A total of 10,576 suspected dengue cases were reported with onset of symptoms in 2007; 10,171 to the PDSS only, 68 to the ICNDSS only, and 337 to both systems. There were 40 suspected dengue deaths reported to these surveillance systems and 4 additional deaths were identified only by the Demographic Registry of Puerto Rico. These latter fatal cases had no diagnostic testing performed and are not considered further in this report.
Of the 40 suspected dengue deaths, one case-patient had both tissue and paired serum specimens submitted, eight had tissue and acute serum, two had tissue and convalescent serum, four had tissue alone, one had paired serum specimens, five had only a convalescent serum specimen, and 19 had only an acute serum specimen. Eleven of the 40 suspected deaths were laboratory-positive dengue cases (); a 0.6% case-fatality rate among the 1,776 hospitalized laboratory-positive dengue cases reported to PDSS. There were no co-infections identified. Of the remaining 29 deaths, 14 were laboratory-negative cases; nine had leptospirosis (three confirmed cases and six presumptive cases) and one had group A Streptococcus detected by tissue IHC. Fifteen deaths were laboratory-indeterminate cases although three met WHO clinical criteria for DHF with gastrointestinal hemorrhage and four met criteria for DF with thrombocytopenia and a hemorrhagic manifestation, but had no evidence of plasma leakage documented in the medical records.
Table 1 Laboratory Results for the Fatal Laboratory Positive Dengue Cases, 2007, Puerto Rico.
Description of laboratory-positive deaths
Of the 11 laboratory-positive case-patients who died, eight were DENV RT-PCR positive in tissue, serum or both, and three were anti-DENV IgM positive in a single serum specimen (). Of the five DENV RT-PCR positive in serum, three were DENV-3, one was DENV-2, and one was DENV-1. Among the six case-patients with an acute serum specimen, four had secondary infections and two had primary infections. In the four laboratory-positive case-patients with tissue specimens, DENV was identified by IHC or RT-PCR in lung, liver and kidney specimens, and the most common histopathologic findings were intraalveolar edema and hemorrhage; congestion in the spleen, liver, and/or kidney; and fatty metamorphosis of the liver.
The median age of laboratory-positive case-patients was 26 years (range: 5 months to 78 years). Five were aged <15 years, four were 20–45 years, and two were >70 years. Seven were male. Five of six adults had at least one co-morbidity: two had asthma; one had an autoimmune hypothyroid disease; one had Type 2 diabetes mellitus (DM II) and hypertension; and one had DM II, chronic anemia, congestive heart failure, chronic obstructive pulmonary disease, and hypertension. In addition, four adults were overweight (i.e., body mass index [BMI] of 25.0–29.9), and one adult and one child were obese (i.e., BMI ≥30.0 or a BMI for age >95%).
Opportunities for early diagnosis and intervention
Seven of the 11 case-patients sought medical care at least once prior to first hospital admission or presenting dead on arrival (DOA) to an emergency department (ED); three were seen by a clinician more than once but only 1 was diagnosed with a “dengue-like-syndrome”. Instead, the most common diagnoses given at these outpatient visits were upper respiratory infection with pharyngitis and/or cough, followed by acute gastroenteritis and viral syndrome. None of the seven case-patients had specimens submitted for dengue diagnostic testing until hospitalization (median 5 days post fever onset; range: 3–9 days) even though they saw clinicians early in the clinical course (median 2 days post fever onset; range 1–5 days). In addition, three case-patients had one or more warning signs for severe dengue at the time of fever defervescence, including persistent vomiting, severe abdominal pain, and narrow pulse pressure, and were sent home. A fourth case-patient, diagnosed with an upper respiratory tract infection as an outpatient, had a seizure at home the day after first being seen as an outpatient and died on the way to the hospital.
Upon final presentation to an ED, the 11 laboratory-positive case-patients had been sick a median of 4 days (range: 1–7 days). Two case-patients presented DOA and four were afebrile, three of which, had signs of shock. A seventh case-patient became afebrile while in ED and developed tachycardia, delayed capillary refill, and a narrow pulse pressure. Six case-patients had warning signs for severe dengue upon arrival to the ED including persistent vomiting (5/9) and abdominal pain (4/9). However, five of the nine case-patients were given a low (least severe) or intermediate severity triage score.
Nine case-patients were admitted to a hospital after a mean ED stay of 15 hours (median 12 hours, range: 3–48 hours) (). Initial complete blood count done in ED found that six case-patients had platelet counts <100,000/mm3 (median 78,000; range 8,000–410,000), five were leukopenic, two were hemoconcentrated (hematocrit 20% above mean for age/sex) and two had a hematocrit <2.5% for age and sex. Six of the nine case-patients met criteria for DF and three met criteria for DHF/DSS. Five case-patients had “dengue” listed in the admission differential diagnosis.
Clinical Features of the Fatal Laboratory-positive Dengue Cases At Time of First Hospitalization, 2007, Puerto Rico.
During their hospital stay, several case-patients developed warning signs for severe dengue including persistent vomiting (1/9), abdominal pain (1/9), restlessness (4/9), and mental status changes (4/9). In six cases, warning signs were not recognized as such as there were no new orders or change in the clinical management.
In the end, six of the 11 laboratory-confirmed fatal cases met criteria for DHF or DSS as determined throughout their clinical course and at autopsy (). Ten of the 11 case-patients had at least 1 hemorrhagic manifestation and nine case-patients had evidence of plasma leakage. Nine of 11 had thrombocytopenia documented.
Clinical Features of the Fatal Laboratory-positive Dengue Cases at Time of Death or End of Hospital Stay, 2007, Puerto Rico.
Monitoring and level of care
Of the nine laboratory-positive case-patients admitted to a hospital, only three had capillary refill time assessed in the ED or at admission. Vital signs were measured at a median of every 3 hours in the ED but most case-patients had less frequent measurements after admission (). Two case-patients were admitted from the ED to the ICU and had vital signs measured every 1 or 2 hours.
Eight of nine hospitalized case-patients died during hospitalization, and the other case-patient was found dead at home within 18 hours of hospital discharge (). Three of the eight case-patients who died in the hospital had no recorded blood pressure measurements during the 8 hours before their terminal event. Five case-patients had their terminal event on the inpatient ward and another case-patient was transferred to ICU and had a terminal event within minutes of the transfer. Of those who died in hospital, six of eight case-patients died during a weekend (between 1701 on Friday and 0759 Monday), and five had a terminal event between 2300 and 0759.
Interventions and supportive care
All nine hospitalized case-patients received intravenous fluids, most commonly 0.9% normal saline (). Four received 0.45% normal saline while in shock. Four received intravenous albumin (5% or 25% solution) during their hospitalization but only one received colloids prior to the terminal event. Three of the nine hospitalized case-patients had signs of fluid overload prior to death including periorbital edema, dyspnea, and abdominal distention documented in their medical record.
There was frequent use of corticosteroids in laboratory-positive case-patients (). Five of the nine hospitalized case-patients received intravenous methylprednisolone as inpatients and one received dexamethasone in the ED before hospital admission. One case-patient who was DOA received oral prednisone during an outpatient visit.
Hematocrit levels were assessed every 17 hours on average (range 10–42 hours) for the six hospitalized case-patients with clinically significant hemorrhage ( and ). Three of these six case-patients were given packed red blood cells; two in response to frank blood per nasogastric tube or rectum and one during the final code. One of these case-patients also received fresh frozen plasma in response to clinically significant bleeding. No case-patients were given whole blood. Two of the case-patients who received packed red blood cells also received platelets; one in response to clinically significant bleeding and one during the final code. Four additional case-patients had platelets ordered but they did not receive them prior to death.
Complications and reported causes of death
Many of the nine hospitalized case-patients developed complications including metabolic acidosis (6/9), prolonged shock (6/9), acute respiratory failure (6/9), fluid overload (3/9), and seizures (3/9) (). Only 1 of the 11 case-patients had evidence of a secondary bacterial infection even though most patients had blood and urine cultures taken. Dengue, DHF, DSS, or status-post dengue syndrome was listed as the cause of death or a contributing factor in only five case-patients. The remaining six death certificates listed causes or contributing factors including hypovolemic shock, hypotension, metabolic acidosis, septicemia unspecified, bronchopneumonia unspecified, viral infection unspecified, brain death, and ischemic cerebral infarct.