By: Aryeh J. Price
Dr. Benjamin Warf, a MacArthur Fellow, directs Neonatal and Congenital Anomaly Neurosurgery at Boston Children’s Hospital and is an Associate Professor of Neurosurgery at Harvard Medical School. In this capacity, he has improved survival and quality of life for hydrocephalus patients by designing an innovative, highly effective surgical technique named endoscopic third ventriculostomy-choroid plexus cauterization (ETV-CPC). Dr. Warf’s influence extends well beyond Boston through his research and clinical work in Uganda and the trans-continental neurosurgical education network he has created.
In addition to his extensive hydrocephalus research, Dr. Warf published the largest ever epidemiological brain tumor series out of Africa based on cases seen at the CURE Children’s Hospital of Uganda. The article, “Presentation, pathology, and treatment outcome of brain tumors in 172 consecutive children at CURE Children’s Hospital of Uganda. The predominance of the visible diagnosis and the uncertainties of epidemiology in sub-Saharan Africa”, appears in the Child’s Nervous System journal. This pioneering paper attempts to provide a robust epidemiological analysis of pediatric brain tumors in Uganda and in the process reveals inherent bias in sub-Saharan African datasets. Dr. Warf’s notion of non-obvious brain tumors remaining undetected and his comprehensive clinical analysis will likely guide future neuro-oncological efforts in Uganda and have generalizability to the rest of the developing world.
1. How would you describe the structure of the health system in Uganda?
The ministry of health has organized a healthcare system into multiple tiers, beginning with rural clinics and then district hospitals, which then feed in to regional hospitals that cover several districts. Things they can’t handle are supposed to get referred to the national referral hospital in Kampala, which is the university hospital. They do a pretty good job with organizational structure, but there are a lot of gaps in the structure that don’t get filled. For instance, you can get referred to a regional hospital and find that there aren’t any doctors there that day, or that they are all at their private clinics. The regional hospital in our area, where we have pediatric neurosurgery was lacking in basic laboratory facilities and x-ray machines. They didn’t have an EKG machine either. So, the structure is there, but there are a lot of big gaps.
The other challenge is funding. Although it is government-funded healthcare, patients are still asked to contribute, and they often just don’t have the resources to pay what they are being asked to pay. Even at the tertiary level, there are big gaps in terms of supplies and organization and things often don’t get done that need to get done.
2. What are the dominant challenges to health care delivery in Uganda?
Poverty—which affects many things. There is a lack of funding at the government level in terms of being able to invest in the healthcare sector. There is a lot of dependence on NGOs and mission hospitals. At one point in recent history when I was in Uganda, the ministry of health said that 60% of the healthcare was delivered by non-governmental type agencies like our hospital. But there is poverty on the patient side: people can’t travel, and they can’t pay for their care when they get to a hospital. There is just a huge breakdown from stem to stern.
Education is also an issue. You don’t know to take your child to the hospital for a particular problem, or you go to a local clinic and your child has a fever and they empirically treat for malaria (because it is so common), but it may well not be malaria. One of the things that we saw specifically, and that we were able to make an impact on just through public education, was in the area of hydrocephalus
In my first year at CURE children’s hospital of Uganda, a lot of the children that were being brought in for treatment had enormously large heads and a lot of past-the-point-of-no-return brain damage, so some of the treatment of those children was more palliative than anything. Most of the brain tumors that we saw and continue to see are of the sort that I call, having a “visible diagnosis”. Either there is obstructive hydrocephalus from a brain tumor and the baby’s head is getting bigger, or there is a lump growing out of the head.
3. What unique challenges are associated with surgery in resource-poor settings? How is the typical operating room outfitted?
The typical operating room is often lacking in modern anesthesia. In some of the government hospitals you can still smell ether in the hallways because they are using drop ether (like we did in the early part of the twentieth century). The operating rooms in many of the hospitals that I have visited are also not as clean, closed off and well maintained as operating rooms in more developed countries. They don’t have a lot of basic instruments and access to more up-to-date, newer techniques such as endoscopic methods of surgery. Patients usually have to purchase the basic supplies like IV fluids and surgical gloves. There is a lot that’s missing.
What there are plenty of are surgeons who are trying to do the best they can under difficult circumstances and are committed to trying to make things better. They are eager to learn and are very happy to get additional supplies and materials that they might not have access to otherwise. The government just doesn’t have the resources to fund it. Unfortunately, a lot of government funding goes to the military. In the private sector, the patient population doesn’t have the money to support a privately funded healthcare enterprise like we have here in the US. There is no health insurance so a lot of healthcare gets done out of the good will of NGOs, which run off of donations from outside the country.
Another challenge is the nursing culture. When we started CURE Children’s Hospital in the little town of Mbale, Uganda, it was a whole separate enterprise of hiring and re-educating nurses. We had to address knowledge that had been missing in their education but also certain standards of quality that just hadn’t been demanded before, including those in the operating room.
4. In the context of such basic educational deficits, task-shifting wouldn’t seem to have been a pragmatic option. Was it attempted at any point?
Actually, task-sharing turns out to be very important. One of the ways we saw this being played out in our own hospital was that we learned to identify people with good work ethic and who were reasonably sharp and eager to learn. A good example is one of our best scrub techs right now, who is terrific; he gets everything exactly right, he knows what to do, he knows what the next step is. His first job at the hospital was cutting the grass. He slashed the grass with what’s called a ponga, it’s a curved blade that they swing like a golf club.
One of the early people that we hired was a young woman who had had a terrible upbringing. She had been an orphan and had been in some abusive employment circumstances before we hired her as a cleaner for the hospital. We noticed that she was a very hard worker and she happened to speak about a half-a-dozen of the local languages. She was bright as a penny so we advanced her from mopping the floors to being the ward clerk. She did such a great job at being the ward clerk that we put her as the coordinator of the outpatient department. She didn’t even have a high school education. During that course of time we helped support her completion of her education and then she went on from there to go to nursing school and now she is a nurse. So just because you have been a nurse for twenty-five years doesn’t mean that you are the best person for the job always. We try to keep a lookout for local talent and have had many people with that kind of story, moving through the ranks and being identified as good people to support in their education.
5. How does overall survival of brain tumors at CURE compare to elsewhere in Africa and the world? Are the modalities of treatment and the ultimate outcomes distinct from the first world?
We don’t know how they compare to other places in Africa because there have been very few reasonable-sized studies out of sub-Saharan Africa that did survival analysis or looked at long-term follow-up in any credible way.
How does it compare to the developed world, our own experience in Uganda? It’s directly related to whether or not the tumor required adjuvant therapy. For the children that had non-malignant tumors that were resectable they compare favorably, very well and in some ways, one example is there is a type of brain tumor called a craniopharyngioma, which is non-malignant but it’s difficult to operate on without hurting the brain. It gets all stuck at the base of the brain and to radically remove those often has a collateral effect: endocrine damage. Some of those kids survive, and they are tumor-free, but they have a very poor quality of life.
In Uganda we didn’t have access to endocrine replacement therapies. So we couldn’t do those kinds of radical tumor resections and we were more conservative, did de-bulkings but didn’t try to radically remove the tumors and would send the children for external beam radiation therapy at the so-called cancer institute in Kampala. We found that we had an excellent survival rate. There has been a trend towards becoming more surgically conservative in this country as well but there we were forced into it because we couldn’t be surgically aggressive.
Kids with malignant tumors like medulloblastomas, don’t do well. They die. But we can’t make the diagnosis without operating on them and taking the tumor out. We give temporary relief. We send them to the oncology centre in Kampala but they just have very basic tools, very basic chemotherapy agents, external beam radiation, whole brain and spine radiation.
Neuropathology is also problematic. It was difficult to know sometimes if the pathology diagnosis was really spot on because there was no neuropathologist in the country. It was a general pathologist at the university who we used to pay to look at slides and did the best we could. They didn’t have any of the diagnostic tools that our neuropathologists have here in terms of genetics or antibody stains and so-forth. Almost at every level, every link in the chain is weak. It makes it tough.
One final thing I’ll mention is that the kids often aren’t in very good shape when they get to us. They can be malnourished, they can be very anemic- often from malaria. And so they may not be ideal surgical candidates in the beginning when we have to take time to sort of bring their nutrition up to speed before they can tolerate having surgery.
6. How do brain tumor patients ultimately arrive at CURE? Do emergency personnel bring them in for acute events or do they independently seek treatment after exhausting the list of-ineffective-alternative therapies?
It’s the latter. We get very few referrals through the healthcare system. It’s almost all word of mouth, self-referral by the families. They know that we are the “head hospital”. If they see something wrong with the head that has been bulging out for the last six months and is getting bigger or the eyeball is progressively bulging out of the head or the nose is obstructed by a mass and they are having trouble breathing, those kinds of things will happen self-referred. We rarely, occasionally, but we rarely got a more typical kind of case of a child who is referred to us because they have had a seizure or because they have had some progressive neurological weakness.
The other things that hold back their referral is the traditional therapies. There is a lot of traditional medicine, what they themselves call “going to the witch doctor” which involves various rituals, killing chickens, cutting the scalp, rubbing animal manure or some kind of herbs into the cuts. They treat the affected area, what they see. A child with a lump more often than not will have scarifications on the lump on the head, on the back, wherever. The family often has exhausted their major resources to pay the witch doctor before they finally make it to us. That also delays treatment.
7. Is the neurosurgical staff predominantly comprised of local employees or are neurosurgeons brought in transiently from abroad? Are there many rigorous surgical training programs in place?
At CURE Children’s Hospital of Uganda the whole staff is Ugandan. There is one American there right now who is the executive director who was hired by CURE international and is responsible for financial matters, human resources, local raising of funds, and that sort of thing. But our two neurosurgeons there now are Ugandan-both of whom I was involved in training, but that’s really where we are at.
I don’t like, and a lot of people do this (and some people don’t like when I say this), but I don’t like so much what I call somewhat pejoratively “hit and run surgery” where a team goes in with the following approach: “line the patients up, we are going to have a surgical camp, put shunts in kids with hydrocephalus and we’re going to see if there are any brain tumors to remove”, that sort of thing. The best model clearly, in my opinion, is developing expertise locally for the long-haul. Our two neurosurgeons there now are excellent. They both got their basic neurosurgery training at the University of Cape Town. When I go back, I don’t go back actually to help them, they don’t really need me, which is great, we were able to dispense with my being important.
In terms of rigorous neurosurgical training programs the best one on the continent is at the University of Cape Town and there is another one I think in Johannesburg in South Africa that I don’t know much about. The other one is in North Africa which is in Morocco. Then there is kind of a fledgling, loosely structured neurosurgical training program in East Africa which I was actually on the original board of to try to start it up, but it hasn’t gone as well as I would have liked. That one involves hospitals in Nairobi, Kampala, Dar-Es-Salaam, and Ethiopia in Addis Ababa. It’s not what we would consider high quality or rigorous but they have started a training program. When I first went to Uganda there was no East African training program. They are trying.
8. How do you envision cancer care for brain tumors becoming sustainable in the long run?
Well, training neurosurgeons, training primary care doctors to think about and being able to clinically be suspicious of a brain tumor, increasing access to neuroimaging, increasing access to neuropathology that is competent-that doesn’t have to be onsite. Today it could be putting a slide under a microscope and sending the image to a neuropathologist in Canada or Germany if people are willing to interact in that way and then read out pathology at a distance. That doesn’t mean that you have to have a pathologist there who is highly trained you just have to develop the kind of networking to do that. We did that, somewhat, and we especially did that with epilepsy-it’s a different thing- but we developed an epilepsy surgery program where we had a local Ugandan doctor trained just literally to do the EEG and we did EEG video of patients that we were monitoring then we uploaded all that data via internet to a neurologist-epileptologist at a university in the U.S. who read it and interpreted it and we did candidate selection that way not having a neurologist onsite but having a neurologist virtually onsite. You can do the same thing with pathology and people are starting to do that kind of thing.
Then adjuvant therapies: being able to have access to drugs and to more tailored kinds of radiation treatments that are safer and more effective and perhaps that are even in line with international standards. I don’t see why we couldn’t bring certain centres in sub-Saharan Africa for instance on line with the pediatric oncology group in North America or whatever and become part of their protocols. It would require some funding but that needs to happen. And then just the basic things like operating microscopes and microsurgical instruments and things that are often lacking for people that are trained in neurosurgery.
It reminds me of the person that I hired as my first partner who is now the medical director there, Dr. Mugamba. He had come from a good training program in Cape Town, came back to Uganda, was practicing and on the staff and faculty at the national referral hospital and he was very frustrated because he didn’t have access to the tools to do what he was trained to do. He was pondering going back to South Africa where he was board-certified and being able to actually practice neurosurgery the way he was trained and so that’s how I was able to capture him, was to say “you can stay in Uganda and we can do this here” and [for] professionals I don’t think its all about money I think there is a lot of brain drain, if you will, in neurosurgery and other disciplines because of professional satisfaction.
9. Are the costs for neurosurgical procedures and oncological regimens subsidized? If so, how broadly? If not, is there political willpower to ease the financial constraints?
I would say there is not political willpower. Cancer in general, and brain tumors in particular, are under the global health radar screen right now. We are sort of in a transition I think in this coming decade in getting away from communicable diseases and more into burdens of other kinds of disease, surgical diseases, brain tumors, that have just not been a high priority in the past and will become a greater priority as we go forward.
Funding right now is just simply not available. It is not really subsidized. If patients can’t afford to pay in those situations there are things that underwrite the cost of their care from donated funds which was true for CURE Children’s Hospital. In the government hospitals there is a certain level of funding but patients are asked to pick up the slack and that is often a barrier to care. I know it’s a barrier to adjuvant treatment of brain tumors because this happened numbers of times where we would send a child to get adjuvant therapy at the centre in Kampala and they just couldn’t come up with the funds. So that’s a real barrier to care.
10. What is being done in the region to spread awareness of cancer and to dispel misconceptions of the efficacy of alternative therapies?
I don’t know of anything. I hadn’t been aware of anything when I was there. There is a lot of knowledge and recognition of Burkitt’s lymphoma which is the most the most common solid childhood cancer there and it’s not just a big thing on the jaw, it can occur elsewhere, we had a couple of cases presenting with spinal cord compression and it responds very well to chemotherapy, it doesn’t require surgical resection. It just requires diagnosis, which can sometimes require surgery. Burkitt’s is I think pretty well managed and very recognized there, brain tumors, are a black box right now as far as I can tell. We’re not doing any particular campaigns to educate the public, if I could invest in something in that regard I think I would invest in educating the primary care givers to think about it and recognize what you look for in a kid whose gait is off, has vision changes, a new seizure or nausea and vomiting every morning. Such cases are being treated for gastroenteritis or worms or something when maybe it is actually a posterior fossa tumor. Again the problem is even if the clinician thinks of it, usually it is out of their league or out of the patient’s realm of possibility to get an imaging study. It is easier now than it was. We used to have one of two or three CT scans in the whole country at our hospital. Now there is a little bit more in the way of access to imaging but it is still not great. For somebody who is an average, rural subsistence farmer in Uganda, the cost of say, an MRI may be close to his annual income. It’s a really tough problem.