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Temporal trend and epidemiological profile of exogenous poisonings in Brazil: an ecological study from 2007 to 2019

Braian Valério Cassiano de Castro1 – braianvcc@gmail.com – orcid.org/0000-0001-7039-287X
Marlene Zannin2 – marlenezannin@gmail.com – orcid.org/0000-0001-7956-9969
Jéssica Donato Antônio3 – jdadonato@gmail.com – orcid.org/0009-0005-6715-1983
Renan Choi Bustamante4 – renan.choi@unifesp.br – orcid.org/0000-0003-2738-2275
Thais Cláudia Roma de Oliveira Konstantyner5 – t.konstantyner@unifesp.br – orcid.org/0000-0002-2289-1866
Lucas Leite Cunha1 – lucas.leite@unifesp.br – orcid.org/0000-0002-1513-1455

1 Escola Paulista de Medicina, Universidade Federal de São Paulo, Programa de Pós-Graduação em Saúde Baseada em Evidências, São Paulo, SP, Brasil
2 Universidade Federal de Santa Catarina, Departamento de Patologia e Toxicologia, Florianópolis, SC, Brasil
3 Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brasil
4 Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
5 Escola Paulista de Medicina, Universidade Federal de São Paulo, Departamento de Medicina Preventiva, São Paulo, SP, Brasil

Abstract

Poisonings are a global public health problem. With the aim of describing their epidemiological profile in Brazil, an ecological time series study was conducted from 2007 to 2019, characterizing individual demographic variables (sex; age), exposure variables (circumstance; toxic agents), health indicators (incidence; mortality; fatality), and temporal trends. Data concerning notifications were extracted from the Notifiable Diseases Information System (SINAN) and stratified by macro-region, sex, age, circumstance, and toxic agents. The indicators of incidence, fatality, and mortality were calculated, and the temporal trend was analyzed using the Prais-Winsten model. Our search obtained 1,166,299 notifications, the majority of which were female individuals (55.6%). The preponderance of cases that resulted in death were referent to male individuals (59.6%). The adult age group was the most reported (60.4%), yet the incidence (50.49/100,000 inhabitants) was higher among children. Medication was the main agent (43.7%), and attempted suicide was the main circumstance related to notifications, deaths, incidence, and mortality. Our findings show a low fatality rate (1.0%) and an increasing trend in incidence and mortality. Thus, the results can guide health promotion and prevention actions in the country.
Keywords: Poisoning; Epidemiology; Brazil; Public Health Surveillance

 
INTRODUCTION

Poisoning is a global public health problem1 and a common reason for seeking emergency care in health services around the world2. In addition to the high prevalence of acute poisoning1,2, which is one of the main causes of emergency hospital care3 and has a high potential to generate severe cases4, poison is frequently used as a method of attempted suicide5. The World Health Organization (WHO) estimates that in 2016 there were 106,683 deaths due to unintentional poisoning worldwide6. Comparing this number with other health conditions, the true magnitude of this figure becomes clear, since dengue, endemic in Brazil and more than 100 countries, is responsible for approximately 21,000 deaths/year worldwide7.
Although the importance of toxicological care has only recently been understood in Brazil, there are already 32 Toxicological Information and Care Centers (CIATox) in 19 states9. These health facilities are part of the Trauma Care Line and the Emergency Care Network (RUE) within the scope of the Brazilian Unified Health System (SUS)10. Given the importance of these locations, the establishment of new centers was recognized as a priority by the United Nations (UN) Agenda 21 at the Rio-92 conference and more recently in the global action plan agreed upon by the International Conference on Chemicals Management (ICCM) held in 20073.
In parallel with the creation of new centers, the regulations referent to the notification of this entity in the country proved to be an important milestone for data collection. In 200411, it was established that poisonings would be subject to compulsory notification, when related to work, and would be recorded in the Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação – SINAN). Later, in 2011, exogenous poisonings became a universally notifiable disease12.
Considering the relevance of the topic and that there are no studies that have sought a detailed epidemiological description of exogenous poisonings in Brazil from 2007 to 201913,14,15,16, our study aimed to describe the epidemiological profile of this condition in the country, characterizing individual demographic variables (sex and age), exposure variables (circumstances and toxic agents), health indicators (incidence, mortality, and fatality), as well as the temporal trend.


METHODS

This work is an ecological time-series study on exogenous poisonings in Brazil from 2007 to 2019. Data from 2020 and 2021 were extracted from SINAN using TABNET, a free software developed by DATASUS that provides access to the public domain database of the Ministry of Health. This information is collected through the Individual Notification Forms, filled out by healthcare units, which are later supplemented with data concerning progression to death, used in the present study to account for notifications and to calculate certain health indicators, such as mortality and fatality rates. The chosen period was due to the fact that 2007 was the first year in which SINAN made information on poisonings publicly available, and 2019 was the last year in which the data were available for access at the time of collection. Data from the years of the pandemic were not included, as there was a change in the global population pattern in relation to poisonings during that period17. The results were stratified for analysis by macro-regions (Southeast, North, Northeast, South, Midwest) according to individual demographic variables (sex and age) and exposure variables (circumstances of poisoning and toxic agents). In addition, incidence, fatality, and general and specific mortality were calculated.
Regarding individual demographic variables, sex was stratified into male and female categories and age group was categorized according to the classification proposed by the WHO18 and the UN19, which groups ages into ≤ 9 years (child), 10 to 19 years (adolescent), 20 to 59 years (adult), and ≥ 60 years (elderly). Regarding exposure variables, the circumstances provided by SINAN include: accidental use, therapeutic use, administrative error, abuse, attempted suicide, violence/homicide, habitual use, environment, medical prescription, self-medication, food intake, attempted abortion, and other. Possible toxic agents are pesticides (agricultural, public health, domestic); veterinary products; cosmetics; metals; toxic plants; medication; rodenticides; household products; chemicals; drugs of abuse; food and beverages; and others.
Regarding the incidence rate and the overall mortality rate (division of the total number of reports of deaths due to poisoning from 2007 to 2019 in a given macro-region or in Brazil, by the total population exposed to the risk), in order to make the analysis more visual and easy to compare, the rates were calculated, respectively, per 100,000 inhabitants and per 1,000,000 inhabitants. The specific mortality rate was calculated by dividing the number of reports of deaths by sex, age group, toxic agent, or circumstance, from 2007 to 2019, in a given macro-region or in Brazil, by the total population exposed to the risk. We describe the time series of the incidence, mortality, and fatality rate of exogenous poisonings in Brazil by macro-regions, sex, age group, circumstance, and toxic agents. Demographic information was obtained from TABNET through population estimates carried out by the Brazilian Institute of Geography and Statistics (IBGE).
The Prais-Winsten model20 was used to analyze temporal trends. The dependent variable was considered to be the transformation of incidence and mortality in a logarithmic base10, while the independent variable was considered to be the years of the historical series (2007 to 2019). To assess the possible trend of rise or fall in incidence and mortality over time, the annual percentage change (APC) was estimated using the formula [-1+10b1]100%, with b1 being the linear regression coefficient, and their respective 95% confidence intervals (95% CI) were estimated using the formula [-1+10b1min]100%; [-1+10b1max]*100%, with "min" being the minimum and "max" being the maximum. The trend was considered present when zero was not contained in the 95% CI of the APC, which rose when APC was positive and decreased when APC was negative. When zero was contained in the 95% CI of the APC, the trend was called stationary20. These analyses were performed using R software, version 3.6.3. In addition, all compiled content was entered, tabulated, and evaluated using Microsoft Office Excel 2016 software.
In accordance with the guidelines of the Research Ethics Committee (Comitê de Ética em Pesquisa – CEP) of Unifesp, and aligned with resolution no. 466 of 2012 of the National Health Council, there was no need to submit this study to the CEP, as it is a study that used a publicly accessible secondary database.


RESULTS

Between 2007 and 2019, 1,166,299 notifications and 11,867 deaths from exogenous poisoning were recorded in Brazil. This represented an increase of 6.84-fold and 3.47-fold between 2007 and 2019, respectively. Around 75.0% of the notifications were due to acute exposure and 3.0% to chronic exposure, while the remaining fields of the form were either ignored or left blank. The highest occurrence of cases and deaths occurred in the Southeast region (47.5%; n=554,350 and 44.0%; n=5,220) and the lowest in the North region (3.5%; n=40,143 and 3.6%; n=415). Considering the distribution of notifications by sex in Brazil and in the macro-regions, a predominance of female involvement (Table 1) was observed; however, the frequency of deaths was higher among males, accounting for approximately 59.6% of the caseload of deaths due to this condition in the country.
Regarding the age range, the data show that most poisonings occurred in adults (60.4%), followed by adolescents (18.6%), children (17.0%), and the elderly (4.0%). With respect to deaths, a similar pattern was observed, with individuals aged 20 to 59 years being identified as the main group during the period (72.1%; n=8,553).
Evaluating the toxic agents and the circumstances of the poisoning, the notifications were predominantly due to the use of medications in the context of attempted suicide (Table 1). Furthermore, the toxic agent and circumstances most related to death were also medications (27.0%; n=3,196) and attempted suicide (60.7%; n=7,290).
Our data show that women were mostly poisoned by medications (56.0%; n=363,483), with attempted suicide being the most commonly reported scenario in this group (49.4%; n=324,538). By contrast, although this was the main toxic agent responsible for poisonings (28.2%; n=146,115) in male, it comprised a smaller percentage of the total, given the greater representation of drugs of abuse (19.9%; n=103,168) and food and beverages (10.7%; n=55,271).
As far as health indicators is concerned, Figure 1 and Figure 2 show the annual increase in incidence and overall mortality rates in Brazil and in each of its macro-regions, with the South region standing out with the highest incidence (59.61 cases per 100,000 inhabitants) and mortality (6.91 deaths per 1,000,000 inhabitants) and the North region with the lowest (18.21 cases per 100,000 inhabitants; 1.88 deaths per 1,000,000 inhabitants). Similar to what was observed in relation to the absolute frequency of notifications according to sex, the highest incidence occurred in females in all major regions of Brazil, mainly in the South region (68.6 cases per 100,000 inhabitants). Specific mortality was higher among males (5.56 deaths per 1,000,000 inhabitants).
The incidence by age group was different from the notifications in absolute numbers previously reported in this study. There was a higher incidence of poisoning in the group of children (50.49 cases per 100,000 inhabitants), followed by the group of adolescents (49.65 cases per 100,000 inhabitants), adults (48.06 cases per 100,000 inhabitants), and the elderly (15.5 cases per 100,000 inhabitants).
Our data show that almost half of the incident cases during the analyzed period occurred due to the use of medications (19.61 cases per 100,000 inhabitants), followed by drugs of abuse (5.33 cases per 100,000 inhabitants) and food and beverages (3.69 cases per 100,000 inhabitants). Regarding the incidence of the circumstances involved, attempted suicide (17.09 cases per 100,000 inhabitants) was the most common, followed by accidental use (8.3 cases per 100,000 inhabitants) and abuse (5.57 cases per 100,000 inhabitants). When analyzing the expression of this problem in each macro-region, we see that medications continue to be the most common toxic agent, followed by drugs of abuse.
Analyzing the toxic agents according to age group, it was clear that medications are the most common agents irrespective of the age range. It should also be noted that the second most common agent in individuals, aged ≤ 9 years is household products; from 10 to 59 years, is drugs of abuse; and from ≥ 60 years, is food and beverages. Finally, with regard to the specific circumstances, the most common in children was accidental use, while in the other age groups it was attempted suicide.
This study also stratified mortality in relation to circumstances and found attempted suicide (2.8 deaths per 1,000,000 inhabitants) to be the most common in each of the major regions. Concerning the stratification of this indicator by age, mortality was identified mainly in the adult group (72.1%; n=8,553; 5.84 deaths per 1,000,000 inhabitants).
Over the years, there has been a significant heterogeneity of toxic agents in the macro-regions related to mortality due to poisoning. However, the change in scenario throughout the country stands out, since in 2007 agricultural pesticides (37.4%; 0.7 deaths per 1,000,000 inhabitants) were main agents involved in the context of death. In 2019, this reality changed, with these agents dropping in ranking to third place (12.9%; 0.75 deaths per 1,000,000 inhabitants), while medications (37.5%; 2.19 deaths per 1,000,000 inhabitants) rose to the top of the list (Table 3). Our results show an increase in deaths due to drugs of abuse in all regions of Brazil, placing this agent (24.1%; 1.4 deaths per 1,000,000 inhabitants) as the second most frequently related to death by poisoning in the country in 2019.
The fatality rate was calculated showing that 1.0% of all individuals who were poisoned died. When stratified by sex and age, it was found that the studied disease was more lethal in males (1.4%) and the elderly (3.2%). Agricultural pesticides (4.2%) and rodenticides (2.7%) also stand out as the most lethal agents in the country during the period studied, with violence/homicide (2.1%) and attempted suicide (1.6%) representing the most lethal circumstances. Regarding the use of agricultural pesticides, it is important to note that the Northeast and North regions, unlike the other regions, presented a much higher fatality rate, reaching 7.3% and 4.2%, respectively.
Finally, when investigating the temporal trend of incidence and mortality, a positive APC was observed in all major regions and in the country over time (Table 2), that is, there was an increasing trend in all of the scenarios. Regarding incidence, the North (APC 19.8%; 95%CI 15.19-24.57) and Southeast regions (APC 18.2%; 95%CI 11.83-24.84) were those that presented the highest APC values, showing the greatest increasing trends over time, while the South region showed the lowest value. As far as mortality, the Midwest region (APC 16.1%; 95%CI 7.05-25.97) presented the highest APC and the South region (APC 4.7%; 95%CI 0.58-9), once again, the lowest (Table 2).


DISCUSSION

During the period analyzed in this study, there was a significant increase in the absolute number of notifications and deaths due to exogenous poisoning in all macro-regions of the country, especially related to the use of medications and in the context of attempted suicide. Consistent with what occurs in global epidemiology21, a higher incidence was noted due to acute exposure, given that it was the main associated circumstance. A higher incidence in children and a higher mortality rate among males was also observed, with both indicators showing an increasing temporal trend.
Globally, the WHO considers poisoning to be an underestimated and underreported public health concern22. Given this reality, it can be inferred that part of the increase in notifications, deaths, incidence, and mortality was due to the reduction in underreporting, something encouraged by the Ministry of Health in 2011, set forth in Ordinance No. 104, which made notification compulsory and universal12, through improvements in the operationalization of CIATox, established in Ordinance No. 1,67810, which determined a fixed financial incentive for each of these Centers, and through the increase in the number of suicide cases in Brazil23, since many are linked to acute poisoning24.
As expected, due to the high female prevalence in each macro-region25 and the global epidemiological pattern of attempted suicide, there was a higher occurrence of the condition in females. Regarding the age group, taking into account the growing importance of attempted suicide as the main circumstance involved in poisonings in Brazil among individuals aged 10 or over, and the fact that underdeveloped countries tend to have high suicide rates among young adults26, the predominance of notifications and deaths in this age group becomes understandable.
Furthermore, medications and drugs of abuse accounted for approximately 55.0% of all agents used during the period. According to the 3rd National Survey on Drug Use by the Brazilian Population, conducted in 2015, around 17,000 people, aged 12 to 65 years, were interviewed throughout the country about drug use. The interviewees reported that obtaining such agents as marijuana, solvents, crack, and cocaine was “very easy”27, corroborating the understanding of the rise in the incidence of drugs of abuse and the circumstances of abuse in all age groups, particularly among male adults and adolescents. Regarding medications, one study, evaluating a 10-year historical series in Brazil, demonstrated that 57.2% of the cases of poisoning by this agent were associated with suicide28, information that is in line with the findings of the present study, since this represented the main toxic agent used in poisonings in the country and the main agent used by patients who died.
Concerning deaths due to poisoning, we found a close relationship with the suicide scenario, since approximately 60.7% of deaths due to poisoning were in the context of attempted suicide. This can be justified by the fact that poisoning is the most common method of attempted suicide worldwide24 and is commonly associated with people with depression, a condition that has increased in Brazil29.
When analyzing the data from a population perspective, one can observe that both the incidence and mortality indicators increased during the study period, showing a growing trend to increase in the upcoming years (Table 2).
It is interesting to note that although the incidence was higher among females in all macro-regions from 2007 to 2019, mortality was higher among males. This is a pattern classically documented in the literature in the context of attempted suicide30. As previously reported, it is well-known that self-harm is mostly linked to depressive conditions. Since this disorder is twice as common in females, this reality corroborates the present study’s results found31. Furthermore, there is a behavioral issue that may be related to these findings, since the literature shows a greater tendency of females to seek health services due to health problems32.
There are risk groups in toxicology, such as children under 5 years of age, who, due to being in a phase of discovery, associated with parental carelessness, along with the bright and attractive colors of medicine and cleaning product packaging, are often victims of exposure and acute poisoning33. Based on this reality, the results of the present study conclude that accidental use represents the second most common circumstance from 2007 to 2019 and accounts for approximately 71.0% of acute poisonings in children, which is the age group with the highest incidence in the country.
In 2007, the main cause of mortality in the country due to poisoning was agricultural pesticides (Table 3). Over the years, likely due to the high consumption of medicines in Brazil (fifth highest in the world)34, the ease with which Brazilians obtain medicines culturally at the popular “pharmacy counter”34, the underreporting of cases35, 36, and the lack of health surveillance of workers in agricultural regions36, medicines have assumed the position of the main toxic agent related to the number of new cases of poisoning, deaths, incidence, and mortality.
The fatality rate found mainly in pesticides is related to their high dangerousness and their various routes of contamination13. According to data from the Institute for Health Policy Studies (IEPS), published in its technical note No. 2837, which analyzed 14 health indicators for Brazilian macro-regions from 2010 to 2020, the North and Northeast regions had the worst health system rates in the country, which may explain the higher fatality rate of toxic agents in these regions. On the other hand, despite the better performance of the health indicators reported in this IEPS document37, the South region has had the highest mortality rate due to attempted suicide in the country for years23, a fact that is in line with the results found in the present study, in which the highest incidence and mortality due to exogenous poisoning occurred in this region. This finding may be related not only to the high socioeconomic growth of the macro-region, which accentuates socioeconomic disparities, but also to the presence of specialized health centers that facilitate access and contribute to a higher number of notifications31. In general, both mortality and fatality rates were low in the country. This data is also present in Brazilian literature in local studies14, which may indicate that the toxic agents used in Brazil, especially medications, have a low probability of leading to serious conditions. However, it should be noted that the greatest fatality observed was with the use of agricultural pesticides and these continue to be highly toxic to human health and the environment36.
As a limitation of the study, we highlight the use of secondary databases dependent on notifications, which present regional and temporal variability. Many of the data collected underwent subtle changes throughout 2020, 2021, and 2022, as they were updated and reviewed by SINAN in TABNET; thus, a slight disparity in the numbers collected was noted, mainly regarding the total number of notifications for each variable. These periodic updates and reviews aim to ensure maximum consistency, integrity, completeness, and regularity, as well as to avoid a possible duplication of notification records. It is the responsibility of the Federal Government, States, and Municipalities to carry out this assessment. Consequently, it is possible that there are inconsistencies in this sense that may compromise the accuracy of the results in some way. Regarding the analysis of the temporal trend, the amplitude of the confidence intervals suggests that there is a non-uniform oscillation of the points in the historical series, reflecting on the accuracy of the estimates and confidence intervals. Since this is a study that uses secondary data, this limitation should be considered when interpreting the results and making inferences. Another limitation concerns the impossibility of determining which drug classes are most frequently used in exogenous poisonings, which was due to a limitation of the DATASUS platform itself, which does not make this type of data available through TABNET. Due to the study design, the relationship between the exposure factor and the event may not be occurring at the individual level, which could lead to ecological fallacy. As a result, the findings were carefully interpreted at the population level. Finally, it is not possible to establish causality regarding the findings, and it is only possible to generate hypotheses.


CONCLUSION

The present study analyzed a 13-year historical series in Brazil, using official data to describe poisonings in relation to demographic and exposure factors. It was concluded that exogenous poisonings are more common among women, mainly associated with the use of medications and suicide, especially in the South and Southeast regions. Although the number of reports was higher among adults, the incidence was higher in children, especially due to accidental exposures. There was a significant increase in poisonings due to drugs of abuse, mainly among adolescents and adults, ranking them as the second most frequent cause of poisoning in the country. Deaths mostly predominated among adult men, mainly due to the use of medications, with an increasing trend of mortality over time. The results suggest the need for targeted public policies, especially for the prevention of suicide, accidental exposures, and substance abuse, with the potential to guide health promotion and prevention actions in Brazil.

FUNDING
Funding Institution: Scholarship from the Coordination for the Improvement of Higher Education Personnel (CAPES)
Funding Code: 33009015.


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