International Journal of Infectious Diseases
Volume 14, Supplement 3 , Pages e54-e59, September 2010

Multiple dengue serotypes and high frequency of dengue hemorrhagic fever at two tertiary care hospitals in Lahore during the 2008 dengue virus outbreak in Punjab, Pakistan

Department of Medicine, Allama Iqbal Medical College and Jinnah Hospital, Maulana Shabbir Ahmed Usmani Road, Lahore 54550, Punjab, Pakistan

Received 15 June 2009; received in revised form 9 October 2009; accepted 15 October 2009. published online 22 February 2010.

Corresponding Editor: Jane Zuckerman, London, UK

Article Outline

Summary 

Objective

The objective of this study was to investigate the clinical characteristics of patients with dengue viral infection during the 2008 outbreak in Lahore in order to better understand the clinical pattern and severity of disease in Lahore.

Methods

We analyzed the clinical characteristics of 110 patients infected with dengue virus; data were collected on standardized data collection sheets at two tertiary care hospitals from September to December 2008. Dengue infection was confirmed serologically or by real-time polymerase chain reaction (RT-PCR).

Results

Out of the total of 110 dengue infected patients, 70 were male and 40 were female. The most common symptoms included fever (100%), myalgia (68.2%), headache (55.5%), nausea (39.1%), skin rash (53.6%), mucocutaneous hemorrhagic manifestations (58.2%), and ocular pain (20%). Classic dengue fever (DF) was seen in 41.8% of the patients, 56.4% had dengue hemorrhagic fever (DHF), and only 1.8% developed dengue shock syndrome (DSS). The mean duration of fever was 6 days. Thrombocytopenia, leukopenia, and abnormal aspartate aminotransferase (AST)/alanine aminotransferase (ALT) were more frequently encountered in DHF and DSS as compared to DF. Viral RNA detection was done by RT-PCR in 17 patients. Ten patients had DEN4, five had DEN2, and two had DEN3 serotypes. The majority of the patients recovered completely without complications.

Conclusion

The high frequency of DHF during the 2008 outbreak and the presence of three different dengue serotypes, emphasize the need to prevent and control dengue infection. Health authorities should consider strengthening surveillance for dengue infection, given the potential for future outbreaks with increased severity. It is also suggested that primary care physicians should be educated regarding recognition of DHF and to identify patients at high risk of developing DHF and DSS.

Keywords: Dengue fever, Dengue serotypes, Dengue hemorrhagic fever, Pakistan

 

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1. Introduction 

Dengue viral infection is the most important arboviral disease of humans; approximately 100 million dengue fever (DF) cases and several hundred thousand cases of dengue hemorrhagic fever (DHF) occur annually.1 Dengue is one of the most frequent diseases in travelers from endemic areas,2 and the large volume of human travel is a major contributing factor to the geographical spread of dengue viruses. The most common vector, Aedes aegypti, although African in origin has spread throughout the world; a result of trade and increased human travel.3

DF is an illness with profound social, economic, and health costs to society.4 In many developing tropical countries outbreaks are a huge economic burden.5 Dengue emerged as a major public health burden in Southeast Asia after the Second World War and has now become more important, with progressively longer6 and more frequent epidemics of DF/DHF in this part of the world. Despite this trend, surveillance for this vector-borne viral disease remains largely passive in most Southeast Asian countries. The most worrisome problem of dengue resurgence is that it comes with increased frequency, severity and a high incidence of DHF, a severe complication of this disease that usually arises upon re-infection with a different serotype.7 In contrast to DF, which is usually a self-limiting viral illness, DHF is a serious complication of dengue infection with significant morbidity and mortality.8

Outbreaks of dengue follow a predictable epidemiological pattern; frequent transmission of the virus with sporadic cases of DHF, followed by increasingly frequent outbreaks that steadily increase in size, eventually establishing a pattern of epidemics occurring every 2–5 years, with sporadic cases in the intervening periods. In the past, outbreaks of a variety of viral hemorrhagic fevers (VHF) including DHF have been reported in Pakistan. The first confirmed outbreak of DHF in Pakistan was reported from Karachi in 1994 and in the following year an epidemic of DF occurred in Baluchistan.9, 10 Later, a large outbreak occurred in Pakistan in 2006; Khan et al. reported co-circulation of DEN2 and DEN3 serotypes during this 2006 outbreak in Karachi.11 Recently, a change in the pattern, clinical spectrum, and outcome of this disease has been reported, with an increased incidence of DHF in clinical practice.12, 13 Also, during recent outbreaks in Asia, it has been noted that DHF is becoming increasingly common, that the circulation of multiple serotypes appears to be established, and that outbreaks of DHF have become more frequent.14, 15

Although dengue has become the most important vector-borne disease in Pakistan over the last decade, published scientific research dealing with the local situation regarding the pattern of clinical disease is limited. We therefore conducted a study to investigate the clinical and pathological profile of the patients with dengue viral infection during the 2008 outbreak in Lahore in order to assess the disease severity and to better understand the clinical pattern of the disease in Pakistan.

The objective of this study was to investigate the clinical and pathological profile of subjects suffering from dengue viral infection presenting to two tertiary care teaching hospitals in Lahore, Pakistan during the 2008 outbreak. The variables investigated were the most common clinical features, disease progression, grades of disease severity, and outcome.

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2. Materials and methods 

From September to December 2008, we collected and analyzed the clinical and laboratory data of 110 patients from the special dengue wards of the two tertiary care teaching hospitals in Lahore, after obtaining informed consent. The study was approved by the Ethics Committee of Allama Iqbal Medical College and Jinnah Hospital, Lahore, Pakistan.

A subject was defined as having a ‘suspected’ case of dengue virus infection if they gave a history of acute onset fever with constitutional symptoms, thrombocytopenia, and a positive IgM alone or positive IgG antibody test. A ‘confirmed’ case of acute dengue viral infection was defined as a suspected case with either positive dengue virus serotyping on real-time polymerase chain reaction (RT-PCR) or a four-fold or greater rise in IgM or IgG antibody titer in a paired serum sample. Only confirmed cases of dengue from these two tertiary care hospitals were included in our study. All confirmed cases of dengue viral infection were classified into one of three subtypes – DF, DHF, and dengue shock syndrome (DSS) – on the basis of their clinical and pathological profile, using the World Health Organization (WHO) criteria.16

Cases were classified as DHF if they met the four necessary criteria, i.e., fever or recent history of acute fever, hemorrhagic manifestations, low platelet count (≤100×109/l), and objective evidence of ‘leaky capillaries’ (evidenced by elevated hematocrit (20% or more over baseline), low albumin, pleural or other effusions, and a positive tourniquet test). Subjects meeting the criteria of DHF with evidence of circulatory failure manifested by a rapid and weak pulse, narrow pulse pressure (≤20 mmHg) or hypotension for age, cold clammy skin, and altered mental status were classified as DSS.

Laboratory investigations were performed on admission and throughout the hospital stay. Laboratory tests included full blood count, prothrombin time, activated partial thromboplastin time (APTT), blood urea nitrogen, serum creatinine, serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum protein, serum albumin, serum electrolytes, urinalysis, anti-dengue IgM and IgG by ELISA, and dengue serotype by PCR. Dengue RNA was isolated from the serum by QIAmp Ultra-sense RNA Mini Kit (Qiagen, Valencia, CA, USA). Dengue RNA in the patient sample was amplified by the Qiagen Dengue Real Time PCR Kit (Qiagen) using the specific standard on Rotor-Gene (Qiagen). In the RT-PCR, the amplified product was detected using fluorescent dyes. These were linked to oligonucleotide probes that were bound specifically to the amplified product. Monitoring the fluorescence intensities during the PCR run allowed the detection and quantitation of the accumulating product without having to re-open the reaction tubes after the PCR runs. Serotyping analysis was performed on the same amplified product and was followed by a melt curve analysis to differentiate the dissociation points of each serotype for dengue virus cDNA. The sensitivity of this dengue assay is 98% and the specificity is 99%.

Clinical information and laboratory abnormalities of patients with confirmed dengue infection were collected by trained researchers on a data collection sheet. Data were compiled and analyzed anonymously using SPSS v.11 (SPSS Inc., Chicago, IL, USA).

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3. Results 

A total of 483 suspected cases of dengue viral infection were admitted to the special dengue wards of the two teaching hospitals during the study period. One hundred and ten confirmed dengue-infected cases aged 15 years and above were enrolled in our study. Seventy of the 110 subjects were male (63.6%). All adult age groups were represented (Figure 1). The total duration of fever, day of presentation after onset of symptoms, and total duration of hospital stay are shown in Figure 2, Figure 3, Figure 4, respectively.

The presenting complaints of all the patients were typical of dengue viral infection, i.e., fever, malaise and myalgias, retro-orbital pain, and skin rash or any hemorrhagic manifestation. The most common symptoms were fever (100%), myalgia (68.2%), headache (55.5%), nausea (39.1%), non-hemorrhagic skin rash (53.6%), mucocutaneous hemorrhagic manifestations (58.2%), and eye strain and retro-ocular pain (20%). Patients were mostly referred from their local general practitioner or primary healthcare center.

On examination, the most common findings included tachycardia, fever, and slight reduction in blood pressure. Frank hypotension was noted in only two patients. Pleural effusion and hepatomegaly was noted in 31 (28.2%) patients. None of the patients developed ascites or pericardial effusion. No focal neurological deficits or altered state of consciousness was observed in any subject.

Cutaneous manifestations were present in 64.5% of patients. The most common observation was a maculopapular or a morbilliform eruption in 53.6% and a hemorrhagic skin rash like purpura, ecchymoses or petechial rash in 51.8%. A non-hemorrhagic cutaneous rash was also more common in patients with DHF as compared to DF. Overall, hemorrhagic manifestations, noted in 64 (58.2%) patients, were usually mild. These included hemorrhagic skin rash in 51.8%, epistaxis in 15.5%, bruises in 10%, hematuria in 9.1%, gingival bleed in 8.2%, hemoptysis in 5.5%, hematemesis in 2.7%, vaginal bleed in 2.7%, hematochezia in 2.7%, and subconjuctival hemorrhage in only 0.9% of the patients (Table 1). Only 3.6% of cases had severe hemorrhagic complications, but they responded well to intravenous fluids, platelet concentrates, and whole blood transfusions.

Table 1. Clinical manifestations of the 110 hospitalized cases during the 2008 dengue virus outbreak in Lahore, Pakistan
Clinical featuresFrequencyPercentage
Fever110100%
Rash5751.8%
Epistaxis1715.5%
Bruise1110%
Hematuriaa109.1%
Gingival bleed98.2%
Hemoptysis65.5%
Hematemesis32.7%
Vaginal bleed32.7%
Hematochezia32.7%
Any hemorrhageb10.9%

aMicroscopic hematuria defined as more than five red blood cells per high-power field.

bOne person developed retinal hemorrhage.

The total duration of fever ranged from 3 to 16 days, while the mean duration of fever was around 6 days. Two patients developed a nosocomial infection during their stay in hospital. Fever responded well to antipyretic therapy and no specific pattern was observed. None of the patients developed seizures, meningo-encephalitis, or encephalopathy.

Among the laboratory abnormalities, thrombocytopenia, a low total leukocyte count, raised hematocrit, and deranged liver function tests were frequently encountered. Abnormal serum creatinine was found in 10/92 (10.9%) of the cases. There was no specific association of these laboratory abnormalities with age, gender or grade of fever, but a definitive association was found with the type of dengue clinical syndrome. Thrombocytopenia, leukopenia and abnormal AST/ALT were more frequently encountered in DHF/DSS as compared to DF (Table 2). Out of 110 patients, 46 were diagnosed as cases of DF, while 62 were diagnosed as DHF and two as DSS.

Table 2. Comparison of laboratory characteristics between the three dengue clinical syndromes in the 2008 outbreak in Lahore, Pakistan
Hemoglobin (%)White cell count (× 109/l)Platelet count (× 109/l)HematocritASTALTSerum proteinSerum albumin
DF12.5±1.675.452±2.203112.739±29.17438.37121±36125±416.75±0.573.39±0.46
(9.8–17)(1.700–10.000)(50.000–190.000) (25–210)(35–230)(5.1–7.8)(2.1–5.2)
N4646463244434043
DHF12.74±2.324.047±2.19147.861±24.08041±6.5126.5+56.5125.7±616.5±0.643.07±0.43
(8.50–17.3)(0.800–10.000)(2.700–97.000)(29–54)(25–230)(28–245)(4.9–8.0)(1.9–4.0)
N6262624946473346
DSS11.55±3.462.200±0.14117.500±0.70727176.5±75.6193.5±945.5±0.702.95±0.07
(9.1–14)(2.100–2.300)(17.000–18.000) (123–230)(127–260)(5–6)(2.9–3.0)
N22212222
Total12.63±2.0754.600±2.29674.440±41.90839.76±6.22124.82±48.4126.9±53.66.63±0.643.22±0.47
(8.5–17.3)(0.800–10.000)(2.700–190.000)(27–54)(25–230)(28–260)(4.9–8)(1.9–5.2)
N1101101108292927591

Results are mean±standard deviation (range).

DF, dengue fever; DHF, dengue hemorrhagic fever; DSS, dengue shock syndrome; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

DHF was more common among males as compared to females (Table 3). Out of the 62 DHF cases, 10 were grade 1, while 52 were grade 2, according to the WHO severity grading for DHF. The two cases of DSS were of grade 3 severity. The proportion of dengue clinical syndromes and severity of disease was similar in the young and old age groups. A total of 17 patients had their viral RNA detected by RT-PCR and had serotyping done. Three different serotypes were detected in this small number of patients. Ten of 17 were of DEN4 serotype, while 5/17 were serotype DEN2 and 2/17 were serotype DEN3.

Table 3. Sex distribution of dengue clinical syndromes during the 2008 outbreak in Lahore, Pakistan
Dengue clinical syndrome
DFDHFDSSTotal
Sex of patient
Female22 (20%)18 (16.4%)–40 (36.4%)
Male24 (21.8%)44 (40%)2 (1.8%)70 (63.6%)
Total46 (41.8%)62 (56.4%)2 (1.8%)110 (100%)

Results are n (% of total).

DF, dengue fever; DHF, dengue hemorrhagic fever; DSS, dengue shock syndrome.

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4. Discussion 

Our study shows that all adult age groups (≥15 years) were equally infected by dengue infection, although a slightly increased frequency was found in the age group 20–30 years. Overall, the outcome for patients was good, and neither the young nor the old were specifically found vulnerable to complications. However, it is very important to include the pediatric age group for accurate assessment of age distribution patterns in dengue. In this study, we focused only on adults presenting with dengue infection, so we cannot compare the incidence of infection between the adult and pediatric age groups for this outbreak. In future studies, we intend to include pediatric subjects with dengue infection in order to understand the whole disease profile. However, an unpublished provincial report of confirmed dengue cases during the 2008 outbreak in Punjab, revealed that out of 1407 reported cases, 785 were under 15 years of age (source: data obtained through personal communication with Punjab's focal person for the prevention and control of dengue fever and the director of Dengue Cell, D.G. Office Punjab, Dr Zafarul Islam). This shows that the majority of the cases were reported in the pediatric age group during this outbreak. Qureshi et al., studied hospital admitted cases during the course of an outbreak of dengue viral fever in Karachi, Pakistan from June 1994 to September 1995 and reported a higher frequency of DF in the younger population.17 A report from India revealed that the highest incidence during the 2003 outbreak in Delhi was among young adults,18 whereas various previous studies have reported the highest incidence in children.19 In Southeast Asia (e.g., Thailand and the Philippines), children are most likely to be affected.19 However, in areas of lower endemicity, such as the Americas, any age group may be affected,20, 21 although the incidence has been reported to be higher in children under 15 years of age.

The majority of patients presented within the first 5 days of the onset of fever, which seems to be due to better public awareness as a result of a very active media campaign. The duration of fever was less than 10 days in the majority of patients (94.5%), while a few patients (5.5%) had a prolonged duration of fever (i.e., 10–16 days). This finding is in contrast to various other previous studies of DF, where the usual duration of fever is reported as being up to 10 days.22 All of the patients having a prolonged duration of fever in our study had relatively more severe disease with a prolonged hospital stay. A characteristic finding among these patients was a persistently high level of aminotransferases. All of these patients were also investigated extensively for any other possible cause of prolonged fever, but no other cause of fever was found. Two out of these six patients with a prolonged duration of fever were in WHO severity grade 3, while four patients were in severity grade 2.

Fever was the most common presenting complaint, while non-hemorrhagic skin rash and hemorrhagic mucocutaneous manifestations like petechiae and epistaxis were also not uncommon as the initial presentation. The most common findings included tachycardia, fever, and a slight reduction in blood pressure, while hepatomegaly, ascites and pleural effusion were not encountered frequently. Neither focal neurological deficits nor an altered state of consciousness was observed in any of the patients.

Leukopenia, thrombocytopenia, and low serum albumin affected patients in a similar fashion as reported from other parts of Asia,15, 18, 23 but an increase in hematocrit was not as commonly seen as in various other studies. This may be because of the judicial use of fluids and supportive therapy in the hospital. Thrombocytopenia and leukopenia were more frequently encountered in DHF and DSS as compared to DF. Another very commonly observed finding was an asymptomatic elevation of liver enzymes, again more frequently encountered in DHF and DSS as compared to DF, and this has also been reported by Faridi et al. in India.23 Multicenter studies integrating different centers in Asia may be beneficial to better understand the changing trends in clinical presentations specific to the region. In our study, only 3% of patients developed acute renal failure, lower than the 5% incidence reported by Lee et al.8 This could be explained by the fact that patients in our study were younger and patients presented earlier during the course of infection. Hence, early recognition of the clinical features and early fluid repletion may play a key role in preventing life-threatening complications.

In our study, a large proportion of hospitalized dengue patients (58.2%) developed hemorrhages. Previous hospital-based studies from other countries of this region, as well as from Pakistan, have revealed relatively lower rates of hemorrhagic manifestations when compared with our study.16, 17, 24

A decade-wise analysis of data on DF from America showed a steady increase in the proportion of DHF. Similarly if we go through the limited data of dengue outbreaks in Pakistan, we see an increase in the incidence and severity of this disease in clinical practice. Chan et al. reported the first confirmed outbreak of DHF in Karachi, which occurred in 1994.9 The following year, in 1995, an epidemic of DF among employees of a construction contractor at a power generation plant in Baluchistan was reported.10 This was an outbreak of DF due to multiple serotypes of dengue virus. The frequency of DHF was less documented in Pakistan until a large outbreak occurred in Karachi in 2006 when Khan et al. reported co-circulation of DEN2 and DEN3 serotypes during this outbreak in Karachi.11 Primary and secondary cases were also found in both groups. During this outbreak, Ahmed et al. reported only two cases of DHF out of 40 confirmed dengue cases.13 Recently, a change in pattern, clinical spectrum, and outcome of this disease has been reported, with a gradual increase in the incidence of DHF in clinical practice at tertiary care hospitals in Karachi.12, 13 All previous studies of DF in Pakistan have mainly been reported from Karachi. So far no dengue data have been reported from Lahore, which is the second most populous city of Pakistan and also the capital of the Punjab, which is the most populous province of Pakistan. This is the first reported outbreak of DF from Lahore.

According to an unpublished provincial report of confirmed dengue cases from 2008, produced by the Dengue Cell, D.G. Office Punjab, there were 113 confirmed cases of dengue viral infection in 2006 and 232 cases in the year 2007. Three deaths occurred in the whole of Punjab during this period due to complicated dengue infection. The figures for 2008 were very high, with 1407 cases reported from all over Punjab; nine deaths were reported due to complicated dengue infection (source: data obtained through personal communication with Punjab's focal person for the prevention and control of DF and director of the Dengue Cell, D.G. Office Punjab, Dr Zafarul Islam). Similarly, the number of cases admitted to the special dengue ward of one of the two tertiary care hospitals was also very high as compared to previous years. There were 63 admissions in 2006 and 71 in 2007, while the number of admissions in 2008 was 293. This may indicate a trend towards a higher frequency of dengue infection with increased severity during this outbreak.

In our study more than half of the patients with a dengue viral infection presented with DHF. The high percentage of DHF amongst hospitalized patients during the 2008 dengue outbreak as compared to previous years is indeed alarming. A comparison of these data with those from previous years indicates a shift from mild illness towards a more severe manifestation of the disease, which could be interpreted as an epidemiologic transition pattern and may be a sign of hyperendemicity of the dengue virus in Lahore and possibly other regions of the country.

In South Asia, all dengue serotypes have circulated periodically. The presence of genotypes 2 and 3 were revealed in Karachi during the 2006 outbreak,11 but in addition to serotypes 2 and 3, we also found 10 cases of serotype 4. Locally acquired DHF with three different serotypes has only been reported recently in our study. The introduction of a new serotype (DEN4) and/or a genotypic shift of endemic serotypes (DEN2, DEN3) may have been the factors involved in the recent outbreak of DHF in this region. A large number of confirmed dengue cases during the 2008 outbreak in Lahore indicates that a substantial proportion were infected with the dengue virus, and because of the multiple dengue serotypes, this population might be even more susceptible to DHF if they receive a subsequent infection with a heterologous dengue serotype in the coming years.

In Pakistan, serologic and virologic conditions are now highly indicative of a locally acquired outbreak of DHF of a large magnitude in the future, so prevention of DF and the control of vectors have become increasingly important. Several simple steps can be taken to reduce the morbidity and mortality associated with dengue viral illness. Apart from vector control, continuing education of clinicians and primary care physicians is crucial for early recognition of DHF, especially in those patients with a prior history of DF. A careful history should be obtained from patients with a suspected dengue virus infection to ascertain the extent of illness during any previous dengue infection. This would help identify patients at high risk for developing DHF and DSS.

Even though dengue infection has contributed to a significant proportion of tropical illnesses in Pakistan, it has not received its due share of attention until recently. One of the aims of this study was to assess whether dengue infection is more than just a simple self-limiting viral infection. As it turns out, all the patients did eventually recover, although more than half did develop DHF, a more severe form of dengue infection. This finding is contrast to what practicing physicians believe. Our study has the potential to divert significant public health monies towards early detection and treatment. Last year, for the first time, the Government of Punjab offered free screening and treatment to the public and designated ‘dengue wards’ in all tertiary care hospitals. Our study will help reinforce the resolve of the Government to continue to strive for prevention and treatment of uncommon yet dangerous tropical diseases such as DF.

Since this was a hospital-based study, it does not reflect the true burden of dengue in our community. Community infection with DF is characterized by the ‘iceberg’ or pyramid phenomenon. At the base of the pyramid, most of the cases are asymptomatic, followed in increasing rarity by DHF and DSS. Since we had a higher number of patients with DHF than the ones with undifferentiated fever in our study population, one can postulate from this study that the base formed by undifferentiated fever may be very large, and thus the endemicity of dengue in the community could be quite high. It is therefore suggested that there is the need for further large clinical studies in Pakistan and other countries of the region to better understand the clinical spectrum, endemic pattern, and population genetics of dengue viral infection.

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Acknowledgements 

We thank Dr Abbas Raza, Assistant Professor of Medicine at Allama Iqbal Medical College and Dr Sobia Qazi, Assistant Professor of Medicine and Infectious Diseases at the Services Institute of Medical Sciences Lahore for providing technical help and writing assistance. We also thank Dr Zafarul Islam, focal person for the prevention and control of dengue fever and director of the Dengue Cell, D.G. Office Punjab for sharing provincial data of dengue infected cases for 2008 and the staff and working members who cared for the dengue patients at these two teaching hospitals.

Ethical approval: This study was approved by the Ethics Review Board and Institutional Review Board of Allama Iqbal Medical College and Jinnah Hospital, and all the International Committee of Medical Journal Editors conditions were met.

Conflict of interest: No conflict of interest to declare.

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References 

  1. Gubler DJ. Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol. 2002;10:100–103
  2. López-Vélez R, Tapia-Ruano C, García-Camacho A, Sánchez R. Dengue: a disease imported from the Indian subcontinent. Enferm Infecc Microbiol Clin. 1994;12:182–186
  3. Gubler DJ. Dengue and dengue hemorrhagic fever: its history and resurgence as a global public health problem. In:  Gubler DJ,  Kuno G editor. Dengue and dengue hemorrhagic fever. New York: CAB International; 1997;p. 1–22
  4. Suaya JA, Shepard DS, Siqueira JB, Martelli CT, Lum LC, Tan LH, et al. Cost of Dengue cases in eight countries in the Americas and Asia: a prospective study. Am J Trop Med Hyg. 2009;80:846–855
  5. Garg P, Nagpal J, Khairnar P, Seneviratne SL. Economic burden of dengue infections in India. Trans R Soc Trop Med Hyg. 2008;102:570–577
  6. Ooi EE, Gubler DJ. Dengue in Southeast Asia: epidemiological characteristics and strategic challenges in disease prevention. Cad Saude Publica. 2009;25(Suppl 1):S115–S124
  7. Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 1998;11:480–496
  8. Lee IK, Liu JW, Yang KD. Clinical characteristics, risk factors, and outcomes in adults experiencing dengue hemorrhagic fever complicated with acute renal failure. Am J Trop Med Hyg. 2009;80:651–655
  9. Chan YC, Salahuddin NI, Khan J, Tan HC, Seah CL, Li J, et al. Dengue haemorrhagic fever outbreak in Karachi, Pakistan, 1994. Trans R Soc Trop Med Hyg. 1995;89:619–620
  10. Paul RE, Patel AY, Mirza S, Fisher-Hoch SP, Luby SP. Expansion of epidemic dengue viral infections to Pakistan. Int J Infect Dis. 1998;2:197–201
  11. Khan E, Hasan R, Mehraj V, Nasir A, Siddiqui J, Hewson R. Co-circulation of two genotypes of dengue virus in 2006 outbreak of dengue hemorrhagic fever in Karachi, Pakistan. J Clin Virol. 2008;43:176–179
  12. Wasay M, Channa R, Jumani M, Zafar A. Changing patterns and outcome of dengue infection: report from a tertiary care hospital in Pakistan. J Pak Med Assoc. 2008;58:488–489
  13. Ahmed S, Arif F, Yahya Y, Rehman A, Abbas K, Ashraf S, et al. Dengue fever outbreak in Karachi 2006—a study of profile and outcome of children under 15 years of age. J Pak Med Assoc. 2008;58:4–8
  14. George R, Lam SK. Dengue virus infection—the Malaysian experience. Ann Acad Med Singapore. 1997;26:815–819
  15. Rai S, Chakravarti A, Matlani M, Bhalla P, Aggarwal V, Singh N, et al. Clinico-laboratory findings of patients during dengue outbreak from a tertiary care hospital in Delhi. Trop Doct. 2008;38:175–177
  16. Bandyopadhyay S, Lum LC, Kroeger A. Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever. Trop Med Int Health. 2006;11:1238–1255
  17. Qureshi JA, Notta NJ, Salahuddin N, Zaman V, Khan JA. An epidemic of dengue fever in Karachi—associated clinical manifestations. J Pak Med Assoc. 1997;47:178–181
  18. Singh NP, Jhamb R, Agarwal SK, Gaiha M, Dewan R, Daga MK, et al. The 2003 outbreak of dengue fever in Delhi, India. Southeast Asian J Trop Med Public Health. 2005;36:1174–1178
  19. Kittigul L, Pitakarnjanakul P, Sujirarat D, Siripanichgon K. The differences of clinical manifestations and laboratory findings in children and adults with dengue virus infection. J Clin Virol. 2007;39:76–81
  20. Isturiz RE, Gubler DJ, Brea del Castillo J. Dengue and dengue hemorrhagic fever in Latin America and the Caribbean. Infect Dis Clin North Am. 2000;14:121–140
  21. Rigau-Perez JG. Clinical manifestations of dengue hemorrhagic fever in Puerto Rico, 1990–1991. Puerto Rico Association of Epidemiologists. Rev Panam Salud Publica. 1997;1:381–388
  22. Shah I, Katira B. Clinical and laboratory abnormalities due to dengue in hospitalized children in Mumbai in 2004. Dengue Bulletin. 2005;29:90–96
  23. Faridi MM, Aggarwal A, Kumar M, Sarafrazul A. Clinical and biochemical profile of dengue haemorrhagic fever in children in Delhi. Trop Doct. 2008;38:28–30
  24. Lee MS, Hwang KP, Chen TC, Lu PL, Chen TP. Clinical characteristics of dengue and dengue hemorrhagic fever in a medical center of southern Taiwan during the 2002 epidemic. J Microbiol Immunol Infect. 2006;39:121–129

PII: S1201-9712(10)00018-4

doi:10.1016/j.ijid.2009.10.008

International Journal of Infectious Diseases
Volume 14, Supplement 3 , Pages e54-e59, September 2010

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