Dengue and chickungunya

2. DENGUE
 Dengue viruses are arboviruses capable of infecting
humans, and causing disease.
 These infections may be asymptomatic or may lead to
 (a)"classical" dengue fever
 (b) dengue haemorrhagic fever without shock
 (c) dengue haemorrhagic fever with shock
 Dengue fever is a self-limiting disease and represents the
majority of cases of dengue infection

3.  Dengue and DHF is endemic in more than 100 countries
in the WHO regions of Africa, the Americas, Eastern
Mediterranean, South-East Asia and Western Pacific
 The South-East Asia and Western Pacific regions are most
seriously affected.
 Detection of all four serotypes has now rendered the
countries hyperendemic.
 It is found in tropical and subtropical regions around the
world, predominantly in urban and semi-urban areas, and
are now spreading to rural areas.

4. DENGUE IN INDIA
 In India, the risk of dengue has shown an increase in
recent years due to rapid urbanization, lifestyle changes
and deficient water management including improper water
storage practices in urban, peri-urban and rural areas ,
leading to proliferation of mosquito breeding sites.
 The disease has a seasonal pattern i.e. the cases peak after
monsoon, and it is not uniformly distributed throughout
the year.
 However, in the southern states and Gujarat the
transmission is perennial.

5. Epidemiological determinants
Agent factors
 (a) AGENT : The dengue virus form a distinct complex within the
genus flavivirus based on antigenic and biological characteristics.
 There are four virus serotypes which are designated as DENV-1, DENV-2,
DENV-3 and DENV-4.
 Infection with any one serotype confers lifelong immunity to that virus
serotype .
 They elicit cross-protection for only a few months after infection by any one
of them.
 Secondary infection with dengue serotype 2 or multiple infection with
different serotypes lead to severe form dengue DHF/DSS .
 The first infection probably sensitizes the patient, while the second infection
with different serotype appears to produce immunological catastrophy.
 All four serotypes have been associated with epidemics of dengue fever
(with or without DHF) with varying degree of severity.

6. (b) VECTOR :
 Aedes aegypti and Aedes Albopictus are the two most
important vectors of dengue.
Aedes aegypti Aedes albopictus
Highly domesticated Peripheral areas of urban cities
Strongly anthropophilic,
Nervous feeder (it bites more than one host
to complete one blood meal )
Aggressive feeder (can complete its blood
meal in one go )
Discordant species (it needs
More than one feed for the completion of
the gonotropic cycle)
Concordant species(does not require a
second blood meal for the completion of the
gonotropic cycle)
Generation of multiple cases and the
clustering of dengue cases in the cities

7. Transmission of disease
 The Aedes mosquito becomes infective by feeding on a
patient from the day before onset to the 5th day (viraemia
stage) of illness.
 After an extrinsic incubation period of 8 to 10 days, the
mosquito becomes infective, and is able to transmit the
infection.
 Once the mosquito becomes infective, it remains so for life.
 The genital tract of the mosquito gets infected and transovarian
transmission of dengue virus occurs when virus enters fully
developed eggs at the time of oviposition.

8. Environmental factors
 The population of Aedes aegypti fluctuates with rainfall and
water storage.
 Its life span is influenced by temperature and humidity,
survives best between 16°C-30°C and a relative humidity of
60-80 per cent.
 It breeds in the containers in and around the houses.
 Being a domestic breeder, it is a endophagic and endophilic.
 Besides that the mosquitoes will bite more frequently because
of dehydration and thus increase man-mosquito contact

9. Dengue in the community
 DF/DHF is characterized by the "iceberg" or pyramid phenomenon.
 At the base of the pyramid, most of the cases are symptomless, followed by
DF,DHF and DSS
High risk patients
1. infants and elderly ;
2. obesity;
3. pregnancy;
4. peptic ulcer disease;
5. women who are in menstruation or have abnormal bleeding;
6. Haemolytic disease such as G6PD, thalassemia and other haemoglobinopathies;
7. congenital heart disease;
8. chronic diseases such as diabetes mellitus, hypertension ,asthma, ischaemic heart
disease, chronic renal failure, liver cirrhosis
9. patients on steroid or NSAID treatment.

10. Clinical mainfestations

11. 1.Undifferentiated fever
 Infants, children and adults who have been infected with
dengue virus, especially for the first time (primary
dengue infection), may develop a simple fever
indistinguishable from other viral infection.
 Maculopapular rashes may accompany the fever or may
appear during defervescence.
 Upper respiratory and gastrointestinal symptoms are
common.

12. 2. Classical dengue fever
 All ages and both sexes are susceptible to dengue fever.
 Children usually have a milder disease than adults.
 Incubation period : 3 to 10 days (commonly 5-6 days).
 The onset is sudden, with chills and high fever, intense headache, muscle and
joint pains , which prevent all movement.
 “Break bone fever”
 Within 24 hours retro orbital pain, particularly on eye movements or eye
pressure and photophobia develops.
 Other common symptoms include extreme weakness, anorexia, constipation,
altered taste sensation, colicky pain and abdominal tenderness, dragging pain
in inguinal region, sore throat and general depression.
 Fever is usually between 39°C and 40°C and lasts for about 5 days, rarely more
than 7 days
 Fever is typically but not inevitably followed by a remission of a few hours to2
days (biphasic curve).

13.  The skin eruptions appear in 80 per cent of cases during the remission or
during second febrile phase, which lasts for 1-2 days.
 The rash is accompanied by similar but milder symptoms.
 The rash may be diffuse flushing, mottling or fleeting pin-point eruptions on
the face, neck and chest during the first half of the febrile period and a
conspicuous rash, that may be maculopapular or scarlatiniform on 3rd or 4th
day.
 It starts on the chest and trunk and may spread to the extremities and rarely to
theface.
 It may be accompanied by itching and hyperaesthesia.
 The rash lasts for 2 hours to several days and may be followed by
desquamation .
 The case fatality is exceedingly low

14. Dengue haemorrhagic fever
 Dengue haemorrhagic fever (DHF) is a severe form of dengue
fever.
 Incubation period : 4 to 6 days.
 The course of dengue illness can be divided into three phases-
1. Febrile phase
2. Critical phase
3. Recovery phase

16. 1. Febrile phase
 The illness commonly begins abruptly with high fever accompanied by facial
flushing and headache.
 Anorexia ,vomiting, epigastric discomfort, tenderness at the right costal margin
and generalized abdominal pain are common.
 During the first few days the illness usually resembles classical DF, but
maculopapular rash usually rubelliform type, is less common.
 Occasionally, the temperature may be 40°C to 41°C and febrile convulsions may
occur particularly in infants .
 The major pathophysiologic changes that determine the severity of disease in
DHF and differentiate it from DF are plasma leakage and abnormal
haemostasis, as manifested by a rising haematocrit value and moderate to
marked thrombocytopenia.
 A positive tournicate test is the most common haemorrhagic phenomenon.
 In DHF, the test usually gives a definite positive with 20 petechiae or more

17. 2. Critical phase
 Around the time of defervescence, (when the temperature drops to 37.5-38°C
or less, and remains below this level, usually on days 3-7 of illness)
 An increase in capillary permeability in parallel with increasing
haematocrit levels may occur. This marks the beginning of the critical
phase.
 The period of clinically significant plasma leakage usually lasts 24-48 hours.
 Progressive leukopenia followed by a rapid decrease in platelet count usually
precedes plasma leakage.
 Pleural effusion mostly on right side and ascites may be clinically detectable.
 Gall bladder oedema has been found to precede plasma leakage.
 Chest X-ray and abdominal ultrasound can be useful tools for diagnosis.
 The degree of increase above the baseline haematocrit often reflects the
severity of plasma leakage.

18.  Shock occurs when a critical volume of plasma is lost through leakage.
 It is often preceded by warning signs of abdominal pain or tenderness,
persistent vomiting, clinical fluid accumulation .
 The body temperature may be subnormal when shock occurs.
 With prolonged shock, the consequent organ hypo perfusion results in
progressive organ impairment, metabolic acidosis and disseminated
intravascular coagulation.
 This in turn leads to severe haemorrhage causing the haematocrit to decrease
in severe shock.
 In addition, severe organ impairment such as severe hepatits, encephalitis or
myocarditis and/or severe bleeding may also develop without obvious plasma
leakage or shock.
 Those who improve after defervescence are said to have non-severe dengue.
 Some cases will deteriorate to severe dengue.

19. 3 .Recovery phase
 If the patient survives the 24-48 hour critical phase, a gradual reabsorption of
extravascular compartment fluid takes place in the following 48-72 hours.
 General well-being improves, appetite returns, gastrointestinal symptoms
abate, haemodynamic status stabilizes and diuresis ensues.
 Some patients may have a rash of "isles of white in the sea of red“ and Some
may experience generalized pruritus.
 Bradycardia and electrocardiographic changes are common during this stage.
 The haematocrit stabilizes or may be lower due to the dilutional effect of
reabsorbed fluid.
 White blood cell count usually starts to rise soon after defervescence but the
recovery of platelet count is typically later than that of white blood cell count.
 Respiratory distress from massive pleural effusion and ascites will occur at any
time if excessive intravenous fluids have been administered.

20. 4 .Severe dengue
 Severe dengue is defined by one or more of the following :
i. Plasma leakage that may lead to shock (dengue shock) and/or fluid accumulation, with
or without respiratory distress
ii. Severe bleeding
iii. Severe organ impairment.
 As dengue vascular permeability progresses, hypovolaemia worsens and results in shock.
 It usually takes place around defervescence, usually on day 4 or 5 (range days 3-7) of illness,
preceded by the warning signs.
 During the initial stage of shock, the compensatory mechanism which maintains a normal
systolic blood pressure also produces tachycardia and peripheral vasoconstriction with
reduced skin perfusion, resulting in cold extremities and delayed capillary refill time.
 Uniquely, the diastolic pressure rises towards the systolic pressure and the pulse pressure
narrows as the peripheral vascular resistance increases.
 Patients in dengue shock often remain conscious and lucid.
 Finally, there is decompensation and both pressures disappear abruptly.
 Prolonged hypotensive shock and hypoxia may lead to multi-organ failure and an extremely
difficult clinical course.

21.  The patient is considered to have shock if the pulse pressure is ≤ 20 mm Hg
in children or he/she has signs of poor capillary perfusion.
 In adults, the pulse pressure of ≤ 20 mm Hg may indicate a more severe
shock.
 Patients with severe dengue may have coagulation abnormalities, but these
are usually not sufficient to cause major bleeding.
 When major bleeding does occur, it is almost always associated with
profound shock since this, in combination with thrombocytopenia, hypoxia
and acidosis , can lead to multiple organ failure and advanced disseminated
intravascular coagulation.
 Massive bleeding may occur without prolonged shock in instances when
acetylsalicylic acid (aspirin), ibuprofen or corticosteriods have been taken.
 Unusual manifestations, including acute liver failure and encephalopathy,
may be present, even in the absence of severe plasma leakage or shock.
 However, most deaths from dengue occur in patients with profound shock,
particularly if the situation is complicated by fluid overload.

22. Laboratory diagnosis
 Epidemiological surveillance requires early determination of dengue virus infection
during the outbreak for urgent public health action towards control, as well as at
sentinel sites for detection of circulating serotypes/genotypes during the inter
epidemic period for use in forecasting possible outbreak.
 The following laboratory tests are available to diagnose dengue fever and DHF :
 1. Virus isolation :
 Specimen is taken during the first 6 days of illness and processed without delay.
 Suitable Specimen for virus isolation are acute phase serum, plasma or washed buffy coat
from the patient , autopsy tissue from fatal case (especially liver, spleen , lymph nodes and
thymus), and mosquitoes collected from the affected areas.
 2. Viral nucleic acid detection : Dengue viral genome , which consists of RNA, can
be detected by reverse transcriptase polymerase chain reaction (RT-PCR) assay and
real time RT-PCR.
 Better specificity and sensitivity compared to virus isolation with a much more rapid
turnaround time.

23.  3. Immunological response and serological tests :
 Haemagglutination inhibition assay (HIA)
 Complement Fixation (CF
 Neutralization test (NT)
 IgM capture enzyme-linked immunosorbent assay(MAC-ELISA)
 Indirect lgG- ELISA, and
 IgM/IgG ratio
 4. Viral antigen detection :
 ELISA and dot blot assays directed against the envelop/membrane (EM) antigens
and nonstructural protein 1 (NS l) can be detected in both patients with primary
and secondary dengue infection upto 6 days after the onset of the illness.
 Besides providing an early diagnostic marker for clinical management, it may also
facilitate the improvement of epidemiological surveys of dengue infection.
 5. Rapid diagnostic test (RDT) :
Rapid format serological test-kits for anti-dengue IgM and IgG antibodies
 6. Analysis of haematological parameters :
Platelet count and haematocrit

24. CLINICAL MANAGEMENT
Grading of the severity of dengue infection
 To decide where to treat the patient, it is important to classify the severity of
dengue infection.
 The presence of thrombocytopenia with concurrent haemoconcentration
differentiates grade I and grade II DHF from DF.
Guidelines for treatment
 A full blood count of the patient should be done at the first visit.
 A haematocrit test in the early febrile phase establishes the patient's own
baseline haematocrit.
 A rapidly decreasing platelet count in parallel with a rising haematocrit
compared to the baseline is suggestive of progress to the plasma
leakage/critical phase of the disease.

26. Management of dengue fever
 Encourage intake of oral rehydration solution (ORS),fruit juice and other
fluids containing electrolytes and sugar to replace losses from fever and
vomiting
 Give paracetamol for high fever
 Instruct the care-givers that the patient should be brought to
hospital immediately if any of the following occur;
 No clinical improvement,
 Deterioration around the time of defervescence,
 Severe abdominal pain,
 Persistent vomiting,
 Cold and clammy extremities,
 Lethargy or irritability/restlessness,
 Bleeding (e.g. Black stools ),
 Not passing urine for more than 4-6 hours.

27. Management of DHF (Febrile Phase)
 The management of febrile phase is similar to that of DF
 Paracetamol is recommended to keep the temperature below 39°C.
 Copious amount of fluid should be given orally, to the extent the patient
tolerates, oral rehydration solution (ORS), such as those used for the
treatment of diarrhoeal disesases and/or fruit juices are preferable to plain
water.
 IV fluid maybe administered if the patient is vomiting persistently or
refusing to feed.

28. Management of DHF Grade I and II
 Hospitalisation.
 All these patients should be observed for signs of shock.
 The critical period for development of shock is transition
from febrile to abferile phase of illness, which usually occurs
after third day of illness.
 A rise of haemo concentration indicates need for IV fluid
therapy.
 If despite the treatment, the patient develops fall in BP,
decrease in urine output or other features of shock, the
management for Grade III/IV DHF/ DSS should be instituted.
 Oral rehydration should he given along with antipyretics
like paracetamol, sponging, etc.

29. Management of DHF Grade III and IV
 Hospitalization
 Haematocrit, platelet count and vital signs should be examined to assess the
patient's condition and intravenous fluid therapy should be started.
 The patient requires regular and sustained monitoring.
 If the patient has already received about 1000 ml of intravenous fluid, it
should he changed to colloidal solution preferably Dextran 40/haemaccele or
if haematocrit is decreasing, fresh whole blood transfusion 10 ml/kg/hour
should be given.
 However, in case of persistent shock when, after initial fluid replacement and
resuscitation with plasma or plasma expanders, the haematocrit continues to
decline, internal bleeding should be suspected.
 Oxygen should be given to all patients in shock.

30. CONTROL MEASURES
1. Mosquito control
The vectors of DF and DHF (e.g., A. aegypti) breed in and around
houses and, in principle can be controlled by individual and community
action, using anti adult and antilarval measures.
2. Vaccines
So far, there is no satisfactory vaccine and no immediate prospect of
preventing the disease by immunization.
3. Other measures
1. Isolation of the patient under bed-nets during the first few days; individual
protection against mosquitoes
2. The personal prophylactic measures are wearing of full sleeves shirts and
full pants; use of mosquito repellent creams, liquids, coils, mats etc.;
3. Use of bed-nets for sleeping infants and young children during day time to
prevent mosquito bite.
4. The environmental measurements are detection and elimination of
mosquito breeding places, management of roof tops, porticos and
sunshades, proper covering of stored water, observation of weekly dry day.

31. Global strategy for dengue prevention
and control 2012-2020
 Dengue is a global threat that requires a global response
involving all possible partners.
 The global strategy promotes co-ordination and collaboration
among multisectoral partners on integrated vector management
approach and sustained control measures at all levels.
 The goals are :
a. to reduce dengue mortality by at least 50 per cent by 2020
b. to reduce dengue morbidity by at least 25 per cent by 2020
c. to estimate the true burden of the disease by 2015.

32. Chikungunya fever
 A dengue-like disease caused by a group A Arbovirus, the chikungunya
virus and transmitted by Aedes mosquitoes.
 It is manifested by high fever and severe articular pains in the limbs and
spinal column.
 The virus was first isolated from patients and mosquitoes during an
epidemic in Tanzania in 1952-53.
 Chikungunya is a local word meaning "doubling up" owing to excruciating
joint pains.
 The virus occurs widely in sub-Saharan Africa, India and in many areas in
Asia.
 During 2006, there was a large outbreak of chikungunya in India, with 1.39
million officially reported cases spread over 16 states; attack rates were
estimated at 45 per cent in some areas.
 No deaths have been attributed to chikungunya fever .

33.  The incubation period of chikungunya fever is 4-7 days,
following which the disease has a sudden onset with fever, chills,
cephalalgia, anorexia, lumbago and conjunctivitis & adenopathy.
 60 to 80 per cent patients have a morbilliform rash, occasionally with
purpura, on the trunk and limbs.
 The cutaneous eruption may recur every 3 to 7 days.
 Other symptoms are coffee-coloured vomiting, epistaxis and petechiae.
 A prominent symptom, seen especially in adult patients is arthropathy.
 The arthropathy is manifested by pain, swelling and stiffness, especially of
the metacarpophalangeal, wrist, elbow, shoulder, knee, ankle and metatarsal
joints.
 It appears between 3rd and 5th day after the onset of clinical symptoms,
and it can persist for many months and even years.

34.  There is no specific treatment of chikungunya infection
 It is usually self limiting.
 Analgesics, antipyretics like paracetamol, diclofenac sodium,
chloroquine along with fluid supplementation are recommended to
manage infection and relieve fever, joint pains and swelling.
 Drugs like aspirin and steroids should be avoided.
 The disease occurs in the rainy season, when the mosquito vector
population is at its peak.

35. DIAGNOSIS
 The virus can be isolated from the blood of febrile patients by the
intracerebral inoculation in suckling mice or on VERO cells.
 In serologic diagnosis, which is the approach most commonly used,
sero-conversion is demonstrated by comparing acute and convalescent
- phase sera in the haemagglutination inhibition, serum neutralization,
or complement fixation test.
 ELISA is used to detect lgM.
 A reverse-transcription polymerase chain reaction (RT-PCR) or nested
PCR technique has also been shown to be useful in
rapidly diagnosing the disease

36. CONTROL
(a) VECTOR CONTROL :
 Eliminate the breeding places of mosquitoes (MainlyAedes aegypti)
 The organophosphorus insecticide, Abate is increasingly being used as a
larvicide.
 It can prevent breeding for upto 3 months when applied on sand granules ; does
not harm man and does not affect the taste of water.
 Antilarval measures can prevent an epidemic, but do not give immediate results
when an epidemic has already broken out.
 In such cases, anti-adult measures alone can bring about a rapid interruption of
transmission.
 Aerosol spray of ultra low-volume (ULV) quantities of malathion or
sumithion (250 ml/hectare) has been found to be effective in interrupting
transmission and stopping epidemics of DHF.
 The tiny droplets kill the mosquitoes in the air as well as on water.
(b) VACCINE : No vaccine has yet been developed that is
considered suitable for use.