(The Lancet) On dengue

[Snowy Owl]

Gratitude to Florida1, Director and President of Flu Trackers

Is there an inapparent dengue explosion?

The Lancet 1999; 353:1101
DOI:10.1016/S0140-6736(05)76461-8

Jos? G Rigau-P?rez, and Duane J Gubler

Authors' reply
Sir?We agree with Scott Halstead that many dengue infections are clinically inapparent, and their frequency varies with the strain of virus and the epidemiological circumstances. Dengue infection causes a spectrum of illness ranging from truly inapparent infection, through mild viral syndrome and classic dengue fever, to DHF. As a result of poor surveillance, many clinically mild dengue infections are not reported as dengue fever but as malaria or viral syndrome.

Annual global reports of dengue cases to WHO averaged over 340 000 for 1991?95.1 Most locations, even with good reporting, will have a ratio of diagnosed to reported dengue fever cases of at least 10/1, and in many areas (owing to mild cases, misdiagnosis, and difficulties of reporting), the ratio of dengue fever cases with symptoms to those actually reported may be higher than 100/1. In view of the poor surveillance for dengue fever in most countries, the high frequency, and expansion of epidemic dengue in past years, we believe that the estimate of 50?100 million aanual cases of dengue fever is valid.

Case fatality rates are the ratio of fatal cases to the number of patients with the illness (usually expressed as a percentage). Halstead cites case fatality rates that refer to groups of patients that differ from the group we examined. The rates he cites for Asian nations (0?05?3?5%) represent the number of deaths per 100 cases of DHF or dengue shock syndrome (DSS).

The case fatality rate for Cuba in 1981 (1?5%) represents the number of deaths per 100 dengue cases admitted to hospital. These values are lower than the case fatality rate for DSS, because the denominators include patients with less severe illness than DSS. The placebocontrolled, double-blind trial of steroid treatment for severe DSS by Tassniyom and colleagues2 done in an academic setting in which there was management experience of DSS showed a case fatality rate of 12?7%. Among four other studies presented in that report, we referred only to the highest reported case-fatality rate, but our phrasing indicates that this is an extreme value (?can be as high as??), and not the benchmark. The few reports available on the case fatality rate of DSS have small sample sizes, and may produce inaccurate estimates. We therefore hope that this discussion will encourage other researchers to report case-fatality rates in dengue patients with well characterised severity stages (such as hypotension or shock). Carerful attention to blood pressure in all patients should result in improved care, because the prognosis for DHF and DSS depends on prevention or early recognition and treatment of shock.

<!--start simple-tail=-->References

1. WHO. Dengue haemorrhagic fever; diagnosis, treatment, prevention and control. Geneva: WHO, 1997:.
2. Tassniyom S, Vasanawathana S, Chirawatkul A, Rojanasuphot F. Failure of high dose methylprednisone in established dengue shock synndrome: a placebocontrolled, double-blind study. Pediatrics 1993; 92: 111-115. MEDLINE

 

[Snowy Owl]

Re: (The Lancet) On dengue

The Lancet 1999; 353:1100-1101
DOI:10.1016/S0140-6736(05)76460-6
Is there an inapparent dengue explosion?Scott B Halstead a

Sir
Jos? Rigau-Perez and colleagues,1 inflation of global annual morbidity data and case fatality rates for dengue could have serious unintended consequences. In their introductory paragraphs, the investigators estimate 50?100 million dengue cases annually. A number of this magnitude was first suggested in 1988.2 It is becoming increasingly clear, however, that most dengue infections are inapparent. Although dengue fever is reported in only a few countries, comprehensive data for dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) have been reported to regional offices of WHO for more than 30 years. Summaries have been published from time to time.3 For many western and other countries, these data include cases of dengue fever, but global totals seldom exceed 500 000 annually. Most of the estimated 50?100 million dengue infections occur in children, and when studied carefully, are largely silent.

In their summary, the investigators state that ?case fatality rates in patients with dengue shock syndrome can be as high as 44%.? This value is taken from a fairly small hospital-based treatment study (the case fatality rate reported in the original text was 38%) in which the most severely ill patients were recruited to allow an evaluation of a putative life saving therapeutic regimen.4 Nowhere are reliable national statistics available for incidence of DSS. As a result, DSS case fatality rates are not well known. Case fatality rates for DHF and DSS are available.3 For 12 Asian countries, cumulative DHF-DSS case fatality rates vary between 0?5% and 3?5%.

Physicians need reliable data on prognosis of DHF and DSS to plan treatment regimens, allocate scarce resources and counsel families. In the Americas, Cuban physicians, confronted for the first time with DHF and DSS, took justifiable pride in achieving a case fatality rate of 1?5% among 10 000 cases admitted in the 1981 epidemic.5 This rate is the benchmark, and not 44%.


<!--start simple-tail=-->References

1. Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue haemorrhagic fever. Lancet 1998; 352: 971-977. Abstract | Full Text | PDF (193 KB) | CrossRef
2. Halstead SB. Pathogenesis of dengue: challenges to molecular biology. Science 1988; 239: 476-481. MEDLINE
3. Halstead SB. Epidemiology of dengue and dengue hemorrhagic fever In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, UK: CAB International, 1997: 23-44.
4. Min M, Tin U, Aye M, Shwe TN, Swe T, Aye B. Hydrocortisone in the management of dengue shock syndrome. Southeast Asian J Trop Med Public Health 1975; 6: 573-579.
5. Kouri G, Guzman MG, Bravo JR, Triana C. Dengue haemorrhagic fever/dengue shock syndrome: lessons from the Cuban epidemic, 1981. Bull Work Health Organ 1989; 67: 375-380.

 

[Snowy Owl]

Re: (The Lancet) On dengue and Encephalitis

Re: (The Lancet) On dengue and Encephalitis

The Lancet 2002; 360:261
DOI:10.1016/S0140-6736(02)09481-3
Encephalitis and dengue
Enid J Garc?a-Rivera and Jos? G Rigau-P?rez

Sir
Richard Whitley and John Gnann (Feb 9, p 507) review common and emerging pathogens associated with viral central nervous system (CNS) infections. Nevertheless, they do not mention dengue, an acute viral disease transmitted by Aedes mosquitoes, and highly endemic in many tropical and subtropical areas of the world.

Indirect effects of dengue infection on the CNS may be an explanation for encephalopathy, but the presence of IgM antibody to dengue in the cerebrospinal fluid (CSF) and reports of virus isolation from brain tissue and CSF of patients with neurological symptoms suggest direct virus invasion of the CNS.

Three types of neurological manifestations have been associated with confirmed dengue infection: non-specific symptoms of headache, dizziness, delirium, drowsiness, sleeplessness, and restlessness; severe syndromes of depressed sensorium, lethargy, confusion, seizures, meningismus, paresis, and coma that are sometimes clinically indistinguishable from encephalitis; and delayed syndromes of paralysis of lower or upper extremities or larynx, seizures, tremors, amnesia, loss of sensation, manic psychosis, depression, dementia, and Guillain-Barr? syndrome.

Neurological complications associated with dengue infection can arise in dengue fever and dengue haemorrhagic fever. Any virus serotype may be involved, but DEN-2 and DEN-3 are most frequently reported as the cause of severe neurological disease. Most reported cases of dengue encephalopathy or encephalitis recover without neurological sequelae.3

The frequency of neurological changes as the presenting sign in dengue is unknown, but neurological complications associated with dengue infection have been recognised since the beginning of the 20th century and reported in almost every country in Asia and in many countries in the Americas.3

In one study in Vietnam, 4% of patients admitted to a neurology ward with suspected CNS infections were infected with dengue virus,4 and in Thailand, 18% of children admitted to a hospital with encephalitis-like illness were confirmed as having dengue infection.5 In Indonesia, 70% of virologically confirmed fatal dengue infections (n=30) presented with one or more neurological signs, and 7% were admitted for viral encephalitis, which was listed as the cause of death.3

The re-emergence of dengue as an important pathogen justifies its inclusion in the differential diagnosis of patients with acute onset of encephalitis in endemic countries or with a travel history suggestive of dengue exposure.


<!--start simple-tail=-->References

1. Whitley RJ, Gnann W. Viral encephalitis: familiar and emerging pathogens. Lancet 2002; 359: 507-514. Abstract | Full Text | PDF (399 KB) | MEDLINE | CrossRef
2. Lum LC, Lam SK, Choy YS, George R, Harun F. Dengue encephalitis: a true entity?. Am J Trop Med Hyg 1996; 54: 256-259. MEDLINE
3. Gubler DJ, Kuno G, Waterman SH. Neurologic disorders associated with dengue infection: proceedings of the International Conference on Dengue/Dengue Hemorrhagic Fever, Kuala Lumpur, Malaysia, September 1983: 290-301.
4. Solomon T, Dung NM, Vaughn DW, et al. Neurologic manifestations of dengue infection. Lancet 2000; 344: 1053-1059.
5. Kankirawatana P, Chokephaibulkit K, Puthavathana P, et al. Dengue infection presenting with central nervous system manifestation. J Child Neurol 2000; 15: 544-547. MEDLINE