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International Health

Nepal and the Department of International Health
A Model Relationship for Global Health Research

For over 20 years, the Sarlahi district of Nepal has been a second home to many Department faculty, staff and students. The Nepal Nutritional Intervention Project-Sarlahi (NNIPS) in the district has been the locus of globally significant maternal, child, and neonatal survival research. Successes in Nepal, however, have come with challenges of all kinds. From logistics to politics, the Department has contended with more than just research questions. Nevertheless, the first vitamin A trial in the late 1980s has spawned countless research opportunities. Multiple subsequent large-scale community-based trials have been completed in the NNIPS area, and three more are underway. This productive relationship with the people and government of Nepal has contributed to innovative public health interventions that continue to save tens of thousands of mothers and children every year in Nepal, the region and the world.  

The Road to Nepal
Vitamin A, Revolutions and CIA Agents 

Vitamin A Revolution
Until the 1980s, conventional wisdom held that poor nutrition in general, not vitamin A deficiency specifically, contributed to high child mortality rates in developing countries. Dean Al Sommer and Professor Keith West’s ground-breaking work in the early 1980s in Indonesia turned conventional wisdom on its head. Their study found a 34-percent drop in mortality among children given vitamin A supplements twice a year compared to those in the placebo group.


NEPAL: Nepal is divided into 14 zones and 75 districts. The Nepal Nutritional Intervention Program-Sarlahi (NNIPS) is located in the southern district of Sarlahi.

In the mid-1980s, Professors James Tielsch, Joanne Katz, and West set out to test the Indonesia findings in the Philippines. They spent several years negotiating with the Marcos government, and when it fell, with the former rebel groups now in power. After securing the necessary authorization for research to begin, the project was brought to an abrupt halt by a small group of physicians working in a remote area of the country, which just happened to overlap with the Hopkins study area. Using low-bandwidth radio and word of mouth, this band of physicians destroyed the reputation of the project. They claimed the vitamin supplements were poisoning mother and infants, causing miscarriages and deaths. Hopkins staff were accused of being agents of the CIA, bent on destabilizing the country and decimating the population. Within a couple weeks of stumbling upon this little-known group of doctors in one of the most remote areas of the country, the study had to be shut down indefinitely. 

A Rocky but Welcoming Start in Nepal
First NNIPS BuildingDuring the mid-eighties, West had also begun to work in Nepal and, after this setback in the Philippines, he and Katz regrouped to address the question of vitamin A and child mortality in this Himalayan kingdom. Finding a new location for the study, West and his family moved to Kathmandu in 1989 to set up the research organization that eventually became known to locals and researchers alike simply as NNIPS, which stands for the Nepal Nutritional Intervention Project-Sarlahi. Located in the southern plains district of Sarlahi district of Nepal, the project area was selected to be broadly representative of the health infrastructure and demography of the southern portion of the country, which is the most populous. The area also broadly reflects the levels of undernutrition and unmet need in much of South Asia.

Political turmoil between the governments of Nepal and India almost derailed the very first vitamin A trial. Not only is Nepal a landlocked country, but most goods are imported along the southern plains of the India-Nepal border. Sarlahi district, which borders India, depends on Indian trade routes for many essential goods. Only months before the project was to get underway, India closed its borders with Nepal, effectively shutting off all trade to the country. NNIPS staff scrambled to stockpile over 5,000 liters of gasoline to fuel the project’s new vehicles, while making contingency plans to run the study with ox carts should gasoline supplies be completely depleted.  After a year of the embargo, during which the first NNIPS trial got underway, the political crisis subsided, the border reopened, and the project continued to its successful completion.

From the start, research staff felt welcomed. The National Society for Prevention of Blindness graciously offered its Kathmandu offices as an official headquarters and home base for the project. The Society’s director, Dr. Pokhrel, also helped locate the study area and gave the project its name. 

NNIPS headquartersEarly in the planning phase, Professor West met the owner of a local sugar mill living there.  When the owner learned that the study’s goal was to prevent child deaths, he immediately offered one of his vacant buildings to the project free of charge.  He had recently lost his young son, and was eager to help prevent the suffering of other parents any way he could. The project eventually took over a building on the sugar mill grounds, still used as the guest house, and purchased land nearby on which a 6,000 square foot eye clinic and research center today stands. 

Early Successes

The first study, NNIPS-1, confirmed that vitamin A supplementation reduces child mortality. These findings, which reinforced Sommer and West’s work in Indonesia, coupled with another study by colleagues in Nepal and faculty advocacy led to the country’s first national vitamin A supplementation policy. Soon thereafter, the government of Nepal began scaling up vitamin A programs among preschool children.  The first phase of the roll-out, however, was not scheduled to include the Sarlahi district. Explains Professor Katz, “The research team felt it was our ethical duty to advocate for the study population. We felt they should be the first to benefit from the research they were a part of.” As a result of their efforts, the government added the district to the first phase of the vitamin A roll-out.

Core NNIPS Research Teams 
Keith West, Jr., Joanne Katz, Subarna Khatry, Steven LeClerq,  Al Sommer, James Tielsch

Keith West, Jr., Parul Christian, Joanne Katz, Subarna Khatry,
Steven LeClerq, Al Sommer

Parul Christian, Joanne Katz, Subarna Khatry, Steven LeClerq, Keith West, Jr.

James Tielsch, Robert Black, Joanne Katz, Subarna Khatry, Steve LeClerq

NNIPS Cohorts Follow-up Study
Keith West, Jr., Parul Christian,  Subarna Khatry, Steve LeClerq, Joanne Katz, William Checkley, Luke Mullany, James Tielsch 

Newborn washing
James Tielsch, Gary Darmstadt, Joanne Katz, Steve LeClerq,  Luke Mullany

Cookstove replacement
James Tielsch, William Checkley,  Joanne Katz,  Luke Mullany, Scott Zeger,
Alison Geyh

Maternal flu vaccine
Mark Steinhoff, Joanne Katz, James Tielsch

Sunflower oil  infant massage
Luke Mullany, Joanne Katz, James Tielsch

NNIPS-2 focused on maternal vitamin A supplements. The main trial involved nearly 45,000 women of whom over 20,000 became pregnant over the 4-year study. Pregnancy-related mortality fell by 40 percent among the women in the intervention group.  Maternal night blindness was also identified as a major risk indicator of mortality in women.  However, its early phase too was met by calamity, this time from a devastating flood during the monsoon of 1993, causing NNIPS to halt trial preparations for several months to provide relief throughout the Sarlahi area.  Still, over the course of NNIPS-1 and -2, construction on the project’s eye clinic and research facility was completed. The center still serves as a clinic and as a headquarters for the research staff working on projects in the area.

Civil War

Ongoing tension between the government and Maoists eventually descended into civil war. Between 1996 and 2006 the population and infrastructure suffered from the conflict. Local employees of NNIPS, now numbering over 500, helped negotiate with the Maoists to keep study workers and property safe. According to IH Research Associate, and NNIPS Field Director since its inception, Steven LeClerq, the Maoists even punished a husband who tried to stop his wife from performing her NNIPS job. After the Maoists publically humiliated him, “everyone else was admonished to help, not interfere, with the work of NNIPS,” retells LeClerq.  On another occasion, an MHS student working on the project was riding in a marked NNIPS vehicle when an army truck was blown up just a few vehicle lengths behind. A local project employee later complained to the Maoists about the close call. “The Maoists said it was no close call, they waited for the NNIPS vehicle to safely pass and then blew up the army truck,” LeClerq remembers.   

The Second Decade

NNIPS-1 and -2 tested the effects of vitamin A supplementation in preschool children and mothers, respectively. The next major trial studied additional antenatal supplements to mothers, including iron, folic acid, and zinc. NNIPS-3 was directed by Dr. Parul Christian, Associate Professor in the Department, whose doctoral work in NNIPS-2 led to a global recognition of night blindness in pregnancy as an indicator of maternal vitamin A deficiency. NNIPS-3 found that antenatal and postnatal micronutrient supplementation reduced the chance of low-birth weight, a good indicator of neonatal mortality. Professor Tielsch led NNIPS-4. His team enrolled 44,000 children over 7 years and found that zinc supplementation improved survival of children 1 year and older, but iron folic acid had no impact on survival. 

Umbilical cord washing with chlorhexidine

Donor Agencies for NNIPS Research
U.S. Agency for International Development (USAID)
The Bill & Melinda Gates Foundation
National Institute for Child Health and Human Development  (NICHD)
National Institute of Environmental Health Sciences
Thrasher Research Fund
Sight and Life Research Institute
Proctor & Gamble
Rotary Clubs of Lalitpur And Vashon Island
Sushil Kedia Seva Mandir

In 2002, Professor Jim Tielsch led the first major non-nutrition research intervention in NNIPS. His team evaluated the effects of a full body wipe of newborns with chlorhexidine, and umbilical cord care with chlorhexidine on neonatal mortality, the first community-based trial of this intervention. The study, conducted in tandem with NNIPS-4, followed infants up to 1 month of age, at which time they became part of the NNIPS-4 trial. Neonatal mortality dropped by a third in newborns receiving the cord care within 24 hours of birth, and mortality was reduced in those receiving the body wipe, especially in low birth weight infants. The umbilical cord care study was replicated with similar results in Bangladesh by IH faculty and in Pakistan by faculty from the Aga Khan University. The Gates Foundation is now sponsoring trials in Zambia and Tanzania to test the intervention’s efficacy in Africa. 

NNIPS Field workersThe government of Nepal recently added umbilical cord cleansing with chlorhexidine to its national health policy, marking another important example of Department-led research resulting in major child survival interventions in Nepal. The NGO Nepal Family Health Project (NFHP) is now leading chlorhexidine operations research to facilitate the scaling up of the program nationwide. Associate Professor Luke Mullany, who wrote his doctoral thesis on chlorhexidine cord cleansing and neonatal survival in Nepal and is currently leading his own neonatal research there, said:

NFHP’s work was instrumental in following our efficacy research from Sarlahi with important operational research and later linking the research results to the Ministry of Health, NGOs, and other stakeholders. As a result, Nepal became the first country to include umbilical cord cleansing with chlorhexidine in its national health policy.

While Sarlahi is not one of the five districts covered by the first phase of the chlorhexidine roll-out, current Hopkins projects will continue to provide chlorhexidine to the NNIPS community.  

Following participants later in life
NNIPS ParticipantsThe continuity of NNIPS affords researchers the unusual opportunity to conduct intriguing follow-up studies. Cohorts enrolled in the first trials are now in their young adulthood. Associate Professor Parul Christian has been at the forefront of this work. She continues to examine the long-term impact these maternal and early childhood interventions have on long-term survival, cognition, and early markers of chronic disease. Working with recent IH graduate Dr. Christine Stewart, now an assistant professor at UC Davis, Dr. Christian found that maternal iron-folic acid supplementation can reduce child mortality by nearly a third. Her team’s work has also found that maternal supplementation with iron folic acid and zinc can reduce the risk of kidney dysfunction and metabolic syndrome among children.

As a result of exciting new technology—the portable spirometer—IH faculty, led by Dr. William Checkley, recently measured increased lung size among children whose mothers had received pre- and post-natal vitamin A supplementation. These results were published recently in the New England Journal of Medicine. And PhD candidate Jane Schmitz recently wrote her dissertation on findings that vitamin A supplementation of children with purulent ear infections during childhood reduces the chance of hearing loss later in life by 40 percent.

Current Projects in NNIPS

Two new IH-led projects are currently under way in the NNIPS area. A third one, led by Professors Mark Steinhoff and Jim Tielsch, will assess the effects of flu vaccine administered to expectant mothers on maternal and infant morbidity. Funded by the Bill & Melinda Gates Foundation, the project is in the process of obtaining all necessary IRB approval. These three innovative projects will each be conducted in roughly separate thirds of the NNIPS area, so that interventions will not encroach upon one another.

Cookstoves and Indoor Air Pollution 
Nepali woman at a traditional stoveProfessor Jim Tielsch is currently enrolling participants in a unique NIH-funded trial to replace traditional stoves with high-efficiency, low-cost models with ventilation. Acute respiratory illness is a leading cause of mortality among young children in Nepal and there are few proven interventions available to combat it. This community-based randomized trial will test whether reducing indoor pollution affects the risk of child pneumonia and low birth weight. 

Because most homes use open unventilated stoves, the study utilizes a stepwise design that will replace stoves in all homes in the study area by the end of the project. Particulate levels and carbon monoxide concentration will be monitored regularly before and after the stoves are replaced.

A special testing facility was built to replicate local conditions to evaluate the performance of various types of stoves. “It turns out that the best type of stove was one built to very precise specifications by trained craftsmen with adobe bricks fired during use. In addition to the time and labor necessary to build the 350 stoves a month needed, it would require thousands of bricks to be fashioned, which is simply infeasible during Nepal’s long monsoon season,” explains Tielsch. For this reason, researchers will use the next best option—the industrially manufactured Envirofit stove. The locally affordable stoves are built in India by the Colorado-based company of the same name  (

Sunflower oil massage vs. Mustard seed Infant oil massage 
Associate Professor Mullany is leading another innovative, NIH-funded program just now getting underway. Infant massage is widely practiced across Nepal and South Asia. Research conducted in Egypt and Bangladesh by former faculty Dr. Gary Darmstadt showed that massage with sunflower oil improved survival of preterm infants over no massage at all. Moreover, research on animals has shown that massage with mustard seed oil causes higher levels of skin trauma and higher rates of water loss through the skin compared to other oils. The same research found sunflower oil to cause the least amount of damage to the skin and prevent the most moisture from escaping. With these findings in mind, Mullany and others conducted several formative studies to assess the acceptability of switching to sunflower oil.  Their promising results led the way to a new 4-year community-based randomized control trial that will compare the outcomes of the two practices across a population of approximately 100,000 and 10,000 live births.

The intervention will promote oil massage across the study area and provide expectant mothers with a supply of oil—with the intervention group receiving sunflower and the control group mustard seed oil. Local health workers will visit new mothers for the first month after birth to provide the necessary supply of oil, to assess the infant, and to determine whether the oil is being used.

 “Infant oil massage is a widely accepted traditional cultural practice. There might be some resistance to using sunflower oil instead of mustard seed, but the choice of oil is only one aspect of the overall practice.  We see the promotion of a different oil as an adaptation of an existing practice, with most of the elements, like the frequency, the timing, the mode of massage still intact. The long-established presence in the community and trust between researchers and community members could help us in ways that might not exist in other settings,” said Mullany about participants’ willingness to switch oils.

Nepal and International Health

While the majority of research in Nepal occurs in the NNIPS area, faculty, staff and students are involved in a variety of activities across the country, from human rights work to childhood feeding projects (see side bar). The NNIPS area, however, has become a model for global health research. The JiVitA project in Bangladesh, for example, owes much of its success and early design features to the lessons learned and accomplishments in Nepal. The site was established, in part, to test and build on NNIPS findings. Its location in the region relative to Nepal also helps to build an evidence base for the whole of South Asia. Interestingly, JiVitA was recently visited by the Bloomberg School’s Health Advisory Board. Princess Maha Chakri Sirindhorn of Thailand, who was part of the most recent delegation, was also a member of the very first Advisory Board visit to NNIPS over a decade ago. These delegations evaluate research sites to ensure that the School is living up to its mission. Both field sites received stellar evaluations from the Board.   

From the start, the Department has had fruitful relationships with the local community, public health professionals and the government in Nepal. “The Nepal Ministry of Health is very proactive and strives to be on the cutting edge of programming. While the standard of living hasn’t increased very much and the country has been affected by political uncertainty, mortality rates have declined and Nepal is one of the few countries on track to reach UN Millennium Development Goals for child, neonatal and maternal mortality. The country is a great example of a successful community-based healthcare approach,” comments Professor Katz, who has been involved in NNIPS since its inception. 

Professor West knew there was great opportunity to set up lasting capacity with the first NNIPS trial. In addition to the research that has helped save countless thousands of lives and the human capital and infrastructure that benefit the local population, “projects  such as NNIPS and JiVitA show how research sites can serve as national and regional resources to advance health and nutrition,” sums up West.

—Brandon Howard, May 2010