Accurately diagnosing pneumonia can be very difficult in the resource-challenged settings of developing nations. IVAC’s PERCH study allows the opportunity to explore a new technology that can help improve the accuracy and speed of pneumonia diagnoses. This type of innovation enables us to reach more children and save more lives, while also furthering our understanding of the epidemiology of this disease. In advance of World Pneumonia Day, marked each year on November 12, we’re excited to offer a look at the digital future of using state-of-the-art technology in diagnosing and treating respiratory illness in the world’s poorest settings.
By Eric D. McCollum, MD
Digital auscultation to record and analyze the breath sounds of a patient, as seen in The Gambia. Photo by Eric D. McCollum.
The scene is familiar, an African healthcare worker with only several months of training but working as the community doctor, is setting up his temporary pediatric clinic in a remote village beneath the shade of a baobab tree. The queue is long, as mothers and their children from this small community and beyond have waited since the early morning for their child to be seen. Some children are sick and need medicine, and some are not and instead need only a weight check and their immunizations. The penetrating tropical sun begins to rise signaling the beginning of the clinic. Fortunately, the girth of the baobab tree provides the necessary relief. “Okay, let’s begin,” the healthcare worker states in the local dialect as his eyes meet with the mother of the first child, a toddling 17 month old girl with only a dirty brown shirt covering her body. “How can I help you?”
“She is sick with fever and cough for four days,” the mother answers, brow tense with concern.
The healthcare worker continues with his routine follow-up questions until this trite scenario takes an unexpected, most interesting turn. He reaches into his pocket and pulls out his mobile phone and attaches to it what looks to be almost a miniature suction cup with fine beads covering its face. Several mothers waiting in the line take notice and turn to each other talking quickly. The worker pushes several buttons on his phone and then presses the device onto the bare chest of the girl, who remains clinging to her mother’s breast. He then sits back, rests against the heavy trunk of the baobab tree, punches a button on his mobile phone, and waits. After several short moments the phone then beeps, and his eyebrows raise up in response. “Your child has pneumonia… and needs antibiotics.”
The continent that skipped over clunky technology like landline phones and large desktop computers in favor of slick mobile phones and the internet may also be leapfrogging what many consider to be the first medical device, the stethoscope. Learning to interpret the sounds captured by the stethoscope can take years of practice. Even then, opinions processed by the ears of vastly experienced physicians can still differ. The stethoscope is quite simply “the art of medicine.” Given these inherent drawbacks of traditional stethoscopes, the World Health Organization’s (WHO) diagnostic criteria for childhood pneumonia intentionally ignores respiratory sounds altogether. This allows healthcare providers with minimal training who work in remote areas, often where childhood pneumonia mortality is greatest, to still diagnose and treat pneumonia. The drawback of the WHO not including respiratory sounds in its diagnostic criteria is that many children with pneumonia are incorrectly diagnosed and thus incorrectly treated, a potential danger to the health of the child and waste of scarce financial resources.
Digital auscultation at work. Photo by Eric D. McCollum.
Art may soon be giving way to cutting edge clinical science and computer technology. Electronic devices exist that act similarly to traditional stethoscopes, except that they generate digital sound waves that can be fed into computer software programs. In fact, they are under active study and continued refinement, such that a small mobile device that contains sophisticated software may soon be able to accurately interpret chest sounds for use in clinical care of children. The Pneumonia Etiology Research for Child Health study, or PERCH, is a large collaborative project funded by The Bill and Melinda Gates Foundation currently ongoing in seven developing countries throughout Africa and Asia. PERCH is utilizing digital stethoscopes to record chest sounds from children hospitalized with life-threatening pneumonia. These sounds are then uploaded onto local internet servers that can be accessed by co-investigators at The Johns Hopkins School of Public Health International Vaccine Access Center and the Johns Hopkins University Engineering Department. These investigators are in turn creating novel computer software algorithms that can interpret these sounds and therefore accurately diagnose childhood respiratory illness. This could mean more efficient use of childhood pneumonia resources and even better outcomes for children sick with pneumonia, the number one cause of childhood mortality globally.
While digital auscultation devices and computer software able to interpret chest sounds from children may still be in experimental phases, it is not unrealistic to envision a time where healthcare professionals located anyplace and anywhere, even beneath a Baobab tree in a remote African village, can utilize this technology to accurately diagnose and provide life-saving treatments to children with pneumonia. So listen up carefully on this World Pneumonia Day, a revolution is coming.
Dr. Eric D. McCollum is a Post-doctoral Fellow in the Division of Pediatric Pulmonology at the Johns Hopkins School of Medicine, and a member of the PERCH study team.
By Dr. Kate O’Brien
IVAC's Acting Director, Kate O'Brien
Today is a notable day for IVAC. We have transitioned from the leadership of Dr. Orin Levine, the founding director, who led the Center through its growth from a single project to a diverse portfolio of projects encompassing numerous vaccine access issues. We are beginning a new IVAC chapter, and I am proud to take the reins as Acting Director while the planning for a permanent Director progresses. Although this role for me at IVAC is new, the institution itself is not. My experience at IVAC includes the stages of visioning what we wanted the Center to be, choosing its name, developing our space from a concrete cavern to a place of warm collaboration, and growing its projects and staff.
IVAC is defined by its people and its partners. You are a dynamic, innovative, and dedicated group, focused on “moving the needle” toward improvements in child health and survival. Our long-term partners – organizations such as the GAVI Alliance, the Gates Foundation, CDC, PATH, Sabin Vaccine Institute, International Vaccine Institute, and fellow academic institutions and research centers around the world – have been central to the successes of IVACs work that aims to expand vaccine access to children in the places where it is most needed. We will continue to extend our efforts across disciplines and partners, guided by the mission of full vaccine access against leading causes of mortality and morbidity like pneumococcus, Hib, rotavirus, dengue, malaria and influenza.
I am very grateful for the opportunity to lead IVAC, an organization that will continue delivering the highest quality and impactful work it is known for. My aim in this next chapter of IVAC is to foster an environment where great work can continue to drive vaccine access, achieving milestones beyond what we believed possible at the beginning of IVAC. Working to collaborate with new partners, strengthen existing collaborations and providing our staff with the means to create and innovate, the work we do will remain firmly grounded in principles of excellence, objectivity, data driven decision making and advocacy using fresh, often unconventional, approaches.
I look forward to working with all of you in my new capacity, and eagerly welcome the discussions, directions and deliberations we are sure to have on the way to accelerating use of life-saving vaccines around the world.
Kate O’Brien, MD, MPH is Acting Director of IVAC. A pediatric infectious disease physician, epidemiologist and vaccinologist, she previously served as Deputy Director of IVAC. She also serves as Associate Director of the Center for American Indian Health.
By Dr. Mathuram Santosham
If you ask a scientist why it’s important to be an advocate, most scientists would probably be puzzled. After all, a scientist’s job is to research and study to find what works, test alternate hypotheses and document findings. Advocating is the job of an activist, they’d likely reply.
And they’d be partly right; advocacy is the job of an activist. But as scientists and medical providers, it is our duty to ensure that the knowledge that we have gained through research and best clinical practices is transferred to appropriate decision makers so that ALL children benefit from these life-saving interventions.
As a doctor, I have seen the grief of parents who have brought their children in for treatment for preventable diseases like pneumonia and diarrhea, only to be told they’ve arrived too late. As a scientist, I have conducted the research and know that vaccines against these diseases are effective and have the potential to prevent millions of unnecessary deaths in the next decade.
Panelists at the ROTA Council session "Translating Evidence Into Policy to Fulfill the Promise of Rotavirus Vaccines" at the 10th International Rotavirus Symposium included Kathy Neuzil, PATH; Tony Nelson, Chinese University of Hong Kong; George Armah, University of Ghana; Mathuram Santosham, Johns Hopkins University; and Andy Seale, PATH.
Rotavirus is one of these diseases. Today, rotavirus diarrhea is a leading killer of children in the developing world and the leading cause of hospitalization all over the world. Time and again, research has demonstrated that vaccines can protect children from rotavirus diarrhea or lessen its severity, yet introduction has been slow, especially in low-income countries where children need it the most. Only 41 countries have introduced the vaccine since it became available in 2006, including only a handful of countries in Africa and Asia, where the burden is greatest.
In the past three decades we have made tremendous advances in science that have allowed us to come up with numerous life-saving interventions. One of the most powerful interventions is vaccination. Vaccines have saved millions of lives in the past 50 years and have the potential to save millions more in the next 50 years. However, many children are deprived of life-saving vaccines, in my opinion partially because we have failed to appropriately communicate available knowledge to parents, healthcare providers, program managers and decision makers.
This is why Dr. Ciro de Quadros and I came together to form the ROTA Council, an organization of technical experts committed to providing the evidence policy makers need to accelerate the introduction of rotavirus vaccines in high-burden countries. Last week we hosted our second strategy meeting in Thailand during the 10th International Rotavirus Symposium, where we shared ideas to amplify our efforts. We also hosted an advocacy session during the Symposium to train and empower other scientists gathered from around the world on how to become advocates for rotavirus vaccines.
Last week’s Symposium offered a breadth of insights on the latest research including surveillance and modeling to confirm the burden of rotavirus mortality and morbidity, the ability of vaccines to reduce death and hospitalizations in real-world conditions, and the safety of the vaccines. There are several promising candidate vaccines in the pipeline from developing country manufacturers which, when ready, should improve vaccine availability and reduce cost. Important research also continues on rotavirus pathogenesis, immunity, vaccine performance and correlates of protection.
ROTA Council members gather for an annual strategy meeting in Bangkok.
Going forward, it is vital that we communicate data like we heard last week to the decision makers who must act in order to accelerate vaccine introduction. As scientists, medical practitioners AND advocates, we are in the unique position of being able to make the evidence come to life in ways that other messengers cannot. We are on the frontlines, conducting the research and treating the patients, and therefore we must add to our responsibilities the job of spreading the word so that policymakers are moved to act. We bring a double bank of knowledge that makes our voices incredibly powerful. The time has come for us as scientists to add our voices to the chorus calling for introduction of rotavirus vaccines.
Mathuram Santosham, MD, MPH, is Co-Chair of the ROTA Council and Professor of Pediatrics and International Health at Johns Hopkins University. He also serves as director of the Center for American Indian Health, director of the International Center for Maternal and Neonatal Health, and a Senior Advisor at IVAC.
By Dr. Chizoba Wonodi
Last month, I had the privilege of sharing the findings from a newly released International Vaccine Access Center study – the Landscape Analysis of Routine Immunization in Nigeria (LARI) – with a group of experts at the Center for Global Development (CGD) in Washington, DC. The talk, which focused on overcoming barriers to routine immunization (RI) in Nigeria, was hosted by IVAC’s Executive Director, Dr. Orin Levine.
I didn’t quite expect the level of interest the talk generated. Kudos to CGD’s Amanda Glassman for convening an impressive “sold out crowd” of donors and implementers including veterans and new entrants in the immunization field. The audience gave my colleagues and I plenty to chew on after we presented our findings. Below are some of the key points from the discussion.
Nigeria is an important country in the immunization world. It’s a large country with high child mortality and low immunization coverage rates. Of the 6 million Nigerian children born every year, more than 1 million fail to get fully vaccinated by their first birthday. But despite systemic weaknesses, Nigeria has taken impressive steps to improve vaccine access in recent years. Over the 2000 to 2010 decade, DTP3 coverage increased from 29% to 69%. And in 2012, Nigeria began a three-year rollout of the pentavalent vaccine.
Polio is still a problem for Nigeria. After nearly finishing the job of elimination in 2010, the country slipped, and in the last two years, the virus has made an unnerving comeback. International condemnation of Nigeria over the polio crisis put the government on notice. Everyone wants to know how to crack the polio nut in Nigeria, and raising routine immunization (RI) rates is part of the answer.
“We want to know the bottlenecks and barriers in routine immunization, to help us prioritize our interventions”.
This was the charge that Dr. Muhammad Pate gave to us at the outset of the LARI study. At the time, he was the Executive Director of Nigeria’s National Primary Health Care Development Agency. He’s now Nigeria’s Minister of State for Health.
We anticipated that solutions for routine immunization in Nigeria would need to be local ones. Our role as researchers was to listen, organize, synthesize and disseminate. Over the course of four months in 2011, we spoke to Nigerians working on RI at all levels of government from a sample of seven states and the federal capital territory.
Where are the bottlenecks?
We found that both supply and demand barriers are important impediments to RI performance. In many places, supply is not robust enough to meet existing demand; therefore focusing on addressing supply constraints was a pragmatic first step. Among the plethora of problems identified, three main interlinked barriers emerged: funding constraints, logistical challenges and lack of leadership. Put another way; no money to run programs when needed; inability to deliver vaccines for immunization sessions and lack of cold chain equipment; and political leaders who don’t prioritize RI.
This short list will come as no surprise to most people – they are typical symptoms of weak systems and fledging institutions. And in Nigeria, responsibility for tertiary, secondary and primary health is devolved across the three levels of government – federal, state and local respectively, but the capacity to handle responsibilities varies considerably, and is much lower at lower levels. Primary Health Care, and by extension, immunization services, which is the responsibility of the Local Government Areas (LGAs), bears the brunt of this capacity/responsibility gap.
Interestingly, funding constraints identified resulted more from the failure to expend than failure to budget. There are federal and state budget line items for routine immunization, but the release of such funds is neither guaranteed nor timely. The same thing happens at the LGAs, and to an even greater extent here, provisions are made but funding disbursements are not.
As such, RI programs struggle to conduct basic operational tasks needed to vaccinate children. For example, in the LARI study, program managers and health workers complained about the lack of funds to fuel vehicles or take public transport to collect vaccines from state or LGA cold stores.
With the country’s unreliable power supply, generators are a necessity. Where generators exist, there is often no money to fuel them to maintain the cold chain. Solar fridges and freezers lay fallow due to lack of maintenance. Partners like GAVI, Gates Foundation, WHO, UNICEF, DFID, EU, NORAD and USAID have helped make strides in some areas, but problems still remain.
The federal government plays an important role in procuring and supplying vaccines to states and providing technical oversight, but because of the structure of Nigeria’s government, the federal government does not have authority to drive change at lower levels. Solutions must be implemented at the state and LGA level, because most barriers are occurring in these areas.
The people we spoke to had many ideas for solutions to the problems of Nigeria’s RI system. In selecting solutions, we emphasized the need for in-country stakeholders to consider both impact & feasibility in order to maximize results with limited resources.
A health clinic in Nigeria.
High impact, simple to implement innovations may include:
Mechanisms to make financing more predictable and flexible to reduce barriers at national and sub-national levels. Ebbs in financial flows can be addressed through the use of basket/pooled funds (these have proven successful in some states). Financial guarantees and flexible funding may improve the likelihood that funds designated for RI are spent on RI—in a timely, efficient manner.
The delivery and supply networks also require urgent improvements, which could be implemented using transportation and cold chain maintenance contracts. These contracts could be designed to boost local economies and/or disadvantaged groups. Leadership and ownership at state and local levels are also critical to success. In the absence of the political will to act, holding governments accountable for their responsibilities can drive improvement. But the question is: how do you make political leaders accountable for delivery of immunization services when public awareness of benefits is low and local authorities don’t view immunization as a priority? These are questions for another day.
The Landscape Analysis of Routine Immunization in Nigeria was conducted at the request of Nigerian authorities with support from the Bill & Melinda Gates Foundation and the GAVI Alliance. Chizoba Wonodi, MBBS, MPH, DrPH is Lead of Nigeria Projects at IVAC. Cross-posted at National Vaccine Summit.
By Orin Levine and Ciro de Quadros
The world is anxious for a dengue vaccine. It is estimated that 40 percent of the global population is at risk, and in too many countries, dengue fever is common and frequently causes outbreaks. When it hits, the effects on families and communities include pain, economic hardship and fear of whether tomorrow will bring a fatal or serious illness to a household member.
Today The Lancet released the first ever results from a dengue vaccine trial with enough cases to measure the vaccine’s effectiveness. The trial’s results provide signals rather than definitive answers, and a mixture of both promise and unresolved challenges. To date, these represent the most promising indications that a safe, effective vaccine to prevent dengue is technically feasible. At the same time, the results on protection were inconclusive, somewhat inconsistent with the measured immune responses, and uneven across the four strains included in the vaccine. Fortunately, a much larger trial already underway in 10 different countries is likely to tell us by 2014 if the signals observed in this trial are accurate or not.
This phase 2b randomized, controlled trial, which was conducted in one dengue-affected area of Thailand called Ratchaburi, allowed the investigators to measure the vaccine’s safety and protective effects. The signal on safety was very promising. There were no significant safety concerns identified in this trial. Larger trials with longer follow up of people will be required to further establish the safety of these vaccines but the absence of safety concerns in a group of approximately 4000 participants is encouraging.
The mixed signals come in the area of protective efficacy. To understand the results you need to remember that dengue is not caused by a single virus, but rather by four different related viruses, known as DENV 1, 2, 3, and 4 and that the vaccine in this trial is designed to protect against all four. This is where the results are mixed and largely inconclusive. On the one hand, there was no overall reduction in dengue cases observed from the use of the vaccine. On the other hand, in sub-analyses of the overall study, there were indications of protective efficacy versus three of the four serotypes (DENV 1, 3, and 4). The disappointing signal was in the fact that no protection was observed versus infections with the DENV 2 virus, which was the most common serotype in this community (and hence, no overall protection was observed when the effects of all 4 were combined). This lack of observed protection vs. DENV 2 was also surprising, given that the vaccine appeared to stimulate good immune responses among those who received it. Deeper analysis of these results are needed to determine what might explain this observation, and more importantly, what might be done to overcome it.
It will be important to see the results of the larger trial and the effectiveness of the vaccine in different epidemiological settings. These results may mirror what we have seen in Thailand, but we could also see stronger results and demonstrably good protection in these larger trials. It’s just impossible at this point to predict. We at the Dengue Vaccine Initiative (DVI) will continue to follow the progress of Sanofi’s vaccine as we work to lay the foundations for the adoption and rollout of a licensed dengue vaccine in the future.
Vaccine research requires focus, creativity, tremendous dedication and multi-disciplinary teams. Success is never guaranteed, and many great ideas for vaccine candidates fail to become successful public health vaccines. For these reasons, the research teams in Thailand and at Sanofi deserve recognition for their tireless efforts to advance the dengue vaccine. We are grateful for the efforts to date, and eager to see what results come out of the next, larger phase 3 trial. In the meantime, the dengue virus better look out. A safe, effective vaccine might be right on its tail and about to overtake it.
Dr. Orin Levine is the Executive Director of the International Vaccine Access Center. Dr. Ciro de Quadros is Executive Vice President of the Sabin Vaccine Institute. Both organizations are members of the Dengue Vaccine Initiative.
Cross-posted at DVI and The Huffington Post.