Hyperendemicity is not simply a bigger version of endemicity. It describes the sustained co-circulation of multiple dengue virus serotypes within the same population, sustained by interacting ecological and social forces including urban density, human mobility, and repeated serotype importation. This matters clinically because infection with one serotype confers durable protection only against that serotype, while cross-protection against heterologous serotypes is temporary. Secondary heterologous infection carries a greater risk of severe dengue, a phenomenon partly explained by antibody-dependent enhancement, although viral factors, host biology, timing of presentation, and quality of care also shape outcomes. For frontline services, the consequence is not just more infections but repeated waves of febrile demand. In one Nepalese outbreak cohort, 538 dengue-suspected patients required assessment and 74.5 percent were confirmed, illustrating that frontline workload extends well beyond laboratory-confirmed cases. In a Sri Lankan tertiary care cohort of 1,064 hospitalized patients with confirmed dengue, only a minority developed severe disease, prompting calls for better algorithms to distinguish patients suitable for ambulatory management from those needing admission.

The central clinical dilemma is that early dengue presents as a non-specific febrile illness overlapping with malaria, chikungunya, leptospirosis, influenza-like illness, and other locally prevalent infections. Individual symptoms have limited ability to distinguish dengue from other febrile illnesses during the first few days. The review emphasizes that recording the day of illness is central, because the diagnostic value of symptoms and laboratory findings changes across the early febrile period, and test selection, interpretation of defervescence, and anticipation of the critical phase all depend on timing. Investigations serve three distinct purposes: confirming dengue, excluding important alternatives, and detecting evolving plasma leakage, bleeding, and organ dysfunction. Molecular tests are most informative early—a 2025 meta-analysis found pooled sensitivity of reverse-transcription polymerase chain reaction at 0 to 4 days after symptom onset of 95 percent with pooled specificity of 89 percent, though access remains limited outside better-equipped laboratories. Non-structural protein 1 testing also performs best early, with pooled sensitivity of 90 percent and specificity of 93 percent for NS1 enzyme-linked immunosorbent assay in the same meta-analysis, but rapid NS1 assays vary by product, illness timing, serotype, and viral load, so a negative result should not exclude dengue when clinical suspicion remains high.

Simple laboratory markers add decision-relevant value. The International Research Consortium on Dengue Risk Assessment, Management and Surveillance multicenter cohort showed that platelet count, white cell count, and their serial change improved discrimination between dengue and other febrile illnesses, outperforming clinical-only models. A retrospective Thai study found significant differences in complete blood count patterns between dengue and other acute febrile illnesses, including leukopenia, thrombocytopenia, and hemoconcentration, varying according to the day of fever. The neutrophil-to-lymphocyte ratio also changes during dengue illness and may provide complementary information, but should not be interpreted independently of the patient’s clinical trajectory. Crucially, the review draws a sharp distinction between diagnostic confirmation and severity prediction: laboratory testing can support diagnosis, but safe disposition depends on repeated assessment of illness day, hemodynamic status, perfusion, urine output, fluid balance, functional decline, and evolving clinical or laboratory trends. Platelet count alone is not a severity proxy and must be interpreted alongside hematocrit, bleeding, hemodynamics, urine output, and disease phase.

Triage, the review argues, is a repeated process rather than a single decision. The WHO 2009 classification remains clinically useful because it provides a practical shared framework of dengue without warning signs, dengue with warning signs, and severe dengue, but individual warning signs have variable predictive performance across settings and should not be used as static binary rules. Findings associated with deterioration include persistent vomiting, abdominal pain or tenderness, mucosal bleeding, clinical fluid accumulation, lethargy or restlessness, hepatomegaly, and rising hematocrit with falling platelet count. Impaired perfusion, reduced urine output, respiratory distress, altered consciousness, major bleeding, and organ dysfunction indicate advanced disease rather than merely increased risk. The absence of warning signs at one encounter does not guarantee a benign course, particularly early in the illness, so repeated assessment around defervescence—when resolution of fever can be mistaken for recovery—is essential. Patients considered for outpatient care should be hemodynamically stable, able to maintain oral intake and urine output, free of warning signs, and able to return promptly. Disposition is both clinical and logistical, because distance, transport, caregiver support, communication access, cost, and referral reliability determine whether apparent stability is actually safe outside the hospital.

Outpatient management, the review insists, is an active care pathway rather than a simple discharge. Guideline-based reviews consistently frame early management around oral fluids, paracetamol, and avoidance of non-steroidal anti-inflammatory drugs, with escalation to observation or intravenous support only when oral intake is not sustained or risk increases. Follow-up should be timed to the illness day and the anticipated transition around defervescence rather than left to vague instructions to return only if symptoms worsen. Discharge education is part of treatment: patients and caregivers need clear instructions on expected symptoms, medicines to avoid, warning features, the date of reassessment, and how to obtain urgent care if deterioration occurs. Evidence for specific support tools remains limited but suggests low-cost structured follow-up can be feasible. A Malaysian pilot trial found a fluid chart acceptable in primary care and associated with numerically fewer admissions and less intravenous fluid use, although differences were not statistically significant, while a Brazilian outbreak study reported no adverse events among low-to-moderate risk patients triaged by nurses and reviewed through telemedicine. A recent Singaporean program saved a mean of 3.3 bed-days per patient, though this evidence comes from a well-resourced tertiary system and should not be generalized uncritically to weaker referral settings.

In the critical phase, which usually begins around defervescence and is defined by transient vascular leakage, hemoconcentration, and risk of shock, bedside management depends on recognizing compensated shock before hypotension becomes obvious. Intravenous fluid therapy remains the cornerstone of severe dengue management, but the evidence supports a feedback-controlled rather than a fixed approach. Reviews and guidelines favor isotonic crystalloids as first-line therapy, with reassessment against perfusion, urine output, hemoconcentration, respiratory findings, and clinical trajectory to match fluid administration to the leak while avoiding overload. Landmark pediatric trials showed that colloids can normalize hematocrit and cardiovascular status faster in some children with shock, but a larger randomized study found Ringer’s lactate appropriate for moderately severe dengue shock syndrome and noted more adverse reactions with dextran. More recent observational data reinforce this caution: among 691 children across seven Southeast Asian hospitals, mixed or liberal colloid strategies were associated with more respiratory compromise and ventilation, and in a Vietnamese pediatric intensive care cohort of 1,278 dengue shock syndrome cases, larger early fluid loads and higher colloid-to-crystalloid ratios were associated with mechanical ventilation and acute kidney injury. A major danger in the late critical and recovery phases is fluid overload, especially when intravenous fluids continue after leakage resolves or in patients with renal, cardiac, hepatic, pregnancy-related, or age-related vulnerability.

Standard management thresholds must also be adapted for vulnerable patients. Infants and young children have limited physiological reserves, and shock can evolve quickly once capillary leak accelerates; reliance on caregivers to detect reduced intake, urine output, or behavioral changes justifies earlier observation and more frequent reassessment. Pregnancy alters the presentation of dengue: gestational hemodilution, widened pulse pressure, leukocytosis, and gestational thrombocytopenia can obscure the usual diagnostic and triage cues, while pre-eclampsia, eclampsia, and HELLP syndrome may mimic or delay recognition of dengue-related deterioration. Pregnancy is associated with higher odds of severe dengue and adverse maternal and fetal outcomes, including maternal mortality, postpartum hemorrhage, preterm birth, fetal distress, and stillbirth. Older adults and patients with comorbidities present a different problem: symptoms may be atypical or muted, baseline values may already be abnormal, and reduced cardiac or renal reserve narrows the tolerance of rapid plasma leakage and intravenous fluid therapy. A Brazilian population-based analysis of 5.8 million confirmed dengue cases from 2024 found that chronic kidney disease was independently associated with increased odds of death. Operational vulnerability is equally consequential: a patient who appears stable at one consultation may still be unsafe for home management if return at defervescence is unlikely because of long travel distance, flooding, conflict, seasonal isolation, absent caregiver support, or unreliable telephone contact.

Preparedness, the review concludes, should be judged by the reliable performance of essential functions rather than by the nominal availability of guidelines, training, diagnostics, or equipment. The strongest direct facility-level evidence comes from Nepal, where 63.4 percent of 131 primary care facilities had suboptimal dengue preparedness, with better readiness associated with facility type, regular facility meetings, and review and trend analysis practices. Functional referral systems require explicit referral criteria, pre-referral stabilization, direct communication with the receiving facility, documentation of status and fluids already given, transport planning, and confirmation that the destination can accept the patient. Surveillance should trigger clinical preparedness actions rather than operate separately from care delivery, and ecological evidence from Brazil suggests that stronger outpatient performance, early monitoring, and learning from hospitalization patterns are associated with fewer dengue deaths and less severe system stress. Practical metrics include documentation of illness day and vital signs, planned reassessment, discharge instructions, observation records such as fluid balance, pre-referral communication, and maintenance of essential stocks—whereas counting printed guidelines, distributed devices, or completed workshops mainly measures inputs rather than readiness.

The evidence base remains clinically useful but inconsistent. Much of the literature on severity prediction, fluid decisions, and complications comes from tertiary hospitals, single-center cohorts, and admitted populations in Asia or Latin America, and cohorts based on hospitalized or laboratory-confirmed dengue likely over-represent more severe illness relative to the far larger group of suspected patients seen in first-contact care. In African, rural, and humanitarian settings—where seven of the 18 African Union member states reporting dengue outbreaks in 2023 were experiencing armed conflict—adaptation should prioritize functions that remain feasible when laboratory, observation, transport, or referral capacity is limited. The authors propose a dynamic dengue-readiness framework integrating severity-informed triage, scheduled reassessment, phase-adjusted supportive management, and predefined escalation and referral, supported by competent staff, structured documentation, observation capacity, essential diagnostics and supplies, patient communication, referral coordination, and surveillance-linked surge preparedness. The most immediate opportunity, they argue, is not more complex guidance but more reliable delivery of a limited number of essential functions during both routine transmission and outbreak surges—moving from knowledge of appropriate dengue care to dependable delivery of care across the entire frontline clinical pathway.

Subject of Research: Dengue clinical triage, case management, and primary care preparedness in resource-constrained settings

Article Title: Dengue in an era of hyperendemicity: clinical triage, case management, and primary care preparedness in resource-constrained settings: a narrative review

Article References: Hassan, A. A., Mohamed, M. D., Sudi, L. A., Ibrahim, I. O., Abdi, M. S., & Abdullahi, Y. B. (2026). Dengue in an era of hyperendemicity: clinical triage, case management, and primary care preparedness in resource-constrained settings: a narrative review. Frontiers in Tropical Diseases, 7, Article 1948853. https://doi.org/10.3389/fitd.2026.1948853

Image Credits: AI Generated

DOI: 10.3389/fitd.2026.1948853

Keywords: dengue, hyperendemicity, dynamic triage, primary care, case management, resource-constrained settings, fluid therapy, Frontiers in Tropical Diseases, clinical, triage, case, management