DENGUE VIRUS & Its SPREAD BY MOSQUITOES:
Dengue fever is a viral infection caused by dengue virus which has four serotypes said to be serotype 1, 2, 3 and 4. In Pakistan the most common serotypes involved are 2 and 3.
The vector of dengue fever is aedes aegypti mosquito but in Pakistan it has been seen that in 50 percent of the cases aedes albopticus mosquito is also involved. Only the female mosquitoes of these before mentioned types are responsible for spread of dengue virus as they lay eggs and need proteins for that purpose and they get that protein from the blood of human beings. Male mosquitoes don’t bite and so are not involved in the spread.
These mosquitoes have a life cycle of total of 2 weeks out of which first week is for the maturation of mosquito and the second week is for reproductive cycle in which these female mosquitoes lay eggs. Every mosquito can lay around 600 eggs in its life , 300 being at a time. These eggs can stay at any place for about 9 months till the weather becomes favorable upon which eggs hatch. Breeding places of these mosquitoes are mostly damp places and clean water outdoor. Parks, pools, lakes, green places which are watered every day being at the top of the list. But the mosquito itself likes to live indoor and usually is seen under the sofa or beds etc and so it mostly bits on ankles and feet. A research has shown that its sting has some local anesthetic effect due to which when the mosquito bites person usually does not feel any pain. The mosquito has white stripes on its body and is very fast and quick. So its like a commando equipped with best ammo ever and with all the abilities of hiding and being very quick. So it’s a bit difficult to smash it if you try to. When the mosquito bites a person with dengue virus in its blood the virus gets transferred to the mosquito. It multiplies in the mosquito and it takes around 2 days to reach tissues of the mosquito and ultimately its salivary glands so that the mosquito might be able to transfer it further to others. So it means that if any aedes aegypti bites a dengue patient and bites you immediately you may not get dengue fever. Furthermore when these mosquitoes with viruses bite human, symptoms develop after around 2 days. So if you develop symptoms of dengue then it does not mean that a mosquito just bit you. Keep it clear that these are due to some mosquito which bit you about 2 days ago. And as its painless sting so you can never be sure when that happened.
** ASYMPTOMATIC
**SYMPTOMATIC
Symptomatic dengue fever can be
1. Undifferentiated fever
2. Classical dengue fever
3. Dengue haemorrhagic fever
Classical dengue fever can further be:
i) Classical dengue fever without thrombocytopenia
ii) Classical dengue fever with thrombocytopenia either with unusual bleeds or without unusual bleeds.
Dengue hemorrhagic fever can further be:
i) Dengue hemorrhagic fever without shock
ii) Dengue shock syndrome (DSS)
IMMUNITY AGAINST DENGUE VIRUS:
As we know that there are four serotypes of dengue virus its very interesting to know that when a mosquito gives you dengue fever infection of any one serotype you get a life long immunity against that serotype. For example if an aedes egypti with dengue virus 1 bites you and you get dengue fever and then you get fine after 10 days, then life long if any aedes would bite you with dengue virus 1 you wouldn’t get dengue fever because you already would have enough anti bodies to avoid any infection. But when you get dengue infection with one serotype you get immunity from other serotypes for just 6 months. For example in same above case after 10 days when person would get fine, for next six months he cant have dengue fever because he has acquired immunity against all serotypes viruses but after 6 months he can have dengue fever from serotype 2,3 and 4 but not from 1 for which he has got life time immunity now.
One more thing to discuss here is that dengue virus is the only virus which has got ANTIBODY MEDIATED REPLICATION. It means that if you have antibodies against any of the serotypes of the dengue virus in your blood and you get infection with some other serotype then the viral multiplication in the blood would be very fast as the antibodies already present in the blood would help it. That is the reason that the secondary infection of dengue is more dangerous as compared to primary (first time) and is more involved in dengue hemorrhagic fever with shock.
MISCONCEPTIONS About Dengue Hemorrhagic Fever:
1. “People think that a mismanaged case of dengue fever gets converted into dengue hemorrhagic fever. That’s totally wrong. Dengue fever classic and dengue hemorrhagic fever both are different diseases. Though they both present in the same way in the start but the hemorrhagic fever is hemorrhagic from the very first day while the dengue fever classic or whatever starts from very first day. These types are not inter convertible. “
2. “A second misconception is that dengue haemorrhagic fever is different from dengue fever classic on the basis of bleeding (hemorrhage). Its wrong too. A case of dengue fever classic can have bleeding while a person can have dengue hemorrhagic fever without having any bleeding. We will further discuss that how we would know that person has classic or hemorrhagic fever. So it is very important that we clear these misconceptions from our minds.”
Presentation OF DENGUE FEVER :
Dengue fever has a duration of around 10 days(in most of the cases) . For ease of understanding we will divide these 10 days into three spans:
1 to 3 days… Common duration
4 to 6 days… Dangerous duration needs appropriate diagnosis
7 to 10 days… Resolution phase
COMMON DURATION (1ST DAY TO 3RD DAY):
By common duration we mean the first 3 days of dengue fever infection. I termed it as the common duration as it’s the time period during which you are not sure what you are dealing with and all the types of dengue fever may it be classic or hemorrhagic have same symptoms during this period and you can never diagnose the type of dengue. If we see a typical case scenario in which patient gets bitten from aedes egypti mosquito which had already bitten a dengue patient 2 days before. After 2 days of mosquito bite the patient may develop symptoms like
** High grade fever around 104 C
** Nausea
** Vomiting
** Head aches
** Muscle and back aches
** Retro orbital pains
** Sever weakness
The symptoms and presentations of patients vary a lot. You may get a patient who may present just with severe weakness without any fever or vomiting or aches and you will further see that he has dengue fever. So the symptoms vary and so the involvement of labs is very important to diagnose the dengue fever. All what we discussed is happening to the patient in first three days and all the patients of dengue either classic or hemorrhagic would present with same symptoms during first 3 days and you cannot tell the difference. Even the lab tests cannot tell us the difference and diagnosis but still its advisable for the patient to get his serial CBC done during these 3 days so that we may get reference values for comparison with deranged ones coming later in the disease.
DANGEROUS DURATION WITH APPROPRIATE DIAGNOSIS (4TH TO 6TH DAY)
Usually the fever of the patient goes during this duration. So its very important to advise the patient that as long as you have fever you are in the safe duration but as soon as your fever would subside must report to a doctor as that’s the time when we have to decide whether patient has dengue hemorrhagic fever or dengue classical fever. During this duration we can make accurate diagnosis of the type of dengue fever. For that purpose we will make use of some signs and some lab test which are as follows
Sings indicating that patient might be going in dengue hemorrhagic fever
1. Persistent vomiting
2. Right hypochondrium pain due to associated hepatitis
3. Decreased pulse pressure
If you see these three sings in any patient on his 4th day onwards of disease suspect dengue hemorrhagic fever in him and get lab tests done and manage accordingly
Tests during dangerous duration for diagnosis
§ CBC
§ Serum albumin
§ Serum cholesterol
§ Regular BP checkup
§ Live function tests
Now how will we diagnose the patient by help of these tests? Lets see. Its really easy. I would suggest that you go back to start of article and see the classification again. Now I would discuss all the classification in a way that you would know the way to diagnose the patient
MANAGEMENT OF DENGUE FEVER:
The most important thing to do about management is counseling the patient about dengue fever. We have to tell them that its not dangerous and if treated accordingly the mortality is very low. We should make patient and his attendants tension free.
Now we will discuss management plans for different types of dengue fever
****AYMPTOMATIC DENGUE FEVER: we don’t have to do anything in this case as the patient already has immuntity against it.
****UNDIFFERENTIATED FEVER: in this case too no treatment is offered and patient gets fine on its own usually.
****CLASSICAL DENGUE FEVER:
· PANADOL (ACETAMINOPHEN) 2 tablets after every 6 hours. We ask the patient not to take any other NSAID for 2 reasons.
First of all NSAIDS are known to have anti platelet action and so as in dengue fever the platelets decrease so we avoid any drug with anti platelet actions. Secondly NSAIDS are known to cause gastric ulcers or to aggravate them. So we avoid them so that if they create such problem in a patient with decreased platelet count we may have to deal with internal GI bleed which can be dangerous.
· IV FLUIDS. As the patient has nausea and vomiting so dehydration would be a common finding. We give IV fluids as ringer lactate or dextrose to the patient
· ANTI EMETICS. To decrease the symptoms of nausea and vomiting anti emetics like metoclopramide are suggested
· NO PLATELETS. No platelet infusion is required in dengue patients. Its indicated in only 0.1 percent of the cases with proper indication. Its seen that it may cause anaphylactic shock in the patient and should be avoided at all costs. Instead patient may be given whole blood if any signs of bleeding or very low platelet count may be seen.
****DENGUE HAEMORRHAGIC FEVER WITHOUT SHOCK:
The reason for emphasizing that the patient must present on 4th day of disease to doctor so as to differentiate dengue hemorrhagic fever from classic fever is the fact that the management plan of both are opposite. So if we continue to treat a case of hemorrhagic fever in same way as that of classic fever we would end up getting a disaster. Lets see how to manage a case of dengue hemorrhagic fever
· COUNSELLING. Tell the patient that crucial phase starts from 4th day and as a clinician we must identify it as well.
· SIGNS OF LEAK. Signs of capillary leakage must be looked for. Patient with persistent vomiting, RHC pain must be identified and managed accordingly
· ACETAMINOPHEN (PANADOL) 2 tablets 6 hourly for fever reduction if fever is still present. No NSAIDs for same reason as written above in management of dengue classical fever
· RESTRICTION OF FLUIDS. We must tell patient to take less fluids because fluid is leaking into extra vascular compartment so we will overload extra vascular compartment and later when the capillary leak would end after 48 hours same fluid would come back to intravascular compartment overloading it and ending into congestive heart failure etc. So we suggest giving diuretics to decrease overload problem after the passage of crucial phase.(But in case of dengue classical fever more fluids must be given as patient has dehydration with no capillary leakage)
· IV DEXTRAN 40. We do not give ringer lactate or dextrose to these patients as we do not want to over load their extravascular compartment due to capillary leakage. So we give patient IV dextran 40 (10ml/kg body weight in half hour). Dextran 40 makes extravascular fluid to come into intravascular compartment and hence protects our patient to go into intravascular overload after 48 hours of crucial phase.
· NO PLATELETS. Again for same reasons as described in management of dengue classical fever platelet transfusion is contraindicated. They are only given in patients with absolute indication but such patients are 1 in 1000. Whole blood transfusion for platelets and clotting factors is a better option.
****DENGUE SHOCK SYNDROME:
It’s a very serious condition which is managed as a case of shock under strict supervision of neurosurgeons and physicians and mortality rate is high. Still timely and correct management can make most of the cases recover. The management plan of dengue shock syndrome is above the level of discussion we are having here.
PREVENTION FROM DENGUE :
As far as prevention is concerned either we will have to stop aedes aeqypti or albopticus mosquitoes to stop breeding by destroying their breeding places or we will have to stop the contact of mosquito with the human beings. We can do this by
·.. Cleaning the parks and not allowing clean water to gather in them
·.. Emptying the pools and all places where water may gather
· ..Even a money plant inside home can be a breeding place so avoid such things
· ..Using mosquito repellants or mosquito killing sprays inside home to avoid contact of mosquito with humans
·.. Massive fumigation programs by government to kill mosquitoes.
·.. Isolation of dengue patients and avoidance of their contacts with mosquitoes to avoid spread
· ..Public awareness by print media and television.
ROLE OF ANTIBODIES IN DIAGNOSING DENGUE FEVER:
Patients can develop dengue hemorrhagic fever in primary infection and even patients getting secondary infection can have simple dengue classical fever. But the incidence of development of dengue hemorrhagic fever in patients with secondary infection is remarkably more. Lets discuss the role of different antibodies helping us to diagnose dengue fever.
IgM antibody shows current infection and is usually positive from 5th day till 10th day.
IgG antibody shows previous infection and is positive usually after 10th day of infection
Viral antigen can be detected during first three days of infection as well.
So lets discuss different scenarios:
** In a patient who has got dengue first time , during first three days we will find viral antigen positive. From day 5 to day 10 IgM would be positive , while after 10 days IgG would be positive for rest of his life.
** In patient who has got dengue second time (secondary infection) during first three days viral antigen and IgG( of previous infection) would be positive. From 5th to 10th days IgM and IgG would both be positive. From 10th day onwards only IgG would be positive and would remain positive throughout his life
Dengue fever is a viral infection caused by dengue virus which has four serotypes said to be serotype 1, 2, 3 and 4. In Pakistan the most common serotypes involved are 2 and 3.
The vector of dengue fever is aedes aegypti mosquito but in Pakistan it has been seen that in 50 percent of the cases aedes albopticus mosquito is also involved. Only the female mosquitoes of these before mentioned types are responsible for spread of dengue virus as they lay eggs and need proteins for that purpose and they get that protein from the blood of human beings. Male mosquitoes don’t bite and so are not involved in the spread.
These mosquitoes have a life cycle of total of 2 weeks out of which first week is for the maturation of mosquito and the second week is for reproductive cycle in which these female mosquitoes lay eggs. Every mosquito can lay around 600 eggs in its life , 300 being at a time. These eggs can stay at any place for about 9 months till the weather becomes favorable upon which eggs hatch. Breeding places of these mosquitoes are mostly damp places and clean water outdoor. Parks, pools, lakes, green places which are watered every day being at the top of the list. But the mosquito itself likes to live indoor and usually is seen under the sofa or beds etc and so it mostly bits on ankles and feet. A research has shown that its sting has some local anesthetic effect due to which when the mosquito bites person usually does not feel any pain. The mosquito has white stripes on its body and is very fast and quick. So its like a commando equipped with best ammo ever and with all the abilities of hiding and being very quick. So it’s a bit difficult to smash it if you try to. When the mosquito bites a person with dengue virus in its blood the virus gets transferred to the mosquito. It multiplies in the mosquito and it takes around 2 days to reach tissues of the mosquito and ultimately its salivary glands so that the mosquito might be able to transfer it further to others. So it means that if any aedes aegypti bites a dengue patient and bites you immediately you may not get dengue fever. Furthermore when these mosquitoes with viruses bite human, symptoms develop after around 2 days. So if you develop symptoms of dengue then it does not mean that a mosquito just bit you. Keep it clear that these are due to some mosquito which bit you about 2 days ago. And as its painless sting so you can never be sure when that happened.
CLASSIFICATION OF DENGUE FEVER
** ASYMPTOMATIC
**SYMPTOMATIC
Symptomatic dengue fever can be
1. Undifferentiated fever
2. Classical dengue fever
3. Dengue haemorrhagic fever
Classical dengue fever can further be:
i) Classical dengue fever without thrombocytopenia
ii) Classical dengue fever with thrombocytopenia either with unusual bleeds or without unusual bleeds.
Dengue hemorrhagic fever can further be:
i) Dengue hemorrhagic fever without shock
ii) Dengue shock syndrome (DSS)
IMMUNITY AGAINST DENGUE VIRUS:
As we know that there are four serotypes of dengue virus its very interesting to know that when a mosquito gives you dengue fever infection of any one serotype you get a life long immunity against that serotype. For example if an aedes egypti with dengue virus 1 bites you and you get dengue fever and then you get fine after 10 days, then life long if any aedes would bite you with dengue virus 1 you wouldn’t get dengue fever because you already would have enough anti bodies to avoid any infection. But when you get dengue infection with one serotype you get immunity from other serotypes for just 6 months. For example in same above case after 10 days when person would get fine, for next six months he cant have dengue fever because he has acquired immunity against all serotypes viruses but after 6 months he can have dengue fever from serotype 2,3 and 4 but not from 1 for which he has got life time immunity now.
One more thing to discuss here is that dengue virus is the only virus which has got ANTIBODY MEDIATED REPLICATION. It means that if you have antibodies against any of the serotypes of the dengue virus in your blood and you get infection with some other serotype then the viral multiplication in the blood would be very fast as the antibodies already present in the blood would help it. That is the reason that the secondary infection of dengue is more dangerous as compared to primary (first time) and is more involved in dengue hemorrhagic fever with shock.
MISCONCEPTIONS About Dengue Hemorrhagic Fever:
1. “People think that a mismanaged case of dengue fever gets converted into dengue hemorrhagic fever. That’s totally wrong. Dengue fever classic and dengue hemorrhagic fever both are different diseases. Though they both present in the same way in the start but the hemorrhagic fever is hemorrhagic from the very first day while the dengue fever classic or whatever starts from very first day. These types are not inter convertible. “
2. “A second misconception is that dengue haemorrhagic fever is different from dengue fever classic on the basis of bleeding (hemorrhage). Its wrong too. A case of dengue fever classic can have bleeding while a person can have dengue hemorrhagic fever without having any bleeding. We will further discuss that how we would know that person has classic or hemorrhagic fever. So it is very important that we clear these misconceptions from our minds.”
Presentation OF DENGUE FEVER :
Dengue fever has a duration of around 10 days(in most of the cases) . For ease of understanding we will divide these 10 days into three spans:
1 to 3 days… Common duration
4 to 6 days… Dangerous duration needs appropriate diagnosis
7 to 10 days… Resolution phase
COMMON DURATION (1ST DAY TO 3RD DAY):
By common duration we mean the first 3 days of dengue fever infection. I termed it as the common duration as it’s the time period during which you are not sure what you are dealing with and all the types of dengue fever may it be classic or hemorrhagic have same symptoms during this period and you can never diagnose the type of dengue. If we see a typical case scenario in which patient gets bitten from aedes egypti mosquito which had already bitten a dengue patient 2 days before. After 2 days of mosquito bite the patient may develop symptoms like
** High grade fever around 104 C
** Nausea
** Vomiting
** Head aches
** Muscle and back aches
** Retro orbital pains
** Sever weakness
The symptoms and presentations of patients vary a lot. You may get a patient who may present just with severe weakness without any fever or vomiting or aches and you will further see that he has dengue fever. So the symptoms vary and so the involvement of labs is very important to diagnose the dengue fever. All what we discussed is happening to the patient in first three days and all the patients of dengue either classic or hemorrhagic would present with same symptoms during first 3 days and you cannot tell the difference. Even the lab tests cannot tell us the difference and diagnosis but still its advisable for the patient to get his serial CBC done during these 3 days so that we may get reference values for comparison with deranged ones coming later in the disease.
DANGEROUS DURATION WITH APPROPRIATE DIAGNOSIS (4TH TO 6TH DAY)
Usually the fever of the patient goes during this duration. So its very important to advise the patient that as long as you have fever you are in the safe duration but as soon as your fever would subside must report to a doctor as that’s the time when we have to decide whether patient has dengue hemorrhagic fever or dengue classical fever. During this duration we can make accurate diagnosis of the type of dengue fever. For that purpose we will make use of some signs and some lab test which are as follows
Sings indicating that patient might be going in dengue hemorrhagic fever
1. Persistent vomiting
2. Right hypochondrium pain due to associated hepatitis
3. Decreased pulse pressure
If you see these three sings in any patient on his 4th day onwards of disease suspect dengue hemorrhagic fever in him and get lab tests done and manage accordingly
Tests during dangerous duration for diagnosis
§ CBC
§ Serum albumin
§ Serum cholesterol
§ Regular BP checkup
§ Live function tests
Now how will we diagnose the patient by help of these tests? Lets see. Its really easy. I would suggest that you go back to start of article and see the classification again. Now I would discuss all the classification in a way that you would know the way to diagnose the patient
MANAGEMENT OF DENGUE FEVER:
The most important thing to do about management is counseling the patient about dengue fever. We have to tell them that its not dangerous and if treated accordingly the mortality is very low. We should make patient and his attendants tension free.
Now we will discuss management plans for different types of dengue fever
****AYMPTOMATIC DENGUE FEVER: we don’t have to do anything in this case as the patient already has immuntity against it.
****UNDIFFERENTIATED FEVER: in this case too no treatment is offered and patient gets fine on its own usually.
****CLASSICAL DENGUE FEVER:
· PANADOL (ACETAMINOPHEN) 2 tablets after every 6 hours. We ask the patient not to take any other NSAID for 2 reasons.
First of all NSAIDS are known to have anti platelet action and so as in dengue fever the platelets decrease so we avoid any drug with anti platelet actions. Secondly NSAIDS are known to cause gastric ulcers or to aggravate them. So we avoid them so that if they create such problem in a patient with decreased platelet count we may have to deal with internal GI bleed which can be dangerous.
· IV FLUIDS. As the patient has nausea and vomiting so dehydration would be a common finding. We give IV fluids as ringer lactate or dextrose to the patient
· ANTI EMETICS. To decrease the symptoms of nausea and vomiting anti emetics like metoclopramide are suggested
· NO PLATELETS. No platelet infusion is required in dengue patients. Its indicated in only 0.1 percent of the cases with proper indication. Its seen that it may cause anaphylactic shock in the patient and should be avoided at all costs. Instead patient may be given whole blood if any signs of bleeding or very low platelet count may be seen.
****DENGUE HAEMORRHAGIC FEVER WITHOUT SHOCK:
The reason for emphasizing that the patient must present on 4th day of disease to doctor so as to differentiate dengue hemorrhagic fever from classic fever is the fact that the management plan of both are opposite. So if we continue to treat a case of hemorrhagic fever in same way as that of classic fever we would end up getting a disaster. Lets see how to manage a case of dengue hemorrhagic fever
· COUNSELLING. Tell the patient that crucial phase starts from 4th day and as a clinician we must identify it as well.
· SIGNS OF LEAK. Signs of capillary leakage must be looked for. Patient with persistent vomiting, RHC pain must be identified and managed accordingly
· ACETAMINOPHEN (PANADOL) 2 tablets 6 hourly for fever reduction if fever is still present. No NSAIDs for same reason as written above in management of dengue classical fever
· RESTRICTION OF FLUIDS. We must tell patient to take less fluids because fluid is leaking into extra vascular compartment so we will overload extra vascular compartment and later when the capillary leak would end after 48 hours same fluid would come back to intravascular compartment overloading it and ending into congestive heart failure etc. So we suggest giving diuretics to decrease overload problem after the passage of crucial phase.(But in case of dengue classical fever more fluids must be given as patient has dehydration with no capillary leakage)
· IV DEXTRAN 40. We do not give ringer lactate or dextrose to these patients as we do not want to over load their extravascular compartment due to capillary leakage. So we give patient IV dextran 40 (10ml/kg body weight in half hour). Dextran 40 makes extravascular fluid to come into intravascular compartment and hence protects our patient to go into intravascular overload after 48 hours of crucial phase.
· NO PLATELETS. Again for same reasons as described in management of dengue classical fever platelet transfusion is contraindicated. They are only given in patients with absolute indication but such patients are 1 in 1000. Whole blood transfusion for platelets and clotting factors is a better option.
****DENGUE SHOCK SYNDROME:
It’s a very serious condition which is managed as a case of shock under strict supervision of neurosurgeons and physicians and mortality rate is high. Still timely and correct management can make most of the cases recover. The management plan of dengue shock syndrome is above the level of discussion we are having here.
PREVENTION FROM DENGUE :
As far as prevention is concerned either we will have to stop aedes aeqypti or albopticus mosquitoes to stop breeding by destroying their breeding places or we will have to stop the contact of mosquito with the human beings. We can do this by
·.. Cleaning the parks and not allowing clean water to gather in them
·.. Emptying the pools and all places where water may gather
· ..Even a money plant inside home can be a breeding place so avoid such things
· ..Using mosquito repellants or mosquito killing sprays inside home to avoid contact of mosquito with humans
·.. Massive fumigation programs by government to kill mosquitoes.
·.. Isolation of dengue patients and avoidance of their contacts with mosquitoes to avoid spread
· ..Public awareness by print media and television.
ROLE OF ANTIBODIES IN DIAGNOSING DENGUE FEVER:
Patients can develop dengue hemorrhagic fever in primary infection and even patients getting secondary infection can have simple dengue classical fever. But the incidence of development of dengue hemorrhagic fever in patients with secondary infection is remarkably more. Lets discuss the role of different antibodies helping us to diagnose dengue fever.
IgM antibody shows current infection and is usually positive from 5th day till 10th day.
IgG antibody shows previous infection and is positive usually after 10th day of infection
Viral antigen can be detected during first three days of infection as well.
So lets discuss different scenarios:
** In a patient who has got dengue first time , during first three days we will find viral antigen positive. From day 5 to day 10 IgM would be positive , while after 10 days IgG would be positive for rest of his life.
** In patient who has got dengue second time (secondary infection) during first three days viral antigen and IgG( of previous infection) would be positive. From 5th to 10th days IgM and IgG would both be positive. From 10th day onwards only IgG would be positive and would remain positive throughout his life
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