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TUBERCULOSIS-HIVCOINFECTION


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OVERVIEWDIAGNOSIS

IMMUNE RECONSTITUTION INFLAMMATORY

SYNDROME(IRIS)

DRUG INTERACTIONS

DRUG REACTIONS

ISONIAZID PROPHYLAXISMDR/XDR TB

INFECTION CONTROL


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TB-HIV COINFECTION

TB is the commonest opportunistic infection in HIV infected adultsand the commonest cause of death.HIV negative TB patients have a 10% lifetime chance of getting Tb

whilst HIV+ have10%/year chance of getting TB again.Sputum + patients, HIV + patients, XDR AND MDR TB are consideredto be the drivers of the Tb epidermicTb accelerates the progression of HIV and vice versa, and despiteadequate tb therapy, both morbidity and mortality are increased inHIV seronegative patientsTb is prevalent at any stage regardless of CD4 cell count


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DiagnosisCulture (growing) of the bacteria is the gold standard distinguishes M.tb from other AAFBs/MycobacteriaAlternatively show the bacteria

Smear microscopy

Histopathological diagnosisNucleic amplification tests on clinical specimens, including sputumRadiographic methodsPhage-based detection methodologySputums only 6 0% of HIV + patients will be HIV positive

Smear positive case -if one acid fast bacillus seen in at least one sputumsampleSmear negative case- At least 2 sputum specimens are negative for AAFBsand


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Pulmonary tuberculosis

Sputums only 6 0% of HIV + patients will be AAFB positiveOnly 25%culture positive in milliary TB)

Smear positive case -if one acid fast bacillus seen in at least one sputum sampleSmear negative case-

at least 2 sputum specimens are negative for AAFBs andradiological abnormalities are consistent with active Tb andthere 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 TBStep 1

Send a third sputum specimen for AFB/ cultureStep 2Supply client with 7/7 broad spectrum antibiotic (amoxil 500mg po tds)

Step 3CXR

* Induced sputa/Bronchoscopy may be used in those with no sputum production.


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Smear negative pulmonary tuberculosis

Chest radiograph is an essential Ix in all smear negative suspectsRadiological findings depend on CD4 countTb pleural effusion can be diagnosed in adults younger than 45years 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 suggestexudate/cytology-neutrophils-Para pneumoniceffusion/lymphocytes tb/atypical cells malignancyAlternatives available include nucleic acid amplification assaywhich is specific for M.tb and is 80% sensitive.In milliary tb alternative specimens e.g. blood cultures 60%sensitive.


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DIAGNOSISTUBERCULIN SKINTEST-Also known as purified protein derivativetest/Mantoux test indicates an immunological memory of previous/ ongoingcontact with M.tb. Also positive in BCG vaccinated and those who had contactwith atypical mycobacteria

Usually gives false negative results in patients with CD4< 200/l

Recently INTERFERON GAMMA RELEASE ASSAYShave 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.


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Treatment

Lesotho 2 007 guidelinesTuberculosis is a stage 3 ( pulmonary)/stage 4 (extra pulmonary)disease thus patients are eligible for HAART regardless of CD4count

It is essential to rule out tb in all patients for ART initiation and treattb as soon as diagnosis is made.Children can be given Ethambutol in view of high resistancerates (3%) rates in Lesotho

Cd4 count When to initiate ART350 Re evaluate after completing ATT


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The Breastfeeding mother and TBA breastfeeding mother who has TB should receive full course ofATT. Timely and efficient Tb therapy is the most effective way toprevent transmission to the baby.

Mom and baby should continue to stay together and thebreastfeeding should be continued.After active TB in the baby is ruled out, the baby should receiveIsoniazid prophylaxis at 5 mg/kg for 6 months after which BCG isgiven.Pyrazinamide is recommended for all breastfeeding and pregnant

mothersStreptomycin is contraindicated in pregnancy.


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Immune Reconstitution inflammatory Syndrome

IRIS results from a pathological inflammatory response driven bythe recovering immune system after ART is started causing clinicaldeterioration. May be

UnmaskingARVs first and then TB presents

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


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Drug interactionsHIV-Tb co-infected patients are often on multiple drugs for the 2conditions apart from medications for comorbidities, nutritionalsupplements and alternative therapies hence great potential for druginteractions. 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 levelsreduced. Use Efavirenz instead/Rifabutin.Fluconazole levels are reduced by Rifampicin and Nevirapine levelsincrease by 100% - possible hepatotoxicityAvoid Phenytoin , Carbamazepine and Phenobarbitone withNevirapine .All reduce NVP levels.Oral contraceptives to be avoided with PIs and NNRTIs.With Rifampicinuse high dose estrogen pills/alternative contraceptive


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DRUG REACTIONS

TB liver Other infection

Hepatitis B/C/ACMV hepatitisSystemic bacterial infection

S/E of drugsPZAINHRifampicin

Differentiate by baseline ALT/AST;If N = S/E

If AbN = probable TB liver.BUT should investigate further to confirm TBinvolvement of liver

Aetiology of jaundice in patient newly started on TBtreatment


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day 1 INH 50 mgday 2 INH 100 mg

day 3 INH 300 mg

day 4-6 Daily ALT monitoring

day 7 Rifampicin 75 mg



day 10 Rifampicin full dose

day 11-13 Daily then weekly ALT monitoring

Management of drug-induced hepatitis 2 o to TBdrugs

ManagementStop TB treatment if ALT/AST

5 ULNMonitor LFT;Start liver friendly TB regimen

Ethambutol and streptomycin instandard doses. Ofloxacin 800mg daily

When bilirubin and transaminasesare approaching normal,rechallenge

Do not reintroduce PZA


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Management of skin reactions2o to TB drugs

ManagementStop TB treatmentStart liver friendly TBregimen

Ethambutol and streptomycin instandard doses. Ofloxacin 800mg daily

When skin reaction subsidedrechallenge but at much

longer intervals vs hepatitis

Listen to your patient!!!

day 1 INH 100 mg

day 7 INH 300 mg

day 14 Rifampicin 300 mgday 21 Rifampicin full dose

Day 28 PZA full dose


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ISONIAZID PROPHYLAXIS THERAPYIPT has been found to be beneficial in certain settings in preventing morbidityand mortality from TB. However due to difficulty of ruling out active TB in HIVpatients and risk of treating TB with a single agent, it is recommended thatIPT 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 patientsIPT prevented TB amongst people with CXR evidence oflatent TB infection

In HIV positive patients showed that IPT prevented TBup 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 TBHigh prevalence TB settings

IPT treatment of 24 people will prevent 1 case of TB disease


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Isoniazid prophylaxis therapyIPT should be given to

HIV positive patients who have POSITIVE TUBERCULIN SKIN TEST with noactive TB= 5mm of induration 48-72 hours after injection of 5iu of ppd

INH 300mg daily x 6 monthsAssess at each visit signs and symptoms of illness

Isoniazid 5mg/kg 6 months with

Pyridoxine 12.5mg if < 3yearsPyridoxine 25mg if >3 yearsHealth care workers who are HIV positive should be offered IPT.


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MDR/XDR TBMDR TB-resistant to rifampicin and IsoniazidXDR TB-resistant to resistant to rifampicin, isoniazid,fluoroquinolones and to at least one injectable drug i.e.capreomycin, amikacin and kanamycin.Su spect MDR TB if;

Retreatment patient who remains sputum positive after 3 monthsintensive phaseTreatment failure and interruption casesClose contacts of MDR TB casesChronic cases

Treatment is with at least 5 drugs that are in vitro active againstcausative strains should be administered for 4 month intensivephase and at least 12 of continuation phase, based on cultureconversion


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Infection controlAdministrative tools- triage procedures, segregation of patients, measuresto rapidly identify patientsEnvironmental factors- enclosed congregate waiting areas compromisehealth and safety

Well ventilated waiting areas for clients OPEN THE WINDOWS!!!!

Maintenance of good air circulation by opening windows and use of fansin waiting areas and consultation roomsUse of ultraviolet germicidal radiation

Personal protection- Strategies to reduce the inhalation of infectious TB particlesby 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 INHprophylaxis if appropriateTraining in infection control strategies


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N95 maskN95 masks will NOT work if

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

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


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REFERENCESLESOTHO NATIONAL TB CONTROL MANUALOxford handbook of HIV medicineHIV 2010

National Antiretroviral treatment guidelinesMedical Management of HIV infection South Africa edit ionReproduction Health & HIV Research Unit Coursehandbook

Dr Tsitsi Vimbayi Chatora

THANKYOU

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