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A febrile man in Italy who had traveled to Cuba in July 2024 was diagnosed with Oropouche fever. Reverse transcription PCR detected prolonged shedding of Oropouche virus RNA in whole blood, serum, urine, and semen. Sixteen days after symptom onset, replication-competent virus was detected in semen, suggesting risk for sexual transmission.

During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances. Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation disturbances. The results were validated in a cohort of dengue virus infected patients in Brazil. In this cohort levels of ferritin and cytokine profiles were determined. Increased levels of ferritin in dengue virus infected patients in Brazil were associated with disease severity and a pro-inflammatory cytokine profile. Altogether, we provide evidence that ferritin can be used as a clinical marker to discriminate between dengue and other febrile illnesses. The occurrence of hyperferritinaemia in dengue virus infected patients is indicative for highly active disease resulting in immune activation and coagulation disturbances. Therefore, we recommend that patients with hyperferritinaemia are monitored carefully.

On 27 May 2024, the Cuban Ministry of Health reported the first outbreak of Oropouche fever on the island. The etiologic agent, Oropouche virus (OROV), is a poorly understood arbovirus that has been known since the 1960s and represents a public health burden in Latin America. We report the whole-genome characterization of the first European OROV isolate from a returning traveler from Cuba with Oropouche fever-like symptoms. The isolate was obtained from the patient’s serum; whole-genome sequencing was performed by next-generation sequencing, followed by phylogenetic analysis and genetic variability studies. The analysis showed that the most closely related sequence was from the French Guiana 2020 outbreak. Interestingly, our isolate is a reassortant virus, included in a highly supported monophyletic clade containing recent OROV cases (Brazil 2015–Colombia 2021), separated from the other four previously known genotypes. More deeply, it was found to be included in a distinct branch containing the sequences of the Brazil 2022–2024 outbreak. The reassortment event involved the S and L segments, which have high similarity with sequences belonging to a new cluster (here defined as OROV_SCDC_2024), while the M segment shows high similarity with older sequences. These results likely describe the viral strain responsible for the current outbreak in Cuba, which may also reflect the ongoing outbreak in Latin America. Further studies are needed to understand how OROV evolves towards traits that facilitate its spread and adaptation outside its original basin, and to track its spread and evolution in the European continent.

Determining the incubation period of Oropouche virus disease can inform clinical and public health practice. We analyzed data from 97 travel-associated cases identified by the Centers for Disease Control and Prevention (n = 74) or the GeoSentinel Network (n = 13) and 10 cases from published literature. Using log-normal interval-censored survival analysis, we estimated the median incubation period to be 3.2 (95% CI 2.5-3.9) days. Symptoms developed by 1.1 (95% CI 0.6-1.5) days for 5% of patients, 9.7 (95% CI 6.9-12.5) days for 95% of patients, and 15.4 (95% CI 9.6-21.3) days for 99% of patients. The estimated incubation period range of 1-10 days can be used to assess timing and potential source of exposure in patients with Oropouche symptoms. For patients with symptom onset >2 weeks after return from travel, clinicians and public health responders should consider the possibility of local vectorborne transmission or alternative modes of transmission.

In a longitudinal study in a first-level hospital in Luanda, Angola, we found rifampin-resistant and multidrug-resistant tuberculosis (TB) in 38 (8%, 95% CI 5.7-10.8) of 474 patients with no previous history of TB. Of note, 2 patients (0.4%, 95% CI 0.1-1.5) demonstrated pre-extensively drug-resistant TB.

We used cross-sectional data from 226 patients with monkeypox virus to investigate the association between anatomic exposure site and lesion development. Penile, anorectal, and oral exposures predicted lesion presence at correlating anatomic sites. Exposure site also predicted the first lesion site of the penis and anus.

Background Physical symptoms of dengue have been documented extensively, but knowledge gaps on dengue-associated mental health hazards remain. We investigated the frequency of psychiatric symptoms (depression, anxiety, and stress) and neurocognitive performance during the first year after a dengue episode. Methods Using DASS-21 scores at 3, 6, and 12 months, we assessed depression, anxiety, and stress in anti-dengue IgM-positive adults and matched controls during the 2021 dengue season in Esmeraldas Province, Ecuador. Patients with DASS-21 scores ≤ 4 were considered normal; those with scores of 5–7, 8–10, and ≥ 11 indicated mild, moderate, and severe depression, respectively; cutoff scores for anxiety and stress were ≥ 5 and ≥ 9, respectively. We also assessed ‘delayed matching to sample’ (DMS) and ‘spatial working memory’ (SWM) using the Cambridge Neuropsychological Test Automated Battery. Results We enrolled 102 cases and 78 controls. At 3 months, 90 cases and 70 controls were available for follow-up, among these 40/90 (44.4%) cases and 12/70 (17.1%) controls had DASS-21 scores ≥ 5 (RR 2.7, 95% CI [1.5–4.7]). Dengue remained a predictor for depression after adjusting for age, sex, and COVID-19 status. We observed no difference in anxiety between the groups, but stress scores increased at month 3 (RR 1.87, 95% CI [1.01–3.4]). DASS-21 scores normalized during follow-up. DMS and SWM did not differ between groups at 3 and 6 months. At month 12, cases had lower SWM than controls did ( p value < 0.001). Conclusions Care providers should be aware of dengue-associated mood disorders and facilitate timely referral to mental health services. Future longitudinal studies are warranted to validate our observations regarding the impact of dengue on mental health and neurocognitive status in affected patients.

Abstract Yellow fever (YF) causes high fever, liver dysfunction, renal failure, hypercoagulopathy and platelet dysfunction and can lead to shock and death with a case-fatality ratio of 20–50%. YF vaccination results in long-lasting protective immunity. Serious adverse events (SAEs), such as YF vaccine-associated neurotropic disease (YEL-AND) are rare. We present a case of a 56-year-old Caucasian man with fever, headache, cognitive problems at the emergency department. He received a primary YF vaccination 4 weeks prior to symptom onset. Cerebrospinal fluid tested positive (POS) for YF virus by reverse transcriptase polymerase chain reaction and confirmed diagnosis of YEL-AND. The patient recovered with symptomatic treatment. We reviewed published clinical reports on YEL-AND indexed for MEDLINE. We identified and analyzed 53 case reports. Forty-five patients were male and eight were female. Twenty-nine cases met criteria for definite YEL-AND and twenty-four for suspected YEL-AND according to YF Vaccine Safety Working Group. We applied the Brighton Collaboration diagnostic criteria to assess the diagnostic accuracy of the clinical diagnoses and found meningoencephalitis in 38 reported YEL-AND cases, Guillain Barré Syndrome (GBS) in seven, Acute Disseminated Encephalomyelitis (ADEM) in six and myelitis in five. Thirty-five patients recovered or improved; however, not all cases had a complete follow-up. The prognosis of YEL-AND presenting with GBS, ADEM or myelitis was poor. Fourteen patients received therapy (corticosteroids, intravenous immunoglobulins and/or plasmapheresis). In conclusion, YF vaccine-associated neurotropic disease is a very rare but SAE after YF vaccination. We described a case of YEL-AND and propose a standardized clinical workup of this condition based on a review of the literature. Centralized registration of complications of YF vaccination is encouraged.

In response to the aggressive global spread of the mosquito-borne chikungunya virus (CHIKV), an accurate and accessible diagnostic tool is of high importance. CHIKV, an arthritogenic alphavirus, comprises three genotypes: East/Central/South African (ECSA), West African (WA), and Asian. A previous rapid immunochromatographic (IC) test detecting CHIKV E1 protein showed promising performance for detection of the ECSA genotype. Unfortunately, this kit exhibited lower capacity for detection of the Asian genotype, currently in circulation in the Americas, reflecting the low avidity of one of the monoclonal antibodies (mAbs) in this IC kit for the E1 protein of the Asian-genotype because of a variant amino acid sequence. To address this shortcoming, we set out to generate a new panel of broad-spectrum mouse anti-CHIKV mAbs using hybridoma technology. We report here the successful generation of mouse anti-CHIKV mAbs targeting CHIKV E1 and capsid proteins. These mAbs possessed broad reactivity to all three CHIKV genotypes, while most of the mAbs lacked cross-reactivity towards Sindbis, dengue, and Zika viruses. Two of the mAbs also lacked cross-reactivity towards other alphaviruses, including O'nyong-nyong, Ross River, Mayaro, Western Equine Encephalitis, Eastern Equine Encephalitis, and Venezuelan Equine Encephalitis viruses. In addition, another two mAbs cross-reacted weakly only with most closely related O'nyong-nyong virus. Effective diagnosis is one of the keys to disease control but to date, no antibody-based rapid IC platform for CHIKV is commercially available. Thus, the application of the mAbs characterized here in the rapid diagnostic IC kit for CHIKV detection is expected to be of great value for clinical diagnosis and surveillance purposes.

Background Three different genotypes of chikungunya virus (CHIKV) have been classified: East/Central/South African (ECSA), West African (WA), and Asian. Previously, a rapid immunochromatographic (IC) test detecting CHIKV E1-antigen showed high sensitivity for certain ECSA-genotype viruses, but this test showed poor performance against the Asian-genotype virus that is spreading in the American continents. We found that the reactivity of one monoclonal antibody (MAb) used in the IC rapid diagnostic test (RDT) is affected by a single amino acid substitution in E1. Therefore, we developed new MAbs that exhibited specific recognition of all three genotypes of CHIKV. Methods Using a combination of the newly generated MAbs, we developed a novel version of the IC RDT with improved sensitivity to Asian-genotype CHIKV. To evaluate the sensitivity, specificity, and cross-reactivity of the new version of the IC RDT, we first used CHIKV isolates and E1-pseudotyped lentiviral vectors. We then used clinical specimens obtained in Aruba in 2015 and in Bangladesh in 2017 for further evaluation of RDT sensitivity and specificity. Another alphavirus, sindbis virus (SINV), was used to test RDT cross-reactivity. Results The new version of the RDT detected Asian-genotype CHIKV at titers as low as 10^4 plaque-forming units per mL, a concentration that was below the limit of detection of the old version. The new RDT had sensitivity to the ECSA genotype that was comparable with that of the old version, yielding 92% (92 out of 100) sensitivity (95% confidence interval 85.0–95.9) and 100% (100 out of 100) specificity against a panel of 100 CHIKV-positive and 100 CHIKV-negative patient sera obtained in the 2017 outbreak in Bangladesh. Conclusions Our newly developed CHIKV antigen-detecting RDT demonstrated high levels of sensitivity and lacked cross-reactivity against SINV. These results suggested that our new version of the CHIKV E1-antigen RDT is promising for use in areas in which the Asian and ECSA genotypes of CHIKV circulate. Further validation with large numbers of CHIKV-positive and -negative clinical samples is warranted. (323 words).