CDC Works For You 24/7

Editor’s Note:  In 2012 we will mark the 20th anniversary of the US Public Health Service recommendation that women of childbearing age should consume 400 micrograms (mcg) of folic acid every day to help prevent certain neural tube defects (NTDs) – spina bifida and anencephaly. Several CDC scientists were involved in the research that led up to the recommendation, or contributed to the subsequent work on folic acid that continues today, including Joseph Mulinare, Robert J. Berry, J. David Erickson, and Godfrey Oakley. The four blogs in this series tell their stories.   

Jose Cordero (l) founding director of the National Center for Birth Defects and Developmental Disabilities; Oakley (r); and Erickson (seated). Photo courtesy of Godfrey Oakley

Godfrey P. Oakley, Jr., MD, came to CDC in 1968 as an EIS officer. He was the initial head of CDC’s first section of birth defects, which developed into a division by the early 1980s and later became a center in the 1990s.

Oakley jokingly often asks people: “Do you know where you were on June 24, 1991 at 5 pm?” It’s a date and time that Oakley vividly remembers. He was at a hotel attending a birth defects meeting, and it was on that day, he says, that the intervention part of folic acid started. “I got a call from Sir Nicholas Wald (he wasn’t a ‘Sir’ then, but is now), and he told me that the randomized controlled trial that he conducted had proved that folic acid would prevent most of spina bifida and anencephaly. I knew we had to get every woman in the world to get 400 micrograms of folic acid. His study was a game changer.”

Later that evening Oakley met with Dave Erickson and Jose Cordero, MD, MPH (later to be director of the National Center on Birth Defects and Developmental Disabilities), “and I told them the most important information I ever had as a professional,” says Oakley.

The big push was on to get a recommendation for women who already had a pregnancy affected by an NTD because the study that Wald conducted was with women who already had an affected pregnancy. The first recommendation was published in the summer of 1991. “That was about the easiest policy thing I ever did,” says Oakley. “It was before a whole lot of emails and stuff, so we did it by faxes; nobody fussed about it. We put it out in MMWR and said that all women who had previously had an affected child should take 4,000 micrograms of folic acid when planning a pregnancy.”

But as important as the recommendation was for women who had had a pregnancy affected by an NTD, it did not target women who had never had an affected pregnancy. “Most women who have a child with spina bifida had not had an affected baby before,” Oakley points out. “High risk women only have 5 percent of the births and low risk women have 95 percent, so if you want a program that’s going to prevent this in the population, you have to have a population approach. That took us a year to get through CDC. Dave (Erickson), Jose (Cordero), Joe (Mulinare) and I and others worked on this. And Steve Thacker and Claire Broome were also helpful.”

During the summer of 1992, Oakley and others often went to Washington to meet with FDA officials and public health representatives, many of whom were resistant to the broader recommendation for folic acid. “So we have this powwow and they picked on certain scientific things that were really trivial,” says Oakley. “Finally, I think what changed the day was a question I asked: ‘Is there anybody in this room who can’t agree with the following statement—that folic acid prevents some of spina bifida but not all of it?’” Ultimately, CDC received the green light to write the recommendation.

“Dave Erickson wrote it up, we sent it back, and it was put in a MMWR article,” continues Oakley, who says the recommendation was released September 11, 1992, just in time for an international meeting on birth defects. “I think it’s one of the most important MMWR articles that’s ever been written—the recommendation that all women who could get pregnant should get 400 micrograms of folic acid,” says Oakley. “That is an enormously important policy document. The FDA signed it, NIH signed it, HRSA signed it—everybody signed it. It’s a public health service recommendation, not just CDC’s.”

Editor’s Note:  In 2012 we will mark the 20th anniversary of the US Public Health Service recommendation that women of childbearing age should consume 400 micrograms (mcg) of folic acid every day to help prevent certain neural tube defects (NTDs) – spina bifida and anencephaly. Several CDC scientists were involved in the research that led up to the recommendation, or contributed to the subsequent work on folic acid that continues today, including Joseph Mulinare, Robert J. Berry, J. David Erickson, and Godfrey Oakley. The four blogs in this series tell their stories. 

Dave Erickson (l) and Godfrey Oakley (r) with Richard Smithells (c), who wrote one of the first papers on folic acid’s ability to prevent spina bifida. Says Oakley, “We were working very hard in South Carolina one afternoon!” Photo courtesy of Godfrey Oakley

J. David (Dave) Erickson, DDS, PhD, who worked with RJ Berry in the China study, was involved from the beginning with CDC’s work on folic acid. He acknowledges that initially there was substantial doubt within CDC about folic acid’s preventive effects. “Richard Smithells did an important but non-randomized trial of the use of folic acid in vitamin supplements as a preventive effect. There was reluctance to move forward on the part of the scientific and public health nutrition community because of the concern about sufficient data.”

Erickson points out another concern. “When I and most of the other people who worked on this had been told in our education that you get all the micronutrients you needed from eating a good diet—this issue of folic acid enrichment kind of flew in the face of that—and that added to the skepticism. It’s fair to say that we spent a lot of time talking about it. That was in 1981 or ‘82.”

Erickson, who retired from CDC in 2006 and now lives in Gainesville, recalls the many collaborations between members of the CDC team as well as people from outside the agency. Over the years, Erickson has worked on various aspects of the folic acid issue: conducting studies, considering policy, writing articles, and being a part of a team that ultimately made a major difference in public health.

“We started in the early ‘80s and ten years later we participated with people outside of CDC to develop a recommendation on the use of folic acid to prevent neural tube defects. There were people from CDC, NIH, HRSA, and the FDA who were involved in what culminated in the recommendation, although the CDC team spearheaded the effort. There were hearings of various advisory committees to the FDA on the issue of requiring fortification in enriched cereal grains—that had to be mandated by the FDA. It was another seven or eight years until the food supply was fortified, a follow-up to evaluate the effect of that, and then an effort by the team which continues today to promote changes in the consumption of folic acid, nationally and internationally.”

Like other members of the CDC team, Erickson says that it has been most gratifying for him to have been part of the group that pushed an issue “that’s done a tremendous amount of good, and will continue to do a tremendous amount of good.” He adds, “These defects that folic acid prevents are hard things to deal with. There have been a tremendous number of babies born without these problems since this work was completed and the public health programs were put in place. And it’s extremely satisfying for me to have been a part of that.”

For more information about CDC’s folic acid success story, go Folic Acid: Helping to Prevent Birth Defects. For more detailed information on folic acid, visit the CDC Folic Acid Web Page on the CDC Works For You 24/7 website. Thanks to Faye McDonald Smith of CDC who wrote the original article on which this blog was based.

Editor’s Note:  In 2012 we will mark the 20th anniversary of the US Public Health Service recommendation that women of childbearing age should consume 400 micrograms (mcg) of folic acid every day to help prevent certain neural tube defects (NTDs) – spina bifida and anencephaly. Several CDC scientists were involved in the research that led up to the recommendation, or contributed to the subsequent work on folic acid that continues today, including Joseph Mulinare, Robert J. Berry, J. David Erickson, and Godfrey Oakley. The four blogs in this series tell their stories. 

RJ Berry, who lived in China during the 1990s to conduct a study on folic acid, recently visited a township in Taicang City, Jiangsu Province. The woman in the white coat worked on the original project on folic acid and the other women had children born during 1994 through 1996. Photo courtesy of RJ Berry

The China study, officially named the Sino American Cooperative Project on Neural Tube Defects, was conducted in two areas during the mid-1990s: in northern China where the background rate was high, and in southern region China where the background rate was comparable to the US. Because there was no folic acid fortification and no other vitamins given to study participants, the study represented a “pure” test of the lone effect of 400 micrograms of folic acid.

The study involved two years of recruitment, between October 1, 1993 and September 30, 1995, with a total of 247,831 women participating. “It’s a number I’ll never forget,” says Robert J. (RJ) Berry, MD, MPHTM, who led the study. Among the 130,142 women who took folic acid at any time before or during pregnancy, 102 fetuses or infants were identified with neural tube defects. Of the 117,689 women who had not taken folic acid, 173 fetuses or infants had neural tube defects.

“In the north, the rate among non-pill takers was 4.8 per thousand. The rate among women who took it at the right time and had the highest compliance was 0.7 per thousand. “That’s an 85 percent reduction, which is unbelievable,” says Berry. “In the south—which started at a much lower value at 1 per thousand—it went down to .6 per thousand, so that’s a 40 percent decrease.”

The study generated a massive organizing effort among thousands of Chinese village doctors who served as intermediaries between the project and the participants. Each month doctors visited the homes of the participants to check on how they were doing, collect the old pill bottle and supply a new one, and compile a report on how many pills were left in the old bottle, which could determine the compliance rate. Each woman averaged about six months of pill-taking.

Editor’s Note:  In 2012 we will mark the 20th anniversary of the US Public Health Service recommendation that women of childbearing age should consume 400 micrograms (mcg) of folic acid every day to help prevent certain neural tube defects (NTDs) – spina bifida and anencephaly. Several CDC scientists were involved in the research that led up to the recommendation, or contributed to the subsequent work on folic acid that continues today, including Joseph Mulinare, Robert J. Berry, J. David Erickson, and Godfrey Oakley. The four blogs in this series tell their stories. 

Joe Mulinare (l) and Dave Erickson collaborated closely during the 1980s and 1990s as part of the CDC team that studied the role of folic acid in preventing certain types of NTDs. Photo courtesy of Godfrey Oakley

When Joseph (Joe) Mulinare, MD, MSPH, came to CDC in 1981 he immediately began to work on researching the role of folic acid in preventing the neural tube defects (NTDs) anencephaly and spina bifida, serious birth defects of the brain and spine. He helped conduct an early CDC study of babies born in metro Atlanta between 1968-1980,that found a reduced risk for having a baby with a neural tube defect among mothers who had taken folic acid around the time of conception.

During the mid-1980s, it was decided that the case control studies that CDC was conducting and other observational studies from the United Kingdom and elsewhere, were not sufficient to show that folic acid really prevented NTDs,” says Mulinare. There was consensus that a randomized controlled trial was needed.

A randomized controlled trial among women who had already had a child with an NTD was conducted during the 1980s and its results were reported in 1991 by the British Medical Research Council (MRC) with principal investigator Nicholas Wald—which showed that folic acid alone prevented NTDs among women who had had a previous NTD-affected pregnancy.

“With that randomized trial and evidence from a couple of other studies that were unpublished at the time, including a randomized trial from Hungary that found that a multi-vitamin containing folic acid actually prevented NTDs among women who had not had a previous NTD-affected pregnancy, we set the stage for writing the September 1992 recommendation for the prevention of the occurrence of NTDs—that all women of childbearing age consume 400 micrograms (mcg) daily,” said Mulinare. “Part of that recommendation also included a repeat of the one we had done earlier in August 1991, which said that all women who had had a previous affected pregnancy should take 4,000 micrograms, 10 times the amount, because the MRC study actually used 4,000 micrograms, not 400.”

Dr. Arnold Castro has developed innovative tests to more quickly diagnose syphilis. As a result, patients may begin receiving treatment sooner.

Editor’s Note: Dr. Arnold received this honor from the Laboratory Science, Policy and Practice Program Office (LSPPPO) in the Office of Surveillance, Epidemiology, and Laboratory Services (OSELS) at CDC. We asked Dr. Castro some questions about his work: 

What do you do at CDC?           

I am a research microbiologist and I am responsible for the development of new innovative point of care (POC) rapid tests for the diagnosis of syphilis using serum, plasma or whole blood. The test is simple, inexpensive, requires no expertise to interpret the results and it is capable of determining the serological status of a patient by screening and confirming the result in a single test within 2 to 15 minutes while the patient waits at the clinical site. I also have other duties related to syphilis detection, including serving as technical advisor for the WHO syphilis Proficiency Testing Program at CDC. 

What personal experience in your work are you proudest of? 

I am very proud of the opportunity to use research to develop new diagnostic tests that would be beneficial for the public health such as the development of the rapid POC test for syphilis. This test can aid in detecting and treating pregnant women and help prevent congenital syphilis. I am also proud to have acquired three patents for my work: 1) “Modified Cardiolipin and Uses Therefore:” U.S. Patent No. 7,888,043 B2. 2); “Methods, Immunoassays and Devices for Detection of Antilipoidal Antibodies:” U.S. Patent Application Number 12/433,626; 3) “Compositions and Methods for Detecting Syphilis Using Synthetic Antigens:” U.S. Patent Application No. 13/333.849.

How does your work save lives/protect people/save money through prevention? 

In the past, the serological testing for syphilis has been performed in laboratory settings, requiring appropriate equipment and trained personnel to interpret results that may not be available for several days after the sample has been collected.  This can be a problem, especially in developing countries and in inner cities; patients may not receive treatment because they fail to return for the results of their laboratory tests.  In these cases, not only does the patient remain untreated, but the disease may be spread to others. By receiving the results more quickly through the “rapid test,” the clinician can make an immediate judgment on the necessity for treatment during a single clinic visit.

What is the biggest barrier you face in doing your work? 

The biggest barrier facing our work is how to transfer our technology to the private sector, where they have established manufacturing procedures that need to be adapted to accommodate and further the principles of our research. 

What is the most important thing for the public to know about what you do? 

The most important thing the public need to know is that their taxes are well invested in facilitating our research. Our development of new methods and techniques will in turn be beneficial to the public at large.

About Dr. Castro:  Dr. Arnold Castro served a tour of duty in the U.S. army as a medical laboratory technologist with specialty in blood banking, and he was stationed at the 42^nd Field Hospital in Verdun, France and at the Regional Medical Center in Landstuhl, Germany.  He became a U.S. citizen in 1965 and worked in the private sector until 1997 in immunohematology and microbiology.  While working full time, Dr. Castro attended night school and obtained an A.A.S. degree in Chemical Technology at the New York City Technical College and a BSc in Chemistry at the University of Miami.  He received his PhD degree in Microbiology from the Veer Narmad University, Surat, India. He also attended the University of Georgia graduate school in the Environmental Microbiology department.  He met his wife Helen in New York City where she was a nurse and married in 1960.  His son is a cinematographer and video tape editor, and his daughter teaches horse riding.

Dr. S. Patrick Kachur grew up on Ohio’s Mosquito Lake. He trained in preventive medicine and public health and has worked on malaria at CDC since 1995.

Meet Dr. S. Patrick Kachur, who oversees CDC’s Malaria Branch. Not only is the Malaria Branch the oldest program at CDC but with more than 60 staff, it’s the largest group of malaria scientists in North America. We recently talked to Dr. Kachur about his work.

What personal experience in your work are you proudest of?

I was fortunate to work with Kenyan and Tanzanian scientists on studies that proved how treated bednets and new combination medicines save lives–even in the remote communities hardest hit by malaria.

How does your work save lives and protect people?

Scientists in CDC’s Malaria Branch help set global and national policies to scale up malaria prevention and treatment.  As a result of CDC’s work, and the efforts of many of our partners, the number of deaths from malaria has fallen from more than 1.5 million to 655,000 in less than ten years.

What is the biggest barrier you face in doing your work?

Even though we have seen tremendous progress in combating malaria in recent years, this could unravel if political will and financial support fall off.  Malaria parasites and the mosquitoes that carry them are constantly adapting and we need to continue our current interventions as well as advance the science that will lead to new tools like the RTS,S vaccine.

What is the most important thing for the public to know about what you do?

CDC started the fight against malaria. Now let’s finish it together.

You can read more about Dr. Kachur and CDC’s malaria team in the CDC Works For You 24/7 article, Malaria Vaccine Trial: Behind the Scenes in Kenya, which describes CDC/Kenya Medical Research Institute’s participation in the RTS,S malaria vaccine Phase III clinical trial.