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Global Medicine
by Eve Jacobs

Preventing and fighting the twin scourges of HIV and TB, and giving kids with facial anomalies a chance at a normal life, take UMDNJ professionals to locales as far away as Botswana, Guyana, Thailand, South Africa, Uganda, China, Brazil and Ecuador.

It’s just under 3,000 miles as the crow flies from Newark, New Jersey to Guayaquil, Ecuador, but human travel is rarely so direct. When the oral and maxillofacial surgery team lands at Simon Bolivar International Airport on Sunday evening, after an exhausting day of travel including a stopover in Houston to pick up additional staff, they look forward to a menu of dinner, then sleep. Come early Monday morning all 16 travelers — four surgeons, two residents, five anesthesiologists and five nurses — need to be sharp. They have a tough five days ahead of them.

At 7 am, 100 mothers and their young children will be lined up at Guayaquil’s largest children’s hospital — Hospital Del Nino — patiently waiting to see the doctors. Each mother is hoping her child will be among those chosen to have their cleft lip and/or palate treated. The team has just four days to do their magic and lives will be transformed, or not, based upon the surgeons’ hard decisions. First the doctors will evaluate their young patients and document their findings. Each waiting child will be assigned a number — 1 for a definite yes, 2 means “if time allows,” or 3, a definite no, due to the complexity of the surgical procedure that needs to be done or an underlying condition that would preclude general anesthesia. The group will try to arrange for these more complicated surgeries to be carried out at a future time in the U.S. (Last year, they saw a young boy missing an eye and arranged for him to come to this country for a prosthesis.)

The team will work in three different operating rooms simultaneously, each surgeon performing about 20 surgeries in four days, each procedure taking about two hours. By week’s end, 60 of these children — age two months to teens — will be visibly transformed. It’s a heavy load. They begin operating at 1 pm on Monday, right after the evaluations are completed, and finish that day’s work in time to have a late dinner, sleep and start all over again at 7 am on Tuesday. That will be their routine until Saturday, when they do hospital rounds in the morning, then spend half a day touring the city, picking up gifts for family members and friends, and maybe spending a few hours at the beach or the park where iguanas sleep by the pond — directly across from their hotel.

Researchers are not sure why cleft lips and palates are far more common in Central America than other parts of the world. Genetics and prenatal folate deficiencies are believed to play a role.

The 100 young faces lined up for the doctors’ scrutiny are simultaneously pictures of deformity and beauty. So many of them, each with a cleft lip or palate, or another major facial defect. These kinds of birth defects are far more common in Central America, according to Shahid R. Aziz, MD, DMD, assistant professor of oral and maxillofacial surgery at UMDNJ-New Jersey Dental School (NJDS) and one of the surgeons on this “Healing the Children” journey. Why are these defects so common? “We don’t really know,” he says. “Probably it’s a combination of genetics and a prenatal vitamin deficiency, specifically a folate deficiency.” Inadequate intake of folate (also known as folic acid) during pregnancy is known to sometimes result in congenital neural tube defects, including malformations of the spine (spina bifida), skull and brain (anencephaly). More recently, this nutritional deficiency has been linked to other birth defects.

Where do all these children come from? Many residents of this gritty city, and the villages and towns surrounding it, are extraordinarily poor, explains Aziz, and paying for a child’s complex surgery is way out of their reach. An advertisement — that runs for a month prior to the surgeons’ arrival — alerts parents to the possibility of getting this life-altering medical treatment for free. And truly, the lives of entire families can be changed in just a matter of hours.

Cleft lips, says Aziz, are chiefly a “cosmetic” problem, but ultimately this deformity will cause the child to be treated as an outcast. Cleft palates, on the other hand, are generally a functional issue, he explains, producing an open path from mouth to nose. This means that a baby will have to struggle for nourishment, since sucking is affected, and milk can enter the nose directly from the mouth. Both defects can affect speech, and in older children, eating. In the U.S., where these facial malformations are relatively rare (1 child in 1,000), cleft lips are usually repaired at 10 weeks of age, cleft palates when the child is nine to18 months. “The surgery is so much harder when the child is older,” says Aziz. An older child may also suffer psychological consequences lasting long after the defect is successfully repaired.

Each cleft presents the surgical team with a different challenge. Cleft lips can range in severity from a slight notch in the upper lip to a complete separation of the lip, extending to the nose, on one side of the upper lip or both. Cleft palates also range in seriousness, from a small opening at the back of the palate to a complete separation of the roof of the mouth, extending from front to back, on one side or both. Surgical repair is more complex than for cleft lips, involving rebuilding the palate, moving tissue from the sides of the cleft to the center of the palate and rejoining muscle. In both cases, the surgical team will have a very high success rate, says Aziz. In Guayaquil, the children usually remain in the hospital for one or two days, and are cared for by the hospital’s nursing staff. The level of care, says the surgeon, is very good.

The group that Aziz travels and operates with is very experienced in this specialty. The team’s leader, Steven M. Roser, DMD, MD, is chief of the Division of Oral and Maxillofacial Surgery at Emory University. He was formerly at the School of Dental and Oral Surgery at Columbia University, and has been heading up such traveling teams to Guatemala and Colombia for almost 10 years. Three years ago, deciding that these sites were not safe for his volunteers, Roser decided to take the team to Ecuador. He recruits most of the group’s members. Aziz — who received his dental degree from Harvard and his medical degree from Columbia — trained under Roser and calls him his mentor. He takes one oral/maxillofacial surgery resident from NJDS on each trip (in 2003 it was Michelle Bergen Shapiro and in 2004 Thomas Chiodo). This year the team will do their work in the city of Manta, located four hours from Guayaquil on the coast.

Each volunteer pays his own travel and hotel expenses, a cost of about $1,000, and solicits monetary donations to underwrite other expenses. The group is often able to raise $20,000 to $25,000, and sometimes donations of equipment and supplies, such as suture material and antibiotics, from manufacturers. These, along with donations of toys and clothing for the children, are sent to the hospital about one month ahead of the team’s travel date. An Ecuadorian medical foundation called Fundacion El Cielo Para los Ninos de Ecuador — dedicated to the repair of cleft lips and palates in that country — makes arrangements with the hospital, advertises for the patients, and arranges for the care of the children post surgery.

Surgeons from “Heal the Children” operate for free. Children come from surrounding villages for the life-altering surgical procedures that their families are too poor to afford.

Aziz, who participates in about 100 facial reconstruction surgeries annually, many as part of the maxillofacial trauma service at UMDNJ-University Hospital, says within a year or two, he would like to lead a group from the University, perhaps to China, Mexico, Guatemala or Costa Rica, or even Pakistan, if it becomes safer for Americans. “The need is definitely there,” he says, “but we have to ensure the safety of the volunteers.”

The surgeon goes on to explain that this humanitarian journey does not only benefit the children; it also has a huge effect on the lives of the medical workers. They gain valuable educational experience – improving their skills in correcting these congenital defects which they see only infrequently in the U.S. — and Aziz says, “They will be reminded about why they went into healthcare. Being a surgeon is about helping people — making a good income is secondary. When you participate in a humanitarian mission like this one, it has a life-changing impact that you can never forget.”

Fighting AIDS on the frontier

In Botswana, where the numbers of lives lost to AIDS — and those devastated by the ripple effect of those losses — is beyond our ability to measure and comprehend, orphans age 8, 9, 10 try to play parent to younger siblings and sometimes to grandparents, too. The shadow of the AIDS stalker is long and scary. With 36 percent of its adult population thought to be HIV positive, Botswana may have the world’s highest rate of infection. (In Francistown, a travel hub and magnet for the young and up-and-coming of the nation, the infection rate is put at 45 to 50 percent.) More than 20 million people worldwide have already died of AIDS, and 42 million are estimated to be living with the virus, 30 million of them in sub-Saharan Africa. Experts say 68 million more people could die of the disease by the year 2020.

Much closer to home, some of the countries lining the Caribbean — where the natural beauty belies the dire situation — have the highest prevalence of HIV/AIDS in the world outside of Africa. The hardest hit are Haiti and Guyana, where studies have shown that HIV infection may run as high as 46 percent among sex workers in Georgetown, the capital and primary port.

Most of us read about the potential wreckage of entire countries and cultures and are overwhelmed, not even able to envision making a dent. But UMDNJ infectious disease experts — many with almost two decades of experience gained fighting HIV domestically — frequently travel into these epidemic hot spots. They know the battle is slow and sometimes dreary, but over the years, they have had some major successes on the home front. Now, they forge professional and personal relationships with other healthcare workers, and political figures, in Botswana, Uganda, Thailand, Guyana, South Africa, Brazil — teaching a weary, but willing, healthcare force how to beat back this killer in their own countries. Of course, a commitment of U.S. dollars — $15 billion by the federal government over five years — is a critical element in what will turn this dire situation around.

Take Mary Boland, PhD, RN, nurse, educator, researcher, HIV/AIDS specialist. She has gained a wealth of expertise during her 14 years leading the development of programs at UMDNJ’s Francois-Xavier Bagnoud (FXB) Center, which has as one its major missions the prevention of mother-to-child transmission of HIV worldwide. She was a natural to tap when the CDC geared up for its new initiatives abroad.

Participating in a humanitarian mission has a life-changing impact, says Shahid R. Aziz, MD, DMD.

Georgetown, Guyana is just one of the locations where she hopes to make serious inroads. Teaming up with Tom Denny, MS, associate professor of pathology and laboratory medicine at UMDNJ-New Jersey Medical School (NJMS), who has 20 years experience in HIV/AIDS laboratory testing, and Guyana’s Ministry of Health, they will build, equip, staff and set in motion an HIV/AIDS reference laboratory there. It may not sound like much, but this lab will make accurate diagnosis possible, she explains, as well as monitoring the immune status of the patients. Without reliable diagnostics and testing, knowing when to start prescribing retrovirals, and when to change the mix of drugs in the cocktail because one or more of them have become ineffective, is purely a shot in the dark. These life-extending therapies are just now becoming more widely available in many developing countries, where the majority of the HIV-infected have gotten no drug treatment at all.

The UMDNJ team will also provide clinical training for Guyana’s health care workers, get HIV/AIDS into the curriculum at universities that train physicians, nurses and social services personnel, and offer mentorships with faculty in Newark. Chuka Anude, MD, and Gisele Pemberton, MPH, have already been hired to provide medical services and run the Georgetown lab. In Botswana, the team will work with an existing lab, but the building of academic, clinical and research relationships– all aimed at saving the lives of the HIV-infected and preventing further infection — will be much the same as in Guyana.

With so many millions infected by this virus in countries where it may take years to adequately bolster the healthcare infrastructure, the pressing issue is what can be done now to make an impact. Unlike conundrums that stymie even the most brilliant, this one has a somewhat obvious answer. Stop vertical transmission — mother to child — and you’ve saved a generation, at least for awhile.

“The regimen for preventing mother-to-child transmission of HIV is much simpler than treating persons already infected with the virus,” explains Paul Palumbo, MD, NJMS professor of pediatrics. He also serves as Vice Chair of the Pediatric AIDS Clinical Trials Group (PACTG), a national organization that devises and carries out HIV/AIDS research protocols domestically and abroad, currently in Brazil, Thailand, and South Africa.
The risk of HIV transmission from mother to newborn, which can occur at the time of birth or while nursing, is about 40 percent. According to Palumbo, a single dose of the drug nevirapine, administered to the mother orally during labor, and a single dose to the infant within 72 hours of being born, have been shown to cut transmission in half.

Because the drug is relatively effective, and cheap, “it is a central approach for countries with limited resources,” he says. Its down side is that “it is the type of drug that HIV develops resistance to easily.” Since nevirapine is frequently part of a three-drug cocktail used to treat HIV-infected children and adults, the researchers are investigating whether a single dose of the drug will bring about treatment failure later on.

“For countries using nevirapine for both prevention and treatment, getting answers to this question now is a high priority,” Palumbo explains.

“There is a lot of research being conducted overseas but we don’t devise a cookbook for how to do this,” says Boland, who works closely with Palumbo conducting research in mother-to-child transmission and drug therapies at four sites, two in South Africa, one in Bangkok and one in ChiangMai. “In each locale, the approach is collaborative and unique to that place. But it’s important to use the same research standards globally. The U.S. is a leader in that area.”

TB just won’t go away

Tuberculosis is a worldwide problem that has a very long history. Despite a number of effective medications both for prevention and treatment, TB just will not go away. One-third of the world’s population, or two billion people, have latent tuberculosis infections, and 10 percent of them will develop active disease in their lifetimes. While aggressive drug therapy has pummeled this infection into submission in the U.S., it is still a massive killer abroad, particularly in locales where HIV travels unchecked. Together, they are a brutal adversary.

George McSherry, MD, NJMS associate professor of pediatrics, and a tuberculosis specialist, has designed a PACTG study that will take place at the Chris Hani Baragwanath Hospital in Soweto, South Africa, the “twin city” of Johannesburg. According to McSherry, there are 30,000 deliveries in that hospital each year, and 25 to 30 percent of mothers are HIV positive.

Because those infected with HIV are more prone to contract tuberculosis, the study will look at how effective the drug Isoniazid (INH) — a mainstay of TB treatment in the U.S. — is in preventing TB and latent TB infection among South African infants who have been exposed to HIV perinatally. These are infants whose mothers have been tested for HIV infection, and have been treated with nevirapine during labor. The newborns have also been treated with one dose of the drug after birth. At the postnatal check-up on day 3, mothers will be asked for permission to enroll the child in the TB prevention trial. If the mother agrees, the child will get INH or a placebo at four months old, and will be treated for two years and followed for an additional two years. “Of course, if the child is suspected of actually having tuberculosis, he will be treated for the disease immediately,” says McSherry.

The research group’s goal is to enroll 1,300 children at two sites in South Africa over 18 to 24 months. “There are many nuances to enrolling kids in clinical trials,” says McSherry, who also collaborates with Boland and Palumbo on HIV/AIDS trials. “It takes years to build trusting relationships with healthcare providers in other countries, and to transfer an entire system and way of thinking.”

The spread of HIV in countries where TB has grown roots “explodes like gasoline to a match,” says Lee Reichman, MD, MPH, professor of medicine at NJMS, whose career has been dedicated to stamping out TB here and abroad. But because we live in a world of global travel, “to control it anywhere, you have to control it everywhere,” he says.
Reichman calls TB (which kills two million people each year) and HIV (responsible for three million deaths annually) the “diseases of mass destruction.” He points out that other headline-grabbing infections are not even in the same league with these two. SARS killed 813 last year, Ebola 244, West Nile 232, anthrax 5, smallpox 0 and mad cow disease 1, he says.
According to Reichman, TB is the world’s most serious infectious threat because, unlike HIV, it is airborne, and can be transmitted without long-term or intimate contact. Coughing, sneezing and even speaking, if the larynx is infected, move these germs quite efficiently from person to person. In his book Timebomb, the Global Epidemic of Multi-Drug-Resistant Tuberculosis, he tells the story of a young Ukrainian man who travels from Paris to New York on a 7-hour-plane flight in September 1998. No one was aware that he had active tuberculosis until three days later when he sought medical treatment at a clinic in Erie County, PA. (It was later reported that he had been coughing during most of the flight.) The physician diagnosed TB, and notified public health officials, who tracked down all passengers sitting near the sick man on the plane, as well as his close contacts in the U.S. Thirteen of these individuals tested positive for tuberculosis infection.

As it turned out, the man’s strain of TB was resistant to six of the nine drugs most commonly used to treat the infection. It took 16 months of aggressive treatment with several drugs until he was pronounced cured.

The Ukraine and other republics of the former Soviet Union have been battling an epidemic of multi drug resistant (MDR) TB for several years. Central to that epidemic are the prisons in Siberia. The disease spreads through crowded cells, and not only are the drugs inadequate, but physicians don’t know how to use them to treat this disease. It’s a recipe for catastrophe. Each year, some of these infected prisoners are released and go home and spread the drug-resistant strains to intimate and even casual contacts. Reichman says that of those who are left untreated, or are inadequately treated, half will die and the other half will go on to spread the tuberculosis.

As distant as TB in Siberia or the Ukraine seems to be from our borders, it’s really as close as one man on a plane — or perhaps an adopted baby. That’s why Reichman and his team have hosted Russian physicians to study at the NJMS National TB Center in Newark, and have traveled abroad to teach medical staff how to curb the spread of these deadly strains. Most recently under a contract from USAID, they have written and published a best practices guide for primary care physicians in Russia. It will serve as a reference in their day-to-day practices. “Multi-drug resistance is always manmade, always the result of medical care gone awry,” Reichman states. This joint project with the World Health Organization is based on focus groups conducted with physicians from the former Soviet Union. The group hopes to write best practices guides for other locales, such as the Philippines, struggling with the same problems.

TB in the time of AIDS and AIDS in the time of TB are beasts like none we’ve known before. Disease has never respected national boundaries, but now deadly germs jump continents and oceans effortlessly, using the very modes of transportation that our global economy depends upon. It turns out that global medicine is not just the domain of the adventurous or the heroic, but simply of those who understand how very tiny is our ever shrinking world.