0 Recommendations

Framework of indicators and targets for laboratory strengthening under the End TB Strategy

By Marguerite Massinga Loembe | 28 Oct, 2016

WHO recently published a useful framework to assist with the planning of laboratory network systems in view of the objectives of the End TB strategy by 2030:
http://apps.who.int/iris/bitstream/10665/250307/1/9789241511438-eng.pdf?ua=1

Particularly useful are recommended methodologies for calculating country-specific targets, based on local epidemiology, TB services access issues etc as opposed to global targets used before (ie: 1 microscopy center per 100,000 population etc) and an associated Excel calculation spreadsheet:
http://www.who.int/entity/tb/publications/calculations_of_lab_capacity.xls?ua=1

I would like to hear thoughts from prospective fellow users (NTP directors and TB lab managers, PMDT consultants, lab advisers) about this tool and eventually exchange tips for its effective use. Notably, I am wondering if NTP/TB lab managers in ressources limited countries or in countries with only partially effective TB lab networks foresee that implementing universal DST testing in the coming years is feasible and get views on how this can be phase in as part of national strategic plans ?

I am also wondering if translation to other languages (ie: French, Spanish) is eventually planned ?

Marguerite

Centre de Recherches Médicales de Lambaréné (CERMEL)
Gabon

Replies

 

Wayne van Gemert Replied at 5:04 AM, 31 Oct 2016

Dear Marguerite and all,

Thanks for having shared the Framework of Indicators and Targets for Laboratory Strengthening under the End TB Strategy (http://www.who.int/tb/publications/labindicators). We are indeed translating it into French, Portuguese, Russian and Spanish, and would welcome any feedback about how we can make the calculation spreadsheet more useful, accurate and user friendly.

The GLI is planning to organize sessions/workshops at regional Union conferences in 2017 in order to give national TB programme and laboratory managers the opportunity to share experiences and best practices in laboratory strengthening activities, including on the implementation of WHO policies and use of GLI products.

May I take the opportunity to also share the recently published GLI Quick Guide to TB Diagnostics Connectivity Solutions (http://stoptb.org/wg/gli/gat.asp). Newer diagnostics, including Xpert MTB/RIF, Bactec MGIT, line probe assays with automated readers, as well as a number of HIV-related instrument-based diagnostics, produce results data in digital format (also known as electronic data). Unlike written data on paper, electronic data can be rapidly and accurately sent and analysed using a diagnostics connectivity solution. This allows for several important uses: the performance of instrument networks can be monitored remotely, results can be transmitted automatically to clinicians, laboratory information management systems or electronic registers, and inventory can be managed in real-time, along with other uses. Connectivity solutions can provide a highly cost-effective way to ensure proper functioning of an instrument network and improve linkage to care and patient management. This GLI Quick Guide provides an overview of diagnostics connectivity solutions, and what is required to establish one and use it effectively. It also contains a link to an online table comparing the functionalities of currently available softwares (http://tinyurl.com/gliconnectivity). The Guide is currently being translated into French, Portuguese, Russian and Spanish. For any questions, contact

Best regards,
Wayne van Gemert
Technical Officer | Laboratories, Diagnostics & Drug Resistance Unit
WHO Global TB Programme

Attached resources:

David Moore Replied at 6:35 AM, 31 Oct 2016

Dear Marguerite (and Wayne)
This is an excellent initiative that will finally give countries a mechanism by which they can understand the needs and shortfalls in TB diagnostic and DST provision. However there are two important concerns - disregard for phenotypic DST and apparent indifference towards isoniazid resistance.

Sadly and inexplicably it seems that the utility of phenotypic testing is becoming increasingly marginalised by WHO, despite the widely known fact that we have incomplete coverage of resistance-conferring mutations for ALL DRUGS.

The introduction of the acronym WRD (for "WHO recommended rapid diagnostics") in this document appears to be exclusively reserved for molecular tests, even though WHO-endorsed phenotypic testing by MODS gives rifampicin and isoniazid DST in 7 days and MGIT can achieve the same within 2 weeks of sputum collection. The term "rapid" was originally applied to tests that undercut the previous 6 week turnaround time inherent to conventional indirect DST such as MODS, the nitrate reductase assay and the ill-fated plaque assay. It has since been appropriated to mean testing within a few hours, the inference being that this translates into a meaningful reduction in pre-treatment loss to follow-up in a way that diagnosis that takes a week does not achieve. Data supporting this purported superiority in closing the diagnosis-treatment gap are lacking.

Countries like Peru, which has been ahead of the game for universal DST through implementation of MODS and latterly Genotype MTBDR-plus, will, using this otherwise excellent Excel tool, return data that erroneously appear to indicate very low levels of testing. Peru recognised early that these less expensive alternatives to Xpert MTB/RIF were capable of delivering more information (resistance to isoniazid and detection of rifampicin resistance overlooked by Xpert MTB/RIF) in a meaningful useful timeframe, with additional advantages (the strain is immediately available for more extended DST if needed, and molecular epidemiology if desirable). And significantly lower cost, particularly of MODS, continues to enable testing of a much larger number of patients for the same limited budget.

Another concern is that this exclusively molecular approach (heavily reliant upon Xpert MTB/RIF) has the effect of downgrading the importance of detection of isoniazid resistance which is a perilous path - this forum hardly needs to be reminded that for patients with undetected INH mono resistance, representing 12-15% of all TB patients globally, continuation phase therapy with RH is effectively RIF mono therapy...

So whilst these new initiatives, and in particular the monitoring tool, are certainly welcomed, there should be room for alternative, equally valid and more affordable strategies to be considered. Countries understandably pay attention to WHO recommendations so there is a responsibility to ensure these recommendations guide but also allow for other approaches - e.g. thousands of MGIT platforms were implemented in labs around the world following an earlier WHO-endorsement and FIND-supported roll-out - to imply they should now be mothballed in favour of molecular-only approaches is a betrayal of the earlier investment in laboratory infrastructure, personnel and sample and result delivery systems and screams of wastefulness in an environment where resources are perennially constrained.

Prof Dave Moore
LSHTM TB Centre

Dr Shanta Ghatak Replied at 7:04 AM, 31 Oct 2016

That was such a good read David. Long pending

Sent from Shanta's iPad

Marguerite Massinga Loembe Replied at 11:00 AM, 1 Nov 2016

Dear Pr David

Thanks a lot for the elaborated and very informative feedback which brings forth questions of high relevance.

Dear Wayne

The various points raised by Dave bring forth concerns of high significance also for countries where TB laboratory capacity is still limited with absent or minimal NRL TB services (ie: several countries in Central Africa are still lacking TB culture facilities): what should be the key factors to consider when implementing DST ? Indeed, specific guidance would be useful to make informed decision when choosing which type of assays (molecular vs phenotypic) to put in place as a priority, keeping in view often scarce financial (and/or human) resources and limited technical/maintenance services onsite. At this stage, should NRL first be equipped for genotypic DST (ie: Xpert complemented by first and second line LPA) to allow rapid diagnosis and tx initiation ? Or should programs aim for technically challenging setup of biosafety compliant TB culture facilities necessary for treatment follow up ? Indeed prospective alternative methods such as MODS are not widely known/promoted. How best should TB diagnostic capacity be phased in ? With currently available options for WHO recommended TB diagnostics where should efforts best be invested (again if staring from no or only limited capacity) in order to have optimal impact on patient management and disease control ? If universal DST access is the final objective, affordability will indeed also be a consideration of utmost importance for program managers.

Best regards

Marguerite

Centre de Recherches Médicales de Lambaréné (CERMEL)
Gabon

Wayne van Gemert Replied at 12:23 PM, 3 Nov 2016

Dear Dave and Marguerite,

Thanks for your feedback and questions.

Like any technology, advancements in TB diagnostics will eventually result in a need to replace equipment and methods over time to achieve better performance and increase patient access. That being said, the recommended technologies today are still largely complementary, and include phenotypic methods for both detection of TB and for drug-susceptibility testing (http://apps.who.int/iris/bitstream/10665/162712/1/9789241508612_eng.pdf). MGIT and LPA continue to play critical roles in detection of second-line drug resistance in particular (see indicator 8 of the Framework).

The Framework of Indicators addresses the WHO End TB Strategy goals of rapid and early detection of TB and drug-resistant disease, together with universal access to rifampicin testing as a marker for multidrug-resistance. This means that increased patient access to DST for rifampicin requires technologies that can be placed at lower levels of a health system, ie. not confined to reference laboratory level. Despite significant efforts in many countries to implement stronger specimen transport networks, highly centralized testing (eg. using MGIT or LPA at reference level laboratories) often entails long distances, associated with very long turnaround times, contaminated specimens and lost results. Gains in global coverage for rifampicin testing were therefore modest until the wider roll-out of the automated Xpert MTB/RIF assay. Furthermore, while Dave mentions the shortcomings in molecular methods for detecting all resistance-conferring mutations, phenotypic testing using MGIT also has well-described shortcomings in detection of borderline rifampicin-resistant strains which are detectable by molecular methods. There is still no technology today that meets all the requirements of accuracy, robustness and ease-of-use.

There are strong grounds to test for rifampicin susceptibility before choosing a TB regimen. Ensuring wide patient access to rapid DST for this drug has therefore been rightfully prioritized as a core indicator by the group of authors and reviewers of the Framework. A similar prioritization was made by the group responsible for development of the High-priority Target Product Profiles for New Tuberculosis Diagnostics in 2014 (http://apps.who.int/iris/bitstream/10665/135617/1/WHO_HTM_TB_2014.18_eng.pdf). Evidence is weaker on how the detection of non-MDR isoniazid resistance could help clinicians decide upon a treatment which would improve outcomes over a 6-9 month first-line regimen. The WHO Global TB Programme is currently assessing the effectiveness of fluoroquinolone-containing regimens in these patients.

In response to Marguerite’s question about how countries should phase in technologies for DST vs treatment monitoring, this is largely country-specific but in general these activities must be planned in parallel. The entire network should be planned comprehensively so that specimen referral systems will allow patients detected with drug resistance using lower level DST technologies to also have access to higher level DST and treatment monitoring as needed.

Best regards,
Wayne

This Community is Archived.

This community is no longer active as of December 2018. Thanks to those who posted here and made this information available to others visiting the site.