Malaria Vaccine Trial: Behind the Scenes in Kenya

From the Centers for Disease Control and Prevention:

Malaria Vaccine Trial: Behind the Scenes in Kenya

Behind the Scenes of the Malaria Vaccine Trial in Kenya, with Dr. Mary Hamel and Team

In 2008, CDC malaria expert Dr. Mary Hamel learned that the Malaria Vaccine Institute was looking for leading research institutions in Africa to conduct Phase III clinical trials of the world’s most advanced malaria candidate vaccine, RTS,S/AS01. Recognizing that CDC’s nearly 30 years of collaboration on malaria research with the Kenya Medical Research Institute (KEMRI) would uniquely qualify it for serving as vaccine trial site, she told herself: “We must apply.”

Says Dr. Hamel, “From the time I started working in western Kenya in 1995, I’ve heard the community asking when they would get a malaria vaccine. And I’ve seen too many children die from malaria. I was thrilled at the prospect that we could be part of a study testing a vaccine that might be able to save hundreds of thousands of children’s lives.”

Malaria killed an estimated 700,000 people around the world in 2010.Most of these deaths were in young African children. In western Kenya, where KEMRI/CDC is located, Anopheles mosquitoes transmit malaria year-round, and malaria is the leading killer of children and the most frequent cause of outpatient visits and hospital admissions.

2008 KEMRI/CDC was selected as one of the leading African research institutions and their Northern academic partners to conduct the trial, which is taking place at 11 sites in 7 African countries—Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and Tanzania—from 2009 through 2014.

KEMRI and CDC’s long collaboration began in 1979 when the CDC/KEMRI Kenya Research Station was established and began to conduct malaria research. Over the years, the partnership has expanded to include HIV, TB, and other diseases, and the Field Station changed its name to reflect its larger mission: the KEMRI/CDC Research and Public Health Collaboration. That close collaborative relationship proved invaluable during the vaccine trial.

The Vaccine Research Team

Dr. Hamel and Dr. Simon Kariuki, KEMRI/CDC Malaria Branch Chief, lead the vaccine trial team at KEMRI/CDC. Other senior staff members of the KEMRI/CDC malaria vaccine research team are Chris Odero, site coordinator; Dr. Martina Oneko, lead pediatrician; Nobert Owino, field supervisor; Tony Sang, pharmacist; Maria Oziemkowskis, regulatory affairs; and Seth Oluoch, quality assurance. Dr. Laurence Slutsker, co–principal investigator, and Dr. Meredith McMorrow, pediatrician and medical epidemiologist, provide support from CDC Atlanta.

Site Coordinator Odero says, “Playing a role in the malaria vaccine trial has been the proudest moment of my life. I saw my cousin suffer from the debilitating effects of severe malaria and then die. Several other cousins also died of malaria. Because of the trial’s encouraging results and the presence of other effective interventions, I feel hopeful that my 8-month-old daughter will not suffer from malaria.”

To meet the demands of the vaccine trial, new clinical officers, nurses, medical officers, and other support staff were added at the district hospital’s pediatric ward. In all, more than 130 people are part of the malaria vaccine research team, including the hospital’s medical superintendent, who serves as a co-investigator, and many doctors, clinicians, and nurses. Already strong relationships were further reinforced, and all sick children who are admitted to the Siaya District Hospital pediatric ward during the trial will benefit from the additional expertise.

Preparations: Training, Equipment, Renovation

Many preparations were undertaken to meet the specific requirements for conducting a clinical trial, including these:

·         training and supporting doctors and clinicians to provide medical care according to the comprehensive Kenyan Basic Pediatric Protocols and Basic Pediatric Life Support Guidelines;

·         providing oxygen cylinders, pediatric monitors, and other clinical equipment required to provide care to severely ill children;

·         building a laboratory with chemistry analyzers, blood culture machines, and other laboratory equipment, and providing the hospital with a new digital x-ray machine; and

·         refurbishing the pediatric ward, repairing a leaking roof, fixing plumbing problems, and improving the acute care room, where the most severely ill children are stabilized.

·      The Trial Begins

·         2009 The Siaya locations began recruiting children aged 6-12 weeks and 5-17 months at age of first vaccination.

·         2010 Recruiting went smoothly and by February 2011, 1,620 participants had been enrolled in the trial. Children were randomly assigned to receive either the RTS,S/AS01 candidate malaria vaccine or a different vaccine (rabies or meningococcal). Neither the researchers nor the children’s parents knew which of the vaccines they received. Children were instructed to come to the study clinic or hospital whenever they became sick. They received free care and, if they had symptoms of malaria, they received a blood test to determine whether they had the disease. Children in the study will be followed for nearly 3 years.

·      Many Opportunities to Save Lives

·         2009–2011 On one occasion, a study clinician examined a very sick baby girl, who was breathing very rapidly. The baby’s mother was worried that her husband would not want the child admitted to the hospital. Dr. Oneko was called and convinced the mother that the child was critically ill and must come into the hospital or risk dying. That night, the child lost consciousness and required life support throughout the night. The following morning, blood test results indicated that the child was suffering from herbal poisoning. The examining clinical officer found evidence of “cupping” (a traditional practice in which a glass is heated and placed on the skin to remove bad spirits). The child’s mother revealed that the father, who preferred traditional to western medicine, had taken the child to a healer for the treatment. Realizing the child’s condition was worsening, the mother and mother-in-law joined forces and brought the child to the study clinic for care.

·         Thanks to the dedication of the study staff, the district hospital’s excellent facilities and the medical care the child received, she recovered. Says Dr. Oneko, “We have numerous examples similar to this one, where the presence of a dedicated study team, caring doctors and clinicians, and a modest but functional health system, resulted in a child’s life being saved. It is gratifying to work on a project where our work goes well beyond the trial itself.”

·      Vaccine Trial’s First Results

·         2011 On October 18, 2011, Bill Gates at the annual Malaria Forum in Seattle announced the trial’s first results: the vaccine had prevented about half of the cases of clinical and severe malaria in the children 5-17 months of age. The vaccine provided this protection in settings where there is ongoing use of other effective malaria prevention and treatment interventions: bed nets, effective antimalarial drugs, indoor residual insecticide spraying to prevent mosquito-borne transmission, and drugs to protect pregnant women and their fetuses from malaria’s adverse effects. “At the moment,” says Dr. Kariuki, “we are on track in the development of RTS,S/AS01 as the first malaria vaccine for African children.”

·      Future Plans

·         2012–2014 Over the next few years, additional trial results are expected to show how well the vaccine works in young infants when they receive it with their routine childhood immunizations and how long the vaccine protection lasts after immunization. These data will be critical to help researchers understand how the vaccine can be used most effectively to control malaria.

·      Trial Highlights Importance of CDC Work "In the Field"

·         The trial also shines a light on the value of CDC work in the field. Remarking on the results, Dr. Kayla Laserson, director of the KEMRI/CDC Research and Public Health Collaboration, said, “Our KEMRI/CDC platform has now contributed to three vaccine trials—rotavirus, malaria, and TB. We are well positioned to apply lessons learned from these trials, such as strict regulatory procedures; clinical, laboratory and diagnostic support; and specimen transportation and management, not only to future vaccine trials but to other life-saving public health research.”

·         CDC-Kenya Country Director Dr. Robert Breiman noted that CDC and KEMRI involvement in the trial “highlights one of the many values of maintaining a strong surveillance and research system in the field.” The KEMRI/CDC Health and Demographic Surveillance System (HDSS) was used during the trial to locate children who were in the age range needed for the trial. Because every household is mapped in the HDSS, the study team was able to approach the parents of children who met the age eligibility criteria. The team visited with the parents in their homes to describe the trial and answer questions. The parents were then invited to come to the study clinic for more information, consenting, and enrollment. The mapping has also helped locate children for monthly visits, or to contact parents when a child’s test results show that treatment is required. Finally, the long-standing relationship KEMRI/CDC has had with the community—resulting in a deep level of trust— has facilitated both enrollment and conduct of the trial. “There is a great deal for us to be collectively proud of as we view these first results from the malaria vaccine trial. First, we continue to evolve and strengthen local capacity to conduct first-rate field research. And, we have taken part in another groundbreaking investigation that we expect will save lives,” he added.

·         Notes CDC Malaria Branch Chief Dr. S. Patrick Kachur, “The benefits of this vaccine research are very tangible for our Malaria Branch programs.  Participating in a multisite trial like this one helps CDC scientists contribute at the cutting edge of new developments for malaria control.  It helps strengthen our decades-long partnership with researchers in Kenya, and helps us forge connections with other leading research groups across the continent.  This helps us to ask better questions that will improve malaria prevention and control across a wide range of settings.”

·      Recent Successes in Malaria Control

·         In the last decade, thanks to sharp increases in global funding for malaria, many malaria-endemic countries have been able to scale up the distribution and use of safe, effective, and affordable life-saving malaria interventions: insecticide-treated bed nets, antimalarial drugs, drugs to protect pregnant women and their fetuses from malaria’s adverse effects, and indoor residual insecticide spraying to prevent malaria’s mosquito-borne transmission. In many of these countries, the scale-up has contributed to decreases of up to 50% in all-cause mortality in children under 5 years of age.

·         This encouraging trial gives hope that the world will soon be able to add another tool to the current malaria interventions that will help move the world closer to the goal of ending malaria deaths.

·      Partnership

·         The successful and rigorous conduct of the trial, which has required standardization across 11 African sites and adherence to Good Clinical Practice and Good Clinical and Laboratory Practice guidelines, is a tribute to the African institutions and scientists leading the trial and a testament to their ability to conduct high quality research, according to Hamel.

·         “I feel honored to be part of this team,” she says. “Working with and learning from African researchers who are some of the world’s leading malariologists has been very rewarding. “ Hamel adds, “I am looking forward to the day when African children at risk receive a malaria vaccine as part of their routine childhood vaccinations, along with an insecticide-treated bed net—and I hope to see that day very soon.”

·      More Information

·         First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children http://www.nejm.org/doi/full/10.1056/NEJMoa1102287 

·         CDC Statement on Results from RTS,S/AS01 Malaria Vaccine Trial http://www.cdc.gov/malaria/features/vaccine_trial_results.html

·         President Malaria Initiative’s 5th Annual Report http://www.pmi.gov/resources/reports/index.html

·         Malaria Vaccine Initiative http://www.malariavaccine.org/

·         World Malaria Report 2011 http://www.who.int/malaria/world_malaria_report_2011/en/

·         Global Malaria Action Plan http://www.rbm.who.int/gmap/

·         CDC’s malaria web site www.cdc.gov/malaria