Prevalence, clinical management, and outcomes of adults hospitalised with endemic arbovirus illness in southeast Europe (MERMAIDS-ARBO): a prospective observational study.
Sigfrid L., Chan XHS., Kasbergen LMR., Hookham L., Wei J., Chen S., Lee JL., Sikkema RS., de Bruin E., Corman VM., Reusken C., Loens K., Popescu CP., Lupse M., Briciu V., Pipero P., Harxhi A., Puca E., Ponosheci Biçaku A., Travar M., Ostojic M., Baljic R., Arapović J., Ledina D., Cekinović Grbeša Đ., Čabraja I., Văsieşiu AM., Kurolt I-C., Halichidis S., Birlutiu V., Sulaver Z., Dumitru IM., Moroti R., Barac A., Stevanovic G., Pyrpasopoulou A., Papanikolaou MN., Koulouras V., Betica Radić L., Roilides E., Markotić A., Galal U., Denis E., Goodwin L., Turtle L., Marincu I., Florescu SA., Ramadani H., Charrel RN., Goossens H., Ieven M., Drosten C., Horby PW., Koopmans MPG., PREPARE MERMAIDS ARBO investigator group None.
BACKGROUND: Arboviruses have expanded into new regions in Europe, yet data indicate gaps in disease notifications and a risk of further spread. We aimed to report on prevalence, clinical management, and outcomes of endemic arbovirus infections in southeast Europe. METHODS: In this prospective observational study (MERMAIDS-ARBO), we enrolled adults (age ≥18 years) hospitalised with an arbovirus-compatible disease syndrome within 21 days of symptom onset across 21 hospitals in seven countries in southeast Europe over four arbovirus seasons (May 1-Oct 31, during 2016-19). We obtained data from case report forms completed by site investigators on admission and discharge. Participants were excluded if they had non-infectious CNS disorders, symptoms of another confirmed cause, an identified focal source of infection, or symptoms caused by recurrence of a pre-existing condition. The primary outcome was the proportion of participants with confirmed or probable acute infections with West Nile virus (WNV), tick-borne encephalitis virus (TBEV), Crimean-Congo haemorrhagic fever virus (CCHFV), or Toscana virus (TOSV), per reference laboratory criteria. Secondary outcomes were the proportions of patients treated with antivirals, antibiotics, or corticosteroids; the proportion of patients requiring intensive care; hospital length of stay; and mortality. FINDINGS: Of 2896 adults screened for eligibility, 929 were recruited and 913 met protocol-defined eligibility criteria (median age 43·1 years [IQR 29·5-59·7]; 550 [60%] men, 361 [40%] women, and two [<1%] with missing data). 530 (58%) participants presented with suspected meningitis, encephalitis, or both, and 318 (35%) with fever plus myalgia, fever plus arthralgia, or both. 820 (90%) reported no international travel within 21 days before symptom onset. 727 (80%) were administered antibiotics, 379 (42%) corticosteroids, and 222 (24%) antivirals. The median length of hospital stay was 9 days (IQR 6-14), and 113 (12%) required intensive care. Of 847 participants with a reference laboratory sample who met full eligibility criteria for analysis, 110 (13%) were diagnosed with 114 confirmed or probable acute arbovirus infections (four had coinfections or cross-reactivity): one (<1%) with CCHFV, 16 (2%) with TBEV, 44 (5%) with TOSV, and 53 (6%) with WNV. There was one death (<1%) of an individual with WNV. Of the 110 participants, 49 (45%) had a local clinician-attributed arbovirus discharge diagnosis. INTERPRETATION: Our data highlight the need to strengthen arbovirus surveillance systems for the early detection of emerging and re-emerging outbreaks, including investments to increase awareness of arbovirus infections among clinicians, to improve access to specialist diagnostics, and to develop effective and accessible vaccines and treatments to protect populations and health systems in southeast Europe. FUNDING: European Commission and Versatile Emerging infectious disease Observatory. TRANSLATIONS: For the Greek, Albanian, Romanian, Bosnian, Serbian, and Croatian translation of the summary see Supplementary Materials section.