Tag: FIND

Categories
Add Resources - Research & Development

Forum discusses research agenda for SARS-CoV-2 antigen rapid diagnostic tests

Participants identify key questions to take technical and programmatic research forward.

ACT-Accelerator diagnostic pillar partners joined in a virtual forum to discuss the development of a collaborative operational research agenda for SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs). 

The forum, held on 29 October 2020, was organized around three breakout groups according to three thematic areas for SARS-CoV-2 Ag-RDTs:

  • Technical research
  • Programmatic research
  • Modelling

Group participants focused on understanding the performance of Ag-RDTs when implemented in real-world settings and across specific populations. 

Priority questions

  • Performance
  • Use cases
  • Samples
  • Bio-safety
  • Quality control
  • Training and delivery
  • Economics and cost.

Participants discussed steps to advance the Ag-RDT research agenda and agreed that there should be multiple future discussions on this. 

Read the report here

Categories
Add Resources - Research & Development

Rapid diagnostic tests for COVID-19

Key takeaway: Both types of RDTs are crucial for effective public health management.

Rapid diagnostic tests (RDTs) for COVID-19 can detect either antigen (Ag) or antibody (Ab), and both types of tests have important roles.

A combination is needed for effective patient management and public health planning.

This May 2020 report outlines general information on Ag- and Ab-detection RDTs for COVID-19, and suggested uses for them.

Polymerase chain reaction (PCR) or Ag

  • Directly detects the virus and should be prioritized for diagnosis and monitoring
  • Prioritize for case management to enable decentralized testing – particularly where PCR testing is limited.

Immune response tests or Ab

  • Tests detecting viral immune response tests can be complementary for clinical care
  • Should be prioritized for seroprevalence and epidemiological purposes
  • Prioritize Ab RDTs for seroprevalence surveys to inform public health measures and testing of contacts to establish previous viral spread.

The value of any test is dependent on factors such as the test performance, or sensitivity/specificity, as well as the epidemiological context, or prevalence in the population where it is used, and timing.

The report also lists unique features of SARS-COV-2 to consider when using RDTs and specifies operational characteristics, such as how to interpret test results. 


Read the report here

Categories
Add Resources - Research & Development Featured Work - Manufacturing Featured Work - Research & Development

US$7 million investment accelerates availability COVID-19 self-tests in low- and middle-income countries

Key takeaway: Successful applicants to manufacture 240 million low-priced tests a month.

On March 31 2021, FIND launched a request for proposals (RFP) to develop, manufacture, and launch to market COVID-19 self-tests in low- and middle-income countries (LMIC). 

The RFP called for quality-assured and easy-to-use self-tests that were accurate and affordable. It was prepared in the context of the Access to COVID-19 Tools (ACT) Accelerator Diagnostics Pillar, co-convened by FIND and the Global Fund.

Innovators, developers and manufacturers of in vitro diagnostics, and LMIC-based diagnostic stakeholders, were invited to submit proposals.

A package of US$7 million was offered in support, funded via grants to FIND from the German Federal Ministry of Education and through KfW and other donors.

International expertiseFrom 80 applicants, contracts were signed with four companies, and their names announced in February 2022:

Each has committed to manufacturing up to 60 million tests per month, priced from US$1–2 per test.FIND will conduct independent clinical evaluations of test performance, with support dependent on meeting project milestones.

Categories
Add Resources - Manufacturing Featured Work - Research & Development

US$21-million investment in molecular diagnostic platforms

FIND chooses four firms with promising new platforms for decentralized diagnosis of COVID-19 and other illnesses.

FIND is investing US$21-million to speed the development, manufacturing and launch of affordable, multi-pathogen, molecular diagnostic platforms.

These platforms are specifically aimed at decentralized settings in low- and middle-income countries (LMICs), and will detect different respiratory pathogens, including COVID-19.  

FIND launched the request for proposals in August 2021, in the context of the Access to COVID-19 Tools (ACT) Accelerator diagnostics pillar, which it co-leads. 

The submission deadline was September and the successful firms announced on December 2021.

The four firms are:

The German Federal Ministry of Education and Research (BMBF) is funding the investments through KfW and other donors. 

Read the full report here

Categories
Add Resources - Manufacturing Add Resources - Research & Development Featured Work - Awareness & Advocacy

Call to boost access to cheaper rapid diagnostic tests

Key takeaway: RDT agreements boost local manufacturing to supply millions of low-cost, high-quality tests for lower-income nations.

In July 2020 FIND and Unitaid launched a call via the Access to COVID-19 Tools Accelerator Diagnostics Pillar for expressions of interest (EOI) to speed up availability and scale up manufacturing of rapid diagnostic tests (RDTs) for COVID-19.

The EOI was geared towards increasing supply of regulatory approved, fit-for-purpose SARS-CoV-2 Ag RDTs that met WHO criteria of quality, cost and accessibility. This was particularly needed in low- and middle-income countries (LMICs).

Innovators, developers and manufacturers of RDTs and in vitro diagnostics, and LMIC-based diagnostic stakeholders, were invited to submit proposals.

Interventions included:

  • Accelerating late-stage product development and optimization
  • Facilitating technology transfer activities
  • Conducting performance evaluation studies to support regulatory submissions
  • Increasing production capacity
  • Addressing supply chain challenges
  • Strengthening local capacity for development and deployment of new tests within national testing strategies. 

Driving down prices and supporting the use of less invasive specimens to enable faster LMIC uptake were also critical. 

Over 100 applications were received, with 34 selected for review by a panel of external experts. 

A first collaboration, with Premier Medical Corporation in India, was announced in January 2021. By July that year, additional technology transfer agreements were signed with stakeholders in Africa and Latin America.

These included an agreement with DCN Dx to transfer know-how to WAMA Diagnóstica (Brazil), and with Bionote and Mologic to transfer know-how to DIATROPIX of the Institut Pasteur de Dakar (Senegal). 

There is a separate partnership between Viatris (South Africa) and Guangzhou Wondfo Biotech (China).

These agreements will lead to a dramatic increase in local manufacturing, ultimately making more than 250 million low-cost (US$2–2.50) tests available for LMICs. 

Categories
Add Resources - Research & Development

SARS-CoV-2 diagnostic use cases

Nine examples of when to use COVID-19 investigative procedures

FIND has supported partner Halteres Associates in developing diagnostic use cases for SARS-CoV-2 tests, which highlight the comparison, contrast and implications for each. 

This report outlines nine diagnostic use cases where further assays or investigative procedures are warranted. 

It provides a description of each use case, other possible technologies required, more information on the sample and comments.

Use cases for SARS-CoV-2 assays

  1. Triage of symptomatic individuals in an epidemic setting
  2. Triage of symptomatic individuals in endemic settings
  3. Triage of at-risk pre-symptomatic and symptomatic individuals in endemic settings
  4. Confirmatory testing
  5. Diagnosis of symptomatic individuals in endemic or epidemic settings
  6. Differential diagnosis in endemic or epidemic settings
  7. Previous SARS-CoV-2 exposure
  8. Surveillance in sites of previous or potential outbreaks
  9. Environmental monitoring.

Learning curve
Before developing systems, however, it is essential that test developers understand the details of use cases for SARS-CoV-2 testing. 

This includes who will be tested, by whom, the site of testing, using which samples, under what conditions, and what the minimum acceptable clinical performance requirements are likely to be. 

The most important component is intended use: what clinical decision the test will enable, and in what patient population. 

For more information, contact us or Halteres Associates.

Read the full text here

Categories
Add Resources - Research & Development

How genomics can help track new SARS-CoV-2 variants

Sequencing data key for monitoring virus and understanding impact of therapeutics.

This report on SARS-CoV-2 variants, developed and published for FIND (11 March, 2021) by PHG Foundation, explains how genomics helps to monitor the evolution of coronavirus “variants of concern”, or VOCs.

It outlines how genomic surveillance and sequencing have supported identification of new variants as well as the impact these variants have had on diagnostic tests and public health measures. 

This process has also significantly advanced vaccine design and development. 

Ongoing surveillance is required not only for known VOCs, but also for new “variants of interest” (VOIs).

Thinking ahead
Data produced has enabled further understanding of the variants, helping to inform future surveillance and the impact mutations may have on vaccines, diagnostics and therapeutics. 

Various countries have invested in sequencing infrastructure and resources to help combat the virus, and have put public health measures in place in response. 

Continued investment in sequencing capabilities and data sharing, as well as a variety of skills and expertise from multiple backgrounds, is needed to make genomic surveillance successful. 

In addition, it is important to limit the spread of the virus to prevent the emergence of additional variants which may be even more transmissible. 

Sequencing data continues to be key for monitoring the virus and understanding the impact of therapeutics.

An appendix on resources actively monitoring VOCs is included.

Read the full report here

Categories
Resource Centre - Publications

SARS-CoV-2 VOCs, Mutational diversity and clinical outcome: Are they modulating drug efficacy by altered binding strength?

The global COVID-19 pandemic continues due to emerging Severe Acute Respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC). Here, we performed comprehensive analysis of in-house sequenced SARS-CoV-2 genome mutations dynamics in the patients infected with the VOCs – Delta and Omicron, within Recovered and Mortality patients. Statistical analysis highlighted significant mutations – T4685A, N4992N, and G5063S in RdRp; T19R in NTD spike; K444N and N532H in RBD spike, associated with Delta mortality. Mutations, T19I in NTD spike, Q493R and N440K in the RBD spike were significantly associated with Omicron mortality. We performed molecular docking for possible effect of significant mutations on the binding of Remdesivir. We found that Remdesivir showed less binding efficacy with the mutant Spike protein of both Delta and Omicron mortality compared to recovered patients. This indicates that mortality associated mutations could have a modulatory effect on drug binding which could be associated with disease outcome.

Download Document


Categories
Resource Centre - Publications

Mutational dynamics across VOCs in International travellers and Community transmission underscores importance of Spike-ACE2 interaction

Health Poverty Action Visiting Hospitals at Kompong Chhnang & Battambong Province

Highlights

  • The mutational landscape of 1567 international travellers and community transmission were characterized across VOCs in India
  • Mutations in LD for VOCs demonstrated differentially altered binding affinity and electrostatic interactions of Spike-ACE2.•
  • Altered Spike-ACE2 affinity among VOCs predicted sudden takeover of Delta over Alpha and BA.2 over BA.1 in India.

Download Document


Categories
Resource Centre - Publications

SARS-CoV-2 Variants of Concern and Variations within Their Genome Architecture: Does Nucleotide Distribution and Mutation Rate Alter the Functionality and Evolution of the Virus?

SARS-CoV-2 virus pathogenicity and transmissibility are correlated with the mutations acquired over time, giving rise to variants of concern (VOCs). Mutations can significantly influence the genetic make-up of the virus. Herein, we analyzed the SARS-CoV-2 genomes and sub-genomic nucleotide composition in relation to the mutation rate. Nucleotide percentage distributions of 1397 in-house-sequenced SARS-CoV-2 genomes were enumerated, and comparative analyses (i) within the VOCs and of (ii) recovered and mortality patients were performed. Fisher’s test was carried out to highlight the significant mutations, followed by RNA secondary structure prediction and protein modeling for their functional impacts. Subsequently, a uniform dinucleotide composition of AT and GC was found across study cohorts. Notably, the N gene was observed to have a high GC percentage coupled with a relatively higher mutation rate. Functional analysis demonstrated the N gene mutations, C29144T and G29332T, to induce structural changes at the RNA level. Protein secondary structure prediction with N gene missense mutations revealed a differential composition of alpha helices, beta sheets, and coils, whereas the tertiary structure displayed no significant changes. Additionally, the N gene CTD region displayed no mutations. The analysis highlighted the importance of N protein in viral evolution with CTD as a possible target for antiviral drugs.

Download Document