Impact of HIV on the TB Epidemic in Africa

Transcription

1 Impact of HIV on the TB Epidemic in Africa Anthony David Harries Senior Advisor International Union against TB and Lung Disease The captain of all these men of death 1

2 Robert Koch 1882: Described the tubercle bacillus and linked it to cause of TB 1882: Ehrlich developed a more rapid stain AFB 1882: Ziehl and Neelsen developed the currently used Z-N stain TB CHEMOTHERAPY 1944 Streptomycin (S) 1945 Para-amino salicylic acid (PAS) 1952 Isoniazid (H) 1954 Pyrazinamide (Z) 1960 Thiacetazone (T) for use in developing world 1962 Ethambutol (E) 1969 Rifampicin 1960s - Standard treatment: months 1970s- Short course treatment: 6 8 months 2

3 1970s 1980s TB is a conquered disease BUT: sharp increase in global TB in 1980s Disease flourished in developing world, but no visibility because subsumed into primary health care TB control neglected everywhere Dissolution of the Soviet Union Advent of HIV and AIDS 3

4 Chimpanzees Sooty-Mangabey Monkeys 1930s 1940s HIV-1 Entered human population in 1930s HIV-2 Global HIV Epidemic: 2007 Region People with HIV Adult HIV-prevalence Sub-Saharan Saharan Africa 22.5 million 50% 5.0% N.Africa + Mid East 380, % Asia and Oceania 4.9 million 0.3% South America/Caribbean 1.9 million 0.5% East Europe/ C. Asia 1.6 million 09% 0.9% West / C. Europe 760, % North America 1.3 million 0.6% Total 33.2 million 0.8% 4

5 Why HIV is so successful Transmitted predominately by sex Long latent interval from infection to disease Targets the CD4 lymphocyte y Mutagenic and can evade ARV drugs and vaccines Reverse Transcriptase Inhibitors Integrase Inhibitors HIV Virus Reverse transcriptase Integrase Protease Inhibitors Entry Inhibitors CCR5 Inhibitors Fusion Inhibitors Protease New HIV Virus 5

6 THE TB-HIV INTERACTION Risk of TB in persons with Mycobacterium tuberculosis Not HIV Infected HIV Infected Life time risk = 5-15% Annual risk = 5-15% 6

7 TB risk in HIV-infected person 1200 TB risk doubles in first year of HIV 1100 CD4 Cell Count (cells/mm 3 ) TB risk increases as CD4 count declines AIDS Weeks Years Death Risk of active TB in PLHIV CD4-lymphocyte count Risk of active TB per year > 350 cells/ul cells/ul 12.0 < 200 cells/ul 17.5 Badri et al, Lancet

8 DUAL INFECTION 14 million people co-infected with HIV and M.TB in the world 11 million people co-infected with HIV and M.TB in sub-saharan Africa (80%) 0/year Reported TB cases/100, Growth in TB incidence in Eastern and Southern Africa, Malawi Botswana Kenya S Africa Zimbabwe

9 Estimated HIV prevalence in new adult TB cases HIV prevalence in TB cases, years (%) or more No estimate Sub-Saharan Africa: 35% TB cases HIV-infected Southern Africa: 60-80% TB cases HIV infected The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO All rights reserved 1990: Global TB incidence = 8 million Global TB deaths = 1-2 million 1993: WHO (Dr Arata Kochi) declared TB a global emergency 9

10 Framework for TB Control DOTS Sustained political commitment Case detection with smear microscopy Standardised short-course treatment Uninterrupted supplies of drugs Standardised monitoring and evaluation Dr. Karel Styblo Director of IUATLD Pioneered the DOTS TB Pioneered the DOTS TB Control Framework in the 1980s in Tanzania, Malawi, and Mozambique 10

11 Find TB suspects through passive case finding Obtain sputum for smear microscopy Get sputum to the laboratory Sputum prepared with Z-N stain or fluorescence and examined by light microscopy 11

12 Z-N stain: AFB on the slide = smear-positive PTB Algorithms for diagnosing smear-negative PTB and EPTB 12

13 Get the patient registered and on TB Treatment as soon as possible Implement directly observed treatment (DOT) Standardised TB Treatment New Cases: 2RHZE/ 4RH or 6HE for new smear-positive PTB and serious EPTB 2RHZ/4RHor 6HE for new smear-negative PTB and not serious EPTB Relapse Cases: 2SRHZE/1RHZE/5R 3 H 3 Z 3 E 3 for relapse smearpositive PTB WHO recommended regimens

14 Systems in place to ensure uninterrupted TB drug supplies Standardised monitoring, recording and reporting 14

15 Quarterly supervision / monitoring of all TB Registration centres and collation of national data Targets for TB Control: set for 2000, then deferred to 2005 To detect 70% of estimated smear-positive PTB cases To cure 85% of detected smear-positive PTB cases In the absence of HIV, target achievement will lead to:- 40% decrease in infected contacts 5-10% decrease in TB incidence 15

16 GLOBAL PROGRESS: 1995: DOTS Programmes initiated worldwide 2005: 189 countries used DOTS 26 million patients treated under DOTS Global TB incidence rate stabilised Global TB case detection rate = 62% Global TB treatment success rate = 84% PROGRESS IN AFRICA REGION: By 2005: TB case detection rate = 51% [target = 70%] TB treatment success rate = 74% [target = 85%] 16

17 EFFECT OF HIV ON TB CONTROL Programme delivery Patient management increased TB cases hot spots of transmission stigma illness in health staff difficult TB diagnosis increased mortality increased recurrent TB spread of MDR- XDR-TB PROGRAMMATIC EFFECTS 17

18 Notified TB cases in Malawi: Sm-TB Sm+PTB % 52% 67% 75% 75% HIV-prevalence rate in TB patients MALAWI: TB and HIV interaction TB cases per annum Adult HIV prevalence 30, Notified ied TB cases Adult HIV-seroprevalence 25, ,000 15, , ,

19 HIV increases the number of young women with TB Ln (% TB patients that are women) Ln (% HIV prevalence in adults, 15-49y) The women s TB ward in QECH, Malawi: beds and 77 patients on initial phase therapy 19

20 An increase in PTB suspects means:- Guidelines for diagnosis of smearpositive PTB are not followed Logistics (sputum containers) fail to keep pace with demand More sputum smears have to be prepared and examined False negative sputum smear rates increase Case detection for smear-positive PTB may decline HOT SPOTS OF TB TRANSMISSION Prisons Refugee camps Boarding Schools Health care facilities Households of TB patients 20

21 WEAKENS HEALTH CARE DELIVERY Staff absenteeism due to illness Staff absenteeism due to attending funerals Staff attrition due to death 21

22 Survey in 40 Malawian hospitals: 1999 Number of health care workers 2979 Number (%) who died in the year 60 (2.0%) Deaths due to TB 28 (47%) Deaths due to AIDS 10 (17%) Deaths due to chronic illness 17 (28%) [Harries et al, Transactions Royal Soc Trop Med Hyg, 2002] The District TB Officer at work 22

23 TB OFFICERS IN MALAWI Year No. in post No. who Died [Salaniponi et al, Int J Tuberc Lung Dis 1999] PATIENT MANAGEMENT 23

24 Difficult diagnosis Advancing HIV immune suppression [less inflammation and granuloma formation] PTB Smear-positive Cavities Upper lobe disease PTB Smear-negative Infiltrations Lower lobe disease EPTB Disseminated disease 24

25 Smear-negative PTB: diagnostic algorithm Cough > 3 weeks No response to antibiotics Three sputum smears negative for AAFB Chest x-ray showing abnormalities Chest x-rays in HIV-positive culture-positive PTB CD4 count 350 CD4 count 50 25

26 Slim Disease Up to 40% of patients with Slim Disease have disseminated TB at autopsy (Lucas et al, BMJ,1993) Deaths in New Sm+ve PTB patients in Malawi % deaths Year 26

27 Deaths in HIV-related TB Smear-negative PTB and EPTB: increased case fatality Early case fatality: 50% or more of TB-treatment deaths in first two months of therapy High rate of recurrent TB after successful treatment HIV+ve HIV-ve Zaire 18% 6% (Perriens et al, 1991) Kenya 17% 0.5% (Hawken et al, 1993) Zambia 22% 6% (Elliott et al, 1995) S.Africa 16% 6% (Sonnenberg et al, 2001) 27

28 Re-infection or re-activation? Estimated incidence of recurrence due to re-infection or relapse in relation to HIV: Recurrences due to HIV- HIV+ Re-infection Relapse [Lambert et al, Lancet Infect Dis, 2003] Rate of recurrent TB and CD4 count Baseline CD4 count Risk of Recurrent TB < (95%CI ) > (95%CI ) Charalambous et al, IJTLD

29 Facilitates spread of drug-resistant TB: XDR-TB in a rural area of Kwa-Zulu, Natal, South Africa XDR-TB: resistant to first and second line medications 53 patients diagnosed with XDR-TB 67% had previous hospital admission 100% of those tested were HIV-infected 98% died (median time to death 16 days) [Gandhi NR et al, Lancet 2006] HIV derails achievement of targets Reduces case detection of smear-positive PTB even though it increases TB case burden Reduces TB treatment success rates 29

30 Millennium Development Goals (MDG) adopted in 2000 MDG 6, Target 8 to halt and reverse incidence of TB by 2015 STOP TB Partnership MDG linked: By 2015: reduce TB prevalence and death rates by 50% relative to 1990 By 2050: eliminate TB as a public health problem (<1 case / million) Will we meet the MDG-STOP TB Partnership goal by 2015? Using the old DOTS approach and with current progress, NO Two other important reasons for potential failure:- Africa: HIV/AIDS (~80% of all HIV-TB) East Europe/China/India: MDR-TB (~75% of all MDR-TB) 30

31 Global Plan to Stop TB, Pursue high quality DOTS expansion Address HIV/TB and MDR / XDR-TB Contribute to health system strengthening Engage all care providers Empower people p with TB, and communities Enable and promote research 10-year Global Plan costed at USD$56 billion: [TB-HIV component costed at $7 billion] How do we decrease the joint burden of HIV and TB? 31

32 PREVENT HIV INFECTION Collaborative activities to reduce burden of TB / HIV Establish collaboration between TB and HIV Prevent TB in people with HIV Joint planning, supervision, monitoring and evaluation Surveillance of HIV in TB pts TB infection control Intensified TB case finding IPT (isoniazid preventive therapy) Treat HIV in patients HIV testing and counselling with TB HIV prevention CPT (cotrimoxazole prophylaxis) HIV care ART (antiretroviral therapy) WHO/HTM/TB/ WHO/HTM/HIV/

33 Should all these activities be implemented? - Criteria National or local HIV prevalence > 1% OR HIV prevalence in TB patients at or > 5% All other situations Recommended activities All activities should be implemented Joint planning and surveillance and measures to decrease burden of TB in PLHIV Joint Collaboration Pre-2003 Little collaboration [HIV-prevention: TB treatment] 2003 onwards Better collaboration Antiretroviral therapy Spread of drug-resistant TB to HIV infected persons 33

34 Prevent TB in HIV-infected persons HIV-infected person Infection control (TB) in high risk settings Intensified screening for TB in high risk areas Ati Active TB No active TB ART Anti-TB Treatment Isoniazid Preventive Therapy 34

35 TB Infection Control Administrative measures Environmental protection Prompt diagnosis and treatment of smear +ve PTB Separate TB cases from other cases Maximize cross-ventilation Personal protection measures HIV test HCWs IPT and ART for HCWs Keep TB suspects away from non-tb suspects Isoniazid preventive therapy: excellent efficacy Primary prevention in HIV+ve persons: reduces frequency of TB by 43% (CI, 21% - 59%) [Wilkinson et al, BMJ, 1998] Secondary prevention in HIV-infected patients with successfully treated TB: reduces frequency of recurrent TB by 50-80% [Fitzgerald et al, Lancet, 2000; Churchyard et al, AIDS, 2003] 35

36 Isoniazid Preventive Therapy [implementation straightforward] so, why has it not been scaled up? We do not know where to set up IPT clinics or who should take responsibility Concerns about difficulties in excluding active TB in HIV-infected persons Fear of creating INH resistance Infection Control (IC) The Three I s Intensified case finding (ICF) Isoniazid Preventive therapy (IPT) [Now being promoted in 2008 by WHO as an HIV service] 36

37 ART reduces TB in people with HIV With massive coverage, ART should decrease the incidence and prevalence of TB Cape Town (16 month follow up) - ART 2.4 TB cases /100 pt-years Non-ART 9.7 TB cases /100 pt-years [Badri et al, Lancet, 2002] Cape Town (40 month follow up) - ART Yr TB cases /100 pt-years ART Yr TB cases / 100 pt-years [Lawn et al, AIDS, 2005] Data from Brazil: risk of TB in relation to ART/ IPT Adjusted hazard ratio No ART 1 ART only 0.55 IPT only 0.36 ART and IPT 0.23 [Golub et al, AIDS 2007] 37

38 Treat HIV in patients with TB Diagnosis of TB registration and anti-tb treatment Provider initiated HIV testing and counselling If HIV-seropositive Starts cotrimoxazole preventive therapy as soon as possible Starts antiretroviral therapy [Timing depends on CD4 count] 38

39 HIV Testing of TB patients: example from Malawi MALAWI TB patients 26,836 26,136 26,019 26,659 25,767 HIV tested 3,983 6, , ,002 21,027 (15%) (26%) (47%) (66%) (83%) Cotrimoxazole Preventive Therapy (CPT): Cheap ($8 per year) and safe Effective: reduces mortality by 20-40%, reduces hospital admissions by 50%, and significantly reduces frequency of malaria and diarrhoea [Wiktor et al, Lancet, 1999; Chintu et al, Lancet 2004; Nunn et al, BMJ 2008] Does not lead to widespread antibiotic resistance in the community Does not select for SP-resistant malaria parasites 39

40 ANTIRETROVIRAL THERAPY [ART] Opportunities for TB Entry point for ART Benefits of ART HIV+ve PTB = Stage III and eligible Reduction in mortality if started early enough HIV+ve EPTB = Stage IV and eligible Reduction in recurrent rates of TB 40

41 Anti-TB treatment and ART: some of the issues When to start ART (early or late) Additive adverse drug effects Drug drug interactions (rifampicin NNRTI) Pill burden and adherence to therapy Immune reconstitution syndrome Providing ART and anti-tb treatment (one stop shop) Need for additional cotrimoxazole and isoniazid We are failing to provide our HIV+ve TB patients with ART Malawi (2006): 29% HIV+ve TB patients placed on ART Kenya (Q4,2006): 30% HIV+ve TB patients placed on ART Rwanda (Q1,2007): 31% HIV+ve TB patients placed on ART 41

42 Are we on target with TB-HIV? Activity Number HIV-positive persons actively screened for TB Number of eligible HIV-positive persons offered IPT Global Plan Country Reports Target 2006 for ,000, ,000 (3%) 1,200,000 27,000 (2%) Number of TB patients tested for 1,600, ,000 (42%) HIV Number of HIV-positive TB patients started on ART 220,000 66,000 (30%) WHO Report 2008 Global Tuberculosis Control WE NEED TO DO BETTER: Global: we have to meet the funding gap (currently USD$ 30 Billion) Countries: we have to implement activities 42

43 1. More money and more efficient money flows to implementers and infrastructure development 2. Human Resources: treat, train and retain and task-shift 43

44 3. Good procurement and distribution systems 4. Supervise, monitor, report and reward performance Mulanje DH: Quarterly Report Number TB cases registered 340 Number TB cases HIV tested 275 Number TB cases HIV+ve 192 Number HIV+TB cases on CPT 186 Number HIV+TB cases on ART

45 5. Research and development A rapid, diagnostic test for smear-negative TB Better and earlier access of TB patients to ART 6. Leadership and Stewardship 45

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