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CHAPTER 42
Dengue, 262 Yellow fever, 265 Further reading, 266
While the most important viral haemorrhagic tor (Aedes aegypti) as well as reinfestation of this fevers numerically (dengue and yellow fever) are insect into Central and South America (it was transmitted exclusively by arthropods, other largely eradicated in the 1960s). Other factors arboviral haemorrhagic fevers (Crimean– include intercontinental transport of car tyres Congo and Rift Valley fevers) can also be trans- containing Aedes albopictus eggs, overcrowding mitted directly by body fluids. A third group of of refugee and urban populations and increasing haemorrhagic fever viruses (Lassa, Ebola, Mar- human travel. In hyperendemic areas of Asia, burg) are only transmitted directly, and are not disease is seen mainly in children. transmitted by arthropods at all. The directly Aedes mosquitoes are ‘peri-domestic’: they transmissible viral haemorrhagic fevers are dis- breed in collections of fresh water around the cussed in Chapter 41. house (e.g. water storage jars).They feed on hu- mans (anthrophilic), mainly by day, and feed re- peatedly on different hosts (enhancing their role Dengue as vectors).
Dengue virus is numerically the most important Clinical features arbovirus infecting humans, with an estimated Dengue virus may cause a non-specific febrile 100 million cases per year and 2.5 billion people illness or asymptomatic infection, especially in at risk.There are four serotypes of dengue virus, young children. However, there are two main transmitted by Aedes mosquitoes, and it is un- clinical dengue syndromes: dengue fever (DF) usual among arboviruses in that humans are the and dengue haemorrhagic fever (DHF). natural hosts. Dengue fever (‘breakbone fever’) has been around for many hundreds of years; Dengue fever dengue haemorrhagic fever (DHF) emerged as This is a classical fever–arthralgia–rash syn- an apparently new disease in South East Asia in drome (Chapter 40), with retro-orbital pain, the 1950s. photophobia, lymphadenopathy and, in about 50% of patients, a rash. This is usually macu- Epidemiology lopapular, but may be mottling or flushing. In Dengue has spread dramatically since the end of addition, there may be petechiae and other World War II, in what has been described as a bleeding manifestations including gum, nose or global pandemic. Virtually every country be- gastrointestinal haemorrhage, but these do not tween the tropics of Capricorn and Cancer is define it as DHF according to WHO criteria— now affected (Fig. 42.1). see below (Table 42.1).About one-third of pa- Factors implicated in the spread of dengue tients have a positive tourniquet test (a blood viruses include poor control of its principal vec- pressure cuff inflated to half way between
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Dengue 263 DISTRIBUTION OF LTMPHATIC FILARIASIS DISTRIBUTION OF LTMPHATIC ellow fever ellow Dengue Y Map showing the approximate distribution of dengue and yellow fever viruses. fever distribution of dengue and yellow the approximate Map showing Key DISTRIBUTION OF DENGUE AND YELLOW FEVER YELLOW AND DISTRIBUTION OF DENGUE ig. 42.1 F GBL42 11/27/03 4:02 PM Page 264
264 Chapter 42: Dengue and Yellow Fever
DISTINGUISHING DF FROM DHF
Plasma Platelets Circulatory Haemorrhagic leakage* (/µL) collapse manifestations
DF No Variable Absent Variable
DHF I Present < 100 000 Absent Positive tourniquet test (or easy bruising) DHF II Present < 100 000 Absent Spontaneous bleeding† with or without positive tourniquet test DHF III Present < 100 000 PP < 20 mmHg‡ Spontaneous bleeding and/or positive tourniquet test DHF IV Present < 100 000 Pulse and BP Spontaneous bleeding and/or undetectable positive tourniquet test
BP,blood pressure; DF,dengue fever; DHF,dengue haemorrhagic fever; PP,pulse pressure. * Identified by haematocrit 20% above normal, or clinical signs of plasma leakage. † Skin petechiae, mucosal or gastrointestinal bleeding. ‡ Pulse pressure less than 20 mmHg, or hypotension for age.
Table 42.1 World Health Organization criteria for or lethargic, and often have tender hepatomegaly distinguishing dengue fever (DF) and dengue or abdominal pain. haemorrhagic fever (DHF) grades I–IV.DHF grades III and IV are collectively known as dengue shock syndrome (DSS). DIFFERENTIAL DIAGNOSIS OF DENGUE systolic and diastolic pressure for 5min pro- duces 20 or more petechiae in a 2.5-cm square Fever with arthralgia or rash on the forearm). • Arboviruses: Chikungunya, O’nyong nyong, sindbis,West Nile, Ross River, Oropouche, sandfly fevers, Colorado tick fever. Dengue hemorrhagic fever • Other viruses: rubella, measles, herpes, Initially,patients have a non-specific febrile illness, enteroviruses. which may include a petechial rash.Then on the • Bacteria: meningococcus, typhoid. third to seventh day of illness, as the fever sub- • Spirochaetes: leptospirosis, Lyme disease, sides, there is a massive increase in vascular per- relapsing fevers. meability (this is the major pathophysiological • Rickettsiae: tick and endemic typhus, Rocky process). This leads to plasma leakage from the Mountain spotted fever. • Parasites: malaria. blood vessels into the tissue, causing an elevated haematocrit, oedema and effusions. In addition, Fever with haemorrhage there is thrombocytopenia and haemorrhagic • Arboviruses: yellow fever, Crimean–Congo manifestations. If a positive tourniquet test is the haemorrhagic fever, Rift Valley fever, Omsk only such manifestation, then this is defined as haemorrhagic fever. DHF grade I (Table 42.1). If there is spontaneous • Other viruses: hantaviruses, fulminant hepatitis (A–E); Lassa; South American bleeding this is grade II. In grade III, the plasma haemorrhagic fevers, Ebola, Marburg. leakage is sufficient to cause shock (defined in •Any severe sepsis with disseminated children as a pulse pressure <20mmHg). In grade intravascular coagulation (DIC). IV, the blood pressure is unrecordable. Collec- • Drug reactions. tively,grades III and IV are known as dengue shock syndrome (DSS). Patients with DHF are restless Box 42.1 Differential diagnosis of dengue. GBL42 11/27/03 4:02 PM Page 265
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Investigations 2 Viral strain differences — e.g. increased viru- Leucopenia and thrombocytopenia are com- lence of South-East Asian strains of dengue-2 mon. In the first few days of illness dengue virus virus. can be isolated from serum or detected by poly- merase chain reaction (PCR). After the fever Prevention subsides, IgM and then IgG antibodies can be de- Prevention is by control of Aedes mosquitoes. tected by ELISA. New enzyme immunoassay Methods include treating stored water with lar- kits allow rapid diagnosis in the field. A lateral vicides (e.g. temephos), educating people to re- chest X-ray may show a pleural effusion in DHF. move collections of water around the house (e.g. in rubbish), and spraying with insecticide Management during epidemics. Dengue fever Future developments include tetravalent Most cases are self-limiting. Oral fluids should vaccines (effective against all four dengue be encouraged, and paracetamol given. Patients serotypes), which are in development, for ex- may have a maculopapular recovery rash and ample, live attenuated vaccines and recombi- prolonged lethargy and depression after recov- nant copy DNA infectious clone vaccines. ery are common.
Dengue haemorrhagic fever Ye llow fever For grades I and II DHF,oral fluids should be en- couraged, vital signs closely monitored, as well Epidemiology as haematocrit and platelet count, which may Yellow fever virus is naturally transmitted warn of deterioration to grades III and IV. For between primates by various mosquitoes in jun- grades III and IV (dengue shock syndrome), cen- gle cycles in Central America and Africa (Fig. tral venous pressure (CVP) should be moni- 42.1). Aedes aegypti transmits the virus to tored if possible. Intravenous crystalloid (10– humans in urban cycles. The disease has re- 20mL/kg/h)should be given, followed by intra- emerged in South America since the 1970s, venous colloid if shock persists. Patients should when the Aedes eradication programme was re- be watched carefully for fluid overload, and infu- laxed. There are an estimated 200000 cases, sions reduced accordingly. with 30000 deaths annually.
Other severe manifestations of Clinical features dengue infection The illness is biphasic and often mild. Severe These include hepatitis, or fulminant hepatic disease is characterized by jaundice, fulminant failure (Reye-like syndrome) as well as neuro- hepatic failure and gastrointestinal bleeding. logical complications (metabolic encephalopa- Faget’s sign is the failure of the heart rate to in- thy, cerebral oedema or, occasionally, viral crease with a rising temperature and is indica- encephalitis). tive of cardiac damage. Elevated liver function tests, leucopenia, thrombocytopenia and clot- Pathogenesis of dengue ting abnormalities may occur.Liver histology re- haemorrhagic fever veals Councilman bodies, which also occur in Current evidence suggests two mechanisms Crimean–Congo haemorrhagic fever and Rift may be important: Valley fever. 1 Antibody-dependent enhancement — antibod- ies against one dengue virus serotype (from a Control previous infection) enhance the entry of a sec- Yellow fever control consists of use of the ond dengue virus into macrophages, leading to a highly effective 17D live attenuated vaccine. more severe infection. Vector control is as for dengue fever. GBL42 11/27/03 4:02 PM Page 266
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flaviviruses. J Infect 2001; 42: 104–15. [Includes im- Further reading portant tick-borne viruses.] World Health Organization. Dengue Haemorrhagic Gibbons RV, Vaughan DW. Dengue—an escalating Fever: Diagnosis, Treatment and Control. Geneva: problem. Br Med J 2002; 324: 1563–6. World Health Organization, 1997. [Very useful Solomon T, Mallewa MJ. Dengue and other emerging manual on dengue haemorrhagic fever.]