Mathuram Santosham, MD, MPH, ’75

Q: How do you see your legacy in public health—from the things you’ve accomplished to the ongoing progress around issues important to your career?

A: Dr. Santosham: When I was five years old, my father was in the Indian Foreign Service. He was posted to Nepal. And in those days, to get from New Delhi to Kathmandu, you went two nights on a train to Kolkata. Then you went on an overnight bus to the border. Then you were carried in a basket or you walked for seven days. I was carried in a basket.

Long story short, my mother took me to the local market in Kathmandu when I was five years old. I could see that many kids had draining ears, visible skin infections (impetigo), and were malnourished. It was obvious, even to a 5-year-old, that these kids were sick. My mother was holding my hands and said, “One day you should become a doctor and help all these kids.”

So that's been my vision all my life.

Specifically, I would say my contributions to preventing deaths and controlling diarrhea through ORS [oral rehydration solution]. ORS has saved something like 50 to 60 million lives. Now it'll be a mistake for me to say I'm the one who did all that, but I did make important contributions to this powerful intervention along with other scientists at Johns Hopkins like Bradley Sack and David Sack.

Another thing that I'm very proud of is my contribution to the control of Hemophilus influenzae type B disease—meningitis. It was a disease that every pediatrician and parent dreaded. When my kids were small, we didn't have the vaccine. I was terrified that they would catch this dreadful disease. Even with the best medical care, the chances of dying were between 5% and 10% and the chances of serious neurological consequences were 30% to 40%. In countries with poor access to care, the mortality was over 50%.

I never thought I would have the opportunity to work on preventing this disease throughout my career. I also never thought that I would end up working with a population that had one of the highest rates of Hib meningitis in the world. My passion became getting it to lower-income countries around the world.

Q: Can you tell me a little more about your work on ORS and Hib? 

A: When I was in medical school in India and was doing my Pediatric rotation, every day I would see many babies dying of diarrhea right in front of my eyes. I decided that I must get trained in Pediatrics. Since there were very few training programs in Pediatrics in India, I applied to the U.S. While in residency, I started working at the Baltimore City Hospitals with the Chief of Pediatrics, Dr. Harold Harrison. He was an expert on diarrhea as well as fluid and electrolyte balance. It was Dr. Harrison who inspired me to work on ORS. He was the first one in the U.S., in 1946, to show that ORS could be used to treat diarrhea. 

The problem with expanding the use of ORS to treat severe diarrhea at that time was that physicians from lower-income countries would ask what they should use to treat severe diarrhea. And we would say ORS. But then they would ask, what do you do for your kids in the U.S.? And then we’d have to say we don't use ORS, we use IVs. 

Fortunately, by this time I had met Dr. Bradley Sack who suggested to me that we should do a study in the U.S. to demonstrate that ORS could be as effective in children in the U.S. as in developing countries. He was able to find the funding and mentored me to conduct the first study in the U.S. to demonstrate that ORS works extremely well in U.S. children. After that, I did a series of other studies and I was invited to consult all over the world.

Brad Sack actually had a diarrhea program in India. After I finished my medical training at Johns Hopkins Hospital, he asked me if I would be interested in working on that program in Kolkata. I was so excited. But then a war broke out between Pakistan and India and all U.S. projects had to leave the country. I was crushed.

Q: What did you do? 

A: Brad soon after got an NIH contract to study diarrhea among the Apache Tribe who were dying from diarrhea at high rates. He asked if I would be willing to go to the Apache reservation for a year, and hopefully by then the political issue between the U.S. and India would get resolved. I talked to my wife Pat who was an anesthesiologist at Hopkins and she and I agreed that we should take the assignment for a year. 

When I arrived at Whiteriver, I was shocked to see the number of deaths from diarrhea on the Apache reservation. It was similar to the rates in several lower-income countries in Asia and Africa. Many children would come in with severe dehydration as a result of diarrhea and were often in a coma. My partner, Ray Reid, MD (Navajo), and I were shocked by the amount of deaths that we saw from diarrhea. We worked very hard to first train the doctors and nurses on ORS. Subsequently, we established a program to distribute ORS packets in the community. Within a couple of years, the diarrheal deaths had pretty much disappeared. 

Q: Can you tell me more about your work with the Hib vaccine? 

A: During one of the diarrhea epidemics on the reservation there were 5 cases of Hib in young children, three of which resulted in meningitis. I knew what the meningitis rates in Baltimore were and realized given the population of the Apache community, if the same numbers were occurring every year, it would be an astronomical meningitis rate—about 50 times the national average. So, I brought a couple of medical students who did a 10-year-chart review. Lo and behold, it really was that high. I realized that we had to do something about this. So, I went to the tribal council and asked if they realized there was a problem called meningitis among their children. I was surprised to hear them say, “Yeah, you mean brain fever?”

Then I asked if they had thought about doing something about it? And one of the leaders said, "Well, you’re from Hopkins, you tell us what we can do."

I consulted two national Hib experts, Richard Moxon and George Siber, about handling the problem. There was nothing at that time for children under 2 years of age. The available vaccines did not produce antibodies in children under 2, and 90% of children with Hib meningitis in the Apache population were less than one year old.

That set me on a path to working on this disease for the next four decades. 

Fortunately for us, the next generation of vaccines became available shortly and they did produce antibody levels in very young infants, even below 6 months. I received funding to test all of them, and the one that seemed to produce the best response after a single dose was by Merck, called PedvaxHIB (PRP-OMP). This was important since 50% of cases on the Apache reservation occurred in infants below 6 months of age.

Together with our Indigenous partners, we conducted a study to evaluate the Merck vaccine and demonstrated that it was more than 90% efficacious and had almost no adverse effects. Based on this study, the vaccine was then licensed in the U.S. We then aggressively introduced the vaccine in both the Apache and Navajo reservations. Once it was introduced to the Apache and Navajo communities the disease rates just plummeted. The disease rates also dropped dramatically in the whole of the country. 

Even though I was delighted that the rates of disease on the reservation and the rest of the country dropped dramatically, I wanted to make sure that the poorest children in the world, especially those in my country of origin—India—had access to this life-saving vaccine. I got a large grant from Gavi and by the time we finished that grant almost every country in the world was using it, which is amazing. And that disease is pretty much gone in most countries with good vaccine coverage.

Q: You deserve much credit for the Hib vaccine being introduced to India. Can you share a bit about that process? 

A: At the time, India would not accept foreign vaccines. We had a meeting at the Indian Council of Medical Research, which is equivalent to the NIH here. We brought in the Ministry of Health officials, academia, and all the thought leaders in the country together to discuss this vaccine. After many hours of discussion, they finally said, "OK, then you have to show us there's enough disease here and that the vaccine works among Indian children before introducing the vaccine. You need to do a study." So we got money from Gavi to do a study in India. But by the time we got the study ramped up, there was so much of the Hib vaccine being used successfully in the private market that it no longer became ethical to randomize children in our study.

I again went to the ministry and said that I as a researcher love to do studies, but I don’t think it is ethical to be doing studies on this disease. We need to vaccinate the children. By 2008, the ministry had tentatively agreed to introduce Hib vaccine into the country. All that was needed was for the secretary to sign the agreement. Unfortunately, it was the secretary’s last day before retirement and he said the new health secretary should sign it. The new health secretary was completely against the introduction of the vaccine and she reversed course. From 2008, it took us another six years of work to get Hib vaccine into the country.

Q: You’ve mentioned before that you noticed that doctors and public health people are not always good communicators. What brought that to your attention and how did that impact your own communication? 

A: That realization came to me primarily for myself. I thought, my goodness, here's a vaccine [Hib] over 95% efficacious with almost no side effects and we had funding support from Gavi for countries that could not afford it. This is a piece of cake. All I need to do is walk into the Ministry of Health in India and say here's the data.

In fact, the very first time I went to the ministry and talked to the health secretary, I presented the data. He asked me how much it cost. When I told him how much it cost per dose, which was $18, he looked at me like I was nuts. He said, “Dr. Santosham, you've been out of India too long. You don't understand our country. We spend about 30 cents per child on all the vaccines we're giving to children now and you want me to come up with $18 per dose?”

There's so much miscommunication between scientists and politicians. We talk about rates and use technical terms like Haemophilus influenzae type B (Hib). We say the mortality rate is 60 per 100,000. When you present it that way to many politicians, they'll say, “Sixty deaths, that’s nothing, there are thousands, if not millions, of kids dying from other diseases.” 

I realized then that we have to learn how to speak to politicians because they have the most influence. So, we went state by state in India and spoke to parliamentarians from both sides, because if you get only one party on your side, the other party will defeat the initiative. We also identified thought leaders in each state and got them on our side.

My team travelled around the country speaking to politicians. We made the data personal. Everybody cares about their families. We got enough momentum going and politicians started raising the issue in parliament and demanding that something be done to prevent children from dying from vaccine-preventable illnesses like meningitis. 

Q: Continuing with communication, if we think of public health in terms of pre-action, action, and reaction, how have you worked with communities around vaccines?

A: Let's use the Hib vaccine as an example. The vaccine is recommended at 6, 10, and 14 weeks of age. It happens to be the time infants can die from sudden infant death syndrome. 

If you vaccinate the whole population, some kids who have received the vaccine will die maybe one or two days after receiving the vaccine, and then the vaccine will often be blamed, incorrectly, for that death.

Therefore, you have to educate all key stakeholders ahead of time. You have to work with academics, the ministry, and the local communities at the grassroot level to be prepared for these types of issues before they occur. 

Q: Mentorship has been a hallmark of your career. It's incredible to think of your continued impact through the remarkable public health careers of your mentees. Can you mention a few of your mentees you’re most proud of? [As we noted earlier, Mathu preferred speaking of his colleagues and mentees during our conversation. We’ve listed a few of the ones he mentioned. Mathu told us many interesting stories about them that we may release in future issues.]

A: I’m proud of all of them. I’ll mention a few in no particular order. 

• Kate O’Brien, Director, Department of Immunization, Vaccines and Biologicals, WHO
• Richard Besser, President and CEO of the Robert Wood Johnson Foundation.
• Samir Saha, Head of the Department of Diagnostic Division of Microbiology at the Dhaka Shishu Hospital for Children; Executive Director of The Child Health Research Foundation, Bangladesh Institute of Child Health 
• Allison Barlow, Executive Director, Johns Hopkins Center for Indigenous Health, Research Professor, Department of International Health, Johns Hopkins Bloomberg School of Public Health
• Abdullah Baqui, Professor, Department of International Health, Director, International Center for Maternal and Newborn Health, Johns Hopkins Bloomberg School of Public Health
• Bill Moss, Professor, Departments of Epidemiology, International Health, and Molecular Microbiology and Immunology, Executive Director of the International Vaccine Access Center, and a Deputy Director at the Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health
• Gary Darmstadt, Professor (Teaching) of Pediatrics (Neonatology), Stanford University
• Laura Hammitt – Professor, Department of International Health, Director of Infectious Disease Programs, Center for Indigenous Health
• Christopher Duggan, Professor in the Department of Nutrition, Harvard T.H. Chan School of Public Health

There are really too many to mention here. I would also like to mention a few of my mentors: Carl Taylor, Tim Baker, and Bradley Sack. Not only did they help build this Department, they helped shape my career. 

Q: How do you see the role of the Department changing in the larger global health space?

A: I think the Department has been an exemplar of how to do global health respectfully and effectively.

I think the global donor community is also going in the right direction, but nothing happens overnight. I think it is appropriate for funders to give funding directly to institutions in LMICs, but they also need to fund groups that can provide technical assistance in areas where capacity may still be low. I think that the time has come when we start to play more of a consultant role, more like a technical advisory group.

Also, let's just remember there's a lot of public health needs in this country and it seems like the Department is doing more and more domestic stuff. I actually think global health can be done in downtown Baltimore as well as globally.

And many of the things that the Center for Indigenous Health has done around early education during pregnancy. I think those are the things that need to be scaled up around this country and around the world. And some of the mental health interventions—which my mentee Allison Barlow has led—that have been done on the reservations, I think they are badly needed around the world right now.

Our conversation continued during which Mathu suggested faculty and alumni to feature in this IH Legacy Series. We also learned more about the accomplishments of Mathu’s colleagues and mentees, some of whom are mentioned above. But, this first IH Legacy story is meant to focus on Mathu, who has contributed so much to individuals, the Department, the School, the University, and public health across the world.

It was such a pleasure to speak with him. His legacy will be felt for years to come and in so many different ways—including through the Mathuram Santosham Chair in Native American Health, currently held by Victoria O’Keefe, Johns Hopkins University's first-ever tenure track faculty member of Native American heritage.

-May 16, 2024