microcephaly in link with Zika virus in order to answer the question about Zika virus as causative microcephaly.
So May we confirm, as WHO and CDC are delivering statement, that microcephaly is definitively related to Zika virus? More evidence required by answering questions.
Comme précédemment évoqué le 9 mars 2016, les résultats d’études publiées sur la toile contribuent à une meilleure connaissance de la maladie Zika mais également de la physiopathologie du virus véhiculé par les moustiques de la famille Aedes (aegypti et albopictus).
Qu’avons nous appris?
- Le virus Zika traverse la barrière placentaire
- Le virus Zika traverse la barrière hémato-encéphalique
- Le virus Zika infecte le foetus:
- présent dans le liquide céphalo-rachidien
- surtout au cours du premier trimestre de grossesse
- Le virus Zika possède un neurotropisme et est responsable:
- de Syndrome de Guillain-Barré;
- de myélite;
- de méningo-encéphalite.
- de destruction de cellules souches embryonnaires
- Le virus Zika est sexuellement transmissible;
- Le virus Zika peut être transmis par une transfusion sanguine.
Il existe de fortes suspiçions, présomptions, indices pour considérer le virus Zika comme le facteur principal mis en cause dans les cas de microcéphalie. Une étude récente, rétrospective, menée par l’institut Pasteur, aborde l’évaluation quantitative du risque de microcéphalie passant de 0.02% en situation “normale” à 1% ou plus si infection par le virus Zika au cours du premier trimestre de la grossesse.
Mais il manque pour autant des preuves pour répondre à certaines questions:
- Pourquoi le Brésil uniquement et principalement le Nord-Est?
- Y-a-t-il des facteurs associés et/ou agravants:
- le climat: El Nino?
- l’environnement: déforestation,décharges,eaux sales?
- les conditions socio-économiques?
- d’éventuels polluants chimiques:pesticides,larvicides?
- Co-infections virales:Rubéole,CMV,Dengue
- une mutation de la souche virale Zika (Asie-Pacifique)
Il sera donc intéressant de comparer l’émergence ou non de microcéphalies en Colombie, pays qui a été touché plus tardivement par l’épidémie de Zika; il est trop tôt (?) pour observer les premières naissances de nouveaux nés présentant des anomalies congénitales et/ou des microcéphalies, de mères infectées par le virus. Nous devrions en apprendre davantage cet été, à partir du mois de juin 2016.
Carte comparative des cas suspectés/confirmés de microcéphalies au Brésil (Mars 2016)
La Colombie annonce observer une baisse des cas de Zika depuis plusieurs semaines ce qui pourrait traduire une inversion dans la courbe de la propagation de l’épidémie.