Primary Immunodeficiency Diseases in Latin America: The Second Report of the LAGID Registry

This is the second report on the continuing efforts of LAGID to increase the recognition and registration of patients with primary immunodeficiency diseases in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report reveals that from a total of 3321 patients registered, the most common form of primary immunodeficiency disease was predominantly antibody deficiency (53.2%) with IgA deficiency reported as the most frequent phenotype. This category was followed by 22.6% other well-defined ID syndromes, 9.5% combined T- and B-cell inmunodeficiency, 8.6% phagocytic disorders, 3.3% diseases of immune dysregulation, and 2.8% complement deficiencies. All countries that participated in the first publication in 1998 reported an increase in registered primary immunodeficiency cases, ranging between 10 and 80%. A comparison of the estimated minimal incidence of X-linked agammaglobulinemia, chronic granulomatous disease, and severe combined immunodeficiency between the first report and the present one shows an increase in the reporting of these diseases in all countries. In this report, the estimated minimal incidence of chronic granulomatous disease was between 0.72 and 1.26 cases per 100,000 births in Argentina, Chile, Costa Rica, and Uruguay and the incidence of severe combined immunodeficiency was 1.28 and 3.79 per 100,000 births in Chile and Costa Rica, respectively. However, these diseases are underreported in other participating countries. In addition to a better diagnosis of primary immunodeficiency diseases, more work on improving the registration of patients by each participating country and by countries that have not yet joined LAGID is still needed. Latin American Group for Primary Immunodeficiency Diseases     

Primary Immunodeficiency Diseases in Norway

This study represents the first national epidemiological survey of primary immunodeficiency diseases in Norway. Uniform questionnaires were sent out in April 1998 to all hospital departments considered relevant. As of February 1999, a total of 372 patients have been registered, of whom 69 patients are deceased. With a population of 4.45 million people, the total prevalence of primary immunodeficiency diseases in Norway February 1, 1999 is 6.82 per 100.000 inhabitants. Distribution between the main immunodeficiency diagnoses is (a) antibody deficiencies 50.8%, (b) combined deficiencies included other immunodeficiency syndromes 12.4%, (c) complement deficiencies 21.0%, (d) phagocytic disorders 6.7%, (e) and immunodeficiency associated with other congenital diseases 9.1%. Compared to previous reports from other European countries, there is a smaller proportion of antibody deficiencies due to few IgA deficiencies registered and a large proportion of complement deficiencies due to many patients with hereditary angioedema.     

Primary Immunodeficiency Syndrome in Spain: First Report of the National Registry in Children and Adults

The Spanish Registry for Primary Immunodeficiency Diseases (REDIP) was organized in 1993. One thousand sixty-nine cases of primary immunodeficiency diseases (PID) were registered in patients diagnosed between January 1980 and December 1995. PID diagnosis was made according to the World Health Organization criteria. The most frequent disorders were IgA deficiency (n = 394) and common variable immunodeficiency (n = 213), followed by severe combined immunodeficiency (n = 61), C1 inhibitor deficiency (n = 52), X-Iinked agammaglobulinemia (n = 49), IgG subclass deficiency (n = 48), and chronic granulomatous disease (n = 32). A comparative study between REDIP and data recently obtained from the European registry (ESID Report, 1995) revealed important differences between phagocytic disorders and complement deficiencies reported in both registries, 4.9 vs 8.7 and 6.0 vs 3.6, while percentages of predominantly antibody deficiencies and T cell and combined deficiencies concurred with those reported in the European registry, 69.3 vs 64.7 and 14.7 vs 20.2, respectively. The heterogeneous nature of the geographical distribution of cases submitted may indicate underdiagnosis of PID in some country areas; surprisingly, the interval between the onset of clinical symptoms and diagnosis was significant, even in immunodeficiency diseases, such as IgA deficiency, which are easy to diagnose.     

Primary Immunodeficiency Disorders in the Republic of Ireland: First Report of the National Registry in Children and Adults

Data collection for the national registry for patients with primary immunodeficiency disorders in the Republic of Ireland commenced in 1996. One hundred and fifteen cases of primary immunodeficiency diseases were registered between December 1996 and February 2003. The most frequent primary immunodeficiency disorders were antibody deficiency (n = 53) and complement deficiency (n = 32). In addition, patients with T cell deficiency (n = 11) and chronic granulomatous disease (n = 11) were identified. A small number of patients with Wiskott–Aldrich syndrome, natural killer cell deficiency, DiGeorge syndrome and chronic mucocutaneous candidiasis were also registered. Comparison of our data with that recently reported in the European registry revealed that complement deficiency was more prevalent in the Republic of Ireland compared to other European countries. Results of our registry point to a significant prevalence of primary immunodeficiency disorders in the Republic of Ireland (2.9 cases per 100.000 population). However, it is likely that these figures underestimate the true prevalence of such cases in the country. We hope, with increased awareness of the national registry among primary care physicians, that more patients will be included and we will be able to identify accurately the frequency and the distribution of these disorders.     

Primary Immunodeficiency Diseases in Egyptian Children: A Single-Center Study

Introduction  Sixty-four primary immunodeficiency patients were registered at the Pediatric Allergy and Immunology Department, Children’s Hospital, Ain Shams University, Cairo, Egypt. Data  Predominantly antibody deficiencies were the most common category (35.9%) followed by combined T- and B-cell immunodeficiencies (29.7%), other well defined immunodeficiency syndromes (18.7%), congenital defects of phagocyte number, function or both (12.5%), and diseases of immune dysregulation (3.1%). The most frequent disorder was common variable immunodeficiency (18.7%). The mean age at diagnosis was 29.9 months. The consanguinity rate was 62.5%. Recurrent severe infections were seen in all categories. Fifteen patients died (23.4%) from infections with the highest mortality for combined T- and B-cell immunodeficiencies (15.6%). Conclusions  Primary immunodeficiency disorders are not rare in Egyptian children. The observed frequency of combined T- and B-cell immunodeficiencies in our cohort is relatively higher than other countries. It is a prerequisite to establish a national registry of primary immunodeficiency in Egypt.     

Primary Immunodeficiency Diseases in Australia and New Zealand

INTRODUCTION: Despite rapid developments in the science of primary immunodeficiency diseases (PID), population characteristics and the burden of disease are poorly characterized. Aggregated data on PID via patient registries are a key component of the public health response. The web-enabled Australasian Society of Clinical Immunology and Allergy PID Register was designed and implemented to address gaps in knowledge of PID. METHODS: The register provided a cumulative, cross-sectional survey of PID patients in Australia and New Zealand via an online, single time point, center-based, voluntarily recalled, and patient-consented questionnaire. RESULT: Eighty-eight centers reported 1,209 patients across 56 separate PID syndromes. The study prevalence (cases per 100,000 population) was 5.6 for Australia, 12.4 for the state of South Australia, and 4.9 for Australia and New Zealand combined. Predominately antibody deficiency syndromes accounted for 77% of patients. Common variable immunodeficiency was the most common diagnosis. Patients were geographically dispersed with 80% of centers reporting caseloads of less than 20 patients. Potentially preventable complications of disease were common. Immunoglobulin replacement therapy was used in 30 conditions with 26.5% of the total recipients having antibody deficiency disorders with normal serum IgG. CONCLUSION: PID in Australia and New Zealand are prevalent, clinically diverse, geographically dispersed, and are characterized by high rates of potentially preventable morbidity and resource utilization. A public health focus on PID is required, including strategies to correct disparities in access to care, improve molecular diagnostics and reduce preventable complications of disease. Further studies in antibody deficiency syndromes with normal serum IgG are required.     

Latin American challenges with the diagnosis and treatment of primary immunodeficiency diseases

Introduction: diagnosis of primary immunodeficiency diseases (PID) is still a challenge in many countries in Latin America (LA), especially those that face social and economic problems. The creation of a society was fundamental to combine efforts that resulted in an effective educational program, establishment of a registry and a network to improve diagnosis.

Areas covered: The focus of this article is to portray the scenario of PID in LA covering different aspects from different countries. For this, a questionnaire was sent to countries that participate in the Latin American Society for Immunodeficiencies (LASID) registry, with questions related to PID challenges in LA. We realized that today the greatest challenge is the availability of laboratory tests to investigate newly described PIDs.

Expert commentary: Despite being faced with many difficulties, the Latin America Society for Immunodeficiencies is supporting clinical immunologists throughout the continent, which has resulted in a greater awareness of these diseases and an increase in the number of diagnosis.     

Asthma in Latin America: a public heath challenge and research opportunity

 Asthma has emerged as an important public health problem in many Latin American countries over the past decade. In Brazil and Costa Rica, the prevalence of asthma and associated morbidity is as great or greater as reported in traditional high prevalence countries such as the US, but remains neglected as a public health priority. Asthma in Latin America is associated particularly with underprivileged populations living in cities but remains relatively rare in many rural populations. The causes of asthma in Latin America are likely to be associated with urbanization, migration, and the adoption of a modern 'Westernized' lifestyle and environmental changes that follow these processes that include changes in diet, physical activity, hygiene, and exposures to allergens, irritants, and outdoor and indoor pollutants. Because of the enormous social, genetic, and environmental contrasts within and between Latin American countries, and the large differences in prevalence associated with these differences, the investigation of asthma in Latin America provides important research opportunities to identify the social and biological mechanisms that underlie asthma development. Asthma in Latin America poses enormous challenges for health policy makers, health services, and researchers to respond to and alleviate the growing burden of asthma disability, particularly among marginalized urban populations.     

Venous thromboembolism in Latin America: a review and guide to diagnosis and treatment for primary care

There are various region-specific challenges to the diagnosis and effective treatment of venous thromboembolism in Latin America. Clear guidance for physicians and patient education could improve adherence to existing guidelines. This review examines available information on the burden of pulmonary embolism and deep vein thrombosis in Latin America and the regional issues surrounding the diagnosis and treatment of pulmonary embolism and deep vein thrombosis. Potential barriers to appropriate care, as well as treatment options and limitations on their use, are discussed. Finally, an algorithmic approach to the diagnosis and treatment of venous thromboembolism in ambulatory patients is proposed and care pathways for patients with pulmonary embolism and deep vein thrombosis are outlined for primary care providers in Latin America.     

Attitudes towards reproduction in Latin America. Teachings from the use of modern reproductive technologies.

The use of modern reproductive technology, such as in-vitro fertilization and its related procedures, has opened new areas of legal, religious and public concern. Thirty years ago, the development of effective methods to control procreation generated a debate on whether couples had the right to enjoy sex in the absence of its procreative effect. Today, assisted reproductive technology (ART) allows couples to have their own children in the absence of a direct intermediation of sex. The Catholic Church has reacted against both contraception and ART, and specific instructions have been directed to the public, the medical profession and legislators. In a recent survey, 88.4% of the population in Latin America claims to be Catholic; therefore, bioethical considerations and legal implications concerning intervention in reproduction are strongly permeated by the moral teachings of Catholicism. In 1996, 83 medical doctors and scientists, participating in the Latin American Network of Assisted Reproduction, produced a consensus document on ethical aspects and legal implications of ART. The document contains minimal ethical guidelines that Latin American professionals have decided to adhere to, even in the absence of legal regulations. This article examines how the medical profession, legislators and the public react to religious influence when confronted by difficult bioethical decisions such as the right to procreate.     

Epidemiology of acute febrile illness in Latin America

BackgroundThe causes of acute febrile illness (AFI) in Latin America are diverse and their complexity increases as the proportion of fever due to malaria decreases, as malaria control measures and new pathogens emerge in the region. In this context, it is important to shed light on the gaps in the epidemiological characteristics and the geographic range for many AFI aetiologies.ObjectivesTo review studies on community-acquired fever aetiology other than malaria in Latin America, and to highlight knowledge gaps and challenges needing further investigation.SourcesPubMed from 2012 to April 2018.ContentWe found 17 eligible studies describing 13 539 patients. The median number of pathogens tested per individual was 3.5 (range 2–17). A causative pathogen could be determined for 6661 (49.2%) individuals. The most frequently reported pathogen during the study periods was dengue virus (DENV) (14 studies), followed by chikungunya virus (nine studies) and Zika virus (seven studies). Among the studies reporting concurrent infections, 296 individuals (2.2%) were found to have co-infections. In-hospital mortality was reported in eight (47%) studies, ranging between 0% and 18%.ImplicationsDENV fever is the febrile illness most frequently reported, reflecting its importance, while chikungunya and zika viruses present increasing trends since their emergence in the region. Studies with systematic and harmonized approaches for detection of multiple pathogens are needed and would probably reveal a higher burden of neglected pathogens such as Rickettsia spp. and arenaviruses. The lack of point-of-care tests and harmonized approach limits the care provided by health professionals and the efficacy of surveillance for AFI in the region.     

Hepatitis E virus infection in Latin America: A review

Data reported during recent years reveal the complex picture of the epidemiology of hepatitis E virus (HEV) infection in Latin America. Whereas in countries like Argentina and Brazil is almost identical to the characteristic of most countries from North America and Europe, HEV in the Caribbean and Mexico involves the water‐borne, non‐zoonotic viral genotypes responsible for epidemics in Asia and Africa. Nevertheless, Latin America has been considered a highly endemic region for hepatitis E in the scientific literature, a generalization that ignores the above complexity. In addition, reports from isolated Amerindian communities, which display well known, important and very specific epidemiological features for hepatitis B and D virus infections are neither taken into account when considering the epidemiology of hepatitis E in the region. This review updates compilation of the available information for the HEV infection, both among humans and other mammals, in Latin America, discusses the strengths and the weaknesses of our current knowledge, and identifies future areas of research. J. Med. Virol. 85: 1037–1045, 2013. © 2013 Wiley Periodicals, Inc.     

Carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii in the nosocomial setting in Latin America

Abstract

Increasing prevalence of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii strains in the nosocomial setting in Latin America represents an emerging challenge to public health, as the range of therapeutic agents active against these pathogens becomes increasingly constrained. We review published reports from 2002 to 2013, compiling data from throughout the region on prevalence, mechanisms of resistance and molecular epidemiology of carbapenem-resistant strains of P. aeruginosa and A. baumannii. We find rates of carbapenem resistance up to 66% for P. aeruginosa and as high as 90% for A. baumannii isolates across the different countries of Latin America, with the resistance rate of A. baumannii isolates greater than 50% in many countries. An outbreak of the SPM-1 carbapenemase is a chief cause of resistance in P. aeruginosa strains in Brazil. Elsewhere in Latin America, members of the VIM family are the most important carbapenemases among P. aeruginosa strains. Carbapenem resistance in A. baumannii in Latin America is predominantly due to the oxacillinases OXA-23, OXA-58 and (in Brazil) OXA-143. Susceptibility of P. aeruginosa and A. baumannii to colistin remains high, however, development of resistance has already been detected in some countries. Better epidemiological data are needed to design effective infection control interventions.     

Population Prevalence of Diagnosed Primary Immunodeficiency Diseases in the United States

Rationale: Although health surveys are routinely used to estimate the population incidence and prevalence of many chronic and acute conditions in the U.S. population, they have infrequently been used for “rare” conditions such as primary immunodeficiency diseases (PID). Accurate prevalence measures are needed to separate the truly rare condition from those that primary care doctors are likely to see in their practices today, if early diagnosis and treatment are to be achieved. Methods: A national probability sample of 10,000 households was sampled by random digit dialing and screened by telephone to identify how many of the nearly 27,000 household members had been diagnosed with a PID. Results: A total of 23 household members in 18 households were reported with a specific diagnosis for PID (CVID, IgA, IgG, XLA, SCID, CGD), whereas additional cases were reported as a PID without a confirmatory diagnosis. These findings suggest a population prevalence of diagnosed PID in the United States at approximately 1 in 1,200 persons. Conclusions: Diagnoses of PID in the United States are far more common than suggested in the literature. Schulman, Ronca & Bucuvalas Inc. (SRBI) for the Immune Deficiency Foundation.     

Pre-historic eating patterns in Latin America and protective effects of plant-based diets on cardiovascular risk factors

In this review, we present the contributions to nutrition science from Latin American native peoples and scientists, appreciated from a historic point of view since pre-historic times to the modern age. Additionally, we present epidemiological and clinical studies on the area of plant-based diets and their relation with the prevention and treatment of cardiovascular diseases conducted in recent decades, and we discuss challenges and perspectives regarding aspects of nutrition in the region.     

Primary Antibody Deficiency in Arabs: First Report from Eastern Saudi Arabia

Epidemiological studies have shown wide geographical and racial variations in the prevalence and pattern of immunodeficiency diseases. As there is no national registry, very little is known of the prevalence and nature of humoral immunodeficiency in the Arabian peninsula. We report here for the first time the analysis of serum immunoglobulin (Ig) levels in 2000 consecutive patients (age, 1–80 years). They were seen over a period of 6 years and were referred to us from six district hospitals for suspected immunodeficiency, autoimmunity, allergy, or immunoglobulin dyscrasia. Forty-six were found to be immunodeficient, in whom at least one of the Ig class was low; 15 had secondary immunodeficiency. The remaining 31 cases, representing 1.5% of the population studied (giving a prevalence of 1550/100,000 hospital registered patients), were categorized into four primary humoral immunodeficiency groups: these included, in order of frequency, (i) selective IgA deficiency (45%; 700/100,000) (ii) common variable immunodeficiency (CVID) (29%; 450/100,000), (iii) agammaglobulinemia (16%; 250/100,000), and (iv) selective IgG deficiency (10%; 150/100,000). Compared with similar hospital-based surveys in the west the prevalence of humoral immunodeficiency seems to be higher in Arabs; this in part may be related to race and higher rate of consanguinity. Most patients with IgA deficiency had either infection, atopy or autoimmunity. Compared with some other races, agammaglobulinemia (X- and non-X-linked) seems to be more prevalent.     

Genetic aspects of Huntington's disease in Latin America. A systematic review

We aimed to present a systematic review on Huntington's disease (HD) in Latin America (LA). PubMed and LILACS were searched up to March 2015, reporting confirmed HD cases in LA. Case series, cross‐sectional, case–control, and prospective studies were included. From 534 communications, 47 were eligible. Population‐based studies were not found; minimal prevalence of 0.5–4/100,000 was estimated for Venezuela and Mexico. Geographical isolates were well characterized in Venezuela and in Peru. CAG repeats at HTT gene varied between 7–33 and 37–112 in normal and expanded alleles, respectively. Intermediate alleles were found in 4–10% of controls. Ages at onset and the expanded CAG repeats correlated with r from – 0.55 to –0.91. While haplotype patterns of Venezuelan and Brazilian chromosomes were similar to those observed in Europeans, haplotypes from Peruvian HD patients did not match the same pattern. The limited number of papers found suggests that HD is poorly diagnosed in LA. Minimal prevalence seemed to be halfway between those of Caucasians and Asians. Range of CAG repeats was similar to those of Europeans. Haplotype studies indicate that majority of HD patients might be of Caucasian descent; an Asian origin for some Peruvian patients was proposed.     

Translation and evaluation of a comprehensive educational program for cardiac rehabilitation patients in Latin America: A multi-national,longitudinal study

ObjectivesTo translate, cross-culturally adapt and validate a comprehensive evidence- and theoretically-based CR education intervention in Latin America.MethodsFirst, best practices in translation and cross-cultural adaptation were applied through 6 steps. Then, the Spanish version was delivered to CR participants from programs in Colombia, Costa Rica and Peru for validation, such that the evaluation was pre-post, uncontrolled, pragmatic, observational, and prospective in design. Participants completed surveys assessing knowledge, health literacy, self-efficacy, and health behaviours. All outcomes were assessed pre-, and post-CR, as well as 6 months after CR completion.ResultsAfter translation of the patient guide from English to Spanish, 5 of the 9 booklets were culturally adapted. Two-hundred and forty-nine patients consented to participate, of which 184 (74 %) completed post-CR, and 121 (48 %) completed final assessments. There was a significant improvement in disease-related knowledge pre- to post-CR, as well as in health literacy, self-efficacy, and health behaviours (all p < 0.05). These gains were sustained 6 months post-program. With adjustment, CR attendance (i.e., exposure to the education) was associated with greater post-CR knowledge (ß = 0.026; p = 0.01).ConclusionA patient education intervention for CR patients in Latin America has been validated, and wider implementation is warranted.Practice implicationsApplication of this first-ever validated CR education program for Spanish-speaking settings may result in secondary prevention.     

Human leukocyte antigen class II and type 1 diabetes in Latin America: a combined meta-analysis of association and family-based studies

Conclusions from association studies could be spurious because of population stratification; therefore we combined association with family studies seeking to confirm which human leukocyte antigen (HLA) class II alleles/haplotypes were associated with type 1 diabetes (T1D) in the admixed Latin America. By calculating the effect summary odds ratios (OR) and their 95% confidence intervals (95% CI), data up to June 2010 showed that risk associations were observed with DRB1*0301-DQA1*0501-DQB1*0201 (odds ratio [OR]: 7.51; 95% confidence interval [CI]: 3.69-15.25) and DQB1*0302 in presence of DRB1*0405 (OR: 11.64; 95% CI: 3.15-43.01) or DRB1*0401 (OR: 5.85; 95% CI: 3.07-11.14). In contrast, DRB1*0404-DQB1*0302 had a nonsignificant TID risk (OR: 2.23; 95% CI: 0.91-5.43). T1D protective associations were observed with DRB1*11-DQA1*0501-DQB1*0301 (OR: 0.24; 95% CI: 0.1-0.56) and DRB1*15-DQA1*0102-DQB1*0602 (OR: 0.35; 95% CI: 0.17-0.73). These results were similar to those observed in Caucasian and other populations, thus highlighting the primary role of class II HLA in T1D regardless of ethnicity. A DRB1*04 risk hierarchy was confirmed with the DRB1*0405 being in the top. A binding prediction analysis disclosed possible receptor-ligand interactions in the HLA-antigenic peptide complex.