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ORIGINAL / RESEARCH
Ultrasound as an Adjunct to Diagnosis of Suspected
Cases of Dengue Fever
M John Santhakumar, Manjula Jagadeesan, M Paul Korath, K Jagadeesan
The diagnosis of dengue haemorrhagic fever is mostly clinical in practice. We report abdominal ultrasonographic findings in dengue haemorrhagic fever cases confirmed by serology and low platelet counts. In dengue haemorrhagic fever cases seen in our series, gallbladder wall oedema was seen in 75% cases, intraperitoneal free fluid in 41.7%, pleural effusion in 33.3%, perinephric fluid collection in 25% and pancreatic oedema, peripancreatic fluid and retroperitoneal fluid in 8.3% cases each, while none of these findings were seen in dengue fever per se. The sensitivity of abdominal ultrasound to diagnose dengue haemorrhagic fever from dengue fever was 0.83, specificity was 1, positive predictive value was 1 and negative predictive value was 0.5. Abdominal ultrasonography may usefully support the early clinical diagnosis of dengue haemorrhagic fever.
INTRODUCTION
Epidemics of dengue fever (DF) due to the four dengue virus serotypes are a major public heath problem in the tropics and subtropics with 100 million cases reported worldwide annually. This is due to lack of effective control of the Aedes aegypti mosquito in endemic areas and transport of dengue virus between populations by air travel.1,2
Clinical findings consist of a biphasic fever, a morbilliform macular rash3-6 sparing the palms and soles, retro-orbital headache, myalgia, arthralgia, sore throat, relative bradycardia, lymphadenopathy, taste aberration, nausea, anorexia and haemorrhagic manifestations. Dengue haemorrhagic fever (DHF) by definition is the occurrence of thrombocytopenia (£ 100000/mm3) and haemoconcentration (haematocrit ³ 120% of the recovery value). There are four grades of illness of
DHF7 based on severity namely:
Grade I : Fever with nonspecific constitutional symptoms, positive tourniquet test or scattered petechiae.
Grade II : Same as Grade I, but with spontaneous haemorrhagic manifestation.
Grade III : Circulatory failure manifested by rapid, weak pulse, narrowing of pulse £ 20 mmhg), or hypotension.
Grade IV : Profound shock with undetectable pulse and blood pressure.
Dengue shock syndrome (DSS) is a combination of DHF and a narrow pulse pressure or hypotension. DHF/DSS occur during second dengue infections with a heterologous dengue virus serotype.7-9 The new virus and the preexisting antibody form an immune complex which is phagocytosed by macrophages but the heterologous virus is not neutralized and continues to multiply. The infected macrophage produces vasoactive mediators that leads to capillary damage.
Laboratory findings include neutropenia followed by lymphocytosis often with atypical lymphocytes. There may be a mild elevation in liver enzymes.10 Thrombocytopenia is common. Chest skiagram may show bronchopneumonia or pleural effusion.11 Specific diagnosis consists of demonstration of specific IgM antibody12 which appears in serum by day 5 after onset and persists for 2 to 3 months. It indicates an active or a recent infection.13,14 Anti dengue IgM antibody may be produced during both primary and secondary dengue infections. Anti dengue IgM antibody can be negative in early cases of primary DF. Diagnosis using IgG requires paired acute and convalescent phase sera to demonstrate a fourfold or greater rise in titre.
Detection and quantification of dengue virus in plasma by virus isolation is time consuming and has variable isolation rates. Recently quantification based on quantitative competitive reverse transcription PCR (RT PCR) of dengue virus RNA has been developed as a sensitive and accurate method. These are too expensive to be done for all patients in developing countries.
Since many of the manifestations of DF are non-specific and can occur in other infectious diseases which are common in the tropics and subtropics, we in the developing countries have to rely on a clinical diagnosis for DF. This is based on presumption in most cases and may be wrong. Ultrasonography (USG) has been reported to be a useful diagnostic tool in evaluating patients with DHF.11 It may usefully support the early clinical diagnosis of dengue haemorrhagic fever.
Aim of the Study The aim of our study is to report on the findings of abdominal ultrasonography in cases of dengue infections and its correlation with the serologic diagnosis.
MATERIAL AND METHODS
Our study is based on probable cases of dengue fever admitted to the KJ Hospital, Chennai, India during May to November 2001 belonging to ages ranging from 6 months to 72 years and including both sexes. Patients who had the typical constellation of symptoms and clinical findings of DF were admitted and studied in the first week of fever. IgM dengue antibody test using dBest-Morepen one step dengue IgM test disk was used in our study so as to pick up a recent dengue infection and obviate the need for paired samples for IgG evaluation. Other causes of fever and inflammatory conditions were excluded by preliminary clinical examination and suitable laboratory investigations. An abdominal and pelvic ultrasound study using Logiq 400 MD Colour Doppler GE with a 2-4MHz convex probe was performed on these patients on the day of admission by a qualified sonologist who was unaware of the serology reports. Platelet counts were determined on the day of admission by bulk dilution method for all patients included in the study. The findings of USG and its frequency of occurrence with the serological diagnosis was evaluated.
RESULTS
Sixty six cases of suspected dengue fever with age ranging from 6 months to 72 years had an antiDengue IgM antibody test performed. Twenty one cases were positive for antiDengue IgM antibody and 45 cases were negative. Seventeen of the above mentioned 21 cases who had a platelet count < 100000/cumm fit into the category of DHF and 12 of these cases had an abdominal and pelvic ultrasound study done. In 10 of the 12 cases of DHF for whom USG was done at our centre at least one of the below mentioned findings were noted viz, striated gallbladder wall oedema was seen in 9 cases (75%). This oedema of the gallbladder wall was always striated and the range of thickening was from 4 mm to 18 mm. Ultrasonographic Murphy’s sign was negative in these cases. Intraperitoneal free fluid centred in the right upper quadrant and/or in the right lower quadrant was seen in 5 cases (41.7%). Pleural effusion dominantly right more than left, isolated right but never isolated left sided was seen in 4 cases (33.3%). Perinephric fluid collection was seen in 3 cases (25%) and pancreatic oedema, peripancreatic fluid and retroperitoneal fluid were noted in 1 case (8.3%) each. Only 2 cases (16.7%) of confirmed DHF had a normal abdominal ultrasound. Two cases in this series which were initially negative and 1 which was borderline positive for antiDengue IgM antibody on admission, had symptoms and signs suggestive of DF and thrombocytopenia. All these three showed abdominal ultrasound findings namely gallbladder wall oedema, pleural effusion, intraperitoneal and retroperitoneal free fluid. These three cases showed a positive antiDengue IgM antibody test a week later confirming the diagnosis. USG was done in two cases from the group who were antiDengue IgM positive and who had no thrombocytopenia which were reported normal. The sensitivity of the abdominal ultrasound findings to diagnose DHF from DF was 0.83, specificity was 1, positive predictive value was 1 and negative predictive value was 0.5. Of the 45 cases negative for antiDengue IgM antibody, 19 had USG done. Liver abscess, acute acalculous cholecysitis, hepatomegaly, fatty liver and fluid collection in hepatorenal pouch were among some of the findings in contrast to those classically seen in DHF cases.
The majority of cases were Grade 1 DHF in our series. Only one patient had haemorrhagic manifestations and was classified as Grade II. The sonographic findings of involvement of abdominal organs in DHF had clinical implications in the cases which we studied. In addition to the classic symptoms of fever, headache and bodyache, a majority of patients had symptoms pertaining to abdominal involvement viz nausea and vomiting (73.3%) and abdominal pain (33.3%). The classic retroorbital pain was noted in only a small percentage (13.3%) of our patients.
DISCUSSION
Sonography has been reported to be a useful diagnostic tool in evaluating patients with DHF.11 In their article Thulkar et al have presented their sonographic findings in 40 adults with severe (Grade III) DHF. These included pleural effusion in 53%, thickening of gallbladder wall in 43%, and mild ascites in 15%. These findings reported by Thulkar et al in their article, contrasts that seen in our hospital where striated gallbladder wall oedema was the commonest sonographic finding followed by intraperitoneal free fluid, pleural effusion, perinephric fluid collection, pancreatic oedema, peripancreatic fluid and retroperitoneal fluid in descending order.
The above sonographic findings are not diagnostic of DHF. Thickening of the gall bladder wall is also found in acute cholecystitis and some nonbiliary disorders namely hepatic cirrhosis, viral hepatitis, chronic congestive cardiac failure, chronic renal failure and hypoalbuminaemia. Since they are commonly found in DHF, they lend supportive evidence to the presence of DHF during a documented regional epidemic.
They majority of cases were Grade I DHF in our series. Only one patient had haemorrhagic manifestations and was classified as Grade II. Certain dengue virus strains produce severe disease by immune enhancement. Also the proportion of patients who have severe disease depends on the immune status of the individual, the age of the patient, and the genetic background of the human host.15-19,7-9 Thus DHF epidemics vary in severity with some epidemics having a high mortality rate.20 A few interesting cases in this study were 11 year old child who had typhoid fever (Salmonella typhi cultured from blood), thrombocytopenia (platelet count 78,000) and anti Dengue IgM negative but IgG positive. Children frequently have concurrent infections with other viruses and bacteria causing upper respiratory symptoms.21 There was another patient who presented with seizures, altered sensorium, CSF showing pleocytosis and high protein content, normal platelet count with anti dengue IgM negative but IgG positive. On CSF culture, no organism was isolated. Neurologic involvement in DF is well known.22 Repeat samples for rise in titre of IgG antibody could not be done as these patients made uneventful recovery and were lost to followup.
Dengue virus type III was isolated during this epidemic by the Madurai Kamaraj University. Virus isolation is being done by reference laboratories in our country and documented from time to time.23 During an epidemic a single serotype may be isolated or there may be multiple serotypes due to co-circulation of all 4 dengue virus serotypes in the same community.24
Management is conservative in Grade I DHF. Adequate oral rehydration and antipyretics may be all that is needed. But patients may progress from Grade I to higher grades. So platelet counts and haematocrit should be measured every 24 hours and signs of shock should be carefully looked for to detect any deterioration at the earliest. Adequate intravenous hydration for patients who show signs of shock should be instituted. Platelet concentrates are indicated in severe thrombocytopenia (platelets < 20,000/mm3) and fresh whole blood or fresh frozen plasma for massive bleeding or consumption coagulopathy. Severe thrombocytopenia and bleeding necessitating platelet and blood transfusion was seen in only 1 patient in our series. DSS was not seen in our series. The mortality rate was nil in our series.
CONCLUSION
Dengue epidemics have been occurring in India from time to time.23 In endemic areas, dengue infections are often clinically nonspecific, especially in children, with symptoms of a viral syndrome. There is no pathognomonic sign or symptom for DF.21 Clinical diagnosis of DHF is based on a knowledge of the geographic distribution, ecology of viral causes of the syndrome, clinical presentation and possible exposure of the patient at an appropriate interval before the onset of the disease. This is likely to be erroneous in many instances. Abdominal ultrasonography may support the clinical diagnosis of DHF during a documented regional epidemic.
REFERENCES
1. Gubler DJ, Trent DW. Emergence of epidemic dengue/dengue haemorrhagic fever as a public health problem in the Americans. Infectious Agents and Diseases 1994; 2 : 383.
2. Gubler DJ, Clark GG. Dengue/dengue haemorrhagic fever: The emergence of a global health problem. Emerging Infectious Diseases 1995; 1 : 55.
3. Siler JF, Hall MW, Hitchens AP. Dengue, its history, epidemiology, mechanism of transmission, etiology, clinical manifestations, immunity and prevention. Philippine Journal of Science 1926; 29 : 1.
4. Sabin AB. Research on dengue during World War II. American Journal of Tropical Medicine and Hygiene 1952; 1 : 30.
5. Waterman SH, Gubler DJ. Dengue fever. In clinics in dermatology. Philadelphia JB Lippincott. 1989: 117.
6. Hayes EB, Gubler DJ. Dengue and dengue haemorrhagic fever. Paediatric Infectious Diseases Journal 1992; 11 : 311.
7. Dengue haemorrhagic fever: Diagnosis, treatment and control, Geneva, World Health Organisation, 1986.
8. Halstead SB. Dengue haemorrhagic fever - public health problem and a field for research. Bulletin of World Health Organisation 1980; 58 : 1.
9. Halstead SB. Observations related to pathogenesis of dengue haemorrhagic fever. VI hypotheses and discussion. Yale Journal of Biological Medicine 1970; 42 : 350.
10. Wahid SF, Sanusi S, Zawawi MM, et al. A comparison of the pattern of liver involvement in dengue haemorrhagic fever with classic dengue fever. Southeast Asian Journal of Tropical Medicine and Public Health 2000; 31(2) : 259-63.
11. Thulkar S, Sharma S, Srivastava DN, et al. Sonographic findings in grade III dengue haemorrhagic fever in adults. Journal of Clinical Ultrasound 2000; 28 (1) : 34-7.
12. Valdes K, Alvarez M, Pupo M, et al. Human dengue antibodies against structural and nonstructural proteins. Clinical and Diagnostic Laboratory Immunology 2000; 7(5) : 856-7.
13. Gubler DJ, Sather GE. Laboratory diagnosis of dengue and dengue haemorrhagic fever. In proceedings of international symposium on yellow fever and dengue. Rio de Janeiro, Brazil, 1990.
14. Kuno G, Gomez I, Gubler DJ. An ELISA procedure for the diagnosis of dengue infections. Journal of Virologic Methods 1991; 33 : 101.
15. Gubler DJ. Dengue. In Monath TP (ed) : Epidemiology of arthropod borne viral diseases. Boca Raton, Fla, CRC Press, 1998.
16. Rosen L. Dengue-An overview. In Mackenzie JS (ed). Viral diseases in Southeast Asia and the Western Pacific. Sydney, Australia, Academic Press, 1982: 484.
17. Barnes WJS, Rosen L. Fatal haemorrhagic disease and shock associated with primary dengue infection on a Pacific island. American Journal of Tropical Medicine and Hygiene 1974; 23 : 495.
18. Guzman MG, Kouri GP, Bravo J, et al. Dengue haemorrhagic fever in Cuba.II. Clinical investigations. Trans Soc of Tropical Medicine and Hygiene 1984; 78 : 239.
19. Rosen L. The Emperor’s new clothes revisited, or reflections on the pathogenesis of Dengue haemorrhagic fever. Am J of Trop Med and Hyg 1977; 26 : 337.
20. Ha DQ, Tien NT, Huong VT, et al. Dengue epidemic in southern Vietnam, 1998. Emerging Infectious Diseases 2000; 6(4) : 422-5.
21. Gubler DJ. Dengue and dengue haemorrhagic fever. Tropical infectious diseases : Principles, pathogens and practice. 1265-74.
22. Solomon T, Dung NM, Vaughn DW, et al. Neurologic manifestations of dengue infection. Lancet 2000; 355(9209) : 1053-9.
23. Dar L, Broor S, Sengupta S, et al. The first major outbreak of dengue haemorrhagic fever in Delhi, India. Emerging Infectious Diseases 1999; 5(4) : 589-90.
24. Lorono-Pino MA, Cropp CB, Farfan JA, et al. Common occurrence of concurrent infections by multiple dengue virus serotypes. American Journal of Tropical Medicine and Hygiene 1999; 61(5) : 725-30.
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