Brazil, Zika and Microcephaly
Over the last year, women in Pernambuco, Brazil have given birth to increasing number of babies with microcephaly, a condition where the baby’s head is much smaller than normal. Up to 5000 cases have been reported, though numbers vary considerably from source to source and it appears that only 400 cases have been confirmed; 400 cases of microcephaly out of approximately 134,000 births annually or .003%. By comparison, we have 25,000 estimated annual cases of microcephaly in the US out of about 4 million births or about .006%, and prior to this presumed linkage, no Zika.
In a scramble to identify the cause, squelch fears, and arguably, direct blame, the Brazilian government attributed the microcephaly to an outbreak of the mosquito-borne virus, called Zika, despite the fact that Zika virus had been around for generations in Brazil (and in other regions), infecting up to 75% of the population. However, until now, it had never induced birth defects, especially those as serious as microcephaly. In fact, the Zika virus causes flu-like symptoms, similar to, but less severe than those observed with Dengue Fever. In an open letter to Brazilian Health Ministry, from the Physicians in Crop Sprayed Villages:
“It [Zika] usually happens as a flu-like syndrome, often confused with other arbovirus infections such as Dengue or Chikungunya. The typical form of the disease is associated with low-grade fever (between 37.8 ºC and 38.5 ºC), arthralgia, especially of small joints in hands and feet, myalgia, headache, retro-orbital pain, conjunctivitis, and maculopapular rash. Digestive problems (abdominal pain, diarrhoea, constipation), ulceration of mucous membranes (thrush), and itching can be rarely observed. Asthenia after infection seems to be common.”
In spite of the apparent lack of evidence supporting a connection, the Brazilian Health Ministry, the American major media, the American medical establishment, the Centers for Disease Control (CDC), the World Health Organization (WHO) and many other institutions of authority, jumped on the Zika bandwagon.
“On 1 February, a committee convened by the World Health Organization said that a causal link between Zika and microcephaly is “strongly suspected, though not yet scientifically proven”.
“As of 2 February, officials there [in Brazil] had investigated 1,113 of 4,783 suspected cases of microcephaly reported since late last year, and confirmed 404 of them — [only] 17 of which have so far been linked to Zika.”
Note that of the 404 confirmed cases of microcephaly only 17 had been linked to Zika – .0001%. Numbers that I would argue question the Zika hypothesis, if not outright contradict it. Admittedly, as the government works its way through the case pool, it is likely Zika numbers will increase somewhat, but not to the level that corresponds to recent hysteria and certainly not to the level of an epidemic.
Despite the clear lack of evidence, prominent medical journals like The New England Journal of Medicine (NJEM) have rushed to publish articles on Zika identification and preparation, each iterating the other and offering what is boasted as definitive proof. This is then parroted broadly by the media and even the CDC. In March NJEM, published the first documented case report of a Zika-infected aborted fetus – a brief case report that had no less than 14 MDs and PhDs as authors plus 11 others listed under research assistance. When there are this many authors listed on a paper for a brief case history, something is amiss. Incredulity aside, does this case tell us anything about a potential connection between Zika virus and microcephaly?
From the report, we know that the mother, having worked in a region where Zika was prominent, developed symptoms of the virus at 13 weeks of gestation. Early fetal monitoring appeared normal but at 28 weeks, reduced fetal movement spurred additional tests at which point severe fetal growth restriction and microcephaly were observed. The fetal autopsy showed significant brain damage (areas of gross calcification) and evidence of the Zika virus in several regions of the brain.
With Zika found in the brain and the corresponding damage, it seems as though we found our smoking gun. The presence of the virus in the fetus establishes what is called vertical transmission from the mother to the child. Vertical transmission is known to occur with other pathogens that cause microcephaly; rubella, for example. Maybe there is something to this Zika panic. Is it possible that Zika was responsible for the neural defects? It is possible, but I would argue not probable and certainly neither necessary nor sufficient to prove a linkage. No other potential causes of microcephaly were reported. Microcephaly can be caused by a myriad of factors; from any insult that disturbs early brain growth including hundreds of genetic syndromes.
Animal studies and human history with Zika show very limited evidence that it is capable of inducing microcephaly on its own. Remember, this virus has been around for generations with no outbreaks of microcephaly prior to Brazil. In other regions, French Polynesia, for example, where Zika outbreaks are common, microcephaly is not, and attempts to link Zika to microcephaly there, have failed. Among its population of 270,000 people, researchers estimate that 66% have been infected with the Zika virus at some point but less than 1% of the 4182 babies born annually develop microcephaly. This is not exactly the strongest support for Zika microcephaly and not even comparable to the infection and damage rates seen with rubella.
Despite the spurious evidence, the NJEM, other medical journals and the media continue to proclaim causation. Indeed, in June, NJEM offered yet another iteration of Zika proof. This time, it included the review of just two epidemiological articles, and of course, the case report cited above.
“Two epidemiologic studies also provide support. In a study conducted during the outbreak in Brazil, 88 pregnant women who had had an onset of rash in the previous 5 days were tested for Zika virus RNA. Among the 72 women who had positive tests, 42 underwent prenatal ultrasonography, and fetal abnormalities were observed in 12 (29%) [notice only 42 of the women who tested positive were given ultrasounds and thus, it is 29% of 42 they are citing as evidence]; none of the 16 women with negative tests had fetal abnormalities. The abnormalities that were observed on ultrasonography varied widely, and some findings lacked postnatal confirmation because the pregnancies were ongoing.”
Based upon these two epidemiological studies that contain weak evidence at best, plus the case study, the authors concluded:
“On the basis of this review, we conclude that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies.”
For the less cynical among us, we seemed to have found our smoking gun. All that remains are the silver bullets – the medications to kill the virus and the vaccines to prevent future outbreaks. Easy peasy.
Is it Zika or Something Else Entirely?
For the more cynical among us, however, and really, anyone with a bit of research experience, this entire scenario seems just a little too clear cut and too contrived to be real. Why would a viral pathogen that has been around for decades, infected large swaths of different populations, suddenly cause such dramatic and severe birth defects? Did the virus mutate in some manner or another into some super pathogen? Or are there other factors that we are ignoring?
I think it is the latter; that there are most certainly other factors involved. Industry shenanigans aside, this just doesn’t feel right. To believe that Zika is responsible for this recent epidemic of microcephaly, not only do we have buy a remarkable set of coincidences aligning just so to position no less than 18 different industries front and center for profits, but also, we have to disregard some pretty damning environmental and pharmaceutical exposures and forget everything we know about the causes of microcephaly. Only then and from within that hazy swath of cognitive dissonance can we recognize the Zika scare. As one astute researcher put it, Zika is so dangerous that, unlike other pathogens, we have to assume it is ‘guilty until proven innocent‘.
Environmental Variables That Induce Microcephaly
How do we get from Zika to microcephaly in Brazil? Certainly, we can ascribe political and financial machinations, but that would be too easy and it wouldn’t really tell us anything useful. If I were pregnant or considering pregnancy, I would want to know more about my real risk of fetal birth defects, particularly if I were traveling in these areas. If it is not Zika, then what is it? And if it is Zika, what are the contributing factors that lead to microcephaly? Remember, according to the Brazilian Health Ministry, out the 1113 suspected cases of microcephaly investigated, only 404 were actually microcephaly and only 17 had evidence of Zika infection. The data point beyond Zika – well beyond. Putting aside that the reported numbers of Zika-presumed microcephaly cases don’t add up, what other variables uniquely predipose the women of Pernambuco, Brazil to bearing microencephalic offspring?
Environmental Components of Microcephaly
Brazil is the world leader in agricultural chemical usage and second largest agricultural biotech producer of genetically modified crops. In fact, Monsanto has been active in Brazil for over 50 years. Glyphosate exposure, for example, along with its extensive carcinogenic and endocrine disrupting actions, is highly teratogenic. An emerging body of evidence suggests that it is capable of inducing the characteristic set of birth defects consistent with those observed in Brazil including: microcephaly, but also, anencephaly and hydrocephaly, as well as other head and skeletal malformations.
Glyphosate is used extensively in Brazil for the cultivation of GM soya in areas where the Zika virus is endemic. It is teratogenic in some fairly specific ways and a case could be made for its involvement in the uptick of microcephaly cases via several mechanisms.
- Glyphosate chelates minerals. Maternal mineral deficiencies have striking effects on fetal neurodevelopment and, as discussed below, maternal nutrient deficiency, vitamins and minerals, can cause microcephaly.
- Glyphosate alters vitamin A metabolism. Too much or too little vitamin A at critical junctures of fetal develop induce a wide variety of fetal brain malformations.
- Glyphosate weakens the blood brain barrier for mom and likely also baby and compromises immune function. A weakened blood brain barrier would provide a mechanism by which Zika, along with other pathogens, could enter the brain and exert influence.
In animal studies, monkeys are carriers of the virus but do not seem to bear microcephalic offspring. Immunocompromised mice are susceptible to the virus, but do not bear microcephalic offspring. A compromised immune system would provide easy access for a viral pathogen to not only cross the placenta, but enter the brain of the developing fetus. Once there, the virus could do damage. Could the virus have reached the brain without glyphosate or another chemicals weakening the blood brain barrier? Probably not. Might glyphosate induce microcephaly without Zika? Evidence suggests that it can.
Pyriproxyfen: Larvacide in the Water Supply
In an effort to stop the proliferation of the Zika-carrying mosquito, a chemical called pyriproxyfen, was added Pernambuco’s drinking-water reservoirs in 2014. The larvacide works as
“… a growth inhibitor of mosquito larvae, which alters the development process from larva to pupa to adult, thus generating malformations in developing mosquitoes and killing or disabling them… It is an endocrine disruptor and is teratogenic (causes birth defects).
The safety research on pyriproxyfen is sparse at best. From the EPA, we know that it is an endocrine disruptor, impacting the androgen pathways most notably. It also induces the CYP enzymes in the liver (and quite a bit of liver damage to boot). Is it a factor in the microcephalic births? Perhaps. Pyriproxyfen exposure certainly taxes an already stressed maternal physiology, perhaps enough to increase vertical transmission of a virus; the very viral transmission the chemical was supposed to prevent.
Brazil instituted third trimester Tdap vaccination for pertussis or whooping cough in 2014. Despite the widespread belief that vaccinations during pregnancy are perfectly safe and the numerous large epidemiological studies that appear to support the safety contention, a deeper dive reveals striking flaws in these studies. The aluminum adjuvants in these vaccines are neurotoxic and induce peripheral and neuro-inflammation, aspects of the vaccine that are neither investigated in the placebo-controlled trials (the placebos contain the aluminum adjuvants and thus are not true placebos) nor in the epidemiological investigations. The vaccine labels themselves indicate that they are not appropriate for pregnancy (pregnancy class C: animal studies have not been conducted) despite the marketing suggesting otherwise. Worse yet, there is emerging evidence that glyphosate plus aluminum is synergistic, enhancing the effects beyond what either would do alone. Third trimester vaccination, when brain development is growing at leaps and bounds, alone could evoke neurodevelopment issues. Together with the other toxicant exposures and in the presence of a circulating virus, a recipe for ill-effects.
Poverty and Malnutrition
The spatial distribution of children born with microcephaly shows a higher concentration in the poorest areas of Northeastern Brazil; areas that also happen to coincide with the highest density of pyriproxefen spraying and glyphosate exposure, and of course, we cannot forget the country-wide maternal vaccination program. As with any impoverished area, malnutrition is likely present. Maternal vitamin deficiency alone can induce microcephaly, plus a myriad of other birth defects and health issues.
Pulling It All Together
To sum up, we have poor, likely malnourished, women exposed to a cocktail of chemical toxicants both before and during pregnancy in a region where a viral pathogen is present. Without the other factors, it is not clear that Zika would pose a threat to fetal brain development. From animal studies, absent immunocompromise, there is no evidence of Zika in the brain. In contrast, without Zika, it is quite possible that any of these other factors, alone or in combination, could initiate the disease process resulting in microcephaly. That is not to say that the Zika virus, once it reaches the brain, wouldn’t wreak havoc and induce damage. Both imaging and cell culture studies suggest that it would. I would argue, however, that it would not reach the brain without some combination of other toxicants and/or maternal malnutrition. I would also argue, that while Zika induces damage once in the fetal brain, it may not be the cause of the microcephaly. That might originate from the toxicant exposures combined with the malnutrition targeting a particular nutrient transporter known to induce microcephaly.
I think the Brazilian microcephaly cases, though coincident with Zika, are not caused by Zika. I think the combination of toxicants induce secondary microcephaly via direct thiamine deficiency and depletion and/or functional or epigenetic alterations to the thiamine transporter SLC25A19. Briefly, thiamine is critical for mitochondrial function, which are critical for energy production for every cell in the body. When we deplete thiamine, all sorts of things go wrong, particularly in the areas requiring the most energy – the brain, heart, etc. (See thiamine deficiency.) When we deplete thiamine during pregnancy, fetal development and neurodevelopment are affected. When we block it severely and/or we block the transporter that takes thiamine from the cell to the mitochondria, we get microcephaly. It is believed that this type of microcephaly is rare and develops largely in consanguineous communities via transmission of a specific set of genetic mutations. Over the recent decade however, researchers have learned that all sorts of functions formally thought to be affected only by mutations, can also be affected epigenetically. That is, via gene activation/deactivation with no mutation necessary. Environmental and pharmaceutical chemicals drive epigenetic modification. Similarly, environmental and pharmaceutical chemicals can drive other functional changes that would serve to reduce thiamine availability. And finally, since thiamine must be derived from diet, malnutrition alone, or in combination with a faulty thiamine transporter, could create a state of maternal thiamine deficiency that results in microcephaly. The chemical environment into which these children were born provides the perfect composition of thiamine damaging factors, likely centered at the level of the thiamine transporter with possible epigenetic alterations in the SLC25A19 gene.
So while Zika has been found in the brains of some of these children and Zika can cause alterations in neural function, at least in a petri dish of cultured neural stem cells, it has no mechanism for vertical transmission without the maternal immunocompromise, making Zika neither necessary nor sufficient to induce microcephaly by itself. In contrast, each of the variables discussed in this paper are capable of producing severe birth defects, including microcephaly without Zika, if the exposures are significant. They are sufficient to cause microcephaly but maybe not necessary. We need one more variable. That variable is thiamine deficiency. Thiamine deficiency whether by nutritional deficits, functional alterations in absorption or usage and/or by problems with the transporter, is both necessary and sufficient to cause microcephaly. Thiamine deficiency sits at the nexus of all of these variables and is the key to understanding the Brazilian microcephaly problem. This means that the environmental and pharmaceutical chemicals, not the Zika virus, are responsible. Zika is secondary. Zika is not THE pathogen. It is simply a pathogen. And it is certainly not the smoking gun we need to forestall microcephaly.