083110 M04-PATHO Infectious Diseases Part 2 Team 09

YL6

Basic Pathology 2 [PATHOLOGY]

31 Aug 2010

MECHANISMS OF INFECTIOUS DISEASES PART II

OUTLINE I. Infectious Agents II. Special Techniques for Diagnostics III. New and Emerging Infectious Diseases IV. Agents of Bioterrorism V. Transmission and Dissemination of Microbes VI. Questions and Answers I. INFECTIOUS AGENTS (Continuation of previous group) A. Prions B. Viruses C. Bacteria D.Fungi D. Fungi Mycology – study of fungi Example: Mushroom truffles- very expensive Tastes like goat’s urine Main function: decomposers as garbage cleaners Eukaryotes (these are the true cells) Possess thick chitin-containing cell walls and ergosterolcontaining cell membranes membranes 2 components of cell wall: chitin and ergosterol. o Chitin is a substance found in crustaceans o Ergosterol is never found in human cells. What is a fungi? Is it an animal or a plant? It’s neither. It’s still in between. What is interesting is that they will grow in different stages based on temperature: o ): round Thermal dimorphism (body temperature: 37  C ): structures which can bud off; regardless of the type of fungi, o as long as it’s 37  C, it assumes a yeast form Yeast form Hyphae form (room temperature) o It is with similarity to plants because it grows mycelia (branches). Means of reproduction: sexual or asexual  Reproduction It is considered more advanced but each – sexual or asexual- has its own advantages. o Sexual (involves meiosis) o Asexual Requirement: male and female counterpart forming a zygote      

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Dr. Ernesto V. Datu Tinea unguium = nails o Tinea versicolor  All these affect affect dead cells. cells. Treatment is difficult. difficult. Not  parenteral but but topical topical treatment. treatment. o

Mycosis Candida albicans is not a normal flora because it does not do anything beneficial. In fact, it can be a source of opportunistic infections Subcutaneous Mycosis o Soil saphrophytes of regional epidemiology introduction o Accidental introduction Deep mycosis o More severe. Some are opportunistic like candida albicans, while some are geographically restricted. Most are not present in the country but because of travel, they could be present  o Dimorphic Systemic Mycosis Geographically restricted-respiratory Opportunistic Systemic Mycosis (more common form) 

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E. Protozoa (can be free living or parasitic) Single-celled eukaryotes that are major causes of disease and death in developing countries. Protozoa can replicate intracellularly within a variety of cells Amoeba Sporozoa—They share a common feature with fungus in that it can produce spores. 

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Flagellates (named because of their means of locomotion )

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Dermatophytosis Imperfect fungi Tinea refers to a fungal infection. It is different from taenia in parasitology. o Feeds on Keratin o Malassezia furfur o Hortaea werneckii  Superficial or dermatophytes o Tinea capitis = scalp o Tinea corporis=body o Tinea cruris = groin Singit, commonly known as “jock itch”. There is constant rubbing in the area that can be prone to other infections o Tinea pedis=feet o Tinea manuum = hand o Tinea faciale = face  

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 Amoeba has a cystic form which is more infective and trophozoite form. They ingest cyst, and develop trophozoite. You get infected by oral fecal route, which is when you eat shit! The organism also is pathogenic. In the figure above, trophozoite with dark spots are stained by iron hematoxyline. The trophozoites are erythrophagocytic which eat red cells. In severe, extreme cases, the lining epithelium of the intestine called an ulcer with flask shaped lesion is oozing out. Entamoeba histolytica entered through the lumen but cannot  penetrate musculari muscularis. s.

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MECHANISM OF INFECTIOUS DISEASES PART II

PATHOLOGY Entamoeba Entamoeba histolytica histolyt ica tropho tr ophozo zoit ites es 

Forms flask-shaped ulcers in the ileum filled with necrotic material

F. Helminths

Entamoeba histolytica trophozoites

Giardia lambdia with dual nucleus in trophozoite stage.

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Trichomonas Trichomonas va inalis.

Toxoplasma Toxoplasma gondii  cysts   cysts in skeletal muscle.

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 Among the the pictures above, which which one would would you like to have? have?

Giardia lamblia   

Lines small intestines, a flagellae Causes steatorrhea steatorrhea It is the flagellae which has dual nucleus in trophozoite stage (two eyes/old man with eye glasses), associated with stool with fat because giargia lamblia prevents absorption of fat

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Highly differentiated multicellular multicellular organisms Nematodes are round worms (ex. Earthworm) which are highly specialized. Cestodes are tapeworms Trematodes are flatworms Cestodes and trematodes  are hermaphrodites (have sex with themselves), and have a complicated lifestyle Helminths  are multicellular organisms, some have their own reproductive organs

Enterobius vermicularis

Trichomonas vaginalis (no quiescent stage) 

 A sexually transmitted transmitted disease where the manifestation manifestation depends on sex o If male, there are no no symptoms, you don’t feel feel a thing but you infect others o If you are a female, vaginal smell changes to something  fishy, symptomatic symptomatic that causes intense pruritus or itchiness

Pinworm that has separate sexes. If the egg contains all males, they all die. If it contains all  females, they also die but it is unlikely to happen. happen. If you are a hermaphrodite, you can reproduce.  Advantage of sexual reproduction reproduction is a mixture of genes. o  Advantage There is pruritis in anus since females crawl out of rectum and lay their eggs around the opening. o Pruritus ani – itchy butt caused by female enterobius vermicularis crawling out of the rectum. Transmission is by scratching the butt or by touching something edible or by eating food  o o

Toxoplasma Gondii 

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More severe example of a protozoal disease that can affect the brain Characteristic sickle cell shape Macrophages have the trophozoites of toxoplasma gondii inside; toxoplasmosis What is not normal there is the trophozoites forming a  pseudocyst Definitive host: cat (ONLY definitive host), comes out in stools of cat as oocyst which is the infective form Infection is quite cosmopolitan. Half of us might be positive  for antibodies antibodies against against toxoplasma toxoplasma Surgeons found out that if you have had infection, the small cysts will go into a quiescent stage called BRADYZOITES. When it reactivates it becomes TACHYZOITES. When immune system becomes compromised, there is wide spread infection. The most severe is encephalitis associated with it. If mom is pregnant and has infection, hydrocephalus is a  possible complication complication in the baby, which can be brought about by other diseases as well

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Round worm

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 Ascaris lumbricoides. lumbricoides. Earthworm found in humans (bolus of ascaris) If there’s too many, it may cause intestinal obstruction or creep up to gall bladder, to esophagus Worst case sir has seen: when he was doing an otoscopic exam because kid was complaining of ear pain. Hence, the earthworm can migrate to any part of the body especially if there is too many of them

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MECHANISM OF INFECTIOUS DISEASES PART II o

Flat worm

PATHOLOGY Ectoparasites make you as source of food and unlike mosquitoes, they will stay with you If you want to be infected: Pediculus capit capitis is Head lice or “kuto”: Pediculus  Sarcop opte tess scab scabie ie Etiologic agent of scabies: Sarc corpori s Sexually transmitted: Pediculus corporis o Has same genus as in conicculus pubis- crabs Others: Flea- purgas (vector) Tick-garapata (vector) Bed bugs – surot 

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Diphyllobotrium latum. 10m long, cestode or a tape worm Diphilomotrium in between cestode and trematodes  scolex  ex  which is the head of the Important part is the scol cestode where all segments come from Treatment: anticestode, look for scolex, do not stop until scolex is not found. Ask patient to collect all stools If you eat the egg, nothing happens to you because the egg will not infect you and you only get infected when you ingest salmon Pleocercoid larvae is the infective stage of diphilobotrium. It is the white stuff found in Salmon which is not advisable to eat Trematodes and Cestodes have several hosts for it to complete its life cycle

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Pediculus capitis

Sarcoptes scabies.

Pediculus corporis.

Echinococcus granulossus/ Hyatid cyst

II. SPECIAL TECHNIQUES FOR DIAGNOSING INFECTIOUS AGENTS Molecular diagnostics to measure treatment and progress of the disease through the following: o Nucleic acid amplification PCR NAT Transcription-mediated Transcription-mediated amplification 

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Shortest tape worm Has 3 segments Scolex Immature proglotids Mature proglotids Life cycle: dog eats prey which is infected by cyst Not common in the country Cystic larval stages found mostly in liver and lungs

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Seen in the picture is the liver with space occupying lesion that can only be removed surgically

G. Ectoparasites Mostly arthropods like ticks, scabies, genital “crabs”, bedbugs Can also be vectors for diseases Insects Arachnids Difference is in the number of legs, but other than that, they are both insects 

Silver stain – for fungi, legionella, pneumocystis (a fungus) Wright stain is used in the Philippines instead of Giemsa

III. NEW AND EMERGING INFECTIOUS DISEASES

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MECHANISM OF INFECTIOUS DISEASES PART II

PATHOLOGY 

Emerging infectious disease threats such as Nipah virus and Hantavirus

V. TRANSMISSION AND DISSEMINATION OF MICROBES Droplet Oral fecal route Direct Contact Anthroponotic Anthroponotic (human to human transmission) transmission) Zoonotic (men are incidental hosts)     

Transmission of Microbes: Innate Physical b arriers  

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HTLV3: HIV Staph aureus can manifest as toxic shock syndrome Hepatitis E as enterically transmitted hepatitis where incidence high in Japan because of blood transfusion, catched through oral fecal means, or through pork

IV. AGENTS OF BIOTERRORISM Category A, B and C (go through this for board exam) High mortality with category A Category B: Morbidity more than mortality Category C: Still under research

A. Skin The only way to get through skin is through pores. Secretions help us prevent colonization of bacteria. There is a purpose why you sweat or smell like so, and bacteria enhances that. We are trying to suppress all these things so normal flora is needed. o Normal flora o Potential opportunists o Damage a. Burns, cuts, penetrating injuries b. Needle sticks c. Vectors  Anopheles mosquito: mosquito: vector vector for malaria malaria and and filariasis filariasis and west nile virus  Aedis aegypti: aegypti: tiger mosquito, mosquito, vector vector for dengue dengue virus (bites in the morning) Kissing bug: bites at mucocutaneous junction, vector  for trypanosoma trypanosoma cruzi (leads to to Chagas disease) disease) Blood sucker: Tse Tse fly (don’t pronounse the “T”)  prevented Africa Africa from becoming Muslim-ize Muslim-ized  d  o Intact skin a. Larval penetration Swimmer’s itch – Cercarial dermatitis (schistosomal  parasites/trematode  parasites/trematodes) s) Blood fluke: has to penetrate skin, resides in superior, inferior hemmorhoidal vein. If you are reactive to it, when you swim in Leyteand Mindanao pools infected by Cercaria, “pag ahon mo, puro larval penetration”  Schistosomiasis 

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Category A Diseases/Agents Diseases/Agents Anthrax (Bacillus anthracis) Botulism (Clostridium botulinum  toxin) Plague (Yersinia pestis) Smallpox (Variola major virus) Tularemia (Francisella tularensis) Viral hemorrhagic fevers (filoviruses [Ebola, Marburg] and arenaviruses [Lassa, Machupo])

B. Category B Diseases/Agents Brucellosis (Brucella sp.) Epsilon toxin of Clostridium perfringens Food safety threats (e.g., Salmonella sp., Escherichia coli  O157:H7, Shigella ) Glanders (Burkholderia mallei) Melioidosis (Burkholderia pseudomallei) Psittacosis (Chlamydia psittaci) Q fever (Coxiella burnetti) Ricin toxin from Ricinus communis (castor beans) Staphylococcal enterotoxin B Typhus fever (Rickettsia prowazekii) Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis]) Vibrio cholerae, Water safety threats (e.g., Cryptosporidium parvum) 

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Category C Diseases/Agents

Cutaneous Larva Migrans a. Filariform larvae Hookworm – Ancylostoma and Necator Hookworm is a round worm but very tiny. Yung sarado ang bibig (closed): infective stage of hookworm. If it Is ope, it is in the feeding stage (rhabdidiform). If you have a high hookworm burden load, you become anemic. B. GIT o Gastric acidity, bile and pancreatic enzymes o Mucosal antimicrobials – Defensins o

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MECHANISM OF INFECTIOUS DISEASES PART II o

PATHOLOGY

Normal flora a. Bacteroides b. E. coli  o Secreted IgA by the MALT-M cells o Resistant to gastric acid and digestive enzymes a. Helicobacter pylori o Enterotoxin production a. S. aureus b. Vibrio cholera and toxinogenic E. coli  o Invasive a. Shigella, Salmonella and Campylobacter o Kill the n ormal flora a. Pseudomembranous colitis Clindamycin and cephalosporins cephalosporins o Toxocara and Anisaki o Diagnosis may involve direct fecal smear o Trichimela spiralis nematode with separate sexes will exist in muscles—it is waiting for its definite host which is the dog. Man is an incidental host. Its target are the rats eaten by dogs and wolves.

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Sexually Transmitted Infections (STI): syphilis, gonorrhea (extremely painful in males since it sloughs off the cellular lining and the lesions come in contact with acidic urine), Herpes simplex, Trichomonas vaginalis ( least painful one)

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C. Respiratory Tract

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Main protecting thing: pseudostatrified pseudostatrified ciliated epithelial cells Influenza Virus o Has been around for a long time; the Spanish flu is believed to have been a strain of influenza virus o Hemagglutinin facilitates viral entry o Neuraminidase facilitates virus release from cells Impairment of ciliary activity H. influenza, Bordetella pertusis and Mycoplasma Mycoplasma pneumonia Rhinovirus – only in the upper airway It is the most common cause of cold. It does not bring about pneumonia, and can only live on external passages Mycobacterium tuberculosis o Cystic fibrosis is a complication o For small microbes that are too small to pass through your primary barriers, your alveolar macrophages (laden with hemosiderin) serve to defend your body 

D. Urogenital Tract Urinary tract infection (UTI) Escherichia coli (common cause, an normal flora) Ascending infection with Pyelonephritis (infections in this region will obviously follow the path of urine) Pyelonephritis (bacterial infection of the kidney) Pelvic inflammatory disease   

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Treponema pallidum causes syphilis. It will disappear after a  few weeks, but in a matter of 6 months to 2 years, you develop skin lesions. Wait until 10 years, until you end up in national orthopedic hospital or national mental institute gonnorhea , pus is coming out of urethral meatus In Neisseri a gonnorhea in males. Another form: what’s coming out is a watery material but unlike females, males do not secrete anything unless sexually stimulated  Chlamydia trachomatis Herpes simplex type 2: with painful-as-hell blisters, but will resolve even if untreated, but can still be transmitted and reactivates once immune system drops; a sexually transmitted disease; once you get infected, you get infected for life (whether immune system is good or not) Trichomona vaginalis: frothy white secretions in the cervix  Females are more prone to UTI as it depends on length of urethra. Manner by which infection is introduced is through urethra. Kidney is always sterile, and urine in urinary bladder is sterile. There is ascending infection. Screen for HIV Patients with prior STDs are more likely to transmit if their hygiene is bad  HIV virus is big! Can a condom stop a virus? Do you think that is closed or rather thick as a barrier enough to prevent virus  from getting through that plastic material? A virus which you can only see through EM? Do you think a condom could really help? YES. Viruses are obligate intracellular parasites. HIV lives in lymphocytes which are blocked by the condom Cervicitis-inflammation of the cervix  Endometritis- inflammation of endometrium Salphyngitis – inflammation of fallopian tubes Inflammation   repair/   repair/ fibrosis  block  block fallopian tubes  Ampulla  Ampulla of fimbriae fimbriae of fallopian fallopian tubes tubes   Uterus  Uterus (pag may  fibrosis, it it may allow allow sperm to to go through through fallopian fallopian tube tube but it cannot allow the zygote to go to the uterus because of  fibrosis)  ectopic   ectopic pregnancy 

Dissemination of Microbes Fetal Infection

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MECHANISM OF INFECTIOUS DISEASES PART II 

Gonorrhea causes Ophthalmia neonatorum. (See picture below)

PATHOLOGY 4.

5. 6. 7.  

Chlamydia trachomatis Herpes simplex 8.

Placental Fetal Route HIV Syphilis Hepatitis B Rubella causes congenital heart disease, mental retardation, retardation, cataracts, or deafness Cytomegalovirus - Congenital malformations You can get STD if you swallow sperm Gononorrhea can also lead to gonorrhea proctitis Protoscopy= looking through the anus 

Fetal Infection may be caused by: a. Herpes simplex b. Gonorrhea c. Chlamydia trachomatis d. a and c e. All of the above Toxoplasma gondii cysts can be found in the brain. True or False. Helminths are highly differentiated unicellular organisms. True or False. Cutaneous Larva Migrans is caused b y various nematodes such as Necator, Ancylostoma, and Strongyloides. True or False. Ciliary activity may be impaired impaired by H. influenza, Bordetella Bordetell a pertusis and Mycoplasma pneumonia. True or False.

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1. C

2. E

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4. D

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Local Dissemination Dissemination Skin, Lymph nodes, Vascular system, Nerve tissue 

Vectors Anopheles mosquito – malaria Aedes aegypti (Tiger mosquito) – dengue Tsetse fly – sleeping sickness (Trypanosomes) Triatoma bugs – suck blood    

Protozoa Amoeba Sporozoa Flagellates

VI. QUESTIONS AND ANSWERS 1.

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Which of the following does not characterize Fungi? a. Eukaryotic b. Capable of sexual reproduction c. Its cell membrane possesses chitin d. Has ergosterol e. None of the above Which statement is correctly matched? a. Tinea cruris = scalp b. Tinea capitis = body c. Tinea pedis = nails d. Tinea unguium = feet e. Tinea manuum = hand All of the following are Category A agents of bioterrorism except? a. Viral Hemorrhagic Fever b. Viral Encephalitis c. Botulism d. Smallpox ENCARNACION. FERRARIS. LEGASPI. MONTELIBANO. MENDERO. NGO. RAMOS. REVOTE. VILLEGAS  

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