WEEK 7 The epidemiology of HIV in LAC and Local response

HIV
-Virus that invases human host to produce a deficiency in host immunity
-invades and reproduces inside immune system cells (CD4-T lym.)
-symtom: fever, fatigue, sore throat, weight loss, swollen lymph nodes
-immune sys. fails 6-10 yrs -> AIDS
-opportunistic infections: pneumocystis, pneumonia, kaposi sarcoma
-ELI/ELISA test for antibody(blood/ saliva)
Transmission modes:
-sexual intercourse
-blood-to-blood
-perinatal(mother to infant)
*body fluid includes blood, semen, vaginal mucus, breast milk, rectal mucus.
Treatment as prevention(to reduce forward transmission)
-couples with HIV+ partner on immediate ART had a 96% reduction in HIV transmission
-mechanism: supperssion of HIV in geniral secretions
Programs:
TLC+(Testing, linkage, care and treatment) Framework and Programs
-HIV+ --linked to care --reengaged in care --retained in care --adherent to ART --suppressed
transmission
-Goal: to re-engage lost HIV clinic patients
-Identify pt. from HIV clinics medical record and HIV surveillance database; enroll them in reengagement intervention
- Intervention: DHSP/APLA SIF Navigation Pilot Program
-Lesson learnt
-a tiered re-engagement intervention is necessary
-use surveillance data to identify patient in/out of care
-transitional retention may help improve long term care retention
Project Engage: to locate and link hard-to-reach HIV+ persons who are out of care
Goal: to test the effectiveness of two techniques for identifying marginalized HIV-infected
persons who are out of care
-social network(snowball sampling)
-direct recruitment(flyers, word of mouth)
Limitation
-limited ability to effectively compare recruitment strategies
-no formal intervention offered
-data collection is still ongoing and retention rates at 6 months are preliminary
-snowball sampling revealed shallow recruitment waves
Improvement
-will contain tiered intervention strategy
-will contain both street outreach and clinic based portion to capture both clients
-will rely on surveillance to target those most in need of linkage services

Summary
-MSM disproportionately impacted
-HIV rates higher, although decreasing in African American
-large# of Latinos with HIV
-increasingly, LAC HIV+ population is older
-HIV+ persons live longer
WEEK 8-1 M. Tuberculosis
TB
-diverged from common bacterial ancesor of Mycobacteria
-approx. of world population infected
-Species of Mycobacteria
M. tuberculosis: man
M. bovis: cattle, man
M. leprae: man
M. africanum: man, monkey
Characteristics of M. tuberculosis
-slightly curved
-acid fast- resists decolorization with acid/alchohol
-mutiples slowly(every 18-24 hr)
-thick lipid cell wall
-can remain dormant for decades
-aerobic
-non-motile
Transmission of M. tb
-person-to-peron (through air)
-less freq. transmitted by -ingestion of M. bovis found in unpasteurized milk;
-labortary accident.
-millions of tubercle bacilli in lung
-coughing projects droplet nuclei into the air
(-large droplets settle to ground
-smaller formdroplet nuclei, which can be remained
airborne)

-70% infected(5%early progession; 95% latent TB); 30% not infected(innated immunity)
after exposure
Infection of macrophages
-intracellarly
-MTB prevent acidification of phagosome
-MTB multiplies for weeks in alveolar macrophages
Latent TB infection:
-not ill
-not contagious

-normal chest x-ray

-skin test +
-tb bacilli dormant but alive
Spread of other parts of body
lungs; pleura; central nervous system; lymph nodes; genitourinary system;bones and joints;
disseminated.
More chance to get infected when:
-coughing, smear+; cavitary diease
-no UV
-indoor with poor air circulation
-greater time with infectious particles
Factors of infectiousness:
-infectivity of contact
-host immunity system
-dose
-time
-droplet size
*High risk latent groups: known contact person with TB; children, young adult, elderly;
jails,prisons; homeless; drug treatment centers; high prevalence area
*High risk reactivation group: HIV-infected; with a history of prior, untreated TB; recent
infection; IDUs; Age(very young/old)
*High risk group for active disease: same as latent groups,+malnourished
*High risk for progression: persons with Diabetes mellitus; chronic rental failure; solid organ
transplantation; certain type of cancer; gastrectomy; underweight/malnourished.
HIV & TB
-increased risk of reactivation
-more likely to have early progession to TB diesease following infection
-TB can occur at any point in the progession of HIV infection
-high risk of recurrent TB
reactivation VS relapse?
reactivation: persons more likely to progress from LTBI to active TB.
BCG vaccine
Current therapy:
-isoniazid
-rifampin
-pyazinamide
-streptomycin
-ethambutol
-thiacetazone
-DOT: direct oberved therapy

-gov. power to quarantine

*treat for at least 6 months with multi drug therapy
*Risk factos for Multi-drug resistance: homeless, drug use, HIV, living or travel in an area
with high prevalence of MDR

WEEK 8-2 Emerging infectious disease: Mad cow& SARS

EIDs
-virus over-represented
-helminths under-represented
-recent cases usually RNA virus
-Taxonomically broad host range
-Phylogenetically conserved cell receptor
-Transmissible between humans
-Occurring in regions undergoing ecological, demographic, or social change
-Species jumps by pathogens require: opportunity and capacity
-Recent species jumps(mostly RNA viruses) adapt to new hosts
-Prion causes new variant
Mad Cow Disease(BSE:Bovine Spongiform Encephalopathy)
-in England
-cattle lose ability to walk straight , then cannot stand
-victims brains filled with holes like a sponge
-caused by a prion related to the scrapie agent
-agent been transmitted to humans

Prion Dieases
-Nonhuman diseases:
-Scrapie: (sheep)
-TME (transmissable mink encephalopathy): mink
-CWD (chronic wasting disease): muledeer, elk
-BSE (bovine spongiform encephalopathy): cows
-Human diseases:
-CJD: Creutzfeld-Jakob Disease
-GSS: Gerstmann-Straussler-Scheinker syndrome
-FFI: Fatal familial insomnia
-Kuru
-Alpers syndrome

CJD & BSE

-Human infection with BSE= variant CJD
-Variant CJD:
-Age: <42 years.
-Psychiatric symptoms followed by neurological deficits.
-Prolonged course.
-Pronounced amyloid deposition.
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-Transmission: blood transfusion; tissue transplantation

-Test: very $$$; takes two weeks to get result; only european and japanese offer 4-6 hr
result
Pre-requisites for the start of pandemic
-A Novel organism must emerge to which the general population has little or no immunity.
-The new virus must be able to replicate in humans and cause serious illness.
-The new virus must be efficiently transmitted from one human to another.
SARS
-Pandemic potential, epidemic since the end of 2003
-animals with SARS isolated
-pandemic savers: asymptomatic cases not improtant; hyperspreader not common; airborne
spread(asymptomatic ppl are impossible to get SARS)
Virus linked to bats (viruses can replicate in bats without harming the bat)
-rabies and other lyssaviuses
-nipah and hendra viruses
-ebola
-marburg virus
Tasmanian devil disease
-live only in Tasanania, extint in autralia because of dingoes
-facial tumors
-spread by cell from animals to animals
-population not genetically diverse
-disease free isolated colonies established
WEEK 9-1 West Nile Virus Infections

Overview:
Agent: Eastern/Western Equine, West Nile viruses
Incubation: 5 -15 days
Reservoir: unknown, probably wild birds
Transmission: bite of infective mosquitoes

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Diagnosis: serologic tests (detecting IgM Ab);
false
positive: people immunized against or with history of yellow fever, Japanese Enceph
or dengue
Treatment: supportive
Prevention: mosquito avoidance/ abatement (habitat elimination; personal protection)

Transmission:
blood transfusion
soft tissue transplantation
intrauterine infection
breast feeding
percutaneous exposure
mosquito bite
Epidemiology:
worldwide distribution
primarily outbreaks of febrile illness in: soldiers, children and healthy adults
1937 first identified; 1999 USA (NYC)
80% asymptomatic infection, 20% febrile illness, <1% west nile neuroinvasive
disease (aseptic meningitis, encephalitis, acute flaccid paralysis), <1% mortality rate
risk factors for neuroinvasive disease: advanced age; diabetes; possibly
hypertension
Birds & WNV:
virus maintained bird-- mosquito-- bird cycle;
WNV replicates well in birds;
life-long immunity;
dead bird surveillance as a predictor of local WNV activity.
Clinical manifestations:
80% asymptomatic infection
20% febrile illness: mild dengue-like illness; duration 3- 6 days; fever,headache, rash
and fatigue
<1% neuroinvasive disease: meningitis, encephalitis, acute flaccid paralysis
syndrome
Predictors of death among WNV-infected patients: change in level of consciousness;
encephalitis with severe muscle weakness; advanced age; possibly diabetes mellitus
or immunosuppression
WNV surveillance:
including humans, birds, horses,mosquito pools and other species;
nationwide

WEEK 9-2 Plague

Overview:
Agent: Yersinia Pestis
Incubation: 2--6 days
Vector: Xenopsyila cheopis(flea)
Transmission:
bite of flea from infected reservoir animals
direct contact with infectious secretions or tissues
inhalation of airborne droplets
Plague presentation:
Butonic: fever, lymphadenitis
Septicemic
Pneumonic
Diagnosis: direct examination of smear; FA test of smear; culture; serologic tests
Treatment: streptomycin-drug; drainage of buboes; isolation
Prevention:
Flea control, followed by rodent control
surveillance testing of rodents
vaccine for high risk persons
screening and prophlaxis contacts
Notify Public Healgh
Endemic Typhus Fever
Overview:
Agent: Rickettsia typhi
Incubation: 1-2 weeks
Reservoir: rats, other small mammals
Transmission: bite of infected flea, flea faces on abraded skin
Presentation: fever, headache,chills prostration, myalgia, rash
Prevention: flea and reservoir animal control
WEEK 9-3 Lyme Disease
Overview:
Agent: Borrelia burgdorferi
Incubation: 3-32 days for early disease; several months for later manisfestations
Reservoir: deer, rodents and their ticks
Transmission: bite of infected tick
Presentation: fever, aches,fatigue (early); arthritis, cardiac conduction defects,
neurologic manisfestations (late)
Prevention: avoidance of tick bites
WEEK 10-1 Malaria
Overview:
highest priority for eradication, biggest challenge

interaction of three complicated genera

most prevalent in the poorest places
~ 1 million human deaths annually: >90% in Africa; mostly in children under 5; one
death every 20~30 s
five species of plasmodium; causes in humans
immunity appears slowly; not fully protective; wanes
Anopheles: the only alternative host for Plasmodium species; only a small proportion
can transmit Plasmodium

P. falciparum: A medical emergency. so dangerous?

ability to infect all age of RBCs
higher multiplication capacity
sequestration
capillary leak syndromes
end organ failure
clinical falciparum syndromes:
asymptomatic or usual symptomatic infection
tropical splenomegaly
gradual progression of organ-specific symptoms to death: cerebral malaria; acute
pulmonary edema, acidosis,hypoglycemia; severe anemia(peak incidence:6-24m),
shock, renal failure.
acute emergency rapid onset of organ-specific symptoms
malaria endemicity:
hypoendemic: little transmission, variable transmission by season/year, low
prevalence: spleen/parasitemia < 10%
mesoendemic: variable transmission intensity between subtropical rural communities:
spleen/parasitemia 10%--50%
hyperendemic: intense but seasonal transmission, immunity insufficient to prevent
symptomatic disease at any age: spleen/parasitemia 50-75%
holoendemic: perennial transmission, with cumulative immune protection with age:
spleen/parasitemia > 75%
Determinants of syndrome:
Agent: species; does; proportion of red cells targeted; new infection superimposed on
recrudescence; mutiple antigens
Host: age; pregnancy; parity; iron deficiency, VA, co-infections; Ab production;
splenic, lymph node phagocytosis; cytokine cascades; genetic traits for hemolytic
disease
Diagnosis:
based on microscopy (gold standard);
lab diagnosis are labor intensive
Treatment:
community health workers are key
chloroquine safe, effective, and cheap
artemisinin combination therapy more effective
Prevention:

reducing the prevalence of reservoirs: symptomatic treatment; mass screening and

treatment
reducing access to reservoirs: residual insecticide spraying; insecticide bed nets
reducing level of transmission: gametocytecides; blood-born insecticide and
sporontocides
reducing vector prevalence: environmental water management; draining/larvacide
breeding sites; stocking fish to eat larvae; spraying sporontocides
reducing vector survival:insecticides; genetic methods
reducing host susceptibility: vaccine (development slow and cost)
Temporary solution for control: cheap impregnated bednets, isolating susceptibles;
surveillance! gradual improvement of local vector control! economic development!

WEEK 10-2 Disease Eradication

Eradication: find the weak link; intervene maximally; maintain surveillance
Successful eradication:
1. smallpox: why?
high case-fatality
effective vaccine
easy surveillance: laypersons recognize
human reservior
transmission only at the bedside
incubation gives time to identify those at risk
no other reservoirs
2. dracunculiasis: succeeding
others potentially eradicable:
Polio:
important cause of death and disability
problems: religious concerns about vaccine; less vaccinated subgroups
Guinea worm :
soon to be eradicated without a vaccine; clean water from tube wells; Sudan and
Ghana
spread from copepods in stagnant water
problems: villagers rely on open water tanks; boring well is expensive; war in Sudan
Measles:
excellent vaccine; eradicated in US and Latin America
problems: extremely infectious; in developing countries, most cases<5 yrs; narrow
window for comprehensive vaccination; vaccine must be refrigerated; concerns about
autism
Leprosy;Filariasis; Malaria; Onchocerciasis; Chagas;Yaws; Rubella
Not potentially eradicable:
cholera-inactive in marine copepods
TB- surveillance insensitive
plague animal reservoirs
tuleremia-animal reservoirs
meningitis-infections by droplet, most asymptomatic

WEEK 11 Herpes
background:
chronic, lifelong viral infection
two types: HSV-1 & HSV-2
the fourth most common STD in the USA
Virology:
infection persists, often with recurrency
virus remains latent indefinitely
reactivated virus may cause a cutaneous outbreak of herpetic lesions or subclinical
viral shedding
Transmission:
sexual & vertical
most asymptomatic
more efficiency from men to women
all infected persons have asymptomatic viral shedding
Neonatal herpes:
55% caused by HSV-2; clinical diseases manifests at 3-30 days of age
90% of transmission occurs at time of delivery
risk factors: primary infection; scalp electrodes
HSV-1:
mostly orolabial
an increasing proportion of cases of primary genital herpes are cased by HSV-1
highest incidence in childhood
HSV-2:
Background:
almost genital; oral infection<5%
Causes > 95% of recurrent genita herpes
76% of persons with HSV-2 antibody also have HSV-1 antibody
seroprevalence is higher in women than men in all age groups and varies by race
Transmission:
sexually and perinatally
70% of transmission during asymptomatic viral shedding
sexual transmission is more efficiency from men to women than from women to men.
longer duration of infection, less possibility of transmission
incubation period: 2- 12 days (average 4)
inactivate HSV: drying, soap, water
Risk factor:
lifetime # of sex partners
female
African American
older age
clinical manifestations:
1. Recurrent symptomatic infection: Ab present; disease usually mild and short
Withour treatment:
prodromal symptoms common
lasts 5- 10 days; recurrences more frequent if primary episode was longer (>30 d)

2.

less severe than primary infection; HSV-2 more prone to recur

usually no systemic symptoms
recurrences less frequent after first year
Asymptomatic infection: serum Ab present
20% asymptomatic; 20% recognized symptoms; 60% unrecognized symptoms
asymptomatic viral shedding: most HSV-2; high frequency in first year
risk for shedding: white race; symptomatic & more recurrences per year

HIV & HSV:

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Diagnosis:
clinical diagnosis: insensitive and nonspecific
lab:
virologic tests: culture; DFA/ELISA; PCR(high sensitivity and specificity)
serologic tests:
Treatment:
Episodic vs. suppressive RX
1. episodic therapy decrease: healing time; pain; shedding; outbreaks
2. short (1-3 m) or long-term suppressive therapy decreases: frequency and severity of
symptomatic recurrences; sub-clinical shedding and viral DNA copies; risk of
transmission;
Prevention:
condom effiency!
disclosing HSV-2 serostatus to partner;
daily suppressive treatment;
no effective vaccine (arguments for vaccine)

WEEK 12: Antibiotics and resistance

Importance
-change in death %, especially in heart infection
Antibiotics resistence problems
-target the ESKAPE bacteria
-Enterococcus (VRE)
-S. aureus (MRSA)
-Klebsiella
-Acinetobacter
-Pseudomonas
-ESBL (e.g., E. coli, Enterobacter)

CRE(Carbapenem Resistant Enterobacteriaceae)

-current: most states have CRE
-cause mortality rate 32-44%
-superbug
E. coli & Quinolones resistance
-Quinolones was used for outpatient gram neg infection for > 40 yrs
->10%-20% resistant now
-Cystitis: recommented nitrofurantion or fosfomycin
-Pyelonphritis: no replacement yet

Microbes vs Humans
-mircrobes: cross-phylum
humans: intra-species
-Equivalent adaptability would require capability to exchange DNA with chimpanzee;
orangutan; grizzy bear/ killer whale; falcon/great white shark
-microbes have been creating and defeating antibiotics for millions of yrs > human known
antibiotics
-There are already spread in nature, resistance mechanisms to antibacterial agents we have
not yet invented

Antibiotics
-animal use > human use
-staggering amount of environmental contamination- 15 million kg per year
-shorter treatment is as good as longer ones
-fear drive abuse
-fear based on diagnostic uncertainty
-rapid diagnostic provide psychological reassurance to overcome the fear
-Need to align physician self-interest with public interest
-There is huge variation in antibiotic utilization across systems
-Antibiotic use should be publicly reported and payments to healthcare systems
benchmarked to reward low use and penalize high use

-Science: low hanging fruit plucked

-Economics: not a good investment
-Regulatory: R&D too risky/expensive
Future Market: (For 80 years, the traditional pharma entrepreneurial business model has
dominated antibacterial development, This model is failing; )
-the future is a defense-contractor model
-drugs are developed and can control post-marketing use

Less Potential to Drive Resistance

-Antibiotics or biologics that disarm the pathogens (decrease virulence or ability to cause
disease) without killing them
-Modulate host inflammatory response
-Sequester host nutrients (e.g., metals) that microbes need to grow
-Probiotics to outcompete pathogens

-Technological solutions (eg, diagnostics, disinfectants, vaccines)dont rely on asking

people to change behavior
-Healthcare policies that align economics with appropriate antibiotic use in humans and
animals
-New business models and regulatory reform to develop Tx for unmet need
-To stop viewing our relationship with microbes as a war, co-exisit instead