Hope for Ashok

By Lucy Horton, M.D., M.P.H '12

"Vanga! Dhayavusaidhe vukkaarungu," I say in tamil, greeting the mother and child standing in the doorway. The mother is dressed in an orange-and-gold sari; she has numerous bangles jingling on her forearms. Her long hair is pulled into a braid, and she has a red bindi on her forehead. Her son, Ashok, is dressed in his school uniform: navy shorts and a blue-and-white pinstriped dress shirt. He wears thick black socks and shoes and carries a backpack and a plastic basket with his tiffin, a stack of small metal boxes that hold his lunch.

After recording his ID code and getting consent from his mother, I roll up the boy's sleeves and take his blood pressure. "Asay-a-day," I say to him, "No moving." I try to ignore the noises from outside - children's voices, loud honks from motorbikes and the occasional grunt from a bull or goat - as I carefully listen for the first and last Korotkoff sounds. Later I will calculate the blood pressure percentile based on Ashok's height, age and gender.

For the past three months, I've spent each afternoon at a clinic on the outskirts of Vellore, India, investigating the alarming rate of chronic kidney disease that is affecting very young children. I am working through the Christian Medical College (CMC), where I am spending this year as a Fogarty International Clinical Research Scholar. Tufts has had a long affiliation with CMC, and there have been many research collaborations, in addition to a training and education partnership through the Department of Public Health and Community Medicine at Tufts Medical School.

In addition to CMC's main 2,000-bed hospital, which sprawls across a city block, there are several low-cost hospitals and clinics throughout the Vellore area that serve the region's poor communities. I am based at the R.N. Palayam Clinic, roughly five miles from the hospital. A small facility with two main rooms and a basic laboratory, it sits on a dirt road, nestled between a butcher's shop and a tea stall. The clinic was founded about a decade ago to treat children participating in CMC epidemiological research in enteric infections in infancy and childhood. In addition to providing basic medical care to children in the community, the clinic also serves as a hub for ongoing studies, including the scope of the transmission of the cryptosporidium parasite, which causes severe diarrhea, and the effectiveness of probiotics as a treatment for diarrhea.

Vellore, a small city in southern India, is described in guide books as a "dusty bazaar town." While Indians consider it small, proportions here are of a different scale than we are used to in the United States: Vellore has a population of 1.3 million, making it about the size of San Diego. The local population is split between Tamil-speaking Hindus and Urdu-speaking Muslims. At least among the women, an individual's ethnic and religious group can usually be determined by how they dress: Muslim women wear all black and head scarves, while Hindu women wear colorful saris. Men of both religions dress more Western, in trousers and shortsleeve buttoned shirts, but the Muslim men sometimes wear a taquiyah, or knit cap.

Jobs are few. The primary occupation is making beedis, thin, hand-rolled cigarettes made from tobacco flakes and a tengu leaf. Women sit in doorways cradling wicker baskets on their laps, rapidly rolling the beedis with precision while chatting and often holding a baby across a shoulder or around their waist. The men trim the leaves and then densely pack the finished cigarettes into wooden boxes to dry in the sun. The cigarettes are shipped by train to New Delhi and sold, producing a large portion of local income.

Living WeLL into Adulthood
Although the neighborhood around the clinic may not look like much, the children who live here have been the focus of almost a decade of cutting-edge epidemiological research, with studies funded by the National Institutes of Health, Wellcome Trust and the Bill & Melinda Gates Foundation. The group of children I work with on the kidney disease study have been followed by CMC researchers from birth until age three for studies on childhood infections and their health implications later in life. Much as the Framingham Heart Study was able to show what risk factors led to chronic cardiac disease, it is our hope that by following this group of children as they grow into adulthood, we can determine the longterm effects of the diarrheal illnesses that are extremely prevalent in Indian children.

Patience is required. After gathering the initial data when our subjects are small, we wait six years before we check in with them again at age nine.Most have little memory of being studied as babies, but evidence of their participation remains readily accessible. Their mothers have carefully preserved the paper cards that contain basic information about their birth history, clinic visits and immunizations. In India, it is the patient's responsibility to provide personal health history, and in my experience, patients are generally good about that. Ashok's mother carries his card neatly tucked into the folds of her sari. She proudly offers it to me.

Since September I have been screening visitors to the Palayam clinic to record blood pressure and obtain urine samples to look for evidence of kidney damage. By linking broad epidemiological data with detailed microbiology, we hope to uncover some clues about which gastrointestinal infections may be risk factors for long-term chronic kidney problems.

Ours are critical data to collect because India is experiencing an epidemic of chronic kidney disease (CKD). Although the precise prevalence is not known, a few observational studies have made estimates of about 0.7 percent of the population, or about 9.4 million people. However, this is probably a gross underestimate: for every patient diagnosed with full-blown CKD, there are dozens of others with preclinical stages of the disease. Patients here tend to present with kidney failure at a young age, and in many cases, the kidneys are so shrunken and damaged that it is impossible to identify the cause of the disease. Several years ago, Madhumathi Rao, a CMC alumnus who is an assistant professor of nephrology at Tufts, and Gagandeep Kang, head of gastrointestinal science at CMC, began exploring why CKD in India differs from that in the West. They hypothesize that recurring diarrhea and the resulting dehydration during infancy may cause chronic kidney disease and long-term damage to those organs. They further suspect that these gastrointestinal infections, in addition to other early-life assaults like low birth weight, malnutrition and immunological disorders, may play a significant role in the early development of renal disease.

I have teamed up with Drs. Rao and Kang to test their hypothesis. We chose to study this particular cohort of children because we already know so much about their health history. In the early days of the study, field workers visited the infants and toddlers at home every other week to gather information on all episodes of disease, and collected stool samples from all episodes of diarrhea. Researchers also compiled socioeconomic data and family medical histories, which we are using to suss out additional risk factors such as poor sanitation and access to clean water. Subtropical India is another world from Boston, but beneath the differences there may be lessons that translate from one place to the other. In the process of my work, not only have I seen diseases and conditions that no longer exist in the U.S., such as polio, measles and tetanus, I have also sifted through multiple social and economic factors that influence and often determine a patient's prognosis and overall health status. The medical system in America undoubtedly will undergo major changes in financing and structure over the next decade - changes that may well include a greater emphasis on prevention in efforts to lower costs. If that happens, CMC's model of community-based care could be applied to any setting with limited resources.

For now, our research goals in Vellore are straightforward. If we can solve the riddle of what's causing so much CKD in India, the hope is that we ultimately can stem its proliferation. And that could give Ashok, with his large brown eyes and wide smile, a better future. tm

To view the entire story including pictures by Lucy please see the Spring 2011 issue of the
Tufts Medicine Magazine.

Horton is a 2010-11 Fogarty International Clinical Research Scholar, a program that gives health sciences students clinical research training at NIH-funded research centers in developing countries.