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Transcript of MSF HIV/TB Guide - samumsf.org HIVTB Guide... · • Toxoplasmosis 3. Respiratory Disease – Big...
MSF HIV/TB GuideHOSPITAL LEVEL February 2018
Published by Médecins Sans Frontières - Southern African Medical Unit (SAMU)
February, 2018
4th Floor, Deneb House, Corner of Main and Browning Roads, Observatory, 7925Cape Town, South Africa
Tel:+27 (0) 21 448 3101
Visit the Southern Africa Medical Unit’s website: www.samumsf.org
© Copyright 2018, Médecins Sans Frontières. Any part of this material may be reproduced, copied or adapted, provided that the parts reproduced are free of charge, that the source is referenced and that notification is sent to Médecins Sans Frontières. All material may only be used for not-for-profit purposes.
Our strategies and protocols in HIV/TB management could be disproved or confirmed when confronted with field experience. Keep it in mind when reading this.And please do refer to national protocols before prescribing any treatment.
Please contact [email protected] if you happened to notice any abnormalities or mistakes.
MSF HIV/TB GuideHOSPITAL LEVEL
INPATIENT NOTES
Name: ………………………………………………………………………….……...
Folder number: ....….……………………………………………………… Date of Birth: …………………………………………………………………..........
REFERRED FROM (CLINIC / HOSPITAL) __________________________________ CLINIC PATIENT ATTENDS __________________________________
RELATIVE'S CONTACT NUMBER 1. ______________________________________
2. ______________________________________
ADMISSION RECORD
Previous admissions
DATE ADMITTED DATE DISCHARGED REASON FOR ADMISSION
1.
2.
3.
4
5.
Date ____________________________
Time ____________________________
Admitting Doctor ____________________________
History: symptoms, duration, functional status
__________________________________________________________________________________________________ __________________________________________________________________________________________________ __________________________________________________________________________________________________ __________________________________________________________________________________________________ __________________________________________________________________________________________________ __________________________________________________________________________________________________ _______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Previous opportunistic infections, additional past medical history:
____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Year of HIV diagnosis: Previous TB - dates of treatment:
basis of diagnosis (circle all that apply): • TB LAM/geneXpert/CXR/abdominal
USS/symptoms/other
Sensitivity: Rif sensitive/Rif resistant/unknown
Current TB - when started:
basis of diagnosis (circle all that apply): • TB LAM/geneXpert/CXR/abdominal
USS/symptoms
Sensitivity: Rif sensitive/Rif resistant/unknown
Adherence:
CD4 counts - give dates and results:
ART - circle one:
ART currently
ART previously
ART naive
ART history:
First line: dates and regimen:
Second line: dates and regimen:
Adherence - circle one:
No interruptions
One interruption
>1 interruption:
Give dates:
Viral load: give dates and results:
Name_____________________________________________
Folder no._____________________________________________
Date of birth________________________________________
TB symptom screen – circle all that apply:
• Cough
• Loss of weight
• Fever
• Night sweats
SOCIAL HISTORY________________________________
Smoking / ETOH / Mining _________________________
Occupation ____________________________________
Lives with ______________________________________ General Examination:
BP P
Temp Sats Hb HGT
Jaundice / Anaemia / Clubbing / Cyanosis
LYMPH NODES (sites)
SKIN KAPOSI Y / N
MOUTH KAPOSI Y / N
CVS Pulse: Volume regular/irregular JVP
Apex Position: Nature: Normal Diffuse Heaving Tapping
Parasternal heave Thrill
DVT
Auscultation: Oedema
RESPIRATORY Inspection: Chest wall shape Chest movement
Trachea central/deviated to right/deviated to left Percussion
Auscultation
ABDOMEN Tenderness: no/yes – where? Hepatomegaly yes/no
Distention yes/no Bowel sounds: normal/none/high pitched
Splenomegaly yes/no
PR Ascites: yes/no Other masses:
CNS GCS: /15 M: /6 V: /5 E: /4 Speech Swallowing
Muscle Wasting Meningism
Involuntary movement
Gait
Cranial nerves
Bladder function Bowel function Sphincter reflex:
LIMBS MOTOR
Sensation Reflexes
Tone Power Cerebellar
UL
R Biceps (C5,6)
Triceps (C6,7)
L Biceps (C5,6)
Triceps (C6,7)
LL
R
Knee (L3,4)
Ankle (L5,S1)
Plantar
L
Knee (L3,4)
Ankle (L5,S1)
Plantar
URINE DIPSTIX: PRENANCY TEST:
PV if indicated: CONTRACEPTION: PAP SMEAR:
MEDICATION Allergies:
Significant results:
___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Problem list: Differential Diagnosis:
_________________________________________ _________________________________________________ __________________________________________ __________________________________________________ __________________________________________ __________________________________________________ __________________________________________ __________________________________________________ __________________________________________ __________________________________________________ __________________________________________ __________________________________________________ __________________________________________ __________________________________________________ __________________________________________ __________________________________________________ __________________________________________ __________________________________________________
Management Plan: ____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Signed: ___________________________ Print name: ____________________________ Date: ___________________
Urine LAM: positive/negative
CrAg: positive/negative
GeneXpert sputum: positive/negative
Continuation notes: SIGN & DESIGNATION
(print name)
Advanced HIV – Seriously Ill Patients SUMMARY
DANGER SIGNS
• Respiratory rate > 30/min• Temperature > 39°C• Heart rate > 120/min• Systolic BP < 90mm Hg • Saturation < 90%• Moderate/severe dehydration• Unable to walk unaided
• Altered mental state: confusion, strange behaviour, reduced level ofconsciousness
• Any other neurological problem:headache, seizures, paralysis, difficultytalking, cranial nerve problems, rapid deterioration in vision
Often there is more than one cause
• Take a good history• Examine the patient• Focus on respiratory &
neurological systems and ARThistory
Disseminated TB is the most common cause of mortality
1. ART failure
2. Neurological disease – Big 3:• TB • Cryptococcal meningitis• Toxoplasmosis
3. Respiratory Disease – Big 3:• Pneumocystis pneumonia• Pulmonary TB• Bacterial pneumonia
4. Severe Diahorroea
5. Other bacterial infections • Bacterial meningitis• Bacteria• Urinary tract
infection
6. Other non-infectiouscauses • Hypoglycaemia• Renal failure• Abnormal sodium,
potassium• Liver disease• Drug side effects
Basic package of point of care tests • HIV Testing• CD4• Serum CrAg• TB LAM• Rapid malaria test• Glucose• Haemoglobin• Urine dipstick
Additional investigations: Do what is available
Basic TB investigations: • TB LAM (urine) • GeneXpert (sputum)
For either test: treat if positive, but a negative result does not exclude TB
Other TB Investigations:: • Sputum Microscopy • GeneXpert on non-sputum.
Samples: urine, CSF, pus • CXR • Abdominal USS
Lumbar puncture: • Necessary if there is any abnormal
neurology • Request: CrAg, cell count and
differential, protein, glucose, gram stain,geneXpert
• If LP not possible or inevitable delay: serum CrAg, empiric treatment as indicated (see Management - Neurology)
Blood tests: • Creatinine, sodium, potassium• Full blood count• VDRL • Jaundice or hepatomegaly: bilirubin, ALT,• Bacterial infection possible: blood/urine
cultures
Initiate without delay
Start empiric treatment (highlighted) for diseases where clinical suspicion is high, but where there is no diagnostic test available or where diagnostic tests cannot exclude the disease. Start second line ART if CD4 <200 and suspected treatment failure
Emergency Management
Respiratory Disease
Neurological Disease:
Clinical indications for immediate empiric TB
treatment:Hypoglycaemia: • 50 mls of 50% dextrose Dehydration, renal impairment*: • IV fluids, electrolytes • Chronic watery diarrhoea: empiric
treatment for Isospora belli (cotrimoxazole)
• Beware nephrotoxic drugs Liver failure*: • Beware hepatotoxic drugs Severe anaemia (Hb < 5g/dL)*: • Transfuse, oxygen Bacterial infection*: • Empiric IV antibiotics
*See relevant algorithm
Respiratory Danger Signs: RR > 30 or saturation < 90%
• Give oxygen • Empiric treatment for
pneumocystis and bacterialpneumonia
• Empiric treatment for TB ifIndicated
No danger signs: • CXR – treat accordingly • CXR not available, consider empiric
treatment: pneumocystis, bacterial pneumonia, TB
Treat for cryptococcal meningitis: • CSF CrAg positive • Abnormal neurology and serum CrAg
positive, LP not possible or CrAg unavailable
• Fluconazole only if serum CrAg positive,CSF negative.
• Serum CrAg positive LP not available andno abnormal neurology
ccc Treat for CNS TB: • Lymphocytes on CSF, and/or high
Protein ccc Treat for toxoplasmosis: • CD4 < 200; new focal neurology; or other
abnormal neurology and no other diagnosis
Do available investigations while starting treatment
• CNS TB likely• Miliary TB or other CXR evidence
of TB • Clinical presentation strongly
suggests TB; investigations not available or unable to exclude TB
• Clinical condition life-threatening, patient deteriorating, or not improvingafter 3 days of hospitalisation
Definition of ‘seriously ill’:
Do not delay investigations and management
One or more danger signs
Mortality is high:
Common causes of mortality: see box
Investigations DO Immediately
Management
ADVANCED HIV – SERIOUSLY ILL PATIENTS DETAIL
DANGER SIGNS
• Respiratory rate > 30/min• Temperature > 39°C• Heart rate > 120/min• Systolic BP < 90mm Hg• Saturation < 90%• Moderate/severe dehydration
• Unable to walk unaided• Altered mental state: confusion, strange behaviour, reduced
level of consciousness• Any other neurological problem: headache, seizures,
paralysis, difficulty talking, cranial nerve problems, rapiddeterioration in vision.
One or more danger signs
Often there is more than one cause Investigations and management focus on these causes
Disseminated TB is the most common cause of mortality: All patients need investigating for TB, and rapid initiation of treatment if indicated
1. ART failure
2. Neurological disease – Big 3:• TB• Cryptococcal meningitis• Toxoplasmosis
3. Respiratory Disease – Big 3:• Pneumocystis pneumonia• Pulmonary TB• Bacterial pneumonia
4. Severe diarrhoea:• Renal failure and abnormal
sodium and potassium levelsare common, and are oftenasymptomatic
5. Other bacterial infections:• ‘Bloodstream’ infections• Meningitis• Urinary tract infections
6. Common non-infectiouscauses: • Hypoglycaemia• Renal failure• Sodium/potassium
abnormalities• Liver disease• Drug side effects: find out all
the medication the patient istaking
Key question 1: is the patient on ART? Patients on ART should be doing well, and not seriously ill:
What has gone wrong?
Key question 2: is the patient taking TB treatment?
Patients on TB treatment should be doing well, and not seriously ill: what has gone wrong? • What is the regimen?
• How long is the patient on ART?< 3 months: TB is very common during this time - ‘unmasking TB’>6 months: is there treatment failure?
ccc
The majority of seriously ill patients nowadays with advanced HIV are failing first line and need rapid switch to second line • If this is not addressed, treating opportunistic infections alone will
not save the patient’s life• Adherence issues must be addressed at the same time as changing
regimen; staying on a failed regimen means the patient will die
Questions to ask: • For how long is the patient on TB treatment?• Was TB proven? Rifampicin sensitive?• Is the admission due to drug adverse effects?• Did the patient improve on TB treatment?
If not – see algorithm ‘Patients deteriorating ornot improving on TB treatment’
• Start with the presentingcomplaint
• Always ask about neurologicaland respiratory symptoms, anddiarrhea
• Ask the 2 key questions (seeright)
Definition of ‘Seriously ill’:
Do not delay investigations and management
Mortailty is high:
Common causes of mortality: see box
• Reassess vital signs• Specifically assess neurological
and respiratory systems, andassess for dehydration
• Look for KS (skin, palate)• Look for CMV retinitis if recent
deterioration in vision
Take a good history
Examine the patient
ADVANCED HIV – SERIOUSLY ILL PATIENTS (Detailed version continued)
If the patient is to be referred to a higher level of care, do as many investigations as possible at the initial facility, and start management
Investigations: Take sample immediately AND collect results within
Basic package of point of care tests:
These should be available 24/7, and all clinical, nursing and lab staff trained in their
use. • HIV Testing• CD4• Serum CrAg• TB LAM• Rapid malaria test• Glucose• Haemoglobin• Urine dipstick
Chest X Ray
TB: • Miliary TB• Pleural effusion,
pericardial effusion• Lymphadenopathy• Pulmonary infiltratePneumocystis pneumonia:• Ground glass pulmonary
infiltrateBacterial pneumonia: • Consolidation, air
bronchograms
All patients need investigation for TB:
TB LAM: • TB LAM positive: start TB treatment• TB LAM negative: TB is not excluded! Continue
investigations, start empiric TB treatment ifindicated (see Management section)
GeneXpert: • Sputum: spontaneous or induced• Non-sputum samples: urine*, CSF*, ascites* pus
GeneXpert positive: start TB treatment GeneXpert negative: TB is not excluded!
Continue investigations, start empiric TBtreatment if indicated (see Managementsection)
Other investigations for TB:
Sputum microscopy: • If geneXpert unavailable
CXR: see left
Abdominal ultrasound: • Lymphadenopathy• Ascites• Hepatosplenomegaly
Indications for LP: • Any neurological symptoms or signs• Serum CrAg positive• LP should be done before antibiotics are
started unless this will delay the firstdose; the sample can be stored in a fridgeovernight
Baseline investigations: • CrAg• Cell count and differential (lymphocyte
count, neutrophil count)• Protein, glucose• Gram stain for bacteria: Streptococcal
pneumoniae: gram positive cocci inpairs/chains Neisseria meningitidis: gramnegative diplococci
• GeneXpert*
If unable to do an LP or if there is aninevitable delay (eg referral isnecessary for LP), empiric treatmentmay be necessary
See Management section: NeurologicalDisease
Lumbar puncture
Centrifuge urine, CSF, ascites and pus
otherwise sensitivity is very
low.
REMEMBER: All neurological
signs are Danger Signs
Blood Tests
• Creatinine, sodium, potassium• Full blood count• VDRL• Jaundice or hepatomegaly:
bilirubin, ALT, hepatitis B
Does the patient have a bacterial infection?
Look for any of the following: • Temp > 38 degrees or < 35
degrees• HR > 120, or RR > 30• White cell count <4 or > 12• Other causes possible: Acute
onset of symptoms suggestsbacterial infection. In doubt, startantibiotics if seriously ill. Diagnosiscan be reviewed upon furtherresults
• Look for the source (pneumonia,meningitis , UTI): blood streaminfections are also common
• Take blood culture*, using steriletechnique; other relevant tests,e.g. urine dipstick, urine culture
Take before antibiotics are started unless this will delay the first dose.
ADVANCED HIV – SERIOUSLY ILL PATIENTS (Detailed version continued)
Management: Start without delay Start empiric treatment (highlighted text) for diseases where clinical suspicion is high, but there is no diagnostic test available, there is an unavoidable delay with results, or if diagnostic test cannot exclude the disease. Start second line ART if CD5<200 and suspected treatment failure.
General Management Respiratory disease Neurological disease
Hypoglycaemia: • Give 50mls of 50% dextrose, monitor PoC glucose 4
hourly until hypoglycaemia has resolved for 24 hours.ccc
Dehydration and/or renal impairment: • Intravenous fluids and electrolyte replacement (NaCl or
Ringer’s lactate), at least 3L per day (if tolerated). • Beware nephrotoxic drugs: see renal algorithm.• If chronic watery diarrhoea is the cause, start empiric
treatment for Isospora belli infection.• If vomiting, start regular IV antiemetics
• ccc
Liver impairment: • Beware hepatotoxic drugs; see liver algorithm
• ccc
Anaemia: • HB < 5g/dl: transfuse, give oxygen• HB < 8g/dl and tachypnoea or active bleeding: transfuse• Assess for likely cause: see anaemia algorithm
• ccc
Is bacterial infection likely? • Start empiric antibiotics according to local guidelines• Review all antibiotic prescriptions every 48 hours to
assess if IV drugs can be changed to oral, or if antibioticscan be stopped: see bacterial infection algorithm.
*Amphotericin B plus fluconazole 800mg
**Fluconazole alone; 800mg if CSF CrAg negative, 1200mg If unable to do serum CrAg
Treat as above for 14 days; continue fluconazoleaccording to protocol in MSF/HIV handbook.
3. CXR evidence of TB (see Investigations page - CXR) 4. Seriously ill (any danger signs), orpatient is after 3 days of hospital admission
Respiratory Danger Signs: RR > 30 or saturation < 90%
• Oxygen by face mask or nasal prongs ccc
Start empiric treatment immediately for: • Pneumocystis pneumonia: cotrimoxazole (480mg/4kg
body wt/d, plus prednisone initially 40mg bd)• Bacterial pneumonia: see local guidelines• TB: if immediate investigations positive, or empiric
treatment indicated (see below) • ccc
Evidence of respiratory disease but no Danger Signs: • CXR if available: see Investigations: CXR
• ccc
CXR not available: consider empiric treatment for: • Pneumocystis pneumonia (dyspnoea, dry cough)• Bacterial pneumonia (acute onset, crepitations)• TB: if investigations positive, or empiric treatment
indicated
1. CNS TB is likely:• Neurological symptoms/signs with evidence of TB
elsewhere or clinical presentation is suggestive2. Clinical presentation strongly suggests TB, and investigations not available or cannot exclude TB
• Peripheral lymph nodes• Night sweats, weight loss, fever, cough • Pleural effusion, pericardial effusion or ascites and
no other more likely cause 3. CXR evidence of TB (see Investigations page - CXR) 4. Seriously ill (any danger signs), or patient is deteriorating, or is not improving after 3 days of hospital admission
Clinical indications for immediateempiric TB treatment:
Treat for Cryptococcal meningitis (CCM)* • CSF CrAg positive• Serum CrAg positive, and LP not possible or unavoidable delay,
and any neurological symptoms/signs• No CrAg available and any neurological symptoms/signsccc
Treat positive serum CrAg, and not for CCM** • Serum CrAg positive and CSF CrAg negative• Serum CrAg positive, and LP not possible or unavoidable delay,
and no neurological symptoms/signs • ccc
Treat for CNS TB (TB treatment plus prednisone 1.5mg/kg): • Suggestive LP (mostly lymphocytes, and/or high protein)• Neurological symptoms or signs with evidence of TB elsewhere, or
clinical presentation suggestive • CSF geneXpert positive
• ccc
Treat for Toxoplasmosis (cotrimoxazole 960mg/8kg body wt) CD4 < 200 or unkown and new onset neurology: • Focal neurology (eg hemiplegia)• Altered mental state, or new headache and no alternative
diagnosis • ccc
Treat for Bacterial Meningitis (see local guidelines): • Acute onset of meningitis symptoms • Meningococcal meningitis: non-blanching petechiae• CSF: neutrophil predominance and/or CSF microscopy shows
bacteria on gram stain, and/or high protein• ccc
If there is no evidence to support bacterial meningitis (neutrophils in CSF) and an alternative diagnosis found (for example CCM), antibiotics can be stopped.
ccc
If LP not available or unavoidable delay – and any neurological symptoms or signs: • Acute onset of symptoms: treat for bacterial meningitis• Serum CrAg positive or not available: treat for CCM• Treat CNS TB and/or toxoplasmosis: see above
Bacterial sepsis: • Common cause of acute confusion• Fever, raised white cell count, low blood pressure• Look for the source: respiratory and urinary tract
infections are common• Start antibiotics immediately
Neurological causes
Metabolic – multiple causes: • Hypoglycaemia• Hypotension• Hypoxia• Hyponatraemia, hypernatraemia• Hypercalcaemia• Renal failure• Liver failureLook for and correct the cause of all metabolicabnormalities
Encephalitis – inflammation of brain:
See ‘neurological problems’ algorithm
In addition to ‘altered mental state’ there may be other symptoms: • Fever• Focal neurology• Signs of the underlying cause, for example
disseminated TB
• LP is normal unless there is also meningitis
Most common causes: The ‘big 3’ neurological opportunistic infections: • Cryptococcal disease• TB – tuberculomas• Toxoplasmosis
When to start empiric treatment for toxoplasmosis: • CD4 known or likely to be < 200 and abnormal
neurology: hemiplegia or other focal neurology, confusion, reduced level of consciousness, or any other form of altered mental state
Medical Causes
Drugs: • Efavirenz, isoniazid, steroids• Alcohol and drugs: intoxication, withdrawal• Change or stop all implicated drugs
HIV encephalopathy – treatment is ART: • Cognitive problems• Behavioural problems & low mood• Motor problemsPsychiatric Disease• Psychosis• Depression
• Useful to ask if there have been previous episodes
Confusion: causes
Diagnoses of exclusion: Exclude neurological and medical causes – using available investigations and clinical assessment
This algorithm is for all forms of ‘altered mental state’: • Confusion• Reduced level of consciousness• Disorientation• Strange behaviour• This algorithm can also be used for convulsions – which can also be caused by neurological or medical abnormalities
Meningitis – inflammation of meninges: • An altered mental state can also occur with meningitis• Meningism, fever, may have focal neurology• CSF may show cells and high proteinCauses:• Cryptococcal: subacute• TB: subacute• IRIS to either of above• Bacterial Meningitis: acute• Neurosyphilis: subacute• Viral meningitis is rare: a lymphocytic CSF in patients
with advanced HIV should be treated as TB meningitis
What do you mean by ‘confusion’? • Reduced consciousness • Confused speech • Disorientation in time/space • Agitation/aggression • Psychosis – hallucinations – delusions -
delirium
Examination: General: • Fever • Hypotension • hypoxia • jaundice Neurological: • Glasgow Coma Score – evaluate whether
improvement/deterioration • Meningism • Focal Neurology: document neurological
examination • Fundoscopy: papilloedema, opportunistic
infection for example CMV?
Immediately look for and correct life- threatening
• Hypoglycaemia • hypoxia • hypotension • malaria
Investigate for opportunistic infections: • Cryptococcal disease • TB
Always look for TB: • Neurological TB and TB IRIS are common • If on TB treatment: diagnosis proven, drug
sensitive?
Investigate for CNS TB: • CSF GeneXpert – but negative result cannot rule
out TB meningitis
Look for TB elsewhere: • Urine LAM • GeneXpert: sputum, urine • other samples: ascites, pleural fluid • CXR
Confusion
Look for other medical problems – initial investigations: • HB, white cells, platelets • Na, K, creatinine • Liver function tests • RPR
Neurological investigation – Lumbar Puncture: Do all investigations available to you:
• Cell count and differential • Gram stain for bacteria • Pandy (protein) • CrAg • RPR (note that rapid syphilis test is not validated for
CSF) • GeneXpert on centrifuged CSF
Causes (see opposite page): • Neurological • Medical • Psychiatric
History: • Most recent CD4 count: CD4 > 200,
opportunistic infections such as toxoplasmosis and cryptococcal disease unlikely
• ARV history – including adherence & viral loads
• TB history • Onset – acute or chronic? • Previous episodes: what was the cause? • Other neurological symptoms: seizures,
headache, fever • Other non-neurological symptoms: e.g. severe
diarrhoea can result in electrolyte problems and renal failure
Medication: • Efavirenz, isoniazid, corticosteroids • Alcohol, other drugs
History and examination Investigations
Global neurological dysfunction (‘encephalitis’): • Altered mental state • Reduced level of
consciousness • Confusion
See also ‘confusion’ algorithm
Meningism: • Neck stiffness • Photophobia • Headache
Be suspicious of meningitis even if there is only one of these symptoms If bacterial meningitis possible and LP cannot immediately be done: • Immediate Dexamethasone 8mg IVI plus Ceftrixone
2mg IVI (Dexamethasone prior to, or at the same time as ceftriaxone)
Acute focal neurology:
• Hemiplegia • Cranial nerve
abnormalities • Abnormal
movements • Ataxia, other
cerebellar signs
Seizures:
• May occur with any neurological problem
• HIV positive patients with even one seizure must be investigated as below
• Prevent further seizures: sodium valproate 300mg bd, increase to 500mg bd
Other relevant symptoms:
• Fever • Wasting • Other symptoms
or signs of TB
Emergency Investigations:
• Glucose • Rapid malaria test – endemic
areas
Lumbar Puncture: • Cell count and differential • Gram stain • Pandy (protein) • CrAg
• RPR (if available; note rapid
test is not validated for CSF)
• GeneXpert: centrifuged CSF
HIV and ART investigations:
• CD4 count • Viral load if on ART > 3 months
Always take a full HIV and ART history!
Emergency Management:
• Hypoglycaemia: 50mls of 50% dextrose IVI and look for and correct the underlying cause
• Malaria: start treatment immediately with artensunate: continue to look for additional causes – malaria may not be the only cause of an altered mental state in a patient with a low CD4 count
Other investigations:
Serum CrAg : • CD4 < 100
TB is a major cause of neurological problems in advanced HIV: • TB LAM • geneXpert: sputum, urine, other body
fluids • Imaging: CXR, abdominal ultrasound
Empiric treatment of TB should be started for all patients with CD4 counts < 200 and
neurological disease if there is no other definitive diagnosis
Look for non-neurological causes Confusion, reduced level of consciousness, any other alteration in mental state: Look for metabolic abnormalities: • Hypoglycaemia • Electrolyte abnormalities • Renal impairment • Liver disease
Neurological Problems: Clinical Presentation
Investigations
Normal Viral Bacterial TB Cryptococcal
CD4 count Any Any Any – often low Low, usually < 100
Onset
acute acute Sub-acute Sub-acute
appearance Clear Clear Often turbid Clear Clear
Cells < 5 lymphocytes no neutrophils See note*
Lymphocytes Usually < 100 *See note below: lymphocytes In advanced HIV mean TB, not viral meningitis*
Cell count high, mostly neutrophils However: • If antibiotics
are given before LP is done, cell count may fall, and bacteria are unlikely to be seen
Lymphocytes Variable, may be several hundreds However: • Cell count may
also be normal • In early TBM,
neutrophils can predominate
Very variable, may be raised with mostly lymphocytes, often normal
Protein (High = Pandy +ve)
Normal Normal Usually high Usually high Normal or high
Glucose Normal Normal Usually Low Usually Low Normal or slightly low
Special tests
Microscopy to look for bacteria: low sensitivity, but gives definitive diagnosis
GeneXpert on centrifuged CSF (note: negative GeneXpert does not rule out TB)
CrAg: sensitivity and specificity very high
As can be seen, there is a lot of overlap between findings in different types of meningitis
*Viral meningitis:
• Most viral meningitis is self-limiting and is caused by viruses such as enterovirus • This causes a rapid onset meningitis, with rapid recovery - most patients are not admitted to hospital because
they recover rapidly at home • As a general rule: a lymphocytic CSF in hospitalised HIV positive patients is TB meningitis and not “viral
meningitis”
Neurological problems: Interpretation of lumbar puncture results
Toxoplasmosis • Reactivation of latent
disease, causing space occupying lesions
• Any abnormal neurology: focal symptoms, any type of altered mental state
Cryptococcal meningitis
• Headache, meningitis symptoms, or altered level of consciousness
• Focal neurology: ophthalmoplegia and visual disturbance are common
Neurosyphilis
In general: • most strokes are caused by
hypertension and diabetes • most strokes cause hemiplegia,
and there may also be a facial nerve palsy (mouth droops on one side)
In HIV patients: • patterns of focal neurology may
be caused by TB or toxoplasmosis
• All HIV positive patients with focal neurology need investigations and empiric treatment if appropriate; plus blood sugar and blood pressure.
Remember Trypanosomiasis in endemic areas: CSF microscopy for parasites
Investigations: • LP - Lymphocyte
predominance, high protein, low glucose
• However LP may be normal • GeneXpert may be positive
on centrifuged CSF • Look for evidence of TB
elsewhere: TB LAM, sputum microscopy, CXR, abdominal USS
Investigations:
• CD4 low (usually <100) • CSF CrAg positive
Investigations: • Toxoplasmosis IgG positive
(if available) • This shows previous
exposure, cannot confirm that there is reactivation
Tuberculosis
• Meningitis • Tuberculomas: space
occupying lesions – causing encephalitis symptoms and focal neurology
Malaria
Bacterial meningitis
• Rapid malaria test positive
• Blood film positive if rapid test not available
• Malaria may not be the only cause of an altered mental state in a patient with a low CD4 count
• Positive CSF VDRL • Rapid test positive
on blood, with suggestive clinical presentation
• Note rapid test is not validated for CSF
• Raised WCC on CSF with > 80% neutrophils
• Organisms may be seen on microscopy
• If LP is done after antibiotics, organisms rarely seen and cell count may be reduced
Treatment: • Amphoterocin B and
fluconazole
• Measurement of opening pressure and therapeutic LPs are essential
• Full protocol: see
MSF guideline
Treatment: • Treat if CD4 < 200 and any
neurological symptoms • cotrimoxazole
400mg/80mg 1 tablet for each 8kg body weight, given in 2 divided doses for 1 month
• Half the dose for 3 months, then continue normal prophylaxis dose.
• There is should be a rapid response to treatment, there should be a clear clinical response within 14 days
Treatment: • Treat for CNS TB if any
abnormal neurology and evidence of TB elsewhere, or CD4 < 200.
• CNS TB and toxoplasmosis cannot be distinguished on clinical grounds; treat for both if CD4 < 200
• Treatment: TB treatment plus steroids: prednisone 1.5mg/kg/day for 6-12 weeks, depending on clinical response
“Big 3” CNS opportunistic infections: Look for all of these in all patients
Other common infectious causes
Cerebral Vascular Accident (stroke)
Other HIV-related causes
CMV - CD4 < 100: • Treat for CMV encephalopathy if altered
mental state in the presence of CMV retinopathy. Treatment is valganciclovir.
Patients not improving on treatment for toxoplasmosis/CNS TB:
Both of the following are clinical diagnoses to consider in patients not responding to
treatment. Diagnosis is generally not available (CT/MRI). Treatment is ART and palliative care.
Progressive multifocal encephalopathy (PML) - CD4 < 200:
• Multiple progressive white matter lesions n brain: cognitive, motor, visual problems
• Most survivors - severe neurological deficits Primary CNS Lymphoma - CD4 < 50:
• Rapidly fatal
What is diarrhoea? • > 3 stools per day • Decreased consistency: ‘takes the
shape of the container’ • Associated symptoms: fever,
abdominal pain, vomiting
Acute vs Chronic: • Acute - < 2 weeks
• Chronic - > 2 weeks
Inflammatory vs Non-inflammatory: Small bowel - non-inflammatory: • Large volume watery diarrhoea: no blood
or mucous Large bowel – inflammatory: • Frequent small volume stools, with blood
and mucous ( WBC on microscopy)
Does the patient have advanced HIV: is CD4 < 200? • Chronic watery diarrhoea is common - caused by
parasite opportunistic infections: Isospora belli, Cryptosporidium
• Dehydration, renal impairment and severe hypokalaemia are common
• WHO stage 4: need effective ART – change to second line if suspect first line failure
Complications: • Dehydration, hypovolemic
shock • Acute kidney injury • Electrolyte abnormalities • Bacteraemia, septic shock
Causes: Infectious: • Viral • Bacterial • Parasites • Mycobacteria: disseminated TB
Diarrhoea in HIV positive patients
3 questions
Chronic diarrhoea
Acute diarrhoea Non-inflammatory:
• Viruses: norovirus, rotavirus • Bacterial: toxin secreting – be alert for
cholera (large volume of rice water stools) • Nausea and vomiting, abdominal cramps
Inflammatory: • Bacteria: Salmonella, shigella,
Campylobacter, E coli, C difficile • Parasites: amoebic dysentery
• Fever, abdominal cramps common • More severe illness: gut mucosa damaged
Investigations: • Creatinine and electrolytes • Stool microscopy if available:
bacteria or parasites found?
Treatment: • Fluid and electrolyte
replacement • Most acute diarrhoea is non-
inflammatory and self-limiting, antibiotics not needed
Antibiotics if bacterial cause or amoebic dysentery: • Fever > 38 degrees • Severe dehydration • Bloody diarrhoea • Mucous, or WBC on microscopy
Which antibiotics: • Ciprofloxacin 500mg x 12 hourly for 3
days • Add metronidazole for 10 days if bloody
diarrhoea or amoebae seen
Non-inflammatory: • CD4 < 200: isospora belli,
cryptosporidium are common WHO stage 4 diseases
• Giardia Lamblia • Vomiting, weight loss,
malnutrition common
Inflammatory: • Parasites: amoebic dysentery,
strongyloides, Giardia lamblia • CD4 < 100: CMV (rare) – look
in eyes to see if there is CMV retinopathy
Investigations: • Creatinine and electrolytes
– renal impairment and hypokalaemia common
• Stool microscopy if available: parasites found?
• 2 or more stool samples may be necessary: parasites are shed intermittently; negative stool does not rule out parasite causes
Treatment: • Fluid and electrolyte
replacement
Anti-parasite treatment: Inflammatory: • metronidazole for amoebiasis (7 days) or strongyloides
(10 days) Non-inflammatory: • Giardiasis is common, treat with metronidazole for 3
days, or single dose tinidazole (2g) • Empiric treatment for Isospora belli: cotrimoxazole 480mg
dose: 1 tablet for each 8kg of body weight per day in divided doses – for 10 days
• Followed by prophylaxis 480mg x 2 tablets per day • Cotrimoxazole hypersensitivity: ciprofloxacin, 500mg bd
for 10 days Some patients have recurrent episodes, despite immune restoration: treat with cotrimoxazole plus ciprofloxacin for 10 days, then maintenance cotrimoxazole 480mg 2 tablets bd
Clinical presentation • Dyspnoea • Cough; productive or dry? • Fever
Respiratory danger signs: • Respiratory rate > 30 • Hypoxia: oxygen saturation < 90% • Haemoptysis
Initial assessment
Emergency management • Oxygen via face mask or nasal prongs if RR > 30 or hypoxia • Initiate antibiotics immediately if bacterial pneumonia suspected • Look for pneumothorax Haemoptysis: • codeine or other opiate for cough suppression (do not ask
patient to give sputum samples) • start empiric TB treatment • check Hb; ensure Hb stays > 8 (or >10 if haemoptysis >
250ml/day)
Acute onset: days
Look for alternative/additional causes
*Pneumocystis pneumonia
• CD4 count generally < 200 • Progressive dyspnoea: often dry cough • Very high respiratory rate (> 40) and hypoxia are
common • Sudden deterioration: pneumothorax is
common and life-threatening • Auscultation: crepitations or may be normal • CXR: ‘ground glass’ infiltrate; look for
pneumothorax Treatment: • Cotrimoxazole 480mg 1 tablet for each 4kg of
body weight, in 3-4 divided doses (if 48 kg, 4 tablets 3 x day)
• Hypoxia: prednisone - 40mg twice daily x 5 days – then: - 40mg once daily x 5 days – then: - 20mg once daily x 11 days
Subacute onset: up to 2 weeks
Look for Kaposi’s Sarcoma
• CD4 often < 200, often higher • Look for KS lesions on skin, palate • CXR: ‘lines and nodules’ –
reticulonodular pattern, radiating from the hilar regions May be bloody pleural effusion
Treatment: • Fast track for ART, chemotherapy
Chronic lung disease
• All CD4 counts • Chronic dyspnoea, chronic cough, chronic
hypoxia • CXR: post TB destructive lung disease –
fibrosis, cavities, bronchiectasis on CXR • Comparison with previous CXRs shows this is
chronic: treat TB if proven, avoid empiric treatment on the basis of CXR alone
* = in red, the “big 3” respiratory diseases! They may co-exist, always look for all 3
Respiratory Problems
All patients are TB suspects
*Tuberculosis: investigations
• Pulmonary TB; any CD4 count • Sputum for geneXpert (microscopy if not
available) • TB LAM if CD4 known or considered < 100 • Other investigations as indicated: eg
pleural tap, LN FNAB Infection control: • surgical mask for patients not needing
oxygen; move to TB isolation area) • Open windows!
History: • Duration of onset, additional
symptoms Examination: look for • lymph nodes • pleural effusion • wasting • skin lesions
Investigations: • All patients are TB suspects! • Investigate for TB • CXR for all patients as soon as
possible • Pleural effusion: diagnostic tap,
therapeutic tap if large and causing respiratory distress
*Bacterial pneumonia
• Occurs with any CD4 count • Auscultation: Bronchial breathing
and crepitations • CXR: Pulmonary infiltrate or
consolidation; empyema may occur (purulent pleural effusion, mostly neutrophils)
Treatment: • Antibiotics • Ceftriaxone 1g: change to oral
antibiotics (co-amoxyclav) after 1-2 days, when clinical improvement shown
• Duration of antibiotics: 5-7 days
Don’t Forget – Respiratory Emergencies: • Pulmonary embolism • Pneumothorax (common
complication of pneumocystis pneumonia)
• Haemoptysis • Empyema
Not drug sensitive TB:
• DR TB • MAC
2. Was TB proven? • How? • When? • Drug sensitive?
3. TB medication history: • When started? Regimen? • Detailed adherence history:
from folder, patient, family
4. ART history: • On HAART? • When started, which regimen • Detailed adherence history:
from folder, patient, family • CD4 and VL history
Drug sensitive Tb proven, therapeutic level of drugs too low: • Dose too low • Malabsorption:
Chronic diarrhoea, vomiting • Rifampicin levels sub
therapeutic
Poor adherence is a common cause: • Poor adherence - why?
Timeline always important: when started, when stopped, when restarted: • Poor adherence: virological failure? • Recently started ART: IRIS • Not taking ART prior to admission, but
prescribed because history of non-adherence not known: IRIS
• If poor adherence – why?
Additional diagnosis:
• Original TB diagnosis correct, but now something extra
Adverse drug effects: • TB meds • ART • Cotrimoxazole • Efavirenz • Others
Alternative diagnosis:
• Original diagnosis of TB not correct
• New OI: eg pneumocystis, cryptococcal disease • Other HIV related problem • HIV unrelated problem
If cause cannot be found: • Retake history… anything missed? • Re-examine patient– again and again
• Infection: viral, bacterial, parasite, fungal Infections may be acute or chronic
• Malignancy: for example KS, lymphoma, lung cancer • Organ failure: cardiac, renal, liver, blood, chronic lung
disease … and look for the cause • Other chronic disease: eg diabetes, • Drugs, alcohol, smoking, traditional medication
If not proven or no sensitivity testing • Send all possible samples • GeneXpert very helpful: sputum, CSF, urine
1. Evolution of illness: • Pattern of
improvement/deterioration
• Initial improvement on TB treatment? • No improvement at all? • Improved with TB treatment, deteriorated
when ART started?
• This is a common reason for admission • Patients on TB treatment should be improving, and not need
hospital admission • It is important to find the reason patients are not doing well,
and correct the cause • Many of these patients have disseminated TB, and non-
specific symptoms It always important to review the initial diagnosis, as per algorithm
Patients deteriorating or not improving on TB treatment
2. Consider specific causes
1. Essential background information 2.
Acute Kidney Injury: • Dehydration • Sepsis • Nephrotoxic drugs :
particularly tenofovir, rifampicin, cotrimoxazole
Often there is more than one cause
Clinical presentation • Kidney disease is often missed: it is often asymptomatic or presents with general symptoms, eg fatigue, nausea • Oedema is a very late sign, and is not seen with HIVAN: its absence does not exclude significant renal disease • The commonest presentation of renal disease is an incidental finding of elevated serum creatinine • Strongly suspect and look for renal disease in all patients with the risk factors in bold listed above • Chronic renal disease may present with anaemia – due to reduced production of erythropoietin
Chronic kidney disease:
• Hypertension and diabetes are major risk factors for chronic kidney disease
• Chronic kidney disease means patients are more vulnerable to acute kidney injury: ie acute on chronic kidney injury
Creatinine
All patients needing hospital admission should have creatinine checked The definition of normal depends on age, weight and gender. Creatinine clearance is more useful. Normal creatinine clearance is > 50ml/min
A useful note: • If creatinine < 100 µmol/L , and weight > 50kg, and age < 50 years and the for
patient is not pregnant, the creatinine will be within normal range
Sodium and Potassium
Abnormal sodium and potassium are common in kidney disease and may be life-threatening
Severe hypokalaemia is common in chronic diarrhoea and acute severe diarrhoea Potassium may be very high in chronic kidney disease
Urine dipsticks
• Protein and blood indicate renal disease. This can be associated with a urinary tract infection (UTI) but findings usually include white blood cells and nitrites
• Always follow up with another dipstick after treatment of a UTI to ensure resolution of the abnormal dipstick findings
• WBC +/- bacteria – show urinary tract infection
Urine microscopy
Renal ultrasound • Shows general anatomy, can suggest underlying HIVAN (large or normal echogenic kidneys), or end-stage kidney disease (small kidneys), but cannot give further information about the underlying cause
Renal Disease in Hospitalised HIV positive Patients
Investigations
HIVAN (HIV associated nephropathy)
• If detected early, HIVAN is
reversible • However it may progress
to chronic kidney disease
Use the CKD-EPI formula to calculate GFR, now considered the most accurate Free app will calculate offline: go to any of usual app stores, type in CKD-EPI and choose
the one with the orange kidney icon. On opening the app, select the top option, “CKD-EPI Creatinine 2009 Equation”
Causes :
Hypo-perfusion - reduced blood flow to kidney: • Hypovolaemia • Other causes of
hypotension, for example sepsis and cardiac failure
REVERSIBLE IF CORRECTED EARLY
Correct the underlying cause : • Severe diarrhoea is a
common cause : correct with fluids, and electrolytes
If not corrected rapidly : • Acute tubular necrosis
develops – see next box
Causes:
Ischaemia • Pre-renal failure not
corrected
Toxins: • Tenofovir • Rifampicin • Amphotericin B • Aminoglycosides • NSAIDS
REVERSIBLE IF CORRECTED EARLY
• Correct the underlying
cause • Fluid and electrolyte
replacement if hypovolaemia
• Stop all nephrotoxic drugs
Causes: • Drug hypersensitivity Most common: • Rifampicin • Cotrimoxazole
Others: • Antibiotics: cephalosporins • NSAIDS • Traditional medicines
REVERSIBLE IF CORRECTED
EARLY
• Stop all implicated drugs: do not re-challenge
• The only exception is rifampicin if there is absolutely no alternative, and there is no doubt about TB diagnosis … re-challenge, frequent creatinine monitoring
General management: • Correct dehydration rapidly – 500 – 1000 ml bolus of crystalloid over 30 mins,
followed by 3 litres normal saline IV in 24 hours, plus oral fluids if tolerated • Correct electrolyte abnormalities, and correct the underlying cause • Look for sepsis : treat infections promptly • Stop all nephrotoxic drugs : for example, change tenofovir to another NRTI • Treat other co-morbidities causing renal disease : eg diabetes, hypertension
• Start with looking for acute kidney injury (marked AKI) : this is reversible if treated rapidly • Look for the underlying causes: dehydration, sepsis and drugs • First ask if there is PRE-RENAL kidney injury? This is common, and reversible if treated early • Next ask if there is ACUTE TUBULAR NECROSIS? Also common, and reversible if treated early • Always ask if HIVAN is likely? Reversible with effective ART • Always look for diabetes and hypertension
Pyelonephritis AKI: • Fever, flank pain • Leucocytes and proteinuria
on dipstick • Treat with antibiotics and
intravenous fluids: 10-14 days of antibiotics necessary, change to oral when there is a clinical response
Glomerulonephritis: • Acute AKI • or Chronic
Clinical presentation: Any of the following: • Proteinuria • Red blood cells in urine • Oedema • Hypertension
Many causes: • Including hepatitis B,
syphilis, diabetes
Often co-exists with other causes of renal impairment
• Proteinuria (must be present for diagnosis; urine dipstick essential ) • No hypertension: but may occur in
patients with existing hypertension • No oedema: It is a salt-losing condition • Often low CD4 counts but may occur at
any CD4 count
Treatment: • Effective ART: if failing first line, switch to
second line • ACE inhibitor to reduce proteinuria;
normal blood pressure is not a contraindication
• Avoid nephrotoxic drugs
Uncommon cause of renal impairment: • Obstruction to urine outflow
Most likely causes: • Urethral obstruction: prostatic
hypertrophy in older men • Ureteric obstruction: Cervical carcinoma,
abdominal lymphadenopathy in disseminated TB, cervical carcinoma
HIVAN
PRE-RENAL AKI
RENAL: DAMAGE IS WITHIN KIDNEY ITSELF
POST-RENAL
Acute Tubular
Necrosis (ATN) AKI
Acute Interstitial Nephritis AKI
Other
Renal disease in hospitalised HIV positive patients:
↓ Red cell production
↑ Red cell destruction
Lack of raw materials Bone marrow not working
• Anaemia of chronic disease: both HIV and TB cause bone marrow suppression;anaemia responds to treatment with ART and TB treatment. This is the mostcommon cause of anaemia in HIV positive patients
Drugs: AZT, cotrimoxazole - also common causes of anaemia due to bone marrow suppression: • Anaemia due to AZT is most likely within the first 6 months and at low CD4 counts• Switch AZT if other NRTIs are available; if possible, check patient is virologically
suppressed before changing one drug in a regimen• Stop prophylactic cotrimoxazole• If cotrimoxazole is for treatment of opportunistic infections, see if there is an alternative
available; primaquine and clindamycin for pneumocystis pneumonia, pyrimethamine,clindamycin and folinic acid for toxoplasmosis; ciprofloxacin for isospora belli diarrhoea.
Nutritional deficiency: • Malabsorption (eg chronic diarrhoea) or poor diet causing –
o Iron deficiencyo Folate deficiency
• Note this is rarely the most important cause in HIV patients=> always look for other causes
Lack of erythropoietin: • Occurs in severe, chronic renal failure• Acute kidney injury does not cause of anaemia• All patients should have creatinine on admission
Think about the following:
• Malaria• Cotrimoxazole• Rifampicin: consider if severe anaemia occurred after starting TB treatment.
Anaemia responds rapidly to stopping rifampicin. As alternatives torifampicin are rarely available, restart rifampicin with close monitoring ifanaemia resolves rapidly. If it does not improve, rifampicin is not the cause.Cotrimoxazole is the more likely cause if the patient is taking both drugs.
• Sickle cell disease – common in some countries
Blood loss – may be readily visible: haemoptysis, haematemesis, malaena. May be clinically silent – always think of the following: Kaposi’s sarcoma: • GIT bleeding is common and is often chronic and not seen by the patient or
medical staff• Always look at the palate, and all of the skin (undress the patient)
Hookworm: • Endemic in many countries: albendazole 400mg single dose
Obstetric and Gynaecological causes: • Ectopic pregnancy, miscarriage• Cervical cancer
Blood loss
Anaemia