Micro Lecture 18; STD

Which are bacterial STDs?

chlamydia, Gonorrhea, and syphilis

Which are Viral STDs?

Herpes simplex type II, HIV, papilloma virus

Which are fungal STDs?

Candida albicans

Which are parasitic STDs?

Trichomonas vaginalis

Are all STDs lethal?

generally, not lethal, more morbidity than mortality (except HIV & HBV/HCV)

How are STD transmitted?

through direct sexual contact, depends on the type and frequency of intercourse and # of partners. Asymptomatic carriers are silent transmitters of STD, infection occurs in packs (individual may have multiple infections)

Vulvovaginitis (in females)

inflammation of all or part of the external vulva

Vagina infection

vaginitis

cervix infection

Cervicitis

Uterus infection

Endometritis; PID (pelvic inflammatory disease)

Fallopian tubes infection

salpingitis

Peritoneal cavity infection

peritonitis

Is there concerns of Bacterial STDs from spreading?

There is concerns for spreading from primary site to other organs like heart, brain, eyes, and joints.

Neisseria Gonorrhoeae

• - Gram-neg, bean shaped diplococci

• - Grow in chocolate agar

• - Oxidase test: Oxidase (+)

Neisseria Gonorrhoeae Virulence factors

• - Fimbriae (pili): Mediate attachment and is antiphagocytic

• - Outer membrane proteins: helps invade mucosal epithelial cells

• - Lipopolysaccharide: Induces over inflammation and tissue damage

• - IgA protease: protects microorganism from mucosal antibody IgA

• - Serological diversity: More than million types in nature

Prevalence of Gonorrhea (CLAP)

Human is the only natural host, gonorrhea is second most commonly reported infectious disease in the US 150 million cases per year in the world

Surface infections of Neisseria gonorrhoeae

• - Urethritis: Mostly symptomatic in men. 2-8 day incubation period, Dysuria, purulent discharge (drip)

• - Cervicitis: 50% of women are asymptomatic

• - Pharyngitis: Infection of the throat from oral sex

• -Proctitis: Infection of the rectum, from rectal exposure

• - Conjunctivitis: infection of the eyes in newborns of infected mother. Called Ophthalmia neonatorum, may lead to blindness if untreated and can be treated with silver nitrate or erythromycin drop at birth

Invasive/ systemic infections of Neisseria gonorrhea

Happens in 10% if infected women who do not get treatment.

• - Pelvic inflammatory Disease (PID); Infection of the female reproductive organs. The rate is highest amongst teenagers, may be asymptomatic two-thirds of the time.

• - Salpingitis: inflammation of the fallopian tubes. Symptoms are Fever, flank pain, painful sex, discharge, abnormal bleeding. Gonococci cause about 40-60% of salpingitis cases.

• -Peritonitis: Infection that spreads beyond the fallopian tubes into the peritoneal cavity

Why is PID dangerous?

Can cause scarring inside the reproductive organs. This can scaring can block or damage the fallopian tubes, potentially leading to infertility.

Disseminated gonococcal infection (DGI)

This is when gonorrhea goes untreated and is spread through the blood to other parts of the body. Which can cause:

• - Arthritis: joint inflammation and pain, which can lead to deformity

• - dermatitis: skin lesions or rashes

• - Conjunctivitis: Inflammation of the conjunctiva

The bacteria can spread beyond the original infection site and cause problems in multiple areas in the body.

Diagnosis of Neisseria gonorrhoeae

based on symptoms like discharge; gram stain the discharge, more difficult in females (need additional tests like Oxidase test)

Therapy of Neisseria gonorrhea infections

For the treatment of uncomplicated urogenital and anorectal gonorrhea, CDC now recommends a single intramuscular dose of Ceftriaxone (cephalosporin) or oral doses of other types of Cephalosporines.

• - Persons with gonorrhea should be tested for possible coinfection with chlamydia trachomatous.

• - If positive, treat with a single dose of Azithromycin 1 g by mouth or with Doxycycline: 100 mg twice a day by mouth for 7 days.

Prevention of Neisseria gonorrhea infections

Long term mutually monogamous relationship with a partner who has been tested and is known to be uninfected. Using latex condoms can also prevent this infection.

• - Contact tracing: Notify all recent sex partners so they can see a health care provider and be treated.

• - Vaccine was unsuccessful since there are more that million types of pili antigen

Chlamydia Trachomatis Biology

Obligate intracellular pathogen (needs hosts cell in order to replicate). Have to grow them in cell cultures. Gram negative structure has no cell wall (PG). Has 2 forms of complex developmental life cycle.

What are the 2 forms of Complex developmental life cycle related to chlamydia trachomatis?

1. 1. Elementary body: is not biologically active, resistant to environmental stresses and can survive outside of a host. Infectious form which converts to reticulate body once in the cell.

2. 2. Reticulate body: Biologically active, dividing form. Noninfectious form which converts back to elementary body.

Virulence of Chlamydia trachomatis

Prevents phagolysosome fusion during intracellular growth and grows within phagosomes (inclusion bodies) of host cells.

Chlamydia Trachomatis

most frequently reported bacterial STD in the United States. An estimated 2.8 million Americans are infected each year.

• - 70% of women and 50% of men are asymptomatic

How are women mainly impacted from Chlamydia trachomatis?

40% of women with chlamydia will develop PID and withing that group, 20% will become infertile and 9% will have a potentially fatal ectopic pregnancy.

• Can be transmitted at birth which may cause eye infection or pneumonia in newborns.

Surface infections of Chlamydia trachomatis in males

NGU (nongonococcal urethritis) 50% of males are asymptomatic may lead to infertility

Surface infections of Chlamydia trachomatis in females

Cervicitis; 70% of women are asymptomatic. May lead to infertility

Surface infections of Chlamydia trachomatis in females and males

leading cause of blindness in the world. Mostly in underdeveloped countries.

Surface infections of Chlamydia trachomatis in newborns

Inclusion conjunctivitis

Invasive disease of Chlamydia trachomatis in males

Prostatitis and epididymitis which may lead to infertility

Invasive disease of Chlamydia trachomatis in females

• -Salpingitis: inflammation of fallopian tubes similar to GC

• - PID: similar to GC, as result of ascending infection of reproductive organs

• - Sterility: chances increase with repeated episodes of PID

• - Lymphogranuloma venereum: Infection if inguinal lymph nodes which may lead to swelling of buboes and may lead to elephantiasis of the genital organs

Invasive disease of Chlamydia trachomatis in newborns

Infantile pneumonia: most common in newborn lung infection in the world. Usually not fatal

Chlamydia Trachomatis diagnosis

Can’t do gram stain or grow on agar plates, have to grow in cell culture. Can do fluorescent antibody staining (FAS), and DNA hybridization.

Chlamydia Trachomatis Therapy

Patient can take Azithromycin (zpack) 1 g orally in a single dose or Doxycycline 100 mg orally twice a day for 7 days.

What should one give to a baby with neonatal conjunctivitis?

Erythromycin by mouth (PO) for 2 weeks

Risk factors for developing PID

Having STD, usually happens to people under 25 that are sexually active with multiple partners. Also, those who douche, which can push germs into the womb, ovaries, and tubes, causing infection and it can also hide the signs of an infection. Not getting tested and treated for any infections before getting an IUD can also lead to developing.

Treponema pallidum (syphilis)

Historical STD, 15th-century epidemics

• - Spirochete: Long spiral shaped organism

• - Very motile with axial filaments. Atypical cell wall (PG)

• -Visualized by Dark field microscopy, cannot be grown in culture

IV. Treponema pallidum Virulence

axial filament allows penetration into tissues

• -pathology (3 stages of syphilis): primary, secondary and tertiary

Primary syphilis

Primary cutaneous lesion (Chancre) is usually the first sign, appearing 10 days to 3 months after exposure on the part of the body where the infection was transmitted (genital organ, rectum, tongue or lips).

• - Untreated, the chancre tends to heal spontaneously in 4-6 weeks, around which time the symptoms of secondary syphilis may occur.

Primary syphilis lesion (chancre)

Indolent, “punched out” appearance, indurated, painless, raised border, red with smooth base, and scant serous secretions.

Secondary Syphilis

Begins 2-8 weeks after the chancre heals. The bacteria spread throughout the body, causing fever, fatigue and aching. And many types of rashes, especially on the palms of the hands and the soles of the foot. These signs and symptoms may disappear within 4-6 weeks or repeatedly come and go for as long as a year.

Latent syphilis

In some people, in which no symptoms are present, may follow the secondary stage. Signs and symptoms may never return, or the disease may progress to the tertiary stage.

Tertiary syphilis

Without treatment 40% of infected individuals progresses to this type of syphilis within 5 to 20 years. The organisms spread to various organs causing lesions or Gummas. Pockets of damage accumulate in various tissues such as the bones, skin, nervous tissue, heart, and arteries. These lesions are called Gummas and are very destructive.

Some of the signs and symptoms of tertiary syphilis are

• - Neurological problems, these may include stroke, meningitis, poor muscle coordination, numbness, paralysis, deafness or visual problems, personality changes, dementia.

• - Cardiovascular problems, these may include bulging (aneurysm) and inflammation of the aorta and of other blood vessels.

Congenital Syphilis

T. pallidum can be passed from mother to child during fetal development or at birth. Newborns may be asymptomatic and are only identified on routine prenatal screening. By definition, early congenital syphilis occurs in children between 0 and 2 years old. After that, they can develop late congenital syphilis.

Diagnosis of syphilis

Dark-field microscopy of lesions. By serological techniques for detecting antibody response to T. pallidum

Therapy of syphilis

Easy to cure in its early stages. A single intramuscular injection of penicillin (Benzathine) treats all stages of syphilis.

• If a pregnant mother is identified as being infected with syphilis, treatment can effectively prevent congenital syphilis from developing in the unborn child, especially if she is treated before the sixteenth week of pregnancy

Prevention of syphilis

No vaccine. Rely on early diagnosis

STD

occur in the same individual, test for others if you see one. All bacterial STDs are treatable.

STD relation to antibiotic resistance

The prevalence of gonorrhea in the United States and abroad, especially under-developed and developing countries, has decreased in the last two decades. As of recently, though, higher rates of infection have been reported due to the increase of antimicrobial -resistant gonococci

Mycobacterium tuberculosis (TB)

Chronic pulmonary disease that is non motile aerobic Bacillus has a very lipid rich wall, they are stained by acid fast stain (acid-fast bacilli).

Cell wall structure of Mycobacterium tuberculosis

Peptidoglycan layer is bound to arabinogalactose-mycolic acid

• Cell wall is overlaid with waxy lipid, waxD

– Protects from desiccation (drying out)

– Allows bacterium to survive in dried aerosol droplets for up to 8 months

Virulence factors of M. TB

Cell wall lipids withstand phagocytic killing and cause necrosis of tissue

• Lipoarabinomannan (LAM) can induce inflammation

• Surface proteins are very immunogenic

– Induces cell-mediated immune response (CTL response)

• Cord factor is important virulence determinant

• Highly infectious (5-200 organisms can start the disease)

Primary TB

Infection of respiratory tract via inhalation of droplets from infected individuals

• Pili allow attachment to lung epithelial cells

• Alveolar macrophages phagocytize the bacteria but cannot destroy them

– Bacteria prevent fusion of lysosomes and phagosomes

• Bacteria replicate within host cells, gradually killing them.

• Inflammatory process attracts more macrophages which also become infected

• Infected macrophages trigger CTL response, recruiting T cells which form a granuloma

(tubercle)

– Tightly packed macrophages and T cells “wall off” infected area

– Collagen layer is deposited around the tubercle – Latent infection (stalemate)

Secondary TB

– Bacteria break stalemate and rupture the

tubercle

– This reestablishes the infection

Disseminated TB

Macrophages can carry the bacteria throughout

the body to various sites, including bone marrow,

spleen, kidneys, spinal cord & brain.

• Complications with infections at lung and

other sites contribute to “Wasting Disease”,

or consumption

– Bloody sputum, malaise, weight loss

Epidemiology of TB

Highly infectious (5-200 organisms can start the disease)

• Worldwide; a third of the world's population is infected with this organism

• Fewer than 15,000 new cases in United States in 2003 (mostly in AIDS

patients)

• Populations at greatest risk for disease are immunocompromised patients (particularly those with HIV infection), drug or alcohol abusers, homeless persons, and individuals exposed to diseased patients

• Humans are the only natural reservoir, Person-to-person spread by infectious aerosols

Diagnosis of TB

Skin testing (Mantoux test ):

• Reactivity of intradermal injection of mycobacterial antigen PPD.

• PPD is purified-protein derivative of bacterial wall.

• Reaction is measured after 48 hours.

• Induration of more than 15 mm is considered as positive skin test (in persons at low risk for tuberculosis)

• Positive skin test is followed up with chest x-ray

TB treatment

Cocktail of antibacterial drugs over long time courses (> 6 months due to slow growing nature of bacteria)

TB epidemiology

Cases declining in USA

– Increase in multidrug-resistant TB in third- world countries.

• Strains of M. tuberculosis with resistance to more 2 or more antibacterials

– Correlates with increase in incidence of TB in US residents of foreign origin.

– Concerns of MDR strains taking hold in US population

TB immunization

• Live attenuated Mycobacterium bovis: Bacillus of Calmette-Guerin (BCG)

– Mycobacterium bovis:

• A cattle pathogen

• Causes disease in zoo keepers

• Can cause pulmonary disease by consumption of contaminated milk but is destroyed by milk pasteurization

• Not for immunocompromised patients

• Recipients become skin test positive for TB

• Reports of efficacy of vaccine varie widely from 80% to zero

• In US, BCG vaccine is not used

– Relative low prevalence, coupled with testing and treatment

Vector-born Lyme borreliosis (Lyme disease)

Genus Borrelia are Gram-negative bacilli that are spirochetes.

• cause Lyme disease in humans

• Borrelia burgdorferi

– The leading cause of vector-borne disease in the Untied States

– Lyme disease

• transmitted by hard-shelled (Ixodes) ticks that lives on rodents, deer, domestic pets.

• Has been shown in 49 states of US

Vector-born Lyme borreliosis (Lyme disease) Virulence factors

* Bacteria can escape from blood and penetrate tissues (similar to PMN)

• Outer surface protein (OSP) is very immunogenic and triggers inflammatory responses within tissues and cause damage

Early manifestation stage of Lyme disease

Incubation period of 3-30 days

– A rash at the site of tick bite; (erythema migrans): occurs in 80% of cases

– Systemic symptoms of fatigue, headache, fever, chills, muscle pain, lymphadenopathy.

– Resolves in 4 weeks due to humoral immunity

Late manifestation stage of Lyme disease

Occurs in 80% of patients. Hard to treat

• Occurs when bacteria escape from blood to tissues and survive there but stimulate immune system which causes the damage

• Occurs within few weeks to 2 years following the onset of the disease

• Late stage has two phases (10-15% of patients and can last for days to months)

– Neurological and cardiac symptoms: meningitis, encephalitis, peripheral nerve neuropathy, heart block, myopericarditis, congestive heart failure

– Arthralgias and arthritis: persist for months to years. Autoimmune arthritis which occurs

89% in people with HLA-DR2+ and HLA-DR4+

Definition of Lyme disease clinical case

Either of the following: Erythema migrans (∼5 cm in diameter)

• At least one late manifestation

• (i.e., musculoskeletal, nervous system, or cardiovascular involvement) and laboratory confirmation of infection

Laboratory criteria for Diagnosis for Lyme disease

At least one of the following:

• Isolation of Borrelia burgdorferi

• Demonstration of diagnostic levels of immunoglobulin

(Ig)M or IgG antibodies to the spirochetes

• Significant increase in antibody titer between acute and convalescent serum samples

Helicobacter pylori

Discovered in 1993 as the cause of peptic ulcer

– Gram-negative curved bacilli with polar flagella.

– Present in stomach of many mammals including human

– Bacteria are highly motile and have several virulence factors

virulence factors of helicobacter pylor

Urease

– enzyme which catalyzes the hydrolysis of urea into carbon dioxide and ammonia

– locally raises the pH from ~2 to a more biocompatible range of 6 to 7

• Adhesins

– Mediate binding to host cells

• Tissue damaging toxins

– Cause damage and inflammation of the lining of stomach which leads to peptic ulcer

– Mode of transmission is by fecal-oral route.

– No animal reservoir

Urease

Produces ammonia which locally raises the pH from ~2 to range of 6 to 7

Adhesions

Mediate binding to cell lining of stomach

Tissue damaging toxins

cause damage and inflammation of the lining of the stomach which leads to peptic ulcer

Epidemiology of H. pylori

* 45% adults in United Stated are colonized

• 70-100% of patients with gastritis, gastric ulcers or duodenal ulcers are infected

• Associated with gastritis, gastric ulcers, gastric adenocarcinoma and gastric MALT lymphoma

• Etiological agent of type B gastritis

• Diagnosis is confirmed by histological microscopic examination of gastric biopsy with upper endoscopy

• Urease breath test relatively sensitive