MSF HIV/TB. clinical guide REFERRAL LEVEL. July 2017

Transcription

1 MSF HIV/TB clinical guide REFERRAL LEVEL July 2017

2 MSF HIV/TB clinical guide REFERRAL LEVEL 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 if you happened to notice any abnormalities or mistakes. Published by Médecins Sans Frontières - Southern African Medical Unit (SAMU) July, th Floor, Deneb House, Corner of Main and Browning Roads, Observatory, 7925 Cape Town, South Africa Tel:+27 (0) Visit the Southern Africa Medical Unit s website: Copyright 2017, 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.

3 INPATIENT NOTES Name:.... Folder number:.... Date of Birth:... REFERRED FROM (CLINIC / HOSPITAL) CLINIC PATIENT ATTENDS RELATIVE'S CONTACT NUMBER Previous admissions ADMISSION RECORD DATE ADMITTED DATE DISCHARGED REASON FOR ADMISSION

4 Date Time Admitting Doctor Name Folder no. Date of birth History: symptoms, duration, functional status TB symptom screen circle all that apply: Cough Loss of weight Fever Previous opportunistic infections, additional past medical history: Night sweats Year of HIV diagnosis: CD4 counts - give dates and results: ART - circle one: ART history: Previous TB - dates of treatment: basis of diagnosis (circle all that apply): TB LAM/geneXpert/CXR/abdominal USS/symptoms/other ART currently ART previously ART naive First line: dates and regimen: Second line: dates and regimen: Sensitivity: Rif sensitive/rif resistant/unknown Current TB - when started: Adherence - circle one: No interruptions One interruption >1 interruption: Give dates: basis of diagnosis (circle all that apply): TB LAM/geneXpert/CXR/abdominal USS/symptoms Sensitivity: Rif sensitive/rif resistant/unknown Viral load: give dates and results: Adherence:

5 SOCIAL HISTORY Smoking / ETOH / Mining Occupation Lives with MEDICATION General Examination: Allergies: BP P Temp Sats Hb HGT Jaundice / Anaemia / Clubbing / Cyanosis LYMPH NODES (sites) SKIN MOUTH KAPOSI Y / N KAPOSI Y / N CVS Pulse: Volume regular/irregular JVP Apex Position: Nature: Normal Diffuse Heaving Tapping Auscultation: Parasternal heave Thrill DVT 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 Cranial nerves LIMBS Involuntary movement MOTOR Gait Bladder function Bowel function Tone Power Cerebellar Sensation Sphincter reflex: Reflexes UL LL R L R L Biceps (C5,6) Triceps (C6,7) Biceps (C5,6) Triceps (C6,7) Knee (L3,4) Ankle (L5,S1) Plantar Knee (L3,4) Ankle (L5,S1) Plantar URINE DIPSTIX: PRENANCY TEST: PV if indicated: CONTRACEPTION: PAP SMEAR:

6 Significant results: Urine LAM: positive/negative CrAg: positive/negative GeneXpert sputum: positive/negative Problem list: Differential Diagnosis: Management Plan: Signed: Print name: Date:

7 Continuation notes: SIGN & DESIGNATION (print name)

8 Advanced HIV Seriously Ill Patients SUMMARY Definition of seriously ill : DANGER SIGNS One or more danger signs Mortality is high: Do not delay investigations and management 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, rapid deterioration in vision Common causes of mortality: see box Often there is more than one cause Take a good history Examine the patient Focus on respiratory & neurological systems and ART history 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-infectious causes Hypoglycaemia Renal failure Abnormal sodium, potassium Liver disease Drug side effects Investigations DO Immediately 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 Management 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 bacterial pneumonia Empiric treatment for TB if Indicated 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 and no 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 lifethreatening, patient deteriorating, or not improving after 3 days of hospitalisation

9 ADVANCED HIV SERIOUSLY ILL PATIENTS DETAIL Definition of Seriously ill : One or more danger signs Mortailty is high: Do not delay investigations and management Respiratory rate > 30/min Temperature > 39 C Heart rate > 120/min Systolic BP < 90mm Hg Saturation < 90% Moderate/severe dehydration DANGER SIGNS 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, rapid deterioration in vision. Common causes of mortality: see box Often there is more than one cause Investigations and management focus on these causes Take a good history Start with the presenting complaint Always ask about neurological and respiratory symptoms, and diarrhea Ask the 2 key questions (see right) Examine the patient Reassess vital signs Specifically assess neurological and respiratory systems, and assess for dehydration Look for KS (skin, palate) Look for CMV retinitis if recent deterioration in vision 1. ART failure Disseminated TB is the most common cause of mortality: All patients need investigating for TB, and rapid initiation of treatment if indicated 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 levels are common, and are often asymptomatic 5. Other bacterial infections: Bloodstream infections Meningitis Urinary tract infections Key question 1: is the patient on ART? Patients on ART 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 6. Common non-infectious causes: Hypoglycaemia Renal failure Sodium/potassium abnormalities Liver disease Drug side effects: find out all the medication the patient is taking 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? 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 or not improving on TB treatment

10 ADVANCED HIV SERIOUSLY ILL PATIENTS (Detailed version continued) Investigations: Take sample immediately AND collect results within 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 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 infiltrate Pneumocystis pneumonia: Ground glass pulmonary infiltrate Bacterial 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 if indicated (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 TB treatment if indicated (see Management section) Other investigations for TB: Sputum microscopy: If genexpert unavailable CXR: see left Abdominal ultrasound: Lymphadenopathy Ascites Hepatosplenomegaly Centrifuge urine, CSF, ascites and pus otherwise sensitivity is very low. Lumbar puncture Indications for LP: Any neurological symptoms or signs Serum CrAg positive LP should be done before antibiotics are started unless this will delay the first dose; the sample can be stored in a fridge overnight Baseline investigations: CrAg Cell count and differential (lymphocyte count, neutrophil count) Protein, glucose Gram stain for bacteria: Streptococcal pneumoniae: gram positive cocci in pairs/chains Neisseria meningitidis: gram negative diplococci GeneXpert* If unable to do an LP or if there is an inevitable delay (eg referral is necessary for LP), empiric treatment may be necessary See Management section: Neurological Disease 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 suggests bacterial infection. In doubt, start antibiotics if seriously ill. Diagnosis can be reviewed upon further results Look for the source (pneumonia, meningitis, UTI): blood stream infections are also common Take blood culture*, using sterile technique; other relevant tests, e.g. urine dipstick, urine culture Take before antibiotics are started unless this will delay the first dose.

11 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 antibiotics can 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 fluconazole according to protocol in MSF/HIV handbook. 3. CXR evidence Respiratory of Danger TB (see Signs: RR > 30 or saturation < 90% Investigations page - CXR) 4. Seriously ill (any danger signs), or patient is deteriorating, or is not improving bd) after 3 days of hospital admission Oxygen by face mask or nasal prongs ccc Start empiric treatment immediately for: Pneumocystis pneumonia: cotrimoxazole (960mg/4kg body wt, plus prednisone initially 40mg 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 Clinical indications for immediate empiric TB treatment: 1. CNS TB is likely: Neurological symptoms/signs with evidence of TB elsewhere or clinical presentation is suggestive 2. 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 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/signs ccc 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

12 Confusion: causes 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 Neurological causes Medical Causes 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 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 Metabolic multiple causes: Hypoglycaemia Hypotension Hypoxia Hyponatraemia, hypernatraemia Hypercalcaemia Renal failure Liver failure Look for and correct the cause of all metabolic abnormalities Drugs: Efavirenz, isoniazid, steroids Alcohol and drugs: intoxication, withdrawal Change or stop all implicated drugs 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 protein Causes: 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 Psychiatric causes First exclude medical and neurological causes! HIV encephalopathy treatment is ART: Cognitive problems Behavioural problems & low mood Motor problems Psychiatric Disease Psychosis Depression Useful to ask if there have been previous episodes

13 Confusion Causes (see page 1): Neurological Medical Psychiatric History and examination Investigations What do you mean by confusion? Reduced consciousness Confused speech Disorientation in time/space Agitation/aggression Psychosis hallucinations delusions - delirium 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 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 lifethreatening Hypoglycaemia hypoxia hypotension malaria Look for other medical problems initial investigations: HB, white cells, platelets Na, K, creatinine Liver function tests RPR Neurological investigation Lumbar Puncture: Cell count and differential Gram stain Pandy (protein) CrAg RPR (omit if only rapid test available; not validated for CSF) GeneXpert on centrifuged CSF Take out when is lumbar puncture contraindicated? 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

14 Neurological Problems: Clinical Presentation 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) Global neurological dysfunction ( encephalitis ): Altered mental state Reduced level of consciousness Confusion See also confusion algorithm 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 Investigations Emergency Investigations: Lumbar Puncture: Other investigations: HIV and ART investigations: Glucose Rapid malaria test endemic areas 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 Cell count and differential Gram stain Pandy (protein) CrAg RPR (if available; note rapid test is not validated for CSF) GeneXpert: centrifuged CSF 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 CD4 count Viral load if on ART > 3 months Always take a full HIV and ART history! 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

15 Neurological problems: Interpretation of lumbar puncture results 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

16 Big 3 CNS opportunistic infections: Look for all of these in all patients Other common infectious causes Malaria Neurosyphilis Bacterial meningitis Cryptococcal meningitis Headache, meningitis symptoms, or altered level of consciousness Focal neurology: ophthalmoplegia and visual disturbance are common Investigations: CD4 low (usually <100) CSF CrAg positive Treatment: Amphoterocin B and fluconazole Measurement of opening pressure and therapeutic LPs are essential Full protocol: see MSF guideline Toxoplasmosis Reactivation of latent disease, causing space occupying lesions Any abnormal neurology: focal symptoms, any type of altered mental state Investigations: Toxoplasmosis IgG positive (if available) This shows previous exposure, cannot confirm that there is reactivation 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 Tuberculosis Meningitis Tuberculomas: space occupying lesions causing encephalitis symptoms and focal neurology 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 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 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 Remember Trypanosomiasis in endemic areas: CSF microscopy for parasites Other HIV-related causes CMV - CD4 < 100: Treat for CMV encephalopathy if CMV retinopathy seen on fundoscopy Treatment: 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 Non-infectious causes Cerebral Vascular Accident (Stroke) Focal neurology: a large stroke may cause reduced level of consciousness Causes: HIV itself diagnosis of exclusion Hypertension, diabetes Medical/metabolic causes: See confusion algorithm

17 Respiratory Problems * = in red, the big 3 respiratory diseases! They may co-exist, always look for all 3 Clinical presentation Dyspnoea Cough; productive or dry? Fever Respiratory danger signs: Respiratory rate > 30 Hypoxia: oxygen saturation < 90% Haemoptysis History: Duration of onset, additional symptoms Examination: look for lymph nodes pleural effusion wasting skin lesions Initial assessment 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 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) All patients are TB suspects Acute onset: days Look for alternative/additional causes Subacute onset: up to 2 weeks *Tuberculosis: investigations *Bacterial pneumonia *Pneumocystis pneumonia Look for Kaposi s Sarcoma 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! 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 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 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 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 Don t Forget Respiratory Emergencies: Pulmonary embolism Pneumothorax (common complication of pneumocystis pneumonia) Haemoptysis Empyema

18 Blood loss 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 Most common causes: Malaria Rifampicin: consider if severe anaemia occurred after starting TB treatment. Anaemia responds rapidly to stopping rifampicin. As alternatives to rifampicin are rarely available, restart rifampicin with close monitoring if anaemia 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 Red cell destruction (erythrocytolyse) Anaemia Red cell production 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 most common cause of anaemia in HIV positive patients Drugs: AZT, cotrimoxazole - also common causes of anaemia 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. For example primaquine and clindamycin for pneumocystis pneumonia, pyrimethamine, clindamycin and folinic acid for toxoplasmosis Lack of raw materials Nutritional deficiency: Malabsorption (eg chronic diarrhoea) or poor diet causing o Iron deficiency o Folate deficiency Note this is rarely the most important cause in HIV patients => always look for other causes Lack of erythropoietin: this is all one box now Occurs in severe, chronic renal failure Acute kidney injury does not cause of anaemia All patients should have creatinine on admission

19 Renal Disease in Hospitalised HIV positive Patients Acute Kidney Injury: Dehydration Sepsis Nephrotoxic drugs : particularly tenofovir, rifampicin, cotrimoxazole Often there is more than one cause HIVAN (HIV associated nephropathy) If detected early, HIVAN is reversible However it may progress to chronic kidney disease 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 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 Investigations 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 Use the Cockcroft-Gault formula: Use the correct formula for the units of creatinine used by your laboratory Creatinine clearance (ml/min) = (140 age in years) x weight (kg) : for women, multiply x 0.85 serum creatinine in µmol/l Creatinine clearance (ml/min) = (140 age in years) x weight (kg) : for women, multiply x x serum creatinine in mmol/dl 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 Urine dipsticks Urine microscopy Abnormal sodium and potassium are common in kidney disease and may be lifethreatening Severe hypokalaemia is common in Potassium may be very high in chronic kidney disease 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 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

20 Renal disease in hospitalised HIV positive patients: 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 General management: Correct dehydration rapidly 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 PRE-RENAL AKI RENAL: DAMAGE IS WITHIN KIDNEY ITSELF POST-RENAL 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 Acute Tubular Necrosis (ATN) AKI 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 Acute Interstitial Nephritis AKI 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 Other 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 Pyelonephritis AKI : Fever, flank pain Leucocytes and proteinuria on dipstick Treat with antibiotics and intravenous fluids: days of antibiotics necessary, change to oral when there is a clinical response 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 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

21 Diarrhoea in HIV positive patients What is diarrhoea? > 3 stools per day Decreased consistency: takes the shape of the container Associated symptoms: fever, abdominal pain, vomiting Complications: Dehydration, hypovolemic shock Acute kidney injury Electrolyte abnormalities Bacteraemia, septic shock Causes: Infectious: Viral Bacterial Parasites Mycobacteria: disseminated TB 3 questions Acute vs Chronic: Acute - < 2 weeks Chronic - > 2 weeks Acute diarrhoea 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 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 noninflammatory 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 Chronic diarrhoea 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

22 Patients deteriorating or not improving on TB treatment 1. Essential background information Evolution of illness: Pattern of improvement/deterioration 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 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 nonspecific symptoms It always important to review the initial diagnosis, as per algorithm Initial improvement on TB treatment? No improvement at all? Improved with TB treatment, deteriorated when ART started? If not proven or no sensitivity testing Send all possible samples GeneXpert very helpful: sputum, CSF, urine 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? 2. Consider specific causes Drug sensitive Tb proven, therapeutic level of drugs too low: Dose too low Malabsorption: Chronic diarrhoea, vomiting Rifampicin levels sub therapeutic Not drug sensitive TB: DR TB MAC Adverse drug effects: TB meds ART Cotrimoxazole Efavirenz Others Additional diagnosis: Original TB diagnosis correct, but now something extra Alternative diagnosis: Original diagnosis of TB not correct 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 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