Differentiating Between Malaria, Dengue, Chikungunya, and Other Diseases

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Comparison Table: Malaria, Dengue, Chikungunya, Leptospirosis, and Hepatitis[edit]

In reality, these diseases may not always present in their classical form according to the table below. For instance, a second infection of dengue tends to have a worse prognosis than the first one (higher chance of becoming dengue shock syndrome (DSS)). There may also be co-infection or comorbidities, which will make diagnosis and management more complex.

Tropical Infectious Diseases
Malaria Dengue Chikungunya Leptospirosis Hepatitis B Typhoid
Agent Plasmodium parasites: P. falciparum (common and severe, 50%), P. vivax (43%), P. ovale, and P. malariae. Dengue virus 1, 2, 3, and 4. Part of the Flaviviridae family. Alphavirus Leptospira bacteria. 13 out of 21 species are pathogenic. Hepatitis B virus. Part of the Hepadnaviridae family. Salmonella bacteria: S. typhi (common and severe, 83%) and S. paratyphi (less severe).
Transmission
Anopheles mosquito

Female Anopheles mosquito (more prevalent during the night, dawn, and dusk)

Aedes aegypti mosquito

Female Aedes aegypti (most common), A. albopictus, A. polynesiensis, and A. scutellaris mosquitoes

Aedes albopictus mosquito

Female Aedes aegypti (more prevalent during the day) and Aedes albopictus mosquitoes

Rat

Urine of rats and other mammals, swallowed or via eyes, nose, or cuts. Not airborne or human-to-human.

Parenteral transmission via vaginal and anal sex is most common

Body fluids/blood. Vaginal/anal sex. Needle-sharing. Vertically, pregnant mother to child.

Contaminated water, perhaps after somebody pooped in the river where the water is sourced from

Consuming food/water contaminated with feces of an infected person.

Incubation 2 weeks, other sources: 10-21+ days 3 to 4 days 1 to 12 days 7 to 12 days 40 to 160 days, average 60 to 90 days. Other source: 2 to 24 weeks. 6 to 30 days
Natural course
  • Febrile phase: High fever, nausea, myalgia, rash, flushed face for 2-7 days.
  • Critical phase: Plasma leakage, abdominal pain, hypotension, liver tenderness for 24-48 hours.
  • Convalescent phase: Increased appetite, rash, normotension, bradycardia, decreased Hct.
  • Acute infection phase (1-14 days): High grade fever for 3-5 days. Polyarthralgia (10+ joints) begins 2-5 days after onset of fever.
  • Persistent symptoms phase: Skin manifestation (40-75%) macular or maculopapular rash. The polyarthralgia becomes more severe and can become polyarthritis, sometimes with tenosynovitis and carpal tunnel syndrome. May complicate to Raynaud's phenomenon (20%).
  • 1st phase (aka acute or septicemic phase): 3–7 days.
  • Asymptomatic phase: 3-4 days. Symptoms disappear. Bacteria in blood. Leptospira antibodies appear.
  • 2nd phase: Fever returns. Hallmark: meningitis.
  • Severe phase (10%): Liver damage (causing jaundice), kidney failure, and bleeding (aka Weil's disease).
  • Can complicate to severe pulmonary haemorrhage syndrome, which is fatal in 50% despite treatment.
  • Usually starts insidiously - with anorexia and nausea and ache in the right upper abdomen.
  • Majority asymptomatic. Indefinite nausea, vomiting, diarrhea, anorexia. More symptoms appear with severity.
  • With or without symptoms (HBsAg +) for >6 months, considered chronic (5-10%), can lead to cirrhosis or liver cancer (25-40%).
  • Rarely (0.1-0.5%), leads to (very fatal) fulminant hepatitis.
  • 1st week: Relative bradycardia. Malaise, headache, cough. Leukopenia, eosinopenia, relative lymphocytosis. Blood cultures (+) for S. typhi. Typhidot (+).
  • 2nd week: Relative bradycardia. Delirium, agitation. Rose spots (33%). Rhonchi in lung bases. Hepatosplenomegaly. Smelly pea-soup diarrhea. Transaminase elevation. Widal (+).
  • 3rd week: Complications: intestinal haemorrhage, dehydration, respiratory diseases. Platelets low.
  • 4th week: Fever subsides.
Signs and Symptoms / Physical Exam Findings
Malaria Dengue Chikungunya Leptospirosis Hepatitis B Typhoid
Skin
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Sweating

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A maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with islands of skin sparing. Petechiae spots on full body except face, from day 3-4. May turn hemorrhagic. Rash disappears under pressure.

Maculopapular-rash-pictures.png

Over face, chest from day 1-3 for 3-7 days, non-hemorrhagic. Maculopapular rash, similar to dengue. Occurs early in illness. 40-75%.

Leptospirosis-rashes.jpg

Usually over legs, from day 4-6, hemorrhagic.

Indefinite rash usually during incubation period. Acute urticaria (20%-30%). Pruritis, especially if jaundice prolonged. Uncommonly, and in chronic: bullous pemphigoid, lichen planus, Gianotti-Crosti syndrome, porphyria cutanea tarda.
Salmonella typhi typhoid fever PHIL 2215 lores.jpg

Rose spots (maculopapular rash) (25%), less visible in dark skinned people, on anterior trunk: these 2-4 mm sized, salmon-colored, raised, blanching spots usually number 5-12, and fade after 3-4 days.

Fever With or without chills.
  • Recurrent (36-48 hrs) or continuous fever in P. falciparum.
  • Tertian fever (every 2 days) in P. vivax and P. ovale.
  • Quartan fever (every 3 days) for P. malariae.
Sudden onset and occasionally biphasic pattern. 1-2 days of fever, remission for 1-2 days, relapse for 1-2 days. aka "breakbone fever" due to accompanying joint and muscle pain. Sudden onset of high fever (up to 40°C) for 1-2 days, remission for 1-2 days (defervescence), relapse for 1-2 days. With chills. With chills. 4-7 days, remission for 1-2 days, and relapse. Mild (<39°C), during incubation period.
  • 1st week: Gradual increase in temperature. (Stepladder fever in <12%).
  • 2nd week: High in afternoons.
  • 3rd week: Constantly high, reaching 40°C.
  • 4th week: Subsides.
Jaundice Mild and rare. Due to intravascular hemolysis (most common), disseminated intravascular coagulation, and, rarely, malarial hepatitis. Only 2% of DSS patients. Mild. Only in severe leptospirosis (Weil's disease). In 10% of younger children, 30-50% of adults. Accompanied by darker urine and lighter feces.
Arthralgia No joint pain. Mild joint pain, specially in febrile phase. Usually of the knees and shoulders. Severe small joint pain and arthritis (joint swelling), polyarticular, bilateral, and symmetric. Begins two to five days after onset of fever. 80%+. Mild joint pain. Not common. Indefinite. Acute and symmetric, morning stiffness.
Myalgia Body aches. Severe muscular pain, especially of the lower back, arms, and legs. And especially in febrile phase. Severe muscular pain. Severe muscular pain. Indefinite, accompanied by fatigue.
Headache Mild to severe Common. Retro-orbital pain. Common Severe and common (75-100%) Indefinite.
Nausea Yes. 50% Yes.
Other findings Enlarged spleen as a result of hemolysis. Enlargement of the liver. Mild hemorrhagic manifestations (eg, petechiae, bleeding gums, epistaxis, menorrhagia, hematuria). Altered taste sensation. Anorexia. Lymphadenopathy. Conjunctival suffusion (55%). Muscle tenderness, splenomegaly, lymphadenopathy, pharyngitis, hepatomegaly, muscle rigidity, abnormal respiratory auscultation, or skin rash occur in 7-40%. Aseptic meningitis in 50-85% if cerebrospinal fluid is examined after seven days of illness.
Lab Findings
Malaria Dengue Chikungunya Leptospirosis Hepatitis B Typhoid
Hemoglobin Low (25%, more in children)
Lymphocytes Lymphopenia. Atypical lymphocytes. Lymphopenia Lymphopenia
Thrombocytes Thrombocytopenia (50-68%) Thrombocytopenia (platelet count < 100 x 109/L) Thrombocytopenia Thrombocytopenia (39%)
Leukocytes Leukocytosis (<5%) Leukopenia Peripheral leukocytosis (3,000-26,000 x 109/L) with a left shift.
Neutrophils Neutropenia
ESR Elevated in acute phase
Liver Enzymes Mild to moderate elevation of AST and ALT. Minimal to moderate elevation (40%) of AST, ALT, and GGT. AST/ALT may be elevated (up to 2000 IU/L), in acute phase and with ALT>AST.
Other Triad of thrombocytopenia, elevated lactate dehydrogenase (LDH) levels, and atypical lymphocytes. These findings should prompt obtaining malarial smears of thick and thin (to know species) blood. Mild coagulopathy, and elevated blood urea nitrogen (BUN), and creatinine may also be found. PCR to detect viral genomic sequences. Fourfold or greater change in reciprocal IgG or IgM antibody titers to one or more dengue virus antigens. Isolation of the dengue virus from serum, plasma, leukocytes, or autopsy samples. In DHF, blood coagulation test: PT prolonged, APTT prolonged, fibrinogen low. Serology is the primary tool for diagnosis in the clinical setting. Immunoglobulin M (IgM) anti-chikungunya virus antibodies (detected by direct enzyme-linked immunosorbent assay [ELISA]) are present starting about five days (range 1 to 12 days) following onset of symptoms and persist for several weeks to three months. Immunoglobulin G (IgG) antibodies begin to appear about two weeks following onset of symptoms and persist for years. Hyponatremia is common in severe leptospirosis. Urinalysis frequently shows proteinuria, pyuria, granular casts, and occasionally microscopic hematuria. Elevated creatine kinase is observed in approximately 50% of patients and may be a useful clue. Gold standard is molecular agglutination test (MAT). A combination of blood culture and MAT has sensitivity of only 55.5%, but specificity is 98.8%. MAT requires high expertise and is only done in top labs. (Ig)M ELISA tests are done in clinical settings instead. Prothrombin time is the best indicator of prognosis. Hepatitis B surface antigen (HBsAg) is the serologic hallmark, and can be detected by radioimmunoassays (RIA) or enzyme immunoassays (EIA). HBsAg appears in serum 1 to 10 weeks after an acute exposure, before symptoms and liver enzyme elevation.
Management
Malaria Dengue Chikungunya Leptospirosis Hepatitis B Typhoid
Prevention Avoid exposure to mosquitoes by not going out at feeding times, using mosquito nets, long-sleeved clothing, and insect repellent. Chemoprophylaxis with antimalarials is recommended before traveling to an endemic area. There is no vaccine. No antiviral agents have been proven to be effective. Minimize mosquito exposure. Doxycycline once a week can be used as chemoprophylaxis to minimize infections during outbreaks in endemic regions. Clean water and rat control can help. Human and animal vaccines are becoming available but still not widespread, not for all species of leptospira, and not effective for long periods. A typhoid vaccine, recommended for high risk people or those traveling to endemic zones, can prevent 30-70% of cases during the first two years and remain partially effective for up to 7 years.
Patient Education
Hospitalization Patients with elevated parasitemia (>5% of RBCs infected), CNS infection, or otherwise severe symptoms and those with P falciparum infection should be considered for inpatient treatment to ensure that medicines are tolerated. Admission for intravenous fluid administration is indicated for patients who develop signs of dehydration. Patients with poor immune systems (elderly, young, immunosuppressed, etc) may require hospitalization. 20-30% are hospitalized for around a couple of days. Rare after correct diagnosis of leptospirosis, and only if severe or if there are complications. However, many patients (especially in dengue-endemic areas) are misdiagnosed as having dengue and admitted. Severe cases of leptospirosis can affect any organ system and can lead to multiorgan failure so these patients must be admitted and continuously monitored for cardiac and renal dysfunction. Usually recommended if there are severe symptoms such as persistent vomiting, severe diarrhea, or abdominal distention. As a precaution, young children are admitted.
Medication
  • P Falciparum: Quinine-based therapy is with quinine (or quinidine) sulfate plus doxycycline or clindamycin or pyrimethamine-sulfadoxine; alternative therapies are artemether-lumefantrine, atovaquone-proguanil, or mefloquine
  • P vivax, P ovale: Chloroquine plus primaquine. But recently there's some evidence for combination of dihydroartemisinin-piperaquine with primaquine.

Oral rehydration therapy. There is no antiviral medication available. Patients with DHF or DSS may require IV volume replacement. Plasma volume expanders can be used in patients who do not respond to isotonic fluids. Acetaminophen (paracetamol) for pain and fever.

Treatment consists of supportive care including anti-inflammatory agents that relieve symptoms in many patients, and analgesic agents for pain relief. Severe leptospirosis: IV penicillin G and 3rd-gen cephalosporins. Mild leptospirosis: Doxycycline, Ampicillin, or amoxicillin. Pregnant patients or allergic to penicillin: Erythromycin. Glucose and salt solution infusions. Dialysis is used in serious cases. Calcium carbonate if hyperphosphatemia occurs. Antiviral drugs, commonly: entecavir and tenofovir. Azithromycin, fluoroquinolones, or third generation cephalosporins. Consider the rapidly growing antibiotic resistance when prescribing.

Sensitivity: cefotaxime (100.0%), ceftriaxone (98.9%), ofloxacin (93.5%), cotrimoxazole (93.5%), chloramphenicol (93.2%).

Malaria Dengue Chikungunya Leptospirosis Hepatitis B Typhoid
Dengue shock vs. septic shock
Dengue phases: febrile, critical, recovery
Dengue phases
Dengue manifestations
Dengue, severe dengue, warning signs

Malaria[edit]

P. falciparum is the most dangerous type of malarial infection. It can cause cerebral malaria in which red blood cells infected by the parasite stick to small blood vessels in the brain. This reduces the flow of blood and the supply of oxygen and nutrients to the brain. If untreated, cerebral malaria can kill the patient in 24–48 hours. It most commonly affects young children. There are also other life-threatening complications of malaria such as hypoglycemia, liver dysfunction, kidney failure, and lactic acidosis.

The distinctive chills in malaria are caused by rapid changes in body temperature. They result from involuntary muscle contractions that occur in response to a sudden lowering of body temperature below the prevailing set point. (Source). So, note that any disease that causes sudden, high fever may cause chills, not just malaria.

Measles, Mumps, Rubella[edit]

Measles is a disease which usually produces fever, cough, conjunctivitis ("pink eye"), a red, bumpy rash, and a rash ("Koplik spots") inside the cheeks. Keep the possibility of measles in mind when faced with these symptoms, which may be similar to the ones presented above.

Typhoid[edit]

aka "enteric fever". Bone marrow culture is the most sensitive routinely available diagnostic tool. Serologic tests such as the Widal test are of limited clinical utility in endemic areas because positive results may represent previous infection.

Typhoid vs Typhus[edit]

Unfortunately, most Indonesians often mix two different diseases together without knowing it: Typhoid Fever and Typhus. They call Typhoid Fever "typhus" (written as "tipus" in Indonesian) and simply don't know that another disease called typhus actually exists. So, if you're one of these people, please stop referring to Typhoid Fever as "typhus".

Cholera[edit]

From Medscape:

Cholera is an intestinal infection caused by Vibrio cholerae. The hallmark of the disease is profuse secretory diarrhea.

The activation of the A1 subunit by adenylate cyclase is responsible for the net increase in cyclic adenosine monophosphate (cAMP). cAMP blocks the absorption of sodium and chloride by the microvilli and promotes the secretion of chloride and water by the crypt cells. The result is watery diarrhea with electrolyte concentrations isotonic to those of plasma.

Fluid loss originates in the duodenum and upper jejunum; the ileum is less affected. The colon is usually in a state of absorption because it is relatively insensitive to the toxin. However, the large volume of fluid produced in the upper intestine overwhelms the absorptive capacity of the lower bowel, resulting in severe diarrhea.

Management[edit]

Set the rate of intravenous infusion in severely dehydrated patients at 50-100 mL/kg/hr. Lactated Ringer solution is preferred over isotonic sodium chloride solution because saline does not correct metabolic acidosis.

The goal of the maintenance phase is to maintain normal hydration status by replacing ongoing losses. The oral route is preferred, and the use of oral rehydration solution (ORS) at a rate of 500-1000 mL/hr is recommended.

Antibiotic treatment is indicated for severely dehydrated patients who are older than 2 years. Because single dose doxycycline has been shown to be as effective as multiple doses of tetracycline, this has become the preferred regimen.

Links[edit]