Coordinator, National Pediatric Cardiology Network William Soler Children’s Heart Center, Havana “Our family wasn’t rich, but we didn’t want for anything,” says Dr Palenzuela by way of introduction. In 1950s Cuba, her father drove a taxi and her mother was a homemaker, raising two daughters—one now an economist and the other a top pediatric cardiologist. […]

ABSTRACT
Forty-three years after it was founded, with billions of dollars invested, the global biotech industry is still not positioned as a mature low-risk sector for the international investor community. Despite the clear commercial success of a number of leading companies and overall growth of the industry’s revenues, most biotech companies are not profitable and many fail to overcome the formidable barrier constituted by the high cost of the sector’s research and development. However, over the last four years, visible signs of change have appeared, which could be harbingers of an approaching turning point in this trend.

This article analyzes the historic background of the biotech industry’s business models and corporate structures, as well as

their impact on the industry’s financial framework. It examines recent changes implemented by the sector’s main actors—including young startups, venture capital funds and big pharma companies—to mitigate financial risk associated with development of new biotechnology products.

Finally, it discusses the challenges and opportunities that these tendencies entail for Cuban biotechnology development and proposes adoption of business policies more tolerant of the financial risk inherent in this sector, as a condition for attracting venture capital.

KEYWORDS Biotechnology, fund raising, risk management, entrepreneurship, Cuba

Cuba’s maternity homes were founded in 1962 as part of the general movement to extend health services to the whole population in the context of the post-1959 social transformations. The overarching goal of the homes was to improve the health of pregnant women, mothers and newborns. Hence, in the beginning when there were few hospitals in Cuba’s rural areas, their initial purpose was to increase institutional births by providing pregnant women a homelike environment closer to hospitals. There, they lived during the final weeks before delivery, where they received medical care, room and board free of charge. Over time, and with expanded access to community and hospital health facilities across Cuba, the numbers, activities, modalities and criteria for admission also changed. In particular, in addition to geographical considerations, expectant mothers with defined risk factors were prioritized. For example, during the 1990s economic crisis, the maternity homes’ role in healthy nutrition became paramount. The purpose of this essay is to provide a historical perspective of this process, describe the changes and results during the 55 years examined, and take a critical look at the challenges to successful implementation of this model, a mainstay at the primary healthcare level of the public health system’s Maternal–Child Health Program.

KEYWORDS Maternal health, maternal–child health, obstetrics, pregnancy, Cuba

Spinocerebellar ataxia type 2 is a degenerative disease that causes physical disability and, ultimately, prostration and death. Globally, reported prevalence is around 3 cases per 100,000 population and Cuba has the world’s highest rates of the disease, affecting both patients and their at-risk descendants. In Holguín Province, which has the country’s highest concentration of cases, incidence is 4.4 per 100,000 population and prevalence is 40.2 per 100,000 population. In 2000, a specialized research center was established in that province. Supplied with the necessary equipment and human resources, the center conducted national multidisciplinary studies involving molecular biology, clinical care, epidemiology, psychology, clinical neurophysiology, imaging, clinical genetics and community medicine, among others. A training and continuing education program also raised scientific capacity. Priority was given to developing international collaborations for academic exchange and training of Cuban researchers.

Multiple results from research involving clinical and epidemiologic characterization of the disease, identification of biomarkers and therapeutic targets, genetic association studies, clinical trials and characterization of the disease’s preclinical stages have been introduced in care of patients and their at-risk descendants. This has been accomplished through various programs including personalized rehabilitation, predictive diagnosis and social services. These results have also been published in high-impact scientific journals and received national and international awards. Such an experience in the context of Cuba’s national health system—which is universal, free, accessible, comprehensive, prevention-oriented and with a record of international cooperation—demonstrates the possibility of providing quality care to affected families. Incorporating research findings into medical practice, with the resulting impact on patients’ health and wellbeing, is a practical example of translational medicine in Cuba.

KEYWORDS Spinocerebellar ataxia type 2, health services research, biomedical research. health care delivery, translational medicine, translational research, health equity, Cuba

Vaccination is one of the most cost-effective interventions for control of communicable diseases. This health achievement could flounder if measures are not taken by health systems to prioritize immunization, increase vaccination rates and educate health professionals to address public concerns about vaccine safety and efficacy. Parents’ refusal to vaccinate their children directly affects public health, because it puts both individual and group immunity in danger; immunization coverage is effective only when high population coverage is attained. The growing number of antivaccination (antivaxxer) groups around the world is alarming, contributing to falling vaccination rates. Troubling consequences include disease outbreaks in several countries globally and in our hemisphere. This article looks at the history and features of antivaxxer movements around the world and proposes ways the Cuban health system, through its National Immunization Program, can address dangers for the population associated with potentially negative influences of social-network antivaxxer campaigns. The paper underscores the role of mass and social media, health professional training and sustained competence, and the importance of a vaccine-related adverse events surveillance system.

KEYWORDS Vaccination, immunization, antivaccination movement, antivaccine groups, primary health care, society, communications media, social media, Cuba

Health is a universal human right, which should be safeguarded by government responsibility and included in all social policies. Only as such it is possible to ensure effective responses to the health needs of an entire population. The Cuban Constitution recognizes the right to health, and the country’s single, free, universal public health system and high-level political commitment promote intersectorality as a strategy to address health problems. Intersectorality is reflected in national regulations that encourage participation by all social sectors in health promotion/disease prevention/treatment/rehabilitation policies and programs. The strategy has increased the response capacity of Cuba’s health system to face challenges in the national and international socioeconomic context and has helped improve the country’s main health indicators. New challenges (sociocultural, economic and environmental), due to their effects on the population’s health, well-being and quality of life, now require improved intersectoral coordination in the primary health care framework to sustain achievements made thus far.

KEYWORDS Universal coverage, public health, health policy, social planning, intersectoral collaboration, Cuba

Cardiovascular diseases are the leading cause of death worldwide, and a health problem in low- and middle-income as well as high-income countries. They also constitute the main cause of death in Latin America, with ischemic heart disease as the principal cause in most countries of the region. In Cuba, heart disease is the first cause of death, followed by cancer and stroke. In its 2030 Agenda for Sustainable Development, the UN recognizes the importance of chronic non-communicable diseases, including cardiovascular diseases.

Cuba has participated actively as lead partner in design and implementation of the two regional technical cooperation projects conducted over the last six years by the International Atomic Energy Agency to address cardiovascular diseases in Latin American and Caribbean member states. These projects have generated greater interest among participating countries in the use of myocardial perfusion for dilated cardiomyopathy and coronary artery disease compared to other imaging techniques; disseminated knowledge about nuclear cardiology techniques and clinical applications in heart failure and coronary artery disease; and made important contributions to implementing harmonized, appropriate and safe clinical protocols. Cuba’s contribution to the International Atomic Energy Agency’s regional cardiology projects has fostered development of human resources and harmonized protocols both nationally and regionally, and demonstrated the importance of region-based scientific cooperation that ensures greater opportunities and more equitable access to resources. This participation has also accrued important benefits to Cuba’s own nuclear cardiology program.

KEYWORDS Cardiovascular disease, myocardial perfusion imaging, nuclear cardiology, scientific cooperation, low-income populations, Latin America, Caribbean region, Cuba

In El Salvador, chronic kidney disease had reached epidemic proportions towards the end of this century’s first decade. In 2011–2012, the Ministry of Health reported it was the leading cause of hospital deaths in men, the fifth in women, and the third overall in adult hospital fatalities. Farming was the most common occupation among men in dialysis (50.7%). By 2017, chronic kidney disease admissions had overwhelmed hospital capacity. In 2009, El Salvador’s Ministry of Health, Cuba’s Ministry of Public Health and PAHO launched a cooperative effort to comprehensively tackle the epidemic. The joint investigations revealed a total prevalence of chronic kidney disease in the adult population of farming communities higher than that reported internationally (18% vs.11%–14.8%), higher in men than in women (23.9% vs 13.9%) and higher in men who were farmers/farmworkers than in men who were not (31.3% vs. 14.8%). The disease was also detected in children. An association was found between chronic kidney disease and exposure to agrochemicals (OR 1.4–2.5). In 51.9% of all chronic kidney disease cases, traditional causes (diabetes, hypertension, glomerulopathies, obstructive nephropathies and cystic diseases) were ruled out and the existence of a particular form of chronic kidney disease of nontraditional etiology was confirmed (whose initial cases were reported as early as 2002). In the patients studied, functional alterations and histopathologic diagnosis confirmed a chronic tubulointerstitial nephritis; most presented with neurosensory hearing loss, altered tendon reflexes and tibial artery damage. The main results of this cooperation were the epidemiologic, physiopathologic, clinical and histopathologic characterization of chronic kidney disease of nontraditional etiology. This characterization facilitated case definition for the epidemic and led to the hypothesis of systemic toxicity from agrochemicals (e.g., paraquat, glyphosate), which particularly affect the kidneys and to which farmers/farmworkers (who may also become dehydrated in the fields) are most exposed. The research thus also laid the foundations for design of comprehensive intersectoral government actions to reduce cases and put an end to the epidemic. KEYWORDS Chronic kidney disease, chronic renal failure, tubulointerstitial nephritis, epidemiology, histopathology, international cooperation, agrochemicals, environmental pollutants, noxae, and pesticides, occupational health, PAHO; El Salvador, Cuba

Every year, meningococcal infection by Neisseria meningitidis causes over 500,000 cases and 85,000 deaths in the world, with 20% of survivors suffering sequelae. In Cuba its incidence in 1980 reached 5.9 cases per 100,000 population; about 80% of cases were serogroup B, prompting health authorities to declare meningococcal disease the country’s main public health problem.

Several provinces reported over 120 cases per 100,000 children aged <1 year, overwhelmingly serogroup B. At that time, no vaccines existed with proven efficacy against N. meningitidis serogroup B, nor was there a vaccine candidate that could be successful in the short term. By 1989, researchers in Havana had developed a Cuban meningococcal B and C vaccine, VA-MENGOC-BC, the world’s first against serogroup B meningococcal disease. Its efficacy of 83% was demonstrated in a prospective, randomized, double-blind, placebo-controlled field study. Vaccine production used vesicle or proteoliposome technology for the first time. The same year, the World Intellectual Property Organization awarded its gold medal to the main authors of the VA-MENGOC-BC patent.

The vaccine was used in a mass vaccination campaign and later included in Cuba’s National Immunization Program, with a cumulative impact on incidence of serogroup B meningococcal disease greater than 95% (93%–98%). Mass, systematic vaccination shifted the spectrum of meningococcal strains in healthy asymptomatic carriers and strains circulating among population groups toward nonvirulent phenotypes. The disease ceased to be a public health problem in the country. VA-MENGOC-BC is the most widely applied vaccine against serogroup B meningococcal disease in the world. Over 60 million doses have been administered in Latin America. In several countries where it has been applied, in which strains other than the vaccine-targeted strains circulate, VA–MENGOC–BC has demonstrated effectiveness against all (55%–98% in children aged ≤4 years and 73%–100% in children aged >4 years). The vaccine and its proteoliposome technology have had an impact and continue to have potential, not only for meningococcal disease, but also for development of other vaccines and adjuvants.

KEYWORDS Neisseria meningitidis, meningococcal disease, meningococcal vaccine, biotechnology, pharmaceutical industry, bacterial meningitis, meningococcal meningitis, immunization, vaccination, Cuba

Cuba’s public health outcomes are rooted in political and social phenomena that have favored achievement of health indicators well above expectations for an economy of its size. A less studied causal component of Cuba’s development in health is the creation, from early in the 1960s, of scientific research capacity throughout the health system, including use of science to launch a domestic industry for manufacturing high-tech products. This component should play an even greater role in meeting Cuba’s 21st century health challenges, especially the demographic and epidemiological transitions, increasing prevalence of chronic diseases, rapid emergence of a complex-product biotechnology pharmacopoeia, greater molecular stratification of diseases, rising health costs, and the need to maintain communicable diseases under control in a global context of climate change and more population mobility.

Tackling these challenges will demand greater scientific influence in the health system, application of a scientific approach in all activities and at all levels, and integration with scientific endeavors of other sectors such as agriculture, industry and education.

KEYWORDS Public health, science, health care costs, health workforce, chronic disease, biotechnology, immunology, aging, Cuba

The Ebola virus is a pathogen that causes high morbidity and mortality in epidemic events during which health personnel are frequently infected. Such an epidemic occurred in West Africa, prompting WHO to issue a call in 2014 for health personnel to be dispatched to affected countries. Cuba responded and signed an assistance agreement under which 265 Cuban health professionals, members of the Henry Reeve Emergency Medical Contingent, volunteered their services in the Republic of Guinea, Sierra Leone and Liberia. This article presents Cuba’s strategy of medical aid and organization of the three medical teams formed; refers to the teams’ contribution to epidemic control in treatment centers where they worked alongside other personnel; and describes measures taken in Cuba to prevent the virus from entering the country through returning volunteers or other means. In the centers where Cuban medical teams worked with other health professionals in West Africa, case fatality decreased from 80%–90% to 24%, contributing to control of the epidemic; no Ebola outbreaks occurred in Cuba. During the epidemic, two Cuban health professionals died of malaria and one physician fell ill with Ebola. This paper includes an overview of the treatment and evolution of the latter case, a doctor who contracted the disease in Sierra Leone and was treated in Geneva and Havana.

KEYWORDS Ebola virus, treatment, strategy, followup, medical collaboration, Republic of Guinea, Sierra Leone, Liberia, Cuba

Sickle cell anemia is the most common hereditary disease in Cuba. On average, 1 in 33 Cubans is a carrier of this severe hemolytic anemia that can cause early death. In early 1980, its incidence in Cuba was calculated at 1 in 1600 births. In 1982, the Cuban public health system established the Sickle Cell Anemia Prevention Program, which aims to prevent the disease through identification of carrier couples and antenatal diagnosis of fetuses with disease-associated genotypes. In 1982–2018, hemoglobin genotypes were tested in 4,847,239 pregnant women. Of these, 168,865 (3.5%) were found to be carriers or to have sickle cell disease. During the same period, 8180 at-risk couples were identified, of whom 79.2% agreed to an antenatal study for detection of the sickle cell gene in the fetus. Among fetuses diagnosed, 20.1% had the SS genotype, the most clinically severe; 76.2% of the associated couples decided to interrupt the pregnancy. This program has resulted in a 3-fold reduction in prevalence of sickle cell disease in Cuba, a

10-fold reduction in the number of infants born with it each year, and a 16-year average increase in life expectancy of sickle cell disease patients of both sexes. Key contributors to these results have been universal screening of pregnant women in primary care, installation of diagnostic laboratories in every province, genetic counseling for couples, testing of fetal DNA (allowing couples to decide whether to continue the pregnancy if the fetus tests positive for the disease) and guaranteed multidisciplinary clinical care for patients. The Cuban experience shows that a middle-income country can mitigate the impact of a genetic disease through a universal preventive program based in primary care, which also pays particular attention to afflicted patients.

KEYWORDS Sickle cell anemia, sickle cell disease, sickle cell disorders, hemolytic anemia, sickle cell trait, sickle cell hemoglobin C disease, HbS disease, prevention, antenatal screening, preventive health services, Cuba

WHO’s 2015 End Tuberculosis Strategy can succeed only through universal health coverage, social protection, poverty alleviation and effective multisector actions to tackle social determinants in general. The pediatric age group is particularly vulnerable to tuberculosis and historically neglected worldwide. However, this group is a priority within Cuba’s National Tuberculosis Control Program that has functioned since 1970, and Cuba is considered a low-incidence country with rates <7 per 100,000 population since 2011. Tuberculosis incidence in children aged <15 years is <1 per 100,000, similar to that reported in high-income countries and representing less than 2% of total cases in Cuba. Since 1999, no deaths from tuberculosis, coinfection with HIV or resistance to the two first-line TB drugs have been reported in affected children, and most diagnosed cases correspond to early, primary forms of the disease. These results place Cuba among the countries on track to eliminate TB by 2050. This article reviews the pillars and components of the 2015 End TB Strategy and the strategies developed by the National Tuberculosis Control Program that enabled Cuba to bring incidence below the 2035 targets of WHO’s End TB strategy. The article also proposes other actions Cuba can take, despite limited resources, to eliminate TB, particularly in the pediatric age group.

KEYWORDS Tuberculosis, communicable disease control, disease control programs, preventive health services, child health, World Health Organization, Cuba

Growth and development is considered the best positive indicator of children’s quality of life and well-being. Studies have been carried out in Cuba since the early 20th century and large scale, periodic anthropometric surveys have been regularly conducted by its National Health System to chart modifications in growth patterns of children and adolescents. These surveys have produced national references for the anthropometric indicators most commonly applied in individual assessment of the health and nutritional status of children and adolescents in health care settings. These have also provided data for estimating the magnitude and characteristics of secular growth trends, and for comparing growth of Cuban children with that of children in other countries and with WHO’s proposed growth standards. The data have also served as evidence of persisting social gradients. The most important results include, as positive data, the positive secular trend in school-aged children’s growth of 9.7 cm between 1919 and 2005, with an average increase of 1.1 cm per decade, and, in preschool children, 1.9 and 1.8 cm in boys and girls, respectively, between 1972 and 2015. More recent studies have detected unfavorable changes associated with a marked increase in adiposity and, therefore, in the prevalence of excess weight and obesity. Another interesting result is the gradual movement toward WHO height-for-age standards in preschool children in Havana, verified in surveys conducted in 2005 and 2015.

KEYWORDS Growth and development, growth, child development, children, adolescents, nutrition, obesity, pediatrics, Cuba

INTRODUCTION In 19th century colonial Cuba, Boards of Health (Juntas de Sanidad) were created to administer public health, in tandem with and later replacing the older Royal Protomedicato Court (Real Tribunal de Protomedicato). Development of the Board of Health in the northeastern city of Holguín reflected local historical processes, as well as class relations and social issues characteristic of this period.

Among the highlights of the Board’s activities were epidemic control during cholera and smallpox outbreaks, monitoring the city’s sanitary conditions, and support for charitable work. Studying the history of such epidemiological surveillance activities may benefit design and implementation of related current research and prevention/control campaigns.

OBJECTIVE Describe the development of the 19th century Board of Health in the city of Holguín.

EVIDENCE ACQUISITION The research was conducted through a critical analysis of primary sources contained in the Historical Archives of (today’s) Holguín Province, specifically relevant documents from the regional and city government (Fondo Tenencia de Gobierno y Ayuntamiento) and town council (Cabildo). Cuban and international scientific publications were also consulted.

DEVELOPMENT The Board of Health was the main institution conducting health and hygiene control and charitable activities in the city of Holguín during the 19th century. It was created mainly to take preventive measures against diseases affecting the population, an effort it undertook with support from the Urban Health Police. Its efforts to confront smallpox and cholera epidemics greatly helped to reduce the toll of these diseases on the population, albeit not sufficiently to prevent their reccurrence. Beginning in the 1870s, weakened government support eroded the Board’s position, and health-related measures were implemented mainly by the Board of Charity, which focused on matters concerning the city’s Civil Hospital.

CONCLUSIONS Although established in 1820, Holguín’s Board of Health carried out preventive actions most actively from 1850 to 1865, with support from the Urban Health Police. Its gradual disappearance from the health policy arena beginning in the 1870s reflects its failure as an institution, in large part due to weak government support.

KEYWORDS Board of Health, prevention, epidemics, Cuba

INTRODUCTION Quantification of lymphocyte subpopulations is useful for evaluating immune response in states of health and disease, including immunodeficiencies, autoimmunity, infections and cancer. Studies have found that concentrations and proportions of different cell subpopulations vary with geographic location, age, sex and ethnicity. Knowing the normal values of these cells and their variation in healthy populations will contribute to improved clinical practice and scientific research.

OBJECTIVE Estimate normal absolute concentrations and percentages of the most abundant lymphocyte subpopulations in peripheral blood and their relation to sex and age.

METHODS A cross-sectional analysis was conducted in 129 healthy adults, 61 men and 68 women aged 18–80 years; 89 aged <50 years and 40 ≥50 years. We included individuals who agreed to participate by written informed consent. Exclusion criteria were chronic disease, or use of tobacco, alcohol or medications that can alter immune system cell numbers and functions.

Through dual platform flow cytometry, we determined absolute and percentage values for T lymphocyte subsets CD3+, CD3+/CD4+T, CD3+/CD8+T, CD19+ B cells and CD3-/CD56+ natural killer cells in peripheral blood, using an 8-color flow cytometer. We estimated medians and the 2.5 and 97.5 percentiles and calculated the Pearson correlation coefficient to evaluate associations. Significance tests were also used to compare groups. The significance threshold was p = 0.05 in all cases.

RESULTS Ranges of absolute values and percentages (%) were: total lymphocytes: 1200–3475 cells/μL (20.2–49.3); CD3+ T cells: 880–2623 cells/μL (56.5–84.7); CD3+/CD4+ T cells: 479–1792 cells/μL (30.3–55.7); CD3+/CD8+ T cells: 248–1101 cells/μL (13.2–42.9); CD19+ B cells: 114–1491 cells/μL (5.4–49.5); CD3-/CD56+ natural killer cells: 70–652 cells/μL (3.7–28.0); and the CD4+:CD8+ index: 0.80–3.92. Absolute numbers––but not percentages––of lymphocytes and CD3+ T cells were higher in those <50 years (p = 0.025 and 0.020, respectively). Absolute values and relative percentages of CD3+/CD8+ and relative values of CD3+/ CD4+ T cells were significantly higher in the younger subgroup (p = 0.004 and p = 0.047). Age was not associated significantly with B lymphocytes or natural killer cells. Absolute and relative values ​​of CD3+/CD4+ T lymphocytes were significantly higher in women (p = 0.009 and 0.036, respectively).

CONCLUSIONS. Absolute numbers of total lymphocytes and T and CD3+/CD8+ T lymphocytes are higher in younger individuals. In percentage values, CD3+/CD4+ T lymphocytes are lower in older persons. Absolute and percentage values ​​of CD3+/CD4+ T phenotype are higher in women. These differences justify adjusting clinical analyses to different values ​​by age and sex.

KEYWORDS T lymphocytes, B lymphocytes, normal values, flow cytometry, age, sex, Cuba