#zika in Colombia: still waiting for a peak of #microcephaly in September…

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.

from @thelonevirologi

 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-and-zikvdenvchikv_2016

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?

#zika / #microcephaly in Colombia / Brazil

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?

  1. Lack of accurate reporting in Brazil leading to overestimation
  2. Possible non identified co-factors:
    • Poverty, poor hygiene, Vitamin deficit/malnutrition
    • chemicals:pesticides,larvicides,…
  3. 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.

Colombia 2

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.

by Vincent Racaniello,Earth’s virology Professor

More and more evidence describing physiopathogenesis of Zika virus and how it affects CNS in adult (GBS,myelitis,meningo-encephalitis) or fetus (birth defects, microcephaly or still born).

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…

#zikasummit in Paris hosted by Institut Pasteur: New pathways

Zika summit ParisLucky 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:
    1. naive population
    2. several waves of outbreaks:
      • Dengue
      • Zika
      • Chikungunya
    3. 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.

Structure 3D Zika virusNo 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…

#Microcephaly / #Zika as Political issues?

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 raisingwho-logo 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 focusingZikaMap 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. white HousePresident 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.

#Zika virus causing #microcephaly in Martinique: May we think differently?

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.”

ZKV Martinique

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:
    1. Flavivirus: might be Dengue (not named)
    2. 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:

  1. co-infection by both Dengue and Chikungunya,
  2. 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.
  3. Zika virus found in amniotic fluid and foetus blood;
  4. 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.

The Mystery of #Microcephaly in Brazil :Questions unanswered.

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?

  1. Zika virus crosses placenta barriers;
  2. Zika virus crosses blood-brain barrier;
  3. Zika virus can infect fetus;
  4. Zika virus has neurotropism;
  5. Zika virus is responsible for:
    • Guillain-Barré Syndrome (GBS)
    • Myelitis
    • Encephalitis
  6. Zika virus is linked with microcephaly during the Q1 of pregnancy.

Colombia_Zika_Report#9When 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:

  1. Has Zika virus mutated since arrival in Americas/Brazil?
  2. Is there possible co-infection:
    • with Dengue?
    • with CMV, Rubella?
  3. 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.

#zika et #microcephaly: mise à jour au 15 mars 2016

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.

Modèle expérimental de la maldie Zika

 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.

 

Brazil risk map mid march 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.

Colombia_Zika_Report#9

A suivre…

#microcephaly and #zika in Brazil: towards a double blind test?

Following the second meeting of the WHO’s Emergency Committee on Zika, there are clearly growing evidences for recognizing link between Zika virus and neurological damages or fetal defects observed: here are now facts:

  • Zika virus is crossing placenta barrier;
  • Zika virus is capable to infect foetus;
  • Zika virus is crossing blood-brain barrier;
  • In vitro, brain cells are damaged by Zika virus;
  • Guillain-Barré syndrome, myelitis caused by Zika virus.
  • Microcephaly = 1% during Zika outbreak in French Polynesia
  • Microcephaly and Timetable: risk exposure = Q1

But where do we stand with regards microcephaly?

  • microcephaly in Americas located in NE Brazil;
  • microcephaly not always related to Zika virus;
  • other causes known for microcephaly worldwide:
    • viral (rubella), infectious (toxoplasmosis)
    • toxic (chemicals,pollutants)
    • malnutrition (Vit. defiency,alcohol,…)

Looking at the map of microcephaly in Brazil:

Brazil risk map mid march 2016

 How could we explain as of today that cases are concentrated in Northeast of Brazil? Scientists are talking about climate change and El Nino in that area; others point out that this area is the first South American location to be hit by Zika and that it is to early to observe microcephaly elsewhere.

I would like to encourage studies on the effects of some pesticides and larvicides to be tested in vitro by combining both Zika virus with pyriproxyfen (e.g). Recently, a report by NECSI refers to this larvicide used in 2014 as a larvicide and poured in the drinking water in the NE Brazil.

“These tests were performed by its producer Sumitomo Chemical. Testing is limited and inconclusive, but includes some evidence for neurodevelopmental toxicity (see below). Such tests should be made public so that they can be critiqued by the scientific community, not just by regulatory authorities whose public summaries are not adequate for evaluation [19, 20]. This is a quite general problem, as the inadequacy of neurodevelopmental toxicity testing has been identified as a global risk [17].”

 You migth be aware that the MSDS for pyriproxyfen is not fully completed with regards Toxicity for reproduction; nevertheless, WHO recommended it as a safe product to eradicate mosquitoes like, Aedes aegypti or albopictus (based on which tests?…). It is unclear today to evaluate possible conflict of interests when reviewing the role and responsibility of pyriproxyfen in microcephaly during zika outbreak in Brazil.

During the meeting held on Wednesday March 9th, it was mentioned that Vector control means, including use of pesticides and larvicides had poor effects on mosquito breeding.

Colombia has been quoted as a group of reference in order to compare with Brazil. Unfortunately, due to late arrival of zika in this country, we have to wait till end of Spring 2016 to know if there is or not a close relationship between Zika virus and microcephaly, knowing that Colombia did not use pyriproxyfen.

Hypothesis:

  1. Abnormal microcephaly rate recorded => Zika virus
  2. No microcephaly recorded: other cause to be explored but mostly larvicide (pyriproxyfen).

So Colombia might be considered as part of a double blind test for Zika virus and microcephaly. To be noticed on mid March 2016 is the decrease of numbers for Zika cases, mainly in North (Carthagena,Bolivar). No microcephaly so far reported but may be still too early…?

Colombia_Zika_Report#9

A good summary as a wishing list done by Ian McKay in his excellent Blog VDU

Taking into account the precautionary Principle, it might be of interest to recommend women of childbearing age or pregnant living in NE Brazil to drink mineral water provided for free by NGO or International autthorities (UN, WHO).

#Zika virus,une maladie tropicale nėgligėe révélée par un larvicide?

L’OMS a déclaré un état d’urgence sanitaire de portée internationale à la suite d’une épidémie de Zika aux Ameriques (centrale et du sud).

Si le virus n’est pas nouveau et découvert en 1947 en Ouganda, il fait parler de lui depuis une dizaine d’années aprés son passage en Asie puis en Polynésie française où des cas de syndrome de Guillain-Barré ont été rapportés en lien avec le virus.

image

Que se passe-t-il donc depuis en Amérique du sud et principalement au nord est du Brésil, autour de Récife? Là et depuis plus d’un an, on y observe des naissances de bébés microcéphales, à petit périmètre crânien et réduction encéphalique.

Pourquoi seulement dans cette région du Brésil et pas ailleurs, en Colombie par exemple? C’est bien cela la question à laquelle l’OMS s’est engagée à répondre. La tentation est grande d’incriminer le réchauffement climatique voire El Nino dans cette région du monde. Mais alors pourquoi la Colombie qui recense plus de 4000 cas n’enregistre pas de cas de microcéphalie?

Microcephaly map Brazil

Y aurait-il un ou plusieurs autres facteurs de risque favorisant l’émergence de la microcéphalie au Brésil? Un groupe de médecins brésiliens et argentins se sont alors interrogés sur de possibles interactions avec des agents biologiques ou toxiques pour la reproduction, ces agents chimiques dangereux appelés aussi CMR pour cancérigène,mutagène et toxique pour la reproduction(tératogène). Leur attention se porte sur une curieuse et opportuniste coïncidence:un larvicide,le peryproxyfène,a été déversé dans les réservoirs d’eau potable pour détruire les larves du moustique Aedes aegypti qui est le vecteur pour les maladies de la dengue,du chikungunya,de la fièvre jaune et du zika. Ce produit est condidéré jusque la comme sûr par l’OMS (2006). On sait que le virus zika possède un neurotropisme,une capacité à agir sur le système nerveux central des mammifères y compris l’homme; ce qui expliquerait les cas de Guillain-Barré  observés ces dernières années.Ce pourrait il que le virus qui franchit la barrière placentaire,soit plus virulent chez les femmes intoxiquées par du peryproxyfène et attaque le système central du foetus conduisant à une microcéphalie?

Devant cette incertitude et face à une catastrophe sanitaire, le ministère de la santé du Brésil vient de décider de suspendre l’utilisation de ce larvicide jusqu’à plus ample infomé sur sa toxicité par absorption orale chez la femme enceinte. saluons cette sage décision au nom de l’application du principe de précaution.

 

#Zika:Is microcephaly in North-East Brazil due to virus or multi-causal?

If WHO has launched a PHEIC with regards Zika virus and possible side effects/defects like Guillain-Barré Syndrome (GBS) or microcephaly, several scientists are now pointing out other root causes for explaining both the nature of the disability and the spread of the outbreak in South America, moslty in North-East Brazil.

Microcephaly map Brazil

Map of microcephaly in Brazil

By reviewing other risk factors which might be responsible or co-acting with the Zika virus, there are at least two questions unanswered about the key role of virus for microcephaly:

  1. Why microcephaly newborns are concentrated in North-East states of Brazil?
  2. Why socio-economics are impacting the rate of microcephaly in this location?
  • Tentative answers raising global warming including but not limited to El Nino to increasing the spread of the zika outbreak by helping the growth of the vector (Aedes aegypti mosquito), are not totally convincing; even if climate change is acting as a promoting/contributing factor.
  • How socio-economics issues could impact women of the childbearing age or pregnant?
    • poverty,malnutrition,low access to health facilities or family planning;
    • environmental factors (air/water/soil pollution or contamination,waste,…);
    • hygiene & sanitation.

all of global health concerns…

larvicide pyriproxyfen

Now by addressing the use of a huge amount of one chemical agent,pyriproxyfen larvicide, for a while in North east Brazil (also since 2014 in Argentina), in order to sterilize potable drinking water by eradicating disease-carrying mosquitos, may we review at International level the root causes tree of microcephaly in Brazil. One critical point is we shall no longer avoid the debate…

“Given these toxic effects of pesticides and that they are more heavily used in Brazil’s northeast region, it is not unreasonable to think that, at least in some cases, microcephaly may be due to excessive use of toxic pesticides and that these effects, have been unmasked by the Zika virus infection. It is also possible to think that microcephaly in children may have a multi-causal origin.”

in “Is microcephaly caused by Zika or pesticides?” by CESAR CHELALA

As always, precautionary measures are recommended before validating the quote:

“Instead Abrasco suggests that this strategy is in fact driven by the commercial interests of the chemical industry, which it says is deeply integrated into the Latin American ministries of health, as well as the World Health Organization and the Pan American Health Organisation.”

in “Argentine and Brazilian doctors suspect mosquito insecticide as cause of microcephaly” by Claire Robinson / GMWatch

larvicide