TB Flashcards
what are the radiologic findings in primary TB?
parenchymal involvement
lymphangitis
localized pleural effusion
regional lymphadenitis
what are the radiologic features seen in chronic pulmonary TB?
local exudative TB- most common finding focal, patch heterogenous consolidation local fibroproductive TB Cavitation- hallmark of TB reactivation Tuberculoma
hallmark of TB reactivation
Cavitation
What are the radiologic findings in miliary TB?
stippling in both lungs –> coalesce –> richly stippled pattern (Snowstorm effect)
Advantages of IGRA vs TST
IGRA is not affected by BCG single patient visit result available in 24hrs booster phenomenon does not occur TST used in children less than 5yo
what is most commonly affected in patients with musculoskeletal TB?
vertebral body
what are the 4 basic types of bone lesions in TB osteomyelitis?
cystic- most common in children
infiltrative
focal erosions
expansile lesions
TB of the joints are mostly
monoarticular; large, weight bearing joints
Triad of TB of the joints (phemister)
juxtaarticular osteoporosis
peripherally located osseous erosions
gradual narrowing of interosseous space
findings in TB meningitis (Imaging)
basal cistern hyperdensity (most specific finding)
most common complication of TB meningitis
communicating hydrocephalus
common complication: Ischemic infarct
most effective bactericidal drug
Isoniazid and Rifampicin
most potent sterilizing drug available
Rifampicin
active against rapidly multiplying TB
Pyrazinamide
used together with other drugs to prevent emergence of resistant bacili
Ethambutol
effective in reducing time to culture conversion in adults with MDR-TB
Bedaquilline
drug effective in increasing the proportion of patients achieving sputum culture concentration after 8 weeks treatment
Delamanid
inhibits mycelia acid synthesis
Isoniazid
may cause hepatitis
increased risk of hemolysis in G6PD
peripheral neuropathy
discontinue H&R if with ST/ALT >3x
inhibits DNA-dependent RNA polymerase
Rifampicin
may cause hepatitis, hypersensitivity, thrombocytopenia, orange discoloration of urine
causes disruption of membrane energy metabolism
Pyrazinamide
causes heptotoxicity
requires dose modification in renal toxicity
inhibits transference enzymes involved in cell wall synthesis
Ethambutol
causes peripheral neuropathy and optic neuritis
Fixed dose combinations
Intensive phase: Rifampicin 75mg + Isoniazid 50mg + Pyrazinamide 150mg
Continuation phase: Rifampicin 75mg + Isoniazid 50mg
mother has TB, can she breastfeed?
breastfeeding is encouraged
What to give in pregnant patients with TB
HRZE with pyridoxine (B6) at 25mg/day
pregnant LTBI at high risk of developing active TB
HIV positive
with contact history reveal tubercular conversion in 2yrs
Asymptomatic pregnant with TST positive result with chest xray
give IPT recommended for 9 months; Isoniazid for 6 months with pyridoxine
pregnant with TB disease
1st line drugs safe except Streptomycin, Capreomycin, Ethionamide, Fluoroquinolones, Cycloserine
Newborns of TB mothers:
Mother has LTBI
give BCG
Newborns of TB mothers:
mother has TB disease
if with treatment for 2 weeks or more still rule out congenital TB
If newborn is well, do not give BCG, give IPT x 3 months then perform TST
If TST negative, stop IPT then give BCG
If TST positive, give IPT for 3 months
if mother has EPTB
monitor infant for congenital TB
If suspected to have congenital TB: do TST, chest X-ray, lumbar puncture and appropriate
Even if negative, give treatment
Mother has current TB disease and no treatment received
Infant should be given Isoniazid
If TB isolate is Isoniazid-resistant: give Rifampicin
send placenta for AFB smear
evaluate for congenital TB
If initial TST is negative, repeat after 3 months
IF TST is positive but chest xray is negative, continue Isoniazid or Rifampicin to complete 6 months
If TST and chest xray are negative; completed treatment: give BCG, discontinue H & R
> /=5mm induration TST is positive in the ff:
close contact
chest xray findings suggestive of TB
clinical findings of PTB
immunocompromised state
standard treatment for pregnant women in intensive phase
Isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE x 2mos)
Pyridoxine Vitamin B6 at 25mg/day
breastfeeding encouraged
advise mother to feed baby before taking anti-TB drugs
*streptomycin avoided due to ototoxicity
Treatment for asymptomatic pregnant women with positive TST results, normal chest radiographic findings, and recent contact with contagious person
Isoniazid Preventive Treatment (IPT)
recommended duration is 9 months
begin in the 1st trimester
management of newborn whose mother has latent TB infection (LTBI)
at birth, infant not separated from asymptomatic TST positive mother with negative chest xray; should be given BCG
management of a newborn whose mother has TB disease
IF with TB disease but has undergone treatment for 2 weeks or more, presumed to be no longer infectious.
Possibility of congenital TB should be ruled out
*if newborn is well, do not give BCG first, give IPT for 3 mos then do TST.
- If TST is negative, stop IPT then give BCG
- If TST is positive baby remains well, IPT for 3 mos
- if after 6 mos of IPT, baby remains well give BCG
- If TST is not available and newborn is well, give 6 mod IPT then BCG
- if mother has not received any tx, give Isoniazid
- If maternal TB isolate is Isoniazid-resistant, give Rifampicin instead
- evaluate baby for congenital TB
- if initial TST is negative, repeat after 3mos
- if positive TST but chest xray is negative, Isoniazid or Rifampicin continued for 6 mos
- If TST and chest xray of mother are negative and tx completed, BCG should be given and Isoniazid or Rifampicin discontinued
mother has extrapulmonary disease such as tubercluous meningitis, miliary, bone or joint TB or genitourinary TB
infant must be monitored closely for possible congenital TB
- if suspected to have congenital TB, TST, Chest xray, LP, appropriate cultures
- regardless of TST result, treatment should be initiated promptly
TB in children with liver disease
LFTs should be carried out before initiating anti-TB meds, monitor ALT 2x a week during the 1st 2 weeks
then on a weekly basis until end of second month
and monthly basis thereafter till the end of treatment
- Isoniazid and Rifampicin are potentially hepatotoxic
- total dose of Isoniazid should not be more than 10mg/kg/day
TB in children with drug-induced hepatitis
- in children less than 5 yrs old with elevated transaminases less than 5x normal and asymptomatic, stopping drugs not warranted
- if GI symptoms such as nausea, vomiting, abdominal pain or jaundice noted –>hepatotoxic first-line drugs should be discontinued or modified depending on levels of AST or ALT
Drug induced livery injury definition
AST level 3 or more times than upper limit of normal in presence of symptoms or 5x more than the upper limit in the absence of any symptoms
- AST less than 5x normal = mild toxicity
- AST of 5-10x more than normal is moderate
- AST 10x or more than normal is severe
how can we restart giving of anti-TB meds for patients with drug-induced hepatitis
restarting done slowly
Rifampicin restarted first bec less likely to cause hepatotoxicity; least hepatotoxic
*if no increase in AST after 1 week, may restart Isoniazid
*if symptoms recur, last drug must be stopped
*if severe hepatitis, PZA must be discontinued and replaced by Ethambutol and INH and Rifampicin continued for 9 mos
TB in children with renal impairment
*recommended TB treatment for patients with renal failure or severe renal insufficiency; 2 months HRZE followed by 4 months HR
- Ethambutol 80% cleared by kidney
- streptomycin should be avoided in patients with renal failure
should be measured in all patients with renal disease prior to treatment
Creatinine clearance
- timing of administration is important
- Drugs administered after hemodialysis to prevent loss during dialysis
Antituberculosis drugs that are significantly dependent on renal clearance
Ethambutol Levofloxacin Cycloserine Kanamycin Capreomycin Amikacin streptomycin
*metabolites of pyrazinamide may accumulate
In severe renal impairment with creatinine clearance less than 10ml/min
- reduction of Isoniazid dose to 200mg is recommended
* Ethambutol is given 8hrs before dialysis at 25mg/kg 3x a week when creatinine clearance is between 50 to 100ml/min
cornerstone of diagnostic method for LTBI is
TST
*>5mm cut off for patients with HIV
primary diagnostic test in symptomatic people living with HIV
Xpert MTB/RIF assay
MTB culture remains a necessary diagnostic tool
Primary prophylaxis for TB in children living with HIV
- Children with HIV more than 12 months of age ; unlikely to have TB disease on symptom based screening and have no contact with TB case:
- should be offered 6 months of IPT
confirmed HIV-infected infant and children should receive CTX prophylaxis
- less than 1 year of age regardless of CD4 or clinical status
- children 1-5yrs old diagnosed with WHO stages 2, 3, 4 regardless of CD4 or any WHO stage and CD4 <25%
- less than 6 years diagnosed with any WHO clinical stage and CD4 <350
minor gastrointestinal upset, anorexia, nausea, abdominal pain
Pyrazinamide and Rifampicin
- continue anti-TB drugs, check doses
- Give drugs with small meal or just before going to bed
joint pains
Pyrazinamide
*NSAIDS
Burning sensation, numbness, tingling in the feet /hands
Isoniazid
*Pyridoxine 10mg per 100mg Isoniazid daily
Orange/red unrine
Discolored contact lenses
Rifampicin
*Reassurance
Itching, skin rash
Thioacetazone (streptomycin, Isoniazid, Rifampicin, Pyrazinamide)
*stop anti-TB drugs
deafness
Streptomycin
*stop streptomycin
dizziness, vertigo, nystagmus
Streptomycin
*stop streptomycin,, use ethambutol
jaundice
pyrazinamide, isoniazid, rifampicin
*stop anti-TB drugs
confusion
most anti-TB drugs
*stop anti-TB drugs
visual impairment
Ethambutol
*stop Ethambutol
Shock, purpura, acute renal failure
Rifampicin
*stop rifampicin
may cause petechial rash due to thrombocytopenia
Rifampicin
*check platelet count, stop RIF and monitor until it normalizes, RIF should not be restarted
if patient taking anti-TB drugs develop rash and has healed, how do we reintroduce?
start with Isoniazid at low dose gradually increasing to normal dose within 3 days
how to restart anti-TB meds in patients with hepatitis
restart with RIF bec it much less likely cause hepatotoxicity and is the most effective agent
*if no increase in ALT after 1 week then restart with INH then Pyrazinamide after 1 week
patient taking anti-TB meds has jaundice, when do we resume medications?
anti-TB drugs be reintroduced 2 weeks after jaundice has disappeared
most common cause of peripheral neuropathy
INH»_space;>Ethambutol
*rarely occurs in children unless severe malnutrition is present
common cause of optic neuritis
Ethambutol»_space; INH
*blurred vision
*“spots” present in patient’s field of vision
red/green color blindness
risk of progression from infection to active disease
age
time of exposure to initial infection
nutritional status
immunosuppression
mycobacteria are
aerobic, non-motile and slightly curved or straight bacilli
BCG is derived from
M. bovis
virulence factors for M. tuberculosis
trehalose dimycolate (cord factor) sulfatides
Man-LAM- dominant mycobacterial antigen; responsible for enhanced bacilli survival and entry into macrophages
classic lesion in primary tuberculosis
Ghon focus
granulomatous hilar LAD plus Ghon focus =
Ghon complex
explain the Wallgren’s Timetable of Tuberculosis
1-3 months: highest risk for TB meningitis and disseminated and miliary TB
3-7 months: secondary airway involvement due to infected lymph nodes in children younger 5 yrs old
1-3yrs: osteoarticular TB in under 5yrs old
More than 3 yrs: calcification completed
5-25 yrs: renal involvement
TB exposure
no signs and symptoms
negative TST
(+) exposure
TB infection
no signs and symptoms
(+) TST
TB disease
(+) signs and symptoms
(+)TST
classify:
Bacteriologically confirmed
Clinically diagnosed
Pulmonary TB: lung and tracheobronchial tree
Extrapulmonary TB: larynx, pleura, LN, abdomen, GUT, skin, joints and bones, meninges
TB lymphadenitis in cervical region
Scrofula
most severe form of EPTB
Tuberculous meningitis
- subacute
- high index of suspicion needed
stages of TBM: first stage
personality changes, fever, irritability listlessness
stages of TBM: second stage
after 1-2 weeks, increased ICP and cerebral damage appear: drowsiness, stiff neck, cranial nerve palsies, inequality of pupils, vomitig, tache cerebrale, absence of abdominal reflexes and convulsions that may be tonic or clonic, focal or generalized
stages of TBM: third stage
coma, irregular pulse and respirations and rising fever
what are the common neuroimaging findings in Tuberculous meningitis
hydrocephalus (80%) basal meningeal enhancement hypodensities cerebral edema nodular enhancing lesions
most important determinant of outcome in tuberculous meningitis
stage of illness
most commonly affected in tuberculous spinal meningitis
dorsal cord–> lumbar –> cervical
in TB of bones and joints, where does lesion usually start?
area of endarteritis in the metaphysis of long bones where blood supply is abundant
most common skeletal site in TB of spine
vertebrae
hip and knee
most common location of TB enteritis
ileocecal area with extension to mesenteric LN and peritoneum
analysis of ascitic fluid with exudative features in TB peritonitis
- elevated protein (25g/dl)
- ascitic fluid- blood glucose ratio <0.96
*non-tuberculous ascitis >0.96
a child is presumed to have active TB if 3 or more of the ff are present:
exposure to an adult/adolescent with active TB disease (Epidemiologic)
signs and symptoms suggestive of TB (Clinical)
positive TST (Immunologic)
abnormal chest radiograph suggestive of TB (Radiologic)
lab findings suggestive of TB (histological, cytological, biochemical, immunological and/or molecular) (Laboratory)
treat as active TB if:
any 3 of the ff:
- (+) exposure
- (+) TST
- (+) s/sx
- abnormal chest xray
- laboratory findings suggestive of TB
most important diagnostic tool in tuberculosis
Tuberculin test
how do we do Mantoux test?
intradermal administration of 0.1 ml solution containing 0.1ug of 5TU of PPD-S or 2 TU of PPD-RT 23
A positive TST can be measured accurately for up to
7 days
negative TST can be read accurately up to
72 hours only
post-BCG tuberculin reactions develop
six to 12 weeks after vaccination
post-BCG tuberculin reactions develop
six to 12 weeks after vaccination
risk factors for acquiring infection
household contact with a newly diagnosed smear (+) case
age less than 5 years
Immunocompromised state
patient who has never had treatment for TB or who has taken anti-TB drugs for less than 1 month
New case
patient who has been previously treated with anti-TB drugs for atleast 1 month in past
Retreatment case
resistant to 1 1st line anti-TB drug only
mono-resistant TB
resistant to more than 1 1st line anti-TB drug
polydrug-resistant TB
resistant to at least both INH and RIF
Multidrug-resistant TB (MDR-TB)
resistant to INH and RIF + any fluoroquinolone + 1 of 4 2nd line drugs
Extensively drug-resistant TB (XDR-TB)
classic lesion of Primary tuberculosis
Ghon focus
most common risk factors for progressive primary TB
immunossuppression and children <2yrs
clinical disease resulting from hematogenous dissemination
Miliary tuberculosis
most common clinically significant form of disseminated TB
Miliary tuberculosis
presumptive TB
any person with signs and symptoms suggestive of TB
age cut-off: 15 years old
symptoms must last at least 2 weeks
any one with s/sx who is close contact of a know TB case
(+) CXR findings
presumptive extrapulmonary TB
Most common EPTB
Scrofula/ TB adenitis
Location: anterior cervical space
Most severe form of extrapulmonary PTB
Tuberculous meningitis
A patient with both pulmonary and extrapulmonary TB should be classified as
Pulmonary TB
What are the CSF findings in Tuberculous meningitis?
High opening pressure
50-100 WBC (early:luekocyte/ later: lymphocyte)
Low sugar
High protein (pedicle forms)
In EPTB of the joints, where does lesion start?
Endarteritis in the metaphysis of long bones
Pathognomonic of Pott’s disease
Calcification with the abscess
Most common area involved in Intestinal TB
Ileocecal area
Renal TB presents as
Painless sterile pyuria with hematuria and albuminuria
Occurs 15-20 years after primary infection
Common site of genital TB in females
fallopian tubes
TST should be postponed at least how many weeks after a live vaccine?
4-6 weeks from live vaccine
After a bout of measles, mumps, varicella and whooping cough, how many weeks should we delay TST?
2 months or 8 weeks
TST should be postponed at least how many weeks after a live vaccine?
4-6 weeks from live vaccine
After a bout of measles, mumps, varicella and whooping cough, how many weeks should we delay TST?
2 months or 8 weeks
Gold standard for diagnosing TB
TB culture
In doing gastric lavage, how much sterile water should be injected through the stomach tube?
25-50ml
Give dose of the 1st line anti-TB drugs
isoniazid 10-15mkday Rifampicin 15 (10-20mkday) max 600mg Pyrazinamide 30 (20-40mkday) Ethambutol 20 (15-25mkday)
Once TB disease has been excluded, IPT is recommended for the ff:
All HIV positive individuals
Children less than 5 years old household contacts of BCTB regardless of TST result
Children less than 5 yrs old who are household contacts of CDTB, if TST is positive
6months course of INH at 10mkdose
Prophylaxis for TB in HIV immunocompromised children
Less than 12 months: IPT if with household contact
more than 12 months: IPT x 6 months
Treatment for TB in HIV children
2 HRZE/ 4 HR then additional 6 months of INH
Do not treat with intermittent regimens
Early start of ART
Pyridoxine supplementation
Anti-TB drug that causes influenza syndrome
Rifampicin
1-2 hours after drug administration
3 indications for IPT
- all children with HIV that was exposed
- less than 5yo and exposure with bacteriologically proven TB case regardless of TST result
- less than 5yo and exposure with clinically proven TB case after TST result is positive
When a patient had TST for possible tuberculosis however returned for reading after 7 days, what should be done?
Repeat the skin test ASAP
A 4 year old patient was given “window treatment” for Tuberculosis, what could this mean?
Negative TST + known exposure to a probably contagious relative
What could explain the reason why children having TB disease are not as infectious as adults?
Nelson’s : Young children with tuberculosis rarely infect other children or adults. Tubercle bacilli are sparse in the endobronchial secretions of children with pulmonary tuberculosis, and cough is often absent or lacks the tussive force required to suspend infectious particles of the correct size.
When will we repeat Xray after TB treatment?
2 months
Usual duration of radiologic clearing in PTB
6-24 months
Which clinical manifestation is most suggestive of childhood TB disease?
Recent weight loss
What si Man-lam?
Enhanced bacilli survival and entry into macrophages
Most common organ involve in EPTB
Meninges
Findings in ascites of TB
Elevated protein (>25g/L)
Ascitic fluid to blood ratio <0.96
Non tuberculous: >0.96
Criteria for congenital TB
One or more of the ff
Present within the 1st week of life
Primary hepatic complex or caseating hepatic granuloma
TB infection of the placenta or endometrial TB in the mother; or exclusion of the possibility of postnatal transmission by excluding TB in other contacts
Clues to possibility of congenital TB
Unresponsive or worsening pneumonia
Infant born to a mother diagnosed with TB
Infant with high lymphocyte counts in the Csf without an identified bacterial pathogen or fever and hepatosplenomegaly
What is presumptive TB in less than 15yo
At least 3 of the following:
Cough/wheeze of 2 weeks or more
Unexplained fever 2 weeks or more
Loss of weight or failure to gain weight
Failure to respond to 2 weeks of appropriate antibiotic therapy
Failure to regain previous state of health 2wks after viral infection
Fatigue, reduced playfulness or lethargy
What is presumptive TB in 15 yo or older
Cough of at least 2 weeks duration with or without the following:
Significant and unintentional weight loss
Fever
Bloody sputum
Chest/back pains not relatable to any musculoskeletal disorders
Easy fatiguability/malaise
Night sweats
Shortness of breath or dob
Unexplained cough of any duration in
Close contact
High risk groups