Transcript Prolnged fever in Egypt

Prolonged fever is defined as fever more than 2
weeks duration greater than 38.3◦C (101◦F)
several occasions. The causes of prolonged
are classified in to 4 major groups:
• infections (most common cause).
• non-infectious inflammatory diseases (NIID).
• malignancies.
• miscellaneous conditions.
on
fever
Infection is the most common diagnosis in most
cases of prolonged fever especially in developing
countries which include:
•Bacterial
(salmonellosis
,
tuberculosis
,brucellosis, and abdominal or pelvic abscesses
,osteomyelitis,
infective
endocarditis,
Pyelonephritis and tuberculous meningitis ).
•Viral (CMV, EBV, Herpes viruses , and HIV).
•Rickettsial (Q fever).
•Parasitic infections.
•
The common infections in Egypt causing
prolonged fever that we will study in this
essay as regard the diagnosis
serology are:
•salmonellosis ,
•tuberculosis(TB) ,
•brucellosis,
•Q fever,
•Epstein-Barr virus (EBV),
•chronic meningitis.
especially the
Common infections causing
prolonged fever in Egypt
Mal-treated typhoid fever
-Typhoid fever (enteric fever) is caused by the
Gram-negative bacterium Salmonella enterica
serotype typhi.
-Estimates for the year 2000 suggest there are
approximately 21.5 million infections and 200,000
deaths from typhoid fever globally each year .
-The clinical manifestations of typhoid fever are
usually nonspecific, and include prolonged fever
and gastrointestinal symptoms.
Typhoid fever in Egypt
-In Bilbeis district (population 664,000) in Lower
Egypt the estimated incidence of typhoid fever
was calculated to be 13 cases per 100,000 persons
per year .
-Also the results of population-based surveillance
in Fayoum governate indicate that incidence of
typhoid fever was 59 cases per 100,000 persons
per year.
Brucellosis
-The causative agent is Brucella spp., ( Gramnegative intracellular coccobacillus discovered by
David Bruce in 1887).
-Brucellosis is a relatively common condition and
may present with prolonged fever without a focus,
however due its wide spectrum of clinical symptoms
it remains an important diagnostic challenge.
-It is a zoonotic disease found worldwide, with a high
morbidity rate.
Brucellosis in Egypt
-Brucellosis is endemic in the middle East.
-In Egypt 11% of the population had serological evidence
of infection with Brucella spp., while in acute febrile
illnesses 3% of all bacteraemias were caused by the
organism .
-Although brucellosis is recognized as a common cause of
fever in various parts of Egypt, it is often misdiagnosed and
mistreated.
-More than half of all brucellosis cases were misdiagnosed
as typhoid, and only a quarter of them received treatment
with more than one antibiotic.
Tuberculosis
-Tuberculosis
is
caused
by
Mycobacterium
tuberculosis complex (MTBC).
-Tuberculosis may involve every organ in the body
but the most common clinical presentation is
pulmonary disease.
-In 2006, 9.2 million new active disease cases (4.1
million being sputum smear-positive) corresponding
to an estimated incidence of 139 per 100,000
population occurred throughout the world.
-The highest incidence rate was recorded for the
African region , mainly due to high prevalence of HIV
infection.
Tuberculosis in Egypt
According to a 1997 report from the
Egyptian National Tuberculosis Program,
revealed that the incidence of smear-positive
cases in Egypt is 16 per 100,000 population,
This report concluded that TB and especially
drug-resistant strains of Mycobacterium
tuberculosis pose serious public health
problems and that multiple drug resistance and
low cure rates are the most important
problems facing TB control efforts in Egypt .
Qfever
Q fever is a widespread zoonotic disease, caused
by Coxiella burnetii (C. burnetii). Wild and domestic
animals are the reservoir of C. burnetii, It is a
zoonosis occurring worldwide.
Q fever is associated with a wide spectrum of clinical
manifestations. In most cases, this illness has a selflimiting febrile course, but it may also manifest with
a variety of non-specific symptoms. As with most
other rickettsioses, Q fever is infrequently suspected
and remain unrecognized .
Infectious mononucleosis
*The clinical triad of pharyngitis, fever, and
lymphadenopathy was first described as “glandular
fever,”.
*IM is caused by the Epstein Barr virus (EBV), which
infects more than 98% of the world’s adult
population .
*The overall clinical incidence is 45/100 000 and it is
particularly common in adolescence.
*IM is a clinical syndrome characterized by fever,
fatigue, malaise, lymphadenopathy and sore throat.
Chronic meningitis
-Chronic meningitis is defined by persistent or
clinically
progressive
signs
and
symptoms
of
meningitis, such as headache, fever, stiff neck,
nausea, vomiting, lethargy, and confusion associated
with cerebrospinal fluid (CSF) changes lasting for a
duration of at least 4 weeks without improvement.
-Chronic meningitis is caused by a wide
variety of infectious and noninfectious
pathogens that remain difficult to
diagnose.
In
Egypt,
Tuberculous
meningitis (TBM) being one of the most
common causes of bacterial meningitis
and being associated with a high mortality
(47%) and it continues to be a significant
public health problem .
Typhoid fever diagnosis
Although the mainstay of diagnosing typhoid fever
is a positive blood culture it is time-consuming and
takes at least 2 to 5 days until the identification of
the organism.
PCR is a better alternative because it is sensitive
and rapid method. PCR-based diagnoses are superior
to the classical serological method, Widal test, and
blood culture test in terms of their specificity and
sensitivity .
Nested PCR had higher efficacy in detecting typhoid
fever than Widal test, blood and urine cultures .
Brucella diagnosis
Isolation of brucella from blood, bone
marrow, lymph nodes or cerebrospinal fluids
remains the gold-standard for diagnosis of
brucellosis in humans.
Despite its high specificity, brucella culture has
several drawbacks such as slow growth and poor
sensitivity.
PCR proved to be a very useful tool not only
for the diagnosis of acute brucellosis but also
as a predictive marker for the course of the
disease and the post treatment follow-up,
which is valuable for the early detection of
relapses .
Tuberculosis (TB) diagnosis
Microscopy is still the backbone of
laboratory diagnostics in TB. Many nucleic acid
amplification methods are much more sensitive
than sputum microscopy, and results can be
available within several hours.
The cost and complexity of existing nucleic
acid amplification methods has limited their
application in resource-poor settings.
Transrenal DNA provides a challenging new
target for molecular tuberculosis diagnosis in all
groups of patients.
Q Fever diagnosis
The isolation of the Q fever pathogen is a
reliable diagnostic method, but it remains timeconsuming and hazardous and requires biosafety.
The PCR assays performed are better tests than
pathogen isolation for the rapid and reliable
diagnosis of Q fever.
Infectious mononucleosis
diagnosis
Quantitative Epstein bar virus (EBV) DNA
measurement is essential for differentiating the
low-level infection of healthy carriers from the high
levels characteristic of EBV-related disease. Realtime PCR is the principal technology used for
modern EBV viral load measurement.
Chronic meningitis
The identification of meningitis etiology is primarily based on
the examination of CSF and other tissues, which includes
direct stain, cultures on aerobic, anaerobic media. However,
even with the use of modern techniques, the etiology of
chronic meningitis remains unknown in a substantial
percentage of patients. The CSF polymerase chain reaction
(PCR) assay represents a significant advance in the diagnosis
of TBM. The results of PCR studies in the CSF have shown a
94—100% specificity but sensitivities ranging from 75% to
100%. CT and MRI are used in the evaluation of TBM and to
identify complications.
Maltreated Typhoid fever
The most widely used serologic test is the Widal
test, However, false-positive results are common
because of antigenic cross sharing with other
salmonella serotypes . Several new serologic tests
for typhoid fever have been introduced which detect
IgM or IgG antibodies to various purified antigens of
S. Typhi. The assay methods used include enzymelinked immunosorbent assay (ELISA), dot-blot ELISA,
immunochromatography and a novel particle
separation method used in TUBEX. The TUBEX test is
simple and rapid to use not only in hospitals but also
for outpatients as well. It is good alternative for
widal test .
Typhidot-M is a dot enzyme immunoassay for
the detection of specific IgM to Salmonella typhi .
Typhidot-M was positive in 97% of cases who
presented with fever of <7 days among blood
culture positives as compared to Widal, which was
positive in 24.2%.
It is a dot-Enzyme Immunoassay (EIA), a new
serologic test based upon the presence of
specific IgM antibodies to a specific 50 kDa
outer membrane protein (OMP) antigen on
Salmonella typhi. The test become positive as
early as in the first week of the fever, the
results can interpreted visually and available
within one hour
Brucellosis
Serological testing often is used for the confirmation of
brucellosis. The agglutination tests in tubes, e.g serum
agglutination test (SAT), or on slides (Rose Bengal) continue
to be the mainstay of laboratory diagnosis . . However, SAT
and the other formats of direct agglutination tests suffer
from high false negative rates in complicated and chronic
cases
ELISA is one method that has been incorporated into
serologic diagnosis of brucellosis. Among its advantages are
speed and automatization. ELISA also allows detection of
antibodies against different bacterial antigenic structures
such as corpuscular antigen, S-LPS or protein antigens .
Tuberculosis
The detection of circulating mycobacterium antigens
using specific monoclonal antibodies (mAbs) has
been shown to be a promising approach to the
detection of active infection.
Recently, developed a simple and rapid dot- ELISA
test based on IgG monoclonal antibody (TB-55 mAb)
specific for a 55-kDa mycobacterial antigen and had
been evaluated in the diagnosis of pulmonary as well
as extrapulmonary TB .
The gold-standard screening method for LTBI is the
tuberculin skin test (TST). The TST has several
limitations, including the need for repeat visits and
trained staff in addition to limited validity of the
results. T-cell–based interferon-γ release assay are
whole-blood enzyme-linked immunosorbentassay
(ELISA)
and
enzyme
linked
immunospot
assay(ELISpot). The whole blood ELISA is available
commercially as QuantiFERON-TB Gold and an “intube” variant, QuantiFERON-TB Gold In-tube . This Tcell-based assay for diagnosing tuberculosis infection
gave promising results .
Q fever
Human Q fever is currently diagnosed by
clinical presentation and supporting serological
responses against fixed, whole-cell phase I and
phase II forms of the C. burnetii. The serological
testing include immunofluorescence, complement
fixation, enzyme- linked immunosorbent assay
(ELISA) and microagglutination.Q fever IgG ELISA is
a specific alternative method for prevaccination
testing and the diagnosis of Q fever. Worldwide, the
most common method used in human diagnosis of
Q fever is the indirect immunofluorescence antibody
(IFA).
Infectious mononucleosis
Detection of IgM antibody against the virus
capsid antigen (VCA) is the best approach for the
identification of primary EBV infection. Indirect
immunofluorescence assay (IFA) of anti-VCA IgM
and IgG antibody has been regarded as the
golden standard for the serological diagnosis of
EBV infection, and other methods, such as
enzyme-linked immunosorbent assays (ELISA)
and chemiluminescent immunoassay (CLIA), were
developed to improve the assay procedure.
Tuberculous meningitis
Immunological methods such as antibody-capture
enzyme-linked immunosorbant assay (ELISA) have
been previously used for diagnosing TBM . The cell
ELISA method allows further confirmation of the
results obtained by antibody-capture ELISA. The
presence of a 30-kD protein antigen in CSF of TBM
patients indicates that this protein carries the
candidate marker antigen which is specific to M.
tuberculosis.
Statistical comparisons for cases of typhoid from
2003 to2008 admitted in Mansoura fever hospital
160
patient n
number
140
120
100
80
60
40
20
0
2003
2004
2005
2006
2007
2008
Statistical comparisons for cases of brucella from 2003 to2008
admitted in Mansoura fever hospital
35
patient n
30
25
20
15
10
5
0
2003
2004
2005
2006
2007
2008
Statistical comparisons for cases of tuberculosis from
2003 to2008 admitted in Mansoura fever hospital
9
Patient n
number
8
7
6
5
4
3
2
1
0
2003
2004
2005
2006
2007
2008
Statistical comparisons for cases of meningitis from
2003 to2008 admitted in Mansoura fever hospital
12
patient n
10
8
6
4
2
0
2003
2004
2005
2006
2007
2008