Studied by 3 people
what is morbidity rate
diseased state, disability, or poor health due to any cause - incidence, prevalence, cumulative incidence of risk of developing a new medical condition
what is mortality rate
number of deaths in a particular population, scaled to the size of that population, per unit time
what Disability Adjusted Life Year (DALY)
measure of the time lived with disability and the time lost due to premature mortality
Quality Adjusted Life Years (QALY)
combines expected survival with expected quality of life into a single number - measure of the value that individuals place on expected years of survival
which infections are the “big four”
HIV, hepatitis C, malaria, and tuberculosis
examples of high threat pathogens
Ebola, several other hemorrhagic fevers, Zika, Nipah, middle east respiratory syndrome, coronavirus, and severe acute respiratory syndrome (SARS)
what is malaria
mosquito-borne parasite that infects the red blood cells of humans caused by four plasmodium parasites
which plasmodium parasites cause malaria
P. falciparum, P. vivax, P. ovale, and P. malariae
symptoms of malaria
flu-like symptoms, fever, chills, sweats, headaches, N/V, body aches, and malaise
severe cases of malaria can cause deadly complications such as:
organ failure, hemoglobinuria (hemoglobin in urine), acute respiratory distress syndrome, hyperparasitemia (more than 5% of red blood cells are infected)
treatment for children and adults with uncomplicated P. falciparum (except for pregnant women in first trimester)
artemether + lumefantrine
artesunate + amodiaquine
artesunate + mefloquine
dihydroartemisinin + piperaquine
artesunate + sulfadoxine-pyrimethamine (SP)
treatment duration for children and adults with uncomplicated P. falciparum (except for pregnant women in first trimester)
3 days
how is artemether in combo with lumefantrine administered
IM, PO
which version of artemisinin is more lipohylic
artemether in combo with lumefantrine
substrate of artemether in combo with lumefantrine
CYP3A4
how is artesunate available
IV, PO
ADRs of artesunate
hypersensitivity (1 in 3000), mild GI, rare QT, rare hepatotoxicity
T/F: caution use of artesunate in patients with renal or hepatic failure
true
family of ebola virus
Filoviridae
genus of ebola virus
Ebolavirus
what is one of the most pathogenic viruses known to science
Ebola
how is ebola transmitted
infected body fluids, through damaged skin, mucosa (eyes, nose, mouth), and parenterally through contact with blood, stool, saliva, sweat, urine, vomit, breast milk, tears, semen
clinical features of the early febrile phase of ebola (0-3 days from symptom onset)
fever, malaise, fatigue, body aches
clinical features of the GI phase of ebola (3-10 days from symptom onset)
primary: epigastric pain, nausea, vomiting, diarrhea
Associated: persistent fever, asthenia, HA, conjunctival injection, chest pain, abdominal pain, arthralgia, myalgia, hiccups, delirium
clinical features of shock or recovery phase of ebola (7-12 days from symptom onset)
shock: diminished consciousness or coma, rapid thready pulse, oliguria, anuria, tachypnea
recovery: resolution of GI symptoms, increased oral intake, increased energy
clinical features of the late complication phase of ebola (>/= 10 days from symptom onset)
GI hemorrhage, secondary infections, meningo-encephalitis, persistent neurocognitive abnormalities
T/F: there is possible transmission after clinical recovery of ebola through sexual contact (semen)
true
what is the M. tuberculosis complex
includes the tubercle bacillus (M. tuberculosis), M. bovis, M.africanum, M. microti, M. canetti, M. caprae, M.pinnipedii, and M.orygis
what is the major constituent of the cell envelope in M. tuberulosis
mycolic acid, a beta-hydroxy fatty acid (this structure defines the genus)
which infection has a slow growth rate?
M. tuberculosis complex ~20-24 hours
how is tuberculosis transmitted?
person-to-person, inhalation of droplet nuclei (airborne particles 1 to 5 microns in diameter)
what procedures result in droplet nuclei associated risk for transmission of TB
endotracheal intubation, bronchoscopy, sputum induction, chest physical therapy, administration of aerosolized drugs, irrigation of TB abscess, autopsy
risk factors in America for TB
substance abuse, nutritional status (underweight, vitamin D, iron status), systemic diseases, immunocompromised, household contacts, birth in TB-endemic area, community settings (homelessness, crowding), socioeconomic status, minority groups, increasing age, male gender
TB pathogen characteristics
acid-fast bacilli, may stain blue or not at all with traditional methods, unique cell wall, and slow-growing
what does MTB do in the body?
blocks fusion of lysosome and phagosome which prevents bacterial hydrolysis
T/F: onset of active TB can occur many years following a period of latent infection
true
screening for TB
PPD/TST for latent disease, Interferon-gamma release assay (IGRA)
what does a PPD/TST test of < 5 mm indicate?
AIDS patient with known close contact to active TB patient
what does a PPD/TST test of > 5 mm indicate?
positive in HIV+ patients, close contact of active contagious disease, abnormal chest radiograph, immunosuppressed patients (chemo, transplant, steroids, TNF-a inhibitors)
what does a PPD/TST test of > 10 mm indicate?
clinical conditions that risk reactivation (diabetes, dialysis, malignancies, IVDU, etc.), children less than 4, foreign born from country with high prevalence, residents/employees in high risk settings
what does a PPD/TST test of > 15 mm indicate?
healthy individuals four or older with low likelihood of TB
CDC recommended screening for children < 5 years old
IGRA is acceptable but TST is preferred
CDC recommended screening for TB if difficulty testing or BCG
IGRA preferred, but TST is acceptable
when can there be false negatives for TB
immunosuppression, evidence of natural waning of immunity, anergy testing with mumps or candida not recommended, measles suppressed tuberculin activity (postpone TST 4-6 weeks after MMR)
when can there be false positives for TB
non--tuberculous mycobacteria, BCG vaccination (childhood BCG vaccination is not a major cause of positive results in adulthood, prior BCG vaccination may be associated with boosting), TST reactivity caused by BCG sensitization can be distinguished from latent TB infection by IGRA
treatment for latent TB disease
isoniazid 300 mg PO daily x 9 months (900 mg PO BIW with DOT 9 months)
what needs to be supplemented in patients taking isoniazid for TB
pyridoxine
alternative latent TB treatments
rifampin 600 mg PO QD x 4 months (NYSDOH preferred regimen)
isoniazid 300 mg PO daily for three months + rifampin 600 mg PO daily for three months.
if patient has been exposed to a resistant TB virus, what should the treatment be?
one or two drugs that the patient is not resistant too: FQ + ethambutol x 12 months
clinical presentation of TB
usually asymptomatic - acute progresses to pulmonary (90% become latent)
symptoms of TB
anorexia, fatigue, weight loss, chills, fever, night sweats, productive cough (hemoptysis in advanced disease), CXR may show patchy or nodular infiltrates
diagnosis of TB
positive CXR findings lend strong suspicion, positive sputum smear (5,000-10,000 organisms/mL), MTB PCR determines species of isolated mycobacterium
how long does it take to get sputum smear results back for TB?
1-3 days
how long does it take for sputum cultures results to be back for TB?
1-3 weeks
what is the treatment duration for TB
intensive phase (two months) followed by a continuation phase (four to seven months)
first line drugs for TB
rifampin (rifabutin), isoniazid, pyrazinamide, ethambutol
how should TB drugs be taken?
on an empty stomach if tolerated, doing with food is acceptable if GI upset, preferable to divide doses or change to second-line agents
T/F: daily dosing is preferred for TB agents
true - intermittent dosing works if used with directly observed therapy (DOT)
active MTB treatment regimen 1
Isoniazid, rifampin, pyroxinamide, ethambutol daily x 8 weeks
which drugs are typically used for continuous TB treatment
isoniazid and rifampin for 4 more months
when should continuous isoniazid/rifampin treatment be extended to 7 months if:
intensive phase didn’t include pyrazinamide, patient has both cavitary pulmonary TB and positive AFB culture after intensive phase (ONE OR THE OTHER)
when can continuous isoniazid/rifampin treatment for TB be shortened to 2 month if:
HIV negative patient with negative sputum cultures, radiographic/symptomatic improvement, absence of alternative diagnosis (ALL REQUIRED)
what drugs can have increased serum concentrations if taken with isoniazid
phenytoin and theophylline
risks of isoniazid?
hepatitis and peripheral neuropathy (highest risk in poor nutritional status, alcoholism, diabetes, or uremia)
what supplement can reduce risk of isoniazid-induced peripheral neuropathy
25-50 mg daily to reduce risk
Interactions with isoniazid
food may decrease absorption and peak concentration, potent inhibitor of 2C19 and can inhibit 3A4, weak inhibitor of 2A6, 2C9, and 2D6, inhibits plasma MAO, avoid high histamine foods which may cause low blood pressure, avoid green tear with MAOIs
how long should dietary changes continue for after stoppng isoniazid
2 weeks
who is at risk for isoniazid induced neuropathy
pregnant women, breastfeeding infants, HIV infected patients, diabetes, alcoholics, malnourished patients, chronic renal failure, advanced age
if patients develop peripheral neuropathy from isoniazid what should be the pyridoxine dose
100 mg/day
signs and symptoms of hepatotoxicity
unexplained anorexia, N/V, dark urine, clay colored stool, icterus, rash, pruritus, persistent fatigue, weakness or fever lasting 3 or more days, abdominal discomfort, easy bruising or bleeding, arthralgias also can occur
MOA of rifampin
inhibits bacterial DNA-dependent RNA polymerase
when is rifampin useful
for treatment of intracellular pathogens
how can absorption be improved when taking rifampin
taking oral dose on an empty stomach
ADRs of rifampin
orang red discoloration of secretions, N/V/D, HA, fever, flu-like symptoms start 1-2 hours after and resolve 6-8 hours later, rash, itching, flushing, hepatitis is infrequent unless combined with other hepatotoxins
DDIs for rifampin
inducer of several enzymes and transporter systems (3A4, 2B6, 2C9, 2C19), weak inducer of 1A2, modest inducer of 2D6, inducer of P-gp
MOA of pyrazinamide
mechanism is unknown - considered bacteriostatic
which drug accelerates sterilizing effect of isoniazid and rifampin
pyrazinamide
ADRs of pyrazinamide
hepatotoxicity, hyperuricemia, N/V, dermatologic and hematologic more rare
how should pyrazinamide be taken in regards to food
can be taken with or without
DDI with pyrazinamide
drugs that alter uric acid levels (thiazides, diuretics, aspirin, NSAIDS), drugs that also cause hepatotoxicity
MOA of ethambutol
mechanism not well understood - bacteriostatic activity by virtue of inhibition of arabinosyl transferase (enzyme turns arabinose into arabinan and then arabinogalactan, a mycobacterial cell wall constituent)
ADRs of ethambutol
visual changes, hematologic, GI, HA, dizziness, confusion
T/F: ethambutol dose is not significantly altered by food, but is reduced by aluminum hydroxide
true
when are ADRs more likely with ethambutol
with increased length of use or increased doses
what test is recommended at baseline before using ethambutol
Snellen test
what are the second line antimycobacterial agents
levo, moxi, streptomycin, capreomycin, Amikacin/Kanamycin, P-Aminosalicylic acid, cycloserine, ethionamide
baseline lab monitoring:
SCr, visual acuity and color perception, hepatitis
routine monitoring:
liver function tests not recommended unless patient is experiencing symptoms, monthly visual acuity and color vision for patients receiving EMB at doses > 15-25 mg/kg or if continuing for > 2 months
