infections Flashcards
what is the role of ART
Suppress viral replication
Control immune activation
Preserve existing immunity and permitting recovery of lost or dysfunctional immunity.
What is the impact of ART in children
Preserves and restores their immunity
Improves growth
Decreased risk for death/ prolong life expectancy
Preserve neurocognitive decline
Reduces infectious disease risk
Preserve vaccine induced responses
Reversal of organ-specific progression to AIDS
The sooner ART is strted the better the outcome
What tests should you do or conditions to exclude before initiating HRT
Full clinical assessment: history & examination
* Review all medication and be aware of potential drug interactions
* Nutritional assessment
* Neurodevelopmental screen
* WHO clinical stage of HIV infection
* Screen for TB
* In older children, screen for mental issues including active depression
* Screen for pregnancy (adolescents)
* Symptom screen for sexually transmitted infections (adolescents)
* Confirm HIV test results
* CD4 cell count and percentage
* Hb, if low do FBC and treat accordingly
* Creatinine and eGFR if tenofovir to be used
* Adolescents: Cryptococcal antigen test if CD4 <100 cells/µL; cervical
cancer screen if female; HBsAg
What renel function tests are done for pregnant women before initiating HRT
Absolute creatinine level
<85 umol/l
What renal tests should be done for adults and adolescents over 16 years before initiating ART
eGFR using MDRD equation
>50
What renal function tests should be done for adolescents at the ages 10-16 before initiating ART
eGFR using Counahan Barratt formula
>80
What are the indications for ART
All people living with HIV (PLHIV) are eligible for ART regardless of age, CD4 count and clinical stage. For all PLHIV
without contra-indications, ART should be started within 7 days
What are the medical indications to defer ART (Contraindications to ART)
- TB symptoms
-Drug susceptible TB (Less than 50 cd4 cells initiate ART within 2 weeks, if more than 50 initiate in 8weeks).
-Children <5 years, If CD4 count ≤200 cells/µL or <15% - initiate ART within 2 wks of
starting TB treatment
If CD4 count >200 cells/µL or >15% - initiate ART 2 – 8 wks of starting TB treatment
-Drug Resistant TB (Initiate ART after 2 weeks of TB treatment, when pt symptoms improving) - Cryptococcal meningitis
- Clinical features of liver disease
What are the prefered 1st line regimens for preterm neonates and neonates <2.3 kg
Seek expert advice
what is the preferred 1st line HIV regimens for Birth (≥2.0 kg) – <4 weeks (<3.0 kg)
AZT (zidovudine) + 3TC (lamivudine) + NVP (nevarapine)
What is the preferred 1st line HIV tx ≥4 weeks (≥3 kg) – <10 years (<30 kg)
ABC (abacavir) + 3TC (lamivudine) + DTG (dolutegravir)
What is the preferred 1st line HIV treatment for children ≥10 years & ≥30 kg
TDC (Tenofovir) + 3TC (lamivudine)+ DTG (dolutegravir) (TLD)
What drug interactions occur with Zidovudine
- Rifampicine decreases the effect of dolutegravir, so increase the dose to 50mg 12hrly
- Polyvalent cations (Mg, Fe, Ca, Al, Zn eg Antiacids, sulfate, multivitamin and nutritional supplements) decrease the effect of dolutegravir.
Soln: Ca and Iron decreases DTG if taken together on an empty stomach, to prevent this, take ca and DTG taken together with food but calcium and iron should be taken 4 hours apart.
Mg and aluminium containing antiacids decrease DTG regardless of food intake, should be taken min 2hours or 6hours before DTG. - Anticonvulsants: Carbamezapine, Phenobarbatal, Phenytoin decrease DTG concentration
Avoid and use alternatives: Valproate, Lamotrigine, Levetiracetam, topiramate. Valproate contraindicated in pregnancy
Double dose of DTG to 50mg 12hrly if alternative anticonvulsant cant be used. - Metformin: DTG increases the effects of metformin
Max dose 500mg 12hourly
WHen do you monitor fofr TDF-induced nephrotoxocity
creatinine at months 3 and 10, thereafter repeate every 12 months
When to monitor for Anaemia and neutropaenia
If on AZR, do Fbc and wcc at month 1 and 3, thereafter repeat if clinically indicated
when to monitor for dislipidemia
Total cholesterol and TGs at month 3, if above acceptable, do fasting cholesterol and TGs
If acceptable, obtain expert advice
When to monitor viral load and response to treatment after initiating ART
Routine monitoring at 3 and 10 months thereafter if virally suppressed, every 12 months
What is virally suppressed
<50 copies/mL = undetectable
(suppressed VL)
What could potentially cause a high VL in a pt on ART
- Adherence
- Bugs (infections)
- inCorrect ART dosage
- Drug Interactions
- rEsistence (if >2yrs on tx)
- poor absorption
- incorrect dosing
What are some of the factors that affect adherence to ART
– Inadequate counselling and education of caregivers
– Caregiver factors: non-disclosure to family, physical illness, depression, untreated affective disorders, substance abuse,
change of caregiver
– The more complex the antiretroviral regimen the less adherent:
number of tablets, frequency of administration, processing such
as crushing, mixing, dissolving & measuring.
– Side effects: patients may discontinue medication to avoid side effects
How to maintain good adherence to ART
(think of causes of poor adherence)
. Education / counselling
* Give patients feedback
* Support groups & treatment clubs
* Simplify medication
* Link medication to daily activities, educate caregivers about
consistency
* Manage side effects
* Provide tools: pill boxes, reminder calls
Which drugs are used for drug susceptible TB in SA and what effects do they have
Isoniazid (high early bactericidal activity, kills actively dividing bacteria)
Rifampicin (major sterilizing agent)
Pyrazinamide (kills dormant or slow dividing bacilli)
Ethambutol (efficacy against actively replicating bacilli)
Ethionamide (high CSF penetration)
Which TB treatment do you give to HIV negative children with minimal PTB
Intensive phase: 2HRZ (Isoniazide, Rifampicin, Pyrazinamide)
Continuation phase: 4HR
Which TB treatment do you give to HIV negative children with extensive PTB or severe forms of extrapulmonary TB
intensive phase: 2HRZE
Continuation phase: 4HR
What TB tx do you give to HIV infected children (with all forms of EPTB except TBM or miliary TB)
Intensive phase 2HRZE
Continuation phase: 4-7 HR
What TB tx do you give to all children (with TBM and miliary TB
Intensive: 2HRZEt
continuation: 4-7 HRZEth (NB Ethionimide has high CSF penetration)
what is multi-drug resistant TB
resistance to both INH and RIF
with/without resistance to other anti-TB drugs
What is Extensive drug-resistent TB (XDR-TB)
resistance to rifampicin
(and may also be resistant to isoniazid), and that is also resistant to at
least one fluoroquinolone (levofloxacin or moxifloxacin) and at least one
additional Group A drug, either BDQ or LZD
How to diagnose drug-resistant TB in paeds
- Culture-unconfirmed TB with a drug-resistant TB contact
– TB treatment regimen is based on the susceptibility of the isolate causing TB in the household/close contact
2* Rifampicin resistance identified by Xpert MTB/RIF Ultra
3* TB isolates cultured from children:
– Hain line probe assay screening for INH & RIF resistance
– If INH & RIF resistance detected on the LPA, DR-TB reflex
testing will be don
Define Pre-extensively drug-resistant TB (pre-XDR-TB)
resistance to
rifampicin (and may be resistant to isoniazid), and that is also resistant
to fluoroquinolones
What is IRIS
unmasking of new TB disease
Paradoxical worsening of established disease
Discuss the manifestations of IRIS
– Swinging fever
– New/worsening lymphadenitis
– New/worsening pulmonary infiltrates, respiratory
failure
– New/worsening pleuritis, pericarditis, ascites
– Intracranial tuberculomas, TBM
– Disseminated skin lesions
– Hepatosplenomegaly, soft tissue abscesses
How do we treat IRIS
– Expectant
– Glucocorticosteroids
How is BCG administered in SA
BCG is injected on the upper right arm at the insertion of the deltoid muscle.
The dose is 0.05 ml administered with a special BCG syringe, at birth.
What are the contraindications of BCG
- Children over 12 months of age not for BCG
- Children with symptoms of HIV infection
- HIV-exposed newborns who are well enough to be discharged should
be given BCG - If HIV-exposed newborns are sick the birth PCR should be checked, and BCG administered if the PCR result is negative
- If mother has TB and is on Anti TB drugs, child should be given TB preventive treatment and BCG only after TB treatment has been completed
What are the complications of BCG
Local BCG disease- papular eruption, ulceration
2. Regional BCG disease- Ipsilateral lymphadenitis, suppuration, fistulation
3. Distant/ disseminated BCG disease- lymphadenitis, pulmonary disease, BCG osteitis, dissemination
- BCG Iris - 3months of starting ART
- Erythema nodusum
- Lupus vulgaris
- Uveitis
Who should be given TB Preveventive tx
All adult, adolescent and child contacts in whom TB disease has been ruled out
what Preventive tx do you give to drug susceptible TB contact after TB exposure
(NB HIV + and HIV neg)
HIV-negative children: Daily isoniazid plus rifampicin for 3 months using the
NDoH dosing recommendations
HIV-infected children: Daily isoniazid for 6 months
What TB preventive tx do you give to Isoniazid monoresistant TB contact
Rifampicin 10-15 mg/kg/day per os for 4 months
What TB preventive tx do you give to Rifampicin monoresistant TB contact
Isoniazid 10 mg/kg/day per os for 6
months
What TB preventive tx do you give to MDR-TB TB contact
▪ Isoniazid 15-20 mg/kg/day plus ethambutol 20-25 mg/kg/day plus
levofloxacin 15-20 mg/kg/day per os for 6 months
▪ Levofloxacin 15-20 mg/kg/day per os for 6 months (likely to be
recommended in the near future)
What TB preventive tx do you give to xDR-TB TB contact
▪ Isoniazid 15-20 mg/kg/day per os for 6 months
▪ Regular follow-up for two years
▪ Ensure household infection control practices are observed
▪ Children who develop active infection should be referred
How effective is TB preventive treatment
Provisional finding ex TB-CHAMP
study:
Levofloxacin preventive treatment
reduced risk of MDR-TB by 56%
How to prevent meningitis
The general stuff: hygiene, tx infections otitis media, head injury etc
Vaccines (bacterial)
Pneumococcal vaccine for over 2months old
Meningococcal vaccines for 11-12 years
H.Influenza type b virus from 2months
Symptoms and signs of meningitis
Fever
Vomiting
Headache
Photophobia
Poor feeding
Hugh pitched cry
Lethargic
Neck stiffness
Bulging fontanelle in babies
Purple-red splotchy rash
Severe
Convulsions
Confusion
Hallucinations
Staggering or swaying when walking
Loss of consciousness
Which organisms cause meningitis
Neonates
Bacterial: Group B strep, Listeria, EColi
In 1year or older
Viruses: CMV, herpes simplex virus, enterovirus
Bacteria: Neisseria meningitis, strep pneumonia, haemophilia influenza
Fungal: cryptococcus
TB
Parasites: toxoplasmosis?
Adults: strep pneumonia, Elderly: listeria
In older
Virus: Polio, enteroviruses
Complications of meningitis
Sepsis/shock
Hearing loss
Brain damage: intellectual disabilities
Long term seizures
Hydrocephalus
Other short term: SIADH presenting as Hyponatremia, cerebral oedema, brain abscesses, secondary infections eg pneumonia, pericarditis
Treatment of meningitis according to the causative organism
Strep pneumonia: IV Penicillin or IV ceftriaxone, if resistant IV Vancomycin
H. Influenza: IV ceftriaxone
Nisseria meningitis: Ciprofloxacin oral single dose or ceftriaxone IM single dose, or IV Penicillin for 7d
What type of meningitis do you get petechia or purpura and hypothermia
Meningococcal
Contraindications to Lp
Infection at site
Signs of raised ICP
Bleeding disorders
Congenital anomalies of lower spine (meningomyelocele)
Extremely ill infant
Drug Tx for raised ICP
Mannitol 0.25-1.5 g/kg in children <12
What is the normal CSF glucose
2.5mmol/l, it is about 2/3 of serum glucose
If lowered, consider bacterial meningitis
Treatment of TB meningitis
Rifampicin 20mg/kg PO as single dose
Isoniazide 40mg/kg PO as single dose
Pyrazinamide 40mg/kg PO single dose
Ethionamide 20mg/kg PO as single dose
Tx is a 6month regimen
