Are peripheral microscopy centres ready for next generation molecular tuberculosis diagnostics?

Abstract

intervention schedules or strategies may be required to maximise the possibility of eradicating bacterial colonisation. Are peripheral microscopy centres ready for next generation molecular tuberculosis diagnostics?To the Editor:Sputum smear microscopy is the primary test for tuberculosis (TB) in most high-burden countries. Direct Ziehl-Neelsen (ZN) microscopy is routinely implemented in these countries via a vast network of decentralised, peripheral microscopy centres (as opposed to centralised reference laboratories), often located within primary or community health centres. This decentralised approach increases access in primary care settings and may help reduce diagnostic delays [1]. However, microscopy has limitations and novel diagnostics are urgently needed, particularly in settings with high prevalence of drug resistance and HIV [1,2].While Xpert1 MTB/RIF (Cepheid, Sunnyvale, CA, USA), a World Health Organization-endorsed test, is already being rolled out in many countries, it is intended for district or sub-district laboratories [3], and not peripheral microscopy centres. In contrast, at least four next-generation nucleic-acid amplification tests (NAATs) are now on the market, with the goal of point-of-care (POC) use in peripheral laboratories [4,5]. Can these so-called ''POC-NAATs'' actually be implemented in peripheral microscopy centres? Is there sufficient expertise (e.g. to extract DNA) and biosafety (e.g. to process sputum)? Will the necessary infrastructure (e.g. stable power supply) be present? Will environmental conditions (e.g. high temperature) limit their use?The introduction of novel diagnostics that aim to replace smear microscopy in peripheral laboratories is more likely to succeed if the new tests are designed with real world conditions in mind. However, there are limited data on landscape of microscopy centres in high-burden countries. We addressed this gap with a survey of 22 high-burden countries. We designed a one-page, 12-question survey. We focused on the most important requirements and considerations for the next generation of TB diagnostics. We included questions about ambient temperature and humidity conditions, safety, infrastructure, availability of equipment and expertise, and communication infrastructure.We contacted at least three experts in each country. If the responses were discrepant, we attempted to obtain at least one additional response from another expert. All contacts had extensive field experience and were either working for the national TB programme or non-governmental organisations, or were carrying out diagnostics or implementation research in the respective countries. Respondents were instructed to focus on the ''typical'' most peripheral microscopy laboratory in the country.We were able to obtain at least three responses from 17 of 22 (77%) high-burden countries. For four countries, we received two responses that were consistent and matched well with other countries of comparable purchasing power parity. For one country, we received only one response; however...

New screening technologies for type 2 diabetes mellitus appropriate for use in tuberculosis patients [Review article]

“…A recent study highlighted that a waste management system in TB microscopy centers existed in only 50% of the 22 high-burden TB countries. 43 The indoor temperature always remained below 35ºC in only 23% of the countries, but 82% had gloves in stock. 43 The DM burden in the 22 high-burden TB countries continues to grow, 3 and it is estimated that globally between 30% and 90% of those with DM are undiagnosed.…”

“…43 The indoor temperature always remained below 35ºC in only 23% of the countries, but 82% had gloves in stock. 43 The DM burden in the 22 high-burden TB countries continues to grow, 3 and it is estimated that globally between 30% and 90% of those with DM are undiagnosed. 28 In examining the various disadvantages associated with current DM screening tests relating to their use in TB patients, it is clear that to address the WHO's recommendation for the universal screening of TB patients for DM, two distinct screening needs emerge: 1) a POC DM assay that requires no patient preparation, is acceptably accurate, sensitive and specifi c, is low cost, requires minimal infrastructure and is easy to use; and 2) an assay that differentiates transient hyperglycemia from pre-diabetes and DM.…”

“…Given the infrastructure constraints experienced by TB microscopy centers in the 22 high-burden TB countries, 43 an ideal test/device would require no maintenance or calibration, and would have no temperature or storage control requirements. There should not be any need for reagents that are not included with the disposable or kit.…”

Tuberculosis diagnostics: which target product profiles should be prioritised?

“…These issues are being addressed by ongoing activities, supported by the Bill and Melinda Gates Foundation (Seattle, WA, USA) and other partners [3,7,11].…”

Molecular diagnosis of tuberculosis: we need solutions that span the healthcare value chain

“…Furthermore, lack of DST makes it challenging to implement this assay in areas with high prevalence of multidrug-resistant TB (MDR-TB). It is unclear whether LMICs can successfully implement this manual technology at the level of peripheral microscopy centers which have limited infrastructure and resources [11,12].…”