Dengue a 7-day illness, and it’s Warning Signs

There are increasing cases of dengue virus infection in the valley, and most of the patients are undergoing home-based treatment. As a rule, a small proportion of patients may go into the critical phase and develop severe dengue, which can be life threatening. There are certain signs that patients should be aware of that can be the first signs of impending severe dengue. These are called warning signs. Most of the signs are clinical, which the patients can monitor themselves at home, and some are laboratory- and imaging-based, for which they should visit a facility. If any one sign is present, the patient should go to visit for hospital-based treatment, and not to take any risk. Untreated severe dengue infection can cause mortality in 10 to 20 out of 100 cases whereas it is reduced to 1 out of 100 with appropriate treatment. This shows how much important it is to observe warning signs for taking timely appropriate steps to overcome severe dengue.

Dengue is a febrile illness caused by one of the four serotypes of Dengue virus (DENV1, DENV2, DENV3, and DENV4), which is transmitted from human-to-mosquito-to-human by the bite of an infected female Aedes mosquito. Female mosquitoes require blood to produce eggs, that’s why they bite humans for their blood meal. Human-to-mosquito transmission can occur up to two days before someone shows symptoms of the illness, and up to two days after the fever has resolved. When they bite an infected person, dengue virus gets entry into them and multiplies through their body system over a period of 8 to 12 days, and they become infectious. After this period, they can transmit dengue virus to any person whom they bite and continue transmitting the virus for their entire lifetime, which is usually three to four weeks. There is also possibility of transovarian transmission of dengue virus from infected mosquito to their offspring via eggs. It is not directly transmitted from human to human, but there is evidence of vertical transmission from infected pregnant mother to fetus during blood transfusion, organ transplantation, and needle stick injuries from infected person. Dengue is the most common and fastest spreading mosquito borne infection in the world.The incidence of dengue has increased 30-fold over the last 50 years. Each year, up to 400 million people get infected with dengue. Approximately 50-100 million people get sick from infection, and 40,000 die from severe dengue.

How to identify the Aedes mosquito
It is very important to identify the Aedes mosquito. If a single Aedes mosquito is seen in the home surroundings, there is possibility of whole cluster of them being there, and so, the infected ones as well. Preventive measures, including mosquito control and personal protection, should be done immediately and effectively to avoid dengue infection.
Aedes mosquitoes have black bodies with unique patterns of light and dark scales on the abdomen and thorax, and alternating light and dark bands on the legs. They characteristically hold their bodies low and parallel to the ground, with the tip of mouth part (proboscis) angled downward when landed. They are daytime feeders, with the peak biting period being early in the morning and in the evening before sunset. They frequently feed multiple times between each egg-laying period, leading to clusters of infected individuals. Female mosquitoes generally lay their eggs above the water line inside containers that hold water, such as tires, buckets, birdbaths, water storage jars, flower pots, and even bottle caps. They live near human habitats and don’t travel long distances during their lifetime (usually less then 200 yards).

Dengue: A 7-day illness
Dengue is usually a seven-day illness unless there are other complications. After an infected mosquito bites, the virus enters into blood circulation and undergoes multiplication. It takes 3 to 10 days, but not more than 14 days, before the symptoms start.

There are the three phases of infection:
1. Febrile phase (1 to 3 or 7 days): It is the first phase identified by sudden onset of high grade fever usually more than 38.5 °C, accompanied by headache, vomiting, eye pain, muscle pain, joint pain, and macular rashes. This phase lasts for three to seven days, after which most of the patients recover completely without any complications. Headache, eye pain, and joint pain occur in 60 to 70% of the cases. Rashes (maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with islands of skin sparing, also called “islands of white in a sea of red”) occur in about 50% of the cases. Usually, rashes occur two to five days after the onset of fever. Apart from these symptoms, some patients may experience gastrointestinal symptoms like anorexia, nausea, vomiting, abdominal pain and diarrhea, and respiratory tract symptoms like cough, sore throat, and nasal congestion. In about 4% of the cases there is biphasic fever or saddleback fever. This means that, after initial peak of fever, it goes down to normal for one to two days, and again followed by second peak of fever lasting for one to two days. Most patients go to recovery phase after seven days without appearance of critical phase.
2. Critical phase (3 to 7 days): During the first phase period of seven days, a small proportion of patients can go into critical phase. This occurs around the time of defervescence, when fever comes down typically on days three to seven, due to development of systemic vascular leak syndrome, characterized by plasma leakage, bleeding, shock, and organ impairment. This phase lasts for 24 to 48 hours.
3. Convalescent or recovery phase: During the convalescent phase, signs of critical phase resolve with resorption of accumulated fluids, characterized by stabilization of vital signs. In some cases, a confluent, erythematous rash with small areas of unaffected skin that is often pruritic may appear within one to two days of defervescence and lasting one to five days. This recovery phase typically lasts two to four days, and some may have profound fatigue for days to weeks after recovery.

Diagnosis
Probable dengue: The patient lives in or has traveled to a dengue-endemic area within the last two weeks, with symptoms including fever and two of the following: headache or eye pain, nausea or vomiting, muscle or joint pain, rash, petechia or positive torniquet test, or leucopenia (decrease in white blood cell count).

Torniquet test: It is a physical examination maneuver often performed on patients suspected of having dengue. It is a test for microvascular fragility seen in dengue infection that can be done manually in home.
• Take the patient’s BP and record it, example 120/80 mm Hg
• Inflate the BP cuff to a point midway between the systolic and diastolic pressure (120+80) /2= 100 mm Hg and wait for 5 minutes
• Count number of petechiae (pin point round spots) per sq. inch

The test is considered positive when 10 or more petechiae per square inch are observed. The test may be negative or only mildly positive in obese patients and during the phase of profound shock.

Lab test: Lab test is done in all probable dengue cases to confirm the diagnosis and monitor its complications. There are various tests to diagnose dengue infection, ranging from RT-PCR to viral culture. Dengue infection is usually diagnosed by detection of viral antigen nonstructural protein 1 (NS1), which is typically positive during the first seven days of illness. Immunoglobulin (Ig)M can be detected as early as four days after the onset of illness, and it signifies recent dengue infection. Immunoglobulin (Ig)G detection differentiates whether the infection is primary or secondary.

Primary infection means that the individual is infected with dengue virus for the first time. Secondary infection is re-infection with dengue virus with history of prior dengue infection. Dengue infection with specific serotype gives life-long immunity to that serotype. Though there is transient cross-protection among the four types, this weakens and disappears over the months following primary infection. So, secondary dengue infection signifies infection due to different serotype of dengue virus. In view of this fact, there is a maximum of four times of possibility of getting dengue virus infection in a person’s entire lifetime. Primary infection is defined as an IgM-negative/IgG-negative or IgM-positive/IgG-negative. Secondary infection is defined as an IgM-negative/IgG-positive or an IgM-positive/IgG-positive.

Primary infection is usually benign, whereas secondary infection may cause severe infection.
Most dengue infected patients recover after seven days through home-based treatment. A small proportion of patients may go into the critical phase. There are warning signs that should be monitored during home-based treatment, and if any one of them is present, they need to undergo hospital-based treatment.

Warning signs include:
• Moderate to severe abdominal pain or tenderness
• Persistent and uncontrolled vomiting
• Clinical fluid accumulation (ascites, pleural effusion)
• Mucosal bleeding (nosebleed, blood in vomitus, stool), flat bluish or purple patches commonly over skin of arms and legs
• Lethargy or restlessness
• Hepatomegaly (liver enlargement)>2 cm
• Rapid and progressive decrease in platelet count to about 100,000 cells/mm3 and a rising hematocrit above 20 % of the baseline may be the earliest signs of plasma leakage. This is usually preceded by decrease in white blood cell count (< 4000 cells/mm3). Normal hematocrit or PCV 37 to 47 % in female and 42 to 50% in male. Normal platelet count is 1.5 to 4 lakhs/microliter
Severe dengue: Warning signs are the signs of impending or existing severe dengue infection. The causes behind severe dengue are:
• Plasma leakage (plasma escapes out of blood vessels into extravascular body compartments, resulting decrease in effective circulationg blood volume and shock)
• Severe bleeding manifestations caused by low platelet count
• Severe organ involvement identified by liver (ASTor ALT level ≥1000 units/L), kidney (rise in urea/creatinine level), neurological (impaired consciousness, seizures), lungs (ARDS), etc.

Plasma leak is characterized by fluid accumulation and shock. Fluid accumulation is identified clinically by progressive abdominal distension (fluid in peritoneal cavity) and difficulty in breathing (fluid in pleural cavity) and confirmed by ultrasound and x-ray. Severe plasma leak is identified by shock, which is also known as dengue shock syndrome (DSS). Initial warning signs for severe plasma leak or impending shock include increase in diastolic blood pressure, causing progressive decrease in gap between systolic and diastolic blood pressure (less than 20mm Hg), increase in heart rate (more than 100 beats per minute) even in absence of fever, signs of some dehydration like decrease in urine output (patient should be able to pass urine in at least six-hourly gaps), dryness of tongue and eyes, dark urine, etc. Progression to shock is identified by cold and clammy skin, feeble or impalpable pulse, fall in systolic blood pressure (less than 90 mm Hg), lethargy or unconsciousness, etc.

Low platelet count, known as thrombocytopenia, may not have any symptoms. Warning signs of severe bleeding include nose bleeding, blood in vomitus, stool, bluish or purple path over skin of arms and legs.

Severe organ involvement include liver, kidney, neurological, or other isolated organ involvement, which could be due to profound shock. Neurological manifestations include febrile seizures in young children, encephalitis, aseptic meningitis, and intracranial bleeding, Gastrointestinal involvement may be seen in the form of hepatitis, liver failure, pancreatitis, or acalculous cholecystitis, and may also manifest as myocarditis, pericarditis, ARDS, acute kidney injury, or hemolytic uremic syndrome.

There should be always hospital-based treatment for severe dengue. Other situations like infancy, elderly, pregnancy, diabetes, and those living alone need to be more cautious and it is better to get admitted for hospital-based treatment.

Dengue, also called Break-bone Fever, commonly presents with high grade fever and severe muscle and joint pain. People usually visit nearby pharmacy and get some pain medicines, including ibuprofen, nimesulide, diclofenac, aceclofenac, naproxen, or aspirin, etc. As these medicines do more harm, complicating hemorrhagic manifestations of dengue, this should be avoided. Only paracetamol in a dose up to a maximum of four grams per day is recommended, and adequate fluid intake, where isotonic fluid is preferable to plain water, is the mainstay of treatment with vigilance against the warning signs and being proactive about severe dengue with timely appropriate medical intervention. Those with warning signs need to be admitted into a hospital and can be initiated on IV fluids, with fluid rate titration based on the patient’s response. Blood transfusion is warranted in case of severe bleeding or suspected bleeding when the patient remains unstable and hematocrit falls despite adequate fluid resuscitation. Platelet transfusion is considered when platelet count drops to <20,000 cells/microliter and there is a high risk of bleeding. Environmental control and personal protection is the most important but commonly overlooked aspect of dengue control measures in day-to-day life.