Recent Trends in the Incidence of Cystic Fibrosis in Paraguay: Analysis of the Period 2018-2023Abstract
A descriptive, retrospective, cross-sectional study was conducted, evaluating data from newborn (NB) samples sent to the PNDN between January 2018 and December 2023. Samples taken by heel prick on Whatman 903 filter paper and analyzed by fluorometric immunoassay for the quantification of immunoreactive trypsin (IRT) were included. An IRT(+)/IRT(+) strategy was adopted, with diagnostic confirmation by sweat test. Descriptive statistics were used to analyze the incidence of CF. Variability in the incidence of CF was observed between 2018 and 2023, with a peak in 2020 (1/4,431) followed by a decrease in subsequent years. In the temporal trend analysis, it was observed that the incidence of CF does not follow a simple linear trend, indicating more complex fluctuations over time, but with an increase in the average incidence being statistically significant (p=0.0385). Management indicators showed improvements in sample processing and analysis times over the years. The distribution of confirmed CF cases by health region did not reflect statistically significant differences, with a higher concentration in the Central Department (26%). The incidence of CF in Paraguay shows a stable trend in recent years. Improvements in management indicators and regional disparities in disease incidence highlight the need for differentiated approaches to CF detection.
Keywords:
Cystic fibrosis; incidence; neonatal screening; temporal trend
Introduction
Cystic fibrosis (CF) has traditionally been defined as a genetic disorder with autosomal recessive inheritance, caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein.[1] The discovery of the CFTR gene over 30 years ago marked a significant milestone in the history of the disease, contributing to improved diagnosis and treatment of patients[2] .
In Latin America, the incidence of CF remains difficult to estimate due to the lack of registries and Neonatal Screening programs, as well as the high ethnic admixture of the population.[1]-[4] . The average incidence is 1/8,000 to 1/10,000,[2] ranging from 1/6,000 to 1/8,000 in Chile,[5] 1/6,500 in Argentina,[6] 1/9,600 in Uruguay,[7] and in Brazil from 1/1,600 in populations with European ancestry to 1/14,000 in Afro-descendants[8] .
The National Neonatal Screening Program (PNDN) in Paraguay has been conducting mandatory and free CF screening, diagnosis, and treatment for all newborns since 2003 selectively; however, it was not until 2005 that open neonatal screening began, achieving 100% coverage of births registered by the Ministry of Public Health and Social Welfare (MSPyBS) in 2015.[9] The incidence described from January 2015 to December 2017 was 1/6,591, 1/4,176, and 1/5,112 for the years 2015, 2016, and 2017 respectively, revealing a stable incidence aligned with the figures reported for the Hispanic population[1] .
The temporal trends observed in incidence result from the combination of many factors. Globally, it has been observed that these can arise from demographic changes (such as increased population admixture, decreased consanguinity, and decreased fertility rates), the implementation of genetics-based health policies that allow for prevention within families or populations (such as genetic counseling), and cultural behaviors towards the use of genetic tests, prenatal diagnosis, and pregnancy terminations as implemented in France. Therefore, the causes of the observed changes in incidence vary by region and population[2] .
Several studies have investigated the temporal trends in CF incidence, most of which reported a decrease, although not in all cases.[2] Studies conducted in France, [10] Italy, [11]and Israel [12] reported significant reductions, even reaching 35% and 60% following the implementation of neonatal screening programs. [1,7]However, comparing the temporal trends of incidence between different countries remains complex due to variability in study periods and the public health policies implemented in those countries [2].
This study aims to analyze recent trends in CF incidence in Paraguay during the period 2018 to 2023 in the population of newborns whose samples were sent to the PNDN for study.
Methods
A descriptive, retrospective, cross-sectional study was conducted in which the results of NB samples sent to the PNDN from January 2018 to December 2023 were analyzed. These samples came from 1,090 sampling sites (STM) distributed across the 18 Health Regions (HR) of Paraguay.
The samples were taken from newborns up to 28 days old, obtained by heel prick on Whatman 903 filter paper, dried at room temperature for 2 to 4 hours, and refrigerated until sent to the PNDN.
The laboratory technique used consisted of the quantification of immunoreactive trypsin (IRT) by the time-resolved fluorometric immunoassay method (DELFIA/PERKIN ELMER’S) on dried blood samples collected on filter paper, using a reference value up to 55µIU/mL[1,13] .
To determine positivity in the PNDN, the IRT(+)/IRT(+) strategy was used, which involves performing an initial immunoreactive trypsin (IRT) test and requesting a second sample from all cases that tested positive in the first test; the same reference value was used for both samples. [14]If both samples showed altered results, diagnostic confirmation was carried out using the sweat test, which involves measuring chloride by the coulometric titration method in sweat samples (Figure 1)[13] .
For data analysis, descriptive statistics were used. The incidence of CF was calculated by dividing the number of samples processed per year by the number of confirmed cases during the same period. The mean and standard deviation of continuous variables were calculated. The comparison of scale-type variables between groups was based on the Student’s t-test for independent samples. The temporal incidence of the data was evaluated using a generalized linear regression model, dividing the number of confirmed cases by the number of samples in the same period. To evaluate differences in confirmed cases by HR during the study period, odds ratio (OR) analysis was used to compare between regions and the Central Department. A Chi-square test was performed to evaluate the statistical significance of the observed differences. A statistical significance level of 0.05 (p < 0.05) was established for all tests. A percentage distribution map was created by calculating the percentage of confirmed CF cases for each HR. For data management, a database was created using Microsoft Excel, and the data were analyzed with SAS software (version 9.4, The SAS Institute, Cary, NC).
Results
During the six-year study period (2018 - 2023), variability in the incidence of CF among NB in Paraguay was observed by year of study. Table 1 summarizes the annual data related to births, samples analyzed, screening coverage, positive cases, and CF incidence. In 2018, an incidence of 1 per 7,947 live births was reported, increasing to 1/6,609 in 2019 and reaching its peak in 2020 with an incidence of 1/4,431. Subsequent years showed fluctuations in incidence, with 1/4,463 in 2021 and further decreases in 2022 and 2023 with 1/7,477 and 1/9,833 respectively, although the total number of births for the latter year was not reported. The differences were not statistically significant (p>0.05).
Figure 2 illustrates the temporal trend in the incidence of CF cases per year (R2=0.0318). It suggests that the incidence of CF in Paraguay does not follow a simple linear trend, indicating more complex fluctuations over time. However, an increase in the average incidence of 0.3802 per 100,000 samples processed during the study period is observed, with a statistically significant difference (p=0.0385).
The number of confirmed cases of Cystic Fibrosis per 100,000 samples processed per year is presented with linear regression lines (blue) with a 95% Confidence Interval.
The management indicators, detailed in Table 2, show a trend towards improvement in the processing and analysis times of the samples over the years. The average age of the newborns at the time of sample collection slightly decreased from 5.41 days in 2018 to 4.74 days in 2022. Similarly, the time from sample arrival to processing showed improvement, decreasing from 5.77 days in 2018 to 5.11 days in 2022. However, a significant increase in processing time was observed in 2019, which subsequently decreased in the following years.
Table 3 and Figure 3 provide a detailed overview of the distribution of samples taken and positive CF cases by HR. Throughout the study period, the Central Department reported the highest number of samples received and positive cases (26%), followed by the Departments of Asunción (19%), Alto Paraná (11%) and Caaguazú (10%). However, the highest rates were achieved in the Departments of Presidente Hayes, Cordillera and Asunción. It is notable that some departments (Paraguari, Ñeembucú, Amambay, Alto Paraguay and Boquerón) did not report positive cases during the study period.
The differences in the distribution of cases between the Departments and health region 11 (Central department recorded the highest number of processed samples and positive cases for CF) were not statistically significant (p=0.054). Although the analysis shows no statistically significant differences in the distribution of positive CF cases between departments compared to HR 11, some regions, such as HR 3 and 15, seem to have a higher probability of receiving positive cases (OR 2.255 and 1.582 respectively).
Discussion
The incidence of CF has shown variability over time, peaking in 2020 before decreasing in subsequent years. This fluctuation in incidence not only reflects the inherent complexity of CF detection and diagnosis but also suggests the influence of multiple demographic, genetic, and public health policy factors on the prevalence of this condition in Paraguay. Comparing these data with trends observed in other regions and evaluating the possible causes behind these changes are crucial to better understand the dynamics of CF in the country and optimize detection and management strategies.
CF is a significant health problem in Latin America, and studies indicate a growing awareness of the disease burden in the region.[3] The incidence of CF in Paraguay has shown a stable incidence that does not present significant differences with those reported for the Hispanic population in the region.[2, 5-8] The latest data published by Ascurra et al. indicate figures that remain between 1/4,176 and 1/6,591 cases for the years 2015 to 2017; however, we observed its peak incidence in 2020, a year characterized by the COVID-19 pandemic, which could have affected both the coverage of analysis and the detection of cases due to health restrictions.
On the other hand, the decrease observed in 2022 and 2023 (similar to the figures reported in Uruguay[7] ) aligns with data recorded in France,[10] Italy, [11]and Israel, [12] which reported significant reductions following the implementation of rigorous neonatal screening programs. It is possible that improvements in screening strategies (reaching coverage above 80%) and awareness in the implementation of health policies (such as genetic counseling) had a positive impact on the incidence of this pathology in Paraguay. A noteworthy point is that the number of confirmed cases per year remains stable throughout the study period, unlike the figures for live births, which show a trend towards a decrease in birth rates, possibly justifying the reduction in incidence figures.
Improvements in management indicators, characterized by an increase in coverage and a reduction in sample processing and analysis times, are a positive indicator of the efficiency of the PNDN in CF detection. The reduction in the average age of newborns at the time of sample collection and the decrease in the time from sample arrival to processing are significant advances towards early detection and timely treatment of CF, which can significantly improve patient prognosis[15,16] .
The regional distribution of samples taken, and positive CF cases reflects disparities in the incidence of the disease across the country. The concentration of cases in specific regions, such as the Central HR, could be related to demographic, socioeconomic factors, and access to health services.[17, 18] This finding underscores the need for public health policies tailored to the specific needs of each region, including resource allocation and the implementation of screening and treatment programs.
This study has some limitations such as the lack of results for subjects not covered within PNDN. Although there are no updated reports on the incidence of CF in Latin America in recent years, the growing knowledge of the pathology in the region and the emphasis on studying CF-related deaths in countries like Brazil suggest an increase in concern and interest in understanding the epidemiology of the disease. [19] The complexity of the disease, as indicated by the genetic mutations found in Ecuadorian patients with CF, [20]further underscores the need to continue researching and monitoring the condition to address the challenges posed by the disease.
Future research should focus on understanding the causes behind the fluctuations in CF incidence and evaluating the effectiveness of the detection and treatment strategies implemented in the country. Additionally, studies exploring the genetic, environmental, and socioeconomic factors contributing to CF incidence in Paraguay could provide valuable information for the formulation of more effective public health policies.
In conclusion, this study provides a comprehensive view of CF incidence in Paraguay, where a trend towards a decrease in recent years is observed, highlighting improvements in management indicators and regional disparities in disease incidence. The findings underscore the need for differentiated and evidence-based approaches to CF detection, as well as the importance of continuous surveillance and detailed analysis of disease trends.
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Data availability
Non-available data. The dataset supporting the results of this study is not publicly available.
Publication Dates
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Publication in this collection
20 June 2025 -
Date of issue
2025
History
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Received
01 Jan 2025 -
Accepted
16 May 2025
