Prion diseases (PrD) are a group of rare, rapidly progressive neurological conditions with no known effective treatment. The etiological agent responsible for PrD, known as PrPSc, consists of a conformational isomer of the prion protein (PrPc), which is naturally found on the cell surface of various cell types, including neurons (Sigurdson et al., 2019). Kuru, Gerstmann-Sträussler-Scheinker syndrome, Fatal Familial Insomnia, and Creutzfeldt-Jakob Disease (CJD) are different subtypes of PrD capable of infecting humans (Appleby et al., 2022). CJD is the most common and affects around 1–2 individuals per million inhabitants worldwide every year (Klug et al., 2013). CJD is classified as sporadic (sCJD), genetic (gCJD), and acquired, which includes iatrogenic (iCJD) and new variant CJD (vCJD) (Geschwind, 2015).

The definitive diagnosis of CJD can only be made post-mortem based on the histopathological study of a brain tissue sample (Kretzschmar and Feiden, 2002). However, other tests are essential to reinforce the diagnostic hypothesis, such as magnetic resonance imaging (MRI) and genetic testing (Araújo, 2013). Electroencephalography (EEG) and cerebrospinal fluid (CSF) studies using the real-time quaking-induced conversion (RT-QuIC) technique or the identification of the 14-3-3 protein are also helpful during the diagnostic investigation process (Rhoads et al., 2020).

Following the vCJD crisis and its association with contaminated cattle herds, several countries established surveillance systems primarily to monitor this disease subtype (Anderson et al., 1996). In 2005, the Brazilian Ministry of Health (MH) included CJD on the national list of compulsory notification of diseases, illnesses, and public health events (Martins et al., 2007), and 603 suspected CJD cases were reported up to June 2018. Of these, 404 were undiagnosed (Cardoso et al., 2015; Ministry of Health, 2018). Difficulties in performing imaging examinations and neuropathological analyses are found in several medical units in Brazil, making diagnosis problematic. Initiatives to make RT-QuIC available are still modest, and some diagnosed patients had samples sent to centers outside the country for biomarker analysis, allowing for more excellent coverage of the diagnostic criteria (Barbosa et al., 2020).

Despite the progress made, the epidemiological profile of CJD in Brazil created by MH still has debilities, mainly because of the misuse of the CJD datasheet, the lack of a specific database focused on the critical information for that disease, and inconsistent data when compared to information released by MH in different documents for the same period. Given the importance of rigorously monitoring the behavior of PrD in Brazil, as this is a critical disease for public health, new research should be dedicated to studying the subject. Therefore, this study aimed to evaluate the Brazilian PrD surveillance system, highlighting some of its weaknesses and pointing out prospects for making it more reliable and efficient.

Between 2005 and 2021, SINAN recorded 1.576 notifications of suspected cases of CJD, which were concentrated in the Southeast, South, and Northeast regions of Brazil, especially in the states of São Paulo (32.5%), Paraná (12%), and Minas Gerais (10%). The 55–74 age group predominated (60.2%), followed by 45–54 (15%) and 75–85 (11.8%).

The years with the highest number of notifications were 2019 (11%), 2021 (9%), and 2014 (9%). The age range with the fewest notifications was 0–24 years (1.7%). In addition, most notified cases occurred among women (53.6%), white individuals (61.4%), and urban dwellers (90%) (Table 1).

Of all the notifications, 547 cases (34.7%) were confirmed based on the following confirmation criteria: laboratory (65.6%), clinical-epidemiological (29.4%), and not informed (4.9%). Just five Brazilian states reported accurate information: Rondônia, Acre, Mato Grosso do Sul, Rio de Janeiro, and Rio Grande do Sul. MH’s Epidemiological Bulletin does not specify which laboratory tests or clinical-epidemiological criteria were used to confirm the cases, which hinders the evaluation of the data presented. On the other hand, in the CJD notification and investigation protocol, the MH cites the clinical and laboratory criteria for classifying a case as possible, probable, and definitive (Ministry of Health, 2018).

It should be noted that the same document also states that only 18.4% of notified cases died from the disease and that 13.1% were cured, which is unexpected for the natural history of the disease, considering the 100% mortality rate of CJD already well established in current literature. In addition, 55.8% of the notifications did not provide data on how the cases evolved, and crucial information, such as the time interval from the onset of symptoms to diagnosis, was also not clarified in the document. Deaths were also more prevalent in São Paulo (38.3%), Minas Gerais (10.7%), and Paraná (8.3%) (Figure 1). Most deaths were recorded in the 65–74 age group (34.1%), followed by 55–64 (27.5%) and finally by 45–54 (14.4%) (Table 2). The highest deaths were in 2014 (12%) and 2016 (11.7%), respectively. Moreover, the information displayed in the tables differs grossly from that found in the text of this document, maybe due to how the raw data was exported from different software.

Only 547 of the 1,576 cases of CJD reported as suspected by the MH between 2005 and 2021 were confirmed. However, considering the estimates in the literature and the Brazilian population for this period, the total number of reported cases should have been close to 3,200, exposing an intense underreporting of this condition (Klug et al., 2013).

We observed that data on PrD in the national territory are still organized in a way that falls short of expectations for creating a rigorous surveillance system for this disease. Among the inconsistencies found in the MH’s epidemiological bulletin of CJD, there needs to be more detail regarding the method used to confirm cases, and there is a deficient description of how the condition evolved in 55.8% of notifications.

The sCJD usually affects older adults, with an average age of 67. On the other hand, cases of vCJD tend to occur in the younger population, with an average age of 26 (National Centre Research & Surveillance Unit, 2016). In this study, most of the notifications of suspected cases occurred in the 55–74 age group. However, the CJD Epidemiological Bulletin from the MH does not refer to the disease subtypes in the data presented, making it difficult to establish an accurate epidemiological profile.

There was also a predominance of females (53.6%) among the reported cases. This finding aligns with a prospective study in Japan, which found a prevalence of 58.1% of women in the sample of patients diagnosed with prion diseases (Nozaki et al., 2010). Concerning race, most of the cases were reported in white Brazilians (61.4%). Other studies in the literature have also reported a higher incidence of PrD in white individuals, which could be explained either by a possible genetic predisposition that has not yet been discovered in this part of the population (Sánchez-González et al., 2020; Tam et al., 2023) or by a notification bias since most reports describe data from high-income, Caucasian-predominant countries.

The Southeast, South, and Northeast were the Brazilian regions with the highest number of suspected cases of CJD between 2005 and 2021. Despite an 11-years gap, these exact locations also occupied the podium for PrD deaths recorded between 2005 and 2010 (Cardoso et al., 2015). This finding shows that these regions could have a more structured epidemiological surveillance system than other regions of the country.

Although diagnostic confirmation can only be made after the patient’s death, some procedures can be carried out while the patient is still alive during the investigative process. Real-time quaking-induced conversion (RT-QuIC), a method that amplifies the pathogenic prion protein in cerebrospinal fluid, has a sensitivity of 90.3% and specificity of 98.5% for CJD (Rhoads et al., 2020). This method is primarily unavailable in Brazil, despite some efforts, such as the report by Barbosa et al. (2020). The authors performed second-generation RT-QuIC in CSF samples from eight patients with suspected CJD and used patients with other neurological conditions as negative controls. Five of seven suspected cases had positive tests; two showed inconclusive results. Among controls, there was one false positive. The presence of the 14-3-3 protein in CSF has good sensitivity in diagnosing CJD, especially in sporadic forms, but this marker has been considered with variable specificity and sensitivity (Satoh et al., 2006).

Data from the CJD Epidemiological Bulletin from the MH suggests that some of the cases were confirmed through clinical aspects, which goes against the scientific premise that PrD can only be definitively diagnosed through histopathological examination. Considering the relevance of MRI in the diagnostic investigation of CJD, this procedure should be more emphasized in the CJD Notification and Investigation Protocol created by Ministry of Health (2018). Furthermore, this same document should define more clearly what constitutes a suspected case of CJD and what criteria are essential for confirmation, since the way it is presented is ambiguous and could cause confusion among non-specialists, because, for example, it does not specify which MRI sequences should be followed to obtain the images.

Unlike Brazil, the United Kingdom has the UK National CJD Research and Surveillance Unit, which is exclusively responsible for registering and monitoring suspected cases of CJD in the country. This is a major advancement, as it allows for the concentration of efforts directed toward surveillance and the creation of more effective diagnostic methods for CJD (Tam et al., 2023). Similarly, in the United States, there is the National Prion Disease Pathology Surveillance Center, which is supported by the US Centers for Disease Control and Prevention, and provides accurate diagnostic tests, such as RT-QuIC, to enable the rapid diagnosis of suspected cases (Sánchez-González et al., 2020).

In 1992, France created the National Surveillance Network of Transmissible Spongiform Encephalopathies, to which laboratories notify suspected cases of CJD through tests, such as the identification of the 14-3-3 protein in the CSF, and which allows physicians to directly contact neurologists to ensure the correct management of cases (Denouel et al., 2023). This model of an organized network of prion disease specialists who can be contacted directly by the attending physician of suspected cases makes the notification and follow-up process much more efficient. In Germany, the National Reference Center for Transmissible Spongiform Encephalopathies, which is linked to the German Ministry of Health, classifies suspected cases of CJD based on contact with health authorities where the case was identified (Hermann et al., 2023).

Despite being a notifiable disease with a high associated mortality rate, CJD surveillance in Brazil is still marked by underreporting of cases. This reality is alarming because, without understanding the real number of cases affecting Brazilians, it becomes unlikely to draw a reliable epidemiological profile of the population groups at highest risk for developing the disease. It is also worth noting that underreporting directly affects the creation of national policies for the prevention and control of the disease, since public health managers are guided by this same epidemiological surveillance data. We believe we can learn from other referral centers, like in the USA, Germany, and others, to create more reliable surveillance for CJD in Brazil.

Retrospective methodological design based on a public database is an important limitation of the study. Studies conducted with secondary data are subject not only to incorrect data entry but also to incomplete data, which favors the persistence of underreporting and significantly interferes with the quality of the data presented. Although SINAN is a government database, the record of cases that progressed to a cure is inconsistent with the prognosis of the disease, exposing biases in the accuracy of the data. In addition, some of the notifications did not contain the evolution of the cases, which reveals that the information made available through SINAN is still very superficial; therefore, although it is a useful tool for monitoring epidemiological outbreaks of certain diseases, the applicability of SINAN in the epidemiological surveillance of CJD, which has a long incubation period, is not ideal.

This document suggests, considering all the points highlighted, a review of how data on the epidemiology of CJD in Brazil are recorded and published, so that this study serves as a foundation for conducting prospective collaborative studies with other research centers, aligning Brazil with international epidemiological surveillance.

We propose that MH and other players, such as researchers, epidemiologists, and neurologists, create a specific PrD database using the CJD report form as the input data, not only the SINAN inputs. Also, MH should review the current protocol, adding more information about differential diagnosis, biomarkers such as RT-QuIC and MRI criteria. Additionally, patients and neurologists must have access to a comprehensive diagnostic protocol (e.g., MRI, CSF, and genetic studies) as a strategy to reduce disparities in care and data collection. All efforts should be pursued to create a comprehensive surveillance system that supports public health authorities in observing trends in CJD in Brazil.