with these FACTS... 2

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1 Gibson Kibiki MD, MMed, PhD KCRI - KCMC Tanzania PRIOR 10 th Nov 2009, Nijmegen, The Netherlands 1

2 with these FACTS... 2

3 The leading causes of death worldwide from preventable infectious diseases 3.0 in 2002 Millions of deaths HIV/AIDS Tuberculosis Malaria Measles 3

4 Nigeria South Africa Ethiopia DRC Tanzania Kenya Uganda Zimbabwe NB: East Africa with the highest number of Tb cases than any other region in Africa 4

5 Estimated new TB cases (all forms) per population No estimate or more 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 5

6 70,000 60,000 50,000 40,000 30,000 20,000 10,000 0 HIV Smear + Return Fail Other Relapse Smear - Extra-P 6

7 80 % TBR TNG MAIN ZNZ TZ 7 SND SHY RVM RKW PWN MZA MTW MOR MBY MRA LND K'NJ KGM KGR IRGA DDM ARA DSM

8 25 20 OUTCOME OF HIV/AIDS PATIENTS AT KCMC HOSPITAL, TANZANIA Deaths Perce entage Good/Better Period (Years) Kibiki GS. PGS,

9 Diagnostic Category N Prevalence Mortality Pulmonary TB % 24% Malaria % 31% Gastroent./Diarrhea % 20% Non-TB chest infections * % 36% N = 1,242 patients * Some maybe missed Tb cases Chest infections contribute to 31% of over-all admission with the in-hospital mortality of 60% Ole-Nguyaine, et al. Ann Trop Med Parasitol. 2004;98:

10 Chest infections are the leading causes of morbidity and mortality Tb in the major cause What is the aetiology of RTI? Is the non-tb RTI real? Is the current Tb Dx approach efficient? Are the current Tb drugs effective What is the MTB, anyway? were among the studies we conducted 10

11 Bronchoscopy and BAL Alveolar - the actual site of Tb and host interaction Rigorously defined Tb cases (Culture + rt PCR) To avoid misdiagnosing of Tb Human data are important to direct future research no animal model can replicate the complexity of (AIDS-associated) Tb Such data are scarce in ssa Where the burden is highest 11

12 causes of chest infection in HIV at KCMC Identified causes in 59.2% (N = 120) In 29.2% - common bacteria higher than previous (14 S. pneumoniae, 1 S. pyogenes, 7 S. aureus, 5 coliform, 5 klebsiella spp, 3 P. aeruginosa) (17% mortality) less that previous In 23.3% - M. tuberculosis (32% mortality) higher than previous In 10% - HHV8 (42% mortality) Never reported previously In 7.5% - P. jiroveci, and rt PCR 14.2% (0% mortality)? In 4.2% - fungi Crypt. neoformans, Asp. fumigatus 12% pts infected by at least 2 organisms 40.8% pts no M.O (12% mortality) widen dx scope Kibiki G et al.. EAMJ. 2007: 84(9);

13 Of 22 patients with cavities only 7 (31.8%) had TB Other cavities were due to Multiple infections Different organisms e.g. bacteria Locations of cavities for both TB and non-tb were nonspecific 13

14 Miliary lesions Of 6 patients with miliary lesion ONLY 1 (16.7%) had TB The other causes of miliary lesions were 1 Klebsiella, HHV8 1 Klebsiella, Crypto, St. aureus, P. carinii 1 Ps. aeruginosa 2 none > 10% of CXR Normal Clinical features were less discriminative of the cause 14

15 Microbiological Tb diagnosis is paramount in HIV infection Atypical presentation Overlap of TB clinical and x-ray features with other causes TB is the leading cause of morbidity and mortality Sputum smear for AFB Widely used Recommended by WHO for ssa 15

16 method Positive n/n (%) Positive (G.S. ) ** sensitivity specificity Culture BAL 28/120 (23.3) BAL AFB 18/120 (15) 2/ Sputum 12/64 (18.8) 0/ culture* Sputum AFB* 8/64 (12.5) 4/ Serology 0/120 (0) 2/ rt PCR 73/120 (60.8) 46/120*** *ONLY 64 patients (53.3%) produced adequate sputum ** G.S. = Gold standard *** None of them was diagnosed to have active TB for 18 months Kibiki G et al, TM & IH. 2007: 12 (10);

17 Bottleneck Sputum scarcity Low sensitivity C T -value (IQR) ZN stain for AFB Serological test p< p< Prolonged Culture time Low specificity of rt PCR Influenced by endemicity of Tb CT 40 in endemic settings Couldn t distinguish active Tb from latent Tb?Low CT value culture + (n=27) culture - (n=42) smear + (n=17) smear - (n=56) 17

18 INH monoresistance is increasing in ssa It leads to MDR In Northern Tanzania (N = 135) 7.2% - INH mono-resistance 1% - to streptomycin. 3.5% - resistant to multiple drugs 2.7% - MDR strains 1.8% - resistant to all four anti-tb drugs Kibiki et al, BMC microbiol

19 Spoligotyping Diversity of genotypes:- EAI, CAS1 Kili, CAS1 Delhi, Manu, T, LAM, Beijing etc New strain Beijing - a major strain Few new unique strains Dominant spoligotypes:- Cas1 Kili and LAM11 ZWE LAM strains in South Africa are associated with XDR High transmission rate and human movement Kibiki et al, BMC microbiol

20 This knowledge has enriched our understanding of Tb and designing control strategies Improved Tb lab improved Dx Equipment, Dx methods (culture media, LED, P3 Safety cabinet) Improving Rx with the current drugs and other potential Tb drugs HighRif Early ART in Tb Toxicity profile of the Tb drugs Fluores Current (mis)use of the potential Tb drugs 20

21 more building contractors came from Europe....and also some young students from Europe came to learn Tb.....and building experts.....and a new generation of researchers was born. 21

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