INVESTIGATION & CONTROL

OF

OUTBREAKS

DENGUE FEVER & DENGUE HAEMORRHAGIC FEVER

National Institute of Communicable Diseases

(Directorate General of Health Services)

22 - Sham Nath Marg, Delhi-110054

2001

2. Notification of cases

   1. Cases of DF/DHF must be reported monthly to Directorate of National anti Malaria Programme (NAMP), 22 Shamnath Marg, Delhi 110054; through the concerned state nodal officer. A report may be endorsed to the Director, National Institute of Communicable Diseases (NICD), 22-Shamnath Marg, Delhi 110054; Phone:-3971060, 3971272, 3913148; FAX: 3922677; Telegram: COMDIS, DELHI.

   2. If there is a sudden increase or clustering of cases or deaths due to DF/DHF, it must be reported immediately to the district health office or to the immediate supervisor.. The district health office must inform the concerned health officer by the quickest mode of communication (Preferably through telephone, Fax or E-mail). The details of the outbreak including investigation and control measures should follow the information as early as possible. The National Institute of Communicable Diseases is expected to be kept informed of the action taken.

3. Causative agent

   DF/DHF is caused by a group B arbovirus (Flavivirus) and include serotypes 1,2,3 and 4 (Den-1, Den-2, Den-3 and Den-4).

4. Incubation period

   The incubation period is usually 5-6 days but may vary from 3 to 10 days.

5. Mode of transmission

   1. The infection is transmitted by the bite of an infected female mosquito- Aedes aegypti. The mosquito usually bites during day time. The mosquito becomes infected by biting a patient with dengue infection. Once the mosquito becomes infected, it remains so for life. The female mosquitoes can survive upto 3 weeks under normal temperature and humidity.

   2. Female mosquitoes get infected after feeding on a viraemic host. It takes 8-11 days for a mosquito which has fed on an infectious case to propagate the virus to levels sufficient to transmit. The ambient temperature range for dengue transmission is 16⁰C to 40⁰C. Below 16⁰C Aedes aegypti ceases to bite.

6. Vector of transmission

   1. Aedes aegypti is the main vector of dengue transmission in India. Dengue outbreaks have also been attributed to Aedes albopictus.

   2. The mosquito has characteristic white strips on the back and legs. It is also known as Tiger mosquito (figure).

   

   Figure. Aedes aegypti

   3. The mosquito rests indoors, in closets and other dark places. Outside, they rest where it is cool and shady. The female mosquito lays eggs in clean water containers in and around houses, schools and work places. The larvae hatch from the mosquito eggs, and live in the water for about a week; they then change into a round pupal stage for one or two days after which the adult mosquito emerges, ready to bite.

   4. The mosquito is a domestic breeder. Mosquito breeding can occur in any water catching or water storage containers such as desert coolers, overhead tanks, discarded buckets, tyres, utensils and large containers used for collecting rain water which are not emptied and cleaned periodically. Since water is essential during the first 8 days in the life of mosquito, emptying containers once a week will greatly reduce the sources for mosquito breeding and thereby the risk of dengue fever.

   5. Aedes mosquito can fly upto a limited distance of 400 meters but can spread over vast distances mechanically in various types of vehicles used by man.

   6. The outbreaks of dengue fever/DHF are most likely to occur in the post-monsoon period when the breeding of the mosquitoes is highest. Outbreaks can also occur in areas with water scarcity if water is stored over long periods.

7. High risk areas

   1. Usually, urban areas, having high population density, poor sanitation and large number of desert coolers, overhead tanks, discarded buckets, tyres, utensils etc. which promote mosquito breeding, are at high risk.

   2. Dengue fever /DHF can also occur in rural areas where the environment is friendly for mosquito breeding. Mosquito breeding can occur in containers used for storing water, for cattle feeding and drinking , discarded tins, tyres, bottles etc which are not emptied and cleaned periodically.

8. Clinical manifestations and case definitions

   1. Dengue fever (DF)

      The clinical case description of Dengue fever is an acute febrile illness of 2-7 days duration with 2 or more of the following.:
      Headache, retro-orbital pain, myalgia, arthralgia, rash,haemorrhagic manifestation and leucopenia.

   CASE DEFINITION OF DENGUE FEVER

   SUSPECT CASE A case compatible with the clinical description. PROBABLE CASE A case compatible with clinical description with one or more of the following: Supportive serology Presence of confirmed case in the area during the same period. CONFIRMED CASE A case compatible with clinical description and laboratory confirmed.

2. Dengue Haemorrhagic Fever (DHF)

   DHF is a severe form of dengue fever. Typically, it begins abruptly with high fever accompanied by headache, anorexia, vomiting and abdominal pain. During the first few days, the illness resembles classical dengue fever, but a maculopapular rash is less common.

   A haemorrhagic diathesis is commonly demonstrated by scattered fine petechiae on the extremities, face and trunk and in the axillae. A positive tourniquet test and a tendency to bruise at venepuncture site are always present. Bleeding from the nose, gums and gastrointestinal tract are also seen. Haematuria is extremely rare.

   The liver is usually enlarged, soft and tender. Approximately 50% of patients have generalised lymphadenopathy.

   The critical stage is reached after 2-7 days, when the fever subsides. Accompanying or shortly after a rapid drop in body temperature, varying degree of circulatory disturbances occur. The patient is usually restless and has cold extremities. Sometimes there may be sweating.

   In less severe cases, the changes in vital signs are minimum and transient. The patient recovers spontaneously or recovers after a brief period of therapy.

   CASE DEFINITION OF DHF

   A probable or confirmd case of dengue fever with haemorrhagic tendencies evidenced by one or more of the following: Positive tourniquet test Petechiae, ecchymoses or purpura Bleeding from buccal mucosa, gastrointestinal tract, injection site or others Haematemesis, malaena Signs of plasma leakage ( Pleural effusion, ascites, hypoproteinaemis). Laboratory criteria for diagnosis Thrombocytopenia (100,000 cells or less per mm.3 ) Heamoconcentration ( >20% rise in average haematocrit for age and sex >= 20% drop in haematocrit following volume replacement treatment as compared to baseline.

    

   STANDARD TOURNIQUET TEST

   Apply sphygmomanometer cuff to the arm and take Blood pressure. Inflate cuff so that it registers a pressure midway between that of systolic and diastolic blood pressure. Hold it for five minutes. Examine the cubital fossa for petechiae, if >20 petechiae in 3 cm diameter circles or 2.5 cm square, the test is positive.

   In more severe cases, shock ensues and the patient may die within 12-24 hours. Prolonged shock is often complicated by metabolic acidosis and severe bleeding, which indicate a poor prognosis. If the patient is appropriately treated before the irreversible shock has developed, rapid recovery is the rule.

    

   Dengue Shock Syndrome:

   A probable or confirmed case of dengue fever and evidence of circulatory failure manifested by rapid, weak pulse, narrow pulse pressure ( 20 mm of Hg) or hypotension for age with cold clammy skin and altered mental status.

   A major cause of deaths due to DHF is leakage of plasma in the pleural and abdominal cavities leading to hypovolaemic shock.
   Continuous monitoring of haematocrit value and platelet count is essential for diagnosis and case management.
   The time course relationship between the fall in platelet count and a rise in haematocrit level appears to be unique to DHF. These changes occur before the subsidence of fever and before the onset of shock and are correlated with the disease severity.

   Encephalitic signs associated with intracranial haemorrhage, metabolic and electrolyte disturbances, and hepatic failure (a form of Reye's syndrome) may occur. They are uncommon but carry a grave prognosis.

9. Differential diagnosis of DHF/DSS

   Early in febrile illness, the differential diagnosis includes a wide spectrum of viral and bacterial infections.
   The presence of marked thrombocytopenia with concurrent haemoconcentration differentiates DHF/DSS from other diseases such as endotoxic shock from bacterial or meningococcaemia. In patients with severe bleeding, evidence of pleural effusion and/or hypoproteinaemia may indicate plasma leakage.

10. Laboratory confirmation of diagnosis

    1. The diagnosis of DF/DHF can be confirmed by serological tests. The tests include detection of IgM antibodies which appear around the end of first week of onset of symptoms and are detectable for 1-3 months after the acute episode.

        

       Laboratory Diagnosis: One or more of the following:

       Isolation of Dengue virus from serum, plasma, leucocytes or autopsy samples. Demonstaration of a fourfold or greater change in reciprocal IgG or IgM antibody titres to one or more dengue virus antigen in paired sera samples. Demonstaration of dengue virus antigen in autopsy tissue by immunohistochemistry or immunofluorescence or in serum samples by EIA Detection of viral genomic sequences in autopsy tissue, serum or CSF sample by PCR ( Polymerase chain reaction)

     

    2. Antigen is produced in limited quantities for operational research and outbreak investigations at the National Institute of Virology (NIV), Pune. With the antigen received from NIV, the National Institute of Communicable Diseases (NICD) provides laboratory support for any outbreak investigation. The antigen is also commercially available.

    3. Blood for serological studies should be carefully collected taking due universal precautions from suspected DF/DHF cases (a) as soon as possible after hospital admission or attendance at the clinic (S-1) (b) shortly before discharge from the hospital (S-2) and (c) if possible, 14-21 days after disease onset (S-3). Although collection of sera and transportation of it to laboratory is very important, the test result may be distorted due to history of previous infection and cross immunity.
       The sera is separated and stored at 4^{0 .}c . It should be sent to the laboratory by the quickest means preferably on dry ice and never be frozen.

    4. Each specimen should be accompanied with the detailed information about the case as given in the box so that the results could be scientifically interpreted.

     

    INFORMATION WHICH SHOULD ACCOMPANY EACH SAMPLE

    name of the patient name of the mother / father age sex complete residential address name of the hospital / PHC sending the sample registration number of the patient date of onset of illness date of hospitalisation date of collection of sample provisional diagnosis brief clinical findings results of clinical laboratory investigations

11. Clinical management

    1. Management of Dengue fever

       The management of dengue fever is symptomatic:
       

       • Bed rest is advisable during the acute febrile phase

       • Antipyretics or sponging are required to keep body temperature below 39⁰C. Salicylates and ibuprofen should be avoided. Paracetamol may be prescribed.

       • Analgesics or a mild sedative may be required for those with severe pain

       • Home available fluids and ORS solution are recommended for patients with excessive sweating, nausea, vomiting or diarrhoea to prevent dehydration.

    Management of DHF

    • Management during febrile phase is similar to that of DF

    • Antipyretics may be indicated but salicylates and ibuprofen should be avoided.

    • Increased fluid intake

    • Fluid and electrolyte replacement by IV fluids, isotonics etc.

    • Plasma expanders, if clinically indicated

    • Fresh frozen plasma may be indicated in some cases

    • Blood transfusion (exceptionally rare cases)

    As thrombocytopenia and concurrent haemoconcentration usually occur well before the onset of shock, the use of these criteria enables the clinician to decide about the fluid replacement for plasma loss. The disease severity can be modified by simply monitoring and evaluating the patient continuously. Prolonged shock is often complicated by severe massive bleeding and carries a bad prognosis.

    Judicious volume replacement is mandatory as the plasma loss is only for 24 to 48 hours and is more rapid around the time of defervescence and/or shock. Haematocrit determination is essential for monitoring the rate of IV fluid infusion and to check overload (which has been recognised as a common problem).

    Isotonic solution (0.9% sodium chloride, also known as normal saline) or a compound solution of sodium lactate is preferred. Saline with or without glucose can be used depending upon availability. Glucose solution without saline do not provide the salt required to restore electrolyte balance and is not recommended.

    Transfusion of platelets does not change the course of the illness and is not recommended. Blood transfusion may be indicated in patients with severe shock, massive bleeding and DIC.
    

    Amount of fluid given should be constantly monitored. Any evidence of swelling, shortness of breath or puffiness may indicate fluid overload.

12. Pathogenesis and pathophysiology

    The pathogenic mechanism of DHF is not clear, but two main pathophysiologic changes occur:

    1. vascular permeability increases which results in plasma leakage, leading to hypovolaemia and shock

    2. abnormal haemostasis, due to vasculopathy, thrombocytopenia and coagulopathy, leading to various haemorrhagic manifestations.

    The severity of DHF as compared with dengue fever may be explained by the enhancement of virus multiplication in macrophages by heterotypic antibodies resulting from a previous dengue infection. There are evidences suggesting that cell mediated immune response may also be involved in the pathogenesis of DHF.

13. Immunity

    Infection with one serotype provides life-long homologus immunity but does not provide protection against other serotypes, and instead may exacerbate subsequent infection.

14. Surveillance in DF/DHF

    Surveillance is prerequisite for monitoring the dengue situation in the area and should be carried out regularly for early detection of an impending outbreak and to initiate timely preventive and control measures. Surveillance should include epidemiological, entomological and laboratory parameters.

    1. Epidemiological surveillance

       The epidemiological surveillance should include the following:

       • Fever surveillance

       • Diagnosis based on standard case definition

       • Reporting of DF/DHF cases to state health authorities

       • During an outbreak situation, samples of about 5% of clinically diagnosed cases should be tested for confirmation of diagnosis by the laboratory.

       The peripheral health staff should be alerted to report increase or clustering of acute febrile illness compatible with the case definition of DF/DHF. Such increase of cases should be investigated locally, including entomological investigation to check for vector density in the area.

       Exercise: I

       Case definition has got an important role during an outbreak situation. To estimate the number of dengue fever cases in the community , a fever survey is undertaken. For framing the case definition, one has to analyse the symptoms and signs of the patient who have been admitted or have been reported. The usual signs, symptoms will constitute the case definition.

       Clinical features of the 53 patients who were admitted in Shahjahanpur, Uttar Pradesh Outbreak is as follows:

       Symptoms	Frequency	Proportion(%)
       Fever	51	96.2
       Chills/rigors	25	47.2
       Joint pain	21	39.6
       Headache/ Bodyache/ myalgia	40	75.5
       Nausea /vomiting	22	41.5
       Gastritis, abdominal pain	16	30.2
       Fatigue, weakness	53	100
       Bleeding	13	24.5

       
       

       Question: What will be your case definition for Dengue in this outbreak situation? How do you prepare a case definition for survey purpose? Please discuss with the facilitator

       Discuss your experience about the case definition with the course facilitator.

       
       

       For each person who fitted the case definition, a full list of symptoms and signs was recorded, along with age sex and week of onset. ( preparation of line list)

        

        

       Exercise: II

       During 1985, in Puerto Rico, 296 febrile illness with rash was notified for serological diagnosis. 94 cases meet the clinical case definition for measles.

       No. that met clinical case defnition for measles during 1985-94 = 94 Serological confirmed for measles       22 (23%) Serological confirmed for Dengue        32 (34%)

       The Case definition of Measles and dengue may mimick each other causing misclassification of cases. So designing of feasible case definition with maximum specificity and sensitivity is desirable.

       A further retrospective analysis of Dengue cases showed that 28 % of all lab.confirmed Dengue in Puerto Rico has the same case definition as measles.

       Question : How do you interpret the above finding in Puerto Rico which is endemic for Dengue ? Discuss the action component of the surveillance with the facilitator.

       Exercise: III

       The available data for Dengue in India is as follows:

       Year	Case	Deaths
       1991	6291	3
       1992	2683	12
       1993	11125	36
       1994	7494	4
       1995	7847	10
       1996	16517	545
       1997	1177	36
       1998	717	18
       1999	944	17
       2000	304	2

       
       

       Question: Comment on the surveillance system from the data showing the incidence of Dengue in India. Discuss with the facilitator about the reporting and how can it be improved?

    
    

    2. Vector surveillance

       Larval surveillance during the pre monsoon and post monsoon is important to find out the extent of prevalence of vectors in a locality. House index, container index and breteau index are usually used. Seasonal fluctuation will help to stratify the areas for further control measures. Adult surveillance will indicate the possible infected mosquitos and may be utilised for virus isolation, susceptibility to insecticides etc.

       A number of indices have been described and are currently used to monitor the vector population in a defined area:

       1. House index - Percentage of houses positive for larvae of Aedes aegypti.

       2. Breteau index- Number of positive containers for Aedes aegypti per 100 houses.

       3. Container index- Percentage of containers positive for Aedes breeding.

       Epidemiological interpretation of various entomological indices
       Entomological indices	High risk of transmission	Low risk of transmission
       Breteau index	50	5
       House index	10%	1%

       
       

       Container index :Container index is mostly utilised for drawing vector control strategy.

       In areas where Aedes aegypti is absent or very scarce and dengue outbreaks occur, a special effort should be made to identify the local vector(s) to develop vector surveillance accordingly.

       Exercise:

       An entomologic study of Aedes mosquitos and larvae was done in the five zones of Beawar city, with the following results.

       Zone	Mohallas searched for larva	Houses searched for adults	Houses positive	Houses positive	Container searched	Container index
       Central	7	252	60	49	1356	31
       East	7	189	53	40	841	19
       North	9	216	55	37	815	21
       West	5	109	60	19	849	11
       South	4	138	64	42	676	25

       
       

       Question : From the entomologic data, would you expect any part of the city to have been spared during the outbreak? Discuss with the facilitator.

    3. Laboratory Surveillance

       It will confirm the clinical diagnosis and provide report to the public health authority

       2. Should report within 24 hrs mentioning the sero types involved and the type of test done

       3. Should receive selected samples from Sentinel Hospitals (early detection of epidemic) from fever of unknown origin for viral detection.

       The physical location of cases in the area or in other cities of the neighbouring states/districts/areas should also be monitored. The objective of the laboratory surveillance is to detect the introduction of the virus, the new strain or serotype of dengue virus to detect any unusual increase in the spread of dengue transmission.

       Exercise V:

       The suspicion of the clinician for Dengue plays a major role while refering the blood samples to the Laboratory for diagnosis. Following is a table showing the number of blood samples from suspected Dengue cases. Ig M-capture enzyme linked immunosorbent assay (MAC- ELISA) which is a simple and rapid test was carried out in all the samples. Only single sample was obtained and it was assumed that the patients were admitted late to the hospital and detectable Ig M is already present in the blood. The positivity pattern is also shown in the table.

       Table : Number of samples tested and positive for Dengue antibody during the year 1998, 1999 and 2000

       										1998										1999										2000
       										Tested					Positive					Tested					Positive					Tested					Positive
       Jan										0					0					2					0					11					0
       Feb										0					0					11					0					9					0
       Mar										0					0					16					0					5					0
       Apr										0					0					5					0					13					0
       May										13					0					11					1					21					0
       Jun										23					0					12					0					15					0
       Jul										17					1					11					0					17					0
       Aug										20					0					27					0					27					1
       Sep										38					4					71					17					55					21
       Oct										160					33					145					35					215					68
       Nov										312					133					145					39					255					104
       Dec										28					16					25					1					45					7
       Total										611					187					481					93					688					201

       
       

       Question : From the above table, what do you interpret? Discuss with your facilitator the importance of the laboratory surveillance vis a vis fever surveillance.

15. Investigation of an outbreak

    1. The investigation of an outbreak of DF/DHF is similar to the investigation of other epidemic prone diseases. The first principle is to receive early signals, confirm diagnosis and to take prompt measures for control of the outbreak. Control measures are most effective when selective measures are applied early.

       • Factors increasing the risk of DF/DHF outbreaks

       • Increasing urban population

       • Expanding mosquito breeding due to:

       • shortage of water supply,

       • traditional water storage,

       • poor garbage collection,
         (create more mosquito breeding places)

       • Changing life style ( use of water coolers etc.)

       • Rapid transportation

    2. Line list of cases, including age, sex and address and other details should be maintained and also reported to district health office (Annexure 2&3). Active search should be made for more cases. Serum samples should be collected for laboratory confirmation of diagnosis.

    3. Vector surveillance should be immediately initiated and should include collection of adult mosquitoes, identification of mosquito species and density, assessment of susceptibility of vectors to available insecticides.

    4. Arrange health educational activities in the community regarding prevention of mosquito bites by use of mosquito nets and mosquito repellent creams, mosquito breeding by drying out water containers at least once a week, wearing of protective clothing and reporting suspected cases at the health facilities early.

    5. On confirmation of an outbreak of DF/DHF, take precautionary measures in other neighbouring high risk areas.

    6. After the outbreak is over, a detailed report must be written. Format for outbreak investigation is given at Annexure-4.

16. Prevention and control of an outbreak

    PREVENTION AND CONTROL OF DF/DHF OUTBREAK

    Initiate vector surveillance and control measures Conduct IEC Motivate for Community participation Improve facilities for case management of patients with haemorrhagic shock Alert health personnel to report increase/clustering of cases

    1. A surveillance system should be established so that DHF is immediately reported to the local health authorities. Necessary field investigations must be carried out in the area of residence of the patient to check for vector.

    2. The preventive measures are directed at reducing the vector density and in taking personal protection to prevent the bite of mosquitoes.

    PREVENT MOSQUITO BITES

    Wear full sleeved clothes and long dresses/trousers that cover arms and legs during outbreak situations Use insect repellents while sleeping at night to keep away mosquitoes. Take additional care of children and the elderly. Use mosquito coils and electric vapour mats during the day Use mosquito nets - to protect babies, old people and others who may rest during the day. The effectiveness of such nets can be improved by treating them with permethrin (pyrethroid insecticide). Curtains (cloth or bamboo) can also be treated with insecticide and hung at windows or doorways, to repel or kill mosquitoes Keep patients protected from mosquito bite in acute phase - Mosquitoes become infected when they bite people who are sick with dengue. Mosquito nets and mosquito coils will effectively prevent mosquitoes from biting sick people and help stop the spread of dengue. Keep the surroundings of the dispensary and Hospital mosquito free

    3. Immediate measures are called for to reduce the density of mosquitoes by use of insecticides. The public should also be informed to take necessary precautions against mosquito bite such as use of full sleeved clothes, mosquito nets at night and mosquito repellent creams, if necessary.

       PREVENT MULTIPLICATION OF MOSQUITOES

       Mosquitoes which spread dengue live and breed in and around houses. Following are the measures to decrease the breeding sites. Drain water from coolers, tanks, barrels, drums, and buckets etc. There should be no water in coolers when not in use. Remove from the house all objects e.g. plant saucers, etc. which have water collected in them. Remove water from refrigerator drip pans every other day. All stored water containers should be kept covered all the time. Discard solid waste and objects where water collects e.g. bottles, tins, tyres etc.

       
       

    4. Long term measures include the recommended steps for vector control under the National Anti Malaria Programme(NAMP).

    5. Pockets of high risk should be identified so that these areas could be given more attention with regard to control measures, health educational activities and field supervision.

    6. Isolation of patients and disinfection of secretions and excretions are not required as DF /DHF virus is not transmitted from person to person.

    7. Patients should be treated in nearby health centre/ hospital where the facilities for platelet count and haematocrit value estimation are available. These parameters are essential to monitor clinical status of the patients. Haematocrit levels are required to know the degree of plasma leakage and determine the impact of fluid replacement to avoid fluid overload.

17. Community participation

    1. Community participation is essential for the prevention and control of an outbreak of DF/DHF. The community must be encouraged to take steps to protect themselves from mosquitoes by eliminating mosquito breeding sites and taking personal measures such as use of bed nets, mosquito repellents etc. The co-operation of the community is also important during the periodic insecticide spray.

    2. In pockets of high risk, active search for mosquito breeding sites by the community should be encouraged and early reporting should be ensured.

    3. Co-ordinated efforts by government departments such as sanitation, urban development, education etc. are essential so that risk factors for mosquito breeding can be reduced and other control measures taken up effectively.

    4. In an event of an outbreak, the co-operation of other government departments will help to bring it more effectively under control. An inter-departmental committee for outbreak prevention and control should be constituted which should meet more periodically. Panchayat members, key community representatives and NGOs should be included as members of the committee. A meeting of the committee should be convened before the expected seasonal increase of water and vector borne diseases. In districts where risk factors exist, status of control measures for DF/DHF should also be assessed. The suggested areas of responsibilities of the various departments is given in Annexure-4