Abstract. Introduction

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1 Dengue fever outbreak in Karachi A study of profile and outcome of children under 15 years of age Saba Ahmed 1, Fehmina Arif 2, Yousuf Yahya 3, Arshaloos Rehman 4, Kashif Abbas 5, Sohail Ashraf 6, Dure Samin Akram 7 Civil Hospital and Dow University of Health Sciences 1-3,7, Liaquat National Hospital 4-6, Karachi. Abstract Objective: To evaluate children with serologically confirmed Dengue fever in order to identify common clinical features, progress of disease, grades of severity and outcome of cases during the outbreak in Methods: A cross-sectional, descriptive study was conducted on serologically positive children with Dengue fever (DF) admitted in Civil Hospital Karachi and Liaquat National Hospital between October and November Various clinical features and laboratory parameters were analyzed for frequencies. Data was also evaluated to identify the common clinical types and grades of infection as classified by WHO. Results: A total of 35 children were evaluated in the study. Mean age of children was 8.3 ± 3.5 years and majority was male (54%). Sixty five percent were under 10 ± 3.5 years of age. Frequent clinical features included fever (97%), vomiting (68%), abdominal pain (68%) and rashes (65%). Gastrointestinal bleeding (61%) and epistaxis (26%) were commonest haemorrhagic manifestations. Thrombocytopenia (86%), anaemia (57%) and Leucopenia (43%) were common laboratory findings. Leukocyte count improved in 2 to 7 days and Platelet count in 2 to 8 days. Dengue haemorrhagic fever (DHF) was seen in 22 children (62%). Majority had Grade-II severity. Mortality was 1 (3%) out of 35 patients. Conclusion: 2006 outbreak of Dengue infection in Karachi showed slight difference in clinical features and course of disease compared to epidemics in other regions, thereby, indicating the need for continuous seroepidemeological surveillance (JPMA 58:4;2008). Introduction Dengue is an important mosquito borne viral infection. It occurred sporadically till the 19th century. Recent years have seen epidemics of this arthropod borne viral disease and presently it is endemic in 112 countries around the world. 1,2 Dengue virus is an RNA virus of flaviridae family, with four serotypes, transmitted by the bite of Aedes aegypti mosquito. It manifests in three ways, a mild atypical form, classic Dengue and Dengue haemorrhagic fever 3 which may evolve into Dengue shock syndrome. Mortality can occur in Dengue shock syndrome unless prompt and adequate management with fluid replacement is provided. 4 J Pak Med Assoc

2 Dengue fever (DF) is endemic in Southeast Asia. First major epidemic was reported from Srilanka in Tropical season, periurbinization with ill planned and crowded areas and improper waste water management are supposedly responsible for DF in this region. In 1980 DHF was found in China, Indonesia, Malaysia, and Thailand. 4 Recent epidemics have also occurred in India (1990) 5 and Bangladesh (2005). 6 In Pakistan Dengue has been around for the past 20 years. The first documented report was in whereby Dengue type 2 virus was isolated in a sero-epidemeological study for encephalitis. The first major outbreak was reported in Another Epidemic has been witnessed in Karachi following heavy rainfalls in During the previous two epidemics in Karachi, Dengue fever was more commonly seen in the 20 to 40 years age group 9, however, some unpublished data did show children as major victims. Recent trends have shown that DF in Southeast Asia causes cyclical epidemics every 2 to 3 years. A change in prevalence of serotypes has also been noticed during these recent outbreaks, as DEN-3 has become more prevalent than DEN-2 serotype. 9 This study was undertaken to evaluate clinical features of serologically confirmed Dengue fever cases in children and to identify common clinical features, progress of disease and grades of disease encountered in patients getting admitted to Civil Hospital and Liaquat National Hospital, Karachi. Methodology Data for the study was simultaneously collected from Paediatric unit of Civil Hospital and Liaquat National Hospital Karachi during the months of October and November, 2006, when epidemic of Dengue fever was at it's peak in the city. All cases of serologically proven Dengue infection, diagnosed on basis of enzyme linked immunoabsorbent assay (Elisa) and Immuno-chromatography (ICT- Dengue), who came to these units as inpatient or outpatient, were included in the study. Children who were found to have any other infectious disease along with serologically positive Dengue were excluded. Data was collected on a pre-tested pro-forma for each child. This included demographic data, signs, symptoms and laboratory investigations for complete blood count, platelet count, coagulation profile and liver function tests (Criteria for positive tests are given in Table 1a). Residential locality of each child was also recorded for mapping the area from where patients had reported. Each child was then thoroughly examined for hepato-splenomegaly, ascites, pleural effusion, and rashes (petaechiae, echymosis, bruises, maculopapular). Blood Pressure (B.P.) was recorded and Tourniquet test was performed to check capillary fragility. (Test was considered positive if more than 20 petaechiae in an area of one inch below the B.P cuff. Children under study were categorized into DF, DHF or DSS according to WHO clinical case definitions (table B) and grading of severity of their illness was done on the basis of WHO criteria for severity of Dengue infection (table C). All children with Leucopenia or Thrombocytopenia were followed till their blood counts were within normal range. Statistical analysis Data was evaluated by using SPSS version10. Descriptive statistics like frequencies and percentages of various variables were calculated where required. Results A total of 39 children with serologically proven Dengue infection were initially enrolled in the study, however, four of them were excluded due to the presence of concurrent malaria. Therefore, a total of 35 patients, 19 males and 16 females, were included in the study. Almost equal number of cases came in months of October (n=17) and November (n=18). Mean age of patients was 8.3 ± 3.55 years (range 2-15 years). 22 (65%) out of 35 patients were less than 10 years of age. Maximum number of cases (n=5) were from Orangi town area, followed by Bihar colony (n=4), Gulshan Iqbal (n=3) and Lyari town (n=2). Rest were reported sporadically from all over the city of Karachi. Spontaneous haemorrhage was seen in 22 (61%) children. Gastrointestinal bleeding was the most common bleeding manifestation seen in 22 (61%) patients followed by epistaxis in 9 (26%). In four out of the 22 patients with bleeding manifestations, prothrombin time and platelet counts were found to be normal. Rashes were seen in 23 patients out of whom 6 (25%) had maculopapular rash, 3 (8.5%) had confluent macular rashes mainly on legs and 14 (40%) had petechiae (Table 2). Laboratory investigations Table 1a. Criteria for positive tests for D.F. Anaemia < 10 gm / dl Leucopenia < 4000/mm3 Thrombocytopenia < 1, Neutrophilia > 60 % Neutropenia Absolute Neutrophyl count (ANC) < 500 I Increased Hematocrit Till 6 years >45% (>20% of normal) 7-14 years >45.6% (>20% of normal) Hypotension < 5 years-systolic pressure < 80mmHg >5 years -Systolic pressure <90 mmhg Vol. 58, No. 1, January

3 Table 1b. WHO criteria for grading of severity in Dengue infection. Grades I II III IV Criteria Fever with non-specific symptoms with only positive tourniquet test or easy bruising. Spontaneous bleeding. Circulatory failure. Profound shock. Table 2. Clinical profile of children with Dengue fever. S.No. Signs / Symptoms Frequency (%) Fever Abdominal pain Vomiting Rash GIT Bleeding Biphasic fever Retro orbital pain/ Headache Arthralgia Hepatomegaly Myalgia Flushing Epistaxis Tourniquet test Coryza Gingival bleeding Splenomegaly Seizure/altered state Jaundice Hypotension Ascites/pleural effusion Table 3. Distribution of Laboratory Data. 34 (97) 24 (68) 24 (68) 23 (65) 22 (61) 14 (40) 14 (40) 13 (37) 13 (37) 12 (34) 10 (29) 9 (26) 2 (1) 3 (9) 3 (7) 2 (6) 0 S.No. Serum Values Number of patients (%) Anaemia (Hb<10) Leucopenia (TLC<4000) Thrombocytopenia (<1,50000) Increased Hematocrit Neutrophilia (>60%) Deranged PT Prolonged SGPT (> 35) IgG-Dengue IgM- Dengue 20 (57) 15(43) 30(86) 4 (11) 7(20) 6(26) 3(8.5) 5 (14) 30 (85) showed anaemia in 20 (57%), leucopenia in 15 (43%) and thrombocytopenia in 30 (86%) patients (Table 3). Following the WHO criteria (Table 1b), majority of the children were classified under DHF (n= 22) and severity of grade 2 was most commonly observed. Two children had DSS out of Table 4. Outcome of the Patients with Dengue Fever. Cases Number of patients (%) DF DHF DSS Mortality Hepatic Encephalopathy Grade 1 Grade II Grade III Grade IV 11 (31) 22 (62) 02 (05) (31) 22(62) 1(3) 1(3) which one expired and one recovered completely. The child who recovered also developed hepatic encephalopathy besides shock (Table 4). Discussion Although this is the second proven epidemic of Dengue Fever in Pakistan, limited data regarding children is available. This study was undertaken to define the natural history of this disease in terms of clinical presentation and outcome in children. The epidemic started in October 2006, the postmonsoon season. This timing can be explained by increased mosquito breeding 10 due to ambient temperature and humidity 11 present in the preceding months. This observation was against the 1994 epidemic of Karachi which occurred from June to September, reason could be delayed onset of monsoon in The pattern is similar to Dengue epidemic in Chandigarh, India. 12 Majority of children were from peri-urban slums that favour mosquito breeding owing to conditions such as inadequate solid and water waste management 13, practices of water collection for domestic usage and over crowded living conditions. Although dengue infection shows bimodal peaks during age groups of less than 1 year and between 5 to 7 years 2, we did not come across Dengue infection in any child below 1 year of age. However, majority of our cases (65%) were under 10 years of age. Reports from other South and East Asian countries have shown Dengue infections occurring in different age groups during previous epidemics. Studies from Punjab and Tamil Nadu, India, have reported lesser number of infected children below 15 years of age 14,15, whereas in Chittagong, Bangladesh, and Chennai, India, 35% and 20% infants respectively were reported. 16,17 Published data from Thailand also showed larger proportion of affected children under the age of 10 years. 18 Male preponderance was observed in our study, as it 6 J Pak Med Assoc

4 has been observed in other studies from Pakistan and India. 8,9,12 This could be due to the fact that in these social regions, males spend more time outdoors than females, thereby have increased risk of mosquito bites. As regards the clinical presentation, experience from numerous outbreaks of confirmed Dengue fever show similar presentation with few exceptions. Fever has been the main finding in all epidemics including ours. Average duration of fever was 5 days and biphasic pattern was seen in 40% cases. Similar findings were observed in Dengue epidemics in Bangladesh and Chennai. 16,17 Coryza is reported to be a common manifestation in young children 20, however, in our series it was exceedingly uncommon compared to other clinical features. Abdominal pain, vomiting, bleeding, headache and arthralgia constituted common clinical manifestations. These were also found to be common presenting features in previous epidemics in Karachi. 2 Rashes were found in 23 (65%) children. Fourteen (40%) had petechiae and bruises, 6 (26%) had maculopapular rashes (mainly on face and extremities) and 3 (8.5%) had confluent red macular rashes involving both legs.these rashes faded in 5 to 7 days and in 2 of these children, were associated with exfoliation.ratageri 21 also reported skin exfoliation in his study. The reason for this is not clear but was probably due to high grade fever. Spontaneous haemorrhage occurred in 31 (87%) children in the form of gastrointestinal haemorrhage and 61 percent of total presented with epistaxis. These figures correspond with reports from Delhi 22 and Bangalore 21 outbreaks. Interestingly in 4 patients bleeding occurred with normal prothrombin and platelet counts. Narayanan 19 also reported similar finding in his study. This feature is perhaps due to the altered functional capacity of platelets during Dengue infection. Positive Tourniquet test has been reported in studies as a regular feature, most likely, occurring due to reduced capillary fragility. 23 However, it was seen positive only in 9 (26%) of our cases Hepatomegaly was found in 13 (37%) cases and Splenomegaly in 2 (6%) patients in this series. This was also observed in Pakistani children during 1994 epidemic which is quite low compared to other studies of South East Asia. 24 Anaemia was observed in 20 (57%) patients, majority of children had decreased haematocrit (88%) and 4 patients had increased haematocrit. Increase in haematocrit of more than 20% in DHF indicates development of DSS, however in our study most of the children had decreased haematocrit because of underlying anaemia. Of the patients who had raised haematocrit only one child developed clinical shock. Plural effusion and ascites which occur due to increased capillary leakage were found in none of the patients although other studies report these features to be increased in dengue fever. 25 Outcome showed DHF was more common, 22 (62%) followed by DF 11 (33%). Two (5%) children developed Dengue shock syndrome which is comparable to epidemics of Bangladesh 6, one child expired due to DSS and cause of death was circulatory collapse. Present study shows slight difference in the presentation and course of patients with Dengue infection compared to epidemics in other parts of the world, thus indicating the need for continuous sero-epidemeological surveillance in Pakistan for identification of clinical features of Dengue infection in our region and for timely implementation of an effective control programme to prevent such outbreaks in future. References 1. Pinheiro FP, Corber SJ. Global situation of dengue and dengue haemorrhagic fever and its emergence in the Americas. 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