Page 1005 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

736 PART 5: Infectious Disorders

TABLE 80-2 Typical Clinical Features of Major VHFs Pathogenesis Infection by one serotype (primary dengue infection) causes
homotypic long-term immunity with development of neutralizing
Criteria Findings antibodies, but only transiently protective cross-immunity to the three
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Incubation Usually shorter than 2 weeks except in hantavirus infections other serotypes. Over time, falling cross-reactive antibodies are unable
(2-5 weeks) to prevent infection by heterotypic serotypes. When subsequent hetero-
Onset Sudden onset except in arenavirus infections (insidious onset) typic infection occurs (secondary dengue infection), there is a greater
risk of severe illness. Secondary dengue infection is associated with
Prodrome All VHFs have a febrile prodrome with multiple manifestations, such antibody-dependent enhancement (ADE): The binding of nonneu-
as chills, headache, myalgia, back pain, nausea, vomiting, abdomi- tralizing heterotypic antibody to DENV creates virus-antibody com-
nal pain, conjunctival injection, retroocular pain, and arthralgia plexes that activate the complement and bind to Fc-receptor-bearing
Severe exudative sore Lassa fever monocytes and macrophages, resulting in increased phagocytosis and
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throat intracellular replication with prolonged viremia. Antibodies to dengue
Severe chest pain Lassa fever structural precursor-membrane protein (prM) are highly cross-reactive
Facial edema Lassa fever; South American HF due to arenaviruses and might be involved in ADE. 30,31 Dengue is more severe in children
Rash Dengue (second to sixth day), Ebola and Marburg (around the between 4 and 12 months old who are born to seropositive mothers:
Maternal antibody that crosses the placenta is initially protective but at
fifth day), Lassa (in Caucasians) low levels may later result in ADE. Dengue HF (DHF) outbreaks are
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Jaundice Yellow fever (always); CCHF, RVF, Ebola, and Marburg frequently recognized in hyperendemic dengue regions where multiple
Severe bleeding Rare in even severe dengue or Lassa fever serotypes cocirculate.
Common in yellow fever, Ebola and Marburg, CCHF, South However the pathogenesis of severe dengue also involves cross-reactive
American HF, the 1% of RVF cases with HF activated memory T lymphocytes, proinflammatory cytokines (IFN-γ,
Severe renal impairment HFRS: severe renal failure is a hallmark TNF-α, and IL-10) that mediate increased endothelial permeability
and the interval between dengue primary and secondary infections.
Yellow fever: common renal impairment A number of host factors (young age, female sex, non-African ancestry,
Severe hypoxia, pleural HCPS: occurs early and is one of the two major manifestations and specific HLA alleles) predict severe dengue. 30,31 Viral factors are
effusions, and low-pres- relevant: The serotypes DENV-2 and DENV-3 are most often found in
sure pulmonary edema severe dengue. Virulent DENV genotypes cause epidemics of DHF and
Shock HCPS: cardiogenic shock is often the cause of death in maximally severe primary dengue. 32
treated patients Epidemiology DF is a global public health problem. After WWII, the inci-
Severe dengue, Lassa, HFRS, CCHF: due to endothelial damage dence of DF greatly increased in Asia where rapid urbanization and
with increased vascular permeability poorly maintained cities led to enormous A aegypti proliferation. The
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Neurological Lassa: sensorineural hearing loss common in convalescence; first DHF outbreak was recognized in the Philippines in the 1950s.
manifestations CNS damage is uncommon Dengue was uncommon in the Americas from 1947 to 1980 due to a
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South American arenaviral HF: severe encephalopathy, tongue successful vector elimination program. Because of rapid urbanization,
the vector reinfested Latin America. From 1981, dengue epidemics were
tremor, dysarthria recognized in Latin America and the Caribbean islands. More recently,
Viral encephalitis: RVF (with or without HF), Kyasanur forest the incidence of DF has increased in Eastern and Western Africa.
disease, Omsk HF Dengue is endemic in more than 100 countries of Asia, Africa, and Latin
Ocular manifestations Retinitis a hallmark of RVF; retinitis can be seen in Kyasanur America with annually a modeled 50 to 100 million infections, 500,000
forest disease DHF cases, and more than 20,000 deaths. DF is common in travelers
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With Marburg and Ebola, uveitis and retinitis are common to Latin America, the Caribbean, and South Central or Southeast Asia. 5,7
Sensorineural hearing loss Lassa fever (common, during convalescence) The Clinical Spectrum DENV causes asymptomatic infections, mild fever, DF,
Orchitis Lassa fever DHF, and dengue shock syndrome (DSS). The incubation period is on
Fetal loss and high Lassa fever average 4 to 7 days (range 3-14 days).
In DF (classic dengue) there is sudden onset of fever associated with
maternal mortality headache, retroorbital pain, low back pain, body aches (break-bone
Case-fatality rate Most patients infected with Lassa, RVF, Puumala, or dengue do fever), anorexia, vomiting, sore throat, and generalized skin flushing or
well, with a minority admitted to the hospital, and <1% mottling. The fever is high (102°F-105°F) for 2 to 7 days, may drop for
overall mortality. The mortality of admitted Lassa cases is 15% 12 to 24 hours then recurs (saddleback fever). A relative bradycardia
The mortality of yellow fever and CCHF is higher (around 20%) is noted. The conjunctivae are injected, extraoccular movements are
The mortality of HFRS depends on the specific virus: Puumala and painful, the pharynx is erythematous, and lymphadenopathy is present.
Seoul are associated with a low mortality (< 1%) but Hantaan A maculopapular rash appears on illness day 2 to 6. Sometimes it is a
and Dobrava are associated with a mortality of 10%-15% generalized erythema with islands of normal skin (“a sea of red with
The mortality of Ebola and Marburg is very high in most islands of white”). Children with dengue tend to appear quiet and
outbreaks (up to 90%) uncomfortable. At the end of the febrile phase, hemorrhagic mani-
festations may appear, usually limited to petechiae or mild epistaxis.
Laboratory tests show leukopenia, neutropenia, thrombocytopenia, and
elevated transaminases. Usually the thrombocytopenia worsens, the
The tiger mosquito (Aedes albopictus) was introduced into the United hematocrit rises, and lymphocytosis appears, but DF is self-limiting.
States with recycled tires in the 1980s and has spread to at least 30 states. In DHF, after a typical prodrome, as the fever resolves, signs of circula-
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DF outbreaks have been seen in Hawaii, Texas, and the Florida Keys. 16,17,27 tory failure and/or hemorrhagic manifestations appear. 26,30-34 Danger signs
A primitive sylvatic transmission cycle of DENV involves canopy- include intense and continuous abdominal pain, persistent vomiting,
dwelling mosquitoes and primates of Asia and Africa. DENV can be clinical fluid accumulation, mucosal bleed, lethargy, restlessness, liver
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transmitted through transfusion. Infection of pregnant women near enlargement >2 cm, and the combination of hemoconcentration and rap-
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term may result in fetal and neonatal illness. 29 idly worsening thrombocytopenia. 36,37 In severe dengue, an acute increase

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