Is there a cause and effect link or merely a correlation of unrelated events? Here is the story and the facts so far. In October 2015 an increase in microcephaly was reported in Brazil. A Brazilian doctor, Adriana Melo, at IPESQ, a research institute in Campina Grande, was the first to report a firm link between Zika and microcephaly. Several months before, there had been an outbreak of Zika virus throughout Brazil. The increase in microcephaly cases occurred only in a coastal state in the northeast of the country. Why not the entire Zika epidemic region?
90% of the 1709 cases of microcephaly and birth defects were concentrated in this limited area. Of this number 1153 were diagnosed as microcephaly. There was no increase in other parts of the country, including an adjoining coastal state with a similar population, which only had 3 cases. This suggests there may be other contributing factors. Socio-economic factors may contribute since most of the mothers of the microcephalic babies were young, single, black and poor, living in small cities near larger cities. Additionally, this same northeastern region has always had the highest incidence of microcephaly in Brazil.
A study by the Latin American Collaborative Study of Congenital Malformations (ECLAMC) called for more controlled studies, and concluded that the data so far is inconclusive of a cause and effect link between Zika infection in the first trimester of pregnancy and microcephaly and similar nervous system defects. For an English translation of the original Portugese summary of the ECLAMC studies, see http://www.nature.com/polopoly_fs/7.33594!/file/NS-724-2015_ECLAMC-ZIKA%20VIRUS_V-FINAL_012516.pdf
This report discusses weaknesses in the methods used by IPESQ, recommendations for further studies and several other factors that may have caused or contributed to the birth defects as listed below.
- Rumor may have caused over reporting due to active searches and over diagnosis. Brazil health authorities estimate that as many as 2/3 of cases are normally not reported to authorities. If the estimate is correct, this would partially account for an increase, but not the degree reported, so other factors must be involved. However, Brazil reports a rate of 0.5 per 10,000 births compared to EUROCAT of 2.85 per 10,000 births, indicating a gross under reporting.
- Broadened criteria for microcephaly diagnosis from 3 standard deviations to 2 standard deviations below normal average age and sex adjusted head circumference, and no confirming follow up brain scans or autopsies in most cases.
- Zika infection in the first trimester of pregnancy cannot be confirmed at the time of birth because the virus is short-lived in the body and will not be present in the mother. Unless the mother was diagnosed early in her pregnancy, occurrence and connection cannot be confirmed.
- In the original studies other known causes were not ruled out such as STORCH (syphilis, toxoplasmosis, “other,” rubella, cytomegalovirus, herpes simplex), prematurity, diabetes of the mother and fetal alcohol syndrome, a major cause of microcephaly in Brazil.
- Also not ruled out are possible co-infections with dengue or chikungunya, both present in the population in recent outbreaks. The dengue virus is similar to the Zika virus and difficult to differentiate in tests.
- A low rate of yellow fever vaccination also seems to correlate to this incident. Yellow fever virus is similar to Zika virus and vaccination may offer some immunity to it.
- At IPESQ Bovine diarrheal virus (BVDV) was found in brain tissue of 3 fetuses in a later study. This virus does not usually infect humans but is known to cause birth defects in cattle. If true, this may be significant, but Dr. Adriana Melo suspects it may be a contaminant in the sampling or testing procedures.
- Contaminated water was not considered, although it is common for small cities without proper sanitation and water purification to have biologically contaminated water.
- Nutrition was not considered in this study other than a mention of general socio-economic influences, although the CDC, NIH and other agencies recognize folic acid (a B vitamin) deficiency as one of the leading causes of neural tube defects (NTD), including microcephaly, anencephaly, and spina bifida. In a recent NIH study they found that other micronutrients may decrease the risk of NTD occurrence, including thiamin (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), betaine (a B vitamin), vitamin A, retinol (A1), vitamin C, vitamin E and iron.
In conclusion, the “link” between Zika virus and microcephaly is far from proven because the original studies lacked scientific discipline and controls. More studies are needed to clarify what role the virus may play in these birth defects. However, it is probably best to take a precautionary approach until more is known.
Is it time to bring back DDT to eradicate the mosquitos that carry Zika and other diseases such as malaria, dengue fever, chikungunya, yellow fever and other diseases? Over 80% of infectious diseases are caused by insects. Assumed adverse environmental and health effects of this important insecticide have failed to materialize in many repeated controlled studies over the last 40 years. See “DDT: A Case Study in Scientific Fraud,” by J. Gordon Edwards, PhD entomology, Journal of American Physicians and Surgeons Volume 9 Number 3 Fall 2004, at http://www.jpands.org/vol9no3/edwards.pdf
“Eclamc Final Document – V.3, Summary and conclusions of Documents 1-5,” December 30th, 2015 http://www.nature.com/polopoly_fs/7.33594!/file/NS-724-2015_ECLAMC-ZIKA%20VIRUS_V-FINAL_012516.pdf
“Neural Tube Defects and Maternal Intake of Micronutrients Related to One-Carbon Metabolism or Antioxidant Activity,” US National Institute of Health, Angela L. Chandler1, Charlotte A. Hobbs1, Bridget S. Mosley1, Robert J. Berry2, Mark A.Canfield3, Yan Ping Qi2, Anna Maria Siega-Riz4, Gary M. Shaw5, and National Birth Defects Prevention Study, in Birth Defects Res A Clin Mol Teratol. 2012 November ; 94(11): 864–874. doi:10.1002/bdra.23068.
- Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital Research Institute, Little Rock, AR 72202
- Centers for Disease Control and Prevention, Atlanta, Georgia
- Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, Texas
- Departments of Epidemiology and Nutrition, University of North Carolina School of Public Health, Chapel Hill, North Carolina
- Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, California
“Brazil’s birth-defects puzzle, Zika virus might not be only factor in reported microcephaly surge.” By Declan Butler, 28 July 2016, Nature, Vol. 535, Page 475-6.
“Zika epidemic uncovers Brazil’s hidden birth defect problem,” by Alex Cuadros, March 1, 2016, Washington Post
“Disease Transmission by Arthropods,” E. J. L. Soulsby and William R. Harvey, Science 176, no. 4039 (1972): 1153–1155.
“DDT: A Case Study in Scientific Fraud,” by J. Gordon Edwards, PhD entomology, Journal of American Physicians and Surgeons Volume 9 Number 3 Fall 2004, at http://www.jpands.org/vol9no3/edwards.pdf