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5 Diagnosis of Drug-Resistant TB
5 Diagnosis of Drug-Resistant TB
Pages 43-54
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From page 43... ...
• A strengthened health care infrastructure in South Africa would sup port detection and treatment of drug-resistant TB. TB patients progress from exposure to cure in discrete steps: infection, symptoms, clinic visit, diagnosis, treatment onset, conversion from an active infection to a noncontagious state, and cure.
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From page 44... ...
Negative patients that are highly clinically suspicious should be managed according to the normal National Health Laboratory Service algorithm for that country, suggested van Helden. Considerations and Trade-Offs in Developing and Adopting Diagnostics In considering what types of diagnostic tests should be developed and adopted within a high-burden country, a number of criteria come into play.
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From page 45... ...
; invasiveness of sample taking; skills, instruments, and personnel required; and central versus decentralized laboratory capacity and logistics. Problems with Current Diagnostics The problem with many diagnostic methods currently in use is that the answer they provide can be both yes and no, said van Helden (Box 5-1 describes some of these methods)
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From page 46... ...
aSince the workshop was held, a new, fully automated DNA test (Xpert MTB/RIF) for TB has been validated and subsequently recommended by WHO for broad implementation as the initial diagnostic for individuals suspected of MDR TB or HIV−TB coinfection.
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From page 47... ...
One evaluation of the use of LRPs in Mexico and South Africa found that they provided susceptibility results with an overall accuracy of 99 percent and had a median turnaround time of 3 days, making them the fastest phenotypic method available. The future direction of LRPs is toward a 1-hour test, extended for XDR TB, as well as the development of reporter phage assays for susceptibility testing with second-line drugs.
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From page 48... ...
CHALLENGES OF LABORATORY CAPACITY5 Coetzee observed that South Africa's response to MDR TB has been limited by the unsatisfactory performance of its laboratory services and inadequate human resources. In 2009 nearly 1 million cultures were performed in South Africa, most of which were followed up with drug susceptibility testing, and these tests identified 9,000 new MDR TB cases.
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From page 49... ...
Positive patients will again receive an LPA test. Because the existing infrastructure could not accommodate new laboratory space, modular park home units were specially designed to be suitable for use as laboratories, and specifically for polymerase chain reaction (PCR)
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From page 50... ...
The project Biomarkers of Protective Immunity against TB in the Context of HIV/AIDS in Africa, which involves 15 partner institutions from Africa, Europe, and the United States, has been seeking to identify correlates of protective immunity and host biomarkers of TB that have prognostic potential for delineating disease susceptibility and protection.8 The project's objectives are to • investigate differences in immune response between individuals who are exposed to TB and protected from the disease and those who develop active disease; and • coordinate to promote the design and testing of new TB vaccines, drugs, and diagnostics, especially in areas with high HIV infection rates. Particular attention is being paid to people coinfected with both M.tb.
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From page 51... ...
WP5 is being used to assess the immune responses to BCG vaccination and the effects on disease progression. About 17,000 individuals from different age groups with a varied spectrum of TB with or without HIV in five African countries are being followed.
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From page 52... ...
These subjects were followed up clinically over the 2 years, with blood samples being taken at three time points -- 0, 6, and 18 months. The objective was to assess immune responses over time using all the platforms described earlier and to identify biomarkers of disease susceptibility and protection, comparing subjects who contracted disease during the course of this followup period with those who remained healthy without succumbing to disease progression.
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From page 53... ...
According to Parida, the objectives include • bringing together basic scientists from the laboratories and clini cians from clinics in the communities and hospitals through effec tive communication and interaction; • achieving a holistic understanding of resistance, susceptibility, and protective immunity, taking an open-minded, global approach; • coordinating initiatives and finding synergies within the scientific community, including interdisciplinary approaches and cross fertilization of ideas; • establishing global, shared, and comprehensive biorepositories; • aligning vaccine trials and intervention studies; • creating an open access policy and enforcing it through the buy-in of all stakeholders; generating public−private−philanthropic partnerships; and • • enhancing functional collateral/symbiotic interactions between basic science and real lives in clinics to translate research knowl edge into products of public health importance. The following issues require further consideration: • the natural history of infection in the context of drug-resistant TB and immune responses; and • differential gene expression patterns of MDR and XDR TB strains, with virulence depending on the host environment.
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