Tuesday, December 5, 2023
| Characteristic | Patient no. and source | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1 (10) | 2 (10) | 3 (12) | 4 (13) | 5 | 6 | 7 | 8 (11) | 9 | 10 | |
| Age, y | 62 | 50 | 74 | 53 | 70 | 54 | 69 | 32 | 59 | 30 |
| Sex | M | F | M | M | M | M | M | F | M | F |
| Rural location | No | No | No | Yes | Yes | Yes | Yes | No | Yes | No |
| Date | 2016 Aug | 2016 Aug | 2018 Jul | 2018 Aug | 2020 Jun | 2020 Jul | 2020 Aug | 2013 May | 2021 Apr | 2021 Jun |
| Risk factors† | Leisure | Nurse | Hunting | Ag | Ag | Ag | Leisure | Leisure | Ag | Leisure |
| Comorbidities | HTN, OSA | None | None | Hepatic steatosis, active drinker | Tongue cancer | TB, |
HTN | None | Diabetes mellitus, dyslipemia | Diabetes mellitus |
| Bakir scale at admission | 7 | 0 | 7 | 6 | 6 | 4 | 8 | 5 | 2 | 5 |
| Outcome | Died | Good | Died | Good | Good | Good | Died | Good | Good | Good |
Table 1. Main epidemiologic data of patients with Crimean-Congo hemorrhagic fever, Spain, 2013–2021*
*Source is indicated if other than this study. Ag, agriculture; HTN, hypertension; OSA, obstructive sleep apnea. †Risk factors include high-risk occupations; agriculture includes shepherding activities.
| Characteristic | Patient no. and source | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1 (10) | 2 (10) | 3 (12) | 4 (13) | 5 | 6 | 7 | 8 (11) | 9 | 10 | |
| Main clinical data | ||||||||||
| Tick bite | Y | N | Y | N | Y | Y | Y | Y | Y | Y |
| First symptom | Fever | Fever | Fever | Fever | Fever | Fever | Fever | Fever | Fever | Fever |
| Fever duration, d | 4 | 5 | 6 | 6 | 9 | 5 | 4 | 4 | 4 | 5 |
| Days from first symptom to admission | 3 | 2 | 4 | 5 | 9 | 7 | 3 | 2 | 4 | 12 |
| Digestive symptoms | Y | Y | Y | N | Y | N | Y | Y | Y | Y |
| Any bleeding | Y | Y | Y | N | Y | N | Y | Y | N | Y |
| Laboratory data† | ||||||||||
| Hemoglobin, g/dL | 13.4 | 13.9 | 13.5 | 14.1 | 14.6 | 15.5 | 13.4 | 14.4 | 17 | 17 |
| Leukocytes, × 103 cells/mm3 | 13.9 | 6.2 | 10.7 | 3.1 | 2.4 | 2.3 | 5.5 | 1.5 | 2.8 | 11.1 |
| Neutrophils, % | 85.5 | 83 | 90 | 62 | 33 | 66.4 | 69 | 63 | 68.5 | 90 |
| Lymphocytes, % | 7.9 | 10.2 | 5 | 27 | 38 | 26.1 | 25 | 31 | 24.4 | 4 |
| Platelets, × 103/mm3 | 30 | 174 | 229 | 41 | 44 | 32 | 7 | 44 | 76 | 159 |
| Glucose, mg/d | 80 | 102 | 83 | 135 | 110 | 134 | 280 | 106 | 116 | 491 |
| Creatinine, mg/dL | 1.69 | 1.24 | 0.83 | 1.33 | 0.92 | 0.75 | 4.8 | 0.67 | 0.85 | 1.1 |
| CRP, mg/L | 87.6 | 2.9 | ND | 15.2 | 0.3 | 0.65 | 3.72 | 0.6 | 0.55 | 52 |
| AST, U/L | 203 | 24 | 20 | 347 | 273 | 273 | 1,305 | 494 | 107 | 72 |
| ALT, U/L | 88 | 37 | 9 | 161 | 281 | 135 | 347 | 171 | 141 | 70 |
| Ferritin, ng/mL | ND | ND | >40,000‡ | 15,718 | 34,044 | 28,393 | 60,000 | ND | 7,878 | 1,147 |
| Bilirubin, mg/dL | 0.9 | 0.5 | 0.5 | 0.7 | 0.43 | 0.35 | 1.4 | 0.29 | 0.58 | ND |
| GGT, U/L | ND | ND | ND | 425 | 272 | 132 | 1,420 | 77 | 136 | ND |
| ALP, U/L | ND | ND | ND | 103 | 84 | 59 | 239 | 58 | 72 | 91 |
| LDH, U/L | ND | ND | 172 | 721 | 358 | 589 | 2,311 | 1,085 | 341 | 272 |
| Triglycerides, mg/dL | ND | ND | ND | ND | ND | 407‡ | ND | ND | 164‡ | ND |
| Prothrombin time, s | 18.1 | 15.6 | 10.7 | 10.2 | 10 | 12 | 13 | 12 | 11 | ND |
| Prothrombin activity, % | 52.8 | 62 | 104 | 106 | 123 | 99 | 86 | 81 | 102 | 84 |
| Partial thromboplastin time, s | 18.1 | 48.7 | 26.2 | 43.8 | 30.2 | 52.7 | 61.4 | 128 | ND | 29 |
| Functional fibrinogen, mg/dL | ND | 265.9 | 320 | 605 | 281 | 304 | 156 | 141 | 272 | 325 |
| D-dimer, ng/mL | ND | 35,200 | ND | ND | ND | 1.3 | 5.5 | 3.48 | ND | ND |
| Genotype | III | III | IV | V | III | III | III | ND | V | ND |
| Treatment | DOX; support | DOX; Ribavirin ev/orally for 9 d | DOX; support | DOX | DOX; ribavirin orally for 10 d§ | DOX; ribavirin orally for 10 d§ | DOX support | DOX; support | DOX | DOX; support |
| Length of stay, d | 9 | 23 | 8 | 6 | 22 | 9 | 2 | 17 | 9 | 8 |
Table 2. Main clinical and laboratory data of patients with Crimean-Congo hemorrhagic fever, Spain, 2013–2021*
*Source is indicated if other than this study. ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C-reactive protein; DOX, doxycycline; GGT, gamma-glutamyl transferase; LDH, lactate dehydrogenase; ND, no data. †Analysis upon admission or during the first 24 hours. ‡Analysis performed during hospital admission. §In accordance with World Health Organization guidelines.
Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™
ABIM Diplomates - maximum of 1.00 ABIM MOC points
This activity is intended for infectious disease specialists and other clinicians who take care of patients who may develop Crimean-Congo hemorrhagic fever.
The goal of this activity is for learners to be better able to evaluate the clinical presentation and common genotypes of Crimean-Congo hemorrhagic fever.
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CME / ABIM MOC Released: 1/23/2023
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Crimean-Congo hemorrhagic fever (CCHF) is a viral infectious disease for which distribution of the main vector, Hyalomma spp. ticks, is expanding. We analyzed all 10 cases of CCHF diagnosed in Spain during 2013–2021; case-patient median age was 56.5 years, and 7 were men. We identified CCHF virus genotypes III and V. Six case-patients acquired the infection in urban areas. Sixty percent of patients were infected in summer and 40% in spring. Two patients met criteria for hemophagocytic syndrome. Seven patients survived. The epidemiologic pattern of CCHF in Spain is based on occasional cases with an elevated mortality rate. Genotype III and, to a less extent also genotype V, CCHF circulates in humans in a common geographic area in Spain. Those data suggest that the expansion pathways are complex and may change over time. Physicians should remain alert to the possibility of new CCHF cases.
Crimean-Congo hemorrhagic fever (CCHF) is a tickborne viral disease caused by the CCHF virus (CCHFV), a negative single-stranded RNA virus of the genus Orthonairovirus in the Nairoviridae family[1]. CCHF is considered an emerging infectious disease because of the expanding distribution of its main vector, ticks of the genus Hyalomma. Consequently, CCHF is listed by the World Health Organization as one of the top-priority diseases for research and development in public health emergency contexts (https://www.who.int/activities/prioritizingdiseases-for-research-and-development-in-emergency-contexts)[2].
The spectrum of clinical manifestations of CCHF ranges from subclinical illness (including fever, headache, malaise, myalgia, sore throat, dizziness, abdominal pain, nausea, vomiting, conjunctivitis, and photophobia)[3] to acute infection with hemorrhage, multiorgan failure, and death[4]. Laboratory findings are frequently remarkable, including leukopenia, thrombocytopenia, and elevated liver transaminases in serum[5]. Some studies have suggested the relevance of the innate immune system in limiting the spread of the virus, but the specific mechanisms leading to asymptomatic versus severe disease remain unknown.
In recent years, the epidemiology of CCHFV has changed; climate change has been identified as one of the factors driving the circulation of the virus. CCHFV has been identified in Africa, Asia, and Europe, in territories located south of the 50th North parallel, the area inhabited by its main vector[6–8]. CCHFV has caused major outbreaks in eastern Europe[9]. In turn, CCHF is considered endemic in areas of southwestern Europe.
Our group identified the first human cases in western Spain in summer 2013[10–13]. In Spain, the CCHFV genotype identified from patients in 2016 and 2018 belonged to the African genotype III, the European genotype V, and the Asian genotype IV where the group Africa 4 is placed[10,12,13]. A strong clinical suspicion is required to obtain fast and accurate diagnosis, initiate supportive treatment if needed, and activate biosafety measures to prevent nosocomial transmission[10]. Herein, we report on the clinical and epidemiologic pattern and the genotype of the virus identified in all patients with CCHF investigated in Spain from 2013 through May 2022.
The Clinical Research Ethics Committee of Investigation with Drugs of the Hospital Universitario de Salamanca (Salamanca, Spain) approved the study protocol (CEIMC PI 91 09/2017). All procedures described were carried out in accordance with the ethical standards described in the Revised Declaration of Helsinki of 2013. All clinical and epidemiologic data were anonymized.
