El concepto de formación

epistaxis) [16]. An intense erythematous rash occasionally occurs as temperature spikes. Petechiae appear in some patients as fever declines at the conclusion of illness. DF is a rarely fatal, self-limiting disease that afflicts mostly younger children. In contrast, DHF occurs mostly in older children or adults, but has been seen in younger children in countries where multiple viruses are endemic. It is characterized by a sudden onset of fever and an acute phase that lasts 2-6 days. The acute phase of DHF is not remarkable and is often difficult to distinguish from DF or other tropical illnesses. Signs of DHF include those of DF in addition to cerebral oedema, pleural effusion, haemoconcentration, haematuria and thrombocytopenia (platelet count ≤100,000/mm3_{) [17]. These symptoms are}

often followed by a sudden deterioration of haemodynamics in the patient. A tourniquet test may suggest increased capillary fragility to attending physicians. During defervescence, plasma leakage can rapidly lead to a haemorrhagic syndrome if not treated promptly. Extensive plasma leakage throughout the body may result in shock and subsequent death.

The 272 patients in the study were considered probable infections when they demonstrated HI titres of ≥1280 on the acute sample or a four-fold titre increase while hospitalized as defined by established WHO criteria [12]. Additionally, primary infections were determined only when acute titres were <10 and convalescent titres were ≤80, and secondary infection was determined when acute or convalescent titres were ≥1280. Serotypes were confirmed by RTPCR or viral isolation. Laboratory-confirmed cases were also classified according to the WHO guidelines. Those cases with haemorrhagic tendencies that could not meet other criteria for DHF (platelet count <100 000/mm3 or plasma leakage) were classified as DF with haemorrhagic tendencies grade I. Patients yielding evidence of a positive tourniquet test, thrombocytopenia and evidence of plasma leakage were grouped as DHF grade I, whilst those cases with spontaneous bleeding manifestations (petechiae, ecchymoses, purpura, mucosal bleeding, haematemesis or melena) were classified as DHF grade II.

THEORY

Since emerging in Southeast Asia in the 1950s, subsequent epidemics of dengue have infected more people and occurred with greater frequency. With one of the highest populations in the region, the disease burden has been particularly harsh in Indonesia where the first well characterized outbreak occurred in 1973 with 10,189 cases, followed 15 years later by an epidemic that resulted in 47,573 cases. The most severe epidemic to strike the country appeared in 1998 when over 72,133 individuals were infected and 1414 deaths were reported (R. Kusriastuti, unpublished data). The intensity of dengue transmission has been of utmost public health concern on the island of Java since the early 1980s [4]. In 1982, 71% of all Indonesian cases occurred in Java, rising to 84% in 1983 and 91% in 1984 [8]. Whilst the influence of increased prevalence on severe disease can only be determined by the conduct of focused cohort-based studies, it is probable that the spread of dengue viruses across the archipelago and the increase in total population also contribute to increased DHF rates across Indonesia.

RESULTS

Between January and February 2004, the Indonesian Ministry of Health reported cases of DF in 30 of 32 providences within the archipelago. In the capital city of Jakarta, a total of 20,503 cases were recorded, with an epidemic peak between March and April (Figure 2). To characterize the outbreak better, hospitalized patients were followed in ten hospitals located throughout the municipality. Patient observations coincided with the epidemic curve seen in Jakarta (Figure 2). Acute and secondary sera were collected from a total of 272 febrile patients surveyed both within paediatric (age 1-14 years) and internal medicine (age >14 years) Wards in the five municipalities of Jakarta: West, 103; Central, 24; North, 47; East, 56; and South, 42 (Table 1). The male to female ratio in the cohort was 1.08 and the age ranged from 1 to 72 years, with a mean of 23.4 years. The majority of cases were over 15 years of age, with 37.9% between 15 and 25 years and 37.5% >25 years old. Just fewer than 5% (13 cases; 4.8%) were 3 years of age or younger and 19.9% were between the ages of 4 and 14 years.

Four dengue virus serotypes found circulating during an outbreak of dengue fever and dengue haemorrhagic fever in Jakarta, Indonesia, during 2004

57

3

Figure 2. Number of reported dengue cases in jakarta (white bars) or cases surveyed (black bars)

over an epidemic week. Each bar represents a week. Data span the time September 2003 to june 2004.

Table 1. Age and sex of patients per hospital site

Hospital _patientsNo. of 0-3 years 4-14 years 15-25 years >25 years Male Female Male Female Male Female Male Female West Jakarta 103 RSSW 87 2 5 9 13 6 22 18 12 Cengkareng 16 0 0 0 0 6 4 2 4 North Jakarta 47 RSPI 23 2 0 3 4 5 5 3 1 Kodja 24 1 0 7 3 2 6 4 1 Central Jakarta 24 St. Carolus 13 0 0 1 1 3 3 4 1 Tarakan 11 0 0 0 1 0 5 4 1 East Jakarta 56 Persahabatan 36 0 0 1 0 10 6 9 10 Budi Asih 20 2 1 2 3 2 1 9 0 South Jakarta 42 Fatmawati 37 0 0 1 5 11 5 8 7 Tebet 5 0 0 0 0 0 1 4 0 Total (%) 272 13 (4.8%) 54 (19.9%) 103 (37.9%) 102 (37.5%)

Dengue infections were confirmed in 180 (66.2%) of the 272 patients. Of these, 137 (76.1%) were termed probable infection upon a four-fold rise in HI titres of DEN antibodies, 35 (19.4%) by HI titres ≥1280 and 8 (4.4%) by positive anti- dengue IgM (data not shown). When clinically assessed, 100 (55.6%) patients were classified as having DF, 31 (17.2%) as DF with haemorrhagic manifestations (DF + HM) and 49 (27.2%) with DHF. The remaining 92 febrile cases showed no evidence of dengue infection, although those tested who were negative by IgM ELISA (60 cases) when tested prior to day five were deemed inconclusive. Signs, symptoms and common laboratory findings in the reported dengue cases included fever (99.4%), headache (92.2%), thrombocytopenia (78.9%) and nausea (67.2%) (Table 2). Symptoms found more frequently in the group of dengue cases included spontaneous bleeding, haemoconcentration, thrombocytopenia (<100,000/mm3_{) and leukopenia. Several findings, such as headache, myalgia}

and positive tourniquet tests, were more common in adults, whereas vomiting, thrombocytopenia and spontaneous bleeding were more common in patients 1-14 years of age.

Table 2. Clinical categorization and age among patients

symptoms 1-14 years 15-25 years >25 years Confirmed

dengue Non-dengue Fever 43/43 (100%) 72/72 (100%) 64/65 (98.5%) 179/180 (99.4%) 32/32 (100%) Headache 38/43 (88.4%) 66/72 (91.7%) 62/65 (95.4%) 166/180 (92.2%) 23/32 (71.9%) Retro-orbital pain 9/43 (20.9%) 21/72 (29.2%) 20/65 (30.8%) 50/180 (27.8%) 6/32 (18.8%) Myalgia 11/43 (25.6%) 32/72 (44.4%) 34/65 (52.3%) 77/180 (42.8%) 12/32 (37.5%) Sore throat 8/43 (18.6%) 9/72 (12.5%) 4/65 (6.2%) 21/180 (11.7%) 4/32 (12.5%) Nausea 27/43 (62.8%) 53/72 (73.6%) 41/65 (63.1%) 121/180 (67.2%) 20/32 (62.5%) Vomiting 22/43 (51.2%) 38/72 (52.8%) 23/65 (35.4%) 83/180 (46.1%) 15/32 (46.9%) Abdominal pain 13/42 (31%) 29/72 (40.3%) 22/65 (33.8%) 64/179 (35.8%) 8/32 (25%)

Positive tourniquet test 6/16 (37.5%) 13/25 (52%) 16/26 (61.5%) 35/67 (52.2%) 9/19 (47.4%)

Spontaneous haemorrhage a _{17/43(39.5%) 19/72 (26.4%) 12/65 (18.5%) 48/180 (26.7%) 1/32 (3.1%)}

Haemoconcentration a _{12/43 (27.9%) 28/72 (38.9%) 18/65 (27.7%) 58/180 (32.2%) 1/30 (3.3%)}

Leukopenia a _{19/41 (46.3%) 40/64 (62.5%) 27/65 (41.5%) 86/170 (50.6%) 4/25 (16%)}

Thrompocytopenia a _{36/43 (83.7%) 61/72 (84.7%) 45/65 (69.2%) 142/180 (78.9%) 17/32 (53.1%)}

Four dengue virus serotypes found circulating during an outbreak of dengue fever and dengue haemorrhagic fever in Jakarta, Indonesia, during 2004

59

3