What are the key facts about dengue fever? How does dengue fever present clinically? What are the warning signs of severe dengue? What are the different phases of dengue fever?

Key Facts About Dengue Fever

Dengue fever is a viral infection that can range from asymptomatic to severe, life-threatening disease. An estimated one in four dengue virus infections are symptomatic, with the most common presentation being a mild to moderate, nonspecific, acute febrile illness. Infection with one of the four dengue viruses will induce long-lasting immunity for that specific virus, but people can be infected with DENV multiple times in their life. Approximately one in 20 patients with dengue virus disease progress to develop severe, life-threatening severe dengue, with the second infection with DENV being a risk factor for this more severe form.

Clinical Presentation of Dengue Fever

The early clinical findings of dengue fever are nonspecific, but require a high index of suspicion as recognizing the early signs of shock and promptly initiating intensive supportive therapy can reduce the risk of death among patients with severe dengue to less than 0.5%. The World Health Organization (WHO) guidelines for classifying dengue define dengue as a combination of at least two clinical findings in a febrile person who traveled to or lives in a dengue-endemic area, including nausea, vomiting, rash, aches and pains, a positive tourniquet test, leukopenia, and the following warning signs: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, and liver enlargement.

Severe Dengue and Warning Signs

Severe dengue is defined by dengue with any of the following symptoms: severe plasma leakage leading to shock or fluid accumulation with respiratory distress; severe bleeding; or severe organ impairment such as elevated transaminases ≥1,000 IU/L, impaired consciousness, or heart impairment. The presence of a warning sign may predict the progression to severe dengue in a patient.

The Three Phases of Dengue Fever

Dengue fever follows three distinct phases: the febrile phase, the critical phase, and the convalescent phase. The febrile phase typically lasts 2-7 days and can be biphasic, with symptoms including severe headache, retro-orbital eye pain, muscle, joint, and bone pain, macular or maculopapular rash, and minor hemorrhagic manifestations. The critical phase begins at defervescence and typically lasts 24-48 hours, during which time most patients clinically improve, but those with substantial plasma leakage can develop severe dengue as a result of a marked increase in vascular permeability. The convalescent phase follows the critical phase, during which time the patient’s condition typically improves.

Recognizing the Warning Signs of Severe Dengue

The warning signs of progression to severe dengue occur in the late febrile phase around the time of defervescence, and include persistent vomiting, severe abdominal pain, fluid accumulation, mucosal bleeding, difficulty breathing, lethargy/restlessness, postural hypotension, liver enlargement, and progressive increase in hematocrit (i.e., hemoconcentration). Recognizing these warning signs early and promptly initiating intensive supportive therapy can significantly reduce the risk of death among patients with severe dengue.

The Importance of Early Recognition and Intervention

Early clinical findings in dengue fever are often nonspecific, but require a high index of suspicion as recognizing the early signs of shock and promptly initiating intensive supportive therapy can reduce the risk of death among patients with severe dengue to less than 0.5%. Clinicians should be vigilant in monitoring for the warning signs of progression to severe dengue, which occur in the late febrile phase around the time of defervescence, and be prepared to provide timely and appropriate supportive care to those patients at risk of developing life-threatening complications.

The Evolution of Dengue Case Definitions

From 1975 through 2009, symptomatic dengue virus infections were classified according to the WHO guidelines as dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (the most severe form of DHF). However, the case definition was changed to the 2009 clinical classification after reports that the previous definition was both too difficult to apply in resource-limited settings and too specific, as it failed to identify a substantial proportion of severe dengue cases, including cases of hepatic failure and encephalitis. The 2009 clinical classification has been criticized for being overly inclusive, as it allows several different ways to qualify for severe dengue, and nonspecific warning signs are used as diagnostic criteria for dengue. Additionally, the new guidelines have been criticized for not defining the clinical criteria for establishing severe dengue (with the exception of providing laboratory cutoff values for transaminase levels), thereby leaving severity determination up to individual clinical judgment.

Clinical Presentation | Dengue | CDC

Key Facts

• Dengue can range from asymptomatic infection or mild illness to severe disease.
• An estimated 1 in 4 dengue virus infections are symptomatic. Symptomatic dengue virus infection most commonly presents as a mild to moderate, nonspecific, acute febrile illness.
• Infection with one of the four dengue viruses will induce long-lived immunity for that specific virus.
• Because there are four dengue viruses, people can be infected with DENV multiple times in their life.
• Approximately 1 in 20 patients with dengue virus disease progress to develop severe, life-threatening disease called severe dengue.
  • The second infection with DENV is a risk factor for severe dengue.
• Early clinical findings are nonspecific but require a high index of suspicion because recognizing early signs of shock and promptly initiating intensive supportive therapy can reduce risk of death among patients with severe dengue to <0. 5%.
• See Box 3-01 for information regarding the World Health Organization (WHO) guidelines for classifying dengue.

In November 2009, WHO issued a new guideline that classifies symptomatic cases as dengue or severe dengue.

Dengue is defined by a combination of ≥2 clinical findings in a febrile person who traveled to or lives in a dengue-endemic area. Clinical findings include nausea, vomiting, rash, aches and pains, a positive tourniquet test, leukopenia, and the following warning signs: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, and liver enlargement. The presence of a warning sign may predict severe dengue in a patient.

Severe dengue is defined by dengue with any of the following symptoms: severe plasma leakage leading to shock or fluid accumulation with respiratory distress; severe bleeding; or severe organ impairment such as elevated transaminases ≥1,000 IU/L, impaired consciousness, or heart impairment.

From 1975 through 2009, symptomatic dengue virus infections were classified according to the WHO guidelines as dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (the most severe form of DHF). The case definition was changed to the 2009 clinical classification after reports that the case definition of DHF was both too difficult to apply in resource-limited settings and too specific, as it failed to identify a substantial proportion of severe dengue cases, including cases of hepatic failure and encephalitis. The 2009 clinical classification has been criticized for being overly inclusive, as it allows several different ways to qualify for severe dengue, and nonspecific warning signs are used as diagnostic criteria for dengue. Lastly, the new guidelines have been criticized because they do not define the clinical criteria for establishing severe dengue (with the exception of providing laboratory cutoff values for transaminase levels), thereby leaving severity determination up to individual clinical judgment.

Dengue begins abruptly after a typical incubation period of 5–7 days, and the course follows 3 phases: febrile, critical, and convalescent.

Febrile Phase

• Fever typically lasts 2–7 days and can be biphasic.
• Other signs and symptoms may include severe headache; retro-orbital eye pain; muscle, joint, and bone pain; macular or maculopapular rash; and minor hemorrhagic manifestations including petechia, ecchymosis, purpura, epistaxis, bleeding gums, hematuria, or a positive tourniquet test result.
• Some patients have injected oropharynx and facial erythema in the first 24–48 hours after onset.

Warning Signs

Warning signs of progression to severe dengue occur in the late febrile phase around the time of defervescence, and include persistent vomiting, severe abdominal pain, fluid accumulation, mucosal bleeding, difficulty breathing, lethargy/restlessness, postural hypotension, liver enlargement, and progressive increase in hematocrit (i. e., hemoconcentration).

Critical Phase

• The critical phase of dengue begins at defervescence and typically lasts 24–48 hours.
• Most patients clinically improve during this phase, but those with substantial plasma leakage can, within a few hours, develop severe dengue as a result of a marked increase in vascular permeability.
• Initially, physiologic compensatory mechanisms maintain adequate circulation, which narrows pulse pressure as diastolic blood pressure increases.
• Patients with severe plasma leakage may have pleural effusions, ascites, hypoproteinemia, or hemoconcentration.
• Patients may appear to be well despite early signs of shock. However, once hypotension develops, systolic blood pressure rapidly declines, and irreversible shock and death may ensue despite resuscitation.
• Patients can also develop severe hemorrhagic manifestations, including hematemesis, bloody stool, or menorrhagia, especially if they have been in prolonged shock. Uncommon manifestations include hepatitis, myocarditis, pancreatitis, and encephalitis.

Convalescent Phase

• As plasma leakage subsides, the patient enters the convalescent phase and begins to reabsorb extravasated intravenous fluids and pleural and abdominal effusions.
• As a patient’s well-being improves, hemodynamic status stabilizes (although he or she may manifest bradycardia), and diuresis ensues. The patient’s hematocrit stabilizes or may fall because of the dilutional effect of the reabsorbed fluid, and the white cell count usually starts to rise, followed by a recovery of platelet count.
• The convalescent-phase rash may desquamate and be pruritic.

Laboratory findings commonly include leukopenia, thrombocytopenia, hyponatremia, elevated aspartate aminotransferase and alanine aminotransferase, and a normal erythrocyte sedimentation rate.

Dengue During Pregnancy

• Data are limited on health outcomes of dengue in pregnancy and effects of maternal infection on the developing fetus.
• Perinatal transmission can occur, and peripartum maternal infection may increase the likelihood of symptomatic infection in the newborn.
• Of 41 perinatal transmission cases described in the literature, all developed thrombocytopenia, most had evidence of plasma leakage evidenced by ascites or pleural effusions, and fever was absent in only two cases. Nearly 40% had a hemorrhagic manifestation, and 1 in 4 had hypotension.
• Perinatally infected neonates typically become ill during the first week of life.
• Placental transfer of maternal IgG against dengue virus (from a previous maternal infection) may increase risk for severe dengue among infants infected at 6–12 months of age, when the protective effect of these antibodies wanes.

How long does it take for a dengue fever rash to go away?

This is an automatically translated article.

In case a patient has dengue fever until about the 7th day of the illness, and the rash appears itchy papule, it is most likely a sign that the dengue fever is about to recover.

1. How long does it take for a patient to have a dengue fever rash?

No more itchy dengue rash Usually, dengue fever clears up on its own within 7 days. From the onset of fever to the appearance of the rash on the body is about 2-3 days. About 3 to 4 days later, the itchy dengue rash will continue to appear and become more and more dense. This is one of the clearest signs that the disease is still progressing.
How long the dengue rash will go away depends on the time when the patient’s body does not appear new red hemorrhagic spots.
Body reduces fatigue Expression of a high fever of 39oC or higher for 2-3 consecutive days is a warning sign that the patient may have dengue fever. At this time, it is necessary to quickly transfer the patient to a medical facility for an accurate examination and diagnosis. Usually, the dangerous phase of dengue fever is marked by high fever continuously lasting for the first 3 days, the next 2-3 days is the time when dangerous complications are likely to appear. Currently, the patient’s body is tired and exhausted.
If it has been 1 week since the onset of fever, but the patient feels that his body is gradually getting better, it means that the disease is recovering, the dengue rash will no longer appear.
Increased excretion Dengue causes the patient’s body to become severely dehydrated, resulting in a small amount of urine, sometimes only a very small part of what it usually is. That is why dengue patients should replenish water and electrolytes to make up for the loss.
When the patient can have almost normal bowel movements, accompanied by more urine and approximately the same amount as before dengue fever, it is also a sign that dengue fever is about to go away.
Eat better Having dengue fever, whether severe or mild, will make the patient’s body exhausted, tired and anorexia, even in many cases the patient can only drink water, slurp porridge.
If one day the patient feels able to eat, the feeling of wanting to eat, appetite, and eating is more appetizing, then the signs of dengue fever are tending to decrease.

Nếu bạn có cảm giác thèm ăn, ăn ngon miệng hơn thì dấu hiệu sốt xuất huyết đang có chiều hướng thuyên giảm

2. What should be done to get rid of dengue fever quickly?

How long it takes for a dengue fever rash to go away depends a lot on the time of examination, treatment and patient care regimen. During the first 3 days of having a fever and detecting illness, the patient should calmly rest and reduce fever at home. On the 4th day, the patient needs to go to the hospital for a follow-up examination (or according to the doctor’s appointment). The patient care regimen should pay attention to the following:
Rest and rehydration First, the patient should take time to rest and arrange to go to the medical facility for examination. When the patient has been to the nearest medical facility, the patient is examined and confirmed to have dengue fever (through test results), at this time the patient should rest at home and actively monitor according to the doctor’s instructions. When the body is having a high fever and itchy rash, focus on resting, reducing fever, drinking enough water, replenishing electrolytes and adequate nutrition. Do not be too confused, worry, go to many places, take medicine arbitrarily because it can seriously affect the patient’s health, making the disease even more complicated.

Không nên tự ý dùng thuốc tùy tiện

Do not arbitrarily use antipyretics At the onset of fever, because it is not yet determined exactly what disease the fever is caused by, the patient needs to go to the doctor to determine exactly, do not arbitrarily use these drugs. hypothermia, especially aspirin and ibuprofen. These two drugs can make the hemorrhagic rash worse, potentially leading to severe, life-threatening stomach bleeding.
Instead, family members can reduce the patient’s fever by having the patient wear light, airy clothes, rest in a well-ventilated place, apply a towel soaked in warm water, squeeze it out, and place it on the patient’s forehead or armpit. to lower body temperature. If you want to take the drug, use it only after consulting your doctor. Absolutely do not shave the patient’s wind.
Do not go to the wind and take a cold shower. The body of a person with a dengue fever rash is very weak and sensitive to cold. Therefore, patients should only rest at home, should not go to the wind, do not take cold showers. When cleaning the body, it should be done by wiping the body with warm water. Cold water has the ability to cause vasoconstriction on the skin, but it dilates the vessels inside the internal organs, which can lead to sudden death if the person is in poor health.
After the dangerous period, the patient with a dengue fever rash will enter the recovery phase and recover from the disease. At this stage, the patient begins to relieve symptoms, stops the rash, begins to recover gradually, has appetite, and hemodynamic tests gradually return to normal.
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Fatal dengue fever

Fatal dengue fever

Website of the publishing house “Media Sfera”
contains materials intended exclusively for healthcare professionals. By closing this message, you confirm that you are a registered medical professional or student of a medical educational institution.

Nadeev A.P.

SBEE HPE “Novosibirsk State Medical University” of the Ministry of Health of Russia

Maltseva Yu.G.

National Healthcare Institution “Road Clinical Hospital at Novosibirsk-Glavny Station”, Novosibirsk, Russia

Shishkina E.Yu.

National Healthcare Institution “Road Clinical Hospital at Novosibirsk-Glavny station”, Novosibirsk, Russia

Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk, Russia;
National Healthcare Institution “Road Clinical Hospital at Novosibirsk-Glavny Station”, Novosibirsk, Russia

Khokhlova N.I.

Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk, Russia

Fatal dengue fever

Authors:

Nadeev A.P., Maltseva Yu.G., Shishkina E.Yu., Porotnikova E . V., Khokhlova N.I.

More about the authors

Magazine:

Archive of pathology.

2020;82(1): 52‑55

DOI:

10.17116/patol20208201152

How to quote:

Nadeev A.P., Maltseva Yu.G., Shishkina E.Yu., Porotnikova E.V., Khokhlova N.I. Dengue fever with fatal outcome. Pathology archive.
2020;82(1):52‑55.
Nadeev AP, Maltseva YuG, Shishkina EYu, Porotnikova EV, Khokhlova NI. Fatal dengue fever. Arkhiv Patologii. 2020;82(1):52‑55. (In Russ.)
https://doi.org/10.17116/patol20208201152

Read metadata

Dengue fever is an acute zoonotic infection from the group of viral hemorrhagic fevers, transmitted by a vector-borne route. Since 2013, mandatory registration of cases of dengue fever has been introduced in Russia. The article presents data on the epidemiology, etiology and pathogenesis of dengue fever, as well as the observation of a fatal outcome in a severe form of dengue fever, and describes morphological changes in organs and tissues.

Keywords:

dengue fever

death

morphology

Authors:

Nadeev A.P.

SBEE HPE “Novosibirsk State Medical University” of the Ministry of Health of Russia

Maltseva Yu.G.

National Healthcare Institution “Road Clinical Hospital at Novosibirsk-Glavny Station”, Novosibirsk, Russia

Shishkina E.Yu.

National Healthcare Institution “Road clinical hospital at Novosibirsk-Glavny station”, Novosibirsk, Russia

Porotnikova E.V.

Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk, Russia;
National Healthcare Institution “Road Clinical Hospital at Novosibirsk-Glavny Station”, Novosibirsk, Russia

Khokhlova N.I.

Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk, Russia

Close metadata

Dengue fever (DF) is an acute zooanthroponotic infection from the group of viral hemorrhagic fevers transmitted by transmissible means. In the last half century, the incidence of LD has increased 30 times, occurs in more than 100 countries of the world, about 39 people have been ill with LD.0 million people [1]. The development of tourism causes an increase in the number of imported cases of LD. In Russia, the first imported cases of LD among tourists were registered in March 2010, and since 2013, mandatory registration of LD cases has been introduced, the number of which is growing every year: in 2010–2012. 71 cases were detected, in 2013 – 170, in 2014 – 105 cases, in 2015 – 136, in 2016 – 140, in 2017 – 163 [2]. The Novosibirsk region is one of the regions with frequent registration of imported LD: in 2011 – 4 cases, in 2012 – 10, in 2013 – 13, in 2014 – 12, in 2015 – 6, in 2016 — 15 in 2017, 15 in 2018, and 22 in 2018. Before the disease, all patients visited countries endemic for LD (mainly Thailand, but also India, Vietnam) [3, 4].

LD pathogens are arboviruses of the antigenic group B, belonging to the family Flaviviridae , genus Flavivirus . There are 4 subtypes of the DENV-1-4 virus. The source of infection is a sick person, monkeys and bats. The transmission of infection from a sick person is carried out by mosquitoes mainly of the species Aedes aegypti and Aedes albopictus [5].

LD occurs in two forms: classical (DF), which has a favorable prognosis and develops during primary infection, and hemorrhagic/shock (DHF/DSS), which occurs upon re-infection with another virus serotype in immune individuals and is characterized by a shock pattern, and/or the development of massive bleeding, and / or severe organ failure. In 2009The WHO recommended a new classification of LD for use, distinguishing LD without precursors ( warning sign ), LD with precursors, and severe LD [6]. In the pathogenesis of severe (shock/hemorrhagic) LD, the main role is played by antibody-dependent damage to the vascular endothelium, followed by an increase in the permeability of the vascular wall, loss of plasma, and hemorrhages [5, 7]. Tourists who repeatedly visit regions endemic for LD have an increased risk of recurrence of the disease with the development of its severe form. About 500 thousand cases of severe LD are registered annually in the world with a mortality rate of 10% in hospitalized and 30% in non-hospitalized patients [6]. In 2014, the first case of death in a woman with LD shock syndrome was registered in Russia [8].

Here is the first case of fatal LD ​​in Novosibirsk in 2018.

A 42-year-old female patient was admitted to the intensive care unit of a city hospital on April 4 with complaints of severe weakness, sleep disturbance, and muscle pain. From the anamnesis it is known that from March 12 to March 24 she was on vacation in Thailand (Phuket), where she noticed mosquito bites on herself. The patient had visited Thailand several times before. Since March 29, a fever to febrile numbers has appeared. On March 30, weakness began to grow against the backdrop of a persistent fever. Since March 31, a decrease in body temperature to subfebrile figures was noted, but weakness remained. From April 2, the condition worsened: a sharp increase in asthenic symptoms, “twisting pains” in the muscles and joints, once loose stools without pathological impurities, nausea, anorexia. On April 3, vomiting joined, the patient called an ambulance, but refused hospitalization. Since complaints persisted, symptoms of hypotension increased, on the evening of April 4, she called an ambulance again and was hospitalized in the intensive care unit due to a serious condition due to the presence of infectious-toxic shock, water-electrolyte exicosis, anuria.

At admission, the general blood test showed signs of pronounced blood clotting: hemoglobin 192 g/l, erythrocytes 6.4 l, platelets 192 10 ⁹ /l, biochemical analysis showed an increase in transaminases in dynamics: ALT 84 U/L, AST 256 U/L, increase in urea up to 11.8 mmol/L, increase in troponin level up to 5938, creatine phosphokinase (CPK) up to 12,000 units, CPK MB 144 units, an increase in the level of C-reactive protein up to 24 units, a decrease in total protein and albumin (52 and 25 g/l, respectively).

Given the positive rapid test for LD (detection of NS1Ag dengue virus in the blood by immunochromatography) performed at the City Infectious Disease Clinical Hospital No. 1 (Novosibirsk), a provisional diagnosis was made: dengue fever. The patient was examined by an infectious disease doctor, samples were taken for LD and other especially dangerous infections, which were sent to the Vector State Scientific Center for Virology and Biotechnology (Novosibirsk).

Despite ongoing intensive therapy, the patient progressed multiple organ failure (cardiovascular, renal), anuria and hypotension persisted against the background of maximum doses of vasopressors and stimulation of diuresis, renal replacement therapy was constantly performed. Cardiac arrest occurred on April 4 at 18:00, the resuscitation measures carried out had a positive effect. At 19h repeated cardiac arrest, resuscitation had no effect. At 19:30, biological death was declared. The patient spent 21 hours in the hospital

Final clinical diagnosis. Main disease: dengue fever, severe course. Complications: systemic inflammatory response syndrome; shock of mixed genesis; multiple organ failure; perimyocarditis.

The results from the State Scientific Center for Biomedical Medicine “Vector” were received the next day after the death: NS1 of the dengue virus antigen and immunoglobulins of classes M and G to the dengue virus were detected in the blood by immunochromatography.

When conducting a pathological-anatomical examination in the pleural cavities, 200 ml of liquid mixed with blood. Heart weighing 350 g, in a heart shirt about 150 ml of liquid stained with blood. The myocardium is red-brown in color with small light brown specks along the back, bottom and side walls, septum. The cavity of the right ventricle is somewhat enlarged, traces of liquid blood in the lumen of the cavities. The wall thickness of the left ventricle is 1.5 cm, the right ventricle is 0.4 cm. Histological examination: plethora in the heart, foci of microhemorrhages, severe interstitial edema; lipofuscinosis of cardiomyocytes, small multiple foci of necrosis; in the interstitium, there are foci of lymphoplasmacytic infiltration (see figure). Myocarditis in dengue fever. Interstitial edema, foci of necrosis of cardiomyocytes, interstitial infiltration by lymphocytes, macrophages, plasma cells. Stained with hematoxylin and eosin, ×100. Striated muscles: foci of microhemorrhages, pronounced dystrophy, in some places there is no transverse striation of rhabdomyocytes, lymphocytic infiltration in the capillary wall. In the vessels of the microvasculature, plethora, desquamation of endotheliocytes, fibrin thrombi.

Based on the clinical picture, the results of virological and morphological studies, a pathological and anatomical diagnosis was formulated. Underlying disease: A91. Dengue fever (reference study of blood serum by immunochromatography (date): the presence of NS1 antigen of the dengue virus, specific antibodies of classes M and G to the dengue virus): productive-necrotic interstitial myocarditis, serous pericarditis (150 ml). Small multiple focal necrosis in the muscles. Sludge, thrombi in the vessels of the microvasculature. Focal hemorrhages in the mucous and serous membranes in the parenchyma of the internal organs. Complications: bilateral hydrothorax. Shock of mixed genesis: necronephrosis, centrobular necrosis in the liver, distelectasis in the lungs.

Thus, the pathoanatomical study confirmed shock LD with damage to the heart (interstitial myocarditis with small multiple focal necrosis of cardiomyocytes), vessels of the microcirculatory bed and small caliber (desquamation of the endothelium with exposure of the basement membrane) with lymphocytic infiltration, with the development of severe interstitial edema, blood clots, sludges and hemorrhages in parenchymal organs. Shock of mixed genesis (toxic and cardiogenic) was the direct cause of death.

Morphological changes in the organs and tissues of the deceased with LD are non-specific, therefore, when formulating a pathoanatomical conclusion in LD, the results of a virological study and epidemiological anamnesis data are important.

The authors declare no conflict of interest.

The authors declare no conflict of interest.

Information about authors

Nadeev A.P. — https://orcid.org/0000-0003-0400-1011; e-mail: [email protected];

Maltseva Yu.G. — https://orcid.org/0000-0002-7434-5699

Shishkina E.Yu. — https://orcid.org/0000-0001-75243-2479

Porotnikova E.V. — https://orcid.org/0000-0003-0763-560X

Khokhlova N.I. — https://orcid.org/0000-0003-4497-3173



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