Mapping of Chagas disease research: analysis of publications in the period between 1940 and 2009

Mapeamento de pesquisa da doença de Chagas: análise da produção de publicações no período entre 1940 e 2009

Abstracts

INTRODUCTION: Publications are often used as a measure of success in research work. Chagas disease occurs in Central and Southern America. However, during the past years, the disease has been occurring outside Latin America due to migration from endemic zones. This article describes a bibliometric review of the literature on Chagas disease research indexed in PubMed during a 70-year period. METHODS: Medline was used via the PubMed online service of the U.S. National Library of Medicine from 1940 to 2009. The search strategy was: Chagas disease [MeSH] OR Trypanosoma cruzi [MeSH]. RESULTS: A total of 13,989 references were retrieved. The number of publications increased steadily over time from 1,361 (1940-1969) to 5,430 (2000-2009) (coefficient of determination for linear fit, R²=0.910). Eight journals contained 25% of the Chagas disease literature. Of the publications, 64.2% came from endemic countries. Brazil was the predominant country (37%), followed by the United States (17.6%) and Argentina (14%). The ranking in production changed when the number of publications was normalized by estimated cases of Chagas disease (Panama and Uruguay), population (Argentina and Uruguay), and gross domestic product (Bolivia and Brazil). CONCLUSIONS: Several Latin American countries, where the prevalence of T. cruzi infection was not very high, were the main producers of the Chagas disease literature, after adjusting for economic and population indexes. The countries with more estimated cases of Chagas disease produced less research on Chagas disease than some developed countries.

Chagas disease; American trypanosomiasis; Trypanosoma cruzi; Bibliometry; Scientific production; Mapping

INTRODUÇÃO: Publicações são frequentemente utilizadas como uma medida de sucesso do trabalho de pesquisa. A doença de Chagas (DCh) ocorre na América Central e do Sul. Porém, durante os últimos anos, a doença tem ocorrido fora da América Latina, devido à migração das zonas endêmicas. Este artigo descreve uma análise bibliométrica da literatura sobre as pesquisas da doença de Chagas indexadas no PubMed, durante um período de 70 anos. MÉTODOS: O Medline foi usado através do serviço online da US PubMed da National Library of Medicine de 1940 a 2009. A estratégia de busca foi: Chagas disease [MeSH] OR Trypanosoma cruzi [MeSH]. RESULTADOS: Um total de 13.989 referências foi recuperado. O número de publicações aumentou de forma constante com 1.361 (1940-1969) para 5.430 (2000-2009) (coeficiente de determinação para o ajuste linear, R² = 0, 910). Oito revistas contiveram 25% da literatura sobre a DCh. Um total de 64,2% das publicações veio de países endêmicos. O Brasil foi o predominante (37%), seguido pelos Estados Unidos da América (17,6%) e Argentina (14%). O ranking da produção foi alterado, quando o número de publicações foi normalizado por casos estimados da doença de Chagas (Panamá e Uruguai), população (Argentina e Uruguai), e Produto Interno Bruto (Bolívia e Brasil). CONCLUSÕES: Vários países da América Latina com uma prevalência não muito elevada de infecção pelo T. cruzi foram os principais produtores, após ajuste para os índices econômicos e populacionais. Os países com mais casos estimados da DCh produziu menos pesquisas em doença de Chagas que alguns países desenvolvidos.

Doença de Chagas; Tripanossomíase Americana; Trypanosoma cruzi; Bibliometria; Produção científica; Mapeamento

Mapping of Chagas disease research: analysis of publications in the period between 1940 and 2009

Mapeamento de pesquisa da doença de Chagas: análise da produção de publicações no período entre 1940 e 2009

José Manuel Ramos^I; Gregorio González-Alcaide^II; Joaquín Gascón^III; Félix Gutiérrez^{I, IV}

^IUnidade de Doenças Infecciosas, Hospital General Universitario de Elche, Alicante, Spain

^IIDepartamento de Historia de la Ciencia y Documentación, Facultad de Medicina y Odontología, Universitat de Valencia, Valencia, Spain

^IIICentre de Salut International, Hospital Clinic, Barcelona, Spain

^IVDepartamento de Medicina Clinica, Facultad de Medicina, Universidad Miguel Hernández, Alicante, Spain

^{Adress to}

ABSTRACT

INTRODUCTION: Publications are often used as a measure of success in research work. Chagas disease occurs in Central and Southern America. However, during the past years, the disease has been occurring outside Latin America due to migration from endemic zones. This article describes a bibliometric review of the literature on Chagas disease research indexed in PubMed during a 70-year period.

METHODS: Medline was used via the PubMed online service of the U.S. National Library of Medicine from 1940 to 2009. The search strategy was: Chagas disease [MeSH] OR Trypanosoma cruzi [MeSH].

RESULTS: A total of 13,989 references were retrieved. The number of publications increased steadily over time from 1,361 (1940-1969) to 5,430 (2000-2009) (coefficient of determination for linear fit, R²=0.910). Eight journals contained 25% of the Chagas disease literature. Of the publications, 64.2% came from endemic countries. Brazil was the predominant country (37%), followed by the United States (17.6%) and Argentina (14%). The ranking in production changed when the number of publications was normalized by estimated cases of Chagas disease (Panama and Uruguay), population (Argentina and Uruguay), and gross domestic product (Bolivia and Brazil).

CONCLUSIONS: Several Latin American countries, where the prevalence of T. cruzi infection was not very high, were the main producers of the Chagas disease literature, after adjusting for economic and population indexes. The countries with more estimated cases of Chagas disease produced less research on Chagas disease than some developed countries.

Keywords: Chagas disease. American trypanosomiasis. Trypanosoma cruzi. Bibliometry. Scientific production. Mapping.

RESUMO

INTRODUÇÃO: Publicações são frequentemente utilizadas como uma medida de sucesso do trabalho de pesquisa. A doença de Chagas (DCh) ocorre na América Central e do Sul. Porém, durante os últimos anos, a doença tem ocorrido fora da América Latina, devido à migração das zonas endêmicas. Este artigo descreve uma análise bibliométrica da literatura sobre as pesquisas da doença de Chagas indexadas no PubMed, durante um período de 70 anos.

MÉTODOS: O Medline foi usado através do serviço online da US PubMed da National Library of Medicine de 1940 a 2009. A estratégia de busca foi: Chagas disease [MeSH] OR Trypanosoma cruzi [MeSH].

RESULTADOS: Um total de 13.989 referências foi recuperado. O número de publicações aumentou de forma constante com 1.361 (1940-1969) para 5.430 (2000-2009) (coeficiente de determinação para o ajuste linear, R² = 0, 910). Oito revistas contiveram 25% da literatura sobre a DCh. Um total de 64,2% das publicações veio de países endêmicos. O Brasil foi o predominante (37%), seguido pelos Estados Unidos da América (17,6%) e Argentina (14%). O ranking da produção foi alterado, quando o número de publicações foi normalizado por casos estimados da doença de Chagas (Panamá e Uruguai), população (Argentina e Uruguai), e Produto Interno Bruto (Bolívia e Brasil).

CONCLUSÕES: Vários países da América Latina com uma prevalência não muito elevada de infecção pelo T. cruzi foram os principais produtores, após ajuste para os índices econômicos e populacionais. Os países com mais casos estimados da DCh produziu menos pesquisas em doença de Chagas que alguns países desenvolvidos.

Palavras-chaves: Doença de Chagas. Tripanossomíase Americana. Trypanosoma cruzi. Bibliometria. Produção científica. Mapeamento.

INTRODUCTION

Chagas disease or American trypanosomiasis is a systemic chronic parasitic infection by Trypanosoma cruzi. Chagas disease occurs throughout Mexico and Central and Southern America. A century ago, Carlos Chagas described the symptoms of the disease, the causative parasitic agent, and the vector. The disease is endemic in 21 countries and continues to present a health threat for an estimated 28 million people, mostly in Latin America^1,2. Currently, the number of infected persons is estimated at 7.7 million¹. Chagas disease is a complex zoonosis mainly transmitted by reduviid insects. During the past years, the disease has been occurring outside Latin America, transmitted in a non-vectorial way^3,4 due to migration from endemic zones^5,6. Today, the eradication of this disease remains elusive; the clinical manifestations and epidemiological characteristics differ with the diverse endemic zones, and there is a lack of proper treatment. Therefore, the Training and Research in Tropical Diseases (TDR) program and the Pan American Health Organization (PAHO) have identified several key gaps with corresponding research priorities².

Research is important for a country's development and progress⁷. Biomedical research projects usually lead to publications in the serial literature. Original articles allow investigators to present their scientific observations, and the publication of an investigator's project allows the information to be shared by the scientific community. Publications are often used as a measure of success in research work. In recent years, there has been a growing interest in developing scientific indicators capable of facilitating the analysis of the results of research activities⁷.

There are international bibliometric studies in different fields of medicine and/or different diseases^8-10. There have been recent publications analyzing the research production in parasitology^11,12, malaria¹³, and tropical medicine¹⁴, and bibliometric analyses of research published in Tropical Medicine and International Health¹⁵, Chinese Journal of Parasitology and Parasitic Diseases¹⁶, and Korean Journal of Parasitology¹⁷; of citation patterns in tropical medicine journals¹⁸, and of anthelmintics¹⁹. To the best of our knowledge, no quantitative studies analyzing the Chagas disease literature worldwide as well as in specific countries/regions have been carried out in the past. The aim of this study was to investigate the Chagas disease research output over a period of 70 years (1940 to 2009) using PubMed and to explore the extent to which the scientific production parallels the extension of American trypanosomiasis.

METHODS

The Medline database, accessible free of charge through the PubMed platform, was selected as the most suitable for references on Chagas disease publications. This database is easily accessible and widely used^8,20. PubMed (http://www.ncbi.nlm.nih.gov/pubmed) was accessed online on 25 May 2010. The subject content analysis of records was conducted according to the structure of the U.S. National Library of Medicine's Medical Subject Headings (MeSH). To retrieve documents, a search was composed with the MeSH terms or descriptors Chagas disease and Trypanosoma cruzi. The query terms were also searched in the Title and Abstract fields. The period of study was from 1940 to 2009.

The document type was used to refer to the type of article and its funding. The impact factor of a journal and its ranking were copied from the Journal Citation Reports (JCR) 2009 Science Edition²¹. The MeSH terms were grouped by topic in order to analyze the focal point of the research by considering the following categories: generalized Mesh terms, human/animals, gender, ages, and countries. The number of papers and the percentage of global scientific production for the top 100 MeSH terms were calculated.

Based on geographic, scientific, and economic criteria, the world was divided into six regions: Latin America and the Caribbean, North America, Europe, Asia, Oceania, and Africa. Latin America was considered as an endemic area for American trypanosomiasis; the other regions were considered as non-endemic areas^5,22. The productivity by country (first participating author) was analyzed by considering the number of papers and the percentage of the world production. In this case, standardized indicators of each country's productivity with respect to the population, the gross domestic product (GDP), and the estimated Chagas disease cases were also provided. To calculate the publication per million inhabitants and the gross domestic product publication per 1,000 million ($) of the GDP, data were obtained from the World Development Indicators 2009 through the online databases of the World Bank²³. To calculate the publication by estimated 10,000 Chagas disease cases, indexes were obtained from the T. cruzi seroprevalence estimates of the Pan American Health Organization²⁴.

RESULTS

In the PubMed database, 13,989 references were retrieved for the whole study period, with 1,361 (9.7%) publications from 1940 to 1969, 3,989 (28.5%) from 1970-1989, 3,593 (25.7%) from 1990 to 1999, and 5,430 (36%) from 2000 to 2009. Figure 1 shows the numbers of PubMed publications on Chagas disease research during the 70-year study period by five-year periods. The yearly average increase in publications was +6.5% throughout the study period although this percentage was much higher from 1940 to 1969 (+10.5%) than from 1970 to 1989 (+3.6%) and from 1990 to 2009 (+4.8%). After fitting the number of publications over time, a better fit was observed for a straight line (coefficient of determination for linear fit, R² = 0.910) than for an exponential curve (R² = 0.805).

Language of publication

The main language was English (76.4%), followed by Portuguese (11%), Spanish (9.2%), French (1.1%), German (0.6%), Russian (0.2%), Italian (0.09%), Japanese (0.08%), and others.

Journal of publication

These articles were published in 1,386 scientific journals. Eight journals contained 25% of the journal literature on American trypanosomiasis. About half of the literature was concentrated in 35 journals, while the remaining half was scattered over 1,241 journals. Moreover, in 641 journals there was only one paper on Chagas disease published. Table 1 shows a list of the 61 journals with the highest number of papers published during the years 1940-2009, as well as their impact factors for the year 2009, with the journal categories according to JCR classification and language. Twelve of these journals were not included in the JCR because they did not have an impact factor. The other 49 journals were included in at least one of 22 subject categories. These source journals mainly include the fields of Parasitology (n = 11), Immunology (n = 9), Tropical Medicine (n = 7), Microbiology (n = 6), General and Internal Medicine (n = 5), Public Health (n = 5), and so on.

Analysis of MeSH/subheading words

The 100 most frequent MeSH words in the manuscripts about American trypanosomiasis published during the 1940-2009 period are shown in Table 2. The main MeSH after T. cruzi and Chagas disease were Chagas cardiomyopathy (10.2%), molecular sequence data (7.8%), and insect vector (7.4%). Table 2 also presents the main subheading or topical qualifiers used for indexing and cataloging the MeSH terms Trypanosoma cruzi and/or American trypanosomiasis and/or Chagas disease. The main subheadings were immunology (24.6%), parasitology (22.1%), metabolism (20.5%), and genetics (16.3%).

Document type of publications

The most common document type was Journal Article, accounting for about 89.3% of the total (n = 12,489). Review and Letter were the second and third most common document types, with 1,057 (7.7%) and 273 (1.9%) documents, respectively. Editorial, Congresses and News accounted for the remaining 4%. Only 0.8% of the documents was subdivided into Controlled Trial (n = 118), 0.5% into Evaluation Study (n = 75) and Biography (n = 73), and 0.3% into Historical Article (n = 47). After 1974, there was research support in 61.7% of documents (7,512/12,163).

Geographic area and country of publication

The institutional address of the first author of the publication was present in 8,785 of the 13,989 articles (62.8%). The data on the absolute production of articles in each country and world region are presented in Table 3. Latin America and the Caribbean was by far the most productive area in the field of T. cruzi infection, with 64.2% of all articles having an address in this area. North America ranked second (17.9%), and Europe ranked third (15.8%).

Sixty-six countries were represented in the sample Table 3. Brazil was the predominant country (37%). The second was the United States (17.6%), which belonged to a non-endemic area, and the third was Argentina (14%). The other main countries from endemic areas are Mexico (3%), Venezuela (2.9%), Chile (2.5%), Colombia (1.4%), and Uruguay (1.2%), while those from non-endemic zones were France (4%), the United Kingdom (3.5%), Spain (2.9%), Germany (1.9%), and Japan (1.3%).

Figure 1 shows the number of publications on Chagas disease research in endemic and non-endemic countries. The coefficient of determination for a linear fit was better in endemic countries (R² = 0.860) than in non-endemic countries (R² = 0.664).

Publications in endemic countries

In Table 4, the ranking of countries based on the crude numbers of retrieved articles, and the numbers of publications for the estimated number of Chagas disease cases, inhabitants, and GDP are shown. If we calculated the ratio of the number of American trypanosomiasis publications to the estimated number of Chagas disease cases, Panama, Uruguay, Brazil, and Chile would become the most productive. Normalized by population, the order of prominence would be Argentina, Uruguay, Brazil, and Chile. Normalized by GDP, the leading countries were Bolivia, Brazil, Uruguay, and Argentina.

DISCUSSION

This study has shown a lineal increase in the number of publications on Chagas disease over the period 1940-2009. The increase in American trypanosomiasis publications seems to be less pronounced than that observed in other diseases and conditions, such as John Cunningham virus or obesity^{9, 10}. This is probably related to the decrease in the prevalence of American trypanosomiasis over the past years and the fact that this disease mostly affects developing countries in Central and South America², which have low expenditures on scientific investigation¹². The continuous interest in the field and the incorporation of new journals in PubMed may have contributed to this lineal increase.

Although the main language of the Chagas disease research output was English (76.4%), this language was less predominant in these researches than in other bibliometric studies based on PubMed, where 85-90% of the documents are in English^8,9. The other languages were Portuguese (11%) and Spanish (9.2%). Chagas disease is endemic to Latin America, which explains the higher prevalence of these languages with respect to other fields recovered from PubMed.

Journal articles were the most commonly retrieved document type (≈90%), similar to other bibliometric studies^8-10. Although controlled trials offer the best evidence for the efficacy of medical interventions²⁵, in this study they represented only 0.5% of the documents, a lower figure than in other fields^8,9.

Nucleus journals (those with high productivity) usually contain the articles with the highest impact in the area, and thus, subscriptions to such journals by indexing and abstracting services would be justified scientifically^{10, 6}. Most of the top journals publishing Chagas disease research were from the subject categories Parasitology Immunology and Tropical Medicine. From the top 10 journals, four were from Brazil: Memórias do Instituto Oswaldo Cruz (second quartile in the Parasitology and Tropical Medicine category), Revista do Instituto de Medicina Tropical de São Paulo (not included in Journal Citation Reports), Revista da Sociedade Brasileira de Medicina Tropical (third quartile in the Tropical Medicine category), and Arquivos Brasileiros de Cardiologia (third quartile in the Cardiac and Cardiovascular Systems category). The top two non-Latin American journals were Molecular and Biochemical Parasitology (second quartile in the Biochemistry and Molecular Biology, and Parasitology categories) and The American Journal of Tropical Medicine and Hygiene (first quartile in the Tropical Medicine and Public Health category). Twenty-one of the top 61 journals were printed in Latin America (Brazil, 14; Argentina, 3; Chile, 2; and Venezuela, 1), 13 were non-English publications (Portuguese and Spanish), and 12 journals were multilingual publications.

Latin America and the Caribbean was the leading area in scientific production on American trypanosomiasis. This was an expected finding since most people with T. cruzi infection live in this area^2,22,24. From non-endemic areas, the highest scientific production came from North America (17.9%), especially the United States, and Europe (15.8%). American trypanosomiasis has reached non-endemic zones through migrants from Latin America^3-5,22. Among countries outside Latin America, the United States led in scientific production on Chagas disease. The field of scientific publications was a very basic theme (immunology, parasitology, and animal model). Other publications came from the Centers for Disease Control and Prevention (Atlanta, Georgia) and the Pan American Health Organization (Regional Office of the World Health Organization localized in Washington). The elevated number of publications from the United States is probably due to the fact that the United States continues to be the most popular country of destination of people infected with T. cruzi, along with the long tradition of U.S. agencies and institutions in implementing research and health programmes, and the network of scientists operating in that country.

The number of Latin American immigrants in Europe has more than doubled from 2001 to 2004^6,22. For example, in Spain the Latin American immigrant population has risen 10-fold from 235,000 in 1998 to 2.45 million in 2009²⁷. Japan, Australia, and Canada have also received substantial numbers of Latin American immigrants in recent years²². The European countries with more Chagas disease scientific researches were France, United Kingdom, Spain, and Germany. France and Spain were more productive than Germany in this field in comparison with other fields^8,9. This is probably due to the existing network of scientists in France and Spain, with several research teams working on Latin American entomology, parasitology, tropical medicine, and public health. In addition, the movement of people from Latin America to Europe, with an increasing number of them settling there, may play a part. The growing number of cases of American trypanosomiasis in non-endemic countries, the efforts to control congenital and blood-borne routes of transmission^{3, 4, 22}, and the worldwide recognition of Chagas disease as a public health issue would probably translate into an increase in research output in the near future, advancing the search for a better way to diagnose, treat, and prevent the disease.

The analysis of the research production of South America and the Caribbean showed that Brazil was the leading country in publication output on Chagas disease, as has also been described in other biomedical fields^8-10, followed by Argentina. Brazil, a country with a moderate prevalence of Chagas disease, led in scientific production on Chagas disease research after adjusting for estimated cases of T. cruzi infection behind after Panama and Chile. Argentina, with a higher prevalence of Chagas disease, was the leading country after adjusting for population behind Uruguay. Argentina has a solid reputation in research activity in general, and this is reflected in the investigation on American trypanosomiasis. The other leading countries in publication output on Chagas disease were Mexico and Venezuela, followed by Chile, Colombia, and Uruguay. Panama, with a low prevalence of T. cruzi infection, was the leading country after adjusting for estimated cases of T. cruzi. This was probably due to the fieldwork of a team in Panama city led by the Instituto Conmemorativo Gorgas de Estudios de la Salud. Moreover, Uruguay, with a low prevalence of Chagas disease, was the second leading country after adjusting for estimated cases of American trypanosomiasis. Uruguay has worked hard to control American trypanosomiasis, reducing the incidence of the disease over the last years. This practical experience was reflected in a number of publications initiated by different departments and faculties from the Universidad de la Republica in Montevideo. Chile is another country that, despite having a low number of cases of T. cruzi infection, occupied a leading position in research. Bolivia had the highest prevalence of T. cruzi infection, and its investigators signed as first authors in 0.6% of the documents. After adjusting for economic parameters, Bolivia emerged as the leading country. Only 0.3% of the Chagas disease research output was from Paraguay, a country with a high prevalence of T. cruzi infection. In Central America, Honduras and El Salvador had a moderate-to-high prevalence of American trypanosomiasis, but few scientific researches published in journals included in PubMed had investigators from these two countries as first authors.

PubMed and the Science Citation Index were found to be the most suitable databases for searching and retrieving references for bibliometric studies^8,20. We used the PubMed database because it is easily accessible and widely used^8,11,14, and the journal index in MedLine has certain criteria for quality²⁰. However, the method we used might have had several limitations. For example, the database mainly included journals published in English, and Spanish and Portuguese journals from Latin American countries were less likely to be found on PubMed. Another limitation was that only the address of the first author appeared in the journal articles in PubMed, whereas the address was not recorded at all in Letters and Editorials. Moreover, it was not possible to estimate the quantity of articles that resulted from multinational collaborations. This might have caused some problems in estimating the research productivity in Latin America. Furthermore, finding the addresses in the manuscripts was possible only in publications from the middle of 1987 and not before, and the accuracy of the address of the first author in PubMed was lower than in the Web of Science databases²⁸. However, even though the bibliometric methodology used might have presented some limitations, and the results could, in some way, be biased⁹, we believe that this study represents a useful tool for scientists and public health policy makers in planning and organizing research on Chagas disease. We should emphasize that other authors should apply the method used in this study to evaluate research production and that our results may be compared to others in the future. Another limitation of the report related to the calculation of the standardized indicators of each country's productivity with respect to the estimated cases of Chagas disease. We obtained T. cruzi seroprevalence estimates from the Pan American Health Organization report²⁴, but the T. cruzi seroprevalence is known to differ depending on the source of the reports. For instance, the nationwide infection rate in Bolivia reported by Schofiel and Dias²⁹ was 15.4%, higher than the 6.7% reported by the Pan American Health Organization. Therefore, the standardized indicators of productivity by 10,000 estimated Chagas disease cases should be interpreted with caution.

In conclusion, we have found a lineal increase in the number of publications on Chagas disease. Brazil led the scientific production on American trypanosomiasis research. Several countries from Latin America where the prevalence of T. cruzi infection was not very high were the main producers after adjusting for economic and population indexes. Efforts should be made to help those countries with the highest prevalence of Chagas disease, such as Bolivia, Paraguay, Honduras, and El Salvador, to develop a network of scientific research (collaborative platform) with other Latin American countries, and North American or Western European countries to increase the research output. The journal Revista do Instituto de Medicina Tropical de São Paulo and its impact factor were included in the JCR in the year 2010 under the Tropical Medicine subject category (12 of 19).

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

FINANCIAL SUPPORT

This study was supported by the Fundacion para la Investigacion Hospital General Universitario de Elche (FIBELX08/08). The funders had no role in the study design, data collection and analysis, preparation of the manuscript, or decision to submit the manuscript for publication.

Address to:

Dr. José Manuel Ramos

Unidade de Doenças Infecciosas

Hospital General Universitario de Elche

Camí de l'Almàssera 11, 3203 Elche, Alicante, Spain

Phone: [phone]; Fax: [phone]

e-mail: [e-mail]

Received in 01/02/2011

Accepted in 01/06/2011

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Publication Dates

• Publication in this collection
  21 Nov 2011
• Date of issue
  Dec 2011

History

• Accepted
  01 June 2011
• Received
  01 Feb 2011