Treatment of lumbar disc herniation: Evidence-based practice

Lumbar disc herniation is a common condition that frequently affects the spine in young and
middle-aged patients. The lumbar intervertebral disc is a complex structure composed of
collagen, proteoglycans, and sparse fibrochondrocytic cells that serve to dissipate forces
exerted on the spine. As part of the normal aging process, the disc fibrochondrocytes can
undergo senescence, and proteoglycan production diminishes. This leads to a loss of hydration
and disc collapse, which increases strain on the fibers of the annulus fibrosus surrounding the
disc. Tears and fissures in the annulus can result, facilitating a herniation of disc material,
should sufficient forces be placed on the disc. Alternatively, a large biomechanical force placed
on a healthy, normal disc may lead to extrusion of disc material in the setting of catastrophic
failure of the annular fibers.
Regardless of etiology, herniations represent protrusions of disc material beyond the confines of
the annular lining and into the spinal canal. Back pain may occur due to disc protrusions that do
not enter the canal or compromise nerve roots. The more treatable condition of lumbar
radiculopathy, however, arises when extruded disc material contacts, or exerts pressure, on the
thecal sac or lumbar nerve roots. The pain associated with lumbar radiculopathy occurs due to a
combination of nerve root ischemia and inflammation resulting from local pressure and
neurochemical inflammatory factors present within the disc material.
Lumbar disc herniations exist on a continuum of degenerative spinal processes that include
intervertebral disc degeneration and lumbar spondylosis. Many studies have demonstrated that
lumbar herniations, protrusions, and annular tears are present in asymptomatic individuals and,
in certain instances, can represent normal aging of the intervertebral disc. The incidence of
lumbar disc herniations, albeit asymptomatic, within certain populations has been estimated to
be greater than 50%. The true incidence of symptomatic lumbar disc herniations, however, has
not been satisfactorily characterized due to a lack of consensus regarding what constitutes a
symptomatic herniation (ie, back pain alone versus radicular pain versus back pain and
radicular pain), as well as a lack of ability to quantify a specific at-risk population. Furthermore,
the complete natural history of this disorder is inadequately described, although a variety of
anecdotal as well as Level IVV evidence exists, suggesting that 90% of patients with lumbar
disc herniations will resolve their symptoms without substantial medical intervention. Disc
disorders, back pain, and/or radiculopathy are often grouped together in terms of economic
considerations, and a discrete estimation of the effect of symptomatic lumbar disc herniation on

the economic system, in terms of days lost to work and reduced productivity, is hard to obtain.
Nonetheless, back-related conditions are a common cause of disability, and the US health care
system spends over $1 billion annually to redress these disorders. Recently, annual Medicare
spending on lumbar discectomy procedures has been estimated to exceed $300 million.
The evidence presented in this article is largely derived from recent prospective, randomized,
controlled trials (RCTs) as well as prospective case-control studies. These include the Spine
Patient Outcomes Research Trial (SPORT) as well as the Maine Lumbar Spine
Study. Therefore, the evidence presented in this paper can be graded as Level III. Sources
used in the preparation of this manuscript included PubMed, MedLine, and the Cochrane
Library. An advanced search was performed using the PubMed database and key words,
including intervertebral disc herniation, lumbar disc herniation, and lumbar disc
displacement. The PubMed search revealed 2370 articles that were potential matches. A
similar search method on the Cochrane database returned 6153 potential articles, and a like
number was obtained with a search using MedLine. Articles with Level I or II evidence were
selected for use in the preparation of this article, as well as other publications found to contain
pertinent or unique information.
The patient who presents initially with an acute episode of lumbar radiculopathy can be
managed by a primary care practitioner. Primary treatments should include judicious use of pain
medication, a short course of rest if indicated, physical therapy, and possible epidural steroid
injections. Injections can be ordered, or referral to physiatry or pain management made, prior to
considering consultation with a spinal surgeon, unless the patient exhibits certain red flags, such
as sensory or motor deficits, progressive neurologic deterioration, or saddle anesthesia with
bowel and bladder incontinence. Magnetic resonance imaging (MRI) is indicated to confirm that
the patients symptoms are attributable to appropriate lumbar disc pathology. The following
treatment recommendations are not necessarily applicable to those patients who have disc
herniations identified on MRI, but present only with back pain.
Potential pitfalls
Patients with progressive neurologic deficits, saddle anesthesia, and/or bowel or bladder issues
should be sent to the emergency room or referred urgently to a spinal surgeon. These patients
should not be considered candidates for nonoperative management. Patients with paresthesias
or motor weakness in the setting of radicular pain should likely be evaluated by a spine care
practitioner prior to the determination of a conservative course of treatment. Patients with

symptoms present for greater than six months should be referred to a spinal surgeon because
nonoperative management may not be indicated in these individuals. Those patients with only
back pain, even with MRI evidence of disc herniation, should not be treated using an algorithm
for patients with radicular symptoms.
Management
Initial management should include rest as indicated, physical therapy, and appropriate use of
pain medication. In most instances, radicular symptoms will abate or resolve within six weeks. If
symptoms persist, consideration can be given to ordering epidural steroid injections. Patients
with symptoms that persist beyond six weeks in the setting of demonstrable MRI disc pathology
are also candidates for surgical referral.
Assessment
Assessment by the primary care practitioner consists of taking a history documenting the onset
of symptoms and any symptomatic progression. Evaluation should focus on the presence of
predominantly back-related symptoms as well as true radicular pain (ie, radiating pain that
extends below the knee in the affected extremity). Primary care physicians must also perform a
neurologic evaluation to assess for the presence of sensory or motor deficits. Patients with a
history of saddle anesthesia must also have a perineal examination and a rectal examination to
determine true sensory loss and/or sphincter involvement. Straight leg raise testing and a slump
test, as described by Majlesi et al,9 are also useful adjuncts. It is important to remember that a
true positive straight leg raise test should reproduce the patients radicular pain, with radiation
below the knee in the affected extremity.
Treatment
Initial treatment can begin with a short course of rest as indicated for the patient with acute
lumbar radiculopathy in the setting of a lumbar disc herniation. Pain management may include
either a prescription for a moderate nonsteroidal anti-inflammatory, such as ibuprofen 800 mg
every eight hours as needed, or tramadol 50 mg every 46 hours as needed. Patients with more
substantial pain can be treated with mild narcotic pain medication, such as hydrocodoneacetaminophen 5 mg/500 mg every 46 hours on an as-needed basis. Physical therapy referral
can be made at the initial office visit, to include mild stretching and pain relief modalities, such
as ultrasound, whirlpool, ice and heat pack therapy, electrical stimulation, and/or massage.
Those individuals found to have perineal anesthesia, an incompetent rectal sphincter, or

significant neurologic deficits by examination should be sent to the emergency room or have an
urgent consultation with a surgeon. Those with significant, but stable, sensory or motor deficits
may be referred to a spine surgical specialist on an urgent basis. Individuals with a history of
more than six months of persistent symptomatology can be referred to a spinal surgeon without
consideration for conservative management, because surgical results have been shown to
deteriorate after 612 months of persistent symptomatology.
Patients who have failed a short course of conservative management (ie, 34 weeks) can be
considered candidates for epidural steroid injection. Those who have failed six weeks of
conservative management and/or derived no relief from steroid injection, may consult with a
spine specialist as a routine referral.
Indications for specialist referral
Urgent specialist referral should be made in the setting of progressive neurologic deficits, saddle
anesthesia, or bowel and/or bladder deficits if these issues are acute. Urgent referral to a spinal
surgeon can be made if the patient has sensory or motor findings on physical examination but
these deficits are stable. Once a patient has failed six weeks of nonoperative treatment, surgical
referral is appropriate if symptoms persist and the patient is amenable.

Summary
Prior to the mid-1990s there was a paucity of high quality literature supporting the treatment of
radicular symptoms resulting from lumbar disc herniation. Since 1996, a number of prospective
studies have reported their findings comparing conservative with nonoperative treatments and,
in addition, several prospective RCTs have been performed. Many spinal surgeons and medical
researchers hoped that well constructed, scientifically rigorous RCTs would definitively answer
the question regarding optimal treatment for lumbar disc herniation. However, due to
methodologic issues and difficulties with patient crossover between treatment groups in these
studies, no gold standard treatment has yet been established.
Although many of these studies showed some early benefit for surgery, with faster relief of
symptoms and return to preinjury functional levels, the findings were not statistically
significant. It is important to note, however, that significant differences between groups become
difficult to identify in intent to treat analyses once patient crossover approaches 50%.1 Only
Webers study from 1983 was able to show significant advantages for surgery at time points up
to one year.
Several publications reporting outcomes for prospective cohorts undergoing discectomy
documented satisfactory results, including symptomatic relief and global health benefits for up to
two years after surgery. The most elaborate prospective study conducted to date remains the
report of the Maine Lumbar Spine Study Group, published in a series over the course of 10
years by Atlas et al. Over 500 individuals were included in this investigation, although decisions
regarding course of treatment were left to the patients. Evaluations at the 1 and 10-year time
points following treatment revealed a continued benefit for surgical intervention, although the

two groups approximated each other after a decade. Levels of satisfaction, however, were
significantly higher among those patients who had undergone discectomy.

Reaction

Spinal disc herniation, also known as a slipped disc, is a medical condition affecting the spine
in which a tear in the outer, fibrous ring of an intervertebral disc allows the soft, central portion to
bulge out beyond the damaged outer rings. Tears are almost always postero-lateral in nature
owing to the presence of the posterior longitudinal ligament in the spinal canal.[1] This tear in the
disc ring may result in the release of inflammatory chemical mediators, which may directly
cause severe pain, even in the absence of nerve root compression.
Disc herniations are normally a further development of a previously existing disc "protrusion", a
condition in which the outermost layers of the fibrous ring are still intact, but can bulge when the
disc is under pressure. In contrast to a herniation, none of the central portion escapes beyond
the outer layers. Most minor herniations heal within several weeks. Anti-inflammatory treatments
for pain associated with disc herniation, protrusion, bulge, or disc tear are generally effective.
Severe herniations may not heal of their own accord and may require surgery. The condition is
widely referred to as a slipped disc, but this term is not medically accurate as the spinal discs
are firmly attached between the vertebrae and cannot "slip".

Therefore, the literature supports both conservative management and surgical intervention as
viable options for the treatment of radiculopathy caused by lumbar disc herniation.
Methodological drawbacks limit the effect that published RCTs can have on informing clinical
practice for this condition. Surgical intervention may result in faster relief of symptoms and
earlier return to function, although long-term results appear to be similar regardless of type of
management. The ultimate decision regarding type of treatment should be based on a surgeonpatient discussion, in light of proper surgical indications, duration of symptoms, and patient
wishes.

Hemorrhoidectomy - making sense of the surgical options

Hemorrhoids, or piles, is one of the most common anorectal disorders, with a
prevalence of 39% of the population, of whom 44.7% are symptomatic. Hemorrhoids may be
internal or external, depending on its relation to the dentate line. There are four grades of
internal hemorrhoids as described by Goligher, and they can be classified using the definitions.
While this common classification of internal hemorrhoids is useful in the selection of treatment
and comparison of therapeutic outcomes, Goligher only classifies hemorrhoids based on the
degree of prolapse and does not describe the size of the hemorrhoids or whether they are
isolated or circumferential; these factors are important in the selection of surgical treatment. The
ideal operation for hemorrhoids should be effective with a low rate of recurrence, minimal postoperative pain to allow early return to normal activities, and safe with minimal morbidity. If
recurrence is the main consideration, conventional hemorrhoidectomy (CH) is still considered
the gold standard. However, it is associated with significant post-operative pain, perianal
discharge, and irritation. Innovation and evolution in hemorrhoidectomy techniques have
focused on achieving the ideal operation. Many options for surgery on hemorrhoids have been
described and multiple trials conducted. Some techniques have been touted to be superior to
others, whilst other techniques have been recommended to be uniformly useful for all
presentations of hemorrhoids.
This review aims to evaluate the current surgical options for hemorrhoids and to make sense of
all the different modalities of hemorrhoid surgery available. A comprehensive literature search
was performed by the authors using MEDLINE, Embase, and the Cochrane Database of

Systematic reviews in January 2014. The search was performed using both medical subject
headings (MeSH) and keyword searches. The terms used for the search included: Hemorrhoids
(haemorrhoids or hemorrhoids), Piles, CH (open hemorrhoidectomy, closed hemorrhoidectomy,
Milligan Morgan hemorrhoidectomy, Ferguson hemorrhoidectomy, or LigaSure
hemorrhoidectomy), Stapler hemorrhoidectomy (Procedure for Prolapsed Hemorrhoids or
Longo hemorrhoidectomy), and Doppler-guided Hemorrhoidal Artery Ligation. The search was
restricted to the last 15 years (2000-2014). Articles that were not available in English were
excluded. Clinical practice guidelines and retrospective studies were excluded from this study.
First described in 1995 by Morinaga et al, Doppler-guided hemorrhoidal artery ligation (DGHAL)
involves using a special proctoscope with an integrated Doppler transducer and a lateral ligation
window. The level of artery ligation is dictated by the length of the Doppler anoscope, but should
be performed above the dentate line. Typically, the intraluminal arteries are located in the right
posterior lateral, right middle lateral, right anterior lateral, left anterior lateral, left middle lateral,
and left posterior lateral (1, 3, 5, 7, 8, and 11 oclock) positions. The arterial signal is clearly
audible when the Doppler probe is directly over the hemorrhoidal artery. A figure of eight stitch
is then placed through the lateral ligation window, and ligation of the vessel confirmed by the
absence of the Doppler arterial signal distal to the suture line. A reduction in the blood inflow to
the hemorrhoidal plexus will facilitate the shrinkage of the internal piles.
DGHAL can be done with local anesthetic and sedation, with the patient in the lithotomy
position. This procedure alone does not deal with hemorrhoid prolapse. In patients with prolapse
piles, procedures have been proposed in addition to DGHAL, such as DGHAL with mucopexy.
The attractiveness of this technique lies in the minimally invasive nature of the procedure with
no actual excision of tissue per se. The systematic dearterialization of the hemorrhoidal tissues
also promises effective intervention for hemorrhoids with recalcitrant bleeding. However, the
ability to reduce severe prolapse is not addressed as effectively when there is tissue excision.

Summary
While debate continues as to which is the best surgical method for the treatment of
hemorrhoids, none of the currently available surgical methods approach the ideal surgical
option, which is one that is effective while being safe and painless. In reality, the less painful the
procedure, the more likely it is to be associated with recurrence post-op. Where hemorrhoids
surgery is concerned, there isnt a one size fits all option. Most of the randomized controlled
trials performed to date include hemorrhoids of various grades and with a focus on only
comparing surgical methods while failing to stratify the outcomes according to the grade of
hemorrhoid. We believe that surgery needs to be tailored not only to the grade of the
hemorrhoids, but also to the size, circumferential nature of the disease, and prevailing
symptomatology.
While the debate continues as to which is the best surgical method for the treatment of
hemorrhoids, none of the currently available surgical methods approach the ideal surgical
option, which is one that is effective while being safe and painless. In reality, the less painful the

procedure, the more likely it is to be associated with recurrence post-op. Where hemorrhoids
surgery is concerned, there isnt a one size fits all option. Most of the randomized controlled
trials performed to date include hemorrhoids of various grades and with a focus on only
comparing surgical methods while failing to stratify the outcomes according to the grade of
hemorrhoid. We believe that surgery needs to be tailored not only to the grade of the
hemorrhoids, but also to the size, circumferential nature of the disease, and prevailing
symptomatology.

Reaction
A hemorrhoidectomy is surgery to remove internal or external hemorrhoids that
are extensive or severe. Surgical hemorrhoidectomy is the most effective treatment for
hemorrhoids, though it is associated with the greatest rate of complications. Incisions are made
in the tissue around the hemorrhoid. The swollen vein inside the hemorrhoid is tied off to
prevent bleeding, and the hemorrhoid is removed. The surgical area may be sewn closed or left
open. Medicated gauze covers the wound.
Surgery can be done with a knife (scalpel), a tool that uses electricity (cautery pencil), or a laser.

The operation is usually done in a surgery center. You will most likely go home the same day
(outpatient).
Therefore, while the debate continues as to which is the best surgical method for the
treatment of hemorrhoids, none of the currently available surgical methods approach the ideal
surgical option, which is one that is effective while being safe and painless. In reality, the less
painful the procedure, the more likely it is to be associated with post-operative recurrence.
Where hemorrhoids surgery is concerned, there is no one size fits all option. Most of the
randomized controlled trials performed to date include hemorrhoids of various grades and with a
focus on only comparing surgical methods, while failing to stratify the outcomes according to the
grade of hemorrhoid. We believe that surgery needs to be tailored not only to the grade of the
hemorrhoids, but also to the size, circumferential nature of the disease, and prevailing
symptomatology. A summary of our recommendations is represented in

Threatened miscarriage: evaluation and management

Threatened miscarriagevaginal bleeding before 20 gestational weeksis the commonest

complication in pregnancy, occurring in about a fifth of cases. Miscarriage is 2.6 times as
likely, and 17% of cases are expected to present complications later in pregnancy. Although
general practitioners and gynecologists often see this condition, management of threatened
miscarriage is mostly empirical. Bed rest is routinely recommended, and about a third of women
presenting with threatened miscarriage are prescribed drugs. However, two thirds of the general
practitioners recommending this do not believe it affects outcome.

In this review, we present available evidence on the initial evaluation and management of
threatened miscarriage, focusing mainly on the first trimester of pregnancy and primary
healthcare settings.
Bed rest
In one study, 1228 out of 1279 (96%) general practitioners prescribed bed rest for heavy
bleeding in early pregnancy, although only an eighth of them felt it was mandatory, and only one
third felt it could affect outcome.3 Only one randomized controlled trial considers the impact of
bed rest on the course of threatened miscarriage; 61 women with viable pregnancies at less
than eight gestational weeks and vaginal bleeding were randomly allocated into either injections
of hCG, injections of placebo, or bed rest. The abortion rates in the three groups were 30%,
48%, and 75%significant differences between hCG and bed rest groups but not between hCG
and placebo groups or between placebo and bed rest groups. Although hCG performed
significantly better than bed rest in this study, the lack of profound benefit over placebo, the
concern about potential development of ovarian hyper stimulation syndrome, and the fact that
threatened miscarriage may be the result of various conditions, irrelevant to luteal function,
prevented further testing and application of hCG treatment in general obstetric practice.
In a retrospective study of 226 women who were hospitalized for reasons related to their
pregnancy and previous threatened miscarriage, 16% of 146 women who were bed resting
eventually miscarried, compared with a fifth of women who did not follow this option (not
significant; P = 0.41). In contrast, a recent observational cohort study of 230 women with
threatened miscarriage who were recommended bed rest showed that women who adhered to
this suggestion had a miscarriage rate of 9.9%, compared with 23.3% of women who continued
their usual activities (P = 0.03). The duration of vaginal bleeding, hematoma size and
gestational age at diagnosis did not influence miscarriage rate. Although there is no definite
evidence that bed rest can affect the course of pregnancy, abstinence from active environment
for a couple of days may help women feel safer, thus providing emotional relief.
Progesterone
Progesterone is prescribed in 13-40% of women with threatened miscarriage, according to
published series. Progesterone is the main product of the corpus luteum, and giving
progestogen is expected to support a potentially deficient corpus luteum gravidarum and induce
relaxation of a cramping uterus. The evidence on progesterone is of low quality. Recently, a

meta-analysis assessed the impact of progesterone supplementation on miscarriage rate in

various clinical settings; however, it did not provide a separate analysis for progesterone in
threatened miscarriage. Four published papers in the meta-analysis were assessing this
relationship, one of them including three different regimens of progestogen, and those data
were reanalyzed. Having miscarriage as outcome, random effects risk ratio was 1.10 (95%
confidence interval 0.92 to 1.31) for progestogens group. In the only studies that provided
sonographic evidence of fetal heart activity at presentation, the relative risk for miscarriage was
1.09 (90% confidence interval 0.90 to 1.33) for the progestogen group. Thus, given the poor
quality of the data, progesterone does not seem to improve outcome in women with threatened
miscarriage. However, local application of a progestogen was found to subjectively decrease
uterine cramping more rapidly than bed rest alone in one small study.
Other regimens
Buphenine hydrochloride (a vasodilator that is also used as a uterine muscle relaxant) was
better than placebo in a randomized controlled trial. But the method of randomization in this trial
was unclear, and no other studies consider tocolysis in early threatened miscarriage.
Apart from its effectiveness, the extent of active support is generally questionable in cases of
threatened miscarriage, since most pregnancies resulting in early fetal loss are chromosomally
abnormal.
Rh prophylaxis
Vaginal bleeding in early pregnancy raises the question of whether to give anti-D
immunoglobulin in Rh D negative women. Unfortunately, there are no conclusive data on this
topic, and all evidence comes from expert or panel opinions (level C). According to the
guidelines of the Royal College of Obstetricians and Gynecologists and the American College of
Obstetricians and Gynecologists, although Rh D alloimmunization attributable to first trimester
threatened miscarriage is rare, giving anti-D globulin should be considered for non-sensitized
Rh D negative women with a threatened miscarriage after 12 weeks of pregnancy, or in cases of
heavy or repeated bleeding or where there is associated abdominal pain, particularly as
gestation approaches 12 weeks. In contrast, anti-D Ig is not considered necessary in women
with threatened miscarriage with a viable fetus and cessation of bleeding before 12 weeks'
gestation.

Summary
Threatened abortion is associated with bleeding and/or uterine cramping while the cervix is
closed. This stage of abortion may progress to spontaneous incomplete or complete abortion.
While this event may be considered a part of the quality control process in human reproduction,
it is important to know the possible etiologies and when therapy might prevent pregnancy loss.
The World Health Organization estimated that 15% of all clinically recognizable pregnancies
and in spontaneous abortion, 50-60% of which are due to chromosomal abnormalities. Apart

from the fetal factors, several maternal and probably paternal factors contribute to the causes of
spontaneous abortion. The maternal factors that may be responsible for abortion include both
local and systemic conditions such as infections, maternal disease states, genital tract
abnormalities, endocrine factors and other miscellaneous causes (antiphospholipid antibodies,
maternal-fetal histocompatibility, excessive smoking and other environmental toxicants, etc.).
This review focuses on the management of threatened abortion, but it should be emphasized
that the management to maintain pregnancy is reasonable only in those cases, in which the
fetus is not seriously affected. It would not be beneficial to provide treatment that would permit
chromosomally and anatomically abnormal embryos to survive to term. Treatment is feasible
first of all in cases with maternal factors. Surgical procedures may precede pregnancy
(correction of septate uterus, removal of a submucous leiomyomata) or may be performed
usually in the second trimester (cervical cerclage). Maternal general diseases (diabetes,
hypothyroidism) and infections should be treated accordingly. The most common entity to be
treated in this category is luteal phase deficiency. Progesterone is the most important hormone
for the maintenance of an early human pregnancy. Besides progesterone administration, human
chorionic gonadotropin (hCG) also is the logical endocrine treatment of choice. In the pregnant
woman hCG stimulates and optimizes hormonal production in the corpus luteum and may also
influence the fetoplacental unit. The contribution of environmental, physical and chemical agents
to the incidence of spontaneous abortion is controversial. They may be abortifacient even if they
are not teratogenic. Exposure to environmental toxicants should be avoided. Paternal leukocyte
immunotherapy has been associated with successful outcome in patients with unexplained
repeated spontaneous abortion. This therapeutic approach is considered experimental, as there
may be some significant risks. Associating maternal antiphospholipid antibodies with
reproductive failure is a rapidly developing field. Administration of corticosteroids with low doses
of aspirin has resulted in fetal salvage in women in whom antiphospholipid antibodies are
present.

Reaction
Threatened abortion is the term used to describe vaginal bleeding that occurs in the
first 20 weeks of pregnancy. Vaginal bleeding could indicate risk of miscarriage. While
miscarriages do occur, many women may experience symptoms of miscarriage and then go on
to carry pregnancies to full term.

Threatened miscarriage occurs often and is a serious emotional burden for women.
Sonographic evaluation at presentation can usually differentiate between intrauterine and
extrauterine pregnancy and offer some prognostic clues. Demonstration of fetal heart activity is
generally associated with a successful pregnancy rate of 85-97%, whereas an empty large
gestational sac or a discrepancy between menstrual and sonographic age of more than a week
indicates a poor prognosis. Advanced maternal age and increasing number of previous
miscarriages deteriorates prognosis.
Serum hCG, progesterone, inhibin A, and CA125 concentrations may be helpful as
predictors; however, these tests may not be useful in primary care settings.
Although many women with threatened miscarriage are given progestogens and are
prescribed bed rest, little evidence supports these policies. There are only four old randomized
controlled trials on progestogens, and their cumulative results show that they do not improve
outcome. Data on bed rest are of even lower quality, as there is only one small randomized
controlled trial, one observational, and one retrospective study, yielding conflicting results.
Although no evidence based suggestions can be made, short term abstinence from usual
activity may be feasible for women if it is likely to relieve their stress.
Rhesus sensitization is rare after first trimester threatened miscarriage; however, consensus
suggests that anti-D immune globulin should be given in cases with bleeding after 12
gestational weeks or cases with heavy symptomatic bleeding near 12 weeks.

Community-acquired pneumonia in children

Vertical transmission of organisms from the maternal genital tract is the main route of entry of
pathogens in the neonatal and early infancy period. The primary organisms responsible for
pneumonia in the first three months of life are group B streptococci, gram-negative bacilli and
occationally Listeria monocytogenes. Between three weeks and three months of life, infants
may present with an insiduous afebrile pneumonitis syndrome caused by Chlamydia
trachomatis. Overall, viruses are the most common causes of pneumonia in the first two years
of life, accounting for up to 90% of pneumonias. The most commonly implicated viruses are
respiratory syncytial virus, parainfluenza virus types 1, 2, and 3, influenza virus types A and B,
adenovirus, rhinoviruses, and less commonly, herpes simplex virus and enteroviruses. With
increasing age, the incidence of pneumonia decreases, but bacterial pathogens
includingStreptococcus pneumoniae, Mycoplasma pneumoniae, and Chlamydia
pneumoniae become more frequent. In children up to 15 years of age, S pneumoniae accounts
for between 17% and 28% of all community-acquired pneumonia cases. The introduction of the
pneumococcal protein-conjugate vaccines in the United States and some Canadian provinces
has led to a substantial reduction in S pneumoniae as a cause of invasive diseases in these
regions, including pneumonias. While the overall rates of invasive pneumococcal infections are
decreasing, the proportion of isolates that are penicillin or ceftriaxone resistant is increasing.
This development should lead to a change in the empiric antibiotic choices for children
presenting with pneumonia in these regions.
Among school-aged children, viruses only account for one-half of the pneumonia cases. M
pneumoniaeis the second most common agent after S pneumoniae and becomes the most
common pathogen in young adolescents, identified in up to one-half of the cases. C
pneumoniae is the second most common agent after M pneumoniae among young adolescents,
accounting for up to one-third of all pneumonia cases.
The symptoms of pneumonia in neonates are nonspecific and include poor feeding, hypotonia,
floppiness, lethargy, apnea, temperature elevation or depression, and hypotension (4). In older
children, presence of respiratory infection may be characterized by tachypnea and occasionally,
hypoxia progressing to apnea and need for ventilatory support. The World Health Organization
has defined clinical criteria for making the diagnosis of pneumonia (18). The criteria consist of
presence of a cough associated with tachypnea. Tachypnea is defined as a respiratory rate over
40 breaths/min in children one to five years old, over 50 breaths/min in children two to 12
months old, and over 60 breaths/min in children under two months old. Use of the World Health

Organization guidelines is associated with a sensitivity of about 70% to 74% and a specificity of
40% to 70% in correctly identifying pneumonia confirmed on the chest x-ray (1920).
The chest x-ray may have discrete airspace or airway involvement, or a diffuse reticulonodular
pattern indistinguishable from the picture seen with hyaline membrane disease. Patients with C
trachomatispneumonia usually present with an afebrile pneumonia associated with staccato
cough, tachypnea, progressive difficulty breathing and chest x-ray findings of bilateral
pulmonary infiltrates and air trapping (57). There is conjunctivitis in half of the cases. Chest
examination may reveal diffuse crackles, but wheezing is not usually a feature. Laboratory
examination may include an elevated total immunoglobulin M and eosinophilia.
Bacterial pneumonia is classically associated with the abrupt onset of chills and rigors, and a
productive sounding cough (truly productive cough is very uncommon in children). The child
more commonly appears toxic and physical examination reveals decreased breath sounds and
crackles that are typically confined to one lobe. Chest x-ray usually confirms lobar involvement.
In contrast, atypical pneumonia has an insidious onset and is associated with a nonproductive
cough, low-grade fever, and generally the children are not as toxic as those with bacterial
pneumonia. The chest x-ray shows more diffuse involvement. It should be noted that typical
bacterial pathogens, such as S pneumoniae and Haemophilus influenzae are most commonly
associated with the classic presentation, and atypical pneumonia is more commonly associated
with M pneumoniae and C pneumoniae. However, all of these organisms may present in either
fashion somewhere between the two extreme clinical pictures (21). Legionella
pneumophila pneumonia is rare in children unless they are immunocompromised (22).
In any child, particularly adolescents who present with cough and fever, consideration should be
given to tuberculosis. A proper history should always include whether the child has lived in a
tuberculosis endemic area or has had contact with persons who are at high risk, such as First
Nations people, immigrants from endemic areas, urban homeless, incarcerated individuals and
persons with human immunodeficiency virus infection. Other clues to tuberculosis include a
subacute presentation, anorexia, weight loss and night sweats (23). Production of sputum and
hemoptysis should differentiate C pneumoniae or M pneumoniae infections from tuberculosis.
Pertussis should be considered in the differential diagnosis of children presenting with
symptoms and signs of CAP, particularly when cough and catarrh are prominent. However,
pertussis rarely causes +radiologically confirmed pneumonia.

Severe acute respiratory syndrome (SARS)-associated coronavirus has recently been added to
the list of pathogens causing pneumonia (24,25). This disease is characterized by temperature
of over 38C and one or more clinical findings of respiratory illness (eg, cough, shortness of
breath, difficulty breathing or hypoxia), and in severe cases, radiographic evidence of
pneumonia or respiratory distress syndrome, or autopsy findings consistent with pneumonia or
respiratory distress syndrome without an identifiable cause (26). In addition, there is need to
have traveled to an endemic area within 10 days of symptom onset or to have had close contact
with a person known or suspected to have SARS. It is unclear whether this condition will remain
a major problem during the coming years. Other important clues to etiology of pneumonia
include exposure to parrots or other psittacine birds (Chlamydia psittaci infection); exposure to
farm animals such as sheep, goats, cattle and cats (Coxiella burnetti); travel to southwestern
United States, northern Mexico and parts of Central and South America (Coccidioides immitis);
and travel to or residence in eastern and central United States and Canada (Histoplasma
capsulatum).

Summary
Community acquired pneumonia (CAP) is common in childhood. Viruses account for most
cases of CAP during the first two years of life. After this period, bacteria such as Streptococcus
pneumoniae, Mycoplasma pneumoniae and Chlamydia pneumoniae become more frequent.
CAP symptoms are nonspecific in younger infants, but cough and tachypnea are usually
present in older children. Chest x-ray is useful for confirming the diagnosis. Most children can
be managed empirically with oral antibiotics as outpatients without specific laboratory
investigations. Those with severe infections or with persistent or worsening symptoms need
more intensive investigations and may need admission to hospital. The choice and dosage of
antibiotics should be based on the age of the patient, severity of the pneumonia and knowledge
of local antimicrobial resistance patterns. The Canadian Pediatric Society recommends the use
of the heptavalent conjugate pneumococcal vaccine, which is efficacious in reducing chest x-ray
positive pneumonia by up to 20%.
Community-acquired pneumonia (CAP) is a lower respiratory tract infection occurring in a child
who has not resided in a hospital or health care facility in the preceding 14 days (1). In a recent
study, the incidence of first episode pneumonia in unimmunized children younger than five years
of age was 55.9 per 1000 person-years. It has been estimated that there are 41,000 Canadian
children younger than five years of age with nonhospitalized CAP, while another 9600 are
hospitalized annually. While the etiology of the pneumonia is not often easy to ascertain in the
clinical setting, the greatest clue is the age of the child.

Reaction
Community-acquired pneumonia (CAP) refers to pneumonia (any of several lung diseases)
contracted by a person with little contact with the healthcare system. The chief difference
between hospital-acquired pneumonia (HAP) and CAP is that patients with HAP live in longterm care facilities or have recently visited a hospital. CAP is common, affecting people of all
ages, and its symptoms occur as a result of oxygen-absorbing areas of the lung (alveoli) filling
with fluid. This inhibits lung function, causing dyspnea, fever,chest pains and cough.
CAP, the most common type of pneumonia, is a leading cause of illness and death worldwide.
Its causes include bacteria, viruses, fungi and parasites.[1] CAP is diagnosed by
assessing symptoms, making a physical examination and on x-ray. Other tests, such
as sputum examination, supplement chest x-rays. Patients with CAP sometimes require
hospitalization, and it is treated primarily with antibiotics, antipyretics and cough medicine.
[2]

Some forms of CAP can be prevented by vaccination and by abstaining from tobacco

products.
Therefore, It has been estimated that about 9000 and 2118 cases of nonhospitalized and
hospitalized CAP cases, respectively, in Canadian children less than five years of age are due
to S pneumoniae (3). A heptavalent pneumococcal vaccine (Prevnar, Wyeth-Ayest, Canada)
has been licensed in Canada since June 2001 and in the United States since February 2000.
When four doses of this vaccine were given to infants at two months, four months, six months
and 12 to 15 months of age, all cases of pneumonia were reduced by 4.3%, but episodes of
pneumonia associated with a positive chest x-ray were reduced by 20.5% among confirmed
cases and by 17.5% on the intention to treat analysis.The vaccine works best in children
younger than one year of age (32.2% reduction in pneumonias associated with abnormal chest
x-ray, compared with 23.3% in infants during the first two years, and 9.1% after two years of
age). Based on these data and the impact on other invasive pneumococcal diseases, the
Canadian Paediatric Society and the National Advisory Committee on Immunization recommend
routine immunization of all Canadian children aged two months to two years, and of older
children in high-risk groups (eg, patients with sickle cell anemia, asplenic patients, those with
human immunodeficiency virus infection, the immunocompromised and those with certain
chronic diseases) with the pneumococcal heptavalent vaccine.

No Evidence of Dehydration with Moderate Daily Coffee Intake:

A Counterbalanced Cross-Over Study in a Free-Living
Population

Maintenance of fluid balance is essential to sustain human life. Water intake balances
fluid losses to achieve adequate hydration of bodily tissues. Although there are
widespread guidelines in scientific literature and media for achieving optimal
hydration status and about the effects that various caffeinated beverages may have on
fluid balance, there is no clear consensus about how much fluid an individual should
consume [1]. One study found total daily fluid intake observed in healthy adults
varied from 0.4164.316 L/day [2]. The current EFSA dietary references values for
water intakes for male adults is 2.5 L/day [3]. However, published guidelines range
from 1.5 L/day [4] to 3.7 L/day [5] for adult males. It has been suggested that
caffeinated beverages should not be included in daily fluid requirement
guidelines [6] and that a glass of water should be consumed with every cup of coffee
or tea to ensure hydration is maintained [7].
Caffeine (1, 3, 7-trimethylxanthine) is a naturally occurring methylxanthine which can
be found in coffee, tea and chocolate. Caffeine acts as an adenosine receptor
antagonist to reduce fractional sodium reabsorption in both the proximal tubule and
distal nephron. When consumed in large doses (500 mg), caffeine elicits a diuretic
effect [8][10]. The diuretic potential of caffeine in humans has been researched for
many years, with the first scientific report published over 80 y ago [11]. The authors
of these early findings suggested that whilst caffeine causes acute diuresis, regular
caffeine consumption may lead to a tolerance developing against its diuretic effect. It
has since been suggested that caffeine withdrawal of as little as 4 days is sufficient for
tolerance to be lost [12]. Following the work of Eddy & Downs [11], there has been a
range of studies that have investigated the effects of caffeine on hydration status
(Table 1). These studies report observations across a range of caffeine forms and doses

on various markers of hydration status in either caffeine-habituated or caffeine-naive

populations (individuals who do not habitually consume caffeine, or those who have
abstained from caffeine consumption for 4 days). Although the data are somewhat
varied, the general trend is that higher doses of caffeine in caffeine-naive individuals
will elicit an acute increase in urine volume, yet a low to moderate dose of caffeine
does not induce a diuretic effect.
Coffee is comprised of many bioactive compounds in addition to caffeine. These
active compounds may interact with each other and therefore coffee consumption
cannot be directly compared to caffeine consumption in its purest form (1,3,7trimethyl xanthine). Interestingly, only two studies have specifically investigated the
effects of caffeine in the form of coffee on hydration status. One study investigated
the effects of six cups of coffee (624 mg caffeine) on urine excretion following a five
day caffeine deprivation period. Over the 24 h period, authors report a 2.7% decrease
in total body water and a 41% increase in urine excretion, with a subsequent 66% and
28% increase in urinary sodium and potassium excretion, respectively. Due to the
study design, which only included caffeine habituated participants who abstained from
caffeine for 5 days prior to testing, the results of the study should be interpreted with
caution before applying to habitual moderate-intake coffee drinkers. Another study
investigated the effects of consuming equal amounts of water, caffeinated cola and
caffeinated coffee (3.10.4 mg/kg caffeine/day) against water with a mixture of
caffeinated colas (1.40.2 mg/kg caffeine/day) or non-caffeinated beverages. The
authors found no effects of coffee consumption compared with non-caffeinated
beverages across a range of hydration markers in caffeine-habituated participants.
Whilst the authors concluded that the advice to exclude caffeinated beverages from
daily fluid requirement was not supported by their findings, the study did not measure
total body water. Total body water (TBW) estimations using the doubly labeled water
dilution technique is considered the gold standard method for assessing body water
fluctuations over time. One recent study investigated the effects of caffeine on TBW
using deuterium oxide. Thirty participants classified as low caffeine users (<100
mg/day) consumed caffeine (5 mg/kg/day) or placebo tablets for 4 consecutive days.
Although these participants could not be classified as caffeine-habituated, no
changes in TBW measured on day 1 and 4 were found between the caffeine or placebo
group. The authors suggested that a moderate dose of caffeine does not alter TBW in
healthy men. To date, no studies have investigated the effects of moderate coffee

consumption on TBW in caffeine-habituated adults using the doubly labelled water

dilution technique.
It is estimated that 1.6 billion cups of coffee are consumed worldwide every day, thus
it is of interest to know whether coffee contributes to daily fluid requirement, or
whether it causes low-level chronic dehydration. In the present study, our aim was to
directly compare the effects of a moderate intake of coffee in caffeine-habituated
adults against equal amounts of water across a wide range of hydration markers,
including the gold standard TBW measure.

Summary
It is often suggested that coffee causes dehydration and its
consumption should be avoided or significantly reduced to maintain
fluid balance. The aim of this study was to directly compare the
effects of coffee consumption against water ingestion across a range
of validated hydration assessment techniques. In a counterbalanced
cross-over design, 50 male coffee drinkers (habitually consuming 3
6 cups per day) participated in two trials, each lasting three
consecutive days. In addition to controlled physical activity, food
and fluid intake, participants consumed either 4200 mL of coffee
containing 4 mg/kg caffeine (C) or water (W). Total body water
(TBW) was calculated pre- and post-trial via ingestion of Deuterium
Oxide. Urinary and haematological hydration markers were recorded
daily in addition to nude body mass measurement (BM). Plasma was
analysed for caffeine to confirm compliance. There were no
significant changes in TBW from beginning to end of either trial and
no differences between trials (51.51.4 vs. 51.41.3 kg, for C and
W, respectively). No differences were observed between trials across
any haematological markers or in 24 h urine volume (2409660 vs.
2428669 mL, for C and W, respectively), USG, osmolality or
creatinine. Mean urinary Na+ excretion was higher in C than W (p=
0.02). No significant differences in BM were found between

conditions, although a small progressive daily fall was observed

within both trials (0.40.5 kg; p<0.05). Our data show that there
were no significant differences across a wide range of
haematological and urinary markers of hydration status between
trials. These data suggest that coffee, when consumed in
moderation by caffeine habituated males provides similar hydrating
qualities to water.

Reaction
Dehydration occurs when you use or lose more fluid than you take in, and your body
doesn't have enough water and other fluids to carry out its normal functions. If you don't replace
lost fluids, you will get dehydrated.
Common causes of dehydration include vigorous exercise, especially in hot weather; intense
diarrhea; vomiting; fever or excessive sweating. Not drinking enough water during exercise or in
hot weather even if you're not exercising also may cause dehydration. Anyone may become
dehydrated, but young children, older adults and people with chronic illnesses are most at risk.
Therefore, Diet was controlled and provided to participants throughout each testing
period, including the control days. The same diet was replicated and provided for each
participant's second trial. Food and fluid intake recorded in the 3-day weighed food diary was
analyzed for macronutrients, sodium and potassium and food fluid content using nutrition
analysis software (Nutritionist Pro, Axxya Systems). Diets were designed and prescribed on an
individual basis to replicate mean energy and fluid intakes from the food diary. Diets were a
standard weight-maintaining composition of for carbohydrate, fat and protein respectively.
A compliance booklet was completed by participants on the morning of each trial day to
ensure all food and beverages from the previous day were consumed at the correct times and
that no unplanned exertions, fluid losses or nutritional variations had occurred. Participants were

instructed to complete the Bristol Stool Chart each morning for indications of disruption to fluid
balance. On the morning of each trial, participants reported to the laboratory at a standardized
time between 07:0009:00. Participants were 10 h fasted and had not consumed any fluids
since 21:30 the previous evening. Participants produced a first morning void (MV) (trial days 1
3) and a separate 24 h urine collection (trial days 23). Nude body weight was recorded and a
venous blood sample collected. Meals and snacks were consumed at standardized times (30
min); breakfast at 07:3009:00 (immediately post testing), morning snack at 10:30, lunch at
13:30, and afternoon snack at 16:30 and evening meal at 19:30.

Dengue and Dengue Hemorrhagic Fever

The disease pattern associated with dengue-like illness from 1780 to 1940 was characterized by
relatively infrequent but often large epidemics. However, it is likely that dengue viruses became
endemic in many tropical urban centers during this time because during interepidemic periods,
when there was no apparent disease transmission, nonimmune visitors invariably contracted a
dengue-like illness within months of their arrival.
The ecologic disruption in the Southeast Asia and Pacific theaters during and following World
War II created ideal conditions for increased transmission of mosquito-borne diseases, and it
was in this setting that a global pandemic of dengue began. With increased epidemic
transmission, hyperendemicity (the cocirculation of multiple dengue virus serotypes) developed
in Southeast Asian cities and epidemic dengue hemorrhagic fever (DHF), a newly described
disease, emerged (37, 48, 61, 63). The first known epidemic of DHF occurred in Manila,
Philippines, in 1953 to 1954, but within 20 years the disease in epidemic form had spread
throughout Southeast Asia; by the mid-1970s, DHF had become a leading cause of
hospitalization and death among children in the region (1). In the 1970s, dengue was
reintroduced to the Pacific Islands and epidemic activity increased there and in the Americas.
During the 1980s and 1990s, epidemic dengue transmission intensified, and there is now a

global resurgence of dengue fever, with expanding geographic distribution of both the mosquito
vectors and the viruses, increased incidence of disease caused by an increased frequency of
epidemic transmission, and the emergence of DHF in many new countries
(36, 39, 41, 45, 48, 61, 63, 110,111, 124).
In Asia, epidemic DHF has expanded geographically from Southeast Asian countries west to
India, Sri Lanka, the Maldives, and Pakistan and east to China (42). Several island countries of
the South and Central Pacific (Niue, Palau, Yap, Cook Islands, Tahiti, New Caledonia, and
Vanuatu) have experienced major or minor DHF epidemics (41). Epidemiologic changes in the
Americas, however, have been the most dramatic. In the 1950s, 1960s, and most of the 1970s,
epidemic dengue was rare in the American region because the principal mosquito vector, Aedes
aegypti, had been eradicated from most of Central and South America (3638, 110). The
eradication program was discontinued in the early 1970s, and this species then began to
reinvade the countries from which it had been eradicated (38, 110). By the 1990s, A.
aegypti had nearly regained the geographic distribution it held before eradication was initiated
(Fig. (Fig.1).1). Epidemic dengue invariably followed reinfestation of a country by A. aegypti. By
the 1980s, the American region was experiencing major epidemics of dengue in countries that
had been free of the disease for 35 to 130 years (3638, 111). New dengue virus strains and
serotypes were introduced (DEN-1 in 1977, a new strain of DEN-2 in 1981, DEN-4 in 1981, and
a new strain of DEN-3 in 1994). Moreover, many countries of the region evolved from
nonendemicity (no endemic disease) or hypoendemicity (one serotype present) to
hyperendemicity (multiple serotypes present), and epidemic DHF emerged, much as it had in
Southeast Asia 25 years earlier (3638). From 1981 to 1997, 24 American countries reported
laboratory-confirmed DHF (Fig. (Fig.2)2) (42, 43, 111).

Factors Responsible for the Increased Incidence

The factors responsible for the dramatic resurgence and emergence of epidemic
dengue and DHF, respectively, as a global public health problem in the past 17 years
are complex and not fully understood. However, the resurgence appears to be closely
associated with demographic and societal changes over the past 50 years
(36, 41, 42, 48). Two major factors have been the unprecedented global population

growth and the associated unplanned and uncontrolled urbanization, especially in

tropical developing countries. The substandard housing, crowding, and deterioration
in water, sewer, and waste management systems associated with unplanned
urbanization have created ideal conditions for increased transmission of mosquitoborne diseases in tropical urban centers.
A third major factor has been the lack of effective mosquito control in areas where
dengue is endemic (36,38, 42, 48). The emphasis during the past 25 years has been on
space spraying with insecticides to kill adult mosquitoes; this has not been effective
(38, 107, 115) and, in fact, has been detrimental to prevention and control efforts by
giving citizens of the community and government officials a false sense of security
(38). Additionally, the geographic distribution and population densities of A.
aegypti have increased, especially in urban areas of the tropics, because of increased
numbers of mosquito larval habitats in the domestic environment. The latter include
nonbiodegradable plastics and used automobile tires, both of which have increased
dramatically in prevalence during this period.
A fourth factor responsible for the global emergence of dengue and DHF is increased
air travel, which provides the ideal mechanism for the transport of dengue and other
urban pathogens between population centers of the world (36, 40, 42, 48). For
instance, in 1994, an estimated 40 million persons departed the United States by air,
over 50% of whom traveled for business or holiday to tropical countries where dengue
is endemic. Many travelers become infected while visiting tropical areas but become
ill only after returning home, resulting in a constant movement of dengue viruses in
infected humans to all areas of the world and ensuring repeated introductions of new
dengue virus strains and serotypes into areas where the mosquito vectors occur
(40, 119).
A fifth factor that has contributed to the resurgence of epidemic dengue has been the
decay in public health infrastructures in most countries in the past 30 years. Lack of
resources has led to a critical shortage of trained specialists who understand and can
develop effective prevention and control programs for vector-borne diseases.
Coincident with this has been a change in public health policy that placed emphasis on
emergency response to epidemics by using high-technology mosquito control methods

rather than on preventing those epidemics by using larval source reduction through
environmental hygiene, the only method that has been shown to be effective (38).
In summary, demographic and societal changes, decreasing resources for vector-borne
infectious disease prevention and control, and changes in public health policy have all
contributed to increased epidemic dengue activity, the development of
hyperendemicity, and the emergence of epidemic DHF.
Dengue in the Continental United States

Each year, dengue cases imported to the Continental United States are documented by
the Centers for Disease Control and Prevention (CDC) (40, 119). These cases
represent introductions of all four virus serotypes from all tropical regions of the
world. Most cases of dengue introduced into the United States come from the
American and Asian tropics, reflecting the increased number of persons traveling to
and from those areas. Overall, from 1977 to 1995, a total of 2,706 suspected cases of
imported dengue were reported to CDC (21, 40, 119). Although adequate blood
samples were received from only some of these patients, 584 (22%) were confirmed
in the laboratory as dengue.
These cases represent only the tip of the iceberg, because most physicians in the
United States have a low index of suspicion for dengue, which is often not included in
the differential diagnosis of acute febrile illness, even if the patient recently returned
from a tropical country. As a result, the majority of imported dengue cases are never
reported (21). It is important to increase awareness of dengue and DHF among
physicians in temperate areas, however, because the disease can be life-threatening.
For example, two cases of dengue shock syndrome (DSS) were recently described in
Swedish tourists returning from holiday in Asia (152). In the United States, imported
cases appear to be increasingly severe (21). From 1986 to 1993, for example, only 13
of 166 patients (8%) with laboratory-confirmed dengue were hospitalized. In 1994
and 1995, however, 6 of 46 patients (13%) and 11 of 86 patients (13%) with
confirmed imported disease required hospitalization, respectively. Moreover, 3 (7%)
of the patients in 1994 had severe, hemorrhagic disease (21). Therefore, it is important
that physicians in the United States consider dengue in the differential diagnosis of a
viral syndrome in all patients with a travel history to any tropical area.

The potential for epidemic dengue transmission in the United States still exists. After
an absence of 35 years, autochthonous transmission, secondary to importation of the
virus in humans, occurred on four occasions in the past 17 years (1980, 1986, 1995,
and 1997) (21, 22). Although all of these outbreaks were small, they underscore the
potential for dengue transmission in the United States, where two competent mosquito
vectors are found (48) (Fig. (Fig.4).4). A. aegypti, the most important and efficient
epidemic vector of dengue viruses, has been in the United States for over 200 years
and was responsible for transmitting major epidemics in the southern states in the 19th
and early 20th centuries (34). Currently, this species is found only in the Gulf Coast
states from Texas to Florida, although small foci have recently been reported in
Arizona (Fig. (Fig.4).4).Aedes albopictus, a secondary vector of dengue virus, was
introduced into the continental United States from Asia in the early 1980s and has
since become widespread in the eastern half of the country. This species currently is
found in 866 counties in 26 of the continental states (22, 105); it has also been found
in Hawaii for over 90 years, as well as in Guam and Saipan. Both A. aegypti and A.
albopictus can transmit dengue viruses to humans, and their presence in the United
States increases the risk of autochthonous dengue transmission, secondary to imported
cases (37, 40).

Summary
Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded
geographic distribution of both the viruses and the mosquito vectors, increased epidemic
activity, the development of hyperendemicity (the co circulation of multiple serotypes), and the
emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquitoborne disease is the most important tropical infectious disease after malaria, with an estimated
100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000
deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever
in the waning years of the 20th century are complex and not fully understood, but demographic,
societal, and public health infrastructure changes in the past 30 years have contributed greatly.
This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by
geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue

fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses,
pathogenesis, surveillance, prevention, and control. A major challenge for public health officials
in all tropical areas of the world is to develop and implement sustainable prevention and control
programs that will reverse the trend of emergent dengue hemorrhagic fever.
Although first reports of major epidemics of an illness thought to possibly be dengue
occurred on three continents (Asia, Africa, and North America) in 1779 and 1780, reports of
illnesses clinically compatible with dengue fever occurred even earlier. The earliest record found
to date is in a Chinese encyclopedia of disease symptoms and remedies, first published during
the Chin Dynasty (265 to 420 A.D.) and formally edited in 610 A.D. (Tang Dynasty) and again in
992 A.D. (Northern Sung Dynasty). The disease was called water poison by the Chinese and
was thought to be somehow connected with flying insects associated with water. Outbreaks of
illness in the French West Indies in 1635 and in Panama in 1699 could also have been dengue.
Thus, dengue or a very similar illness had a wide geographic distribution before the 18th
century, when the first known pandemic of dengue-like illness began. It is uncertain whether the
epidemics in Batavia (Jakarta), Indonesia, and Cairo, Egypt, in 1779 were dengue, but it is quite
likely that the Philadelphia epidemic of 1780 was dengue. A more detailed discussion of the
history of dengue viruses has recently been published.

Reaction
Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded
geographic distribution of both the viruses and the mosquito vectors, increased epidemic
activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the
emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquitoborne disease is the most important tropical infectious disease after malaria, with an estimated
100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000
deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever
in the waning years of the 20th century are complex and not fully understood, but demographic,
societal, and public health infrastructure changes in the past 30 years have contributed greatly.
This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by
geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue

fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses,
pathogenesis, surveillance, prevention, and control. A major challenge for public health officials
in all tropical areas of the world is to develop and implement sustainable prevention and control
programs that will reverse the trend of emergent dengue hemorrhagic fever.
Dengue is a resurging mosquito-borne disease that is often contracted in U.S. travelers
to Latin America, Asia, and the Caribbean. The clinical symptoms range from a simple febrile
illness to hemorrhagic fever or shock. The clinical course has a wide range of outcomes, and
adequate supportive care can reduce mortality rates dramatically. Repeated exposures to the
virus can lead to a more complicated clinical course.
The endemic area for dengue fever extends over 60 countries, and approximately 2.5
billion people are at risk of infection. The incidence of dengue has multiplied many times over
the last five decades at an alarming rate. In the endemic areas, waves of infection occur in
epidemics, with thousands of individuals affected, creating a huge burden on the limited
resources of a countrys health care system. While the illness passes off as a simple febrile
episode in many, a few have a severe illness marked by hypovolemic shock and bleeding.
Iatrogenic fluid overload in the management may further complicate the picture. In this severe
form dengue can be fatal. Tackling the burden of dengue is impeded by several issues,
including a lack of understanding about the exact pathophysiology of the infection, inability to
successfully control the vector population, lack of specific therapy against the virus, and the
technical difficulties in developing a vaccine.