Sunday, December 8, 2013

Breakbone Fever

AKA Dengue Fever. The name fits, because the bone pain suffered by some individuals is severe.

Nicaragua Dispatch, an online English-language newspaper, ran this headline October 30, 2013 
Dengue Claims 14th Victim in Nicaragua. 
The headline a week earlier on October 24, 2013 - Nicaragua on Red Alert for Dengue.
After reading these articles, a review of Dengue seemed prudent. 
Dengue is caused by a virus and there are four different serotypes. Individuals who live in an endemic region such as Nicaragua are usually infected by several or all of the strains over their lifetime.

In 2004 a prospective study of about 3800 children, 2 to 9 years of age, was started in Managua, the capital of Nicaragua. The children had annual blood tests to identify infection with dengue virus. Over the first four years of the study, 22 to 40% of the two year-olds and 90 to 95% of the nine year-olds showed evidence of Dengue. So, every child is eventually infected.


Infection with one dengue serotype confers lifelong immunity, but only to that serotype. Most adults are immune.

The virus is transmitted by a female Aedes mosquito. These mosquitoes thrive in stagnant water such as might be found in old tires or other small containers around a home.

The mosquitoes acquire the virus when they feed (bite) an individual already infected with the virus. The mosquito can immediately transmit the virus if the insect bites another individual, which is common, and which accounts for epidemics. Entire families often develop infection within a 24 to 36 hour period, presumably from the bites of a single infected female mosquito.


Once inoculated into a human, dengue has an incubation period of 3 to 14 days (average 4 to 7 days).


The majority (50 to 90%) of infected individuals have no symptoms and do not realize they are infected. Data from a 1997 Cuban epidemic suggest that for every symptomatic case of dengue fever, there are 14 unrecognized cases.


Classic dengue fever is defined by the Pan American Health Organization (PAHO) as an acute febrile illness of 2 to 7 days duration associated with two or more of the following - severe headache, pain behind the eyes, severe muscle pain, joint pain, characteristic rash, hemorrhagic manifestations, low white blood cell count.


Many patients experience a prodrome of chills, red mottling of the skin, and facial flushing, which is considered a sensitive and specific indicator of dengue fever. The prodrome might last for 2 to 3 days. The illness presents with the rapid onset of high fever. The fever might reach 41°C. In addition to the symptoms and signs above, the patient might also have weakness, vomiting, sore throat, or altered taste sensation. The rash is a centrifugal, maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with islands of skin sparing. The rash typically begins on day 3 and persists 2-3 days. Fever typically resolves with the cessation of viremia.


Leukopenia and thrombocytopenia are common findings in dengue fever and might be caused by direct destructive actions of the virus on bone marrow precursor cells. Approximately one third of patients with dengue fever have mild hemorrhagic symptoms, including petechiae, gingival bleeding, and a positive tourniquet test.


Dengue fever is typically a self-limiting disease with a mortality rate of less than 1%. Supportive care with analgesics, fluid replacement, and bed rest is usually sufficient. Acetaminophen can be used to treat fever and relieve other symptoms. Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids should not be used.


A small percentage of persons who were previously infected by one dengue serotype and who are later infected with a second serotype, develop the potentially fatal complications
Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). The severity of the secondary dengue infection appears to intensify as the interval increases between the infections.

When a previously infected individual is later infected with a different serotype, non-neutralizing antibodies recognize the dengue virus but do not neutralize or inhibit virus replication. Instead, the virus and antibody form an antigen-antibody complex. This complex is recognized by receptors on macrophages, which then internalize the immune complex and allow the virus to replicate unchecked. This phenomenon is called antibody-dependent enhancement. The affected macrophages release vasoactive mediators that increase vascular permeability. This serious complication usually develops just as the dengue fever episode is resolving.

Abdominal pain in conjunction with restlessness, change in mental status, hypothermia, and a drop in the platelet count presages the development of DHF.

Ninety percent of patients with DHF are younger than 15 years of age.


In persons with DHF, the fever reappears, as a biphasic or "saddleback" fever curve. Along with this biphasic fever, patients with DHF have more obvious hemorrhagic manifestations and plasma leakage. The critical feature of DHF is plasma leakage. Plasma leakage is caused by increased capillary permeability. Bleeding is caused by capillary fragility and thrombocytopenia. DSS is essentially DHF with progression into circulatory failure, with ensuing hypotension, and, ultimately, shock and death. Death can occur within 8-24 hours after onset of signs of circulatory failure. The most common clinical findings with impending shock include hypothermia, abdominal pain, vomiting, and restlessness. DHF has a mortality rate of 2-5% when treated and up to 50% when not treated. In the October 24th Nicaragua Dispatch article, Sonia Castro, the Sandinista Minister of Health, is quoted,


I want the population to know that if they are showing serious signs of dengue, there is a 50% chance they could die even if they are in the health clinic. So we have to destroy the mosquitos' nests for breeding.

This statement is an official acknowledgement that the health care available in Nicaragua is not sufficient to offer the modern intensive medical care necessary. If you live in Canada, the mortality rate is 2 to 5%. If you live in Nicaragua, the mortality rate is 50%. 

The only treatment is supportive care with hydration, blood pressure support with pressors, and platelets and plasma for bleeding. No specific antiviral medication is available.


Prevention is therefore fundamental for control.

Nicaragua insecticide spray program in operation. 
The worker is not wearing a mask. Ouch!!!!! 
Photo courtesy of Nicaragua Dispatch.
The mosquito that transmits the virus bites only by day so mosquito nets are of limited use. Only takes one bite, and the ankles and the back of the neck are the preferred sites.

The only way to prevent dengue virus is to avoid bites. Susceptible individuals should wear N,N-diethyl-3-methylbenzamide (DEET)–containing mosquito repellent and protective clothing, preferably impregnated with permethrin insecticide. They should choose well-screened or air-conditioned places. Larval habitats (stagnant water) should be eliminated or treated with larvacides. Indoor sprays should be considered to eliminate mosquitoes.


References


Trends in Patterns of Dengue Transmission over 4 Years in a Pediatric Cohort Study in Nicaragua. J Infect Dis. 2010;201:5-14.


Nicaragua Dispatch 

http://www.nicaraguadispatch.com/news/2013/10/dengue-claims-14th-victim-in-nicaragua/8301

eMedicine
http://emedicine.medscape.com/article/215840-overview

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