Setting the Stage

In rural sub-Saharan Africa and South Asia, regions home to 90 percent of the world’s poorest populations, most people living with severe, chronic NCDs (such as type 1 diabetes, sickle cell disease, and rheumatic and congenital heart disease) must travel long distances for many essential healthcare services. Ultimately, hundreds of thousands of people living with these life-threatening conditions—many of them children and adolescents—are left without options for affordable treatment.  

As a result, one in two children with type 1 diabetes in rural sub-Saharan Africa dies before diagnosis (1), and in South Asia, people living with type 1 lose an average of 45.2 healthy years from their lifespan. (2) Half of the nearly one thousand babies born with sickle cell disease in Africa each day will not live to see their fifth birthday. (3) And children with rheumatic heart disease in low- and lower-middle-income countries have a greater than 70 percent chance of dying before the age of 25. (4)

How have these disparities persisted, often flying well below the radar of the global NCD and child health agendas?

As these global health movements gained momentum in the 2010s, multilateral and bilateral success metrics (often tied to funding) were intentionally designed to reach the most people possible, with a focus on overall population health. This approach failed to acknowledge the priority of severe, but individually less common conditions when designing public health movements. Accordingly, global NCD and child health policies promoted interventions that many people will need across their life course, such as vaccines, hypertension drugs, education campaigns, and public policies that foster behavior modifications.

As an unintended consequence, conditions such as type 1 diabetes, sickle cell disease, and childhood heart disease have become largely invisible on the global stage, underfunded through public financing or public health systems. Vertical programs—many run by disease-specific organizations and accessible nearly exclusively to urban populations—sought to fill this gap. Yet the Lancet Commission on Reframing NCDs and Injuries for the Poorest Billion (the NCDI Poverty Commission) found that, in the absence of integrated care delivery strategies, hundreds of thousands of the world’s children, adolescents, and young adults living in lower-income rural areas would go without lifesaving care for severe conditions that almost
 always lead to premature death if left untreated. (5)

The Promise of PEN-Plus

PEN-Plus was born out of this context. In 2006, a group of clinicians began developing a new, 
integrated care-delivery model for people living 
with severe, childhood-onset NCDs at two public district hospitals in rural Rwanda, as part of a long-term collaboration between the Ministry of Health and Inshuti Mu Buzima (Partners In Health–Rwanda). 

Their guiding thesis was that the most effective and sustainable way to reach all people living with severe NCDs would be to move beyond vertical, centralized, and nongovernmental-organization-led interventions. Instead, healthcare leaders should identify a viable pathway for governments to provide these services through integration and decentralization of care within public health systems. The clinicians built the model as a complement to an earlier strategy: the WHO Package of Essential Noncommunicable (PEN) Disease Interventions. WHO PEN focuses on more common NCDs—such as hypertension, type 2 diabetes, and asthma—at the health center and community levels.

The innovation of PEN-Plus was in the design. The clinicians trained mid-level healthcare providers to diagnose and treat a cluster of severe NCDs that shared certain clinical cadences. This training proved especially crucial in treating type 1 diabetes and childhood heart disease, for which too much or too little medication can mean the difference between life and death.

The PEN-Plus approach also took advantage of shared space, workflow patterns, and training needs. Providers—principally nurses and clinical officers—could be effectively trained in just three months. Soon only two or three of these advanced care professionals were needed to staff each clinic, where they saw 15 to 30 patients a day. Physicians supervised initial consultations and confirmed initial diagnoses, and specialists visited the clinics every month or two to provide ongoing mentorship, consult on more complex cases, and link patients to referral hospitals for more acute specialty interventions, such as cardiac surgery.

Poised for Scale

The first PEN-Plus clinics offered a model for how lower-income country health systems could feasibly, safely, and effectively integrate care for patients with severe NCDs into their existing operations. By 2017, the Government of Rwanda had successfully scaled PEN-Plus clinics to each of its 42 district hospitals, with the original clinics serving as national training sites. 

Following the national scale-up in Rwanda, research studies confirmed high levels of feasibility and penetration of PEN-Plus implementation. Three years after the national-level training of nurses, all PEN-Plus clinics were staffed by at least one nurse with advanced training. Overall, the clinics had a high availability of national essential medicines for PEN-Plus conditions and a good adherence to PEN-Plus clinical protocols. (6)

Research also provided robust evidence of the effectiveness of the PEN-Plus model in addressing patient needs, increasing health workforce capacity, and remaining cost-effective even in low-resource settings. (7,8) In addition, a microcosting study from the Burera district of Rwanda found that the ongoing annual operating costs of PEN-Plus were only $0.23 per capita, suggesting the model’s affordability even for resource-constrained governments. (9)

Taken together, these results led to pilot programs in Haiti, Malawi, and Liberia that validated the adaptability of the PEN-Plus model to different contexts. (10) Based on these experiences, PEN-Plus served as a centerpiece of the Lancet NCDI Poverty Commission Report published in 2020, which presented detailed evidence of the urgent need for these types of services across all lower-income countries. (11)

Not content with leaving these findings to academia, the report authors joined with representatives of 15 lower-income countries to form the NCDI Poverty Network. This coalition of lower-income country governments and technical, policy, funding, and advocacy partners united in a single cause. The mandate of the Network is to support local leadership, financing infrastructure, and pathways to scale to ensure the PEN-Plus model reaches everyone, everywhere it is needed.

Achieving this goal is beyond the capacities of any single funder, government, or nongovernmental organization. Rather, it demands a coordinated effort across the value chain—and at local, national, and global levels—to shift entrenched systemic barriers and raise our collective expectations of what is possible.

Over time the Network grew to include hundreds of organizations, a coalition of unprecedented breadth and depth working toward a shared goal: to ensure that the poorest people living with severe NCDs in lower-income countries have access to quality care close to home. This commitment has coalesced into a Network initiative we now call the PEN-Plus Partnership, both a rallying cry and a coordinated, multi-sector effort to support countries’ progress in ensuring high-quality, fully integrated, person-centered care for people living with severe NCDs.

Thanks to the Network’s efforts, in the past three years PEN-Plus has transformed from an effort run by a single nongovernmental organization to a model endorsed by all 47 member states of the WHO African Region, with care being delivered in 15 countries. (12) UNICEF’s leadership has played a key role in seeding initiation in Bangladesh and expansion within Malawi, Mozambique, Nepal, and Zimbabwe. 

The WHO African Region has also assumed a major leadership role in rolling out technical support for member states to move toward PEN-Plus initiation. (13) That work received global interest in 2024, when the WHO African Region hosted the first International Conference on PEN-Plus in Africa, which convened representatives from 52 nations.

In 2022–23 alone, more than 400 additional healthcare workers—including nurses and clinical officers—received PEN-Plus training and ongoing mentorship. Even more dramatically, more than 11,000 people with severe, chronic NCDs now receive treatment in PEN-Plus clinics.

In partnership, national and global experts in the type 1 diabetes, sickle cell disease, and childhood heart disease communities are contributing their combined efforts to PEN-Plus patient populations. The Scottish Government has incorporated PEN-Plus into its global health strategy. And U.S. legislators are beginning to engage on this issue by including language about the needs of people living with childhood-onset NCDs in their guidance to USAID.

This swift progress has been driven forward and supported by shifting macro trends in global health capacity and investment. National government leadership and an increasing global focus on health-system-strengthening investments have raised the overall capacity of health systems in lower-income countries to address severe conditions. Many health systems can now provide appropriate referrals for acute episodes, have functioning laboratories and specialized equipment, and employ providers trained in the dosing and management of potentially toxic medications.

Severe NCDs are also broadly recognized as a growing and urgent global priority, opening space to highlight the gap in treatment access and to foster momentum to address that gap through a proven model of care. It is a testament to the progress of decades of investment in broader NCD and childhood public health efforts that PEN-Plus is positioned to scale exponentially. The groundwork has now been laid for a monumental leap forward in access to care for children, adolescents, and adults living with severe NCDs. 

Endnotes

1. Gregory G, Robinson TIG, Linklater SE, et al. Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study. Lancet Diabetes Endocrinol 2022;10(10):741–760.

2. Breakthrough T1D. Type 1 Diabetes Index. (https://t1dindex.shinyapps.io/dashboard)

3. Modell B and Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008;86(6): 480–487.

4. Hewitson J and Zilla P. Children’s heart disease in sub-Saharan Africa. SA Heart J 2010;7(1):18–29.

5. Bukhman G, Mocumbi AO, Atun R, et al. The Lancet NCDI Poverty Commission: bridging a gap in universal health coverage for the poorest billion. Lancet 2020;396(10256):991–1044. 

6. Niyonsenga SP, Park PH, Ngoga G, et al. Implementation outcomes of national decentralization of integrated outpatient services for severe non-communicable diseases to district hospitals in Rwanda. Trop Med Int Health 2021;26(8): 953–61.

7. Eberly LA, Rusingiza E, Park PH, et al. 10-Year Heart Failure Outcomes From Nurse-Driven Clinics in Rural Sub-Saharan Africa. J Am Coll Cardiol 2019;73(8):977–80.

8. Tapela N, Habineza H, Anoke S, et al. Diabetes in rural Rwanda: high retention and positive outcomes after 24 months of follow-up in the setting of chronic care integration. Int J Diabetes Clin Res 2016;3:1–6.

9. Eberly LA, Rusangwa C, Ng’ang’a L, et al. Cost of integrated chronic care for severe non-communicable diseases at district hospitals in rural Rwanda. BMJ Glob Health 2019;4(3):e001449.

10. Ruderman T, Chibwe E, Boudreaux C, et al. Training mid-level providers to treat severe non-communicable diseases in Neno, Malawi through PEN-Plus strategies. Ann Glob Health 2022;88:69.

11. Gupta N, Mocumbi AO, Arwal S, et al. Prioritizing Health-Sector Interventions for Noncommunicable Diseases and Injuries in Low- and Lower-Middle Income Countries: National NCDI Poverty Commissions. Global Heal Sci Pract 2021;9:3:1–14.

12. World Health Organization. PEN-Plus: A regional strategy to address severe noncommunicable diseases at first-level referral health facilities. AFR/RC72/4. WHO Regional Office for Africa. Brazzaville. 2022.

13. Moeti M, Mocumbi AO, Bukhman G. Why there is new hope for the care of chronic diseases in Africa. BMJ 2023;383:2382.