Global peer community sets standards to save vulnerable children from infectious diseases

While survival for pediatric cancer in the U.S. now exceeds 85%, prognosis in much of the world remains at less than a 20% five-year survival rate. The major culprit is not actually cancer itself: Infectious diseases cause over half of all mortality during pediatric cancer treatment. 

Physicians are aware of the problem infectious diseases pose to childhood cancer patients, but various challenges and barriers confound infectious disease prevention and control globally. The St. Jude Global Infectious Diseases Transversal program was created to help institutions worldwide develop the expertise to overcome them.

“We address the issue of hospital safety for children, employees and parents,” explained Miguela Caniza, MD, MPH, Infectious Diseases Transversal Program director, St. Jude Global and St. Jude Departments of Global Pediatric Medicine and Infectious Diseases member. “Decreasing infection risk and impact is the first step to provide safe cancer care. Our focus is to create effective, sustainable, scalable processes that reduce the incidence and impact of infectious diseases and childhood catastrophic diseases, especially in underserved areas.”

The burden of infections is daunting in low- and middle-income countries, and a significant effort is needed to address it. “We have shown that 72% of deaths not related to cancer itself are sepsis or infection-related,” said Sheena Mukkada, MD, MPH, St. Jude Department of Global Pediatric Medicine assistant member, who is also part of the Infectious Diseases Transversal program. Mukkada is a co-author of a study in The Lancet Oncology cataloging sources of mortality in pediatric oncology in countries of varying income levels. “We have a key part to play in addressing that immediate need, which is why we [the St. Jude Global Infectious Diseases Transversal Program] exist and will continue to do so,” she added.

Finding creative ways to train infectious disease preventionists

In high-resource settings, hospitals often have infection preventionists, infectious disease specialists, microbiologists, pharmacists and many other medical disciplines that cooperate to prevent and treat infections. The situation in low- and middle-income countries is quite different. These institutions have limited resources, including personnel and expertise. Infectious disease management may fall to pediatricians and oncologists, who may not have the necessary background in the subject. 

Even if an infectious disease specialist is present, their workload may be immense. “A lot of times they might be the only infectious disease specialist working in their hospital or even in their general area,” said Maysam R. Homsi, DrPH, MPH, CCRP, Infectious Diseases Transversal program manager. “There’s no one to bounce ideas off or say, ‘OK, we did all these things that we generally do. I have not seen this before. What would you do?’” 

“The crux of the issue is that there are not enough infectious diseases specialists in all of these settings,” said Sergio Licona, MD, MBA, St. Jude Infectious Diseases Transversal program coordinator. “So, we need creative ideas on how to address the need and scale them up.”

The transversal program addresses the gap in infectious disease specialty care in two ways: training and community-building. 

For training, the group provides courses on infection prevention and control for infection preventionists and on leadership in infectious diseases for physicians caring for infections. These courses deliver eight-week foundational online coursework, followed by one to two weeks of in-person intensive instruction. These intensive trainings are delivered yearly by collaborative institutions that are close to home to encourage local participation and spread knowledge. Since many hospitals have no dedicated infectious diseases specialists, training just one person can have a major impact. 

“We are already seeing that having a person on site with infectious disease knowledge can be very helpful,” Caniza said.

For community-building, the program is developing the Global Infectious Diseases (ID) Network.

“We decided to form the Global ID Network,” Caniza said, “which has become a fantastic community of health care providers and training graduates. They come together to collaborate and to share their experiences and research.” 

The network keeps people in contact with St. Jude and each other after completing the training program. As problems in resource-limited settings are different from those in wealthier countries, such a peer network can be an invaluable source of practical information. 

For example, network members meet weekly to discuss their challenging patient cases through an initiative hosted by Global ID. “We established a weekly case discussion forum,” said Milka Vazquez, Infectious Diseases Transversal program coordinator. “We’ve created a place for them to bring their very hard, complex clinical cases and discuss them with people and experts around the world facing similar challenges in similar settings.” 

The discussions alternate weekly between Spanish and English. Even with this forum to share clinical experience on individual cases and speed knowledge sharing, it has become clear that collaborators need to perform their own research to collect local data and apply it in their ecosystem to lower infectious disease risks and improve control programs.

Facilitating research in resource-limited settings

“My hope is that every center that cares for children with catastrophic illnesses will be able to provide care that is safe and prevents, controls and cares for infections,” Homsi said. “But also, that they’re able to study and generate information from their own sites.”

Even after training in infectious disease prevention and treatment, a gap remains. Research from high-income countries does not cleanly translate to clinical practice in resource-limited settings. The Global ID Network physicians see an opportunity: performing their own research, the results of which will be more relevant to their situations. But first, they need to learn the basics of research.

“Our collaborators ask us, ‘How do you apply for grants and funding to support your research projects? How do you write a grant that looks good to reviewers? How do you get access to statistical analysis?’” Homsi said. 

St. Jude provides basic training to navigate research proposal development in collaboration with other network members. Research proposals are submitted, reviewed and critiqued, then given back to their authors to improve and send to funding agencies or begin research projects. 

“Currently, 96 members from 58 institutions and 28 countries are participating,” Caniza said. “We bring them to St. Jude once a year in the annual network meeting to share their research and continue collaborating.” 

Many members wish to collaborate or are actively executing multi-site projects. However, they have significant barriers. Regulations vary by country and institution, slowing many projects. For example, one institution may not require Institutional Review Board (IRB) approval for retrospective studies, while another may require researchers to track down every patient in a registry from decades ago. Time is also limited as many of these physicians work 14-hour or longer days, sometimes at multiple hospitals. Often outside of physicians’ normal expertise, navigating politics and convincing institutional leadership of the value of research can add to the challenge. 

“Multi-site projects are very complex,” Vazquez said. “So, one of the things we do is discuss the barriers they’re facing with the leaders of ongoing multi-site projects. They’ve talked about protocols, regulations and navigating the bureaucracy within three or four different institutions. Despite that, they thought it was worth it to exchange ideas, strategies and experiences as collaborators.”

Regardless of roadblocks, physician-scientists in low- and middle-income countries are still finding ways to navigate these challenges and address their research questions. They are making time because the results are potentially that valuable. Infection prevention and control, tailored to the institutions’ capabilities, has the chance to save children’s lives at their hospitals, a powerful motivating force to improve infectious disease management. 

“Ideally, I would love to see all these centers improve to meet a set of global standards for preventing and controlling infections in pediatric cancer patients,” Homsi said. That leads to the final challenge: What are the standards? And who sets them?

A St. Jude–led collaboration is setting the standard for infectious diseases management

While St. Jude has standards for care, the same challenges facing research and training also stymie guideline implementation. Standards and guidelines require modification of resource-limited settings where such modifications require direct input by the physicians whom those standards would bind. 

“Much of the work we do is guideline development,” said Mukkada. “And we re-examine the paradigms for how we create guidelines, adapted for different settings where they don’t have supportive care resources to contend with the expected toxicities of treatment, which is a vulnerability to infectious diseases.” 

Once standards are agreed upon, the St. Jude program helps implement them and then tracks outcomes. One example is a now-deployed fever registry.

“We co-created febrile neutropenia guidelines in Central America and the Caribbean and helped them implement the guidelines in their settings using a robust methodology,” Licona explained. “Then we worked together to adapt those guidelines to a site-specific context; we also track outcomes and adherence to those guidelines. Our basic work is guideline development, implementation and outcome tracking to identify intervention opportunities.”

“After we agreed on the guidelines, I developed a monitoring system, a registry for fever and neutropenia complications, to look at how people follow the guidelines and what the outcomes are,” Mukkada said. “We try to help collaborators understand that cycle should inform the next iteration of guidelines with locally relevant and produced data.” St. Jude houses the data, but local partners have exclusive access. 

The program continues to pursue that pattern of guideline development, implementation and tracking. Still, challenges remain, such as how to develop guidelines for issues that transcend locality and potentially impact many countries.

Tackling global antimicrobial use guideline development

While most guidelines are developed primarily for the care of individual patients, antimicrobial use is different. Broad use of antibiotics drives the growth of antimicrobial-resistant organisms, decreasing long-term efficacy for patients everywhere. Therefore, responsible antimicrobial usage is a high priority, where local decisions can have a global impact. However, poor access to an appropriate selection of antibiotics makes good stewardship difficult for many institutions in low- and middle-income countries. 

“In some places, lack of access to specific drugs sometimes leads to overly broad coverage because you can’t target treatment to a specific resistant bug,” Mukkada explained. “In other cases, you don’t have access to a broad enough selection of drugs to be able to treat what you would like to. So, the problem is very complex, including both under and overuse of antimicrobials.” 

Mukkada started an international collaborative to tackle the complexities of developing guidelines and standards for antimicrobial stewardship. The first partner was at St. Jude: Randall Hayden, MD, St. Jude Global Pathology and Laboratory Medicine (GPLM) Transversal program director, who co-founded the effort. Now, they are recruiting participants from around the world to represent many medical disciplines, ask the right questions, define challenges and create a plan. The collaborative is still in its infancy, but with over 100 participants so far, it has already taken its first steps to improve future antimicrobial use.

Creating a future to prevent and control the greatest threat to pediatric cancer patients

“We, as a program, are tackling the leading cause of treatment-related mortality in children with cancer,” Licona said. “The need is huge, and the only way to do it is to have strong relationships with all these institutions and allies.”

St. Jude continues to help lead the way in better infection control and infection. Across the globe, the hospital is already well known for its pediatric oncology care. The world is just beginning to recognize the value of the institution’s infectious disease expertise. The Global Infectious Diseases Transversal Program is there now, with training, locally adapted guideline development and peer connection, driving more and better research to save more lives.

“Organizations outside that know us — they know we’re St. Jude; we’re the leader in pediatric oncology, so they come to us,” Vazquez explained. “We use that leverage, that success St. Jude has had, to be able to work with them to help them implement their own programs to protect their children with cancer from infectious diseases.”