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TUBERCULOSIS-HIV COINFECTION

OVERVIEW
‡ DIAGNOSIS ‡ IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME(IRIS) ‡ DRUG INTERACTIONS ‡ DRUG REACTIONS ‡ ISONIAZID PROPHYLAXIS ‡ MDR/XDR TB ‡ INFECTION CONTROL

TB-HIV COINFECTION
‡ TB is the commonest opportunistic infection in HIV infected adults and the commonest cause of death. ‡ HIV negative TB patients have a 10% lifetime chance of getting Tb whilst HIV+ have 10%/year chance of getting TB again. ‡ Sputum + patients, HIV + patients, XDR AND MDR TB are considered to be the drivers of the Tb epidermic ‡ Tb accelerates the progression of HIV and vice versa, and despite adequate tb therapy, both morbidity and mortality are increased in HIV seronegative patients ‡ Tb is prevalent at any stage regardless of CD4 cell count

Diagnosis
‡ Culture (growing) of the bacteria is the gold standard distinguishes M.tb from other AAFBs/Mycobacteria ‡ Alternatively show the bacteria
Smear microscopy Histopathological diagnosis Nucleic amplification tests on clinical specimens, including sputum Radiographic methods Phage-based detection methodology Sputums only 60% of HIV + patients will be HIV positive Smear positive case-if one acid fast bacillus seen in at least one sputum sample ‡ Smear negative case-At least 2 sputum specimens are negative for AAFBs and
‡ ‡ ‡ ‡ ‡ ‡ ‡

Pulmonary tuberculosis
‡ Sputums only 60% of HIV + patients will be AAFB positive ‡ Only 25% culture positive in milliary TB)
‡ Smear positive case-if one acid fast bacillus seen in at least one sputum sample ‡ Smear negative case‡ ‡ ‡ ‡ ‡ at least 2 sputum specimens are negative for AAFBs and radiological abnormalities are consistent with active Tb and there is laboratory confirmation of HIV or strong clinical evidence of HIV infection; Decision by clinician to treat with full course of antituberculosis chemotherapy

Improving the diagnosis of smear-negative TB
‡ Step 1 ‡ Send a third sputum specimen for AFB/ culture ‡ Step 2 ‡ Supply client with 7/7 broad spectrum antibiotic (amoxil 500mg po tds) ‡ Step 3 ‡ CXR * Induced sputa/Bronchoscopy may be used in those with no sputum production.

Smear negative pulmonary tuberculosis
‡ Chest radiograph is an essential Ix in all smear negative suspects ‡ Radiological findings depend on CD4 count ‡ Tb pleural effusion can be diagnosed in adults younger than 45 years if the fluid is not purulent and is clinically an exudate(straw coloured that forms clot on standing) ‡ In adults over 45 , blood fluid total protein ratio of >0.5 suggest exudate/cytology-neutrophils-Para pneumonic effusion/lymphocytes tb/atypical cells malignancy ‡ Alternatives available include nucleic acid amplification assay which is specific for M.tb and is 80% sensitive. ‡ In milliary tb alternative specimens e.g. blood cultures 60% sensitive.

DIAGNOSIS
‡ TUBERCULIN SKIN TEST-Also known as purified protein derivative
test/Mantoux test indicates an immunological memory of previous/ ongoing contact with M.tb. Also positive in BCG vaccinated and those who had contact with atypical mycobacteria
‡ Usually gives false negative results in patients with CD4< 200/µl

‡ Recently INTERFERON GAMMA RELEASE ASSAYS have been introduced for diagnosis of TB. They detect secretion of IFN by peripheral blood mononuclear cells induced by specific MTB peptides. More specific and sensitive than TST for diagnosis in immunosuppressed patients.

Treatment
‡ Lesotho 2007 guidelines ‡ Tuberculosis is a stage 3( pulmonary)/stage 4(extra pulmonary) disease thus patients are eligible for HAART regardless of CD4 count ‡ It is essential to rule out tb in all patients for ART initiation and treat tb as soon as diagnosis is made. ‡ Children can be given Ethambutol in view of high resistance rates(3%) rates in Lesotho
Cd4 count <200 201 - 350 >350 When to initiate ART 2 to 8 weeks after initiating ATT After 8 weeks of ATT Re evaluate after completing ATT

The Breastfeeding mother and TB
A breastfeeding mother who has TB should receive full course of ATT. Timely and efficient Tb therapy is the most effective way to prevent transmission to the baby. ‡ Mom and baby should continue to stay together and the breastfeeding should be continued. ‡ After active TB in the baby is ruled out, the baby should receive Isoniazid prophylaxis at 5 mg/kg for 6 months after which BCG is given. ‡ Pyrazinamide is recommended for all breastfeeding and pregnant mothers ‡ Streptomycin is contraindicated in pregnancy.

Immune Reconstitution inflammatory Syndrome
‡ IRIS results from a pathological inflammatory response driven by the recovering immune system after ART is started causing clinical deterioration. May be ‡ Unmasking
‡ ARVs first and then TB presents

‡ Paradoxical
‡ TB treatment ARVs and then worsening of symptoms ‡ Paradoxical TB IRIS occurs in 8 -43% of pt started on ART whilst on TB treatment, typically 1-4 weeks after initiating ART. ‡ It is generally advised that ART be continued and effective treatment of the condition be started, in severe cases corticosteroids may be considered in consultation with a specialist. ‡ Where the reaction is life threatening and not responding to steroids, it may be necessary to interrupt ART.

Drug interactions
‡ HIV-Tb co-infected patients are often on multiple drugs for the 2 conditions apart from medications for comorbidities, nutritional supplements and alternative therapies hence great potential for drug interactions. Furthermore there is potential for shared toxicities, ‡ Below are a few to look out for ‡ Rifampicin decreases levels of Kaletra-increase dose of Ritonavir by 75% ‡ Avoid Nevirapine with Rifampicin.Possible hepatotoxicity + NVP levels reduced. Use Efavirenz instead/Rifabutin. ‡ Fluconazole levels are reduced by Rifampicin and Nevirapine levels increase by 100% - possible hepatotoxicity ‡ Avoid Phenytoin, Carbamazepine and Phenobarbitone with Nevirapine.All reduce NVP levels. ‡ Oral contraceptives to be avoided with PIs and NNRTIs.With Rifampicin use high dose estrogen pills/alternative contraceptive

DRUG REACTIONS
Aetiology of jaundice in patient newly started on TB treatment
‡ TB liver ‡ Other infection
‡ Hepatitis B/C/A ‡ CMV hepatitis ‡ Systemic bacterial infection

Differentiate by baseline ALT/AST;
If N = S/E If AbN = probable TB liver. BUT should investigate further to confirm TB involvement of liver

‡ S/E of drugs
‡ PZA ‡ INH ‡ Rifampicin

Management of drug-induced hepatitis 2o to TB drugs
‡ Management ‡ Stop TB treatment if ALT/AST 5×ULN ‡ Monitor LFT; ‡ Start liver friendly TB regimen ‡ Ethambutol and streptomycin in standard doses. Ofloxacin 800 mg daily ‡ When bilirubin and transaminases are approaching normal, rechallenge ‡ Do not reintroduce PZA

day 1 day 2 day 3

INH 50 mg

INH 100 mg INH 300 mg Daily ALT monitoring Rifampicin 75 mg Rifampicin 150 mg Rifampicin 300 mg Rifampicin full dose

day 4-6 day 7 day 8 day 9 day 10

day 11-13 Daily then weekly ALT monitoring

Management of skin reactions 2o to TB drugs
‡ Management
‡ Stop TB treatment ‡ Start liver friendly TB regimen
‡ Ethambutol and streptomycin in standard doses. Ofloxacin 800 mg daily

day 1 day 7 day 14 day 21 Day 28

INH 100 mg INH 300 mg Rifampicin 300 mg Rifampicin full dose PZA full dose

‡ When skin reaction subsided rechallenge but at much longer intervals vs hepatitis ‡ Listen to your patient!!!

ISONIAZID PROPHYLAXIS THERAPY
‡ IPT has been found to be beneficial in certain settings in preventing morbidity and mortality from TB. However due to difficulty of ruling out active TB in HIV patients and risk of treating TB with a single agent, it is recommended that IPT be instituted at national scale only if active TB can be excluded.

‡ Does IPT work?
‡ Early studies showed that
‡ IPT prevented TB amongst contacts of TB patients ‡ IPT prevented TB amongst people with CXR evidence of latent TB infection

‡ In HIV positive patients showed that IPT prevented TB up to 2 years after giving 6 months IPT.
‡ Combined analysis of all trials revealed
‡ Effect of IPT varies with the baseline (community) risk of acquiring TB

‡ High prevalence TB settings ‡ IPT treatment of 24 people will prevent 1 case of TB disease

Isoniazid prophylaxis therapy
‡ IPT should be given to
‡ HIV positive patients who have POSITIVE TUBERCULIN SKIN TEST with no active TB ‡ = 5mm of induration 48-72 hours after injection of 5iu of ppd

‡ INH 300mg daily x 6 months
‡ Assess at each visit signs and symptoms of illness

‡ Isoniazid 5mg/kg × 6 months with
‡ Pyridoxine 12.5mg if < 3years ‡ Pyridoxine 25mg if >3 years ‡ Health care workers who are HIV positive should be offered IPT.

MDR/XDR TB
‡ MDR TB-resistant to rifampicin and Isoniazid ‡ XDR TB-resistant to resistant to rifampicin, isoniazid, fluoroquinolones and to at least one injectable drug i.e. capreomycin, amikacin and kanamycin. ‡ Suspect MDR TB if;
‡ Retreatment patient who remains sputum positive after 3 months intensive phase ‡ Treatment failure and interruption cases ‡ Close contacts of MDR TB cases ‡ Chronic cases

‡ Treatment is with at least 5 drugs that are in vitro active against causative strains should be administered for 4 month intensive phase and at least 12 of continuation phase, based on culture conversion

Infection control
Administrative tools- triage procedures, segregation of patients, measures to rapidly identify patients Environmental factors- enclosed congregate waiting areas compromise health and safety
Well ventilated waiting areas for clients OPEN THE WINDOWS!!!! Maintenance of good air circulation by opening windows and use of fans in waiting areas and consultation rooms ‡ Use of ultraviolet germicidal radiation Personal protection-Strategies to reduce the inhalation of infectious TB particles by staff and clients present in health care facilities (personal protection) ‡ Use of N95 masks to prevent inhalation of TB ‡ Encouraging clients and staff to know their HIV status, and to take INH prophylaxis if appropriate ‡ Training in infection control strategies ‡ ‡

N95 mask
‡ N95 masks will NOT work if
‡ ‡ ‡ ‡ ‡

They are not properly fitted If the wearer has facial hair (beard) preventing a proper fit They are damaged or crushed They are saturated (reused until the filter capacity has been exceeded) They get wet (even if they dry again) or oily

‡ Reusing masks
‡ Each staff member should reuse the same mask (it is helpful to write the staff member s name on the mask) ‡ Keep the mask dry, clean. ‡ Replace if undamaged or if two weeks old.

THANK YOU
REFERENCES
LE SO THO NATIO NAL TB CO NTR O L M ANUAL O x fo rd h an db o o k o f HIV m edic in e HIV 2010 Natio n al An tiretro v ira l treatm en t g u idelin es M edic al M an ag em en t o f HIV in fec tio n So u th Afric a editio n R ep ro du c tio n Health & HIV R esearc h U n it Co u rse h an db o o k

Dr Tsitsi Vimbayi Chatora

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