National Tuberculosis Reference Laboratory Challenges in Capacity in SA for diagnosing DR-TB March 2010 Gerrit Coetzee
Rapid response to XDR-TB WHO Global Task Force on XDR-TB, October 2006 Accelerate access to rapid tests for rifampicin resistance Adherence to WHO Drug Resistance Guidelines; improve programme management; access to MDR-TB drugs including DOT; HIV+ cases adequately treated and started on ART Implementation of IC measures, especially among HIV+ Strengthen laboratory capacity to diagnose, manage and survey DR; rapid survey to determine size of XDR-TB problem Initiate information sharing strategies that promote prevention, treatment and control of XDR-TB
Challenges in TB control Health systems weaknesses one of the greatest challenges in TB control Laboratory services one of the weakest links Lack of diagnostic capacity a crucial barrier preventing an effective response to the challenges of HIV-associated TB and drug-resistant TB 500,000 new MDR-TB cases estimated annually 10% of MDR-TB cases XDR-TB and present in more than 50 countries SA: 4 th highest total number MDR reported 2007 5% of MDR-TB cases projected to be treated in 2009 and 3% only under GLC standards
Why laboratory performance is unsatisfactory Inadequate human resources Biosafety concerns Lack of recognition of laboratory importance in TB control Weak communication between NTP and laboratory services Insufficient financial resources Problems of laboratory availability and accessibility Delay in technology transfer to resource-limited settings
TB CULTURES PER PROVINCE PER YEAR (excl KZN) PROVINCE 2004 2005 2006 2007 2008 2009 Grand Total EC 35,132 47,866 69,229 96,496 140,559 154,600 543,882 FS 18,240 22,434 29,288 37,072 36,629 31,569 175,232 GP 79,481 124,193 155,780 172,968 223,785 225,889 982,096 LP 4,128 5,315 8,407 13,504 16,884 19,550 67,788 MP 13,246 13,813 15,616 21,047 34,880 46,237 144,839 NW 14,312 17,864 24,036 36,134 44,388 41,842 178,576 NC 20,016 25,062 31,949 35,133 41,362 44,250 197,772 WS 115,300 135,106 158,584 177,710 211,902 230,228 1,028,830 Total 299,855 391,653 492,889 590,064 750,389 794,165 3,319,015
Number of NEW MDR-TB patients diagnosed by the NHLS by province per year PROVINCE 2004 2005 2006 2007 2008 2009 Total EC 379 545 836 1,092 1,501 1,858 6,211 FS 116 151 198 179 381 253 1,278 GP 537 676 732 986 1,028 1,307 5,266 KZN 583 1,024 2,200 2,208 1,573 1,773 9,361 LP 59 40 77 91 185 204 656 MP 162 134 139 506 657 446 2,044 NW 130 203 225 397 363 520 1,838 NC 168 155 188 199 290 631 1,631 WC 1,085 1,192 1,179 1,771 2,220 2,078 9,525 Total 3,219 4,120 5,774 7,429 8,198 9,070 37,810
Number of NEW XDR-TB patients diagnosed by the NHLS by province per year PROVINCE 2004 2005 2006 2007 2008 2009 Total EC 3 18 61 108 175 123 488 FS 1 6 3 4 3 3 20 GP 5 14 19 38 30 65 171 KZN 59 227 336 241 181 254 1,298 LP 2 5 2 2 6 17 MP 12 14 18 44 NW 1 5 9 4 4 13 36 NC 4 10 3 7 19 40 83 WC 12 16 28 42 60 72 230 Total 85 298 464 458 488 594 2,387
Genome of M. tuberculosis H37Rv 4,411,529 bp 4000 genes
Line probe technologies endorsed by WHO in 2008 for the rapid detection of MDR-TB katg RMP INH # 1 2 3 4 5 CC AC TUB WT1 WT2 WT3 WT4 WT5 WT6 WT7 WT8 MUT1 MUT2A MUT2B MUT3 WT MUT1 MUT2 katg katg katg katg WT1 WT2 MUT1 MUT2 MUT3A MUT3B inha inha inha inha inha inha inha TUB MUT katg WT katg MUT inha WT inha MUT sensitive resistant sensitive ++ - + - + - + + +- + - + + - + + +- +- - + + + - + - +- + + + - - - - +- + resistant + + + + Detects resistance to both rifampicin and isoniazid Licenced for use on AFB smear positive processed sputum specimens and positive cultures inha
South African LPA roll out DNA STRIP Technology HAIN LIFESCIENCE
NHLS LPA Roll out LPA endorsed by WHO, will be part of National TB Control Programme Roll out over 2 years ~20 additional regional sites Now have LPA for 2 nd line anti-tb drugs Other systems eg gene Xpert also developing
LPA Roll out: Objectives Provide rapid diagnosis of MDR-TB Timeously effect appropriate treatment Prevent further development of resistance to antituberculosis drugs Prevent further transmission of tuberculosis Cut down on the cost of diagnosing TB by screening drug-susceptible TB out of conventional drug susceptibility testing (DST) using the LPA Decrease the cost of treating TB by reducing unnecessary transmission through early diagnosis, as well as preventing development of drug-resistant TB which is more expensive to treat
Project goals roll the assay out to additional 20 laboratories by December 2010 implement the assay with as little disruption to the normal flow as possible standardize the performance, reading, interpretation and reporting of results across laboratories
Project Approach Phase I: Secure laboratory space (renovate existing labs or erect mobile labs) Phase II:Order and install equipment Phase III:Recruit staff (technicians/medical scientists) Phase IV: Train staff Phase V: Implement the assay Phase VI: Review success of initial roll out and start the procedure for the next cycle
Laboratory name Dr George Mukhari Completed 18August 2009 Edendale Completed 7 August 2009 PE Completed 5 August 2009 Status of laboratory renovations / mobile lab construction Mafikeng Completed 14 September 2009 Baragwanath Ngwelezane (M- PROJECTS) Helen Joseph Paarl Worcester Welkom Madadeni (M-PROJECTS) Ermelo No. 1 (M-PROJECTS) Ermelo No. 2 (M-PROJECTS) Polokwane (PARK HOMES) East London Tshepong (PARK HOMES) George Letaba Nelspruit Rustenburg Kokstad PCR labs completed; DNA extraction room renovations to go on tender Completed to sign off Awaiting Hospital approval Awaiting Hospital approval Ready for tender, on hold pending DOH Contractor busy, estimated to finish by end of October Ground work quote finalized, Park Home Lab ready for delivery Ground work quote finalized, Park Home Lab ready for delivery Park Home Lab ready for delivery, to be adapted as a culture lab Awaiting ground work quote, busy manufacturing Park Home Lab Awaiting Hospital approval for Park home Awaiting ground work quote, busy manufacturing Park Home Lab Awaiting Hospital approval Awaiting Hospital approval. Business manager is following up Space for mobile lab verbally allocated, though no formal letter. Concern is that space is about 200m from the lab & next to a crèche. Space to be renegotiated. Two rooms at Rustenburg lab previously ear marked for viral loads, could be used as an alternative. Approval for placing a mobile lab will first be requested. Space for mobile lab identified. Awaiting hospital approval
LPA inter-laboratory comparison 10 DNA samples Include fully susceptible, INH/Rifampicin mono-resistance, MDR, MOTTS Excellent performance 4x pa.
Development of an Algorithm Simplify current algorithms Capacity of laboratories to inactivate sputum to PCR friendly state Cost to NTP should not increase Laboratory capacity/physical structure for LPA PCR Available technical skills At least provisionally confirm MDR phenotypically Technical problems eg amplicon contamination
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