The Early Clinical Features of Dengue in Adults: Challenges for Early Clinical Diagnosis

Dengue infection in adults has become increasingly common throughout the world. As most of the clinical features of dengue have been described in children, we undertook a prospective study to determine the early symptoms and signs of dengue in adults. We show here that, overall, dengue cases presented with high rates of symptoms listed in the WHO 1997 or 2009 classification schemes for probable dengue fever thus resulting in high sensitivities of these schemes when applied for early diagnosis. However, symptoms such as myalgia, arthralgia, retro-orbital pain and mucosal bleeding were less frequently reported in older adults. This trend resulted in reduced sensitivity of the WHO classification schemes in older adults even though they showed increased risks of hospitalization and severe dengue. Instead, we suggest that older adults who present with fever and leukopenia should be tested for dengue, even in the absence of other symptoms. This could be useful for early clinical diagnosis in older adults so that they can be monitored and treated for severe dengue, which is especially important when an antiviral drug becomes available

Age-specific features of using fever and leukopenia for probable dengue diagnosis.

<p>Leukopenia is defined as WBC<4,500 cells/µxL.</p><p>AUC indicates area under the curve.</p><p>PPV and NPV denote positive and negative predictive values, respectively.</p><p>Values in parentheses are the 95% confidence intervals.</p

Age-group specific WBC in patients with dengue, OFI and influenza in the first 72 hours of illness.

<p>Box and whiskers (maximum and minimum) indicate the mean and spread of WBC in the different groups of patients. Dotted line indicates threshold for leukopenia (WBC<4,500 cells/µL). ***indicates p<0.0001 as determined using the Mann Whitney U test.</p

Laboratory parameters in dengue patients who received hospitalized or ambulatory care only.

<p>Shown are median values with the 25^th and 75^th percentiles in parentheses.</p><p>Chi-square test with Yates' continuity correction was used except where indicated.</p><p>*Mann Whitney U test.</p><p>∧Cp indicates crossover point on the real-time RT-PCR, which is a semi-quantitative indicator of viremia levels. Lower Cp values indicate higher viremia levels and vice versa.</p>#<p>IgG seropositivity indicates secondary dengue infection.</p><p>WBC indicates white blood cell count.</p

Demographics of the hospitalized dengue cases with severe or non-severe dengue.

<p>Chi-square test with Yates' continuity correction was used except where indicated.</p><p>*Mann-Whitney U test.</p>#<p>One patient was admitted for a total of 37 days due to lack of a caregiver at home. Data from this patient was treated as an outlier and removed from analysis.</p

Age-specific features of probable dengue diagnosis using the WHO 1997 or 2009 classification schemes.

<p>PPV and NPV denote positive and negative predictive values, respectively.</p><p>Values in parentheses are the 95% confidence intervals.</p

The WHO 1997 and 2009 classification schemes and the parameters used in this study.

<p>The WHO 1997 and 2009 classification schemes and the parameters used in this study.</p

The early clinical features and outcomes of dengue, OFI and influenza.

<p>∧Shown are median values with the 25^th and 75^th percentiles in parentheses.</p><p>Chi-square test with Yates' continuity correction was used except where indicated. *Mann Whitney U test.</p><p>*Mann Whitney U test.</p

Demographics of the dengue, OFI and influenza patients enrolled into the study.

<p>All P values shown are analysed in comparison to dengue. Chi-square test with Yates' continuity correction was used to determine statistical significance for all parameters except mean age.</p><p>*Mann Whitney U test was used to determine P value.</p><p>∧Some patients in these categories have more than one pre-existing co-morbidities.</p