Bali Infectious Disease Symposium-6

The Etiology of Acute Febrile Illness Requiring Hospitalization (AFIRE)

Tuti Parwati Merati
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine- Sanglah Hospital Denpasar
ABSTRACT
Febrile illnesses account for approximately 20-25% of hospitalizations in Indonesia
and present a major cause of morbidity and mortality. Fever can be attributed to
noninfectious causes. However in developing countries a clinical presentation with fever is
usually linked to an infectious etiology. Though several studies have been implemented to
study specific infectious disease agents such as dengue, diarrhea, or influenza-like illness,
large-scale studies to identify causes of febrile illnesses in Indonesia have not been
conducted. Further there are a reasonable percentage of patients for whom the cause of
the infectious etiology is unknown. To identify the etiology of infectious diseases,
microscopic examinations, bacterial and viral cultures, molecular, antigen or antibody
assays are needed. Clinicians often make the diagnoses solely on the clinical presentation
as laboratory diagnostic capacities are lacking, high costs involved in specialized
diagnostic testing, or the inability of a majority of patients to afford testing. This can lead to
inappropriate clinical management and inappropriate use of expensive antibiotics, which
may contribute to increasing drug resistance. Several studies have been conducted to
evaluate febrile illness in various contexts in Indonesia. These studies have identified
pathogens in specimens collected from several acute undifferentiated fever studies.
AFIRE study is an observational cohort study of hospitalized patients with fever.
The amount of sample used in this study N = 1600, which consisted of 100 subjects
children and 100 subjects adult in each site, where there are 8 sites are conducting this
study. The study population consisted of men and women aged 1 year. Subject
recruitment period for 1 year The study collects demographic data, history of illness, signs
and symptoms, results of laboratory tests, clinical course, treatment and outcome. The
primary objective of the study is to identify the etiology of acute febrile illness cases and
evaluate clinical manifestations and outcomes. Moreover, the secondary objectives are to
provide clinical data that are essential for improving and/or developing clinical
management and health policies, to enhance research capacity and networking for

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infectious diseases in Indonesia by improving clinical research site capability in conducting

research relevant to public health, and to establish a repository of biological specimens for
future study, such as determining the etiology of undiagnosed fever and/or its
pathogenicity and its public health importance.
The total enrolled from local data (Sanglah Hospital/site 520) since July 2013 until
November 2014 were 122 subject, there were 630 subjects screened (adult 415 and
pediatric 215).Most clinical diagnosis based on research data from Sanglah Hospital (site
520) since July 2013 until November 2014 were dengue infection, respectively respiratory
infection, thypoid infection, gastro intestinal infection. The total laboratorium confirmed 40
subject (32,8%), consist of serology (18) Viral (9), Bacterial (6) ; Culture (12): Bacterial
(9), Fungal (3) ; serology and culture (5): Bacterial (4), Bacterial and viral (1) ; antigen (2):
Viral (2) ; microscopy (3): Amoeba (3). The total not laboratorium confirmation were 82
subjects (67,2% ).

Bali Infectious Disease Symposium-6

FEVER AND RASH IN ACUTELY ILL PATIENTS

Made Susila Utama, Tuti Parwati Merati
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine- Sanglah Hospital Denpasar
Evaluating the patient who presents with fever and a rash can be challenging
because the differential diagnosis is extensive and includes minor and life-threatening
illnesses. The clinical picture can vary considerably. The etiology of acute fever and rash
was including a variety of infectious and non infectious. In most cases, a systematic
approach based on clear history, careful clinical examination with the special attention to
the types and other characteristics of rash and their relation to fever and other signs and
symptoms, along with the properly targeted epidemiological clues can aid to establish
possible diagnosis and select those patients who need immediate medical intervention
without applying specific laboratory tests.
Therefore, making a specific diagnosis in an adult with fever and rash can be
extremely important. An accurate characterization of the skin lesions and a thorough
history can help narrow the differential diagnosis for a specific patient. A detailed history
can be quite helpful in identifying the cause of fever and a rash. A history of recent travel,
woodland or animal exposure, drug ingestion or contact with ill persons should be noted. A
complete medical history can help to determine whether the patient is at increased risk for
specific conditions associated with valvular heart disease, sexually transmitted diseases or
immunosuppression from chemotherapy. Immune status is particularly important because
many of the diseases that result in fever and a rash present differently in
immunocompromised patients. Details about the rash should include site of onset, rate
and direction of spread, presence or absence of pruritus, and temporal relationship of rash
and fever. It is also important to know whether any topical or oral therapies have been
attempted.

Bali Infectious Disease Symposium-6

FEVER OF UNKNOWN ORIGIN (FUO)

Anak Agung Ayu Yuli Gayatri
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine- Sanglah Hospital Denpasar
ABSTRACT
Fever of unknown origin (FUO) in adult population remain one of the most common
and difficult diagnosis problem faced daily by clinicians. The most likely cause can then be
assigned to one of four broad categories; infection, inflammation, malignancy or
miscellaneous. These broader classes help guide initial diagnostic test and avoid
unnecessary, more invasive procedures. A through history, physical examination and
standard laboratory testing remain the basis of the initial evaluation of the patient with
FUO. Newer diagnostic modalities including update serology, magnetic resonance imaging
(MRI) and positron emission tomography (PET) scan have important role in the
assessment. It is important to realize FUO may represent uncommon manifestation of
common disease. Hence work-up should be cost effective and thoughtful and clinically
appropriate. Nevertheless despite a thorough workup, as many as 30% of all FUO cases
are never solved. The current evidence points to a favourable prognosis for these cases
and thus empirical treatment sometimes maybe justified, however one should remember
that treatment should not be worse than disease.

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Early Detection of Bacterial Infection in Acute Febrile Illness: How do We Use

Markers of Infection?
Dewi Dian Sukmawati
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine- Sanglah Hospital Denpasar
Acute febrile illness defined as non specific terms for any illness of sudden onset
accompanied by fever. The fever, elevation in core body temperature above the daily
range for an individual, can be a characteristic feature of most infection: either bacterial,
viral, fungal or protozoan; and also found in a number of noninfectious diseases such as
autoimmune or auto-inflammatory diseases. In the process of making a diagnosis, clinical
history and physical examination has been the cornerstone of teaching medical student,
navigator and analytical foundation in diagnostic process. A good clinical skill protects
patients from unnecessary investigations with the risk of false positive results and clinical
risks that these investigations entail. Diagnostic study including laboratory evaluation will
add to focus diagnosis.
An ideal marker for bacterial infections should allow an early diagnosis, give insight
into the course and prognosis of a disease and able to facilitate the therapeutic decision.
Despite the advanced development in laboratory and diagnostic study, currently no ideal
markers were available for diagnosis of bacterial infection. The diagnosis of bacterial
infection will continue require critical clinical skills, careful history taking, physical
examination and culture for diagnosis confirmation.

Bali Infectious Disease Symposium-6

SPECIMEN CULTURE: INDICATION AND INTERPRETATION BY CLINICIAN

I Ketut Agus Somia
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine- Sanglah Hospital Denpasar
The definitive diagnosis of bacterial infections is most commonly accomplished by
the the cultural recovery of the causative agent from body surfaces, fluids, tissue or
excreta of the affected patient. Bellow will be discussing about indication and interpretation
of specimen culture.
True infection is almost always present if the culture is positive for one of the
following organisms: streptococci (non-viridans), aerobic and facultative-gram negative
rods, anaerobic cocci, anaerobic gram-negative rods and yeast. Negative growth does not
rule out infection. Suspect contamination if only one of several cultures is positive, if
detection bacterial growth is delayed (5 days), or if multiple organisms are isolated from
one culture. Common contaminations include the following: S epidermidis, Bacillus
species, proionibacterium acnes, Corynebacteium species, Viridans streptococcus and
Candida tropicalis.
When are sputum Gram stains and cultures indicated? - There is considerable
controversy about the utility of sputum specimens in community-acquired pneumonia
(CAP). The value in nosocomial pneumonia, especially ventilator associated pneumonia
(VAP), is more universally acknowledged.
Interpretation: culture results are reported in a semiquantatative manner (1+ to 4+ in
some laboratories, rare-few-moderate-abundant in others). Most true pathogens are
present in at least 3+ (moderate) amounts. Quantitative thresholds for BAL and PSB
cultures have been extrapolated from quantitative cultures of infected lung tissue5. The
generally accepted breakpoints for bronchoalveolar lavage (BAL) and protected specimen
brush (PSB) are 103 and 104 colony forming units (CFU)/mL, respectively.
Urine culture should be ordered for patients with symptoms and risk factors for
urinary tract infection. Clinical judgement should exercised in ordering urine cultures for
aymptomatic individuals with one or mor risk factor.
A positive of urine culture is based on the growth of bacteria at high number of colony
forming unit (CFUs). Urine culture results should be interpreted in conjunction with clinical

Bali Infectious Disease Symposium-6

symptoms of urinary tract infection, such as dysuria, urinary frequency, suprapubic pain,
flank pain and fever. For clean-catch urine samples, a positive urine culture as indicated
by the growth of bacteria greater than 100.000 CFUs/ml is suggestive of UTI; growth of
1.000 100.000 CFUs/ml may still indicate UTI, especially for specimen taken at
cystoscopy or other invasive procedurs. Growth of 2 or more different bacteria or
polymicrobial growth is likely to the result of contamination

Bali Infectious Disease Symposium-6

Management Acute Febrile Illness in Pediatric Patient

Dwi Lingga Utama
Division of Tropical and Infectious Disease
Department of Pediatric Health
Udayana University School of Medicine- Sanglah Hospital Denpasar
Abstrak
Demam pada anak merupakan hal yang paling sering dikeluhkan oleh orang tua mulai di
ruang praktek dokter sampai ke pelayanan unit gawat darurat. Penyebab demam pada
anak sangat bervariasi sesuai dengan umur anak, epidemiologi penyakit, ada tidaknya
kegawatan yang menyertai. Menentukan penyebab demam pada anak merupakan hal
penting dalam penatalaksanaan yang optimal. Oleh karena itu strategi penelusuran harus
menjadi perhatian seorang klinikus. Managemen Acute Febrile Illness (AFI) pada anak
sesuai dengan penyebab yang dicurigai mengacu pada umur anak, epidemiologi penyakit,
ada tidak kegawatan dengan merujuk pada algoritme managemen yang ada.

Bali Infectious Disease Symposium-6

ANTIBIOTIC USING IN ACUTE FEBRILE ILLNESS

I Ketut Agus Somia
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine- Sanglah Hospital Denpasar
Fever is a common presenting complaint in the developing world, but there is a
paucity of literature to guide investigation and treatment of the adult patient presenting with
fever and no localizing symptoms. Febrile illness can be localized to organ systems or non
localized / systemic, commonly referred to as acute undifferentiated febrile illness (AUFI).
Acute febrile illnesses usually develop within several hour to several days, and either
subside in a few day (e.g. viral upper respiratory tract infection ) or, because of their
severity or associated symptoms, lead to early medical evaluation and diagnosis.
Subacute illnesses are those which last longer than 7 to 10 days. While any process, that
can cause fever may have an acute onset and could involve a wide variety of infectious,
inflammatory, or other disorder, the vast majority of acute febrile illnesses are due to
infection. The common infectious acute febrile illnesses are upper respiratory infections,
lower respiratory infections, gastroenteritis, cellulitis and soft tissue infections, viral
exanthems, bacteremia and meningitis.
Chronic febrile illnesses, i.e. those lasting several weeks, often have a subtle onset:
they may be more difficult to diagnose, and when infectious that are most often caused by
pathogen that are sheltered from host defenses (e.g., intracellular or in abscesses, bone,
or endocardium). In addition, more often than not, chronic febrile illnesses are
noninfectious in etiology.
Empirical antibiotic therapy should be discouraged as a general response to acute
febrile illnesses until the possible answers to these questions have been addressed in the
individual patient. Excessive using of antibiotic in patients for which no indication has
contributed to increase of antimicrobial resistance and may cause unwanted reactions. If
the patients has a severe or life-threatening illness for which antibiotic therapy would be
indicated as part of treatment, it is quite appropriate to initiate treatment before culture
result are known. The approach to antibiotic therapy of infections involving different organ
systems and syndromes are discussed bellow..

Bali Infectious Disease Symposium-6

Acute Retroviral Syndrome

Tuti Parwati Merati
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine- Sanglah Hospital Denpasar
Sindrom retroviral akut atau ARVS

merupakan kumpulan gejala penyakit yang

timbul beberapa minggu setelah seseorang terinfeksi virus HIV. Sindrom ini menyerupai
gejala flu (flu like syndrome) atau menyerupai infeksi mononucleosis (mononucleosis like
syndrome) . Pada fase ini viral load cukup tinggi sehingga sangat infeksius, namun
belum terbentuk antibodi yang cukup untuk menimbulkan tes antibody HIV positif,
sehingga sering kali berakibat tidak terdiagnosis dengan pemeriksaan laboratorium yang
rutin. Keadaan ini juga disebut infeksi HIV primer dimana secara laboratorium,

fase

infeksi akut ini ditandai dengan terdeteksinya RNA virus HIV atau antigen p24 dalam
darah dan antibodi HIV negatif. Diagnosis akut retroviral syndrome
tantangan karena belum dapat terdiagnosis dengan baik, padahal

masih menjadi
infeksi HIV akut

merupakan saat yang penting untuk mencegah perjalanan penyakit lebih lanjut, misalnya
pada

ibu hamil dan bayi-bayi yang lahir dari ibu HIV positif. Sindrom ARVS yang

merupakan gejala infeksi HIV primer timbul setelah 6 minggu infeksi. Gejala infeksi akut
biasanya sembuh sendiri tanpa gejala sisa.

Bali Infectious Disease Symposium-6

WHEN USE ANTI RETRO VIRAL (ARV) IN ACUTE RETROVIRAL SYNDROME (ARVS)
?
Made Susila Utama, Tuti Parwati Merati
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine- Sanglah Hospital Denpasar
Acute human immunodeficiency virus (HIV) infection, also known as primary HIV
infection or acute retroviral syndrome (ARVS), is the period just after initial HIV infection,
generally before seroconversion. It is estimated that 40-90% patients with primary HIV
infection experience ARVS. The development of ARVS typically coincides with high level
viremia and the hosts initial immunological response. Symptoms typically occur 2-6 week
after exposure and last for 14 days but may persist as long as 10 weeks. The clinical
features of acute retroviral syndrome are non-specific. An acute infectious mononucleosislike illness occurs in up to 93% of patients but many organ systems can be affected,
causing a wide array of symptoms and signs mimicking other clinical entities.
Constitutional symptoms of fever, malaise or fatigue, anorexia, weight loss, maculopapular
skin rash, mucosal membrane ulcerations, pharyngitis and diffuse lymphadenopathy are
common.
When clinicians suspect acute infection (e.g., in a patient with a report of recent risk
behavior in association with symptoms and signs of the acute retroviral syndrome), a test
for HIV RNA should be performed. High levels of HIV RNA detected in plasma through use
of sensitive amplification assays (PCR, bDNA, or NASBA), in combination with a negative
or indeterminate HIV antibody test, support the diagnosis of acute HIV infection. Low-level
positive PCR results (<5000 copies/mL) are often not diagnostic of acute HIV infection and
should be repeated to exclude a false-positive result. HIV RNA levels tend to be very high
in acute infection; however, a low value may represent any point on the upward or
downward slope of the viremia associated with acute infection. Plasma HIV RNA levels
during seroconversion do not appear significantly different in patients who have acute
symptoms versus those who are asymptomatic. Viremia occurs approximately 2 weeks
prior to the detection of a specific immune response. Patients diagnosed with acute HIV
infection by HIV RNA testing still require antibody testing with confirmatory Western blot 3
to 6 weeks later.

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Symptoms of primary HIV infection can usually be managed in the primary care
setting by the general practitioner. Decisions about antiretroviral therapy need to be made
in conjunction with an HIV experienced clinician. Rational for ARV therapy in ARVS such
as to reduce the risk of viral transmission, preserve HIV-specific immune function,
including promoting the survival of CD4 cells that are involved in the initial response to HIV
infection, suppress the initial burst of viral replication and decrease the magnitude of viral
dissemination, potentially lower the initial viral setpoint, which may ultimately affect the rate
of disease progression, potentially reduce the emergence of viral mutations as a result of
the suppression of viral replication. Disadvantage of ARV in ARVS, adverse effects on
quality of life as a result of drug toxicities and complex treatment regimens, potential for
the development of drug resistance if therapy fails due to non adherence or to insufficient
suppression of viral replication, which may limit future treatment options, earlier
commitment to lifetime ARV therapy, less time to educate the patient about ARV therapy
and insufficient data regarding effectiveness of early treatment. In the absence of
randomized controlled trials data demonstrating clinical benefit of antiretroviral therapy
intervention in primary HIV infection, clinical guidelines remain unclear. Intervention seems
a logical strategy to counter the high viraemia, enhanced onward transmissibility, and
immunological destruction which occurs during primary HIV infection. The nature, duration
and timing of that intervention after HIV acquisition remains unknown. The clinician and
the patient should be aware that therapy for acute HIV infection is primarily based on
theoretical considerations, and the potential benefits should be weighed against the
potential risks.

Bali Infectious Disease Symposium-6

ETIOPATHOGENESIS OF TYPHOID FEVER

Anak Agung Ayu Yuli Gayatri
Division of Tropical and Infectious Disease
Department of Internal Medicine
Udayana University School of Medicine- Sanglah Hospital Denpasar
ABSTRACT
Typhoid fever one of the major bacterial infections worldwide, is caused by a virulent
bacterium called Salmonella typhi thriving in conditions of poor sanitation and crowding Gve bacilli in family Enterobacteriaceae. For every ten cases of S typhi infection, there are
one or two cases of paratyphoid fever, caused by the human adapted S enteric serovars
Paratyphi A, Paratyphi B and Paratyphi C, transmitted by ingestion of food or water
contaminated with the typhoid bacillus. Salmonella organism penetrate the mucosa of both
small and large bowel, coming to lie intracellularly where they proliferate. Initially S. typhi
proliferates in the second part of Payers patches of the lower small intestine from where
systemic dissemination occurs, to the liver, spleen and articuloendothelial system. From a
period varying from 1 to 3 weeks the organism multiplies within this organs. Rupture of
infected cell occurs, liberating organism into the bile and for a second time cause infection
of the lymphoid tissue of the small intestine particularly in the ileum. Invasion of the
mucosa causes the epithelial cells to synthesis and release various pro-inflammatory
cytokines including IL-1, IL-6, IL-8, TNF , INF, GM-CSF etc.

Bali Infectious Disease Symposium-6

Antimicrobial Therapy of Typhoid Fever

Julius Daniel Tanasale

Typhoid fever is a systemic bacterial disease caused by Salmonella enterica subsp.

enterica serovar typhi (commonly known as S. typhi) and characterized by insidious onset
of sustained fever, severe headaches, malaise, anorexia, a non-productive cough in the
early stage of the illness, a relative bradycardia, splenomegaly and abdominal discomfort
(1). A transient, macular rash of rose-colored spots can occasionally be seen on the trunk
(1). In adults, constipation is more often seen than diarrhea. The clinical picture can vary
from mild illness to severe clinical disease with abdominal discomfort and other
complications. The severity of illness is dependent on the infecting dose, the virulence of
the bacterial strain, duration of the illness before initiation of appropriate treatment, age,
and vaccine history (1). Complications such as ulceration of Peyerss patches in the ileum
causing intestinal haemorrhage or perforation (in about 1% of cases) can occur, especially
late in untreated cases. Case fatality rate can fall to <1% with prompt, appropriate
antimicrobial treatment (1). Relapses (generally milder than the initial clinical illness) can
occur depending on what antimicrobials are used in treatment