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Children’s ward in the National Hospital, Kampala. |
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| Dr. Benjamin Warf, Professor of Neosurgery, Harvard Medical School |
He also founded a hospital with the help of CURE International, a charitable organization which builds children's hospitals worldwide. Most of them are orthopedic, but Ben was a neurosurgeon for children. And this would be the first and so far only dedicated hospital to children's neurosurgery in the developing world.
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| Dr. Moses Ochora, Pediatrician at Mbarara University of Science and Technology, CONRIM-U project investigator |
While there Dr. Warf discovered a strong correlation between the Hydrocephalus (“Water on the Brain”) cases he was seeing in infants there, and an infection early in life. These infections also seemed to correlate to instances of Neonatal Sepsis (a severe infection in the first month of life). He began doing studies.
The standard treatment for hydrocephalus was to put in a shunt, which drains the fluid in the brain to the abdomen. But shunts can have up to a 30-40% failure rate each year, and when they fail it can prove fatal unless the infant can get to a hospital right away – a dim prospect in the remote villages in Uganda.
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| Grace Nakato, one of 800 recruits for the Village Health Team |
There is another common treatment called ETV (Endoscopic Third Ventriculostomy), which didn’t provide as much success as Dr. Warf hoped for. So he added another older procedure called CPC (Choroid Plexus Cauterization – don’t ask) and his success rate markedly increased. And if the procedure did fail, there was more time to get to a hospital.
Ben first reported this finding in 2005 in the Journal of Neurosurgery. He had single handedly alerted surgeons throughout the world that they should reconsider current practice for hydrocephalic infants, and that there was an important voice for improving the surgical care of these children throughout the world coming from a small hospital in Eastern Uganda. Ben received the MacArthur Prize (the ‘genius award’) for his work on infant hydrocephalus in 2012. He is now the Director, Neonatal and Congenital Anomaly Neurosurgery, and Professor of Neurosurgery, Harvard Medical School.
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| Inside a neonatal NICU. The hospital is on a shoestring budget but hope lives here. |
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| Premature twins at the Jinja Regional Referral hospital. |
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| Dr. Steve Schiff, Harvey and Kate Cushing Professor of Neurosurgery at Yale, Vice Chair for Global Health in Neurosurgery, and Professor of Epidemiology in School of Public Health |
Dr. Schiff had always wanted to do work in Africa since he was 11. While in Uganda he noticed that every day there would be at least 2 or 3 of these babies with large heads coming from all over the country in the arms of their mothers to the door that hospital.
At the end of the week, Steven looked at Ben and said, “Ben, you have a lot of problems practicing neurosurgery here in Africa. What's the most important problem you can't solve?”
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| Dr. Abraham Muwanguzi, PhD Manager, Science and Technology department, NPA; Team Lead – Policy and Planning, Office of Science, Technology and Innovation Secretariat, Office of the President, Uganda |
“Well, Steve, maybe you could help figure out what makes these kids sick.” And Steve immediately replied, "Okay". “How hard can it be?” he asked himself, naïvely.
Turns out it was plenty hard. The first problem was getting funding. After many failed attempts, he landed a high-risk, high-reward research grant from the National Institutes of Health (NIH). He says it was a blessing because nobody knew how to solve this problem.
“Shockingly, we have little idea what the majority of the pathogens are that cause young infants after birth to get infected”, says Steve. “And the numbers are hard to come by. We think we lose anywhere from half a million to maybe three quarters of a million newborn infants in the first four weeks of life to infection around the world. I've testified to Congress about that.”
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| Henry Masengere, Microbiology Lab technician |
It took 20 years for Dr. Schiff and his team of diverse experts to find the cause of the infections: It is a new strain of a bacteria that was previously thought to be harmless, Paenibacillus thiaminolyticus, which the medical community had known about since 1950 but this is a much more difficult strain. It’s difficult to culture and grow using conventional methods. It eats Thiamine. It grows spores, so it might be as lethal as Anthrax to those who come in contact with it. And it was found in the brains of the infants at 2 or 3 months of age, when they came in for treatment.
Now What?
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| Ronnie Mulondo, Associate Research Scientist, Yale School of Medicine, dept. of Neurosurgery |
With the Paenibacillus bacterium identified, Dr. Schiff is now in the process of shifting gears: he is now on a dual mission to discover better treatments, and also to understand how these children are getting infected to begin with. Is it the soil? Something in the water? Is it being inherited from the mother? (That last option has been ruled out.) Could it be the practice of putting various materials (sometimes including cow dung) on the babies' open umbilical cords just after birth?
Dr. Schiff has been working the political end of the spectrum as well, since you just can’t show up in an African village and say, “Hi, your babies have a had a bad infection and we'd like to learn where it comes from and put holes in your farm fields and test your water and the dung from your animals.” The people there are incredibly poor, and most of these villages don't have running water or electricity. They're trying to raise their children in these difficult environments. “We’re working with villages where children with these conditions have terrible early starts to life and often suffer the stigma of being a diseased or disabled child. So we have to have a lot of sensitivity.”
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| The team at the children’s ward at Madhvani Childrens' Hospital. |
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| Dr. Jessica Ericson, Pediatric Infectious Diseases physician at Penn State University |
So he is setting up a massive field project in Uganda in one of the worst hit areas from these infections. To this end his team has just recruited over 800 people for their Village Health Team (VHT) army, whose job will be part prenatal care and part medical ambassador to the villagers who are skeptical of modern medicine and often prefer using traditional healers. “People in my village never wanted what we call immunization”, says Grace Nakato, one of the VHT members who has been working as a medical ambassador since 2008. “But through education, step by step people are beginning to accept the idea. Same with counseling for HIV and family planning. Pregnant women never went to hospitals before either. It was said that pregnant women shouldn’t use the toilet because the baby might fall into it. Now they are getting neo-natal care at the hospitals starting at 8 weeks before birth.”
“The VHT’s will be our eyes and ears on the ground”, says Dr. Schiff. “It should result in higher immunization rates, we'll be able to monitor and observe almost every case of neonatal sepsis and another preventable condition, which is a congenital abnormality called neural tube defects or spina bifida, those are children who are born paralyzed and usually develop hydrocephalus. The very best thing we can do is prevent as much of those types of diseases as possible.”
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| An advanced Hydrocephalus case. |
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| Ray Ruddy, Board of Directors for Maximus Inc, Grantor at Gerard Health |
“I personally believe that Dr. Schiff’s discovery, after 20 years of research, of the bacteria that causes infectious hydrocephalus in this region of Africa is worthy of the Nobel Prize in Medicine. However, realizing that Nobel Prizes are generally provided for actually curing diseases, we still have a way to go”, says Ray Ruddy, the founder of Gerard Health Foundation who has become an important funder of Dr Schiff’s current efforts. “The Gerard Health Foundation was founded with one objective only, and that is saving lives. And the most lives we can save the better.” Ray’s foundation had funded HIV AIDS prevention in Uganda more than 25 years ago, and also been supporting hydrocephalus operations out of one of the CURE Hospitals. He hooked up with Dr. Warf once he introduced the ETV-CPC process as a more effective treatment of hydrocephalus. And that connection led to meeting Dr. Schiff.
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| Dr Harriet Nambuya, Head of Pediatrics, Jinja Regional Referral Hospital |
Mr. Ruddy takes an unusually hands-on approach for being a grantor, accompanying Steve on trips to Uganda, understanding the medical issues deeply and also helping smooth over any political issues. And he was very excited when he learned about the bacterium that was the source of the infections. “Once you uncover the bacteria that causes hydrocephalus, you're able to work with Big Pharma to try and cure it without an operation. And in addition, you can find where it exists in the well or in the soil. It represents a tremendous ability to eradicate hydrocephalus off the face of the Earth. It's wonderful!”
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| Dr. Starlin Tindimwebwa, CURE Children's Hospital |
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| Dr. Schiff and the King of Busoga in 2024. The King is backing Dr. Schiff’s work by providing resources and office space near the Parliament building. |
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| Judith Mutabazi, a senior planner in charge of Health Policy at the National Planning Authority |
Unfortunately, with a newly discovered infection, especially one so lethal and destructive as this one, there is still a lack of good guidelines to tell physicians the best way to treat this (like which antibiotics are best, how long should they be used for, etc.). “I had thought that once we answered Ben’s question about what made these kids sick we would be done”, says Steve. “Instead, we now face innumerable critical questions to follow: which antibiotics are best, how long to use them, are there other medications that would be important to add, and what would be the best way of timing surgery with antimicrobial treatment.”
The successful outcome of this large undertaking cannot be guaranteed. But time is of the essence since similar cases of these diseases are starting to show up in the U.S.
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| This young girl was born with Spina bifida. She had surgery and then developed Hydrocephalus (water on the brain) after 4 months. The mother hasn't been to a hospital for follow up for about a year due to lack of funds and transportation, and the baby's head is large with accumulated fluid. Dr. Schiff and the team arranged for the girl and her mother to attend the CURE hospital the next day. |
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| The mother of the above girl. She has five other children at home, and she had to choose between paying school fees for the children or getting the 6th child to the hospital. |
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| The 3-month old boy in the striped shirt is named Peter. He is a typical case of neonatal sepsis. At about 3 days old he developed a fever and excessive crying, and eventually his head started swelling. He eventually went to the CURE hospital, where they first performed an ETV and then they installed a shunt when the ETV failed. |
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| Dr. Schiff addresses some of the 800 Village Health Team members that have been recruited for outreach and “being the eyes and ears in the villages”. This meeting occurred in Jinja, a part of Uganda where the incidence of deaths is abnormally high. |
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Ray Ruddy and Steve Schiff talk logistics. |
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One of the big problems of treating this recently identified bacterium (which is the root cause of so many infections in newborns) is that it is difficult to culture, and difficult to grow in the lab. Once those are done, though, it can develop spores which, like Anthrax, might be fatal to the hospital staff and others who come in contact with it. Pictured is Sophia, one of the lab technicians at the Jinja Regional Referral Hospital, with a state-of-the-art Bactec Blood Culture machine for the rapid on-site detection of a variety of bacterium. Dr Schiff is working closely with Sophia to ensure that they take a very high level of precautions in efforts to grow the new bacterium safely in her laboratory |
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| Medical ward in the National Hospital, Kampala. |
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This is a portable, low-energy MRI machine. It costs about $500,000 USD compared to millions of dollars for conventional MRI machines which can take up the space of an entire room. One of the tradeoffs is that the images are low resolution compared to their larger bretheren, but a person familiar with the kinds of infections being sought should have enough information to make a diagnosis. The team is experimenting with running the low-res image through an AI program to up-res the scan based on a boatload of training data. Upon hearing this, the following conversation took place: Me: "You know there's a risk of the AI hallucinating, resulting with false diagnoses that could lead to unnecessary death, right?" Dr. Schiff: "Yes, that is certainly a concern." Me: "Since you're writing your own software, why not have the AI program scan it's training set and flag any new scan that doesn't match, saying "Insufficient information to make a diagnoses. Please try a more conventional method."? That should cut the hallucinations to zero." About 10 seconds silence occurred before Dr. Schiff gave his answer: "We hadn't thought of that!" My work here is done. :-) |
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| Part of the traveling bus entourage. Carol and I are centered. |
Trying to Identify the Source
This was the 4th remote village that Dr. Schiff and his medical team had visited, as part of a multi-disciplinary effort to find out why there have been so many newborn infections, which if infants survive long enough can lead to Hydrocephalus (water on the brain) requiring surgery. Is it in the water? The soil? Through the mother? Traditional after-birth practices that have been used for thousands of years, and still persist despite the heightened risk of infections?
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| Dr. Carmit Cohen, a veterinarian and a microbiologist, joined the team on this trip. |
To find out, a multi-pronged master plan was devised:
1) An army of Village Health Team (VHT) workers has been assembled to go out to the remote villages and canvas the health of the babies, filling out questionnaires on their cell phones and electronically sending the results to a central database.
2) On-site sampling of the environment including soil, water, and animal feces.
3) Creation of a Geographical Information System to understand correlations between measurable ground conditions and increases in the infection rates.
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| The field team. Missing from this shot is Dr. Ericson, an infectious disease specialist, who flew in a day later. |
What Took so Long?
“I think it went rather smoothly”, Dr. Schiff responds. “We had to assemble a team of laboratory technicians and set up the lab. We had to assemble an army of about 750 volunteers to form the Village Health Team, we had to create the electronic questionnaire, the database and the dashboard to help us visualize all of the data in real time. Then we had to get permission to do all of the field work.”
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| Everything is being measured. |
It turns out that getting the permission took the greatest amount of time, starting with the Ugandan ethics committee. "They very carefully went through all of our proposals, asked us questions, we would respond, and revised our proposals, and finalize the proposals and consents. The consents are also translated into local languages. In the end, there were, I think, 31 documents that had to be approved.”
“Once that’s done it goes to the Ugandan government oversight agency, the Ugandan National Council on Science and Technology (they’re responsible for all of the ethics committees). It takes them awhile to review things. Then when they approve, it all goes to the United States’ Institutional Review Board. They have more questions. They want other changes to be made. So we went back and forth a few times with our ethics committee, and in the end we have to unify the protocols. Separate consent was also needed for the electronic questionnaire and consent to sample from the homes and village that we developed.”
Who knew? 😊
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The Field Work Begins
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| After the interview, the mother is thanked with a care package consisting of diapers, crackers, sugar, and rice. |
“When was the baby born?”, asked the Village Health Team volunteer. “Was he or she healthy? Does/Did the baby have any of these symptoms?”, and then a whole laundry list of possible problems were listed: fever, fast breathing, not feeding, convulsions, redness around the umbilical stump…
Now that the surveillance was fully approved, this was the first opportunity Dr. Schiff had to actually witness the VHTs in the field conducting the study and examine the conditions the babies were living in. In doing so, some problems with the way the questions were written began to surface. Some of the names of common medications were unknown to both the mother and the VHT member. And the experience of the young mother who had a stroke prompted changes to the survey, to ask whether the postpartum mothers are ill, or to report whether a mother has died following childbirth. The purpose of this survey is to just gather data; there is no budget for actually arranging for medical transport or to pay for health services. The team intends to layer onto this surveillance system strategies to substantially reduce the preventable causes of neonatal and infant mortality that they are focusing on: infections and congenital malformations such as the open spines of Spina Bifida.
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| The walls are made of a mixture of mud and cow dung. Could this be a source of some of the infections? |
During my visit, four villages were visited to perform sampling of the soil, water, animal feces, and to look for any other possible source of infection, such as the walls of the dwellings which are made up of a combination of mud and cow dung. The team was joined by Dr. Carmit Cohen, a veterinarian from Israel who’s also a molecular biologist. (“Because what do us surgeons know about cows?” Dr. Schiff jokes.)
The villages are all completely off the grid and self-sufficient in terms of growing food and livestock. Everyone wore western-style clothing and most had access to a cell phone; solar panels on the roofs provided a means of charging. The children roamed carefree and seemed happy. It was quite picturesque.
Cultural Barriers
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| Looking for correlations in mountains of data at the Jinja Regional Referral Hospital. The left side is a map where all 60,000 villages in Uganda were fused with the satellite climate map grid, and mapped onto it were the locations of 20 years' worth of postinfectious hydrocephalus cases. The right graph suggests an increase in hydrocephalus when the rains come two weeks before birth. |
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| Henry Masengere and Dr. Ericson prepare the samples for lab testing. |
In addition to the environment, there are many traditions, some of them thousands of years old, that are making the problem worse. One is the practice of placing foreign materials (sometimes including cow dung) on the open umbilical cord. One is the use of a traditional birthing attendant, which was outlawed in 2010 due to high maternal and child mortality rates, which were attributed to poor hygiene, unhygienic conditions, and a lack of training. (They are sometimes still being used despite the ban.) Then of course there are the traditional healers which often make matters worse. Add to that the lack of access to supplements to prevent malformations, and medications to treat infections, and this kind of mission becomes a real uphill battle.
The traditional healer incident described at the beginning of this story has already catalyzed some progress. After some tense phone calls, they now have an agreement in place with the traditional healers to meet and discuss working together and avoid incidents like this in the future.
Other Images
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| Ready for testing |
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| A short meeting takes place in the break room at Mulago National Hospital, where the autoclave had previously exploded. |
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| New mothers in line to have their infants examined. It's hard to tell if the babies have fevers, or they're too bundled up in this 80 degree F heat. |
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| Cow dung was tested too... |
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| An underground spring is the source of water for this village. |
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| This all proved to be interesting work. :-) |
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| Prepping the sample for a deep freeze so it can be safely transported to the lab in the U.S. |
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| "The Dashboard" - a web-based interface to the database of data being collected. Here you can visualize locations of outbreaks, with overlays that include weather and temperature. |
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| Ward 7 of the Jinja Regional Referral Hospital |
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| When hospital wards are full, they put the excess on mattresses in the hallway. |
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| Drs. Schiff and Ericson examine a premature baby with a growth at the base of her spine. After birth she had a little difficulty breathing which is typical of premature babies because their lungs are underdeveloped. She was born on an island on one of the lakes so they took a boat to the mainland and then went to a lower-level health center. They were then referred to a regional hospital so they then took a motorcycle taxi to the regional hospital. She’s now getting oxygen for her respiratory needs. The rather large 2-inch “squishy mass” at the base of her back prompted concerns about either a type of spine defect or perhaps a type of tumor that can be hard to distinguish from a spine defect without special imaging. So once her respiratory illness is improved, she’ll be sent to one of the hospitals that has a CT scan and a neurosurgeon to have either the defect repaired, or an associated tumor removed. |
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| The growth at the base of the spine. |
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| Dr. Ericson consults with a nurse about a new premature baby. |
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| Dr. Cohen, an Israeli, has been around the world but this was the first country to be excited about her visitation. Christianity has a strong presence here, and people got excited because Israel is the place where all of the biblical stories they've been reading about takes place. "I'm in recovery; can you bless my journey?" |
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| Dr. Cohen obliged. |
Epilogue
Dr. Schiff's work continues, both in Africa and Vietnam, despite some funding challenges from the NIH. Some of that shortfall is made up by some very gracious private donors.
As of this writing, the lab samples are in frozen storage, waiting for transport to Yale to be arranged. It might be months before the tests results are known.
Tests from last year have ruled out the infections happening through the mother.
Environmental infections should be preventable, and Dr. Schiff wants to craft policy to address the sources and routes of infection that they identify. The Dashboard lets the team, and the Ugandan and Kingdom collaborators, see right away if policies are reducing the number of newborns that fall ill or not. Schiff is hoping to start the first infection prevention trials soon. Preventing the malformations will require additional studies which he hopes to begin organizing soon.
In the end, the goal is to have a major impact on these preventable causes of infant mortality in regions of sub-Saharan Africa such as this where infant mortality rates are far too high.
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For more shots of Jinja and its people, please have a look at the youtube video I shared with you last month - it will give you a really good feel for this trip.
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