Figure 1

Figure 1. Regions of the Iberian Peninsula where human infections with Crimean-Congo hemorrhagic fever virus were reported. Red star indicates fatal case of Crimean-Congo hemorrhagic fever, Portugal, 2024; yellow triangle, the seropositive...

Figure 2

Figure 2. Timeline for fatal case of Crimean-Congo hemorrhagic fever, Portugal, 2024. Created using BioRender.com. CCHFV, Crimean-Congo hemorrhagic fever virus; ICU, intensive care unit; MSF, Mediterranean spotted fever; N, nucleoprotein; s.l., sensu...

On July 12, 2024, an 83-year-old man was admitted to Bragança Public Hospital (Bragança, Portugal) with complaints of fever (39.5°C) and myalgia. The patient reported removing a tick on July 10 (Table 1) from the periumbilical region 1 day before the onset of symptoms on July 11. He lived in the district of Bragança, in a rural environment, and mentioned participation in outdoor social events and activities from June 29–July 7; he had no history of international travel (Figure 1). We made a presumptive diagnosis of Mediterranean spotted fever (MSF), and initiated treatment with doxycycline (200 mg/d) before discharge. However, on July 16, day 6 of symptoms, the patient was readmitted with gastrointestinal symptoms (nausea, vomiting, diarrhea) and persistent myalgia and fever. On physical examination, his temperature was 38.5°C, heart rate 125 beats/min, respiratory rate 25 breaths/min, and blood pressure 90/56 mm Hg; and he had a small periumbilical eschar and a petechial rash on his legs. Laboratory testing revealed thrombocytopenia, prolonged activated partial thromboplastin time, hypofibrinogenemia, elevated transaminases, lymphopenia, and hepatocellular cytolysis (Table 2). His condition gradually worsened, and gingival bleeding and epistaxis required transfusion. We treated the patient symptomatically: correction of hypovolemia and electrolyte imbalance caused by gastrointestinal disorders, correction of hemostasis (platelet transfusion and fibrinogen), and antimicrobial drug administration. On July 18, he was transferred to the intensive care unit because of multiple organ failure. We collected a second serum specimen on July 19 that tested negative for various tickborne pathogens. However, the specimen was positive for IgG against Rickettsia by using Rickettsia conorii IFA Slide (BIOCELL Diagnostics, https://biocelldx.com), which indicated past exposure to a spotted fever group Rickettsia. The patient died on July 22 (Figure 2).

The case was reviewed at a regular hospital medical meeting because of the unclear cause of death. Because of the recent CCHF cases in the neighboring regions in Spain, a day 9 serum sample from the patient was sent to the reference laboratory of the Portuguese National Institute of Health for CCHFV testing and PCR for Rickettsia spp. by using the Genesig PCR Kit (Primerdesign Ltd, https://www.genesig.com). The sample tested positive for CCHFV. We inactivated the sample in the Biosafety Level 3 facility by using the QIAamp Viral RNA Kit (QIAGEN, https://www.qiagen.com), followed by extraction under Biosafety Level 2 conditions. We conducted molecular testing by using the RealStar CCHFV RT-PCR Kit 1.0 (Altona Diagnostics, https://altona-diagnostics.com) and confirmed by using an in-house real-time reverse transcription PCR (RT-PCR) protocol (12). We purified a fragment (122 bp) from the small segment that was amplified by conventional RT-PCR by using the primers described previously (12) and conducted Sanger sequencing (GenBank accession no. PQ200212). Similarity searches within the GenBank dataset by using the BLAST algorithm (13) showed 100% similarity to CCHFV genotype III strains circulating in Spain (2014 and 2016) and Mauritania (1984). We tested for the presence of specific antibodies against CCHFV by using the Crimean-Congo fever virus Mosaic 2 immunofluorescence assay (EUROIMMUN, https://www.euroimmun.com) for IgM and IgG against the glycoprotein (GPC–glycoprotein precursor) and nucleoprotein antigens. The patient’s serum was positive for the IgM nucleoprotein-specific antigen at 128 titers (cutoff for positivity >16) (Figure 2).

We describe an autochthonous case of CCHF in Portugal in a deceased patient infected by a tick bite. The patient resided in Bragança, a district with a high incidence of MSF, and was initially misdiagnosed as having MSF because of overlapping epidemiologic, clinical, and laboratory features with CCHF (2,14). At admission on July 11, the patient showed no signs of severe illness. Of consequence, doxycycline, the standard antimicrobial for MSF, was administered, and the patient was then discharged. Of note, the patient had not traveled outside the district in the 2 weeks before symptom onset. Although CCHFV circulation has long been recognized in Portugal (4) and routine surveillance by RT-PCR is performed on Hyalomma spp. ticks collected throughout the country (5), the virus had not previously been detected by RT-PCR. All risk factors considered for CCHF infection in Portugal are similar to those known in Spain, including a favorable climate, the widespread presence of a tick vector, the country's geographic location along the migratory route of birds from CCHFV endemic areas, and proximity to Africa (15).

This case highlights the public health threat posed by CCHFV in Portugal, particularly because of the widespread distribution of Hyalomma ticks in the country. Increased vector surveillance and studies with more tick samples from ungulates, especially red deer, as well as serosurveys in wildlife and humans are urgently needed. Public awareness campaigns should focus on preventative behaviors for avoiding tick exposure, especially among outdoor enthusiasts and professionals in nature-related activities.

Although attention to CCHF is most often drawn by severe cases, the clinical manifestations might be mild and could go unnoticed by clinicians. This case emphasizes the importance of including CCHF in the differential diagnosis list of MSF. Because of the high biologic risk of CCHFV transmission and the biosafety conditions required for its handling, prompt risk assessment is critical for rapid diagnosis of suspected cases.