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Dengue

Dengue is the most rapidly spreading mosquito borne viral disease in the world Dengue as spread in the last 50 yrs with a 30 fold increase Known in historical times as water poison in China the word Dengue is derived from Swahili phrase denoting cramp like seizure Same distribution as malaria ( tropics ) and about 2.5 billion people live in dengue endemic countries ( more than 125 countries are known to be dengue epidemic ) Estimated 50 million infections annually (WHO 2009 ) Risk factors are influenced by local spatial variations of rainfall , temperature , relative humidity , degree of urbanization and quality of vector control services in urban areas
( WHO ) Geographic expansion and rapid increase in incident cases , epidemics and hyperendemicity has resulted in more severe forms of dengue WHO has cited that dengue may be more widespread than estimated by academic groups and factors as inadequate disease surveillance , misdiagnosis and low levels of reporting contribute towards this discrepancy It is also estimated that dengue is likely to spread further due to factors as modern dynamics of climate change , globalization , travel . trade , socioeconomics , settlement and viral evolution

 

DENV -Small single stranded enveloped RNA virus Arthropod-borne flaviviruses – studies show that virus production is immunologically regulated Four antigenically distinct virus serotypes DEN V1 to 4 ( all originate from the same family Flaviviridae and genus Flavivirus ) Asian genotypes of DEN-2 and DEN 3 frequently associated with severe disease Geographic variations are common – for e.g in Asia the risk of developing severe disease is greater in children < 15 than in adults whereas in the Americas mainly the adult population is affected causing a mild disease

 

Transmission in humans is by Aedes mosquito Primary vector is A aegypti a highly domesticated day biting mosquito that breeds in human- made containers ( A albopictus also responsible ) Infection with one serotype confers lifelong immunity → to that specific serotype (cross protection to other serotypes lasts only 2-3 months ) this means you can only have dengue 4 times in life or have dengue more than once No long term cross-protective immunity Secondary infection with a different serotype or multiple infections with different serotypes → may cause ↑ risk of DHF and DSS (Antibody-dependent enhancement ie antibodies against one serotype enhances the entry of 2nd dengue virus into macrophages → more severe infection ) Occurs in rainy season and immediately afterwards ( July to Oct in India ) No person to person transmission (No special infection control measures required ) Can also be transmitted via infected blood products , organ donation and vertical transmission ( ie DENV can be transmitted from an infected , viremic woman to fetus in utero and neonate at parturition )

 

Presentation-The virus can cause symptomatic infection or asymptomatic seroconversion Incubation period is 5-7 days and the illness starts abruptly Infants and young children may present with undifferentiated febrile illness with rash The symptoms last 2-7 days In patients with moderate to severe disease 3 phases can be seen In the early febrile phase it may be difficult to distinguish dengue from non-dengue febrile illnesses.

 

WHO suggests that Dengue should be suspected when a high fever ( 40° / 104° F ) is accompanied by 2 of the following- ( patient lives / traveled to dengue endemic area ) severe headache pain behind the eyes muscle and joint pains nausea vomiting swollen glands rash.

 

Febrile phase -After 5-8 /7 following bite→ sudden onset ↑↑ fever 
( up to 40° ) Headache , chills , muscle aches Typical duration 0-7 days -During febrile phase – leukopenia . ↓ platelets , ↑↑ AST, ALT and ↓↓ Na may be seen

 see warning signs

 

Critical phase -Occurs in defervescence 
( fever ↓ to 38° or less) around day 3-8 after the onset of illness Period where ↑ capillary permability and plasma leakage can happen ( lasts 24-48 hrs ) Severe leakage → shock when a critical vol of plasma is lost Seen more frequently in secondary dengue infection ↓↓ Platelets and ↑↑ in hematocrit.

 

Critical phase -After 24-48 hrs a gradual reabsorption of extravascular compartment fl takes place in 48-72 hrs Gen well being improves Appetite returns GI symptoms abate HD stability , ↑ diuresis some may have gen itching

 

Warning signs -Persistent vomiting Severe abdominal pain Lethargy and / or restlessness or a sudden change in behaviour Bleeding for e.g
○ epistaxis
○ malena / haematemesis
○ heavy vaginal bleeding
○ haematuria Postural hypotension – dizziness Pale , cold clammy hands Reduced oral intake and urine output Problems breathing Hepatomegaly > 2 cm Clinical fluid accumulation e. g ascites Rise in haematocrit with a fall in platelet count

 

Dengue fever -Abrupt onset symptoms 3-14 days after bite ( mostly 4-7 days) Fever ( may be biphasic ) , severe frontal headache , retro-orbital pain Intense myalgia and arthralgia ( break bone fever ) Anorexia and nausea Blanching rash after a few days
 ( transient ) Mild haemorrhagic manifestations Main complications are febrile seizure and dehydration Avoid aspirin- bleeding risk

 

WHO case definition DHF -starts same as DF but after 2-7 days ( when fever subsides ) signs of bleeding and ↑ vascular permeability manifest Fever or h/o acute fever Haemorrhagic tendencies -shown by
+ ve tourniquet test
petechiae , ecchymoses or purpura
bleeding Thrombocytopenia Signs of plasma leakage for e.g ^ in Hct or clinical signs as ascites , pleural effusion

 

Dengue shock syndrome -Criteria of DHF + Circulatory failure
 ► Rapid pulse and narrow pulse pressure
 ►Hypotension for age , restlessness and cold clammy skin
 Fatality rates can be 10 % or ↑ but with early recognition and treatment can be < 1 %

 

Severe dengue infection can cause complications as liver failure , disseminated intravascular coagulation , encephalopathy , myocarditis , acute renal failure and haemolytic uraemic syndrome

 

Differentials dengue -Infectious mononucleosis Chickengunya viral infections Coxsackie and other enteroviral infections Rickettsial infections Rubella Parvovirus B19 infections Leptospirosis Influenza

 

Acute gastroenteritis Urinary tract infection or pyelonephritis Asthma attack Cholecystitis Hepatitis Leptospirosis Meningococcemia Malaria Toxic shock syndrome Kawasaki disease

 

Reduced platelet counts of < 100 x 109
( best indicator of plasma leakage ) Leucopenia ( early in disease ) Atypical lymphocytosis Abnormal coagulation profile Reduced serum component levels Low albumin Positive tourniquet test.

 

Virus can be isolated from serum , plasma or leucocyte Ideally blood should be collected before 5th day of illness Reverse transcription PCR ( RT-PCR ) provide same or next day diagnosis of DENV NS1 antigen capture ELISA ( during the febrile phase ie 1st 5 days of fever ) Serology – more useful once fever has settled 

A combination approach may be necessary for a patient who may present at a different stage in their infection for virus and / or viral product detection.

 

Management is supportive and depends upon the phase of illness and the clinical status ( restoration of plasma volume is the mainstay of Rx in DHF ) Consider admitting patients with
○ thrombocytopenia and poor appetite / poor clinical condition
○ infants
○ obese patients
○ pregnant mothers
○ elderly
○ patients with co-morbidities 
○ patients with likely complications as shock , fluid accumulation with respiratory distress , bleeding or severe organ involvement.

References

  1. Manson’s Tropical Disease E-Book – Jeremy Farrar et al Saunders Ltd October 2013
  2. Dengue , Dengue Haemorrhagic Fever and Dengue Shock Syndrome in the Context of the Integrated Managenent of Childhood Illness WHO / FCH/ CAH/05.13
  3. Dengue Guidelines For Diagnosis , Treatment and Prevention and Control : New Edition 2009
  4. WHO Dengue :
  5. Oxford Handbook of Tropical Medicine Edited by Robert Davidson et al Oxford University Press January 2014
  6. Dengue Fever BMJ 2015 ;351 : h4661
  7. Dengue cases in India doubled in 2014-15 BMJ 2015 ;351: h6676
  8. Dengue Fever : National Health Portal of India accessed via 
https://www.nhp.gov.in/disease/musculo-skeletal-bone-joints-/dengue-fever
  9. National Guidelines for the Management of Dengue Fever : National Vector Borne Disease Control Programme Government of India Feb 2015
  10. Dengue in India Nivedita Gupta et al Indian J Med Res . 2012 Sep ; 136(3) :373-390
  11. Manoj Murhekar, Vasna Joshua, K. Kanagasabai, Vishal Shete, M. Ravi, R. Ramachandran, R. Sabarinathan, B. Kirubakaran, Nivedita Gupta, Sanjay Mehendale,
    Epidemiology of dengue fever in India, based on laboratory surveillance data, 2014–2017,
    International Journal of Infectious Diseases,
    Volume 84, Supplement,2019,
  12. Murray, Natasha Evelyn Anne et al. “Epidemiology of dengue: past, present and future prospects.” Clinical epidemiology vol. 5 299-309. 20 Aug. 2013, doi:10.2147/CLEP.S34440
  13. Lum, Lcs et al. “Managing dengue fever in primary care: A practical approach.” Malaysian family physician : the official journal of the Academy of Family Physicians of Malaysia vol. 9,2 2-10. 31 Aug. 2014
  14. CDC Dengue training Noninfectious Etiologies (cdc.gov)
  15. Malavige GNFernando SFernando DJ, et al
    Dengue viral infections
  16. Zhang QChen YFu Y, et al
    Epidemiology of dengue and the effect of seasonal climate variation on its dynamics: a spatio-temporal descriptive analysis in the Chao-Shan area on China’s southeastern coast
  17. Clinical Manifestations and Management of Dengue/DHF/DSS
    Siripen Kalayanarooj
    00 Published online 22 December, 2011 Tropical Medicine and Health Vol. 39 No. 4 Supplement, 2011, pp. 83-87
    doi:10.2149/tmh.2011-S10 The Japanese Society of Tropical Medicine
  18. Chan, Hui Bin Yvonne et al. “Definitive tests for dengue fever: when and which should I use?.” Singapore medical journal vol. 58,11 (2017): 632-635. doi:10.11622/smedj.2017100
  19. Dengue vaccine WHO | Dengue vaccine research

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