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Acta Tropica 105 (2008) 3944

Clinical profile and outcome of hospitalized patients during

first outbreak of dengue in Makkah, Saudi Arabia
Nasim A. Khan a,,1 , Esam I. Azhar b,2 , Suzan El-Fiky c,3 ,
Hosam H. Madani d,4 , Maha A. Abuljadial d,4 , Ahmad M. Ashshi e,5 ,
Abdulhafis M. Turkistani f,6 , Esam A. Hamouh f,6
a

Division of Rheumatology, University of Arkansas for Medical Sciences, Mail Slot - 509, 4301 West Markham, Little Rock,
AR 72205, United States
b Special Infectious Agent Unit, King Fahd Medical Research Center, P.O. Box 80216, Jeddah 21589, Saudi Arabia
c Department of Infection Control, Al Noor Specialist Hospital, Makkah, Saudi Arabia
d Jeddah Regional Laboratory, Jeddah, Saudi Arabia
e Department of Clinical Laboratory Medicine, Hera General Hospital, Makkah, Saudi Arabia
f General Directorate of Health Affairs, Makkah Region, Hera General Hospital, P.O. Box 10513, Makkah, Saudi Arabia
Received 22 March 2007; received in revised form 16 July 2007; accepted 26 September 2007
Available online 29 September 2007

Abstract
Objective: To describe clinical profile of patients with dengue virus infection hospitalized at a single center during the first outbreak of dengue in
Makkah, Saudi Arabia from April to July 2004.
Methods: Clinical information and laboratory abnormalities of patients with suspected dengue infection were collected by a standardized data
collection sheet and review of medical records. Dengue virus infection was confirmed by a positive IgM capture ELISA or RT-PCR.
Results: Of the 160 clinically suspected patients, 91 were confirmed (64 by IgM ELISA, 14 by RT-PCR and 13 by both) to have dengue virus
infection. Dengue serotypes 2 and 3 were identified in 19 and 4 patients respectively. Most patients were young adults with median age of 26
(range = 694) years and male:female ratio of 1.5:1. The common symptoms were fever (100%), malaise (83%), musculoskeletal pain (81%),
headache (75%), nausea (69%), vomiting (65%) and abdominal pain (48%). According to World Health Organization (WHO) classification (10
patients were excluded due to lack of serial hematocrits), 75 (93%) had dengue fever (DF) and 6 (7%) had dengue hemorrhagic fever (DHF). Only
one patient with DHF was in pediatric age group. Twenty-one patients (5 with DHF and 16 with DF) developed one or more clinical complications
that included bleeding (14), shock (4), seizures (3), acute renal failure (2), meningo-encephalitis (1), and secondary bacterial infection (1). Only one
patient with shock had dengue shock syndrome (DSS) by WHO classification. Development of clinical complications was significantly associated
with absence of musculoskeletal pain (p-value = 0.03), lower platelet counts (p-value = 0.03) and higher serum aspartate aminotransferase levels
(p-value = 0.04). The median duration of symptoms and hospitalization was 8 days (range = 318) and 4 days (range = 110) respectively. No
mortality was noted.
Conclusion: Occurrence of dengue virus infection in Makkah, Saudi Arabia is documented. Continued surveillance and effective vector control
programs are warranted due to unique population dynamics of Makkah that receives millions of pilgrims annually from all over the world.
2007 Elsevier B.V. All rights reserved.
Keywords: Dengue virus; Dengue hemorrhagic fever; Saudi Arabia; Clinical symptoms; Complications; Epidemiology

1
2
3
4
5
6

Corresponding author. Tel.: +1 501 686 6700; fax: +1 501 603 1380.
E-mail address: nakhan99@yahoo.com (N.A. Khan).
Formerly at Department of Internal Medicine, Al Noor Specialist Hospital, Makkah, Saudi Arabia.
Tel.: +966 26400000x25049; fax: +966 26952076.
Tel.: +966 2566500x1105.
Tel.: +966 26375233.
Tel.: +966 25201604.
Tel.: +966 25203535; fax: +966 25201554.

0001-706X/$ see front matter 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.actatropica.2007.09.005

40

N.A. Khan et al. / Acta Tropica 105 (2008) 3944

1. Introduction
Dengue virus is the most important arbovirus that causes
human disease. It belongs to Flaviridiae family, and is transmitted by mosquitoes Aedes aegypti and Aedes albopictus. There
are four related but antigenically distinct serotypes of dengue
virus designated as DEN-1, DEN-2, DEN-3, and DEN-4. Most
individuals with dengue virus infection are asymptomatic, or
develop dengue fever (DF) characterized by fever and nonspecific constitutional symptoms. A minority of patients develop
severe disease in the form of dengue hemorrhagic fever and
dengue shock syndrome (DHF/DSS) that begins like DF but is
characterized by abrupt development of severe vascular leakage
which may rapidly lead to shock or death (Gibbons and Vaughn,
2002). Dengue has become a global disease being reported from
more than 100 countries, with 2.53 billion people living in
areas at potential risk of dengue transmission. It is estimated
that 50100 million patients of dengue infection occur annually of which 250,000 progress to DHF/DSS resulting in 24,000
deaths (WHO, 1997).
Dengue like disease was observed in the Arabian Peninsula
in the late 19th century (18701873). The disease appeared in
Zanzibar, in Dar el Salam, on the East African coast, in Arabia
(Aden, Mecca, Madina and Jeddah) (Gubler, 1997). In Saudi
Arabia, dengue virus (DEN-2 serotype) was first isolated from a
fatal case of DHF in Jeddah, a port city on the Red Sea, in 1994
(Fakeeh and Zaki, 2001). Surveillance from 1994 to 2002 at a
referral laboratory in Jeddah reported 319 confirmed patients
of dengue viral infection, most of whom (91%) were detected
during 1994 epidemic. DEN-2, DEN-1 and DEN-3 serotypes
were identified in that order of frequency (Fakeeh and Zaki,
2003).
Makkah is a city in Western Saudi Arabia located 75 km
inland from Jeddah. It is considered the holiest city in Islam
visited by more than four million pilgrims from all parts of
the world to perform Hajj and Umrah (minor pilgrimage). It
has a resident population of 650,000. The city is served by six
major hospitals. In this paper, we describe clinical features and
outcome of patients with dengue infection that were hospitalized at Al Noor Specialist Hospital, a 550-bed teaching hospital
managed by the Ministry of Health, during 2004 epidemic in
Makkah.
2. Patients and methods
Suspected dengue virus infection was defined as the presence of fever and any two of the following: myalgia, headache,
arthralgia, skin rash, retro-orbital pain, hemorrhagic manifestation(s), or leucopenia (white blood cell [WBC] count of
<4 109 L1 ). Confirmation of dengue virus infection was
based on either positive IgM antibody detection by enzyme
linked immunosorbent assay (ELISA) or positive reverse transcriptase polymerase chain reaction (RT-PCR) for dengue virus.
A standardized form was used, on the day of admission, to
collect information from suspected patients with dengue fever
about demographic details and following symptoms: fever,
chills, malaise, myalgia, arthralgia, retro-orbital pain, headache,

anorexia, nausea, vomiting, pain abdomen, and bleeding. Details

about other symptoms, signs on physical examination, clinical
course and laboratory investigations were obtained by review of
the daily progress notes from patients medical records. The
duration of illness was assessed by the numbers of days it
took to return to usual health status from the disease onset.
Approval for the study was obtained from the Medical Research
Committee of the hospital and Ministry of Health, Saudi
Arabia.
The World Health Organization (WHO) grading system was
used to classify patient as having classic dengue fever (DF)
and dengue hemorrhagic fever (DHF) (WHO, 1997). DHF
was defined as fever with thrombocytopenia (platelet count
<100 109 L1 ) and evidence of plasma leakage as manifested
by either a increase in hematocrit of 20% during the course
of hospitalization or a rise in hematocrit to more than 20%
of the average for Saudi Arabian population (average normal
hematocrit ratio for males: 0.45 and for females: 0.38) (AlBuhairan et al., 1999). As tourniquet test was not performed
on most of our patients to elicit development of petechiae as a
hemorrhagic manifestation, DHF was graded as DHF grade 1
(DHF1, no spontaneous hemorrhage) and DHF grade 2 (DHF2,
spontaneous hemorrhage). Dengue shock syndrome (DSS) was
diagnosed if patient fulfilled criteria for DHF along with signs
of shock as manifested by rapid and weak pulse, narrowing of
pulse pressure, or hypotension (DHF3); those with profound
shock with unrecordable blood pressure and pulse were classified as DHF4. A composite of clinical complications was defined
to include patients who had hemorraghic manifestations, shock,
seizures, altered mental status, acute renal failure and secondary
bacterial infection.
Blood samples were collected on the day of admission
and serum separated from the clotted blood was sent for
confirmatory tests for dengue infection to Jeddah Regional Laboratory, Jeddah of Ministry of Health and King Fahd Medical
Research Laboratory, Jeddah, Saudi Arabia. Serologic studies were performed with the qualitative dengue IgM capture
ELISA and dengue indirect IgG ELISA (PanBio Ltd., Brisbane, Australia) as per the manufactures instructions (Groen et
al., 2000). RT-PCR was done by the extraction of viral RNA
from serum using Qiagen QIAmp viral RNA extraction kit
(Qiagen Germany, catalogue number 29504), amplification of
cDNA and detection of amplified products. Primer and probes
used were as described before (Lanciotti et al., 1992). Blood
cell counts were performed using Coulter Gen-S TM system 2 hematology analyzer. Serum chemistry was performed
using Roche/Hitachi 912 clinical chemistry analyzer. Activated partial thromboplastin time (aPTT) and prothrombin time
(PT) were measured by Dade Behring Sysmex automated
coagulometer.
Data was analyzed using SPSS version 11.0 (SPSS Inc.,
Chicago, IL). Values are expressed as mean standard deviation. Chi-square test and fisher exact t-test were used to compare
categorical variables. Crude odds ratio (OR) and 95% confidence intervals (CI) were calculated. MannWhitney test was
used to compare means of continuous variables. The level of
significance for all statistical tests was p-value <0.05.

N.A. Khan et al. / Acta Tropica 105 (2008) 3944

3. Results
Of the 160 clinically suspected patients, confirmatory studies
for dengue viral infection were performed on sera of 136 (84%)
patients (all had serological studies; 96 patients had RT-PCR).
Dengue infection was confirmed in 91 (66.9%) of the tested
patients (64 by IgM ELISA alone; 14 by RT-PCR alone; and 13
by both). Serological studies showed presence of IgM antibodies in 77 (58.8%) and IgG antibodies in 44 (32.4%) clinically
suspected patients. Thirty five patients had both IgM and IgG
antibodies present. IgM antibodies were detectable after median
of 5 days (range 311 days) after the onset of symptoms. RTPCR was done in 96 patients of which 27 (28.1%) were positive.
Specific dengue serotype identification was performed on sera
of 23 patients by RT-PCR. DEN-2 and DEN-3 were identified
from 19 and 4 patients respectively. Twelve (13.1%) patients
were admitted in April, 52 (57.1%) in May, 21 (23.1%) in June
and 6 (6.6%) in July of 2004.
Most patients were young adults with median age of 26
(range = 694) years. Seventeen (18.7%) patients were in pediatrics age group (age 18 years). Fifty-seven (62.6%) patients
were males. Patients had symptoms for median of 5 (range:
214) days prior to hospitalization. Table 1 shows the common
clinical manifestations seen in the 91 patients with confirmed
dengue viral infection. Notably, a large proportion of patients
(79%) had one or more gastrointestinal symptoms. Less common
symptoms included cough in 10, dizziness in 5 and dysuria in 4
patients. The mean temperature at the time of hospitalization was
38.5 1 C. Tachycardia (pulse rate 100 min1 ) was present
in 66 (74.1%) patients. Skin rash was relatively uncommon.
Lymphadenopathy was present in nine patients. Hepatomegaly
was documented in only one patient and none had splenomegaly.
One patient had jaundice. None of the patients had clinical
evidence of pleural effusion or ascites. However, ascites was
detected in two patients on abdominal ultrasonogram done to
evaluate severe upper abdominal pain and vomiting. Both the
patients fulfilled all the criteria for DHF.
WHO classification could not be used for assessing severity
in 10 patients, as they did not have serial hematocrit evaluation done. Among remaining 81 patients, 75 (92.6%) had DF

Table 1
Clinical presentation of patients with confirmed dengue virus infection
Symptoms

Patientsa

Musculoskeletal pain
Malaise
Temperature 38 C
Headache
Anorexia
Nausea
Vomiting
Abdominal pain
Diarrhea
Sore throat
Skin rash

74 (81)
74/89 (83)
69 (76)
68 (75)
66 (72)
63 (69)
58 (64)
44 (48)
20/51 (39)
25/41 (61)
17 (19)

Number of patients with finding/total number of patients (%). Denominator

for total number of patients = 91 unless otherwise indicated.

41

and 6 (7.4%) had DHF. Among DHF patients two patients

had DHF1 and three patients had DHF2. One patient fulfilled
all the criteria for DSS. The patient with DSS was 45 year
old male who presented with blood pressure of 73/53 mmHg
and had hemoptysis. Only one case of DHF occurred in pediatric age group. Patients with DHF had lower temperature on
admission (37.9 0.6 C versus 38.6 1 C, p-value = 0.05),
were less likely to have musculoskeletal pain (OR = 0.1, pvalue = 0.02) and had higher prevalence of abdominal tenderness
(OR = 13.2, p-value = 0.02). DHF patients had significantly
lower platelet count on admission compared to DF patients
(66 22 109 L1 versus 100 43 109 L1 , p-value = 0.04).
Dengue serotype 2 was detected in two patients among DHF
patients by PCR serotyping. Three patients presented with
hypotension and shock. All of them had thrombocytopenia and
two had hemorrhagic manifestations but none showed evidence
of hemoconcentration and could not be classified as having DHF.
Twenty-one patients had one or more clinical complications.
Hemorrhagic manifestations occurred in 13 (13.2%) patients.
Table 2 shows the various clinical presentations of hemorrhagic manifestations. Hemorrhagic manifestations occurred
between Day 3 to Day 7 of the illness. Most patients had
mild, self-limited bleeding; only one patient, who had DHF,
required anterior nasal packing to control epistaxis. Three
patients had generalized tonicclonic seizures (one episode
in two patients; two episodes in one patient). One patient
developed headache, altered sensorium and clinical signs of
meningismus during hospitalization. His cerebrospinal fluid
studies were consistent with viral meningitis. Four patients
presented with shock in Emergency Department. Two patients
presented with acute renal failure at time of admission that
resolved with conservative treatment during hospitalization.
One patient, who had DHF, developed a secondary bacterial
urinary tract infection. Patients who had clinical complications were less likely to have musculoskeletal pain (OR = 0.23,
p-value = 0.03). They had significantly lower admission
(78 34 109 L1 versus 105 44 109 L1 , p-value = 0.01)
and nadir (58 24 109 L1 versus 82 47 109 L1 , pvalue = 0.03) platelet counts. They also showed more severe
hepatic involvement with significantly higher aspartate aminotransferase (AST) levels upon admission (159 126 IU/L
versus 105 90 IU/L, p-value = 0.03) and during hospitalization (196 135 versus 143 114 IU/L, p-value = 0.04). DHF
patients were significantly more likely to have clinical complications (OR = 18.4, p-value < 0.01).
Table 2
Hemorrhagic manifestations observed in patients with dengue viral infection
Bleeding presentation

No. of patients

Epistaxis
Skin petechiae
Gum bleeding
Rectal bleeding
Melena
Hematuria
Hemoptysis

5a
2
2a
2
1
1
1

One patient had both epistaxis and bleeding from gums.

42

N.A. Khan et al. / Acta Tropica 105 (2008) 3944

Table 3
Comparison of clinical chemistry and coagulation abnormalities between
dengue fever (DF) and dengue hemorrhagic fever (DHF) patients
Variable

DF (n)

ALTa
ASTa
ALPa
Bilirubin, totalb
Albuminc
LDHa
CPKa
PTd
aPTTd

126
152
117
0.7
3.7
772
379
15.5
45.6

DHF (n)
121 (74)
118 (72)
77 (53)
0.6 (54)
0.4 (60)
343 (68)
421 (18)
1.5 (58)
10.8 (58)

199
268
323
0.8
3.3
1121
1330
16
52.2

99 (6)
133 (6)
243 (5)
0.1 (5)
0.3 (4)
697 (6)
1879 (3)
1.4 (6)
22.3 (6)

p-Value
0.19
0.14
0.05
0.06
0.02
0.37
0.36
0.13
0.76

Abbreviations: n, number of patients tested; ALT, alanine aminotransferase;

AST, aspartate aminotransferase; ALP, alkaline phosphatase; apt, activated partial thromboplastin time; PT, prothrombin time; LDH, lactate dehydrogenase;
CPK, creatine phosphokinase.
a Values in IU/L.
b Values in mg/dL.
c Values in g/dL.
d Values in seconds.

Leucopenia and thrombocytopenia developed in 76/82

(93%) and 63/81 (78%) patients with mean nadir counts of
2.6 1.2 109 L1 and 76 44 109 L1 respectively. Severe
thrombocytopenia (platelet count <20 109 L1 ) was present in
two patients at admission and developed in two more patients
during hospitalization with lowest platelet count of 5 109 L1 .
Seven patients developed severe neutropenia (absolute neutrophil count <0.5 109 L1 ). Serum alanine aminotrasnsferase
(ALT) and AST were elevated in 66/86 (72.8%) and 80/85
(94.6%) patients with peak elevation on Day 6.9 2.4 and Day
6.6 2.5 after symptom onset respectively. Most patient had
modest elevation with only four patient each having AST and
ALT levels more than 10 times the upper normal limit. AST
levels were higher than ALT levels in 75% patients. Three
patient had mildly elevated total bilirubin level (>1.4 mg/dL)
with maximum level of 3.5 mg/dL. Alkaline phosphatase (ALP)
was elevated in 14 of 63 (22.2%) patients tested. Three patients
had ALP elevation more than three times upper normal limits.
None of the patients developed fulminant hepatitis. Hypoabuminemia (serum albumin <3.5 g/dL) was present in 14 of the
68 (21.9%) patients. Among the 65 patients tested, prolongation
of aPTT (aPTT > 36 s) and PT (PT > 17.5 s) was found in 53
(81.5%) and 4 (6.1%) patients respectively. Two patients have
elevation more than twice the upper normal limit. Elevated CPK
(CPK > 170 IU/L) was found in 13 of 21 (61.9%) patients tested.
Table 3 shows the comparison of common clinical chemistry and
coagulation values according to the WHO severity.
All patients received hydration, either orally or intravenously
(isotonic saline or 5% dextrose isotonic saline), during hospitalization. They were treated symptomatically with acetaminophen
and medications for gastrointestinal symptoms. Two patients
with platelet count <10 109 L1 received platelet transfusion.
Information about the total duration of symptoms was available for 59 patients. The mean duration of symptoms was
7.6 2.4 (range = 318) days. Patients were hospitalized for
mean of 4 1.7 (range = 19) days. Among these 59 patients,
34 (57.6%) remained hospitalized for a mean of 1.7 0.2 days

after resolution of their symptoms due to non-improving trend

in the abnormal hematological or clinical chemistry tests. Nine
patients were discharged with platelet counts between 30 and
50 109 L1 . None of them was readmitted for any complications. There was no significant relationship of duration of
admission with WHO severity (p-value = 0.16) or development
of any clinical complications (p-value = 0.06). There was no
mortality.
4. Discussion
This is the first study that documents the occurrence of
dengue virus infection in Makkah, Saudi Arabia. Previous studies from Saudi Arabia have reported surveillance data for dengue
infection (Fakeeh and Zaki, 2001, 2003) and clinical features
of hospitalized patients in Jeddah (Ayyub et al., 2006). The
presence of indigenous Aedes aegypti mosquitoes allowed the
establishment of dengue fever in Jeddah in 1994. It was suspected that a viremic Indonesian visitor to Jeddah had infected
local mosquitoes which then transmitted it to the local population (Scrimgeour, 2003). A casecontrol study found that water
storage containers, in or near construction sites, served as breeding sites for Aedes aegypti and were focal points of dengue
virus infection in Jeddah (Ghaznawi et al., 1997). Makkah and
Jeddah are located close to each other with a large number
of people traveling between the two cities daily. It is possible that dengue infection may have been introduced in Makkah
by viremic patients acquiring the infection during the ongoing
epidemic in Jeddah (Ayyub et al., 2006).
We used IgM capture ELISA and RT-PCR for confirmation of
dengue virus infection. Detection of two serotypes (DEN-2 and
DEN-3) is indicative of hyperendemic transmission of dengue
virus. The IgM ELISA has a high sensitivity and specificity for
dengue viral infection (Guzman and Kouri, 2002). As the serum
collection for some patients was done within 5 days of symptom
onset and none had collection of convalescent serum (as recommended by WHO guidelines), we may have missed the diagnosis
in some patients. Secondary infection is the one of the main risk
factor implicated in development of severe disease (Guzman and
Kouri, 2002; McBride and Bielefeldt-Ohmann, 2000). Classification of dengue infection as primary and secondary infection
requires using ELISA requires either measurements in acute and
convalescent serum or increased molar fraction ratio of IgM to
IgG in a single specimen (WHO, 1997). Our use of only qualitative serological tests, with the results being reported as either
positive or negative, precluded such classification.
Most patients were young adults. The relatively smaller proportion of children may partly be due to a presence of an
exclusively pediatrics hospital in the city. The symptoms and
signs present in our patients were mostly similar to what is
described for dengue fever (Harris et al., 2000; WHO, 1997).
However gastrointestinal symptoms, particularly nausea and
vomiting, were unusually common. Leucopenia and thrombocytopenia were present in most of the patients. Though seven
patients had severe neutropenia, none developed a secondary
bacterial infection. This might have been due to the short duration of neutropenia. Liver involvement as evidenced by elevated

N.A. Khan et al. / Acta Tropica 105 (2008) 3944

transaminases was commonly seen. The pattern of elevation of

liver enzyme was similar to what has been described before (Kuo
et al., 1992). Significantly lower serum albumin levels in DHF
patients are consistent with plasma leakage as the major pathophysiology in these patients (McBride and Bielefeldt-Ohmann,
2000).
The clinical complications seen in order of frequency were
hemorrhagic manifestations, shock, seizures, acute renal failure,
meningo-encephalitis and secondary bacterial infection. Seizure
and meningo-encephalitis are the most common reported neurological complications of dengue infection (Solomon et al.,
2000). Patients with clinical complications had significantly
lower platelet counts and higher AST levels on admission and
during hospitalization compared to those with uncomplicated illness. There was no mortality among our patients. However, two
virologically confirmed and three clinically suspected patients
died elsewhere in Makkah during this epidemic (Personal Communication: Dr. Ahmad M. Ashshi).
WHO classification is used to grade the severity of dengue
viral infection. Dengue hemorrhagic fever (DHF), characterized
by transient increase in vascular permeability, is considered to be
represent severe infection that may progress to shock and even
death. Only six of our patients could be strictly classified as having DHF using the WHO criteria. Most of our DHF patients were
adults unlike the hyperendemic areas in Southeast Asia where
DHF is predominantly a disease of children (Guzman and Kouri,
2002). Patients with DHF had significantly lower temperature
at admission and were less likely to have musculoskeletal pain
while had higher prevalence of abdominal tenderness. Presence
of hemorrhagic manifestations and thrombocytopenia did not
differ significantly between DF and DHF patients..
In our patient population, WHO classification did not completely account for the clinical severity of dengue virus infection.
Only 4 of the 13 patients with hemorrhagic manifestations had
DHF. Three patients presented with shock but did not strictly
fulfill all criteria for DHF. It is possible that hemoconcentration
may have been prevented due to prompt intravenous hydration.
Similar clinical profile have been noted in other outbreaks where
patients developed shock without meeting all the WHO criteria
for DHF (Harris et al., 2000; Murgue et al., 1999; Phuong et
al., 2004). Three of the four patients with neurological manifestations and both patients with acute renal failure had DF.
We also encountered practical difficulties in applying the WHO
classification. Ten patients could not be classified due to lack
of serial hematocrit measurements. We concur with suggestions
to modify or develop alternatives to the current classification
system that is clinically simpler to apply and is more accurately
predictive of the severity (Deen et al., 2006).
More than half of the patients stayed for a mean of 1.7
days in hospital awaiting improving trends in hematological
and clinical chemistry parameters. None of these patients were
observed to have any adverse event during this time period. A
study of hospitalized patients with dengue fever from Singapore
also noted prolongation of hospital stay among asymptomatic
patients while waiting for improvement in platelet counts (Tai
et al., 1999). The approach to discharge from hospital once
patients are asymptomatic should be formally evaluated as this

43

may shorten their hospitalization leading to reduction in the cost

to the healthcare system.
Makkah is the site of annual pilgrimage (Hajj) that is performed by nearly three million Muslims from all over the world.
Also, throughout the year, many visit Makkah to perform the
minor pilgrimage (Umrah). Due to this unique movement of
population from all over the world, Makkah has special epidemiological significance for the infectious diseases. Epidemics of
several infectious diseases have been reported among pilgrims
(Ahmed et al., 2006). Many of the pilgrims come from areas that
are hyperendemic for dengue infection especially from Southeast Asia and South Asia. These visitors may be potentially
viremic on their arrival in Makkah and presence of vector may
facilitate spread of a strain of dengue that causes severe disease.
Similarly, they can acquire dengue infection locally and carry it
back to their own countries. Continued surveillance and effective vector control programs are necessary to detect change in
clinical pattern and outbreaks of dengue in future.

References
Ahmed, Q.A., Arabi, Y.M., Memish, Z.A., 2006. Health risks at the Hajj. Lancet
367, 10081015.
Al-Buhairan, A.M., Khalil, S.H., Oluboyede, O.A., 1999. Reference range values of hematological parameters in Saudi healthy adults. Saudi Med. J. 20,
757762.
Ayyub, M., Khazindar, A.M., Lubbad, E.H., Barlas, S., Alfi, A.Y., Al-Ukayli,
S., 2006. Characteristics of dengue fever in a large public hospital, Jeddah,
Saudi Arabia. J. Ayub Med. Coll. Abbottabad 18, 913.
Deen, J.L., Harris, E., Wills, B., Balmaseda, A., Hammond, S.N., Rocha, C.,
Dung, N.M., Hung, N.T., Hien, T.T., Farrar, J.J., 2006. The WHO dengue
classification and case definitions: time for a reassessment. Lancet 368,
170173.
Fakeeh, M., Zaki, A.M., 2003. Dengue in Jeddah, Saudi Arabia, 19942002.
Dengue Bull. 27, 1318.
Fakeeh, M., Zaki, A.M., 2001. Virologic and serologic surveillance for dengue
fever in Jeddah, Saudi Arabia, 19941999. Am. J. Trop. Med. Hyg. 65,
764767.
Ghaznawi, H.I., Al-Khateeb, T.O., Akbar, N., Afifi, H., Nasser, A., 1997. Surveillance for dengue fever in Jeddah. East Mediterr. Health J. 3, 567570.
Gibbons, R.V., Vaughn, D.W., 2002. Dengue: an escalating problem. BMJ 324,
15631566.
Groen, J., Koraka, P., Velzing, J., Copra, C., Osterhaus, A.D., 2000. Evaluation
of six immunoassays for detection of dengue virus-specific immunoglobulin
M and G antibodies. Clin. Diagn. Lab. Immunol. 7, 867871.
Gubler, D.J., 1997. In: Gubler, D.J., Kuno, G. (Eds.), Dengue and Dengue
Hemorrhagic Fever: Its History and Resurgence as a Global Public Health
Problem. CAB International, Wallingford, UK, pp. 122.
Guzman, M.G., Kouri, G., 2002. Dengue: an update. Lancet Infect. Dis. 2, 3342.
Harris, E., Videa, E., Perez, L., Sandoval, E., Tellez, Y., Perez, M.L., Cuadra,
R., Rocha, J., Idiaquez, W., Alonso, R.E., Delgado, M.A., Campo, L.A.,
Acevedo, F., Gonzalez, A., Amador, J.J., Balmaseda, A., 2000. Clinical,
epidemiologic, and virologic features of dengue in the 1998 epidemic in
Nicaragua. Am. J. Trop. Med. Hyg. 63, 511.
Kuo, C.H., Tai, D.I., Chang-Chien, C.S., Lan, C.K., Chiou, S.S., Liaw, Y.F.,
1992. Liver biochemical tests and dengue fever. Am. J. Trop. Med. Hyg. 47,
265270.
Lanciotti, R.S., Calisher, C.H., Gubler, D.J., Chang, G.J., Vorndam, A.V., 1992.
Rapid detection and typing of dengue viruses from clinical samples by
using reverse transcriptase-polymerase chain reaction. J. Clin. Microbiol.
30, 545551.
McBride, W.J., Bielefeldt-Ohmann, H., 2000. Dengue viral infections; pathogenesis and epidemiology. Microbes Infect. 2, 10411050.

44

N.A. Khan et al. / Acta Tropica 105 (2008) 3944

Murgue, B., Deparis, X., Chungue, E., Cassar, O., Roche, C., 1999. Dengue: an
evaluation of dengue severity in French Polynesia based on an analysis of
403 laboratory-confirmed cases. Trop. Med. Int. Health. 4, 765773.
Phuong, C.X., et al., 2004. Clinical diagnosis and assessment of severity of
confirmed dengue infections in Vietnamese children: is the world health
organization classification system helpful? Am. J. Trop. Med. Hyg. 70,
172179.
Scrimgeour, E.M., 2003. Epidemic infections and their relevance to the Gulf
and other Arabian peninsula countries. SQM J. Sci. Res.: Med. Sci. 5, 14.

Solomon, T., Dung, N.M., Vaughn, D.W., Kneen, R., Thao, L.T., Raengsakulrach, B., Loan, H.T., Day, N.P., Farrar, J., Myint, K.S., Warrell, M.J., James,
W.S., Nisalak, A., White, N.J., 2000. Neurological manifestations of dengue
infection. Lancet 355, 10531059.
Tai, D.Y., Chee, Y.C., Chan, K.W., 1999. The natural history of dengue illness
based on a study of hospitalised patients in Singapore. Singapore Med. J.
40, 238242.
WHO, 1997. Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention
and Control. World Health Organization, Geneva.