The third session of the workshop focused on integrating and revamping health care delivery models and interventions to address the convergence of infectious diseases and noncommunicable diseases (NCDs). The session included four presentations that discussed how health systems are responding to the dual burden of infectious diseases and NCDs and how to leverage existing structures and build local capacity. The presenters offered examples of models that incorporate community-based and people-centered approaches to integrating care that have aimed to improve quality and expanded access to care. They also explored how primary care can help address the convergence in low- and middle-income countries and highlighted some approaches needed for prevention and control at the local and country levels. The session was moderated by Marcos Espinal, director of communicable diseases and health analysis at the Pan American Health Organization.
The first presenter was Miriam Rabkin, associate professor of medicine and epidemiology at the Mailman School of Public Health, Columbia University, and director for health systems strategies at ICAP Columbia, who discussed how the scale-up of HIV services can be leveraged to provide NCD services in health systems. Sylvester Kimaiyo, executive director of the Academic Model Providing Access to Healthcare (AMPATH), Kenya, described the successful outcomes of the AMPATH model in his country over the past two decades. Gene Bukhman, director of the Program in Global Noncommunicable Disease and Social Change at Harvard Medical School, provided an overview of the new discipline of integration science and how it can help to address the convergence of infectious disease and NCDs. Finally, Catherine
Oldenburg, assistant professor and Francis I. Proctor Foundation faculty member at the University of California, San Francisco, described how the use of mass administration of antibiotics can contribute to reducing child mortality.
Miriam Rabkin, associate professor of medicine and epidemiology at the Mailman School of Public Health, Columbia University, and director for health systems strategies at ICAP Columbia, explored how the scale-up of HIV services can be leveraged to provide NCD services in health systems. Rabkin described ICAP’s work on HIV, which has been a primary focus of the global health center and aims to deliver transformative solutions to strengthen health systems around the world through projects in more than 30 countries. In addition to policy-focused work, ICAP has extensive experience in implementation around HIV services and systems. Through ICAP-supported HIV services, more than 35 million people have been tested for HIV, more than 650,000 women have received antiretrovirals to prevent HIV transmission to their babies, approximately 2.5 million people have been enrolled in HIV care, and 1.5 million people have begun HIV treatment (ICAP, 2019; Rabkin, 2019).
Leveraging HIV Platforms to Deliver Care for Noncommunicable Diseases
Rabkin described the rationale for leveraging HIV platforms to deliver care for NCDs (Shigayeva et al., 2010; Rabkin et al., 2014). Many countries have both a high prevalence of HIV and a high prevalence of NCDs, although the colocated epidemics—or possibly syndemics—can play out quite differently in different contexts and geographies. Another reason to leverage HIV programs is that the expansion of HIV treatment and prevention services has been remarkably successful with the leadership of communities and ministries of health and support from the global community and donors. Population health impact surveys from several countries in sub-Saharan Africa demonstrate that today those countries have better HIV control than the United States (El-Sadr et al., 2019). HIV and certain NCDs also have shared systems challenges, such as the need for continuity of care—including primary prevention, secondary prevention and treatment—over the life cycle, rather than episodic, symptom-based care. The prevalence of NCDs and NCD risk factors among people living with HIV is at least as high as the rest of their communities, and even higher in some cases, she noted. Rabkin cited the relative resource wealth of HIV programs compared with NCD programs as another reason to leverage HIV platforms. Although diverting funds from
HIV platforms and redirecting them toward NCDs is not leveraging per se, it highlights the dearth of resources available for both prevention and treatment of NCDs in discussions about synergies or integration, she stated. In the landscape of available funding, there is no significant money for NCDs (Nugent, 2016). She said, “One plus zero is still one. You can’t integrate something that does not exist.”
Lessons from Scaling Up the Delivery of HIV Services
Rabkin outlined lessons gleaned from scaling up of the delivery of HIV services that are applicable to NCDs, particularly in austere health systems, which are characterized by a lack of health care providers and weak laboratory, infrastructure, drug procurement, monitoring, and governance systems (El-Sadr et al., 2017; Rabkin et al., 2018a). The first lesson is to use the public health approach to deliver services at scale through delivery mechanisms and platforms that do not require specialist physicians and academic health centers, she noted. Rather than focusing on how to treat symptomatic people who come to a hospital or clinic, the public health approach emphasizes the burden of a condition in the community and the associated cascade of the number of people:
- that have this condition,
- linked to treatment,
- who have engaged with treatment, and
- who have been successfully treated.1
Another lesson from HIV scale-up is the need to be realistic and innovative in dealing with health workforce constraints, said Rabkin. If platform services cannot be delivered by a nonphysician clinician, then they cannot be delivered at all in many parts of the world. HIV scale-up demonstrates the importance of engaging the private sector, faith-based organizations, and civil society organizations, as well as the need to prioritize meaningful involvement by people who are actually receiving the services. For instance, at meetings focused on HIV, there are generally attendees representing the recipients of HIV care, noted Rabkin. Further lessons from HIV scale-up are the importance of a rights-based approach, of working toward universal health coverage, and of investing in policy-relevant data systems.
1 Treatment success can be operationalized differently for different conditions. For example, Rabkin said that treatment success for HIV may mean viral suppression, while for diabetes it may mean good glucose control.
Defining Key Terms and Concepts
Rabkin explored some of the different meanings associated with the concept of integration of services, systems, and programs. Although integration is an intuitively appealing strategy that is often presumed to be cost-effective, the evidence base from implementation science on the benefits of integration remains scant and is undermined by a lack of common understanding about what integration involves (Shigayeva et al., 2010). Precision is helpful when discussing integration, she said. Integration can refer to integrating clinical services at the point of care so people with more than one condition receive care for both that is holistic and not fragmented—such as integrating HIV and tuberculosis (TB) testing, prevention, and treatment services or integrating maternal and child health services with services to prevent mother-to-child transmission of HIV. Integration can also refer to integrating programs and systems on multiple fronts, including financing, budgeting, strategic planning, procurement and logistics, monitoring and evaluation systems, and health workforce and training plans.
Discussions about leveraging HIV platforms typically refer to leveraging HIV programs, said Rabkin. In many low- and middle-income countries, HIV programs were the first large-scale, public-sector continuity care initiative for chronic diseases (Rabkin and El-Sadr, 2011). These programs were designed to provide prevention and treatment throughout the life cycle in health systems with limited resources, and they were developed to be delivered by nonphysician clinicians, community health workers, and laypeople through a public health approach (Rabkin and El-Sadr, 2011). Initially, these programs were often vertical and siloed, although they are now more often diagonal (Farmer et al., 2013). The lessons learned around focusing on the public health approach and using nonphysician clinicians should not have to be relearned for NCDs, said Rabkin. This dialogue needs to center around people, with support from system components such as governance, information, financing, service delivery, human resources, and medicines and technologies, she said. Table 7-1 outlines the types of functions that HIV programs need to deliver, which are the same functions that many NCD programs also need to deliver, such as systems, strategies, a capacitated health workforce, and point-of-care delivery diagnostics to support people throughout the care cascade (Rabkin and El-Sadr, 2011).
Integrating Noncommunicable Disease Services into HIV Programs
To illustrate how NCD services might be integrated into HIV programs, Rabkin described the HEART study, an example of implementation science research carried out in Eswatini, also known as Swaziland. The prevalence and burden of both HIV and cardiovascular disease are high in the country
|Key Elements of Chronic Care Delivery Systems||Examples Common to HIV and NCD Programs|
|Diagnosis and enrollment||Identification of risk factors, early diagnosis, opportunistic case-finding, point-of-service diagnostics, standardized diagnostic protocols.|
|Retention and adherence||Appointment systems, defaulter tracking, patient counseling, expert patients, secure medication supply chains, pharmacy support.|
|Multidisciplinary family-focused care||A multidisciplinary team of health care providers and community members delivers care in partnership with the patient.|
|Longitudinal monitoring||Health information systems have standardized and easily retrievable data.|
|Linkages and referrals||Links within the health facility (to lab, pharmacy, others), between facilities, and between facility and community.|
|Self-management||An informed, motivated patient is an effective manager of his/her own health.|
|Community linkages and partnerships||Need functional partnerships between health facility-based providers and community-based groups that facilitate access to services across the care continuum.|
SOURCES: Rabkin presentation, June 12, 2019; ICAP, 2011.
(UNAIDS, 2017; WHO, 2018c). Swaziland has the highest prevalence of HIV in the world, but 11 percent of deaths are actually caused by cardiovascular disease (Palma et al., 2018). Cardiovascular disease risk factors (CVDRFs) screening and management are recommended for people living with HIV, but they are not routinely performed (Rabkin et al., 2015). The HEART study sought to explore the feasibility and acceptability of introducing CVDRF screening for people living with HIV into a busy HIV treatment clinic.2 Additionally, the study compared integrated management of CVDRFs—with the HIV provider managing both HIV and CVDRFs during HIV clinic
2 CVDRF screening for patients aged ≥ 40 years receiving antiretroviral treatment included blood pressure measurements to detect hypertension, point-of-care HbA1c tests for diabetes, point-of-care cholesterol test, and tobacco history. A subset of people who screened positive for CVDRF (with hypertension and/or ≥ 10 percent 10-year CVD risk) were randomized to integrated or referred management.
visits—versus referred management to an outpatient department, in which the HIV provider manages HIV clinical concerns at HIV clinic visits and a general internist manages CVDRFs at outpatient clinic visits. She noted that both randomized groups were treated in different departments of the same physical facility. The study randomized those who screened positive and collected data using screening results, exit interviews with screened patients, time-motion studies, key informant interviews with health care workers, and key informant interviews with patients randomized to integrated versus referred management.
Screening was high yield, with 39 percent of almost 1,800 people screened having at least one CVDRF (primarily hypertension) (Rabkin et al., 2018b). Screening added about 11 minutes per visit, Rabkin noted, largely because staff had to wait for the results of the point-of-care tests. It may seem trivial, she said, but this had substantive effects in a clinic where an average refill visit is about 5 minutes. Staffing challenges were a significant barrier to screening, although the screening and the wait time were acceptable to 100 percent of the patients who took part; 77 percent reported being willing to receive screening annually, even if it took more than 10 minutes (Rabkin et al., 2018b). Improvement in hypertension and diabetes control was seen in both integrated and referred arms, and retention rates were also similar in the two arms (Palma et al., 2018; Rabkin et al., 2018b).
Rabkin cited another study that compared the resources, systems, structures, job aid, and tools developed for HIV projects with those developed for diabetes services. The latter were being carried out in a relatively less resourced way, for example, using less organized, handwritten registries (Rabkin and Nishtar, 2011). In an Ethiopian setting, researchers leveraged HIV programs to support diabetes services. They tried to duplicate the systems used for the HIV clinic for the nearby diabetes clinic by implementing the same types of training, tools, job aids, and peer education program (Rabkin et al., 2012b). Compared to baseline, follow-up results showed increases in the following services documented at least once in a patient’s three most recent visits:
- Blood pressure services (35 percent increase)
- Funduscopic examination (49 percent increase)
- Foot exams (78 percent increase)
- Neurological exams (53 percent increase)
- Oral or dental exams (76 percent increase)
- Visual acuity testing (37 percent increase)
In conclusion, Rabkin highlighted some barriers and opportunities to address gaps in HIV–NCD integration and to learn from HIV programs in implementing NCD programs for the general population. Regarding
challenges, she noted that funding barriers persist for NCD services and related implementation science research. Opportunities include the integration of NCD prevention, screening, and treatment services into HIV programs; sharing lessons, strategies, and tools from HIV scale-up to enhance selected NCD programs; and the integration of continuity care systems for chronic infectious and noninfectious diseases (Rabkin et al., 2012a).
Sylvester Kimaiyo, executive director of AMPATH, Kenya, described the outcomes of the AMPATH model in Kenya over the past two decades. AMPATH, an acronym for Academic Model Providing Access to Healthcare, was formed to seek funds from outside the realms of universities, hospitals, and ministries of health to support care, research, and training (Mamlin et al., 2004; Einterz et al., 2007). AMPATH differs from other university consortia in that care leads the way, but care is integrated with research and training. AMPATH has achieved its goals in terms of bringing funders and supporters to the table, Kimaiyo reported, including the U.S. Agency for International Development (USAID) and the U.S. Centers for Disease Control and Prevention.
Kimaiyo traced AMPATH’s journey from its origin in 2001 with a nascent HIV care program in two clinics in and around Eldoret in western Kenya. In 2008, AMPATH expanded its focus to include chronic diseases and primary care, and in 2010, a memorandum of understanding was signed with the ministry of health in Kenya to work on NCDs (Bloomfield et al., 2011). In 2016, population health began in Busia and Uasin Gishu (Kimaiyo, 2019). As of 2019, AMPATH supports more than 800 clinics across Kenya, with a catchment population of about 15 million and about 150,000 patients currently receiving treatment (AMPATH, 2019). Along the way, they had to address challenges with respect to space, progressing from services delivered in tents to purpose-built structures, the latest addition being the Chandaria Cancer and Chronic Diseases Center. Staff-related challenges included morale, burnout, and transferral, according to Kimaiyo. Additional challenges have related to the availability of antiretroviral therapies, record keeping, addressing food security and poverty, transparency and accountability, and the development of exit and sustainability plans (Kimaiyo, 2019).
Foundational Elements of AMPATH’s Success
Multiple factors have contributed to the success of AMPATH, said Kimaiyo. One advantage is that AMPATH has one “central nervous system.” AMPATH is a parastatal of the government of Kenya, but it acts like a nongovernmental organization with autonomous financial management
when it receives funding. He noted that AMPATH has benefited from academic partnerships with Moi University College of Health Sciences and the Moi Teaching and Referral Hospital in Kenya, as well as a consortium of universities led by Indiana University. AMPATH also works closely with 10 county governments and the national ministry of health. Institutional and governmental support have been helpful in providing innovative, interactive medical education. The community-based education and service program has been a major contributor to AMPATH’s success, providing a foundation for partnering with the community and the ministry of health, leveraging the potential of academic medical centers, creating the foundation for AMPATH’s care system, providing opportunities for research, and influencing national policy and health indicators.
The AMPATH medical record system was developed as an electronic data repository of every visit in an open medical record system platform (Mamlin and Biondich, 2005). The numbers of patients treated are indicators of AMPATH’s success, said Kimaiyo. AMPATH enrollments for HIV/AIDS increased from around 800 in 2002 to almost 200,000 in 2015 (Kimaiyo, 2019). Cumulative AMPATH research and training grants by year have followed a similar trajectory, from less than $1 million in 2002 to more than $125 million in 2018, as have the numbers of AMPATH publications per year—around 200 publications on their work in 2017 and 2018 alone, he stated.
Novel Models for Delivering Integrated Care
Kimaiyo described four projects related to integration that AMPATH has under way in Kenya. Three are existing novel models of care. In Busia and Trans Nzoia counties, AMPATH is providing integrated screening and care for chronic conditions (hypertension, diabetes mellitus, cervical cancer, and breast cancer) at the primary care level (Kimaiyo, 2019). Comprehensive community- and facility-based hypertension and diabetes screening and care are ongoing in Bungoma (Kimaiyo, 2019). In Uasin Gishu a population health model is providing comprehensive community- and facility-based screening and care to achieve universal health coverage (Kimaiyo, 2019). The fourth project was slated to begin in Bungoma in 2019 to evaluate the effect of strategies tailored to increase male participation in hypertension and HIV screening activities, as well as their linkage and retention in care. The model will implement comprehensive community- and facility-based hypertension and HIV screening. He reflected that integration may not be appropriate at all levels of the health system, but it is beneficial in at least a few levels.
Gene Bukhman, director of the Program in Global Noncommunicable Disease and Social Change at Harvard Medical School, discussed how to address the convergence of infectious disease and NCDs with integration science. He began by distinguishing between integration science and what is conventionally referred to as implementation science. Implementation science is an existing approach to studying how well delivery models perform, their uptake, and their barriers to uptake (Bauer et al., 2015). Integration science, which is still in its infancy, is the science of design of delivery and employs different kinds of techniques and approaches other than research trials (Bukhman, 2019).
The Long Tail of the Burden of Disease
To discuss integrated interventions for addressing NCDs, Bukhman drew on his clinical experience working in Rwanda with Partners In Health. The top panel of Figure 7-1 depicts the burden of disease in Rwanda in 2005, showing larger burdens of communicable, maternal, perinatal, and nutritional conditions on the left side and NCDs and injuries forming the long tail on the right side. The larger-burden conditions shown on the left side of the curve were addressed through vertical interventions—such as universal access to antiretroviral therapy and insecticide-treated bed nets—as well as interventions that were more integrated. For instance, the World Health Organization’s (WHO’s) Integrated Management of Childhood Illness guidance was used to manage diarrheal disease, malaria, and pneumonia in children.3 Bukhman noted that vertical initiatives do not have a comparable population effect on NCDs and injuries that vertical strategies can have on other diseases, such as cancer-specific vertical initiatives. Because the conditions in the long tail are heterogeneous, interventions need to be packaged or clustered to address the aggregate burden of disease.
The bottom panel of Figure 7-1 provides a closer view of the lower-burden conditions in the long tail of the curve with examples of packaged interventions. Bukhman noted that from an ethical standpoint, many of the conditions in the long tail share properties with the larger-burden conditions on the left side of the curve, both in terms of cost-effectiveness and an affected population that skews toward children and the poor. Thirty years later, the curve of the ranked causes of all-age disease burden in Rwanda looks starkly different. Mortality attributable to diarrheal diseases and major
3 More information about Integrated Management of Childhood Illness is available at https://www.who.int/maternal_child_adolescent/child/imci/background/en (accessed July 31, 2019).
childhood illnesses have also declined dramatically. Bukhman described this new epidemiological phase as “all tail.” He said that these outcomes were largely achieved through community-based interventions that were not contingent on a strong health system or functioning health centers. Achieving a population health effect requires thinking managerially and operationally about how to integrate services through clustering, he emphasized.
Developing a Science of Integration in Global Health Delivery
Declines in major causes of childhood deaths—such as diarrheal diseases and major childhood illnesses—have flattened the distribution of the global burden of disease, said Bukhman. Increasingly, the problems related to infectious disease and reproductive, maternal, neonatal, and child health are also “long-tail problems.” The infectious disease space, for example, is now dealing with conditions like drug-resistant TB that are complex but not significantly affecting public health. Bukhman listed a set of more than 20 interventions for NCDs that he considers to be just as cost-effective and as compelling from an equity standpoint as interventions that are currently prioritized for infectious disease and maternal and child health.4,5 These interventions cannot be operationalized or scaled up in isolation, so Bukhman offered three general principles of planning interventions for the long tail:
- Leverage inefficiencies in existing space and staffing.
- Decentralize progressively.
- Optimize clustering of related services.
Bukhman maintained that moving toward a new science of integration would help to provide operational clarity and to link up evidence-based interventions, health-sector priority setting, and implementation. He offered a provisional definition for the science of integration in global health delivery: “the study of delivery model design, including optimal clustering of tasks among providers, and interfaces within and outside of the health system.” A first step in developing an integration science is to define what is being optimized, such as equity, cost-effectiveness, and/or financial risk protection. The next step is to define the properties of interventions and related competencies to understand their underlying structures. Studying the historical team structure and task distribution within health systems can then be used to model the optimal redistribution of tasks. Existing
4 The 23 interventions that Bukhman listed included the following: appendectomy, broken fractures, colostomy, combination therapy for moderate to severe rheumatoid arthritis, fracture reduction, gallbladder removal, hernia repair, integration debridement, management of bowel obstruction, management of epilepsy with generic antiepileptic medications, management of type 1 diabetes, medical management of acute decompensated heart failure, prophylaxis for bacterial infections in sickle cell anemia, relief of urinary obstruction by catheterization, repair of perforations, secondary prophylaxis of rheumatic fever, shunts for hydrocephalies, sickle cell screening, surgical treatment of early-stage breast cancer, trauma ileostomy, trauma-related amputations, treatment of acute pharyngitis, and urethrectomy.
5 During the discussion, Bukhman noted that among the priority NCD interventions he listed during his presentation, most were acute care and surgical interventions, not chronic care interventions as conventionally understood.
computer-based techniques for supporting system design and analysis may be important to consider for smaller systems (Bellman and Landauer, 2000). However, constructing and integrating large systems will require an actual science of integration supported by principles and corresponding analytic methods, he added.
Chronic Care Decentralization and Integration in Rwanda
Bukhman described an example of an intuitive approach to chronic care decentralization and integration from Rwanda (Gupta and Bukhman, 2015). After the devastation of Rwanda’s health system in the mid-1990s, health services were highly centralized and essentially limited to teaching hospitals, Bukhman recounted. Over time, there were progressive decentralization cascades based on shared competencies (Sekabaraga et al., 2011). Mental health and TB-HIV care were among the first to be decentralized to district hospitals (Binagwaho et al., 2014; Mohand et al., 2017). By 2005, a gap emerged in decentralized care for severe NCDs, such as type 1 diabetes and advanced rheumatic heart disease, Bukhman continued. To address this gap, they developed a delivery model for use at the referral center level. By 2015, the delivery model had been implemented in all central hospitals. In 2019, Rwanda is decentralizing simpler, more standardized chronic care for NCDs to health centers (PIH, 2011). They are also developing integrated chronic care at health centers and in the community (PIH, 2011).
Although the intuitive approach to decentralization used in Rwanda has benefits, Bukhman suggested that a more structured, model-based approach would be superior in determining the optimal clustering of interventions and in developing a typology of chronic care services. The experience in Rwanda demonstrates the benefits of decentralization cascades and the rationale for prioritizing the rollout of intervention packages in district-level hospitals at an early stage in the process, said Bukhman. The approach has the potential to reach the highest-risk individuals and provides an opportunity to build leadership for training, supervision, and mentorship of services at the health center level.
Ongoing Work in Integration Science
In many systems, an initial goal of complete coverage of complex chronic care service packages at the district-level hospitals is achievable in the short term, noted Bukhman. WHO has a Package of Essential Noncommunicable Disease Interventions (WHO PEN)6 that is a set of cost-effective interven-
tions for primary care in low-resource settings, but it does not encompass services for more severe and chronic types of NCDs that cannot be managed well at the primary care level. To address this gap, the proposed PEN-Plus strategy would create specialized outpatient NCD clinics at first-level hospitals (Tapela et al., 2006; Kwan et al., 2013; Bukhman et al., 2015; Habineza et al., 2017; Eberly et al., 2018a,b, 2019; Rusingiza et al., 2018). The Global Health Delivery Partnership, comprising Partners In Health, teaching hospitals in Boston, and Harvard Medical School, is working with more than 15 low- and middle-income countries that have undertaken national NCDs and injury poverty commissions. They are exploring how emerging theories of health system integration can be applied to address NCDs and injuries among poor and vulnerable populations.
In her presentation, Catherine Oldenburg, assistant professor and Francis I. Proctor Foundation faculty member at the University of California, San Francisco, discussed the mass administration of antibiotics to reduce child mortality. She described how this integrated intervention emerged out of mass administration campaigns to prevent blinding trachoma. The Proctor Foundation, an organized research unit within the University of California, San Francisco, was originally founded for the elimination of blinding trachoma in the American Southwest. After that goal was achieved in the 1950s, they expanded the focus to eliminating trachoma worldwide through a combination of approaches, with mass distribution of azithromycin as a cornerstone.
Mass Drug Administration for Infectious Disease
Mass drug administration is a platform that can be used to administer preventive chemotherapy to an entire community or populations at risk when there is transmission of infectious disease. Oldenburg explained that mass administration is typically carried out using campaign-style delivery once or twice per year. More frequent administrations are not generally feasible because of associated logistic and supply chain complexities. These campaigns typically involve either door-to-door delivery or delivery at central points of distribution that are publicized and supported by mobilizers. Mass administration interventions require a safe, effective, and low-cost drug, said Oldenburg. For example, mass administration with doxycycline would not be appropriate for an infection that is predominantly affecting children because of the risk of adverse events. Common examples of mass drug administration include
- chemoprevention of seasonal malaria in areas with highly seasonal malaria epidemics,
- prevention of onchocerciasis using ivermectin,
- prevention of soil-transmitted helminths using albendazole,
- prevention of lymphatic filariasis using ivermectin, and
- prevention of trachoma using azithromycin.
Mass Azithromycin Administration for Trachoma Control and Mortality
Oldenburg described the natural history of trachoma, an infection caused by the Chlamydia trachomatis bacteria. In an infected child with an inflammatory response, the characteristic pattern is that after years of repeated infections—generally before the age of 10—the inflammation turns into scarring. Eventually the eyelash begins to turn and touch the cornea, so the eyelash rubs painfully on the cornea with each blink of the eye. This eventually results in a corneal infection that is no longer amenable to widely available treatments. Corneal transplant options are not available to most of the patients with end-stage trachoma. She said that progress is being made and rates are declining globally, but trachoma remains one of the most common infectious causes of blindness in the world (Bourne et al., 2013; Cox et al., 2017). A cluster randomized trial administered four annual mass treatments of azithromycin to an entire community in Ethiopia with hyperendemic trachoma.7 The prevalence of ocular chlamydia decreased from about 40 percent at baseline to around 5 percent toward the end of the study (Gebre et al., 2012).
Azithromycin is a broad-spectrum antibiotic that also has activity against other bacteria. Oldenburg explained that during the early stages of some azithromycin trials for trachoma, there were questions about possible spillover effects of mass azithromycin administration, particularly on infectious burden in children. Studies that have looked at the effect of mass administration of azithromycin on diarrhea, malaria, and respiratory infections in children have generally shown positive results (Coles et al., 2011; Oldenburg et al., 2019). The children who received azithromycin for trachoma control also had reduced burdens of diarrhea, malaria, and respiratory infections—some of the most common causes of postneonatal mortality in areas where trachoma is endemic (Coles et al., 2011). A 2009 study established that mass administration of azithromycin for trachoma had significant benefits for the child recipients in Ethiopia (Porco et al., 2009). The study found a 50 percent reduction in mortality among children who lived in communities that received azithromycin for trachoma compared to children from communities in which
7 Trachoma programs treat children who are 6 months of age and older, and those who are younger than 6 months get topical tetracycline.
treatment was delayed for 1 year. Oldenburg described this as a remarkable reduction in mortality for a single-dose administration.
Oldenburg presented the results of the MORDOR study in Malawi, Niger, and Tanzania, which was designed to reproduce the observed mortality benefits of azithromycin, but in rural communities with no trachoma (Keenan et al., 2018). Between 2015 and 2017, more than 1,500 communities were randomized to receive either biannual mass azithromycin or biannual placebo. Children between ages 1 month to 59 months were treated, because they are the subset of the population under 5 years of age that has the highest mortality. Communities were followed for 24 months with a biannual census to ascertain mortality. The deaths per thousand person years in the control arm varied widely, with the largest mortality rates, not unexpectedly, seen in Niger. Overall, there was 13.5 percent reduction in mortality in the azithromycin communities compared to placebo communities in each country (Keenan et al., 2018). When disaggregated by country, this effect was driven by the 18.1 percent mortality reduction in Niger, which had the largest national burden of child mortality in the study (Keenan et al., 2018). There was no evidence of a difference in Malawi and Tanzania specifically, but the study was not powered for country-level comparisons (Keenan et al., 2018).
Oldenburg noted that the absolute number of deaths averted per age group may give the impression that targeted administration to certain age groups would be preferential. However, the research suggests that mass treatment is the most effective way to reduce mortality, she said. The risk of mortality is higher in younger children, but the absolute number of deaths averted is lower because of the relative sizes of the population. Therefore, it is best to treat all children under 5 years in order to maximize the number of people that benefit, she said.
Mass Administration and Antimicrobial Resistance
Oldenburg described the results of a systematic review of adverse events following mass azithromycin for trachoma control, which looked at all of the evidence of antimicrobial resistance (O’Brien et al., 2019). In general, mass drug administration with azithromycin leads to increased selection for macrolide resistance in pneumococcus (O’Brien et al., 2019). The increase in resistance tends to follow immediately after the mass administration, she noted. Although there is some evidence that the resistance persists over time, it tends to reduce once the antibiotic selection pressure is removed. More research is needed to examine antibiotic resistance following mass administration targeted only at children, she noted. Short-term changes have also been observed in the composition of the microbiome—specifically, reduction in bacterial diversity—after mass azithromycin administration
(Oldenburg et al., 2018). Studies looking at longer-term changes to the microbiome following azithromycin treatment are ongoing, she added.
Targeting and Scaling Up Mass Administration
Mass drug administration works where there is a large burden of disease, said Oldenburg. Global child mortality rates are changing fairly rapidly over time, so consideration of where to implement mass administrations needs to be informed by the background mortality rate of the setting—for example, selecting geographic regions with more than 100 under-5 deaths per 1,000 live births (Golding et al., 2017). Discussions about the potential for global scale-up of mass administered azithromycin for child mortality are considering how to use existing mass drug administration platforms that are already in place for neglected tropical diseases. She noted that mass azithromycin administration for child mortality could potentially be integrated into existing trachoma programs or into other programs focused on overlapping epidemics. It could also be integrated into other existing platforms, such as vaccinations, through which children are already being treated. Regardless of the strategy, any scale-up will need to include monitoring for antimicrobial resistance, she added.
Following the presentations, the discussion portion of the session began with all four panelists. To open up the discussion, Marcos Espinal, director of communicable diseases and health analysis at the Pan American Health Organization, asked the presenters to identify some of the greatest bottlenecks to integration.
Bukhman replied that there are structural bottlenecks within WHO and ministries of health that are affecting the operational transformation toward strategies for chronic care integration. WHO has units focused on chronic care coordination and integration that are distributed across the range of categories—for example, rehabilitation services, mental health, and chronic care for infections and NCDs. He indicated that as part of its broader reforms focused on universal health coverage, WHO has an opportunity to break down the walls between units with a disease-specific focus and chronic care integration units. Ministries of health face similar problems, but developing chronic care integration units would allow for more operational clarity and better planning than units focused exclusively on NCDs, he added.
Kimaiyo cited financing as a barrier. Although HIV is well funded, programs that are candidates for integration with HIV programs typically do not have their own funding or staffing. The transition toward universal
health coverage could provide an opportunity for governments to assume more autonomy, he suggested, but the reality is that donors tend to prefer funding vertical projects.
Rabkin added that administrative silos tend to follow the funding. In her experience, ministries of health are not resistant to the idea of integrated chronic care, but NCD departments are severely underresourced compared with HIV departments. She predicted that this bottleneck will not be overcome without more funding for chronic diseases, even with the best of will and the best of science.
Bundling HIV Services with Noncommunicable Disease Services
Espinal opened the floor for questions. First, Emily Erbelding, director of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, commented that The President’s Emergency Plan for AIDS Relief (PEPFAR) was designed to be a siloed, vertical program. However, the consequent stigma associated with receiving PEPFAR-funded services, especially among men, has reduced the program’s efficiency to an extent. Given that PEPFAR made gains when HIV testing was included as part of a chronic disease package, she suggested that HIV services might be enhanced if they were bundled with NCDs. Rabkin clarified that HIV testing uptake has been shown to improve when it is combined with testing and screening for other conditions, regardless of whether those other conditions are NCDs (Kabami et al., 2017; Young et al., 2018).
In Western Kenya, some of the approaches to finding men with HIV have taken an integrated screening approach, said Rabkin. However, follow through for NCD care tended to be poor owing to the expense of medications and transport and the lack of peer educators. Rabkin said that there are benefits to integration of NCDs into HIV programs, as well as benefits to the HIV programs into which the other programs are integrated. However, screening is not effective without funding for prevention, care, and treatment for the other conditions being detected, she noted. Kimaiyo emphasized that PEPFAR saves lives and has created invaluable infrastructure. PEPFAR’s mistakes are not the issue, he said—the issue is the global community’s neglect of other diseases.
Mass Administration: Barriers, Surveillance, and Long-Term Effects
Jay Siegel, retired chief biotechnology officer and head of scientific strategy and policy at Johnson & Johnson, remarked that most drugs used in mass administrations were initially developed for treatment of individuals, not entire populations. He asked if mass administration efforts ever encounter regulatory barriers in obtaining drugs or in importing drugs into
other countries. Oldenburg replied that azithromycin is approved for use and is indicated in the WHO guidelines for treating trachoma in children 6 months of age and older. The MORDOR study treated infants down to 1 month of age, giving rise to discussion about how the WHO guidelines may facilitate the entry of the drug for younger age groups. Patricia García, professor at the Cayetano Heredia University School of Public Health, Peru, said that in her experience as a health minister, most countries have fast tracks for the entry of medications associated with public health if it is properly coordinated with the ministry of health and aligned with existing guidance.
Rachel Nugent, vice president for the Chronic Noncommunicable Diseases Global Initiative at RTI International, remarked that the mechanism of mass drug administration becomes less effective as the disease burden declines and disease reservoirs shrink to progressively smaller areas. She asked about the potential benefit of bringing NCDs into existing surveillance mechanisms to better understand co-occurrences within specific populations. Oldenburg replied that mass drug administration and community surveillance programs developed for neglected tropical disease platforms have the power to bring care into communities, rather than requiring people to travel long distances from the community to a health care post. Going forward, leveraging platforms currently used for screening and epidemiological tracking can ensure that people actually receive care if they are referred, she added.
García asked about plans for follow-up research on the long-term effect of recurring mass administration of antibiotics, both on the microbiota and on antimicrobial resistance. She noted that these types of large-scale interventions can change the microbial ecosystem and cause unexpected consequences. Oldenburg replied that a long-term open-label extension of the MORDOR study is ongoing in Niger (Keenan et al., 2019). Communities are going into their fourth year of surveillance, with rectal and nasal swab samples collected from children to look for antibiotic resistance as well as microbiome changes. Other studies are evaluating different frequencies of administration and dosing strategies. Changes in the intestinal microbiome of children who received azithromycin compared to placebo are observed at 5 days after treatment—both changes in composition and a decrease in microbial diversity. Observed changes in the community microbiome tend to last slightly longer, but those changes are not as pronounced as the short-term changes seen in individual children. She added that ongoing studies are sampling children more frequently to analyze longitudinal changes and to evaluate the length of time it takes the microbiome to return to normal, if it does at all. The longer-term implications of mass azithromycin administration in the microbiome of children over the life course are not yet known, she stated. She added that children who receive mass azithromycin administra-
tion tend to receive, on average, far fewer courses of antibiotics than children in the United States, for example.
Domestic and External Funding Considerations
The discussion transitioned into a focus on funding. Bukhman stated that external funding needs to increase because the poorest countries simply do not have sufficient domestic resources. Chronic care integration presents an opportunity to galvanize global health solidarity around more severe diseases affecting children, then disaggregating the argument and explaining that chronic conditions are also within the remit of global health responsibility based on those same premises. Lumping all NCDs together from the outset could potentially do them a disservice, he cautioned. Nugent called for careful consideration about the specific objectives that could be achieved with different actions—such as better outcomes, cost savings, financial risk protection, or expanding services—and strategically selecting which ones to focus on.
Espinal highlighted a tension between national governments’ responsibilities to fund care for their populations and the negative consequences of excluding donor funding. Funding concerns are not limited to low-income countries. Funds are also dissipating in middle-income regions like Asia and Latin America, where a common misconception is that NCDs are only a problem of high-income countries. Increasing and integrating care for NCDs will likely be beyond the financial capability of many middle-income countries. He noted the potential effect of having large-scale international donors push for integration based on lessons learned from investing in diseases and programs over the years.
Bukhman was concerned that maintaining the current disease-specific focus and architecture of development financing—in which, for example, countries graduate and move into middle-income status—will lead to a decline in development assistance. Instead, he offered the idea that financing structures for development assistance could be reframed to prioritize highly equitable and cost-effective interventions for the poorest people in the world, rather than specific diseases. Spending funds in that way will require broadening the mandate to account for transitioning burdens of infectious diseases and NCDs, however. This could lead to inequitable allocation of funds in middle-income countries, he cautioned, because some lower-middle and upper-middle countries may be better off than others in terms of domestic resources.
Espinal noted the need to broaden the focus beyond the African region. Latin America, for example, has the greatest inequity of all six WHO regions. Wealth is growing, but it is not well distributed, leaving many sub-populations vulnerable and lacking access to care. García added that coun-
tries’ specific needs should be taken into account in funding decisions. For example, countries in Latin America may need only catalytic funding to pilot innovative, cost-effective interventions that governments can then take over, while countries in Africa may need more resources. Kimaiyo remarked that even in a country that has adequate domestic resources, the government’s management of those resources can be challenged by corruption, political pressures, or poor prioritization of funding. A new USAID initiative called the Journey to Self-Reliance is trying to support and strengthen governments’ management capacities.8
Person-Centered Approach to Integration
Finally, offering her perspective as the former minister of health in Peru, a middle-income country, García emphasized the need for changes in mindset on three fronts. First, communities need to be meaningfully empowered with knowledge as well as with practical tools to improve their health. Second, she suggested funding agencies should shift from a paternalistic focus on disease-centered responses to a focus on people-centered responses. Third, barriers to integration need to be addressed rather than ignored, she added. Years ago, Peru had no domestic funding for its HIV program. USAID offered funding that was contingent on creating a parallel program to the ministry of health. García and her colleagues were opposed to this idea, because it ran counter to the existing structure of the health system. In some countries in Africa, however, such parallel systems tend to be created because they are easier than working within existing systems, which she noted are often hampered by corruption.
One of García’s major challenges as a health minister was dealing with corruption. She was adamant that corruption is a pervasive issue that needs to be dealt with head on with scientific rigor—perhaps through a new discipline of “anticorruption science”—rather than sweeping it under the rug. She added that the practice of creating new clinics in a parallel system is also a product of the myopic focus on HIV. She argued that everyone in the enterprise—from funders to researchers to politicians—have a responsibility to shift from a disease-funding mindset to a people-centered mindset as the fulcrum to achieving integration.