MED J MALAYSIA VOL 61 NO 3 AUGUST 2006
EDITORIAL
COST EFFECTIVE MEDICINE AND DOCTORS
S M Aljunid, MD. MSc, Professor of Health Economics, Department of Community
Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Tenteram,
56000 Cheras, Kuala Lumpur
Constraint in health care resources in developing countries is a major factor
leading to inadequate provision and limitation in access to essential health
care services. While health care costs continue to escalate in most countries
around the world, the overall health care spending in developing countries
continues to stay below 5% of the GDP, the level suggested by the WHO back in
1977 when the Primary Health Care concept was launched. In Malaysia, it is
estimated that total spending on health care services is around 3.8% of the
GDP with 42% of the spending contributed by individuals and households and
the remaining 58% by the government. This pattern of health care spending is
in marked contrast to developed countries. Among the OECD countries for
example, the total health care spending is between 7% to 10% of their GDPs
with the government as the main contributor providing between 65% to 80% of
the total expenditure. The Macroeconomics and Health Commission of WHO
estimated that low and middle income countries need to allocate between USD
30 to 40 per person per year to cover basic health services but at the moment
these countries can afford to spend only USD 13 to USD 24 per person per
year.
One of the many factors which raises health care cost is the growth of new
technologies which include new medical equipment, consumables and drugs.
These new technologies were developed with the aim of improving the outcome
of care but quite frequently they are costly and may not be affordable by
most sections of the population in the world. In order to ensure that limited
resources are wisely spent, monitoring and control mechanisms have to be put
in place in a health care system. This is to ensure that interventions that
are proven to be effective and efficient are allowed to be introduced into
the health care system. 'Effectiveness' refers to the ability of such
intervention to achieve the desired outcome. In health care, the desired
outcome is improvement in health status. To put it simply, effectiveness is
doing the right thing. Effectiveness alone is inadequate in evaluating an
intervention as it ignores cost that has to be borne by health providers and
consumers in order to achieve the desired outcome. Efficiency provides a
wider perspective in dealing with the choices between various interventions
available to manage a patient or provide solutions to solve health problems
in the community. Efficiency refers to the ability of an intervention to
produce an output at the lowest possible costs or to maximize the output at a
given cost. Cost-effective analysis is a technique to assess both
effectiveness and efficiency in health care systems.
There are many ways to ensure efficiency and effectiveness in health care
systems. In the late 70's and early 80's, the focus was on development of
national formularies based on the WHO essential drug list with generic drugs
as the preferred choice. In this approach, doctors and other health care
providers can only prescribe drugs which are proven to be effective at
reasonable cost funded by the government. The first essential drugs list was
released by WHO in 1977 and since then it has gone through more than ten
revisions. This initiative is given high priority by WHO and many other
international agencies such as UNICEF and the World Bank because the
proportion of expenditure on drugs as a percentage of an overall health
spending is higher in developing countries which are lacking in control
mechanisms to over over-prescription of drugs by medical practitioners. It
was observed that while developed countries spend less than one-fifth of
their total health spending on drugs, many developing countries in the world
spend between 25% to 66% of the total national health expenditure. In most
low income countries, pharmaceuticals are the largest public expenditure on
health after personnel costs and the largest household health expenditure.
Among the criteria used by WHO Expert Committee on Drugs when choosing drugs
in the same therapeutic category is relative cost-effectiveness by comparing
the unit cost with the level of efficacy.
However, having a National Drug Formulary alone may not necessarily be
adequate to control over prescriptions and over-spending in drugs. Doctors
and health care workers need to be trained and monitored to ensure that they
practise according to proper guidelines. In this volume of the Medical
Journal of Malaysia, Teng et al have shown how prescribing habits of medical
officers can be improved with simple intervention detailing and distribution
of leaflets with guidelines on management of upper respiratory tract
infections. This intervention could be extended to include other conditions
as well as in hospital settings where costly drugs are more widely used.
In some countries, efforts have been made to improve efficiency in health
care system by controlling the importation of new and expensive equipment.
Certificate of Needs have been introduced in many European countries to
ensure that new and expensive medical equipment are introduced in an
appropriate number to avoid inefficiency in health care spending. The control
of expensive equipment to be acquired by hospitals was made simply to avoid
their inappropriate use by doctors and investors with the aim to recover
their capital investments. Health economists usually use the term "moral
hazards and doctors and hospitals" to describe the inappropriate and overuse
of expensive medical equipment.
Due to the lack of control mechanisms in some developing countries, the rates
of growth of expensive medical equipment acquired by hospitals and clinics
are higher than in many developed countries. In Thailand, for example, the
population of CT Scanners ratio is higher than in United Kingdom, Italy and
France. In a five-year period between 1996 and 2001, the values of imported
medical equipment in Thailand grew by more than 100%.
More systematic approach to encourage cost-effective practice is by having a
national body to carry out economic evaluation on selected interventions and
provide input to practitioners to guide them. In Canada, for example, the
Canadian Agency for Drugs and Technologies in Health is a national body that
provides Canada's federal, provincial and territorial health care decision
makers with credible, impartial advice and evidence-based information about
the effectiveness and efficiency of drugs and other health technologies. An
agency with a similar function was established in United Kingdom in 1999
called the National Institute for Clinical Excellence or NICE. This
institution is a government funded agency responsible to assess new
technology and provide clinical guidance to health professionals and
organizations that employ them in England and Wales. Cost-effectiveness of
the selected interventions is an important part of the assessment by NICE.
The Institute functions as an independent entity outside NHS which gives it
the freedom to carry out the assessment objectively. Even though it is argued
that NICE should look into the equity aspect as well as efficiency in
assessing new technologies, the organisation plays an important role
providing information which helps key policy decisions within the NHS.
in
In some countries, to ensure that the guidelines provided by health
technology assessment agency are followed by practitioners, funding agencies
use these input to guide their reimbursement packages. In other words, only
cost-effective interventions based on guidelines by health technology
assessment agency are reimbursed by the funding bodies. List of benefits
under the national health insurance schemes in many countries are drawn up
based on input from health technology assessment agencies.
In Malaysia, the Health Technology Assessment Unit is currently under the
Medical Divison of Ministry of Health. Established in 1995, the Unit has
carried out a number of health technology assessments and published the
reports which can be downloaded from their website. The capacity of this Unit
to carry out economic evaluation of new and existing health technology is
probably limited since there is no health economist among the staff listed in
their website. In order to make it more effective, it is high time that an
independent Health Technology Assessment Agency is established outside the
Ministry of Health so that it can provide more objective assessment for both
public and private health sector in this country. This is in line with the
on-going efforts by the government to establish the National Health Care
Financing Scheme which will cover services provided by both public and
private providers.
In conclusion, with limited resources available for health care services in
developing countries, the practice of cost-effective medicine is very
crucial. New and existing medical interventions should be fully and
continuously be evaluated from the perspective of effectiveness and
efficiency to ensure that whatever resources available within the health
sector are not wasted but used to the maximum level to improve the health
status of the population. At the same time, reforms in the health care system
are required particularly in developing countries so that mechanisms to
control and monitor effectiveness and efficiency of health interventions are
put in place and fully functioning. Only by taking these necessary steps can
the objectives of health care system in improving and maintaining health
status and quality of life of the population can be achieved and sustainable
in the long term.
MINIMALLY INVASIVE SURGICAL APPROACHES TO THE SPHENOID SINUS, SELLA,
PARASELLAR AND CLIVAL REGION : CURRENT AND FUTURE PERSPECTIVES
B S Gendeh, MS (ORL-HNS), Department of Otorhinolarygology, Head and Neck
Surgery, Faculty of Medicine, Hospital National University of Malaysia, Jalan
Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur
Since its original description in 1907, surgery of the pituitary gland has
undergone a remarkable evolution. While open transphenoid approaches gained
interest, they were mostly abandoned in favour of craniotomy because of
concern of inadequate tumour resection. However, with widespread use of
antibiotics in the 1950s and introduction of surgical microscope in the
1960s, the transphenoidal approach gained popularity as the procedure of
choice in the management of pituitary neoplasms. Widespread application of
endoscopic surgery for diseases of the sinuses in the 1980s and 1990s,
including the management of skull base tumours and CSF leaks, led to the
development of the technique of minimally invasive pituitary surgery.
Endoscopic endonasal pituitary surgery has gained in popularity because of
the remarkable visualization provided by the endoscope in addition to the
reduced morbidity and rapid recovery afforded by this technique. Now, it is
almost routine at many centres to extend transnasal endoscopic-assisted
surgery beyond the sinuses to the orbit and skull base. Providing excellent
transnasal visualization, endoscopes are now used to perform frontal sinus
drainage procedures, to repair CSF leaks, for orbital and optic nerve
decompression and to perform dacryocystorhinostomies.
The transseptal trans-sphenoid pituitary surgery (initially via the sublabial
and then the transnasal approach) is routinely performed as a joint rhinosurgical procedure between the Otorhinolarygnologist and Neurosurgeons at the
Medical Faculty, UKM, Hospital Kuala Lumpur and subsequently via the
endoscopic endonasal approach at Hospital UKM, Cheras, since 1986 and 1998
onwards. Over 250 cases of transseptal pituitary surgery has been performed
as joint rhinosurgical procedure. Lesions in this area, which most commonly
include pituitary adenoma, meningiomas and craniopharyngiomas may have
significant suprasellar component thus requiring precision surgery.
The various surgical approaches to the pituitary gland are listed in Table 1.
The initial intracranial approach used routinely by the neurosurgeon to the
pituitary is becoming less popular due to its disadvantages which includes
fits due to brain retraction, anosmia, pain due to craniotomy and prolonged
hospital stay. Initially, the sublabial approach was widely used as the
standard technique as a joint rhino-surgical procedure at our referral centre
for wide midline exposure through sphenoid regardless of size of nose. The
disadvantages were limitation of exposure from the overhanging upper lip,
hypoaesthesia of the upper gum, retraction of the columella due to resection
of anterior nasal spine causing tip depression and difficulties with dentures
and feeding for two to three weeks post-surgery. The sublabial-transseptal,
transnasal and direct transphenoid approach were significantly improved with
the operating microscope prior to the advent of endoscopes. The transeptal
transphenoidal approach was favoured over other approaches because it was
midline and safer and provided equal access to both sides of the sphenoid
sinus and sella. It avoids access through the oral cavity. The limitations of
the transseptal transnasal approach via alatomy or external rhinoplasty are
alatomy scar and transcolumellar scar. Unfortunately, the author has no
experience to comment on the external ethmoidectomy, sublabial transantral or
the transpalatal approach to the pituitary.
Table 1 : The Various Surgical Approaches to the Sphenoid Sinus, Sella and
Parasellar Region
A) Transcranial
B) Extracranial
Transantral
Sublabial
Transseptal
Sublabial
Transnasal
With alotomy
With external rhinoplasty
Transnasal non-septal
Transethmoid
Transpalatal
Direct Transsphenoid
A direct transnasal transsphenoid approach to the pituitary was introduced in
1987. It has increased in popularity because of improved patient comfort and
the elimination of the complications of lip numbness, oronasal fistula,
septal perforations, chronic nasal crusting and nasal deformity. It provides
reasonably good midline exposure and is the least invasive procedure
described thus far. Some Neurosurgeons use this endoscopic approach for
removal of other intracranial lesions and masses. Use of angled nasal
endoscopes (0, 30 and 70 degrees) and navigational fusion imaging technology
allows precise view of suprasellar or clival extension of sella tumour. Thus,
endoscope is a helpful tool for the Neurosurgeon for tumours with suprasellar
and parasellar extension utilizing the transsphenoidal technique. The
hospital stay will be significantly shortened, minimal to no nasal packing
and patient comfort is enhanced. The advantages of the transnasal non-septal
direct transphenoid approach is the least traumatic and less invasive using
the four hand technique advocated by Dr Heinz Stammberger from Graz. The
disadvantages is, it is off the mid-line technique and its potential
complications.
The increased utilization of endoscopes was accompanied by the development of
new generations of radiographic imaging modalities (CT, MRI) and specialized
surgical instruments such as shaped bipolar forceps, angled extra-long drill
handpieces with diamond burrs, powered microdebrider instrumentation and
image guidance systems. Anatomically, the pituitary gland sits behind a thin
layer of bone in the superior posterior sphenoid sinus. A logical application
of the endoscopic anterior skull base surgical approaches from the sphenoid
extending to the cribrifoam, sella, parasellar and clival region as shown in
Fig. 1 (please refer to page 276 of the Journal). The advantages is that the
exposure is midline, it does not involve any brain retraction and facial
incision is not required.
A pre-operative coronal/axial CT scan, an MRI, as well as an endocrine
evaluation and a visual field examination is essential. A pre-operative nasal
endoscopy is also performed to determine if there are any anatomic
obstruction or polyps. Post-operative visual evaluations were performed only
in patients who showed pre-operative visual impairment. Formal post-operative
endocrine evaluations were performed in all our patients.
In contrast to the limited visualization of the anterior wall of the sella
offered by the microscope, the endoscope provides an excellent view of optic
and carotid protuberances, opticocarotid recesses and clival indentation
which minimizes the chances of catastrophic injury to vital structures on the
lateral wall of sphenoid sinus. Although, the microscope provides a three
dimensional view, the viewable surgical field is restricted by line of sight.
The endoscope has been found to be a highly efficient tool for use in narrow
surgical fields. In microsurgery of the pituitary gland, it provides
excellent fields of vision of the natural ostium of the sphenoid bone and
enables opening of the sphenoid sinus using powered instruments in a very
simple and accurate manner. In addition, by using angled endoscopes,
intrasellar inspection can be performed which allows for more complete tumour
removal. Should there be inadvertent CSF leak, the endoscope allows for
immediate identification and repair. The disadvantages of the endoscope
include its lack of binocular vision and the fact that it does not allow the
surgeon freedom of both hands.
Since most pituitary tumours are in the midline, an endoscopic transseptal
sphenoidotomy provides direct access to the sella. In this issue, the
approaches
highlighted
are
the
hemitransfixation
incision
with
or
trancolumellar approach (external rhinoplasty). It provides wide midline
access to the sphenoid with shorter operating distances without manipulations
of the upper lip, maxillary crest or anterior nasal spine. It simultaneously
allow for the correction of nasal deformities such as the correction of
dorsal hump and tipplasty. The disadvantages of the transcolumellar approach
is the noticeability of the collumelar scar, swelling and stiffness of the
nasal tip which is dependent on the individual skin thickness.
In the small Oriental nostrils, it is almost impossible to introduce the 4mm
endoscope and surgical instrumentation through the nostril that makes
surgical
manipulation
very
difficult.
The
transcolumellar
approach
highlighted in this issue that has been used for rhinoplasty by the author
for patients undergoing transsephoidal pituitary surgery is an alternative
option. In Orientals with small nostrils and females in particular, to
accomodate the Hardy's speculum frequently used by the Neurosurgeons in
Malaysia, an alatomy is a disadvantage for it can produce a visible scar 1.
The advantages of the direct endoscopic sphenoidotomy access are multifold.
Since the patient does not require sublabial or nasal mucosal incision and
dissection from the nasal septum, potential complications of the orodental,
septal and paranasal sinuses areas are eliminated. In majority of the cases,
post-operative obstructive nasal packing is not necessary. In terms of
surgical trauma, the patients were ready to be discharged the day of surgery,
although the surgeon opted to hospitalize them further in order to rule out
post-operative diabetes insipidus. Newer instrumentation is now available for
minimally invasive pituitary surgery as highlighted by Cappabianca et al. The
availability of surgeon-friendly endoscope irrigating systems is essential in
avoiding the 0, 30 or 70 degree scope being frequently being obscured by
blood during pituitary surgery.
Thus, it appears that the endonasal endoscopic approach to the sphenoid
sinus/sella, extending to the cribrifom, parasellar and clival region poses
new frontiers and challenges to the Otorhinolaryngologists and Neurosurgeons
in Malaysia. As a joint team effort, this extended applications beyond the
sphenoid sinus/sella needs a lot of planning and coordination for proper
patient selection and optimal care. The incidence of tumour recurrence will
be very much reduced with the endonasal endoscopic approach. The use of
powered instruments with navigational fusion imaging is most beneficial
especially in revision cases. If need be, the Neurosurgeon can alternate
between the microscope and the endoscope to allow for more complete tumour
removal. Emphasis on on-going cadaver dissection skills are essential to
enhance precision skills in endoscopic anterior skull base surgery.
ORIGINAL ARTICLES
MANAGING CONGESTIVE HEART FAILURE IN A GENERAL HOSPITAL IN MALAYSIA.
ARE WE KEEPING PACE WITH EVIDENCE?
S P Chin, MRCP*, S Sapari, MMed*, S H How, MRCP*, K H Sim, FACC**
*Medical
Department,
Hospital
Tengku
Ampuan
Afzan,
Kuantan,
Pahang,
**Department of Cardiology, Sarawak General Hospital, Jalan Tun Ahmad Zaidi
Adruce, 93586 Kuching, Sarawak
Summary
Evidence-based heart failure management now includes beta-blockers and
spironolactone in addition to diuretics and angiotensin-converting enzyme
inhibitors. We aim to determine if these recommendations had been applied in
practice for acute and chronic stable heart failure, and what difficulties
there might be. Data from 80 consecutive patients hospitalized for
decompensated heart failure ('acute') between May and July 2003 were analyzed
at admission, upon discharge and at 12 weeks follow-up; along with 74
cardiology
clinic
out-patients
with
stable
congestive
heart
failure
('chronic' - no decompensation or admission in previous six months). Less
than half of study patients with prior left ventricular dysfunction were on
ACE-inhibitors (47%), diuretics (39%), ATII antagonists, spironolactone or
digoxin (5% each). All 'acute' patients were commenced on diuretics and ACEinhibitors in hospital. Six patients died or transferred to another centre.
Compliance with clinic appointment at 12 weeks was 85% despite telephone
reminders. Drug prescription at 12 weeks was significantly lower for
diuretics and ACE-inhibitors compared to prescription at discharge (all p <
0.05) but higher compared to patients with chronic HF. Diuretics and ACEinhibitors remain under-utilized for patients with recurrent heart failure.
Use of spironolactone and beta-blocker is slow due to limited medical
experience and funding. Clinic non-attendance is significant and due to
patient factors.
Key Words
Compliance
:
Heart
Failure,
Evidence-Based
Medicine,
Medical
Therapy,
MAXILLARY SINUS TUMOURS - A REVIEW OF TWENTY-NINE PATIENTS TREATED BY
MAXILLECTOMY APPROACH
S Mazlina, MBBS*, S H A Primuharsa Putra, MS ORL-HNS*, M A R Megat Shiraz, MS
ORL-HNS*, M Y S Hazim, MS ORL-HNS*, R Roszalina, FDSRCS**, A R Roslan Abdul,
FDSRCS**
*Department of Otorhinolaryngology - Head & Neck Surgery, Faculty of
Medicine,
Universiti
Kebangsaan
Malaysia,
**Department
of
Oral
and
Maxillofacial Surgery, Faculty of Dentistry, Universiti Kebangsaan Malaysia
Summary
A retrospective data of 29 patients who underwent various types of
maxillectomy from January 1998 till January 2004 in UKM hospital were
reviewed. There were 21 males (72%) and 8 females (28%) with mean age of 42
years. Malays were the majority of patients 17 (59%), Chinese 11 (38%) and
Indian 1 (3%). Seventeen patients (59%) presented with malignant tumours
while 12 patients (41%) with benign tumours. Inverted papilloma (50%) was the
commonest benign tumour and squamous cell carcinoma (36%) was the commonest
malignancy. Medical maxillectomy was performed in 10 patients (35%), total
maxillectomy in 7 patients (24%), 3 patients (10%) had near total, 3 patients
(10%) had partial maxillectomy and 6 patients (21%) underwent inferior
maxillectomy.
Key Words : Maxillary Sinus Tumours, Maxillectomy
THE RISK FACTORS OF GASTROINTESTINAL BLEEDING IN ACUTE ISCHAEMIC
STROKE
B B Hamidon, MMed, A A Raymond, FRCP
Neurology Unit, Department of Medicine, Faculty of Medicine, Universiti
Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Cheras,
Kuala Lumpur
Summary
Gastrointestinal (GI) bleeding is one of the most serious complications after
an acute ischaemic stroke and may affect stroke outcome. We identified
predictors and the eventual outcome of gastrointestinal bleeding during the
in-patient period followind the commencement of aspirin. This was a study of
patients with acute ischaemic stroke admitted to Universiti Kebangsaan
Malaysia Hospital from June 2000 to January 2001. A single observer, using
pre-defined diagnostic criteria recorded information on demography, risk
factors and GI bleeding that occurred during the in-patient period. Onehundred and fifteen patients with acute ischaemic stroke were enrolled in the
study. Gastrointestinal bleeding was observed in 6 (5.2%) patients. Using
univariate analysis, the independent predictors of gastrointestinal bleeding
were age (OR 1.25; 95% CI 1.07 to 1.50) and middle cerebral artery (MCA)
territory infarcts (OR 9.47; 95% CI 1.62 to 55.5). Using multivariate
analysis, the presence of gastrointestinal bleeding increased mortality (OR
24.97; 95% CI 1.97 to 316.91). Older age and large MCA infarct predict the
development of gastrointestinal bleeding. Stroke mortality was independently
predicted by gastrointestinal bleeding. Prophylactic treatment in elderly
patients with large cerebral infarcts may be an area for further
investigation.
Key Words : Gastrointestinal Bleeding, Ischaemic Stroke, Mortality
AN EPIDEMIOLOGICAL CLUSTER PATTERN OF DENGUE OUTBREAK AMONGST CLOSE
CONTACTS IN SELANGOR, PENINSULAR MALAYSIA
K T Ang, MPH*, I Ruhaini, MPH**, K B Chua, FRCPE***
*Department of Health, Shah Alam, Selangor, Ministry of Health Malaysia,
**Gombak District Health Office, Department of Health, Selangor, Malaysia,
***National Public Health Laboratory, Ministry of Health, Lot 1853, 47000
Sungai Buloh, Selangor, Malaysia
Summary
Dengue fever is a major public health problem especially among the highly
urbanized States of Malaysia, such as Selangor and Kuala Lumpur Federal
Territory. We report an epidemiological cluster pattern of dengue outbreak in
the district of Gombak, Selangor that may mimic other acute febrile illnesses
in which the transmission mode is via close contact. This dengue outbreak
consisted of two waves; an initial cluster of three cases (including the
first deceased, JI) which occurred between 20th and 21st of July, followed by
a later larger cluster of 11 cases that occurred between 1st and 8th of
August 2005. This epidemiological clustering pattern of acute dengue virus
infection among close contacts suggests an intense rate of dengue virus
transmission within the vicinity of the first deceased's house.
Key Words : Dengue Fever, Cluster Pattern, Outbreak
RUBELLA OUTBREAK AMONGST RESIDENTIAL
VOCATIONAL SCHOOL OF MALAYSIA
STUDENTS
IN
A
MILITARY
A B Muhd Yusof, MD*, S Selvanesan, BSc**, I Norizah, BSc**, H Zuridah, PhD**,
V Kumarasamy, MPH**, M Mariam, MPH**, K B Chua, FRCPE**
*C808, Rumah Sakit Angkatan Tentera, 71050 Port Dickson, Negri Sembilan,
**Makmal Kesihatan Awam Kebangsaan, Lot 1853, 47000 Sungai Buloh, Selangor
Summary
An outbreak of rubella occurred amongst 303 newly recruited residential Form
IV students in a military vocational training school in Malaysia. Of the 303
Form IV students, 77 gave a history of acute illness. Rubella specific IgM
was detected in the sera of 46.5% (141/303) whereas rubella specific IgG was
detected in 100% of all Form IV students. Sixty-five students with no
clinical history of acute illness during the outbreak period had detectable
rubella IgM in their sera and rubella specific IgM was detected in the sera
of all symptomatic students except one. Maculopapular rash was the commonest
presenting clinical feature among students with acute rubella infection in
this outbreak (97.4%) followed by fever (88.2%). The duration of rash ranged
from one to nine days with a mean of 4.6 days. Of the 65 students that had
both fever and rash, 56 (85.2%) students had maculopapular skin eruption on
the same day as the date of onset of fever, six (9.2%) developed the rash a
day after the onset of fever and three (4.6%) had the rash after two days of
fever. The duration of fever ranged from one to eight days with a mean of 3.5
days. The duration of conjunctivitis ranged from one to four days with a mean
of 2.3 days, and all those who developed conjunctivitis had mild eyedischarge without photophobia. The duration of arthralgia ranged from one to
three days with a mean of 2.1 days. The commonest type of joints affected was
knee joints (66.7%, 12/18), followed by elbow and shoulder joints (27.8%,
5/18) and wrist joints (5.6%, 1/18). A good clinical history of the temporal
relationship between the occurrence of rash and fever during the outbreak
could easily differentiate rubella illness from that of measles.
Key Words : Rubella, Outbreak, Malaysia
AUTOANTIBODIES TO SURVIVIN IN THE SERA OF PATIENTS WITH INFILTRATING
DUCTAL CARCINOMA OF THE BREAST
F S Al-Joudi, PhD, Z A Iskandar, MSc
Department of Biomedical Science, Faculty of Allied Health Sciences, National
University of Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur
Summary
Autoantibodies to survivin have been reported in lung cancers and in
gastrointestinal cancers. A few reports have also described a low prevalence
of autoantibodies to survivin and at low titres in the sera of breast cancer
patients with no implications for their clinical usefulness. This study was
designed to re-examine the prevalence and the clinical correlations of
autoantibodies to the tumour protein survivin in the sera of patients with
infiltrating ductal carcinoma of the breast using an ELISA assay. In spite of
the low prevalence of autoantibodies to survivin (7%, n = 57), their presence
was associated with grade III tumours, with tumour sizes exceeding 10cm, with
axillary lymph nodal involvement and with metastases. Moreover, all the
autoantibody-positive
cases
were
estrogen
and
progesterone
receptors
negative. Furthermore, all the autoantibody-positive cases expressed survivin
wtih high scores.
Key Words : Autoantibodies, Survivin, Breast Cancer
ROLE OF MID-TRIMESTER TRANSVAGINAL CERVICAL ULTRASOUND IN PREDICTION
OF PRETERM DELIVERY
S Hebbar*, K Samjhana**
*Department of O & G, Melaka Manipal Medical College, Melaka, **Postgraduate,
Department of O & G, Katurba Medical College, Manipal
Summary
Ultrasonographic cervical length assessment is increasingly being utilized
clinically to identify women at risk for spontaneous preterm delivery. In a
randomized prospective longitudinal study involving 200 women, we measured
cervical length and internal os diameter by transvaginal scan at 20-24 weeks
and analysed their ability to predict preterm birth. The risk of spontaneous
preterm delivery increased steeply as cervical length decreased. At cut-off
value of ≤ 2.5 cm, the cervical length measurements had sensitivity,
specificity, positive predictive value and negative predictive value of 77%,
95%, 56% and 98% respectively. However, internal os diameter lacked
sensitivity and specificity. Our data suggests that the duration of pregnancy
is directly related to length of the cervix : the shorter the cervix, the
greater the chance of preterm delivery.
Key Words : Cervical Length, Trans-vaginal Ultrasound, Preterm Delivery
PERIOPERATIVE MORTALITY REVIEW IN RELATION TO PREGNANCY-RELATED
DEATHS
K Siva Achana, FRCOG*, A M Zaleha, MRCOG**, Sachchithanantham, FRCOG***, A
Mohd Farouk, MRCOG****
*Perak Royal College of Medicine, No. 3, Jalan Greentown, 30450 Ipoh, Perak,
**Universiti
Kebangsaan
Malaysia,
Cheras,
***Hospital
Melaka,
Melaka,
****Hospital Tengku Ampuan Rahimah, Klang
Summary
Pregnancy-related deaths in four published perioperative mortality review
reports were analysed. The aim is to look at the quality of surgical and
anaesthetic services along with the perioperative care provided. The audit
identified shortfalls in the logistic and support services and recommended
remedial strategies. The review was conducted by a committee consisting of
practising anaesthetists, surgeons and obstetricians who analysed the
questionnaires collectively. A consensus was reached to categorize the death.
There were 280 pregnancy-related deaths. Post-partum haemorrhage accounted
for 31.8%, followed by hypertensive disorders of pregnancy (20.0%), obstetric
embolism (16.1%), sepsis (10.7%) and associated medical conditions (21.4%).
In brief, there were shortcomings in pre-operative, intra-operative and postoperative care in some of the cases. Increased consultant input, clinical
audit, improvements in monitoring and expansion of critical care facilities
were the integral issues recommended.
Key Words : Critical Care Facilities, Clinical Audit, Emergency
Post-Partum Haemorrhage, Perioperative Pregnancy-Related Deaths
Surgery,
ENDOSCOPIC ASSISTED TRANSSEPTAL TRANSPHENOIDAL HYPOPHYSECTOMY
S Mallina, MBBS*, S Harvinder, MMed (ORL-HNS)*, S Rosalind, MMed (ORL-HNS)*,
R Philip, MMed (ORL-HNS)*, S Gurdeep, MS (ORL-HNS)*, S Anil, FRCS**
*Department of ENT & **Department of Neurosurgery, Hospital Ipoh, Jalan
Hospital, 30990 Ipoh, Perak
Summary
Eight patients with pituitary tumours were operated via the transseptal
transphenoidal approach from April to November 2004 at Hospital Ipoh. Seven
patients presented with visual disturbances while three also had endocrine
abnormalities. The post-operative follow-up period was between six months to
a year. There was no mortality in this series. There were no complications
related to the approach, i.e. nasal or septal related. All patients with
visual impairment showed improvement. Only one patient had hormonal
irregularities. The endoscopic assisted transseptal approach to the sphenoid
sinus for pituitary surgery was found to be easy and without sinonasal or
labial complications often found with the sublabial approach.
Key Words : Pituitary Adenoma, Transseptal Transphenoid Surgery, Endoscopic
Hypophysectomy
MODIFYING ANTIBIOTIC PRESCRIBING : THE EFFECTIVENESS OF ACADEMIC
DETAILING PLUS INFORMATION LEAFLET IN A MALAYSIAN PRIMARY CARE SETTING
C L Teng, MMed*, F I Achike, MD*, K L Phua, PhD*, M I Nurjahan, FAFPM*, I
Mastura, MMed**, H Nor Asiah, MMed**, A M Mariam, MMed**, S Narayanan,
MMed**, A Norsiah, MMed**, I Sabariah, MMed**, I Sharifah, MMed**, K Siti
Rokiah, MMed**, M A Siti Zubaidah, MMed**, C N Koh, M OccMed***, I Rosnah,
MPH****
*International Medical University, **Family Medicine Specialist, Klinik
Kesihatan in Negri Sembilan, ***Head, Klinik Kesihatan Seremban, Negri
Sembilan, ****Director, State Health Department, Negri Sembilan
Summary
We assessed the effectiveness of an educational intervention in reducing
antibiotic prescribing in public primary care clinics in Malaysia. Twentynine medical officers in nine clinics received an educational intervention
consisting
of
academic
detailing
from
the
resident
Family
Medicine
Specialist, as well as an information leaflet. The antibiotic prescribing
rates were assessed for six months - three months before and three months
after the intervention. A total of 28, 562 prescriptions were analyzed. Among
participating doctors, general antibiotic prescribing rates for pre- and
post-intervention phases were 14.3% and 11.0% (post-intervention vs preintervention RR 0.77, 95% CI 0.72 to 0.83). The URTI-specific antibiotic
prescribing rates for pre- and post-intervention phases were 27.7% and 16.6%,
respectively (post-intervention vs pre-intervention RR 0.60, 95% CI 0.54 to
0.66). No significant change in antibiotic prescribing rates was observed
among primary care practitioners who did not participate in the study. This
low cost educational intervention using both active and passive strategies
focusing on URTI produced a statistically significant (and clinically
important) reduction in antibiotic prescribing.
Key Words : Prescribing, Primary Care, Upper Respiratory Tract Infection,
Academic Detailing, Information Leaflet
SEASONAL VARIABILITY OF SERUM LIPIDS IN ADULTS : TEHRAN LIPID AND GLUCOSE
STUDY
F Hadaegh, MD, H Harati, MD, A Zabetian, MD, F Azizi, MD
Endocrine Research Centre, Shaheed Beheshti University of Medical Sciences,
Tehran, Iran
Summary
There are contradictory results regarding the pattern of seasonal variation
of serum lipids. The aim of this study was to compare serum lipid levels in
different seasons in participants of the Tehran Lipid and Glucose Study. This
was a cross-sectional study among 2,890 men and 4,004 women 20-64 years old
from the participants of Tehran Lipid and Glucose Study (TLGS) between 1999
and 2001. Mean values of serum lipids in different seasons were compared with
Analysis of Covariance (ANCOVA) after adjustment for age, physical activitiy
level, smoking, BMI and waist-to-hip ratio. In men, there was a significant
trend for change in the values of cholesterol, LDL-C and HDL-C in different
seasons, with higher cholesterol and LDL-C values in winter than in summer (P
< 0.05). In women, only the mean values of triglycerides were significantly
different between different seasons with values lower in winter than in
summer. There was a 26.2% relative increase in the prevalence of
hypercholesterolemia (≥ 240 mg/dl) in winter than in summer in men. The
corresponding increase in the prevalence of high LDL-C (≥ 160 mg/dl) was
26.7% and 24.9% in men and women, respectively (P < 0.05). The prevalence of
high triglycerides (≥ 200 mg/dl) in women significantly decreased (23.8%) in
winter relative to summer (P < 0.001). This study showed that there is
seasonal variability in serum lipid values and this variability is greater in
men than women. The increase in the prevalence of high LDL in winter in both
sexes must be considered in population screening and in the follow-up of
hyperlipidemic patients.
Key Words : Seasonal Variation, Lipids, Adults
EARLY OUTCOME OF REAMED INTERLOCKING NAIL FOR NON-UNION OF TIBIA
W I Faisham, MMed, A R Sulaiman, MMed, A Y Sallehuddin, MMed, W Zulmi, MS
Department of Orthopaedic, School of Medical Science, Universiti Sains
Malaysia, 16150 Kubang Kerian, Kelantan
Summary
Aseptic non-urine is a major problem following complicated fracture tibia,
which carries significant morbidity and prolonged course of treatment. Plate
fixation and autogenous bone grafting has been established as a method of
treatment. However the risk of infection, implant failure and donor site
morbidity are high. We reviewed twelve consecutive cases of established nonunion tibia treated by closed reamed interlocking nail in our centre. All
patients had clinical and radiological union at three months. Three patients
were complicated with infection and one required removal of implant and rereaming to eradicate infection. Reamed interlocking nailing is an alternative
treatment for selected non-union of fracture tibia with promising results.
Key Words : Aseptic Non-Union, Tibia, Reamed Interlocking Nail
THE ROLE OF ENDOSCOPIC ENDONASAL APPROACH TO PITUITARY TUMOURS :
HUKM EXPERIENCE
B S Gendeh*, M Doi*, B M Selladurai**, B A K Khalid****, T Jegan**, K
Misiran***
*Department of Otorhinolaryngology, Head & Neck Surgery, **Neurological Unit,
***Department of Anaesthesiology, ****Department of Medicine, The National
University Hospital, UKM, Cheras, Kuala Lumpur
Summary
Surgery for pituitary tumours at our institution was performed by
rhinosurgical
route
by
combined
procedure
by
otolaryngologist
and
neurosurgeons. A retrospective review of case records of patients who had
endonasal endoscopic transsphenoidal approach for pituitary tumours from
September 1998 to December 2004 was performed. A total of 81 transphenoidal
surgeries were performed during this study period. Only 68 case records with
adequate information were available for review, 56 patients were included in
the study and 12 were excluded. There were 24 males (42%) and 32 females
(58%). The ethnic distribution were 29 Malays, 24 Chinese, 2 Indians and 1
other. The age ranged from 16 years to 76 years, with a mean of 46 years. The
majority of our patients presented with visual symptoms (38), headache (28),
menstrual cycle disturbance or impotence (14) and acromegalic features (16).
Forty patients had macroadenoma (71%) and 16 had microadenomas (29%). Thirtysix patients out of 40 macro-adenoma had suprasellar extensions (90%). Only
11 patients had lumbar drain inserted prior to commencement of the surgery
and the majority of these were macroadenomas. The common complications
encountered were diabetes insipidus (4), cerebrospinal fluid leak (2),
meningitis (3), epistaxis (2), septal perforation (2), intercavernous sinus
haemorrhage (3) and anterior pituitary insufficiency (2). Our study reveals
that endonasal transsphenoidal approach is a safe and effective method of
management of pituitary adenomas.
Key Words : Pituitary Tumours, Endoscopic Transsphenoidal Approach, Surgical
Technique, Presentation, Complications
THE TRANSCOLUMELLAR TRANSSPHENOIDAL APPROACHTO PITUITARY TUMOURS :
ADVANTAGES AND LIMITATIONS
B S Gendeh, MS (ORL-HNS)*, M S Sakina, MBBS*, B M Selladurai, FRCS**, T
Jegan, MS**, K Misiran, FANZCA***
*Department
of
Otorhinolaryngology,
**Department
of
Neurosurgery,
***Department of Anaesthesiology, Hospital Universiti Kebangsaan Malaysia,
Jalan Yaacob Latiff, 56000 Cheras, Kuala Lumpur
Summary
A retrospective review was performed on 11 patients who had undergone the
transcolumellar transsphenoidal hypophysectomy in our center. There were
eight females and three males with age ranging from 17 to 72 years (mean 50
years). Ten patients had pituitary macroadenomas and one had suprasellar
cyst. The mean follow-up duration for these 11 patients post-surgery was 7.2
months. Complications included two cerebrospinal leaks, one post-operative
sphenopalatine bleed, one septal perforation and one patient developed
numbness of the tip of the nose. We found that this approach is a preferred
alternative technique especially in smaller Oriental noses with lower
complication rate and better aesthetic result.
Key
Words
:
Hypophysectomy
Transcolumellar,
Transsphenoidal,
Pituitary
Approach,
CONTINUING MEDICAL EDUCATION
MELIOIDOSIS : A POTENTIALLY LIFE THREATENING INFECTION
S H How, MMed*, C K Liam, FRCP**
*Department of Internal Medicine, Kulliyyahof Medicine, International Islamic
University Malaysia, P.O. Box 141, 27510 Kuantan, Pahang, Malaysia,
**Department of Medicine, Faculty of Medicine, University of Malaya, 50603
Kuala Lumpur, Malaysia
Introduction
Melioidosis
is
caused
by
the
gram-negative
bacillus,
Burkholderia
pseudomallei, a common soil and fresh water saprophyte in tropical and subtropical regions. It is endemic in tropical Australia and in Southeast Asian
countries, particularly Malaysia, Thailand and Singapore. However, only few
doctors in these endemic areas are fully aware of this infection. Hence, the
management of this infection is often not appropriate and sub-optimal. A
recent study in Pahang has shown the incidence of this infection in Pahang is
comparable with that in northern Thailand. The overall mortality from this
infection remains extremely high despite recent advancement in its treatment.
In the Pahang study, only 32% of patients were given an appropriate
antibiotic empirically and about half of the culture-confirmed cases were not
treated with appropriate intravenous antibiotic chemotherapy and most cases
were not given eradication therapy. This review is to present to doctors
working in endemic areas about the diagnosis and proper management of
melioidosis.
Epidemiology
The incidence of melioidosis varies between countries and also in different
parts of the same country. For example, in Thailand, it is most commonly seen
in the north-eastern region with an incidence of 4.4 per 100,000 population
per year. In Northern Australia, the incidence is higher (16.5 per 100,000
populations per year) than that in Thailand. The incidence in Pahang and
Singapore is 6.1 per 100,000 population per year and 1.7 per 100,000
population per year, respectively. However, the true incidence may be higher
than that reported as most of these studies included culture-confirmed cases
only. Furthermore, some patients with mild infection from the rural areas may
not present to the hospital. More and more melioidosis cases are being
reported from previously unreported parts of the world especially southern
China, Taiwan, India, Laos and Vietnam but the true endemicity in these areas
is not established. Also isolated cases have been reported in the temperate
countries among travellers returning from endemic areas.
Melioidosis is a disease involving all age groups but commonly occurs in
people between the ages of 40 to 60 years and is related to farming. It is
less common in the paediatric age group. In the Australian study, only 4% of
patients were younger than 15 years whereas in Malaysia, 7.6% and in
Thailand, 10-17% of patients were in this age group. It is more common in
males than females with the male to female ratio being 1.5:1 to 4.5:1. This
may be due to more males being exposed in soil related occupations. Farming
has been shown to be strongly associated with incidences of melioidosis. For
instance in Thailand, 81% of melioidosis patients were rice-farmers and their
family members. Currently, the postulated mode of transmission is direct
entry of the organism into the blood stream via very minor wounds or skin
abrasions. Therefore, a definite history of injury is uncommon (5-2%). The
second commonest mode of infection is inhalation of contaminated dust. Strong
wind increases number of melioidosis cases during the raining season. Other
common modes of infection reported are drowning, motor vehicle accident, via
breast milk, perinatal transmission and human-to-human transmission.
Melioidosis occurs commonly (53-85%) in adults with underlying diseases that
predispose them to infection. In contrast, less than 20% of the paediatric
patients have underlying diseases and almost all cases of localised disease
in this age group have no predispose factors. In adults, diabetes mellitus is
the commonest underlying disease (20-74% of cases). Alcoholism and the
consumption of kava (an extract of the root of the plant consumed by the
Aboriginal people in Australia in place of alcohol) seem to be a major factor
associated with melioidosis in Australia. However, such habitual risk factors
are less common in Southeast Asia. Other underlying diseases throught to be
associated with melioidosis are chronic renal failure, renal calculi, chronic
lung
disease
(especially
cystic
fibrosis
in
Australia),
human
immunodeficiency virus (HIV) infection, intravenous drug abuse, malignancy,
systemic lupus erythematosus and corticosteroid therapy. Table 1 summarizes
the epidemiology and mortality of melioidosis in some of the endemic
countries.
Table 1 : Epidemiology and Mortality of Melioidosis in Endemic Countries
Australia
No. of Cases
252
Incidence*
16.5
Median Age (Year)
49
Male : Female Ratio
3:1
Paediatric Patients (%)
4
Bacteraemia (%)
46
Mortality Rate (%) :
19
Overall
37
Bacteraemia Cases
Underlying Disease (% 80
of cases)
37
10
At least one
Diabetes Mellitus
39
Renal Disease
27
8
Alcoholism
Chronic Lung Disease
Kava Consumption
* Per 100,000 populations per year
Thailand
423
4.4
45
1.4:1
60
44
-
Pahang,
Malaysia
(Adults Only)
135
6.1
51
3.6:1
7.6
92
54
54
Singapore
372
1.7
55
4.5:1
2.4
39
40
55
53
20
13
<1
-
85
74
6
1
3
-
77
57
6
10
-
Clinical Manifestation
Asymptomatic seroconversion is common in endemic countries as evidenced by
positive serology in up to 50% of healthy adults in these countries. As in
the case of Mycobacterium tuberculosis B. pseudomallei may remain dormant in
macrophages for many years following infection before causing disease when
the host's immune system deteriorates. This is evident in American soldiers
who developed melioidosis many years after returning from Vietnam. Currently,
there is no data on the outcome of these asymptomatic patients with positive
serology or whether treatment is necessary.
There
are
several
classification
of
the
clinical
manifestation
of
melioidosis. It may present as acute or chronic infection (defined as more
than two months of symptoms). The acute form of the disease commonly presents
with septicaemia and is associated with very high mortality. On the other
hand, the chronic form commonly presents as long-standing suppurative focal
abscesses with fever and wasting and is associated with a good prognosis. In
endemic areas, 88-90% of cases present with the acute form of melioidosis. It
can also be classified as localised or disseminated infection. The latter is
seen in 15-30% of cases. The widely accepted classification is the presence
or absence of bacteraemia as this is an important predictor of the ultimate
outcome. The reported incidence of bacteraemia is 46-92% in most of the
endemic areas. The highest incidence of bacteraemia of 92% reported in the
literature is from Malaysia. This is probably related to late presentation as
the patients normally seek traditional treatment before presenting to the
hospitals. A higher frequency of diabetes mellitus in this study may be
another contributing factor as individuals with diabetes are at higher risk
of bacteraemic melioidosis. In Northern Thailand, 20% of community acquired
septicaemia is due to melioidosis and this infection contributes to 39% of
the mortality due to septicaemia.
Fever is the commonest presentation and is present in almost all patients.
The duration of fever may vary from a few days to months. Melioidosis is one
of the causes of pyrexia of unknown origin in endemic areas. Symptoms and
signs depend on the site or organ involved. Patients presenting with shock
have a poor prognosis and have mortality in excess of 80% even in a good
centre.
White blood cell counts on admission commonly (55.6% of cases) show
leucocytosis but may be normal or low (3.7% of cases). Other evidence of
sepsis such as thrombocytopenia, disseminated intravascular coagulopathy,
renal impairment, abnormal liver function, metabolic and respiratory acidosis
are common presentations in severe infections.
Pulmonary Melioidosis
Pneumonia is the commonest clinical manifestation and is present in half of
the cases. Patients may present with acute fulminant pneumonia with
septicaemia which commonly requires mechanical ventilation and intensive
care. This manifestation is associated with a mortality exceeding 80%. On the
contrary, a more indolent presentation is associated with a better outcome.
Cough is commonly productive of purulent sputum and associated with fever.
Haemoptysis is rare in acute disease but may be present in up to 31% of
patients with the chronic form of the disease. The chest radiograph in acute
disease commonly shows either a localised patch or bilateral diffuse patchy
alveolar infiltration or multiple nodular lesions which may coalesce,
cavitate (cavities are usually thin-walled and rarely contain air-fluid
level) and form abscesses. In the chronic form of the disease, the chest
radiograph findings may be difficult to distinguish from that of pulmonary
tuberculosis which typically involves the upper lobes with patchy alveolar
infiltrates and cavitations. Sparing of the apical region and lack of
calcification suggest the likelihood of melioidosis rather than pulmonary
tuberculosis. Pleural involvement occurs in 9-33% of cases and thoracic
empyema is occasionally seen. Pyopericardium and hilar lymphadenopathy are
rare. There was a case report on bronchiolitis obliterans organising
pneumonia associated with pulmonary melioidosis that responded well to
steroid therapy.
Skin and Subcutaneous Involvement
Skin and subcutaneous involvement is the second commonest presentation.
Blisters, superficial erythematous pustules, clusters of violaceous skin
abscesses, cellulites and subcutaneous abscesses are commonly seen. Skin
biopsy or aspiration of the pustules or vesicles may yield the organism.
Lymphadenitis or lymph node abscess is commonly seen in children. The
cervical lymph nodes are most commonly involved mimicking tuberculous
lymphadenitis.
Intra-Abdominal Abscesses
Liver and/or spleen abscesses are present in 4-17% of adult melioidosis.
Liver abscesses are frequently (82%) multiple and less likely to cause right
upper quadrant pain and tenderness as compared to other pyogenic abscesses.
Liver abscess is associated with splenic abscess in 56% of cases which are
commonly multiple as well. Serology is not useful in differentiating liver
abscesses due to melioidosis from other pyogenic abscesses in endemic areas
but the presence of multiple nodular opacities on the chest radiograph
strongly suggests melioidosis. In Northern Thailand, the majority of liver
and splenic abscesses are due to melioidosis. Other rare intra-abdominal
lesions are empyema of the gall bladder, pancreatic abscess and adrenal
abscess.
Urogenital Tract Infection
About 18% of adult males with melioidosis in Australia had prostatic abscess
and the patients commonly presented with fever, abdominal pain, dysuria,
diarrhoea and acute urinary retention requiring catheterisation. However,
prostatic abscess is not commonly seen in Thailand and Malaysia probably due
to under-diagnosis as not all melioidosis patients undergo abdomen and pelvic
CT scan examination. Digital rectal examination is useful to detect prostatic
involvement but it cannot differentiate between prostatic abscess and acute
prostatitis
due
to
other
causes.
Other
urogenital
complications
of
melioidosis are pyelonephritis, perinephric abscess and scrotal abscess.
Neurological Melioidosis
Melioidosis involving the central nervous system is less common, 4% in the
Australian series. However, it can involve the whole central nervous system
causing macroscopic or microscopic brain abscesses, meningo-encephalitis,
brain stem encephalitis and transverse myelitis. Headache is another common
symptom together with fever. Other presentations include unilateral limb
weakness, cerebellar signs, brainstem palsies (commonly VI, VII and bulbar
palsy) or flaccid paraplegia. Cerebrospinal fluid examination commonly shows
high protein with predominantly mononuclear cells. The glucose level in the
cerebrospinal fluid may be normal or slightly decreased. Initial brain CT may
be normal or show non-specific changes. Magnetic resonance imaging is the
investigation of choice and shows abnormality in all cases. The common
finding is multiple diffuse high signal lesions reflecting the clinical
findings. Nearly half of the patients may require mechanical ventilation with
a mortality rate of 25%.
Musculoskeletal Melioidosis
Septic arthiritis most commonly affects the knee (50%) followed by the ankle
(13%), wrist (10%) and elbow (10%) joints. Osteomyelitis is less common.
Other Organs that are Rarely Involved
It may be difficult to know the site of infection in some patients as they
succumb to the disease (37-65%) within 48 hours of admission before
investigation could be performed. Other rare presentations of melioidosis are
mycotic aneurysm, pericardial effusion psoas abscess and infected thyroid
cyst.
Melioidosis in Children
As in adults, melioidosis in children may present as an acute septicaemia
with foci of infection in the lungs (the most frequently involved organ),
liver, spleen or other organs. Progression into shock is rapid and mortality
rate is also high. Localised infection is common in childhood, especially
involving the head and neck region. Unilateral suppurative parotitis has been
reported to account for 40% of localised melioidosis in Thailand and patients
commonly present with fever and cheek pain. Physical examination commonly
shows unilateral parotid swelling with abscess formation that may cause
facial nerve paralysis, periorbital cellulitis and conjunctivitis. Purulent
discharges at the opening of Stensen's duct and the ear (if spontaneous
rupture of the abscess into the auditory canal occurs) may be seen. It can
rarely cause dissemination or septicaemia. Pharyngocervical melioidosis is
also common and the child commonly presents with fever and sore throat with
or without cervical lymphadenopathy. It mimics upper respiratory tract
infection caused by other bacteria and as such diagnosis is difficult without
culture confirmation from throat or pus swab. Fortunately, the prognosis for
localised infection is generally good.
Mortality
Mortality due to melioidosis is extremely high especially in the bacteraemic
form. A study by Puthucheary et al many years ago showed the mortality was
65% in patients with bacteraemic melioidosis. The higher mortality in this
study was probably due to undertreatment as only 24% of the patients received
appropriate empirical antibiotic therapy. A more recent study in Australia
(1989 to 1999) reported a lower mortality of 37% with bacteraemic
melioidosis. This was probably due to the wider use of ceftazidime or
carbapenams and better intensive care. However, this lower mortality rate has
not been recorded in all endemic areas as the most recent study in Malaysia
from 2000 to 2003 revealed a mortality of 54% in bacteraemic melioidosis.
This was probably due to the lack of awareness among doctors in Malaysia
regarding the appropriate treatment of melioidosis as only 52% of cultureconfirmed cases in that study received an appropriate antibiotic. In
Singapore (1997 to 2001), the mortality was 53% and was higher among those
with pneumonia (73%).
The overall mortality in Australia (19%) was lower than that of other regions
probably because of a lower incidence of bacteraemic melioidosis (46%) in the
Australia series. In Pahang, the overall mortality rate was 54% (92%
bacteraemic form) compared to 44% in Thailand (60% bacteraemic form). Other
possible factors associated with high mortality include a shorter duration of
fever, lower platelet count, higher blood urea and presence of pneumonia,
multi-organ involvement and septicaemia of unknown source.
Relapse and Recurrence
A study by Chaowagal et al found that 23% of their patients had culture
proven relapse with a yearly relapse rate of 15%. The mortality rate
associated with relapse was 27% and patients with septicaemia, disseminated
infection, short course of maintenance therapy and intensive therapy with
antibiotics other than ceftazidime had higher risk of relapse. In the
Australian study, 13% of patients had bacteriologically confirmed relapses
with 11% mortality. Half of the relapses were due to poor adherence to the
eradication therapy and another 37% of the relapses were related to
doxycycline monotherapy.
Laboratory Diagnosis
Isolation of B. pseudomallei is best achieved using Ashdown medium that
contains aminoglycoside to which this organism is resistant. Blood agar and
chocolate media can be used for sterile specimens. More than 90% of the
isolates are sensitive to ceftazidime, cefoperazone-sulbactam, doxycycline,
chloramphenicol
amoxycillin
clavulanate
and
imipenem.
Resistance
to
trimethoprim-sulfamethoxazole has been reported to be more than 50% by the
disc diffusion method as compared to less than 10% by either the E-test,
Microscan or agar dilution method. Specimens for culture should be obtained
from blood, urine and other sources which include joint fluid, sputum,
cerebrospinal fluid, pus and tissue depending on suspected organ involvement.
In patients who are unable to produce sputum, throat swab has been shown to
have 100% specificity with 38% and 47% sensitivity in adult and paediatric
patients, respectively. Throat swab has the advantage of allowing early
presumptive identification of the organism within 48 hours as compared to 3-4
days from blood culture. It is useful in paediatric patients and in patients
who are too ill to produce sputum.
Serology has been studied extensively but a high background of positive
serology in the general population limits its usefulness in an endemic area.
A study in north-eastern Thailand has shown the indirect haemagglutination
test (IHA) to have a sensitivity of 95% but a specificity of 59% by using a
cut-off level of 1:20 dilution. In that study, some of the non-melioidosis
septicaemia patients had positive titres of more than 1:1,280. However, acute
seroconversion in a clinically septic patient strongly suggests melioidosis.
Serology is useful to monitor disease activities and relapse. Antigen
detection using specific monoclonal antibody and specific chain reaction are
newer methods that may give an earlier diagnosis but these tests are not yet
commercially available.
In suspected or confirmed cases, chest radiograph should be taken as 50% of
cases have lung involvement. Ultrasound examination should be done to locate
intra-abdominal abscesses even in the absence of positive physical signs.
Abdominal
and
pelvic
CT
scan
may
be
more
sensitive
in
detecting
microabscesses and prostatic abscess. Trans-rectal ultrasound can be used to
detect prostatic abscess which is commonly multiple and larger than other
bacterial prostatic abscesses. Figure 1 summarises the list of investigations
recommended in patients suspected to have melioidosis.
Figure 1 : Recommended Investigations for Suspected and Confirmed Melioidosis
In suspected or confirmed cases, the following investigations are necessary :
1. Blood culture and sensivity
2. Urine culture and sensivitiy
3. Melioidosis
serology
(Immunofluorescent
antibody
test/IFAT)
(Titre of 1:80 is suggestive of melioidosis; if the titre is less than
1:80, repeat the test 2 weeks later)
4. Throat swab culture
5. Ultrasound examination of abdomen to detect abscesses in the liver,
spleen, kidney, adrenals and prostate
6. Chest X-Ray
Other useful investigations :
1. Culture and sensitivity of pus, cerebrospinal fluid, joint fluid,
sputum, etc. depending on the clinical suspicion of organ(s) involved.
2. Gram staining of clinical specimens (commonly shows one to five
organisms per low-power field, short Gram-negative bacilli with a
granular or safety-pin appearance).
3. CT abdomen and pelvis or trans-rectal ultrasound of prostate if
prostatic abscess is suspected
4. PCR of joint fluid, urine, pus, etc.
Management
The general management of melioidosis is the same as for any infection.
Severe and life-threatening melioidosis should be managed in the intensive
care unit. Large abscesses should be drained especially when patients are not
responding well to antibiotic therapy. Fever may persist for a week or more
despite appropriate antibiotic therapy. Patients with persistent fever
lasting more than a week require further examination and investigations to
look for occult abscesses. Control of blood sugar is important in diabetic
patients.
Definitive antibiotic treatmetn of melioidosis can be divided into an
intensive and an eradication phase. The conventional regimen for the
intensive phase was intravenous (IV) chloramphenicol, tetracycline and
cotrimoxazole. These drugs are bacteriostatic and toxic. High dose of
ceftazidime has replaced this conventional regimen after two randomised
controlled trials showed treatment with ceftazidime resulted in 50% reduction
in mortality of severe melioidosis. Simpson et al compared treatment with
ceftazidime and imipenam and found no difference in mortality but treatment
with the former was associated with a higher failure rate. There was one
randomized study comparing intravenous co-amoxiclav to ceftazidime and found
no difference in mortality but less failure rate in the ceftazidime group.
Two
studies
comparing
cefoperazole-sulbactam
wiht
co-trimoxazole
and
ceftazidime
with
co-trimoxazole,
respectively
found
similar
efficacy,
mortality rate and bacteria clearance rate. Both studies used a lower dose of
cefoperazole-sulbactam. In a non-randomised retrospective study, meropenam
treatment was associated with a lower mortality than ceftazidime in severe
sepsis patients, defined as patients requiring intensive care, clinical
failure or intolerant to ceftazidime (25% versus 76%). However, this study
listed a few confounding factors especially the use of granulocyte colonystimulating factor (G-CSF) which might have contributed to the reduction in
mortality.
After at least two weeks of intensive therapy with intravenous drug and
clinical improvement, oral therapy should be recommenced to prevent relapses.
The conventional regimen for oral maintenance therapy was the combination of
chloramphenicol, doxycycline and co-trimaxazole. Several studies have used
various single drug regimens (co-amoxiclav or doxycycline alone) or a
combination of ciprofloxacin and azithromycin compared to the conventional
regimen and the latter combination has been shown to be more effective in
preventing relapses. Recently, a randomized open labelled study found the
combination of doxycycline and co-trimoxazole is as effective as the
conventional regimen and is associated with fewer side effects. In this
study, treatment of less than 12 weeks was associated with a shorter time to
relapse or death. The Australian experience for the past ten years found a
very low failure rate of less than 1.6% with co-trimaxazole alone but whether
adding doxycycline is beneficial or not requires further evaluation. There
have been no randomized trials of treatment of melioidosis in children due to
the low incidence of this infection in the paediatric population. From the
currently available data, we propose the treatment of melioidosis as shown in
Figure 2.
Figure 2 : Recommended Antibiotic Treatment for Melioidosis
A.
Treatment
in
Adults
Intensive Therapy
Life threatening melioidosis (presence of respiratory failure requiring
mechanical ventilation, impaired consciousness, acute renal failure requiring
dialysis, DIVC or multi-organ failure).
• IV meropenem (25 mg/kg/dose; usual dose for adult : 750 mg to 1 gm TDS)
with trimethoprim (8 mg/kg/day) and sulfamethoxazole (40 mg/kg/day)
(usual dose 2,880 mg/kg/day) for at least two weeks. May substitute
meropenem with imipenam (50 mg/kg/day). Consider IV G-CSF 300µg daily
for ten days in patients with septicaemia shock.
Severe
melioidosis
(presence
of
organ
dysfunction,
hypotension
or
disseminated infection).
• IV ceftazidime (100 mg/kg/day; usual dose for adult, 2 gm TDS) with
trimethoprim (8 mg/kg/day) and sulfamethoxazole (40 mg/kg/day) for at
least 2 weeks. May substitute ceftazidime with cefoperazone-sulbactam 1
gm TDS. Consider IV G-CSF 300µg daily for ten days in patients with
septicaemia shock.
Mild to Moderate Melioidosis
•
IV amoxycillin=clavulanate (160 mg/kg/day in six divided doses daily)
for at least 2 weeks.
Eradication Therapy
•
Oral co-trimoxazole (trimethoprim 8 mg/kg/day and sulfamethoxazole 40
mg/kg/day)
and
doxycycline
dose
960
mg
co-trimexazole
BD
and
doxycycline 100 mg BD) are the standard oral combination regimen and
should be administered for a total of 20 weeks. Amoxycillin/clavulanate
(45 mg/kg/day) combined with amoxycillin (30 mg/kg/day) in four divided
doses daily, is an alternative and can be used in pregnant women (for
the same duration).
B. Treatment in Children
In children with severe melioidosis, IV ceftazidime 40 mg/kg/day dose eight
hourly should be given for two weeks. IV meropenem 25 mg/kg/dose may be
considered in life threatening cases.
Maintenance
therapy
:
Co-trimoxazole
(trimethoprim
8
mg/kg/day
and
sulfamethoxazole 40 mg/kg/day) and doxycycline (4 mg/kg/day in two divided
doses) are the standard oral combination regimen and should be administered
for a total of 20 weeks. Amoxycillin/clavulanate 15 mg/kg/dose for 8 hourly
should be used instead of doxycycline in children below 8 years.
Localized melioidosis should be treated with incision and drainage with cotrimoxazole (trimethoprim 8 mg/kg/day and sulfamethoxazole 40 mg/kg/day) and
doxycycline (4 mg/kg/day in two divided doses) for 6-8 weeks. Replace
doxycycline with amoxicillin/clavulanate in children below 8 years.
References & MCQs on Melioidosis : A Potentially Life Threatening Infection :
Kindly refer to the August 2006 issue of the Medical Journal of Malaysia,
Volume 61, Issue No. 3