Chymase Level Is a Predictive Biomarker of Dengue Hemorrhagic Fever in Pediatric and Adult Patients.

Background: Most patients with dengue experience mild disease, dengue fever (DF), while few develop the life-threatening diseases dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). No laboratory tests predict DHF or DSS. We evaluated whether the serum chymase level can predict DHF or DSS in adult and pediatric patients and the influence of preexisting conditions (PECs) on chymase levels. Methods: Serum chymase levels were measured in patients presenting with undifferentiated fever to hospitals in Colombo District, Sri Lanka. The value of serum the chymase concentration and clinical signs and symptoms as predictors of DHF and/or DSS was evaluated by multivariate analysis. We assessed the influence of age, PECs, and day after fever onset on the robustness of the chymase level as a biomarker for DHF and/or DSS. Results: An elevated chymase level in acute phase blood samples was highly indicative of later diagnosis of DHF or DSS for pediatric and adult patients with dengue. No recorded PECs prevented an increase in the chymase level during DHF. However, certain PECs (obesity and cardiac or lung-associated diseases) resulted in a concomitant increase in chymase levels among adult patients with DHF. Conclusions: These results show that patients with acute dengue who present with high levels of serum chymase consistently are at greater risk of DHF. The chymase level is a robust prognostic biomarker of severe dengue for adult and pediatric patients.

Proceedings of the dengue endgame summit: Imagining a world with dengue control.

The first dengue "endgame" summit was held in Syracuse, NY over August 9 and 10, 2023. Organized and hosted by the Institute for Global Health and Translational Sciences at SUNY Upstate Medical University, the gathering brought together researchers, clinicians, drug and vaccine developers, government officials, and other key stakeholders in the dengue field for a highly collaborative and discussion-oriented event. The objective of the gathering was to discuss the current state of dengue around the world, what dengue "control" might look like, and what a potential roadmap might look like to achieve functional dengue control. Over the course of 7 sessions, speakers with a diverse array of expertise highlighted both current and historic challenges associated with dengue control, the state of dengue countermeasure development and deployment, as well as fundamental virologic, immunologic, and medical barriers to achieving dengue control. While sustained eradication of dengue was considered challenging, attendees were optimistic that significant reduction in the burden of dengue can be achieved by integration of vector control with effective application of therapeutics and vaccines.

A prospective clinical study on the use of reverse transcription-polymerase chain reaction for the early diagnosis of Dengue fever.

Laboratory testing for dengue virus is used to confirm the diagnosis of dengue virus infection and to differentiate dengue from other febrile tropical illnesses. There are few data on the clinical use of reverse transcription-polymerase chain reaction (RT-PCR) for diagnosis of dengue virus infection. We prospectively evaluated 121 consecutive patients with possible dengue who had samples submitted for RT-PCR, IgM serology, and virus culture. Results were compared with the final discharge diagnosis. Semi-nested RT-PCR was performed using genus- and serotype-specific NS3 consensus primers. Results of 112 patients were available for the final analysis. The RT-PCR was positive in 40 of 62 patients with dengue. Patients who were RT-PCR-positive alone showed a mean of 4.4 days to RT-PCR positivity compared with 5.9 days in patients who were RT-PCR-negative and IgM serology-positive (P = 0.03, Mann-Whitney U-test). The sensitivity, specificity, negative predictive value, and positive predictive value were 70, 100, 84, and 100%, respectively, for samples analyzed within 5 days of illness onset. The RT-PCR also provided epidemiological data regarding the prevailing dengue virus serotypes: 25 with Den-2, eight with Den-3, and seven with Den-1 infection. We propose an algorithm of dengue testing that uses RT-PCR within 5 days of illness onset, whereas IgM capture enzyme-linked immunosorbent assay is preferred for those presenting later.

Severe acute respiratory syndrome without respiratory symptoms or abnormal chest radiograph findings.

We report a serologically confirmed case of severe acute respiratory syndrome (SARS) in a 27-year-old health care worker. The patient reported no respiratory complaints, and the findings of serial chest radiographs were normal. This case illustrates the wide spectrum of clinical illness caused by infection with SARS coronavirus.

Emergence potential of sylvatic dengue virus type 4 in the urban transmission cycle is restrained by vaccination and homotypic immunity.

Sylvatic dengue viruses (DENV) are both evolutionarily and ecologically distinct from human DENV and are maintained in an enzootic transmission cycle. Evidence of sylvatic human infections from West Africa and Southeast Asia suggests that sylvatic DENV come into regular contact with humans. Thus, this potential of emergence into the human transmission cycle could limit the potential for eradicating this cycle with vaccines currently in late stages of development. We assessed the likelihood of sylvatic DENV-4 emergence in the face of natural immunity to current human strains and vaccination with two DENV-4 vaccine candidates. Our data indicate homotypic neutralization of sylvatic and human DENV-4 strains by human primary convalescent and vaccinee sera but limited heterotypic immunity. These results suggest that emergence of sylvatic strains into the human cycle would be limited by homotypic immunity mediated by virus neutralizing antibodies produced by natural infection or vaccination.