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 re-engagement 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. ⅓ 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 form”droplet 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 ● ; ; : : 1 : ; ; ;1 ● 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)

● less severe than primary infection; HSV-2 more prone to recur ● usually no systemic symptoms ● recurrences less frequent after first year 2. 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: ()- ;1 (,- (,- : 2 : ; ;2

: : 1 ; 1 ;1 : 22 ; (,- : 1 ;1 : ;2 ; ()- 1 ;1 ; ; ;2 ()-1 ; 2 1 ; 2 1 : ()- 1 ;1 ; ; ;2

2 ; 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)—don’t 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