Rapid diagnostic tests and antimicrobial stewardship programs for the management of bloodstream infection: What is their relative contribution to improving clinical outcomes? A systematic review and network meta-analysis.

BACKGROUND: Evidence about the clinical impact of rapid diagnostic tests (RDT) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (BC) embedded within antimicrobial stewardship programs (ASP) is unknown. METHODS: We performed network meta-analyses (NMA) using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS) and time to optimal therapy (TOT). RESULTS: Eighty-eight papers were selected, including 25,682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The NMA showed a significant reduction in mortality associated with the use of RDT + ASP vs BC alone (OR 0.72, 95%CI 0.59, 0.87) and with the use of RDT + ASP vs BC + ASP (OR 0.78 95%CI 0.63, 0.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP vs BC alone (0.91, 95%CI 0.84, 0.98) while no difference in LOS was shown between any other groups. A reduced TOT was shown when RDT + ASP was compared to BC alone (-29 h, 95%CI -35, -23), BC + ASP (-18 h, 95%CI -27, -10) and to RDT alone (-12 h, 95%CI -20, -3). CONCLUSION: The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC.

Mortality, hospital length of stay, and recurrent bloodstream infections associated with extended-spectrum beta-lactamase-producing Escherichia coli in a low prevalence region: A 20-year population-based large cohort study.

OBJECTIVES: This population-based study aimed to investigate the risk factors and effect of extended-spectrum beta-lactamase (ESBL) production on clinical outcomes in Escherichia coli bloodstream infection (BSI) patients. METHODS: The study population was defined as patients aged ≥15 years with E. coli BSI in Queensland, Australia, from 2000 to 2019. Outcomes were defined as 30-day case fatality, hospital length of stay (LOS), and recurrent E. coli BSI. RESULTS: A total of 27,796 E. coli BSIs were identified, of which 1112 (4.0%) were ESBL-producers. Patients with ESBL-Ec BSI were more frequently older, male, with comorbidity, recurrent E. coli BSI, and less likely with community-associated community-onset infections as compared to non-ESBL-Ec BSI patients. The standardized mortality rate of ESBL-Ec BSI increased 8-fold from 2000 to 2019 (1 to 8 per million residents) and case fatality was 12.8% (n = 142) at 30 days from positive blood culture. Patients with ESBL-Ec BSI were not at higher risk of 30-day case fatality (adjusted hazard ratio [HR] = 0.98, 95% CI: 0.83-1.17), but had higher risk of recurring episodes (adjusted subdistribution HR = 1.58, 95% CI: 1.29-1.92) and observed 14% longer LOS (adjusted incidence rate ratio = 1.14, 95% CI: 1.10-1.18) than non-ESBL-Ec BSI patients. CONCLUSION: In this large patient cohort, ESBL-Ec BSI did not increase case fatality risk but observed higher hospital LOS and recurrent E. coli BSI than non-ESBL-Ec BSI. Clinical resources are warranted to account for the higher morbidity risk associated with ESBL production and incidence.

Melioidosis Queensland: An analysis of clinical outcomes and genomic factors.

BACKGROUND: The clinical and genomic epidemiology of melioidosis varies across regions. AIM: To describe the clinical and genetic diversity of B. pseudomallei across Queensland, Australia. METHODS: Whole genome sequencing of clinical isolates stored at the melioidosis reference lab from 1996-2020 was performed and analysed in conjunction with available clinical data. RESULTS: Isolates from 292 patients were analysed. Bacteraemia was present in 71% and pneumonia in 65%. The case-fatality rate was 25%. Novel sequence types (ST) accounted for 51% of all isolates. No association was identified between the variable virulence factors assessed and patient outcome. Over time, the proportion of First Nation's patients declined from 59% to 26%, and the proportion of patients aged >70 years rose from 13% to 38%. CONCLUSION: This study describes a genomically diverse and comparatively distinct collection of B. pseudomallei clinical isolates from across Queensland, Australia. An increasing incidence of melioidosis in elderly patients may be an important factor in the persistently high case-fatality in this region and warrants further investigation and directed intervention.

A decision support tool for risk-benefit analysis of Japanese encephalitis vaccine in travellers.

BACKGROUND: During pre-travel consultations, clinicians and travellers face the challenge of weighing the risks verus benefits of Japanese encephalitis (JE) vaccination due to the high cost of the vaccine, low incidence in travellers (~1 in 1 million), but potentially severe consequences (~30% case-fatality rate). Personalised JE risk assessment based on the travellers' demographics and travel itinerary is challenging using standard risk matrices. We developed an interactive digital tool to estimate risks of JE infection and severe health outcomes under different scenarios to facilitate shared decision-making between clinicians and travellers. METHODS: A Bayesian network (conditional probability) model risk-benefit analysis of JE vaccine in travellers was developed. The model considers travellers' characteristics (age, sex, co-morbidities), itinerary (destination, departure date, duration, setting of planned activities) and vaccination status to estimate the risks of JE infection, the development of symptomatic disease (meningitis, encephalitis), clinical outcomes (hospital admission, chronic neurological complications, death) and adverse events following immunization. RESULTS: In low-risk travellers (e.g. to urban areas for <1 month), the risk of developing JE and dying is low (<1 per million) irrespective of the destination; thus, the potential impact of JE vaccination in reducing the risk of clinical outcomes is limited. In high-risk travellers (e.g. to rural areas in high JE incidence destinations for >2 months), the risk of developing symptomatic disease and mortality is estimated at 9.5 and 1.4 per million, respectively. JE vaccination in this group would significantly reduce the risk of symptomatic disease and mortality (by ~80%) to 1.9 and 0.3 per million, respectively. CONCLUSION: The JE tool may assist decision-making by travellers and clinicians and could increase JE vaccine uptake. The tool will be updated as additional evidence becomes available. Future work needs to evaluate the usability of the tool. The interactive, scenario-based, personalised JE vaccine risk-benefit tool is freely available on www.VaxiCal.com.

Population-Based Incidence and Characteristics of Adult Escherichia coli Bloodstream Infection in Queensland, Australia, From 2000 to 2019.

Background: There is increasing morbidity and mortality attributed to escalating incidence of Escherichia coli bloodstream infection (BSI). The epidemiology of E. coli BSI is dynamic and differs across populations. This study aimed to describe this epidemiology in Queensland, Australia. Methods: Incident E. coli BSIs (new or recurring ≥30 days from previous BSI) in adult (≥15 years) Queenslanders were identified from 2000 to 2019 using Queensland Health databases. Incidence rates, crude and standardized by age and gender, were calculated. Negative binomial regressions were performed to determine predictors of E. coli BSI incidence. Results: From 2000 to 2019, 30 350 E. coli BSIs in 27 793 patients were detected; the standardized incidence rate almost doubled from 34.1 to 65.9 cases per 100 000 residents. Predictors of higher incidence rate were older age (≥65 years), comorbidity, and community-onset infection. Despite holding these factors constant, the incidence rate was estimated to increase 4% (adjusted incidence rate ratio [IRR], 1.04; 95% CI, 1.03-1.04) annually over the study period. Approximately 4.2% of E. coli isolates produced extended-spectrum beta-lactamase (ESBL-Ec), with most (95%) detected after 2010. The incidence rate of ESBL-Ec increased 25% (IRR, 1.25%; 95% CI, 1.2-1.3) annually, significantly faster than that of non-producers. Amikacin and carbapenems remain effective in vitro against ESBL-Ec BSI in Queensland. Conclusions: The rise in E. coli BSIs is driven both by a higher infection rate and shifting epidemiology toward community-onset infections. These are likely attributed to an aging Australian population with increasing chronic comorbidity. The rapid expansion of ESBL-Ec in recent years is concerning and should be acknowledged for its implication in the community.

Performance of BioFire Blood Culture Identification 2 Panel (BCID2) for the detection of bloodstream pathogens and their associated resistance markers: a systematic review and meta-analysis of diagnostic test accuracy studies.

BACKGROUND: Early identification of bloodstream pathogens and their associated antimicrobial resistance may shorten time to optimal therapy in patients with sepsis. The BioFire Blood Culture Identification 2 Panel (BCID2) is a novel multiplex PCR detecting 43 targets directly from positive blood cultures, reducing turnaround times. METHODS: We have performed a systematic review and meta-analysis of diagnostic test accuracy studies to assess the BCID2 performance for pathogen identification and resistance markers detection compared to gold standard culture-based methods (including phenotypic and/or genotypic characterization). RESULTS: Nine studies were identified reporting data to build 2 × 2 tables for each BCID2 target, including 2005 blood cultures. The pooled specificity of the assay was excellent (> 97%) across most subgroups of targets investigated, with a slightly broader confidence interval for S. epidermidis (98.1%, 95% CI 93.1 to 99.5). Pooled sensitivity was also high for the major determinants of bloodstream infection, including Enterobacterales (98.2%, 95% CI 96.3 to 99.1), S. aureus (96.0%, 95% CI 90.4 to 98.4), Streptococcus spp. (96.7%, 95% CI 92.8 to 98.5), P. aeruginosa (92.7%, 95% CI 83.1 to 97.0), E. faecalis (92.3%, 95% CI 83.5 to 96.6), as well as blaCTX-M (94.9, 95% CI 85.7 to 98.3), carbapenemases (94.9%, 95% CI 83.4 to 98.6) and mecA/C & MREJ (93.9%, 95% CI 83.0 to 98.0). Sensitivity for less common targets was slightly lower, possibly due to their under-representation in the included studies. CONCLUSIONS: BCID2 showed good performance for detecting major determinants of bloodstream infection and could support early antimicrobial treatment, especially for ESBL or carbapenemase-producing Gram-negative bacilli and methicillin-resistant S. aureus.

Incidence and predictors of Escherichia coli producing extended-spectrum beta-lactamase (ESBL-Ec) in Queensland, Australia from 2010 to 2019: a population-based spatial analysis.

The dissemination of Escherichia coli producing extended-spectrum beta-lactamase (ESBL-Ec) is evident in the community. A population-based spatial analysis is necessary to investigate community risk factors for ESBL-Ec occurrence. The study population was defined as individuals with ESBL-Ec isolated in Queensland, Australia, from 2010 to 2019. Choropleth maps, global Moran's index and Getis-Ord Gi* were used to describe ESBL-Ec distribution and identify hot spots. Multivariable Poisson regression models with or without spatially structured random effects were performed. A total of 12 786 individuals with ESBL-Ec isolate were identified. The crude incidence rate increased annually from 9.1 per 100 000 residents in 2010 to 49.8 per 100 000 residents in 2019. The geographical distribution of ESBL-Ec changed from random to clustered after 2014, suggesting presence of community-specific factors that can enhance occurrence. Hot spots were more frequently identified in Outback and Far North Queensland, future public health measures to reduce transmission should prioritise these communities. Communities with higher socioeconomic status (RR = 0.66, 95% CI 0.55-0.79, per 100 units increase) and higher proportion of residents employed in the agricultural industry (RR = 0.79, 95% CI 0.67-0.95, per 10% increase) had lower ESBL-Ec incidence. Risk factors for occurrence appear differential between remote and city settings and this should be further investigated.

Development of a diagnostic assay by three-tube multiplex real-time PCR for simultaneous detection of nine microorganisms causing acute respiratory infections.

Acute respiratory infections are widespread in vulnerable populations of all ages and are characterized by a variety of symptoms. The underlying infection can be caused by a multitude of microorganisms, including viruses and bacteria. Early detection of respiratory infections through rapid pathogen screening is vital in averting infectious respiratory disease epidemics. This study utilized a multiplex real-time PCR system to develop a three-tube reverse transcription-PCR (RT-PCR) assay, enabling simultaneously detect nine respiratory pathogens, including: influenza A and B, adenovirus, respiratory syncytial virus (RSV), Streptococcus pneumoniae, Legionella pneumophila, Haemophilus influenzae, Chlamydia pneumoniae, and Mycoplasma pneumoniae. This technique utilizes a one-step assay, with specifically designed TaqMan primer-probe sets combined in the same tube. This assay provided rapid and simplified detection of the nine prevalent pathogens, as well as increased sensitivity and reduced cross-contamination. This assay was evaluated using 25 related viral/bacterial strains as positive references, the other 25 irrelevant strains as negative controls, and clinical specimens from 179 patients. All positive strains were detected with no amplification of the non-target microorganism mixtures and the assay's detection limits ranged between 250-500 copies/ml (1.25-2.5 copies/reaction). A total of 167 (93.3%) samples tested positive for at least one of the pathogens identified; 109 of these samples were from patients confirmed to have RSV infections. The diagnostic accuracy of our assay was further confirmed by matching results from classical direct immunofluorescence assay and nucleotide sequencing. These data demonstrate the innovative multiplex real-time PCR assay as a promising alternative to the current approaches used for early screening of acute respiratory infections.

Achromobacter Species: An Emerging Cause of Community-Onset Bloodstream Infections.

BACKGROUND: Case reports and small series indicate that Achromobacter species bloodstream infection (BSI) is most commonly a complication of hospitalization among patients with chronic lung disease. The aim of the present study was to determine the incidence, risk factors, and outcomes of Achromobacter sp. BSI in an Australian population. METHODS: Retrospective, laboratory-based surveillance was conducted in Queensland, Australia (population ≈ 5 million) during 2000-2019. Clinical and outcome data were obtained by linkage to state hospital admissions and vital statistics databases. BSI diagnosed within the community or within the first two calendar days of stay in hospital were classified as community-onset. Community-onset BSIs were grouped into community-associated and healthcare-associated. RESULTS: During more than 86 million person-years of surveillance, 210 incidents of Achromobacter sp. BSI occurred among 195 individuals for an overall age-and sex-standardized annual incidence of 2.6 per million residents. Older individuals and males were at highest risk (2.9 vs. 2.0 per million, IRR for males 1.5; 95% CI, 1.1-1.9; p = 0.008). Most (153; 73%) cases were of community-onset of which 100 (48%) and 53 (25%) were healthcare- and community-associated, respectively. An increasing proportion of community-onset cases were observed during twenty years of surveillance. Underlying medical illnesses were common with median (interquartile range) Charlson Comorbidity Index (CCI) scores of 3 (1-5). CCI scores of 0, 1, 2, and 3+ were observed in 37 (18%), 27 (13%), 40 (19%), and 105 (50%) of cases, respectively. All but one of the cases were admitted to hospital for a median (interquartile range) length of stay of 12 (5-34) days. All-cause case-fatality rates in hospital by day 30 and by day 90 were 30 (14%), 28 (13%), and 42 (20%), respectively. The 90-day case-fatality rate increased with increasing comorbidity and was 3% (1/37), 11% (3/27), 25% (10/40), and 27% (28/105) among those with Charlson Comorbidity Indices of 0, 1, 2, and 3+, respectively (p = 0.004). CONCLUSIONS: Although comorbidity is an important determinant of risk, most Achromobacter sp. BSI are of community-onset and one-fifth of cases occur in patients without significant underlying chronic co-morbidities. This study highlights the value of population-based methodologies to define the epidemiology of an infectious disease.

Association of systemic vitamin D on the course of dengue virus infection in adults: a single-centre dengue cohort study at a large institution in Singapore.

INTRODUCTION: Host immune responses may impact dengue severity in adults. Vitamin D has multiple immunomodulatory effects on innate and adaptive immunity. METHODS: We evaluated the association between systemic 25-hydroxyvitamin D [25-(OH) D] and dengue disease severity in adults. We measured plasma for total 25-(OH) D levels with an electrochemiluminescence immunoassay using stored samples from participants with laboratory confirmed dengue who were prospectively enrolled in 2012-2016 at our institution. RESULTS: 80 participants (median age 43 years) were enrolled. Six participants had severe dengue based on the World Health Organisation (WHO) 1997 criteria (i.e. dengue haemorrhagic fever/dengue shock syndrome) and another six had severe dengue based on the WHO 2009 criteria. Median 25-(OH) D at acute phase of dengue was 6.175 µg/L (interquartile range 3.82-8.21; range 3.00-15.29) in all participants. 25-(OH) D showed inverse linear trend with severe dengue manifestations based on the WHO 2009 criteria (aRR 0.72; 95% confidence interval 0.57-0.91; p < 0.01) after adjustment for age, gender and ethnicity. CONCLUSION: Limited studies have evaluated the role of systemic 25-(OH) D on dengue severity. Our study found low systemic 25-(OH) D was associated with increased dengue disease severity, particularly for severe bleeding that was not explained by thrombocytopenia. Further studies investigating the underlying immune mechanisms and effects on the vascular endothelium are needed.

Carriage Duration and Household Transmission of Enterobacterales Producing Extended-Spectrum Beta-Lactamase in the Community: A Systematic Review and Meta-Analysis.

An attributing factor to Enterobacterales producing extended-spectrum beta-lactamase (ESBL-E) community spread is human-to-human transmission. This systematic review and meta-analysis aimed to estimate the duration of ESBL-E carriage in the community and the rate of household transmission. Literature search was performed on PubMed, EMBASE, and Scopus. Dose-response meta-analysis was planned to model the proportion of ESBL-E carriers and household transmission over time. Twenty-six studies (n = 2,505 participants) were included. The median carriage duration was 2 months. Approximately 22% (95% confidence interval: 16-28) had persistent carriage after 12 months. Travelers had significantly shorter carriage (median 1-2 months) than discharged hospital patients (median 6 months) at all measured time points. There were insufficient data to robustly meta-analyze household transmission. Nonetheless, five longitudinal studies reported 18.4% to 35.2% of contacts acquired ESBL-E within 4 to 36 months from hospital discharge of index case. Transmission events from travelers to their contacts appeared lower. Travelers with travel-acquired ESBL-E had significantly faster decolonization rate than discharged patients, suggesting that travel-associated import of multidrug-resistant pathogen may have limited contribution to community transmission of ESBL-E. The substantial prevalence of persistent carriers warrant consideration for additional measures to mitigate exposure risk of ESBL-E from discharged patients in the community and from readmitting patients in the hospital.

Adverse clinical outcomes associated with carbapenem-resistant Acinetobacter (CRA) infections: a systematic review and meta-analysis.

BACKGROUND: Carbapenem-resistant Acinetobacter (CRA) infections have been associated with increased morbidity and mortality in hospitalized patients. This systematic review and meta-analysis aimed to quantify the association between CRA infections and adverse clinical outcomes. METHODS: Three databases (i.e. PubMed, EMBASE and Scopus) were searched for epidemiological studies that compared mortality, severe sepsis or shock, or bacteraemia among adult inpatients with CRA infections and those with carbapenem-susceptible Acinetobacter (CSA) infections. The pooled ORs for the three outcomes were estimated using the inverse variance heterogeneity model. RESULTS: Thirty-four studies were included. Patients with CRA infections had higher odds of mortality (31 studies, OR = 2.10, 95% CI: 1.58-2.79, I 2=60.6%) and severe sepsis or septic shock (7 studies, OR = 1.51, 95% CI: 1.09-2.09, I 2=0%) compared with CSA-infected patients. There was no difference in the odds of bacteraemia (four studies, OR = 1.39, 95% CI: 0.79-2.46, I 2=38.1%). CRA-infected patients presented with worse comorbidity at admission (e.g. APACHE score) (eight studies, standardized mean difference = 0.25, 95% CI: -0.01 to 0.52) and had lower frequency of appropriate antibiotic therapy. Results were consistent when pooling 16 study-adjusted risk estimates for mortality. There was no difference in risk of mortality from CRA infection when compared across geographical regions, country income, median year of enrolment and day of mortality from infection onset. CONCLUSIONS: CRA-infected patients had worse clinical outcomes. This might be due to delay in appropriate antibiotic therapy, patients being sicker at admission and CRA strains potentially being more virulent than CSA strains. Improving appropriateness of antibiotic therapy in CRA-infected patients could reduce adverse clinical outcomes.

Genomic surveillance, characterization and intervention of a polymicrobial multidrug-resistant outbreak in critical care.

Background. Infections caused by carbapenem-resistant Acinetobacter baumannii (CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole-genome sequencing (WGS) response to a persistent CR-Ab outbreak in a Brisbane hospital between 2016-2018.Methods. A. baumannii, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa isolates were sequenced using the Illumina platform primarily to establish isolate relationships based on core-genome SNPs, MLST and antimicrobial resistance gene profiles. Representative isolates were selected for PacBio sequencing. Environmental metagenomic sequencing with Illumina was used to detect persistence of the outbreak strain in the hospital.Results. In response to a suspected polymicrobial outbreak between May to August of 2016, 28 CR-Ab (and 21 other MDR Gram-negative bacilli) were collected from Intensive Care Unit and Burns Unit patients and sent for WGS with a 7 day turn-around time in clinical reporting. All CR-Ab were sequence type (ST)1050 (Pasteur ST2) and within 10 SNPs apart, indicative of an ongoing outbreak, and distinct from historical CR-Ab isolates from the same hospital. Possible transmission routes between patients were identified on the basis of CR-Ab and K. pneumoniae SNP profiles. Continued WGS surveillance between 2016 to 2018 enabled suspected outbreak cases to be refuted, but a resurgence of the outbreak CR-Ab mid-2018 in the Burns Unit prompted additional screening. Environmental metagenomic sequencing identified the hospital plumbing as a potential source. Replacement of the plumbing and routine drain maintenance resulted in rapid resolution of the secondary outbreak and significant risk reduction with no discernable transmission in the Burns Unit since.Conclusion. We implemented a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting.

Adverse clinical outcomes associated with infections by Enterobacterales producing ESBL (ESBL-E): a systematic review and meta-analysis.

OBJECTIVES: Enterobacterales producing ESBL (ESBL-E) have been notable for their rapid expansion in community settings. This systematic review and meta-analysis aimed to summarize evidence investigating the association between ESBL-E infection and adverse clinical outcomes, defined as bacteraemia, sepsis or septic shock, and all-cause mortality in adult patients. METHODS: Database search was conducted in PubMed, Scopus and EMBASE. In general, studies were screened for effect estimates of ESBL-E colonization or infection on clinical outcomes with non-ESBL-producing Enterobacterales as comparator, adult populations and molecular ascertainment of ESBL gene. Meta-analysis was performed using the inverse variance heterogeneity model. RESULTS: Eighteen studies were identified, including 1399 ESBL-E and 3200 non-ESBL-E infected patients. Sixteen of these studies included only bacteraemic patients. Mortality was studied in 17 studies and ESBL-E infection was significantly associated with higher odds of mortality compared with non-ESBL-producing Enterobacterales infection (OR = 1.70, 95% CI: 1.15-2.49, I 2=58.3%). However, statistical significance did not persist when adjusted estimates were pooled (aOR = 1.67, 95% CI: 0.52-5.39, I 2=78.1%). Septic shock was studied in seven studies and all included only bacteraemic patients. No association between ESBL-E infection and shock was found (OR = 1.23, 95% CI: 0.75-2.02, I 2=14.8%). Only one study investigated the association between ESBL-E infection and bacteraemia. CONCLUSIONS: Infections by ESBL-E appear to be significantly associated with mortality but not septic shock. Available studies investigating bacteraemia and shock as an intermediate outcome of ESBL-E infections are lacking. Future studies investigating the relationship between clinical outcomes and molecular characteristics of resistant strains are further warranted, along with studies investigating this in non-bacteraemic patients.

Longitudinal Study of Cellular and Systemic Cytokine Signatures to Define the Dynamics of a Balanced Immune Environment During Disease Manifestation in Zika Virus-Infected Patients.

Background: Since its unexpected reemergence, Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection. Methods: Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Plasma immune mediators were profiled via multiplex microbead assay, while changes in blood cell numbers were determined with immunophenotyping. Results: Data showed the involvement of various immune mediators during acute ZIKV infection accompanied by a general reduction in blood cell numbers for all immune subsets except CD14+ monocytes. Importantly, viremic patients experiencing moderate symptoms had significantly higher quantities of interferon γ-induced protein 10, monocyte chemotactic protein 1, interleukin 1 receptor antagonist, interleukin 8, and placental growth factor 1, accompanied by reduced numbers of peripheral CD8+ T cells, CD4+ T cells, and double-negative T cells. Levels of T-cell associated mediators, including interferon γ-induced protein 10, interferon γ, and interleukin 10, were high in recovery phases of ZIKV infection, suggesting a functional role for T cells. The identification of different markers at specific disease phases emphasizes the dynamics of a balanced cytokine environment in disease progression. Conclusions: This is the first comprehensive study that highlights specific cellular changes and immune signatures during ZIKV disease progression, and it provides valuable insights into ZIKV immunopathogenesis.