Differential Diagnosis

CHIKUNGUNYA
Symptoms

Most people infected with chikungunya virus will develop some symptoms.

Symptoms usually begin 37 days after being bitten by an infected mosquito.

The most common symptoms are fever and joint pain.

Other symptoms may include headache, muscle pain, joint swelling, or rash.

Chikungunya disease does not often result in death, but the symptoms can be severe
and disabling.

Most patients feel better within a week. In some people, the joint pain may persist for
months.

People at risk for more severe disease include newborns infected around the time of
birth, older adults (65 years), and people with medical conditions such as high blood
pressure, diabetes, or heart disease.

Once a person has been infected, he or she is likely to be protected from future
infections.
Diagnosis

The symptoms of chikungunya are similar to those of dengue and Zika, diseases
spread by the same mosquitoes that transmit chikungunya.

See your healthcare provider if you develop the symptoms described above and have
visited an area where chikungunya is found.

If you have recently traveled, tell your healthcare provider when and where you
traveled.

Your healthcare provider may order blood tests to look for chikungunya or other
similar viruses like dengue and Zika.
Treatment

There is no vaccine to prevent or medicine to treat chikungunya virus.

Treat the symptoms:

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Get plenty of rest.
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Drink fluids to prevent dehydration.
o
Take medicine such as acetaminophen (Tylenol) or paracetamol to reduce
fever and pain.
o
Do not take aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS
until dengue can be ruled out to reduce the risk of bleeding).
o
If you are taking medicine for another medical condition, talk to your
healthcare provider before taking additional medication.

If you have chikungunya, prevent mosquito bites for the first week of your illness.
o
During the first week of infection, chikungunya virus can be found in the blood
and passed from an infected person to a mosquito through mosquito bites.
o
An infected mosquito can then spread the virus to other people.
The principal symptoms of dengue are:

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High fever and at least two of the following:

Severe headache
Severe eye pain (behind eyes)
Joint pain
Muscle and/or bone pain
Rash
Mild bleeding manifestation (e.g., nose or gum bleed, petechiae, or easy
bruising)
Low white cell count

Generally, younger children and those with their first dengue infection have a milder illness
than older children and adults.
Watch for warning signs as temperature declines 3 to 7 days after symptoms began.
Go IMMEDIATELY to an emergency room or the closest health care provider if any of the
following warning signs appear:

Severe abdominal pain or persistent vomiting

Red spots or patches on the skin
Bleeding from nose or gums
Vomiting blood
Black, tarry stools (feces, excrement)
Drowsiness or irritability
Pale, cold, or clammy skin
Difficulty breathing

Dengue hemorrhagic fever (DHF) is characterized by a fever that lasts from 2 to 7 days, with
general signs and symptoms consistent with dengue fever. When the fever declines, warning
signs may develop. This marks the beginning of a 24 to 48 hour period when the smallest
blood vessels (capillaries) become excessively permeable (leaky), allowing the fluid
component to escape from the blood vessels into the peritoneum (causing ascites) and
pleural cavity (leading to pleural effusions). This may lead to failure of the circulatory system
and shock, and possibly death without prompt, appropriate treatment. In addition, the
patient with DHF has a low platelet count and hemorrhagic manifestations, tendency to
bruise easily or have other types of skin hemorrhages, bleeding nose or gums, and possibly
internal bleeding.
Treatment
There is no specific medication for treatment of a dengue infection. Persons who think they
have dengue should use analgesics (pain relievers) with acetaminophen and avoid those
containing ibuprofen, Naproxen, aspirin or aspirin containing drugs. They should also rest,
drink plenty of fluids to prevent dehydration, avoid mosquito bites while febrile and consult a
physician.
As with dengue, there is no specific medication for DHF. If a clinical diagnosis is made early,
a health care provider can effectively treat DHF using fluid replacement therapy. Adequately
management of DHF generally requires hospitalization.
Transmission of the Dengue Virus
Dengue is transmitted between people by the mosquitoes Aedes aegypti and Aedes
albopictus, which are found throughout the world. Insects that transmit disease are vectors.
Symptoms of infection usually begin 4 - 7 days after the mosquito bite and typically last 3 10 days. In order for transmission to occur the mosquito must feed on a person during a 5day period when large amounts of virus are in the blood; this period usually begins a little
before the person become symptomatic. Some people never have significant symptoms but
can still infect mosquitoes. After entering the mosquito in the blood meal, the virus will
require an additional 8-12 days incubation before it can then be transmitted to another
human. The mosquito remains infected for the remainder of its life, which might be days or a
few weeks.

In rare cases dengue can be transmitted in organ transplants or blood transfusions from
infected donors, and there is evidence of transmission from an infected pregnant mother to
her fetus . But in the vast majority of infections, a mosquito bite is responsible.
In many parts of the tropics and subtropics, dengue is endemic, that is, it occurs every year,
usually during a season when Aedes mosquito populations are high, often when rainfall is
optimal for breeding. These areas are, however, additionally at periodic risk for epidemic
dengue, when large numbers of people become infected during a short period. Dengue
epidemics require a coincidence of large numbers of vector mosquitoes, large numbers of
people with no immunity to one of the four virus types (DENV 1, DENV 2, DENV 3, DENV 4),
and the opportunity for contact between the two. Although Aedes are common in the
southern U. S., dengue is endemic in northern Mexico, and the U.S. population has no
immunity, the lack of dengue transmission in the continental U.S. is primarily because
contact between people and the vectors is too infrequent to sustain transmission.
Dengue is an Emerging Disease
The four dengue viruses originated in monkeys and independently jumped to humans in
Africa or Southeast Asia between 100 and 800 years ago. Dengue remained a relatively
minor, geographically restricted disease until the middle of the 20th century. The disruption
of the second world war in particular the coincidental transport of Aedes mosquitoes
around the world in cargo - are thought to have played a crucial role in the dissemination of
the viruses. DHF was first documented only in the 1950s during epidemics in the Philippines
and Thailand. It was not until 1981 that large numbers of DHF cases began to appear in the
Carribean and Latin America, where highly effective Aedes control programs had been in
place until the early 1970s.
Global Dengue
Today about 2.5 billion people, or 40% of the worlds population, live in areas where there is
a risk of dengue transmission. Dengue is endemic in at least 100 countries in Asia, the
Pacific, the Americas, Africa, and the Caribbean. The World Health Organization (WHO)
estimates that 50 to 100 million infections occur yearly, including 500,000 DHF cases and
22,000 deaths, mostly among children.
JAPANESE B
Signs and symptoms
Most JEV infections are mild (fever and headache) or without apparent symptoms, but
approximately 1 in 250 infections results in severe clinical illness. Severe disease is
characterized by rapid onset of high fever, headache, neck stiffness, disorientation,
coma, seizures, spastic paralysis and ultimately death. The case-fatality rate can be as
high as 30% among those with disease symptoms.
Of those who survive, 20%30% suffer permanent intellectual, behavioural or
neurological problems such as paralysis, recurrent seizures or the inability to speak.
Symptoms

Less than 1% of people infected with Japanese encephalitis (JE) virus develop clinical
illness.

In persons who develop symptoms, the incubation period (time from infection until
illness) is typically 5-15 days.

Initial symptoms often include fever, headache, and vomiting.

Mental status changes, neurologic symptoms, weakness, and movement disorders

might develop over the next few days.
Seizures are common, especially among children.
Japanese encephalitis (JE) should be considered in a patient with evidence of a
neurologic infection (e.g., meningitis, encephalitis, or acute flaccid paralysis) who has
recently traveled to or resided in an endemic country in Asia or the western Pacific.
Laboratory diagnosis of JE is generally accomplished by testing of serum or
cerebrospinal fluid (CSF) to detect virus-specific IgM antibodies. JE virus IgM
antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30
to 90 days, but longer persistence has been documented. Therefore, positive IgM
antibodies occasionally may reflect a past infection or vaccination. Serum collected
within 10 days of illness onset may not have detectable IgM, and the test should be
repeated on a convalescent sample. For patients with JE virus IgM antibodies,
confirmatory neutralizing antibody testing should be performed. In fatal cases,
nucleic acid amplification, histopathology with immunohistochemistry, and virus
culture of autopsy tissues can also be useful.
Diagnostic testing for JE virus IgM antibodies is commercially-available. Confirmatory
testing is only available at CDC and a few specialized reference laboratories.
Healthcare providers should contact their state or local health department or the CDC
Arboviral Diseases Branch (telephone: 970-221-6400) for assistance with diagnostic
testing.

MALARIA
Infection with malaria parasites may result in a wide variety of symptoms, ranging from
absent or very mild symptoms to severe disease and even death. Malaria disease can be
categorized as uncomplicatedor severe (complicated). In general, malaria is a curable
disease if diagnosed and treated promptly and correctly.
All the clinical symptoms associated with malaria are caused by the asexual erythrocytic or
blood stage parasites. When the parasite develops in the erythrocyte, numerous known and
unknown waste substances such as hemozoin pigment and other toxic factors accumulate in
the infected red blood cell. These are dumped into the bloodstream when the infected cells
lyse and release invasive merozoites. The hemozoin and other toxic factors such as glucose
phosphate isomerase (GPI) stimulate macrophages and other cells to produce cytokines and
other soluble factors which act to produce fever and rigors and probably influence other
severe pathophysiology associated with malaria.
Plasmodium falciparum-infected erythrocytes, particularly those with mature trophozoites,
adhere to the vascular endothelium of venular blood vessel walls and do not freely circulate
in the blood. When this sequestration of infected erythrocytes occurs in the vessels of the
brain it is believed to be a factor in causing the severe disease syndrome known as cerebral
malaria, which is associated with high mortality.
Incubation Period
Following the infective bite by the Anopheles mosquito, a period of time (the "incubation
period") goes by before the first symptoms appear. The incubation period in most cases
varies from 7 to 30 days. The shorter periods are observed most frequently with P.
falciparum and the longer ones with P. malariae.
Antimalarial drugs taken for prophylaxis by travelers can delay the appearance of malaria
symptoms by weeks or months, long after the traveler has left the malaria-endemic area.
(This can happen particularly with P. vivax and P. ovale, both of which can produce dormant

liver stage parasites; the liver stages may reactivate and cause disease months after the
infective mosquito bite.)
Such long delays between exposure and development of symptoms can result in
misdiagnosis or delayed diagnosis because of reduced clinical suspicion by the health-care
provider. Returned travelers should always remind their health-care providers of any travel
in areas where malaria occurs during the past 12 months.
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Uncomplicated Malaria
The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of

a cold stage (sensation of cold, shivering)

a hot stage (fever, headaches, vomiting; seizures in young children)
and finally a sweating stage (sweats, return to normal temperature, tiredness).

Classically (but infrequently observed) the attacks occur every second day with the "tertian"
parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the "quartan"
parasite (P. malariae).
More commonly, the patient presents with a combination of the following symptoms:

Fever
Chills
Sweats
Headaches
Nausea and vomiting
Body aches
General malaise

In countries where cases of malaria are infrequent, these symptoms may be attributed to
influenza, a cold, or other common infections, especially if malaria is not suspected.
Conversely, in countries where malaria is frequent, residents often recognize the symptoms
as malaria and treat themselves without seeking diagnostic confirmation ("presumptive
treatment").
Physical findings may include:

Elevated temperatures
Perspiration
Weakness
Enlarged spleen
Mild jaundice
Enlargement of the liver
Increased respiratory rate

Diagnosis of malaria depends on the demonstration of parasites in the blood, usually by

microscopy. Additional laboratory findings may include mild anemia, mild decrease in blood
platelets (thrombocytopenia), elevation of bilirubin, and elevation of aminotransferases.