Introduction To Infectious Disease-Revisi

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PENYAKIT INFEKSI
KAPITA SELEKTA
EDITOR :
Djaja Rusmana, dr., M.Si.
Dr. Meilinah Hidayat, dr., M.Kes.
UNTUK KALANGAN SENDIRI

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Dilarang memperbanyak karya tulis ini dalam bentuk dan dengan

cara apapun, termasuk fotokopi, tanpa izin tertulis dari penerbit.
Kapita Selekta
PENYAKIT INFEKSI
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KATA SAMBUTAN
Puji syukur kehadirat Allah yang Maha Pengasih, berkat perkenan-Nya buku materi
pengetahuan, penuntun praktikum, panduan tutorial dan buku keterampilan klinik edisi kedua
dapat diterbitkan.
Buku-buku tersebut diperlukan untuk kelancaran proses belajar mengajar dalam
Kurikulum Berbasis Kompetensi (KBK) yang telah dilaksanakan di Fakultas Kedokteran
Universitas Kristen Maranatha sejak tahun akademik 2006.
Khususnya buku materi pengetahuan merupakan gabungan pengetahuan preklinik dan
klinik yang isinya terbatas sesuai dengan blok atau sistim organ. Oleh sebab itu mahasiswa
diharapkan membaca juga buku teks standar yang terkait untuk menambah pengetahuan karena
KBK menuntut active learning sehingga pada gilirannya menjadi lifelong learning. Lifelong
learning dapat diartikan lifelong, voluntary, and self-motivated.
Saya sangat menghargai para Kontributor, Editor dan Tim Medical Education Unit
Fakultas Kedokteran Universitas Maranatha atas jerih lelahnya sehingga buku-buku tersebut
dapat diterbitkan, terima kasih.
Karena keterbatasan manusia walaupun sudah direvisi tentu masih ada kekurangannya,
mohon asupan-asupan untuk melengkapi kekurangan dan untuk dilakukan perbaikan
sebagaimana mestinya.
Bandung, Oktober 2014

Dekan Fakultas Kedokteran
Universitas Kristen Maranatha
Jo Suherman,dr., MS., AIF
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KATA SAMBUTAN
Puji syukur kami panjatkan kepada Tuhan Yang Maha Esa, karena berkat perkenan-Nya
Buku Materi Pengetahuan, Buku Keterampilan Klinis Dasar, dan Buku Penuntun Praktikum
dapat diterbitkan.
Kurikulum Berbasis Kompetensi (KBK) yaitu Kurikulum Inti Pendidikan Dokter
Indonesia (KIPDI) III Dokter Pelayanan Primer/Dokter Keluarga telah dilaksanakan di Fakultas
Kedokteran Universitas Kristen Maranatha sejak angkatan 2006.
Melalui kurikulum ini diharapkan agar mahasiswa menjadi pusat pembelajaran dan
senantiasa belajar aktif dan mendiri sekalipun peranan dosen tetap menjadi fasilitator utama
guna terlaksananya kurikulum berbasis kompetensi ini. Dalam kurikulum ini diharapkan agar
mahasiswa diberi kesempatan untuk mengembangkan kemampuan dirinya dalam melakukan
proses belajar untuk mencapai tujuan pembelajaran yang telah ditentukan di dalam Standar
Kompetensi Dokter Indonesia (SKDI).
Seiring dengan perkembangan zaman, ilmu kedokteran senantiasa mengalami
perkembangan dan kemajuan, dan terkadang banyak teori yang sudah tidak dianut kembali dan
digunakan teori yang lebih baru sesuai dengan hasil penelitian terkini. Informasi kini sangat
mudah didapat selain dari buku teks, ebook, jurnal, dan berbagai penelitian dan tulisan yang
dapat diunduh dari internet. Oleh karena itu perlu dilakukan revisi materi pembelajaran KBK,
dan di Fakultas Kedokteran Universitas Kristen Maranatha kini sedikit demi sedikit
diperkenalkan materi di dalam bentuk ebook agar dapat senantiasa direvisi bila seandainya
dibutuhkan khususnya untuk materi pengetahuan.
Buku Materi Pengetahuan, Buku Keterampilan Klinis Dasar, dan Buku Penuntun
Praktikum dalam pelaksanaannya masih banyak kekurangan dan butuh penyempurnaan lebih
lanjut, dan oleh karenanya saran dan kritik untuk perbaikan diharapkan dari berbagai kalangan
termasuk dari mahasiswa itu sendiri. Dengan revisi dan terbitnya seri buku materi terbaru, kami
berharap dapat meningkatkan kualitas pembelajaran di Fakultas Kedokteran Universitas Kristen
Maranatha.
Bandung, Agustus 2014

Ketua Medical Education Unit (MEU) FK-UKM,
Heddy Herdiman, dr., M.Kes

NIK : 110970
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PRAKATA
Puji dan syukur kami panjatkan pada Tuhan Yang Maha Esa, karena dengan izinNya
lah Materi Pengetahuan Infeksi blok 21 Edisi ke- 3 ini dapat terwujud. Materi Pengetahuan
Infeksi blok 21 Edisi ke- 3 disusun agar dapat digunakan oleh mahasiswa/i kedokteran sebagai
panduan dalam mempelajari infeksi.
Pokok bahasan Materi Pengetahuan Infeksi 21 meliputi Patologi Anatomi,
Mikrobiologi, Farmakologi dan Ilmu Penyakit Kulit dan Kelamin yang berhubungan dengan
penyakit infeksi.
Kami menyadari bahwa Materi Pengetahuan ini masih banyak kekurangan, oleh karena
itu kami membutuhkan masukan, saran dan kritik dari pembaca. Semoga dengan mempelajari
Materi Pengetahuan ini dapat membantu meningkatkan wawasan mahasiswa/i kedokteran untuk
menjadi dokter yang baik di masa yang akan datang.
Kami ucapkan terima kasih yang sebesar-besarnya kepada semua pihak yang telah
membantu dalam mewujudkan penerbitan Materi Pengetahuan ini.
Bandung, 24 Januari 2015
Editor
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DAFTAR KONTRIBUTOR
Prof. Topo Harsono, dr., Sp.PA(K). (alm.)

dr. Roro Wahyudianingsih, Sp. PA
Ernawati Giri-Rachman, S.Si., M.Si., Ph.D.
dr. Caroline Tan Sardjono, Ph.D.
dr. Fanny Rahardja, M.Si.
dr. Djaja Rusmana, M.Si.
dr. Johan Lucianus, M.Si.
dr. Triswaty Winata, M.Kes.
Dr. dr. Sugiarto Puradisastra, M.Kes.
Dra. Endang Evacuasiany, Apt., MS.
Dr. dr. Diana Krisanti Jasaputra, M.Kes.
dr. A. Fattah Madani, Sp.KK(K).
dr. Dian Puspitasari, Sp.KK.
dr. Rosalin Naomi Harsono, Sp.KK.
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DAFTAR ISI
KATA SAMBUTAN
PRAKATA
DAFTAR KONTRIBUTOR
DAFTAR ISI
BAB I
PENDAHULUAN INFEKSI
1. INTRODUCTION TO INFECTIOUS DISEASE
2. GENETIKA PROKARIOT DAN BAKTERIOFAGA
3. FISIOLOGI DAN BIOKIMIA PROKARIOT
4. PATOGENESIS BAKTERI
5. DIAGNOSIS BAKTERI
BAB II
BAKTERIOLOGI, VIROLOGI UMUM DAN MIKOLOGI
6. BAKTERI BATANG GRAM NEGATIF DAN BAKTERI ANAEROB
7. STAPHYLOCOCCUS, NEISSERIA DAN BATANG GRAM POSITIF
8. VIROLOGI UMUM
9. MIKOLOGI
BAB III
FARMAKOLOGI
10. ANTIMIKROBA PENGHAMBAT SINTESIS PROTEIN
11. OBAT ANTI MALARIA
12. OBAT ANTI JAMUR
13. OBAT ANTIVIRUS (NONRETROVIRAL)
14. LEPROSTATIK
BAB IV
ILMU PENYAKIT KULIT DAN KELAMIN
15. PIODERMA
16. INFEKSI MENULAR SEKSUAL (I M S)
17. KUSTA
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21 INTRODUCTION TO INFECTIOUS DISEASES
PENDAHULUAN INFEKSI
INTRODUCTION TO INFECTIOUS DISEASES
Topo Harsono
INFECTIOUS DISEASE (ID)
A disease caused by a pathogenic microorganism, the etiologic agent of which may be a

bacterium, virus, fungus or animal parasite, and may be transmitted from another host or arise
from the hosts indiginous micro flora. (DORLANDs Med. Dict.)
COMMUNICABLE DISEASE
An infectious disease transmitted from one individual to another, either by direct contact or
indirectly by means of a vector or vomites.
CONTAGIOUS DISEASE
A communicable disease transmitted by contact or aerosol.

Despite of the availability and effective use of vaccines and antibiotics, infectious diseases
(ID) remain an important cause of death in the US and worldwide:
In the US 2 of the top 10 leading causes of death are infectious diseases: pneumonia and
influenza and septicemia.
ID are particularly important causes of death among the elderly and people wih AIDS,
those with chronic diseases and those receiving immunosuppressive drugs.
In developing countries unsanitary living conditions and malnutrition contribute to a
massive burden of infectious diseases that kills more than 10 million people each year. Most
ot these deaths are among children, especially from respiratory infections and diarrhea.
The history of pathology of ID are intertwined with that of microbiology:

Edward Jenner (1749 1823), developed the process of producing immunity to smallpox by
inoculation (vaccination) with cowpox (vaccinia) vaccine.
Louis Pasteur and Robert Koch were pioneers in establishing the microbial etiology of ID.
Pasteur is credited with proving that microorganisms can cause disease (the germ theory of
disease). He also created the first attenuated vaccines, incl. rabies vaccine in 1885. In 1882
Robert Koch championed criteria for linking a specific microorganism to a disease (Kochs
postulate). Koch was also responsible for the isolation of the bacteria that causes
tuberculosis (Mycobacterium tuberculosis) and anthrax (Bacillus anthracis).
KOCHS POSTULATE:
1. The organism is found in the lesions of the disease,
2. The organism can be isolated as single colonies on solid media,
3. Inoculation of the organism causes lesions in experimental animals,
4. The organism can be recovered from the experimental animal.
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Ronald Ross, an English military physician posted in India, demonstrated in 1897 that
mosquitoes carry mal-aria. Rosss demonstration that Anopheles mosquitoes transmit malaria
led to public health efforts to reduce malaria through control of mosquitoes.
Walter Reed, an American military physician, led a team to Cuba in 1900 who
demonstrated that yellow fever, like malaria, is transmitted by the bite of mosquitoes.
Volunteers allowed themselves to be bitten by mosquitoes that had previously bitten people
sick with yellow fever. Following Reeds result Dr. James Carroll showed in 1901 that
yellow fever was caused by a virus. This was the first demonstration that a virus caused disease
in humans.
Peyton Rous found the first evidence for an infectious causes of cancer in 1909. In
1911 Rous demonstrated that a virus cause sarcoma in chickens. Although a viral cause has
not been found for most human cancers, but we now know that viruses can contribute to the
development of some, such as human papilloma virus and cervical cancer. It is now agreed that
Epstein-Barr Virus is closely linked to certain types of lymphomas.
In 1944 Oswald Avery initiated modern microbiology based on molecular genetics. He
transferred DNA from a virulent to avirulent Streptococcus pneumonia, thereby transferring
the latter into a virulent genotype. This showed that DNA is the genetic material, leading to an
explosion of research in molecular genetics.
MAJOR DISCOVERIES IN MICROBIAL PATHOGENESIS

1796 Edward Jenner Vaccination against Smallpox
1843 Wendell Holmes Discovery of the iatrogenic nature
of black death of childhood
1865 Louis Pasteur Proof of germ theory and the beginning
of modern biology
1882 Robert Koch Kochs postulate (4)
1884 Elie Metchnikov Description of phagocytosis by macrophages
1902 Ronald Ross Identification of mosquito vector for
Plasmodium falciparum malaria
1906 Paul Ehrlich Description of chemotherapeutic agents
1908 Ellermann & Bang Viral oncogenesis in chicken
1933 Rebecca Lancefield Serotyping of organisms and association of bacterial
clones with disease
1945 Avery Identification of DNA as genetic material
and start of Molecular biology revolution
1949 Franklin Enders Culture of viruses and production of poliovirus
vaccine
1983 Luc de Montagnier Identification of HIV as cause of AIDS
& Robert Gallo
NEW EMERGING INFECTIOUS DISEASES

1973 Rotavirus Infantile diarrhea
1975 Cryptosporidium parvum Acute and chronic diarrhea
1977 Ebola virus Epidemic haemorrhagic fever
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Hantaan virus Hemorrhagic fever with renal disease

Legionella pneumophila Legionnaires pneumonia
Campylobacter jejuni Enteritis
1980 HTLV-I T-cell lymphoma or leukemia
1980 Staphylococcus aureus Toxic shock syndrome
1980 HTLV-II Hairy cell leukemia
Escherichia Coli Hemorrhagic colitis , hemolytic-uremic
(O157:H7) syndrome
Borrelia burgdorferi Lyme disease
1983 HIV AIDS

Helicobacter pylori Chronic gastritis
1985 Enterocytozoon bieneusi Chronic diarrhea
1988 HHV-6 Exanthem subitum
Hepatitis E Enterically transmitted hepatitis
1989 Hepatitis C Non-A and Non-B hepatitis
1992 Vibrio cholerae (O139) New epidemic cholera strain
1993 Encephalitozoon cuniculi Opportunistic infections
1995 KSHV (HHV-8) Kaposi sarcoma in AIDS
2002 Corona virus Severe Acute Respiratory Syndrome
2004 N5H1 virus Avian Flu Syndrome
HUMAN VIRAL DISEASES AND THEIR PATHOGENS
RESPIRATORY
Adenovirus Upper/lower respiratory tract infection
Echovirus Upper respiratory tract infection , pharyngitis
Rhinovirus Upper respiratory tract infection
Coxsackievirus Hand-foot-mouth disease
Influenza virus A-B Influenza
Parainfluenza virus Upper/lower respiratory tract infection.
DIGESTIVE
Mumps virus Mumps, pancreatitis, orchitis
Rotavirus Childhood diarrhea
Hepatitis A virus Acute viral hepatitis
Hepatitis B virus Acute or Chronic hepatitis
Hepatitis C virus Acute or Chronic hepatitis
Hepatitis D virus Acute or Chronic hepatitis
Hepatitis E virus Enterically transmitted hepatitis
SYSTEMIC WITH SKIN ERUPTIONS

Measles virus Measles (rubeola)
Rubella virus German measles (rubella)
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Parvo virus Erythema infectiosum

Vaccinia virus Smallpox vaccine
Varicella-zoster virus Chickenpox, HerpesZoster
Herpes simplex v.1 Cold Sore
Herpes simplex v.2 Genital herpes
SYSTEMIC WITH HEMATOPOIETIC DISORDERS

Cytomegalovirus Cytomegalic Inclusion Dis
Epstein-Barr virus Infectious mononucleosis
HTLV-I Adult T-cell leukemia
HTLV-II Role uncertain

HIV-1 and HIV-2 AIDS
ARBOVIRAL AND HEMORRHAGIC FEVERS

Dengue virus 1-4 Dengue hemorrhagic fever
Yellow Fever virus Yellow fever
Colorado tick fever Colorado tick fever
Regional Hemorrhagic Ebola, Marburg disease
Fever viruses Hantaan hemorrhagic fever
Chikungunya virus Dengue type fever
CENTRAL NERVOUS SYSTEM

Polio virus Poliomyelitis
Rabies virus Rabies
Arboviral encephalitis Encephalitis
CATEGORIES OF INFECTIOUS AGENTS
I. PRIONS:
Composed of modified host protein prion protein (PrP).
Cause transmissible spongioform encephalopathies:
Kuru, associated with human cannibalism
Creutzfeldt-Jakob disease (CJD), associated with corneal transplants
Bovine spongioform encephalopathy (BSE)
Mad cow disease
Atypical C-J disease transmitted to humans from BSE
II. VIRUSES:
All viruses depend on host cell metabolism for their replication Obligate intracellular
parasites
Classified by the nucleic acid content of their core (DNA or RNA) and their shape of
coat or capsid
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More than 400 species inhabit humans but only some cause acute illnesses to humans:
common colds or influenza.
Others are capable of lifelong latency and of long-term reactivation (Herpes viruses) or
may give rise to chronic diseases (Hepatitis viruses)
III. BACTERIOPHAGES, PLASMIDS AND TRANSPOSONS

Mobile genetic elements that encode bacterial virulence factors: adhesins, toxins or
enzymes that confer antibiotic resistance.
Ability to infect bacteria and incorporate themselves into their genome: toxin genes of
Vibrio cholerae and Shigella flexneri.
Exchange of these elements between bacterial strains and species endows the recipients
either with survival potentials or capacity to cause disease
IV. BACTERIA
Bacterial cells lack nuclei and endoplasmic reticulum
Cell walls are rigid, composed either of two phospholipid bilayers with a peptidoglycan
layer in between (Gram-negative species) or of a single bilayer covered by
peptidoglycan (Gram-positive bacteria)
Bacteries synthesize their own DNA, RNA and proteins but depend on the host for
favorable growth conditions.
Some thrive mainly on the bodys surface layers (skin), including staphylococcus and
propionibacteriums, the agent responsible for adolescent pimples
A large amount reside inside the gastrointestinal tract of which 99 % are anaerobes
Prion
Any of several protease-resistant, insolubel, transmissible isoforms of the 27 - 30 kD core of
prion protein that cause a group of progressive neurodegenerative diseases.
Plasmid
An extrachromosomal self-replicating structure found in bacterial cells that carries genes for
a variety of functions not essential for cell growth.
Bacteriophage
A virus that lysis bacteria
Transposons
A small mobile genetic (DNA) element that can move around within the genome or to other
genomes within the genomes within the same cell transposable elements
BACTERIAL, SPIROCHAETAL AND MYCOBACTERIAL DISEASES
PYOGENIC BACTERIA
Staphylococcus aureus Abscess, cellulitis, sepsis
Streptococcus pyogenes Upper respiratory tract infection,
scarlet fever, sepsis
Streptococcus pneumoniae Lobar pneumonia, meningitis
Neisseria meningitidis Cerebrospinal meningitis
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Neisseria gonorrhea Gonorrhea
GRAM-NEGATIVE BACTERIA (common)

Escherichia Coli Urinary tract infections, wound
Klebsilla pneumoniae infections, abscess, sepsis
Ent. Aerogenes Endocarditis
Bacteroides sp. Anerobic infections
Legionella pneumophila Legionnaires disease
GRAM-NEGATIVE BACTERIA (rare)

Klebsilla rhinoscleroma Rhinoscleroma, ozena
Haemophylus ducreyi Chancroid (soft chancre)
Calymmatobacterium Granuloma inguinale donovani
CONTAGIOUS CHILDHOOD BACTERIAL INFECTIONS

Hemophilus influenzae Meningitis, Up/Low. Resp. tract infections
Bordetella pertusis Whooping cough
Corynebacterium diphtheriae Diphteria
ENTEROPATHIC INFECTIONS
Escherichia Coli
Shigella sp. Invasive or noninvasive gastroenterocolitis
Vibrio cholerae
Campilobacter jejuni
Samonella typhi Typhoid fever
CLOSTRIDIAL INFECTIONS
Clostridium tetani Tetanus
Clostridium botulinum Botulism
Clostridium perfringens Gas gangrene
ZOONOTIC BACTERIAL INFECTIONS

Bacillus anthracis Anthrax
Yersinia pestis Bubonic plague
Francisella tularensis Tularemia
Brucella spp. Brucellosis
Leptospira spp. Leptospirosis, Weil disease
Borrelia recurrens Relapsing fever
Borellia burgdorferi Lyme disease
Bartonella henselae Cat-scratch disease
Spirilium minus Rat-bite fever
HUMAN TREPONEMAL INFECTIONS

Treponema pallidum Syphilis
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Treponema pertenue Framboesia (Yaw)

Treponema carateum Pinta (Mal del pinto)
MYCOBACTERIAL INFECTIONS
Mycobacterium tuberculosis Tuberculosis
Mycobacterium leprae Leprosy
Mycobacterium avium Atypical mycobacterial infections
Mycobacterium ulcerans Buruli ulcer
ACTINOMYCETACEAE
Nocardia asteroides Nocardiosis
Actinomyces israeli Actinomycosis
V. CHLAMYDIAE, RICKETTSIAE AND MYCOPLASMAS

Has similarities with bacteria divide by binary fission
susceptible to antibodies
but lack of certain structures:
lack of cell wall or lack of certain
metabolic capabilities (ATP synthesis)
Most rickettsiae are transmitted by insect vectors (lice, ticks and mites) and are obligate
intracellular agents, replicating in cytoplasm of endothelial cells cause a
hemorrhagic vasculitis often visible as skin rash, transient pneumonia, hepatitis, CNS
injuries and death.
Mycoplasma pneumoniae spreads from person to person by aerosols, binds to the
surface of epithelial cells in the airways by an adhesin (P1) and causes an atypical
pneumonia.
VI. FUNGI
Fungi possess thick, ergosterol-containing cell walls and grow as perfect, sexually
reproducing forms in vitro and as imperfect forms in vivo, including budding yeast
cells, hyphae and conidia.
Tinea group of fungi are confined to superficial layers of the skin (athletes foot).
Other dermatophytes damage the hair shaft or nails. Some fungal species invade
subcutaneous tissue causing granulomas or spread systemically destroying vital organs
in immunocompromised hosts.
VII. PROTOZOA
Parasitic protozoa are single-celled organisms endowed with motility, pliable plasma
membranes and complex cytoplasmic organelles.
Trichomonas vaginalis is transmitted sexually from person to person.
Intestinal protozoas are spread by the fecal-oral route: Entamoeba histolytica and
Giardia lamblia.
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Blood-bourne protozoa (Plasmodium, Tryponema and Leishmania specieses) are

transmitted by blood-sucking insects, in which they undergo a complex succession of
life stages before passed to new human hosts.
Toxoplasma gondii is acquired either by contact with oocyst-shedding kittens or by
eating cyst-ridden undercooked meat.
VIII. HELMINTHS
Parasitic worms are highly differentiated multicellular organisms with a complex life
cycle: alternation of sexual reproduction in the definitive host and the asexual
multipliacation in an intermediary host or vector.
Thus, depending on the parasitic species, humans may harbor either adult worms
(Ascaris) or immature stages (Toxocara canis) or asexual larval forms (Echino coccus).
Adult worms, once residing in humans, do not multiply in number but generate eggs or
larvae destined for the next phase of the cycle.
Important consequences of the lack of replication of adult worms:
disease often caused by inflammatory reponses to the eggs or larvae rather than to
the adult forms
disease is in proportion to the number of organisms infecting the individual
Parasitic worms are of three classes:
[1] First class: Nematodes (roundworms)
Intestinal: Ascaris and Strongyloides
Tissue invaders: Filariae and Trichinella
[2] Second class: Cestodes (flat worms)
Tapeworms and cystic tapeworm larvae:
Cysticerci and hydatid cyst
[3] Third class: Trematodes (flukes)
oriental liver and lung flukes
IX. ECTOPARASITES
Ectoparasites are arthropods (lice, ticks, bedbugs and fleas) that attach to and live on the
skin.
Scabies: example of severe dermatitis caused by mites burrowing into the Stratum
Corneum.
Arthropods can be vectors for other pathogens: Lyme disease caused by spirochetes
(Borrelia burgdorferi) transmitted by deer ticks
CONTAMINATION, SPREAD AND DISSEMINATION
Development of an infectious disease is the ultimate result of interaction

of microorganism and host:
symbiosis: living together or close association of two dissimilar organisms:
mutualism: beneficial to each other
commensalism: beneficial to one but no effect on the other
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parasitism: beneficial to one but detrimental to the other

Contamination: process of attachment / adherence of organism to parts of the human body
Different modes of contaminations:
- Direct :
Direct contact: most contagious diseases measles
Airborne: most pulmonary diseases TBC
- Intermediary:
Food and waterborne: most GI tract infectious diseases hepatitis virus, rota virus,
cholera
Soil contamination: helminthic infections
- Vertical:
Transplacental: syphilis, toxoplasma, CMV, HIV
Perinatal: gonorrhea
- Zoonotic: Animal transmission: rabies
MICROORGANISMS [MO] AND INJURY / DISEASE
1. Direct contact and entry in host cells creating cellular damage and death
2. Do not disseminate but produce and release
Endo and exotoxins that kill cells from a distance
Release enzymes that degrade tissue components
Damage blood vessels, causing ischemic necrosis
3. Induce host cellular responses that, although directed against MO, may cause additional
tissue damage:
Suppuration
Scarring
Hypersensitivity reaction
HOST BARRIERS, SPREAD AN DISSEMINATION
1. Most formidable barriers to infection are:

Intact host skin
Mucosa surfaces
Secretory-excretory products:
Lysozyme secreted by tear glands degrades the peptidoglycans of bacterial cell
walls and protects eyes from infection.
Acid gastric juice is lethal for some enteric pathogens: - Vibrio cholerae are killed
by gastric juice - Shigella and Giardia are resistant to acid
2. Once implanted microbes spread on the surface of moist and warm mucosae grew faster
than on cool and dry skin.
3. Some superficial pathogens stay confined to the lumen of hollow viscera cholera
bacilli.
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4. Others adhere or proliferate exclusively in or on epithelial cells papilloma virus and

dermatophytes.
5. A variety of pathogenic bacteria, fungi and helminthes are invasive pathogens by virtue of
their motility or ability to secrete lytic enzymes sreptococcal hyaluronidase and
schistosome protease.
6. Spread through serosal cavities (pleura, peritoneum and meninges) is particularly fast and
dangerous.
7. Microbes may also ascend the lymphatics from their entry site to the regional nodes and
enter the bloodstream.
8. Secondary foci of infection established through the blood-stream may take the form of
abscesses or granulomas.
9. Viruses may propagate from cell to cell by fusion or axonal transport (polio virus), but like
other intracellular pathogens (tubercle bacilli), they can enter the bloodstream and can be
carried to distant sites by migratory macrophages (HIV-1).
10. Major manifestations of infectious diseases may arise at sites distant from those of parasite
entry:
Chicken pox and measles viruses enter through the airways but manifest themselves
first as rashes.
Polio virus is ingested and multiplies inside the gut wall before proceeding to viremic
invasion and killing of motor neurons
11. Bloodstream invasion by sporadic low-virulent or nonvirulent microbes is a common event
but is quickly suppressed by the normal host defences. By contrast, sustained bloodstream
invasion with dissemination of pathogens (viremia, bacteriemia, fungemia or parasitemia) is
a serious insult and manifests itself by fever, low arterial blood presser and multiple other
systemic septic signs and symptoms.
12. The placental-fetal route is an important mode of transmission. Infectious organisms reach
the pregnant uterus through the cervical orifice or the bloodstream and are able to traverse
the placenta, severe damage to the uterus may result:
Bacterial or mycoplasmal placentitis may cause premature delivery or stillbirth.
Treponema pallidum breaches the placenta by the end of the second trimester and
causes manifestations of congenital syphilis in the infant.
Transmission of maternal viruses or of Toxoplasma infections is most dangerous
during early pregnancy and can result in flagrant systemic diseases of fetus (CMV):
fetal maldevelopment, deafness and congenital heart disease (Rubella).
Maternal transmission of HIV results in opportunistic infections in 50 % of untreated
children during the first year of life.
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Contamination
27
Port of Entry
Local Defence Incubation Period

Mechanism
Local reaction
Aborted (Inflammation)
Local and
Aborted Systemic DM Signs and
Cured (Cellular and Hu- Symptoms
moral Reaction)
Cured
Local and
Systemic DM
(Humoral and
Modes of Dissemination Cured
Cellular reaction)
Cured Chronic
Carrier
Death
MECHANISMS OF VIRAL INJURY
Viruses damage host cells by entering the cell and replicating at the hosts expense. Viral
tropism is in part caused by binding of specific viral surface proteins to particular host cell
receptor proteins:
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EBV binds to complement receptor on macrophages (CD2)

Rabies virus binds to acetylcholine receptors on neurons
Rhinoviruses bind to adhesion protein ICAM-1 (Intercellular Adhesion Molecule-1) on
mucosal cells.
HIV binds to two different proteins on target cells:
CD34 protein on lymphocytes
Chemokine receptors on macrophages and microglia (CCR5,CCR3 or CCR 2b)
Viral proteins on surface of host cells are recognized by immune system and virus infected
cells are attacked by host lymphocytes (acute liver failure during Hepatitis B infection).
Once attached, the entire virus or a portion containing the genome and essential polymerase
penetrates into the cell cytoplasma by one of three ways:
1. Translocation of the entire virus across the plasma membrane,
2. Fusion of the viral envelope with the cell membrane, or
3. Receptor mediated endocytosis of the virus and fusion with endoscopal membranes.
Many of these effects are mediated by viral homologs of host regulatory proteins: a serpin
homolog of myxoma virus inhibits urokinase and plasminogen activator and so reduces
inflammation.
Viral infections can be:

Abortive: with incomplete viral replicative cycle,
Immediate: contamination directly followed by appearance of signs and symptoms of
disease
Latent: in which the virus persists in a cryptic state within the dorsal root ganglia and
then presents as painful shingles (herpes zoster)
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Persistent: virions are synthetized continuously with or without altered cell function
(hepatitis b)
Viruses damage cells involved in host antimicrobial defense, leading to secondary infection:
viral damage to respiratory epithelium allows subsequent pneumonias caused by
pneumococcus or haemophilus, and HIV depletes CD4+ helper lymphocytes.
Viral killing of one cell type causes the death of other cells that depend on them:
polio virus causes motor neuron injury and atrophy of distal skeletal muscle supplied by
such neurons.
In addition to causing cell injury, viruses also induce cell proliferation and transformation which
results in neoplastic growth:
HBV, EBV or human papiloma virus.
Viruses have numerous means for circumventing the host immune responses:
1. Blocking complement activation (vaccinia) or using complement receptors to enter B
lymphocytes (EBV).
2. Inhibiting interferon induced antiviral responses (adenovirus, EBV, HIV).
3. Blocking production of cytokines or response to cytokine (cowpox, adenovirus and HBV).
4. Suppressing major histocompatibility complex class 1 ( adenovirus).
5. Reducing B-cell activation (EBV).
TRANSFORMING VIRAL INFECTIONS
EPSTEIN-BARR VIRUS [EBV]

- EBV causes infectious mononucleosis, a benign, self-limited lymphoproliferative disorder,
and is associated with the development of hairy leukoplakia and a number of neoplasms,
most notably certain lymphomas and nasopharyngeal carcinoma.
- Infectious mononucleosis is characterized by fever, generalized lymphadenopathy,
splenomegaly, sore throat and the appearance in the blood of atypical activated T
lymphocytes (mononucleosis cells).
- Some patients develop hepatitis, meningoencephalitis and pneumonitis. Infectious
mononucleosis occurs principally in late adolescents or young adults among upper
socioeconomic classes in developed nations. In the rest of the world, primary infection with
EBV occurs in childhood and is usually asymptomatic.
- EBV is transmitted by close human contact, frequently with saliva during kissing. The viral
infection begins in nasopharyngeal and oropharyngeal lymphoid tissues, particularly the
ton-sils. Either through transient infection of epithelium or transcytosis into the
submucosa, EBV gains access to submucosal lymphoid tissues.
- The symptoms of infectious mononucleosis appear upon ini-tiation of the host immune
response. Cellular immunity mediated by cytotoxic CD8+ T cells and NK-cells is the most
impor-tant component of this response.
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- The atypical lymphocytes seen in the blood, so characteristic of this disease, are mainly
CD8+ cytotoxic T cells, but also in-clude CD16+ NK-cells. The reactive proliferation of T
cells is largely centered in lymphoid tissues, which account for the lymphadenopathy and
splenomegaly.
- Particularly in hosts with acquired defects in cellular immunity (e.g. AIDS), this initial
infection can progress through a multi-step process to EBV-associated B cell lymphomas.
One such example is Burkitt lymphoma, in which a chromosomal translocation of 8 : 14
involving the c-myc oncogene is a critical additional oncogenic event.
- The major alterations involve the blood, lymph nodes, CNS and occasionally other organs.
The peripheral blood shows absolute lymphocytosis with a total white cell count
between 12.000 and 16.000 cells per ml., more than 60 % of which are lymphocytes
- Many of these lymphocytes are large atypical lymphocytes, 12 to 16 m in diameter, with
an abundant cytoplasm containing multiple clear vacuolas, an oval indented, or folded
nucleus and scattered cytoplasmic azurogranules.
- The lymph nodes are enlarged throughout the body, specially in the posterior cervical,
axillary and groin regions. On histologic examination, the most striking feature is the
expansion of paracortical areas by activated T cells (immunoblasts).
- The spleen is enlarged, weighing between 300 to 500 gm and is usually soft and fleshy with
a hyperemic cut surface. The his-tologic changes are similar to those of the lymph nodes.
- Infectious mononucleosis:
Absolute lymphocytosis 12,000 to 18,000 cells per ml, more than 60 % are
lymphocytes,
Appearance of atypical lymphocytes, 12 to 16 m diameter, with abundant cytoplasma

and multiple clear vacuolations, oval intended or folded nucleus and scattered
cytoplastic azurophilic granules
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Pathways of transmissions of EB virus.

In individuals with normal immune
function, infection leads to
mononucleosis.
In cases of cellular immunodeficiency,

proliferation of infected B-cells is
uncontrolled and may lead to B-cell
neoplasms, such as Burkitt lymphomas,
nasopharyngeal carcinoma, Hodgkin
disease and other Non-Hodgkin
lymphomas.
HUMAN PAPILLOMA VIRUS (HPV)
- Human papilloma virus (HPV) are non-enveloped DNA viruses, member of the Papova
virus familiy. Based on DNA se-quence, papiloma viruses are classified into 100 types.
Some HPVs cause papillomas (warts) and benign tumors of squamous cells on the skin.
- Other HPVs are associated with warts that can progress to malignancy, particularly
squamous cacinoma of the cer-vix and the anogenital area. Papiloma viruses are mainly
transmitted by skin or genital contact.
- HPVs infect squamous epithelial cells, but their life cycle is not well understood since
these viruses cannot be cultured in vitro. The expression of viral genes depends on the
differentiation state of of the epithelial cells.
- Papilloma viruses initially infect basal cells in the epithelium, but there is limited expression
of viral genes in these cells. As the epithelial cells differentiate, additional HPV genes are
expressed.
- Mature virions are produced in the cells with granular layer and shed from the stratum
corneum. In the upper spinous layers of the epidermis, HPV leads to a characteristic
perinuclear vacuolisation in the epidermis cells (koilocytosis).
- HPV DNA is maintained as an episomal plasmid, and virus-encoded proteins promote cell
growth and malignancy
DENGUE HAEMORRHAGIC FEVER (DHF) AND DENGUE SHOCK SYNDROME

(DSS)
- Dengue virus caused about 100 million cases of acute febrile disease annually, including
more than 500,000 reported cases of DHF and DSS. Currently dengue is endemic in 112
countries: in Africa, North America, Asia and South East Asia. The worlds largest
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known epidemic of DHF and DSS occur-red in Cuba in 1981, with more than 116,000
persons hospitalized and as many as 11,000 cases reported in a single day. In Singapore,
there are about 4,000 to 5,000 cases reported every year. In the year 2003, there were 6
deaths from DSS
- The disease is transmitted to humans by the Aedes aegypti (AE) mosquito, which feeds
during the day. The mosquito becomes infected if the host has viremia, usually during the
time of fever. The virus develops in the mosquito for about 8 to 10 days where the virus
migrates to the salivary glands. Once infected the mosquito remains infected for the
duration of its lifespan which is estimated to be 2 to 4 weeks.
- AE is one of the most efficient transmitters of arboviruses because it lives in close
proximity to humans, often indoors. AE mosquito is difficult to eradicate because its eggs
can with-stand dessication for as long as a year.
- AE is a day-biting species with increased biting activity for 2 hours after sunrise and
several hours before sunset. It is a domestic breeder and breeds in water containers,
discarded tyres, coconut shells and overhead tanks.
- DHF and DSS are caused by one of four closely related, but antigenically distinct virus
types: DEN-1, DEN-2, DEN-3 and DEN-4, of the genus Flavivirus and family Flaviviridae.
These subtypes are different strains of dengue virus that have 60 80 % homology between
each other. The major difference for humans lies in subtle differences in the surface proteins
of the different dengue types.
- After a person is infected with dengue, he or she develops an immune response to that
subtype. The immune response produces specific antibodies to that subtypes surface
proteins that prevent the virus from binding to macropahage cells and gaining entry. If
another subtype of dengue virus infects the individual, the virus will activate the immune
system as if it was the first subtype. The body releases cytokines that cause the endothelial
tissue to become permeable which results in hemorrhage and plasma loss from the blood
vessels.
- Increased vascular permeability leads to plasma loss from the vascular compartment. This
results in haemoconcentration and low pulse pressure. When the plasma loss becomes
critical, shock ensues.
CLINICALLY DENGUE INFECTION
1. Asymptomatic: Many infected individuals remain asymptomatic. This may be one reason
why dengue remains endemic and makes isolation of cases ineffective.
2. Undifferentiated: Infants and younger children may present with an undifferentiated febrile
illness sometimes accompanied by a non-specific maculopapular rash
3. Dengue fever: This is the classical severe febrile syndrome that is recognized as DF.:
Fever: acute onset, last 2 7 days. Starts acute, abrupt and rises rapidly.
Headache, backache, myalgia with retroorbital pain.
Rash: maculopapular or flush, petechiae with islands of sparing.
Nausea and vomiting.
Thrombocytopenia.
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Complications: epistaxis, gum bleeding, hematuria, menorrhagia and life-threatening

gastrointestinal bleeding.
4. Dengue Hemorrhagic Fever (DHF)
Fever: high plus
Bleeding manifestations: (petechiae, ecchymois, epistaxis, gum bleeding, hematemesis,
melena) plus
Thrombocytopenia (<100 X 10/ml) plus
Evidence of increased capillary permeability (Hematocrit inreased by > 20 % above
base line; pleural effusion; hypoalbuminaemi)
Neurological disturbances (seizures, cranial nerves signs and coma) may also occur.
Constitutional symptoms similar to DF comes with fever: loss of appetite, vomiting,
nausea, headache, myalgia, bone pain
5. Dengue Shock Syndrome (DSS)
All the above Plus
Evidence of circulatory failure: hypotension, narrowed pulse pressure (< 20 mm Hg)
and impaired organ perfusion (rapid and weak pule, cold clammy skin and altered
mental status)
About 1/3 of patints with DHF will develop shock. It usua-ly occurs around the time
when the fever subsides. The patient can rapidly go into shock.
If shock is not recognized and treated in time, the patient passes into a state of profound
shock when pulse becomes imperceptible and blood pressure unrecordable.
Both the onset and progression of shock is rapid
MECHANISMS OF BACTERIA-INDUCED INJURY
Bacterial virulence depends on:
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1. Ability of bacteria to adhere to host cells

2. Ability to invade cells and tissues
3. Ability to produce toxic substances
as determined by a multitude of genes and gene products.

Bacterial adhesins are responsible for the attachement of bacteria to host cells, limited in
type but with a broad range of host cell specificity.
In contrast to viruses, which can infect a broad range of host cells, facultative intracellular
bacteria infect mainly epithelial cells, macrophages or both cell types.
- Entry into macrophages is for the most part directed by receptors that recognize antibodies
or complement on the surface of bacteria.
- Entry into epithelial cells is dependent on an interaction between a bacterial surface and
epithelial cell receptors, which stimulate host signalling pathways and subsequent
cytoskeletal rearrangements. Many bacteria attach to integrins Legionella and M.
tuberculosis bind to CR3, the cell receptor for the complement iD3b.
- Bacterial endotoxin is a lipopolysacharida that is a structural component in the outer wall
of gram-negative bacteria. Lipopolysacharida is somposed of a long-chain fatty acid anchor
(lipid A) connected to a core sugar chain, which are the same in all Gram bacteria
- Bacterial exotoxin secretes a variety of enzymes (hemolysin, hyaluronidases, coagulases,
fibrinolysins) that act on their respective substrates in vitro. The role of bacterial
exotoxins is well established and the molecular mechanisms of most of their ac-tions are
known.
- Diphtheria toxins consists of:
B fragment at the end of the carboxyl end of the molecule and is essential for the
attachment to host cells, and
A fragment which is at the amino end and linked to B fragment by a disulfide bridge.
- Bound diphtheria toxins enter the acidic endosome of cells, where it fuses with the
endosomal membrane and enters the cell cytoplasm. There the disulfide bond of the toxin
is broken, releasing the enzymatially active A fragment that catalyse the covalent transfer of
adenosine diphosphate (ADP)-ribose from nicotinamide adenine dinucleatide (NAD) to
EF-2 which is an elongation factor involved in protein synthesis. One molecule of
diphtheria toxin can kill a cell by ADP-rybosilating more than a million EF-2 molecules.
Diphtheria toxin creates a layer of dead cells in the throat, on which Corynebacterium
diphtheriae outgrows competing bacteria. Subsequently, wide dissemination of Diphtheria
toxin causes the characteristic neural and myocardial dysfunction of Diphtheria.
- Another well understood toxin is the alpha-toxin produced by the gram-positive anaerobic
Clostridium perfringens, the agent of gas-gangrene. The alpha-toxin is a lecithinase that
disrupts plasma membranes of erythrocytes, leukocytes and endothelial cells, resulting in
tissue injury
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Effect of Diphtheria exotoxin.

*Corynebacterium produce
exotoxin composed of A & B
fragments linked by a disulfide
bridge.
*Bound Diphtheria toxin fuses
with endosome cells entering the
cell plasma.
*A fragment is released catalizing
the covalent transfer of ADP-
ribose from NAD to EF-2.
*One molecule of Diphtheria
toxin can kill a cell by ADP-
ribosylating more than a milion
EF-2 molecules
SPECTRUM OF INFLAMMATORY RESPONSE TO INFECTION
Organisms induce several patterns of tissue reaction:

(1) Suppurative (Polymorphonuclear) inflammation:
Suppurative inflammation is characterized by increased vascular permeability of
neutrophils. They are attracted to the site of infection by release of chemoattractants
from the rapidly dividing pyogenic bacteria that evoke this response, mostly
extracellular gram-positive cocci and gram-negative rods.
The bacterial chemoattractant include secreted bacterial peptides, which contain N-
formylmehtionine residues at their amino termini that are recognized by specific
receptors on neutrophils.
Alternatively, bacteria attract neutrophils indirectly by releasing endotoxin that
stimulate macrophages to secrete IL-I or TNF or by cleaving complement into
chemoatractant peptides.
Massing of neurtophils results in the formation of pus or abscesses. The sizes of
exudative lesions vary from tiny miroabcesses to diffuse involvement of entire lobe of
lungs in pneumococcal infetions.
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Adjecent lobes filled with purulent exudates and vascular congestion of capillaries in the wall of
pulmonary lobes.
The many consequences of staphylococcal infection
Granulomatous inflammation occurs when aggregates of macrophages form,

sometimes around a central necrotic focus, or fuse together to form giant cells.
These distinctive lesions are usually evoked by relatively slow dividing agents
(M. Tuberculosis) or by those of relatively large size in the presence of T-cell
mediated immunity
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(2) Mononuclear and granulomatous infections.
Diffuse, predominantly mononuclear interstitial infiltrates occurs in response to viruses,

intracellular bacteria, spirochetes, intracellular parasites or helminths. Which mononuclear
cell predominates within the inflammatory lesion depends on the host immune response
to the organism.
Plasma cells are mostly seen in the chancre of primary syphilis, mostly lymphocytes
with active HBV infection or Lyme disease or in viral infections of the brain. These
lymphocytes reflect cell mediated immunity against pathogens or in pathogen-infected
cells.
(3) Necrotizing and chronic inflammation.

Clostridium perfringens and other organisms that secrete strong toxins cause rapid
and severe tissue damage that cell death is the dominant feature. Because in this process
very few inflam-matory cells are involved, these lesions resemble ischemic necrosis
on microscopy.
Entamoeba histolytica causes colonic ulcers and liver abscesses characterized by
extensive tissue destruction with liquefective necrosis in the absence of a prominent
inflammatory infiltrate.
The final common pathway of many infections is chronic inflamation, leading to
complete healing or extensive scarring. For some organisms that are relatively inert, the
scarring response is a major cause of dysfunction:pipe-stem fibrosis of the liver
caused by deposition of schistosome eggs or the constrictive fibrous pericarditis in
tuberculosis.
IMMUNE EVASION BY MICROBES
Microorganism can escape the immune system by several mechanisms:

(1) being inaccessibe to the immune system,
(2) resisting complement-mediated lysis and phagocytosis
(3) varying or shedding antigens
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(4) causing spesific or nonspesific immunosuppressions
Microbes that propagate in the lumen or the intestinal tract (toxin producing Clostridium
difficile) or gallbladder (Salmonella typhi) are inaccessible to the host immune defences,
including secretory immunoglobuline (IgA).
Viruses that are shed from keratin surfaces of epithelial cells (CMV in urine or milk
and polio viruses in stools), or those that infect the keratinized epithelium (poxviruses) are
also inac-cessable to the host humoral immune system.
Some organisms establish infections by rapidly invading host cells before the humoral
respons becomes effective (malaria parasites).
RESPIRATORY INFECTIONS
City inhabitants inhale some 10.000 microorganisms per day, including potentially
pathogenic viruses, bacteria and fungi. Most of the larger inhaled microorganisms are
trapped in the mucocilliary blanket of the upper airways. Those that manage to reach
the trachea are either coughed up pushed back toward the throat by cilliary action, than
swallowed and cleared.
Only small particles reach the alveoli, where they are attacked and interiorized by alveolar
macrophages or by neutrophils attracted to the site by cytokines.
This normal clearing system is most efficient, but mucociliary action can be impaired
by smoking, aspiration of acid stomach contents, or due to trauma by intubation. Some
respiratory viruses posses hamaglutinins which attached to epithelial surface
carbohydrates and may intervene the mucociliary process
VIRAL RESPIRATORY INFECTIONS
Viral respiratory disorders are the most frequent and least preventable of all infectious
diseases and range in severity from the self-limited common cold to life-threatening
pneumonias.
Viral infections damage bronchial epitelium and obstruct air ways and so may lead to
superinfection with bacteria, including Pneumococcus, Staphylococcus and
Haemophilus.
Of the many viruses capable of causing upper respiratory tract infections (rhinitis,
sinusitis, otitis media, pharyngitis and tonsilitis) and lower respiratory tract infections
(laryngotracheobronchitis, bronchiolitis, interstitial pneumonia and pleuritis)
rhinovirus and influenza virus are the most important and the best studied.
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RHINOVIRUSES
Rhinovirus accounts for 60 % of common colds. The other causes are coronavirus (15
%). Other causes are influenza viruses, parainfluenza viruses, adenoviruses and
enteroviruses (each 1 to 10% of colds).
Rhinoviruses are members of the picorna virus family (small RNA viruses), which
includes poliovirus, hepatitis A virus and coxsackievirus.
The human rhinovirus receptor is ICAM-1, a member of the immunoglobulin gene
superfamily. The site of binding of rhino-virus on the ICAM-1 molecule is the same as
that used by the leukocyte adhesion molecule LFA-1, the integrin on the surface of
lymphocytes that mediates T lymphocyte-specific, antigen-specific responses and
leukocyte emigration into inflammatory sites.
Rhinoviruses infect humans and higher primates, who have ICAM-1 on their epithelial
cells. The infection is confined to the upper respiratory tract because the viruses grow best
at 33 to 35 o C. Damage or injury to epihtelial cells are slight, but inflammatory mediators
such as bradykinins cause excessive mucous secretions characteristic of common cold.
Rhinoviruses induce serotype-specific IgC and IgA antibodies, which prevent reinfection
with the same rhinovirus but not with other serotypes
INFLUENZA VIRUSES
Influenza viruses are larger and more complex than rhinoviruses. The spherical surface of
influenza virus is a lipid bilayer (envelope) containng the viral Hemaglutinin and
Neuraminidase, which determine the subtype of the virus (H1-H3; N1 or N2).
Influenza viruses of type A infect humans, pigs, horses and birds and are the major cause of
pandemic and epidemic influenza infections. Epidemics of influenza occur through
mutations of the hemagglutinin and neuraminidase that allow the virus to escape most
host antibodies (antigenic drift). Pandemics, which are longer and more widespread than
epidemics, may occur when both the hemagglutinin and the neuraminidase are replaced
through recombination of RNA segments with those of animal viruses, making all
individuals susceptible to the new influenza virus (antigenic shift).
Influenza virus types B and C, which do not show antigenic drift or shift, infect mostly
children, who develop antibodies against reinfection in a manner similar to chickenpox,
mumps, and other childhood viral illnesses.
Viral URT infections are marked by mucosal hyperemia and swelling with a
predominantly lymphomonocytic and plasmacytic infiltration of the submucosa
accompanied by overproduction of mucus secretions. The swollen mucosa and viscid
exudate may plug the nasal channels, sinuses or eustachian tubes and lead to suppurative
secondary bacterial infection. Virus-induced tonsilitis with enlargement of the lymphoid
tissue within Waldeyer ring is frequent in children, especially if supperimposed with
streptococcal and staphylococcal infection
In laryngotracheobronchitis and bronchiolithis, there is a vocal cord swelling and abundant
mucous exudation. Impairment of bronchociliary function invites bacterial superinfection
with more marked suppuration
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BACTERIAL RESPIRATORY INFECTIONS

Bacterial peumonias are some of the most common bacterial infections in humans and are
particularly important because they are most frequently cited as the immediate cause of
death in hospitalized patients. Almost any type of virulent bacterial species can cause
pneumonia
HAEMOPHILUS INFLUENZAE
H. Influenzae is a pleiomorphic, gram-negative microorganism that is a major cause of
acute lower respiratory tract infections and meningitis in young children.
H. Influenzae is a prominent colonizer of the pharynx, where it exists in 2 forms:
encapsulated (5%) and unencapsulated (95 %).The encapsulated form dominates the
unencapsulated forms by secreting an antibiotic called hemocin that kills the
unencapsulated H. Influenzae. Type B H. Influenzae is the most frequent cause of severe
invasive disease.
H. influenzae pneumonia is a pediatric emergency with a high mortality rate. Descending
laryngo-tracheo bronchitis results in airway obstruction, as the smaller bronchi are plugged
by dense fibrin-rich exudate of PMN cells. Before a vaccine was widely available H.
Influenzae was a common cause of suppurative meningitis in children up to 5 years of age.
TUBERCULOSIS (MYCOBACTERIUM TUBERCULOSIS)

M. Tuberculosis infects about one third of the world population and is the cause of death
of 3 million patients each year and so is the single most important infectious cause of
death on earth. With increase of population and overcrowding in underdeveloped
countries the number of patients suffering from TB is expected to increase, in spite of
improvement in medical assistance.
In countries where the number of AIDS patients are increasing, esp. African countries, so
does the number of TB patients. Individuals suffering from AIDS have a reduced T-cel
mediated resistance to different diseases, this will include TB.
Etiology and Pathogenesis

Mycobacteria are aerobic, non-spore-forming, non-motile bacilli with a waxy coat on the
surface acid-fast bacilli. Two species of mycobaterium are infectious to men: M.
tuberculosis and M. bovis. M. tuberculosis is transmitted through inhalation of infective
droplets coughed or sneezed in the air by a TB patient. M. bovis is transmitted by milk
from diseased cows and first produce intestinal or tonsillar lesions. In developed coutries,
control of diary products and pasteurization of milk has drastically reduced / eradicated this
mode of infection.
M. Avium and M. intracellulare have virulence in normal host but cause disseminated
infection in 15 % to 24 % of patients with AID.
Pathogenicity of M. Tuberculosis is related to its ability to escape killing by macrophages
and induce delayed type of hypersensitivity:
Cord factor, a surface glycolypid cause virulent strains of M. Tuberculosis to grow in vitro.
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Lipoarabinomannan (LAM), a major heteropolysacharida inhibits macrophage activation

by interferon.
Complement activated on the surface of mycobacteria may opsonize the organism and
facilitate its uptake by the macrophage complement receptor.
Primary infection: begins with inhalation of the mycobacteria and ends with a T cell-
mediated immune response that induce hypersensitivity to the organism and control 95 %
of infection.
The inhaled MO is phagocytised by alveolar macrophages and transported to hilar
lymphnodes. Most of the macrophages are unable to kill MO, which multiply, lyse the host
cell and infect other macrophages. In some cases the MO disseminate through the blood
to other parts of the lung and elsewhere in the body. After a few weeks Tcell- mediated
immunity develops as demonstrated by a positive purified protein derivative (PPD) test
reaction.
Lysis of macrophages results in the formation of caseating granulomas. Direct toxicity of
the mycobacteria to the macrophages may contribute to the necrotic caseous centers.
Mycobacteria can not grow in this acidic, extracellular environment lacking in oxygen. The
ultimate residuum of the primary infection is a calcified scar in the lung parenchyma
and the hilar lymphnode the Ghon foci / lesion.
Phagocytosis of MO by
alveolar macrophages
and transported to hilar
lymph nodes.
Most macrophages are unable to

kill MO lysis of host cells
resulting in formation of
caseating granulomas
Secondary and Disseminated Tuberculosis

Some individuals become reinfected with mycobacteria, reactivate dormant disease, or
progress directly from primary mycobacterial lesion into disseminated disease. This maybe
because the microbacterium is particularly virulent or the host is particularly susceptable.
Granulomas of secondary TB most often occur on the apex of the lungs (Simons foci), but
may be widely disseminated in the lungs, kidneys, meninges and other organs.
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These granulomas, which fail to contain the spread of the mycobacterial infection are the
major cause of tissue damage in tuberculosis and are a reflection of delayed type of
hypersensivity. Two special features of secondary tuberculosis are caseous necrosis and
cavities. Necrosis may cause rupture into blood vessels, spreading mycobacteria throughout
the body, and break into airways, releasing infectious mycobacteria in the aerosols.
A common involvement is pleurisy, fibrosis, intestinal or bone tuberculosis.
Other complications are: - disseminated miliary TB
- meningitis TB
- osteomyelitis TB
- vertebral TB (Potts disease)
- involvement of the genitals
LEPROSY
Leprosy or Hansen Disease is a slowly progressive infection caused by Mycobacterium
leprae, affecting the skin and peripheral nerves, resulting in disabling deformities. ML is for
the most part contained within the skin, but is likely to be transmitted from person to
person through aerosols from lesions in the upper respiratory tract. Inhaled ML, like MT, is
taken up by alveolar macrophages and disseminates through blood, but grows only in
relatively cool tissues of the skin and extremities. Despite its low communicability, leprosy
remains endemic among estimated 10 to 15 million people living in poor tropical countries.
M. leprae is an acid fast obligate intracellular organism that grows poorly in ordinary
culture but can be grown in the armadillo. Like MT, ML secretes no toxins and its virulence
is based on properties of its cell wall, so that immunization with bacille Calmette-Guerin
confers some protection against M. leprae infection
Cell-mediated immunity is reflected by delayed type hypersensitivity reaction to dermal
injections of a bacterial extract called lepromin.
Leprosy has two strikingly different patterns:

(1) Tuberculoid leprosy (TL) A less severe form with dry scaly skin lesions that lack
sensation because of large asymmetric peripheral nerve involvement. TL begins with
localized skin lesions that are first flat and red but enlarge and developed irregular shapes
with induration, elevated hyperpigmented margins and pale centers. Nerve degeneration
causes skin anaesthesia and skin and muscle atrophy with indolent skin ulcers.
Contractures, paralysis and autoamputation of fingers and toes may ensue. Facial nerve
involvement may lead to the eyelids, keratitis and corneal ulceration. On microscopic
examination all sites of involvement disclose granulomatous lesions resembling TB, but
TB-bacilli are never found.
(2) Lepromatous leprosy (LL) also called anergic leprosy. More severe form with
symmetric skin thickening and nodules. Cooler areas of skin (incl. earlobes and feet) are
more severely affected than warmer areas such as axilla and groin. Damage to the
nervous system comes from widespread invasion of the mycobaterium into Schwann cells
and endoneural/perineural macrophages. In advanced cases of LL mycobacteria is present
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in sputum and blood. LL involves the skin, peripheral nerves, testis, hand and feet. Vital
organs and CNS are rarely affected, because the core temperature is probably too high for
the ML to grow. LL lesions contain large aggregates of lipid-laden macrophages (lepra
cells), often filled with masses of acid-fast bacilli (globi). Macular, papular or nodular
lesions form on the face, ears, wrists, elbows and knees.The nodular lesions on the face
may coalesce to yield a leonine facies. Most skin lesions are hypoesthetic or anesthetic.
Lesions in the nose may cause persistent inflammation and bacilli-laden discharge.
Peripheral nerves, especially ulnar and perineal nerves where they approach the skin
surface, are symmetrically invaded with mycobacteria with minimal inflammation. Loss
of sensation and trophic changes in the hands and feet follow the nerve lesions.
Lymphnodes show aggregation of foamy macrophages in the paracortical areas (T-cell
areas) with enlargement of germinal centers.
(3) Borderline or intermediate forms of Leprosy. This type of leprosy shows a wide range of
histologic changes, depending on whether a case is one of borderline tuberculoid or
borderline lepromatous leprosy. Generally, the cutaneous lesion show granulomatous
aggregates containing both foamy macro-phages and epitheloid cells.
HISTOPLASMOSIS
Histoplasma capsulatum infection is acquired by inhalation of dust particles from soil
contaminated with bird or bat droppings that contain small spores (micronidia), the
infectious form of the fungus. Like M. tuberculosis, H. capsulatum is an intracellular
parasite of macrophages. It has also some resemblance with M. tuberculosis:
(1) A self-limited and often latent primary pulmonary involvement,
(2) A chronic, progressive, secondary lung disease localized at the lung apices and
cause cough, fever and night sweats,
(3) Localized lesions in extra pulmonary sites: mediastinum, liver or meninges,
(4) Widely disseminated involvement, esp. in immunosuppressed patients
Differentiation from tuberculosis is made by eliciting a delayed type hypersensitivity

response to skin injection of a fungal lysate (histoplasmin test), or by identifying the
fungus in lung, lymph node or bone biopsy specimens in patients with dissemi-nated
histoplasmosis.
Histoplasma infection produce epitheloid cell granulomas, which usually undergo
coagulation necrosis and coalesce to pro-duce large areas of consolidation, but may also
liquefy to form cavities. With spontaneous or drug control of the infection, these lesions
undergo fibrosis and calcifications.
In fulminant disseminated histoplasmosis, which occurred in immunosuppresived
individuals, epitheloid cell granulomas are not formed, but instead focal accumulations
of mononuclear phagocytes filled with fungal yeast throughout tissues and or-gans of the
body. The reticuloendothelial system is overloaded with histoplasma yeast.
SEVERE ACUTE RESPIRATORY SYNDROME (SARS)

SARS first appears in November 2002 in Guangdong Province of China and subsequently
spread to Hong Kong, Taiwan, Singapore, Vietnam and Toronto. The ease of travel
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between continents clearly contributed to this pandemic. Between fall of 2002 and spring
of 2003, there were more than 8.000 cases, including 774 deaths.
After an incubation period of 2 to 10 days, SARS begins with a dry cough, malaise,
myalgias, fever and chills. Compared to other atypical pneumonias SARS less commonly
gives rise to symptoms related to URT infection such as sore throat.
A third of patients improve and resolve the infection, but the rest progress to severe
respiratory disease with shortness of breath, tachypnea and pleurisy
Nearly 10 % of patients die from the illness, for which there is no specific treatment.
The cause of SARS is a previously undiscovered corona virus.
Nearly 1/3 of URT infections are caused by coronavirus however SARS virus differs
from previously known corona virus in that it infects the LRT and spreads throughout
the body. The SARS virus seems to be first transmitted to humans to contact with wild
civets that are eaten in China. Sub sequently cases were spread person-to-person, mainly
through infected respiratory secretions although some may have been contracted from
stool.
SARS can be diagnosed either by detection of the virus or by PCR, or by detection of
antibodies to the virus. Levels of the virus are low initially and peak 10 days after the onset
of illness. Detection of antibodies specific for the SARS virus is a very sensitive and
specific test, however patients may not have a measurable antibody response for up to 28
days after infection
The SARS corona virus isolated from most human cases has a 29 nucleotide deletion in the
RNA when compared to the virus found in wild animals. This variation may enhance
trans-mission or pathogenicity of the virus in humans.
The lungs of patients who have died of SARS show diffuse alveolar damage and
multinucleated giant cells.
AVIAN INFLUENZA (AI)

Avian Influenza virus belong to Influenza virus type A which is known to be one of the
24 subtypes of virus influenza causing Avian Influenza esp. wild fowl (virus natural hosts).
Contrary to SARS 50 % of cases of AI died of the disease (55 cases from total of 109
infected with AI virus).
Person to person transmission has not been reported.
Reported cases of death of patients are infected from fowl who were previously infected
with AI.
GASTROINTESTINAL INFECTIONS
Barriers to infections of the GI Tract

Most GI Tract pathogens are transmitted by food or drink contaminated with fecal material
Where hygiene fails, diarrheal disease become rampant.
Normal defences against ingested pathogens include:
(1) Acid gastric juice,
(2) The viscous mucous layer covering the gi tract,
(3) Lytic pancreatic enzymes and bile detergents,
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(4) Secreted iga antibodies, made by b cells located in malt

Pathogenic organisms must compete for nutrients with abundant commensal bacteria
resident in the lower gut, and all gut microbes are intermittently expelled by defecation.
Host defences are weakened by low gastric acidity, by antibiotics that unbalance the
normal bacteria flora, by stalled peristalsis or by mechanical obstructions.
Most enveloped viruses are killed by the digestive juices, but non-enveloped ones may be
resistant (Hepatitis A virus, Rotavirus, reoviruses). Rota viruses directly damage the
intestinal epithelial cells they infect, whereas reoviruses pass through mucosal M cells
into the bloodstream without any detectable local injury.
Enteropathogenic bacteria elicit gastrointestinal disease by a variety of ways
(1) While growing on contaminated food, certain staphylococcal strains release powerful
enterotoxins that on ingestion, cause food poisoning symptoms without any bacterial
multiplication in the gut.
(2) Vibrio cholerae and toxigenic E. coli multiply inside the mucous layer overlying the
gut epithelium and release powerful exotoxins that cause the gut to secrete excessive
volumes of watery diarrhea.
(3) By contrast, Shigella, Salmonella and Campylobacter invade and damage the
intestinal mucosa and lamina propria and so cause ulceration, inflammation and
haemorrhage, clinically manifested as dysentery.
(4) S. typhi passes from the damaged mucosa through Peyer plaques and mesenteric
lymph nodes and into the bloodstream, resulting in a systemic infection
Fungal infection of the GI-tract occurs mainly in immunologically compromised patients.
Candida shows a predilection to stratifed squamous epithelium, causing oral thrush or
membranous esophagitis.
Cyst forms of intestinal protozoa are essential for their trans-mission because cysts resist
stomach acid. In the gut, cysts convert to motile trophozoites and attached to sugars on the
intestinal epithelia through surface lecithins
VIRAL ENTERITIS and DIARRHEA

Rotavirus is an encapsulated virus with a segmented double-stranded RNA genome and is
the major cause of infant diarrhea. They invade and destroy mature host epithelial cells in
the middle and upper villus.
Viral diarrhea is caused by a decreased absorpion of sodium and water from the bowel
lumen, in contrast to toxin-mediated bacterial diarrhea, which is caused by increased
secretion from host epithelial cells.
Corona viruses are pleiomorphic enveloped viruses with a large club-shaped projections
(crowns corona). They cause diar-rheal and URT infections and are usually endemic
rather than epidemic.
Enteric viruses are genetically and morphologically different
but the lesions they cause in the intestinal tract are basically similar blunting and
destruction of villus epithelial cells, which contain viruses visible by electron microscopy or
immunofluorescent staining.
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BACTERIAL ENTERITIS
SHIGELLA BACILLARY DYSENTERIA
Dysenteria refers to diarrhea with abdominal cramping and tenesmus in which loose
stools contain blood, pus and mucus. Bacillary dysentery, which results in as many as
500.000 deaths among children in developing countries each year, is caused by Shigella
dysenteria, Shigella flexneri, Shigella boydii and Shigella sonnei as well as certain O
type E.coli.
Shigella species are gram-neg facultative anaerobes which infect only humans. S.
flexnerii is the major cause of bacillary dysentery in endemic locations of poor hygiene,
including large regions of the developing world.
Transmission is fecal-oral and is remarkable for the small number of organisms that may
cause disease: 10 ingested organisms in 10 % volunteers 500 in 50 % of volunteers
Dysentery is caused when bacteria escape the epithelium cell phagolysosome, multiply
within the cytoplasm and destroy host cells. Shiga toxins cause haemorrhagic colitis and
haemolytic-uremic syndrome by damaging endothelial cells in the microvasculature of the
colon and glomeruli respectively.
In severe bacillary dysentery the colonic mucosa becomes hyperemic and edematous.
Enlargement of lymphoid follicles (Peyers plaques) creates small, projecting nodules.
Within the course of 24 hours, a fibrinosuppurative exudat slowly covers the mucosa and
produce a dirty gray to yellow pseudomembrane.
The inflammatory reaction within the intestinal mucosa builds up, the mucosa becomes soft
and friable, and irregular superficial ulcerations appear. If the infection is severe, large
tracts may be denuded leaving only islands of preserved mucosa.
On histologic examination, there is a predominantly mono-nuclear leucocytic infiltrate
within the lamina propria, but the surface of the ulcers are covered with an acute,
suppurative, neutrophilic reaction accompanied by congestion, marked edema, fibrin
deposition and thromboses of small vessels. As the disease progresses, the ulcer margins
are transformed into active granulation tissue. When the disease remits or heals, this
granulation tissue fills the defect and the ulcers heal by regeneration of the mucosal
epithelium.
CAMPYLOBACTER ENTERITIS
Important cause of chronic gastritis, enterocolitis and septicemia name changed to
Helicobacter pilory.
Often associated with consumption of poorly cooked chicken.
Closely associated with following symptoms:
Diarrhea
Dysenteria
Enteric fever
Inflammation may involve the gut from jejunum to anus. In invasive infection the colonic
mucosa appears friable or superficially eroded on proctoscopy, with hyperemia, edema and
infiltrates consisting of neutrophils, lymphocytes and plasma cells. There may be colonic
crypt abscesses and ulcerations resembling ulcerative colitis
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SALMONELLOSIS AND TYPHOID FEVER

Salmonellae are flaggelated, gram-negative bacteria that cause a self-limited food and water-
borne gastroenteritis or a life-threatening systemic illness marked by fever (esp. Salmonella
typhi). Humans are the only host of S. typhi, which is shed in faeces, urine, vomites and oral
secretions by acutely ill persons and in the faeces by chronic carriers without overt disease.
Therefore, typhoid fever is a disease of developing countries where sanitary conditions are
insufficient to stop its spread. Typhoid fever is a protracted disease that is associated with
bacteriemia, fever and chills in the first weeks, widespread reticuloendothelial
involvement with rash, abdominal pain and prostration in the second week, ulceration
of the Peyer plaques, with intestinal bleeding and shock in the third week.
Salmonellae invade intestinal epithelial cell as well as tissue macrophages. Invasion of

intestinal epithelial cells is controlled by invasion genes that are induced by the low oxygen
tension in the gut.
Intestinal lesions are limited to the ileum and colon and include erosion of the epithelium
and mixed inflammation in the lamina propria:
Variable numbers of PMNs are found in the stools, depending on the severity of
infections. S. typhi cause proliferation of phagocytes with enlargement of reticulo
endothelial and lymphoid tissues throughout the body.
Peyer patches in the terminal ileum become sharply delineated, with plateau-like
elevations up to 8 cm in diameter, with enlargement of draining mesenteric lymphnodes
In the second week the mucosa over the swollen lymphoid tissue is shed resulting in
oval ulcers with their long axis in the direction of bowel flow
CHOLERA
Vibrio Cholerae are comma-shaped gram-neg bacteria that have been the cause of seven
great long-lasting epidemics of diarrheal disease. Many of these epidemics begin in the
Ganges Valley of India and Bangladesh and then move East. Of the 140 serotypes only the
O1 serotype was associated with diarrhea. In 1992 a new serotype (0139-Bengal) has been
associated with severe watery diarrhea.
The vibrios never entered the mucosa epithelium but remained within the lumen and
secreted toxin which is encoded by a virulent phage. The vibrio hemagglutinin, which is a
amelloprotease, is important for the detachment of vibrio from epithelial cells
Macrophages containing bacteria, red blood cells (erythrophagocytosis) and nuclear debris
from small nodular aggregates in Peyer patches.
The spleen is enlarged, soft and bulging with uniformly pale red pulp, obliterated follicular
markings and prominent sinous histyocytosis and reticuloendothelial proliferations.
The liver shows randomly scattered foci of parenchym necrosis.
Gallbladder colonization are the basic conditions of chronic carier state.
AMEBIASIS
Entamoeba histolytica is considered to be the cause of infecting approximately 500 million
persons in developing countries. E. histolytica cysts, which have a chitin wall and four
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nuclei, are the infectious form because they are resistant to gastric acid. In the colonic
mucosa, cysts release trophozoites, the ameboid form that reproduce under anerobic
conditions without harming the host.
The parasites lack mitochondria or Krebs cycle enzymes and therefore are obligate
fermenters of glucose to ethanol.
Metronidazole, the best drug to treat invasive infections with entamoebae, targets
ferredoxin-dependent pyruvate oxydoreductase, an enzyme critical in such fermentation
that is present in these organisms but is absent in humans.
Amebae cause dysentery when they attach to the colonic epithelium, lyse colonic epithelial
cells, and invade the bowel wall. Amoeba proteins that may be involved in tisue invasion
include:
1. cysteine proteinases, which are able to break down proteins of the extracellular matrix,
2. a lectin on the parasite surface that binds to carbohydrates on the surface of colonic
epithelial cells and red blood cells.
3. channel-forming protein called amebapore, which make holes in the plasma
membrane of host cells and lyses them. The amebapore is a small peptide that has
the same structure as the NK-lysin of killer lymphocytes
A major unsolved question is why only 10 % of persons infected develop dysentery. One
posible explanation is the existence of two genetically distinct forms of amebae: E.
histolytica that cause disease and E. dispar that does not. The cysts of virulent and
nonvirulent amebae have a similar structure in stools, but the presence of trophozoites
containing ingested red blood cells is indicative of tissue invasion by virulent E. histolytica.
Amoebiasis most frequently involves the coecum and ascending colon, followed by the
sigmoid, rectum and appendix. In severe fullblown cases the entire colon is involved.
Amebae can mimic the appearance of macrophages because of their comparable size and
large number of vacuoles. The parasites however have a smaller nucleus containing a large
karyosome.
Amebae invade the crypts of colonic glands, burrows through the tunica propria and are
halted by the muscularis mucosae. There the amebae fan out laterally to create a flask-
shaped ulcer with a narrow neck and broad base.
As the lesion progresses, the overlying surface mucosa is deprived of its blood supply and
sloughs. The earliest amebic lesions show neutrophilic infiltrates in the mucosa, which later
develop into ulcers that contain few host inflammatory cells and areas of extensive
liquefective necrosis.
The mucosa between ulcers is often normal and mildly inflamed. An uncommon lesion is
the ameboma, a napkin-like constrictive lesion which represents a focus of profuse
granulation tissue response to the parasites
In about 40 % with amebic dysentery parasites penetrate portal vessels and embolize to the
liver to produce solitary or less often multiple discrete abscesses, some exceeding 10 cm in
diameter. Amebic liver abscesses have a scant inflammatory reaction at their margins and a
shaggy fibrin lining. Because of haemorrhage into cavities, the abscesses are often filled
with a chocolate-colored, odorless, pasty material
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Amebiasis of the colon with a portion three E. histolytica trophozoites
PARASITIC INFECTIONS
PROTOZOA
MALARIA
Malaria, caused by the intracellular parasite Plasmodium is a worldwide infection that
affects 300 million and kills 1 milion people each year.
Plasmodium falciparum, the most infectious type and the three other malaria parasites: P.
vivax, P. ovale and P. malariae, are transmitted by female Anopheles mosquitoes that are
widely distributed throughout Africa, Asia and Latin America.
Nearly all of the approxmately 1500 new cases of malaria each year in the US occur in
travellers or immigrants
Worldwide PH efforts to control malaria in the 1950 and 1980s failed, leaving mosquitoes
resistant to DDT and malathion and plasmodium resistant to chloroquine and pyrime-
thamine.
P. vivax, P. ovale and P. malariae cause low parasitemia, mild anemia, and in rare instances
splenic rupture and ne-phrotic syndrome.
P. falciparum causes high levels of parasitemia, severe anemia, cerebral symptoms, renal
failure, pulmonary edema and death.
The infectious stage of malaria, the sporozoites, is found in the salivary glands of female
mosquitoes. When the mosquito bites sporozoites are released into human blood and
within minutes attach to and invade liver cells by binding to the hepatocyte receptor for
the serum proteins thrombospondin and properdin.
Within liver cells, malaria parasites multiply rapidly, so as many as 30.000 merozoites
(asexual, haploid forms) are released when each infected hepatocyte ruptures. P. vivax and
P. ovale form latent hypnozoites in hepatocytes, which cause relapses of malaria long after
initial infection.
Once released from the liver Plamodium merozoites bind by a parasite lectin-like molecule
to sialic residues on glycophorin molecules on the surface of red blood cells. Within the
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red blood cells, the parasites grow in a membrane-bound digestive vacuole, hydrolyzing
hemoglobin through secreted enzymes.
The trophozoite is the first stage of the parasite in the red blood cell and is defined by the
presence of a single chromatin mass.
The next stage, the schizont, has multiple chromatin masses, each of which develops into a
merozoite. On lysis of the red blood cell, the new merozoites infect additional red blood
cells
P. falciparum (PF) causes more severe disease than the other Plasmodium species do to the
following characteristics:
PF is able to infect red blood cells of any age, leading to high parasite burdens and
profound anemia.
PF causes infected red blood cells to clump together (rosetting) and to stick to
endothelial cells lining small blood vessels which blocks blood flow. Ischemia due to
poor perfusion causes the manifestations of cerebral malaria, which is the main cause
of death due to malaria in children.
PF stimulates production of high levels of cytokins. Glycosyl phosphatydil inositol
(GPI) linked proteins, including merozoite surface antigens, are released from
infected red blood cells and induce cytokine production by host cells. These cytokins
suppress production of red blood cells, increase fever, induce nitric oxide production
leading to tissue damage.
HOST RESISTENCE TO PLASMODIUM

1. Inherited alterations in red blood cells make people resistant to plasmodium. People who
are heterozygous for the sickle cell trait (HbS) become infected with P. falciparum, but
they are less likely to die from infection.
2. Repeated or prolonged exposure to Plasmodium species stimulates an immune response
that reduces the severety of illness caused by malaria.
PATHOLOGY OF MALARIA
P. falciparum infection initially causes congestion and enlargement of the spleen, which
may eventually exceed 1000 grm in weight. Parasites are present within RBC wth
increased phagocytic activity of the macrophages in the spleen.
In chronic malaria infection, the spleen becomes increasingly fibrotic and brittle, with a
thick capsule and fibrous trabeculae. The parenchyma is gray or brownish-black because of
phagocytic cells containing brown-black granules of hemozoin pigment. In addition
macrophages with engulfed parasites, RBCs and debris are numerous.
With progression of malaria, the liver becomes progressively enlarged and pigmented.
Kupfer cells are heavy laden with malaria pigment, parasites and cellular debris. Pigmented
phagocy-tic cells may be found dispersed throughout the bone marrow, lymphnodes,
subcutaneous tissues and lungs. The kidneys are often enlarged and congested with
pigments in the glomeruli and hemoglobin casts in the tubules
In malignant cerebral malaria caused by P. falciparum, brain vessels are plugged with
parasitized RBCs, Each cell containing dots of hemozoin pigment. About the vessels there
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are ring haemorrhages that are probably related to local hypoxya caused by the vascular
stasis and small focal inflammatoty reactions.
With more severe hypoxia there is degeneration of neurons, focal ischemic softening and
occasionally scant inflammatory in filtrates in the meninges.
Nonspecific focal hypoxic lesions in the heart may be induced by the progressive anemia
and circulatory stasis in chronically infected patients. In some, the myocardium shows focal
interstitial infiltrates. Finally, in the nonimmune patient, pulmonary edema or shock with
Disseminated Intravascular Coagulation (DIC) may cause death, sometimes in the absence
of other characteristic lesions.
P. Falciparum infected red cells marginating within a vein in cerebral malaria
SEXUALLY TRANSMITTED DISEASES
GONORRHEA
Gonorrhea is caused by Neisseria gonorrhea, a pyogenic, encapsulated , gram-neg
diplococcus.
In men infection will create urethra strictures and chronic infections of epidymis, prostate
and seminal vesicles. In woman it may result in infections of the falopian tubes (salpingitis)
resulting in scars with increase rates of sterility and ectopic pregnancy.
Gonococcal bacteriemia leads to an arthritis-dermatitis syndrome, whereas conjunctivitis
may appear in adults from auto-inoculation
N. Gonorrhea is a facultative intracellular pathogen that binds to and invades epithelial
cells.
All gonococcal lesions show exudative and purulent reactions followed by granulation
tissue formation, plasma cell infiltration and fibrosis. Gonococcus in men cause a
mucopurulent discharge from an edematous and inflamed urethral meatus 2 to 7 days after
exposure. If untreated, suppurative inflammation with focal abscesses spreads to the
posterior urethra, epididymis, prostate and seminal vesicles. Chronic inflammation may
lead to urethral strictures and sterility
In women, urethral inflammation is less prominent, whereas abscesses frequently cause
bulging of Bartholin and Skene glands. Gonococcal cervicitis results in few sequelae,
whereas salpingitis may seal the fallopian tube, which become massively distended with
pus and may be left severely scarred. Tubo-ovarian abscesses and pelvic peritonitis result
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from further extension and may create multiple adhesions and points of blockage of the
oviducts.
Perinatal infection to the newborn may result from gonococcal cervicitis and if not detected
early may lead to congenital blindness.
SYPHILIS
Syphilis is caused by the spirochete Treponema pallidum sub-species pallidum, a chronic
venereal disease with multiple clinical presentations. Other closely related treponemas are:
- Treponema pallidum subspecies pertenue, that cause Yaws or Frambosia.
- Treponema pallidum subspecies curateum, that causes Pinta
Sexual intercourse is the usual mode of spread. Transplacental transmission of TP occurs
readily and active disease during pregnancy may result in congenital syphilis.
Public Health Programs and penicillin treatment reduced the number of cases of syphilis
throughout the world dramatically, but total reduction of cases is hard to achieve because
its transmission is closely linked to a biological function.
CLINICAL AND PATHOLOGICAL STAGING OF SYPHILIS

STAGE PATHOLOGY
PRIMARY Chancre
SECONDARY Palmar rash

Lymphadenopathy
Condyloma latum
TERTIARY Neurosyphilis: Meningovascular

Tabes dorsalis
General paresis
Aortitis : Aneurysm
Aortic regurgitation
Gummas : Hepar lobatum
Skin, bone, others
PRIMARY SYPHILIS
The primary stage of Syphilis, occuring approximately 3 weeks after contact with an
infected individual, features a single firm, nontender, raised, red lesion (chancre) located at
the site of trepanosomal invasion on the penis, cervix, vaginal wall or anus.
The chancre heals in 3 to 4 weeks with or without therapy. Spirochetes are plentiful within
the chancre and can easily be seen by dark-field or immunofluoresent stains.
Spirochetes spread throughout the body by hematologic and lymphatic dissemination
even before the appearance of the chancre.
SECONDARY SYPHILIS
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The secondary stage usually occurs 2 to 10 weeks after the primary chancre and is due to
spread and proliferation of the spirochetes within the skin and mucocutaneous tissues.
Secondary syphilis occurs in approximaely 75 % of untreated patients. The skin lesions,
mostly on the palms or soles of the feet, may be maculopapular, scaly or pustular.
Most areas of the skin, such as the anogenital region, inner thighs and axillas, may have
condyloma lata, which is a broad-based elevated plaque. All these painless superficial
lesions contain spirochetes and so are infectious.
Lymphadenopathy, mild fever, malaise and weight loss are also common in secondary
syphilis. The symptoms of secondary syphilis last several weeks after the patient enters
the latent phase of the disease.
TERTIARY SYPHILIS
The tertiary stage of syphilis occurs approximately 1/3 of untrated patients, usually after a
latent period of 5 years or more. It has three main manifestations: cardiovascular syphilis,
neurosyphilis and so-called benign tertiary syphilis, occuring alone or in combination.
Cardiovascular syphilis, in the form of syphylitic aortitis, accounts for more than 80 % of
cases of the tertiary disease. The aortitis leads to slowly progressive dilatation of the aortic
root and arch, which causes aortic valve insufficiency, aneurysm and ending in rupture.
Neurosyphilis may be symptomatic or asympyomatic, manifestating in chronic
meningovascular disease, tabes dorsalis and generalized brain parenchymal disease called
general paresis
Asymptomatic neurosyphilis, which account for about 1/3 of neurosyphilis, is detected upon
examination of CSF. Presence of abnormalities such as pleiocytosis, elevated protein
levels or decrease glucose level.
Gummas are nodular lesions related to development of hipersensitivity of the bacteria.
They occur most commonly in bone, skin and the mucous membranes of upper airway and
mouth. Skeletal involvement causes local pain, tenderness, swelling and sometimes
pathological fracture.
CONGENITAL SYPHILIS
Congenital syphilis occurs when T. pallidum crosses the placenta from an infected mother
to the fetus.
Maternal transmission happens most frequently during primary or secondary syphilis, when
the spirochetes are most numerous. It is also rare if maternal syphilis has been present for
more then 5 years.
Manifestation of congenital syphilis may be subtle, routine serologic testing for syphilis is
mandatory in all pregnant woman. Intrauterine and perinatal death occurs in 25 % of
untreated congenital syphilis.
Early congenital syphilis is often manifested by nasal discharge and nasal congestion in
the first few months of life. Hepatomegally and skeletal abnormalities are also common.
Nearly half of untreated children with neonatal syphilis will develop late manifestations,
which include Hutchinson triad: notched central incisors, interstitial keratitis with blindness
and deafness from 8th cranial nerve injury.
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Congenital
Late abortion or stillbirth
Infantile:
Skin rash
Osteochondritis
Periostitis
Liver & Lung fibrosis
Childhood:
Interstitial keratitis
Hutchinson teeth
8th Nerve deafness
Serological Tests for Syphilis
Although PCR tests for syphilis have been developed, serology remains the mainstay of
diagnosis. Serological tests for syphilis include Non-Treponemal Antibody tests (NTA-test)
and Anti-Treponemal Antibody tests (ATA-test).
Nontreponemal tests measure antibody to cardiolipin, a phospholipid that is present in
both host tissues and the T. pallidum. These antibodies are detected in the Rapid Plasma
Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests.
NTA-tests typically become positive 4 to 6 weeks after infection and are nearly always
positive in secondary syphilis. They may become negative in late or tertiary syphilis,
despite the presence of low levels of spirochetes.
The VDRL and RPR are used as screening tests for syphilis and to monitor response to
therapy as these tests become negative after successful treatment of infection.
However: NTA tests are often negative during the early stage of disease, even in the
presence of a primary chancre.
Up to 15 % of positive VDRL tests represent biologic false positive results, which may be
transient or persistent, increasing in frequency with age.
CHANCROID (SOFT CHANCRE)
Chancroid is an acute, sexually transmitted, ulcerative infection caused by Haemophilus
ducreyi, most common in tropical and subtropical areas, more prevalent in lower
socioeconomic groups and among men who have regular contact with prostitutes.
Four to 7 days after inoculation, the patient develops a tender, erythematous papule
involving the external genitalia. In males, the primary lesion is usually on the penis; in
females most lesions occur in the vagina or the periurethral area. After several days the
surface of the primary lesion erode to produce an irregular ulcer, which is more apt to be
painful in males than in females.
In contrast to the primary chancre of syphilis, the ulcer of chancroid is not indurated, and
multiple lesions may be present. The base of the ulcer is covered by shaggy, yellow-gray
exudate. The regional lymphnodes, particularly in the inguinal region, become enlarged and
tender in about 50 % of cases within 1 to 2 weeks of the primary inoculation. In untreated
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cases, the inflamed and enlarged nodes (buboes) may erode the overlying skin to produce
chronic, draining ulcers.
Microscopically, the ulcer of chancroid contains a superficial zone of neutrophylic debris
and febrin, with an under-lying zone of granulation tissue containing areas of necrosis and
thrombosed vessels. A dense lymphoplasmacytic inflammatory infiltrate is present beneath
the layer of granulation tissue.
GRANULOMA INGUINALE
G I or donovanosis is a chronic inflammatory disease caused by Calymmatobacterium

donovani, a minute encapsulated coccobacillus that is closely related to the Klebsiella
genus and is sexually transmitted.
This disease is endemic in rural areas in certain tropical and subtropical regions. Untreated
cases are characterized by the development of extensive scarring, often associated with
lymphatic obstruction and lymphedema (elephantiasis) of the external genitalia.
Culture of the organism is difficult and PCR assays are still in development, so diagnosis is
made by morphologic examination of smears or biopsies of the ulcer.
GI begins as a raised papular lesion involving the moist, stratified squamous epithelium of
the genitalia or, rarely, extragenital sites including the oral mucosa or pharynx.
The lesion eventually undergoes ulceration, accompanied by the the development of
abundant granulation tis-sue, which is manifested grossly as a protuberant soft, painless
mass. As the lesion enlarges, its borders become raised and indurated.
Disfiguring scars may develop in untreated cases and are sometimes associated with
urethral, valvular, or anal strictures.
Regional lymph nodes typically are spared or show only nonspecific reactive changes, in
contrast to chancroid.
Daftar Pustaka
Robbins pathology
39

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UNTUK KALANGAN SENDIRI

Dilarang memperbanyak karya tulis ini dalam bentuk dan dengan

Bandung, Oktober 2014

Jo Suherman,dr., MS., AIF

Bandung, Agustus 2014

Heddy Herdiman, dr., M.Kes

Bandung, 24 Januari 2015

Prof. Topo Harsono, dr., Sp.PA(K). (alm.)

INFECTIOUS DISEASE (ID)

A disease caused by a pathogenic microorganism, the etiologic agent of which may be a

A communicable disease transmitted by contact or aerosol.

The history of pathology of ID are intertwined with that of microbiology:

MAJOR DISCOVERIES IN MICROBIAL PATHOGENESIS

NEW EMERGING INFECTIOUS DISEASES

Hantaan virus Hemorrhagic fever with renal disease

1983 HIV AIDS

HUMAN VIRAL DISEASES AND THEIR PATHOGENS

SYSTEMIC WITH SKIN ERUPTIONS

Parvo virus Erythema infectiosum

SYSTEMIC WITH HEMATOPOIETIC DISORDERS

HTLV-II Role uncertain

ARBOVIRAL AND HEMORRHAGIC FEVERS

CENTRAL NERVOUS SYSTEM

CATEGORIES OF INFECTIOUS AGENTS

III. BACTERIOPHAGES, PLASMIDS AND TRANSPOSONS

Neisseria gonorrhea Gonorrhea

GRAM-NEGATIVE BACTERIA (common)

GRAM-NEGATIVE BACTERIA (rare)

CONTAGIOUS CHILDHOOD BACTERIAL INFECTIONS

ZOONOTIC BACTERIAL INFECTIONS

HUMAN TREPONEMAL INFECTIONS

Treponema pertenue Framboesia (Yaw)

V. CHLAMYDIAE, RICKETTSIAE AND MYCOPLASMAS

Blood-bourne protozoa (Plasmodium, Tryponema and Leishmania specieses) are

CONTAMINATION, SPREAD AND DISSEMINATION

Development of an infectious disease is the ultimate result of interaction

parasitism: beneficial to one but detrimental to the other

MICROORGANISMS [MO] AND INJURY / DISEASE

HOST BARRIERS, SPREAD AN DISSEMINATION

1. Most formidable barriers to infection are:

4. Others adhere or proliferate exclusively in or on epithelial cells papilloma virus and

Local Defence Incubation Period

MECHANISMS OF VIRAL INJURY

EBV binds to complement receptor on macrophages (CD2)

Viral infections can be:

TRANSFORMING VIRAL INFECTIONS

EPSTEIN-BARR VIRUS [EBV]

Appearance of atypical lymphocytes, 12 to 16 m diameter, with abundant cytoplasma

Pathways of transmissions of EB virus.

In cases of cellular immunodeficiency,

HUMAN PAPILLOMA VIRUS (HPV)

DENGUE HAEMORRHAGIC FEVER (DHF) AND DENGUE SHOCK SYNDROME

CLINICALLY DENGUE INFECTION

Complications: epistaxis, gum bleeding, hematuria, menorrhagia and life-threatening

MECHANISMS OF BACTERIA-INDUCED INJURY

Bacterial virulence depends on:

1. Ability of bacteria to adhere to host cells

as determined by a multitude of genes and gene products.

Effect of Diphtheria exotoxin.

SPECTRUM OF INFLAMMATORY RESPONSE TO INFECTION

Organisms induce several patterns of tissue reaction:

The many consequences of staphylococcal infection