Diagnostic tools developed

Diagnostic tools developed


Diagnostic test Commercial partner(s) Disease area Registration WHO recommended Description
Line probe assays (LPA)
LPA for first-line drugs (1st generation) Hain Lifescience TB CE mark 2018 Molecular assay for the rapid determination of genetic mutations associated with resistance to first-line TB drugs: fluoroquinolones, aminoglycosides (kanamycin, amikacin), cyclic peptides (capreomycin), ethambutol and streptomycin

Involves DNA extraction from culture isolates or AFB smear-positive respiratory specimens, followed by PCR amplification and reverse hybridization

Provides a visual reading of test results on nitrocellulose strips in 5 hours, versus 1–2 months with conventional methods

LPA for first-line drugs (2nd generation) Hain Lifescience; NIPRO Corporation TB CE mark 2016 (2nd generation & competitor NIPRO) Enables a rapid result from a pulmonary specimen and culture material

Can diagnose patients after treatment failure and relapse, with unknown anamnesis and originating from high prevalence areas of multi-drug resistant TB

Also used for diagnosing patients in high-prevalence TB countries and high-burden multi-drug resistant TB regions

Can also be applied for screening purposes to develop country-specific TB action plans

LPA for second-line drugs Hain Lifescience TB CE mark 2016 Same format as the LPA for 1st line drugs

Can detect resistance to some fluoroquinolones (ofloxacin and levofloxacin) and all second-line injectables (kanamycin, amikacin, and capreomycin), and ethambutol

Quick results identify those who could respond to the recently introduced shortened TB drug regimen

GeneXpert® assays
Xpert HIV-1 Qual Cepheid HIV (paediatrics) CE mark 2015; PQ Qualitative 90-minute test enabling early HIV detection in high-risk and paediatric patients, including infants

Allows for testing of children as young as 2 months old at district and sub-district levels

Xpert HIV-VL Cepheid HIV CE mark 2017; PQ Viral load assay for monitoring HIV infection, which is most relevant worldwide to monitor the therapeutic efficacy of ART (anti-retroviral therapy)

Both the HIV-1 and the HIV-VL have the same levels of sensitivity and specificity as centralized tests, can be maintained at the district laboratory level, and can be integrated with TB testing at this level

Xpert HCV-VL Cepheid HCV CE mark (no precedent yet, only HCV EID) Decentralized hepatitis C RNA confirmatory test, considered a point-of-care test with whole blood cartridge
Xpert Ebola Cepheid Ebola CE mark; FDA (EUA) 2015; EUA Rapid, high-throughput, near-patient diagnosis for Ebola

Facilitates contact tracing, disease surveillance and treatment monitoring critical in outbreak situations

Connectivity of the GeneXpert machines allows secure, accurate and rapid transmission of test results electronically for essential outbreak surveillance

Xpert® MTB/Rif Cepheid TB CE mark; FDA 2010
2013 Children, extra-pulmonary TB
Uses a sputum sample (simple one-step sample preparation) to simultaneously detect TB and rifampicin resistance in less than 2 hours (versus 90 days for culture-based resistance testing)

Sensitivity is significantly higher than microscopy, particularly in people coinfected with HIV

Xpert MTB/Rif running on the GeneXpert machine has radically changed the diagnostic landscape for TB

Xpert MTB/Rif Ultra Cepheid TB CE mark 2017 10x more sensitive than Xpert MTB/Rif (designed to replace the older assay)

Presents a unique opportunity for detecting TB in children using stool samples

Rapid diagnostic tests (RDTs)
SILVAMP TB LAM RDT Fujifilm TB CE mark Detects low concentrations of LAM-antigen in the urine of people with TB/HIV co-infection

Builds on a decade of research conducted by FIND and partners; opens a pathway to point-of-care assays that enable highly sensitive antigen detection

TB LAM RDT Alere (now Abbott) TB CE mark 2015 First ever urine-based RDT for TB, recommended for use in HIV-positive patients

Developed by Alere, building on FIND’s early work and reagents

HAT RDT 1st generation (native proteins) SD/Alere (now Abbott) HAT Korean FDA 2013 Detects antibodies for Trypanosoma brucei gambiense, the parasite responsible for more than 90% of HAT (sleeping sickness) cases

Affordable, simple to use and can be performed by health workers with minimal training

Results obtained after 15 minutes.

Can be stored at ambient temperatures and does not require specialized equipment or electricity

HAT RDT 2nd generation (recombinants) SD/Alere (now Abbott) HAT CE mark (no mechanism, but may get a letter of recommendation as for 1st generation) Uses recombinant antigens (cheaper to produce and easier to standardize than the native antigens used for the first-generation test), which has driven down the price of testing while improving test quality
Malaria highly sensitive RDT SD/Alere (now Abbott) Malaria CE mark 2016 Analytical sensitivity one order of magnitude better than the best RDTs currently available on the market.

Designed to improve detection of people with asymptomatic infections in screen-and-treat programmes to accelerate malaria elimination

CRP/malaria combination test SD Biosensor Fever / malaria CE mark Provides results for both malaria and CRP (cut-off 20 mg/L) from one finger stick sample (increased CRP levels are indicative of a bacterial infection and patients with CRP levels below 20 mg/L do not need antibiotics)

Supports malaria elimination efforts by enabling integrated fever management

Loop-mediated isothermal amplification (LAMP) tests
TB LAMP EIKEN CHEMICAL TB CE mark; Japanese MoH regulatory 2016 Provides fast results (15–40 min) that can be detected with the naked eye (does not need an imaging system)

Requires only a heat block (isothermal)

Robust to inhibitors and reaction conditions that usually adversely affect PCR methods

Malaria LAMP EIKEN CHEMICAL Malaria CE mark 2014 Intended as a field tool to detect very low-density malaria infections, to help identify hidden infections in screening programmes for elimination

Serves as a reference standard against which RDTs and other malaria diagnostics can be evaluated, to confirm the presence or absence of malaria parasites in complex cases and to support clinical trials

Malaria P. vivax LAMP EIKEN CHEMICAL Malaria CE mark Comprehensive molecular solution introduced for the diagnosis of malaria

When combined with pan and P. falciparum-specific LAMP tests, can differentiate between pan species, P. falciparum and P. vivax

HAT LAMP EIKEN CHEMICAL HAT Japanese COFS export only 2012; CE mark (no mechanism) Detects trypanosomal DNA sequences in patient blood

More sensitive and specific than current serological tests

Used as a screening tool in elimination settings

Visceral leishmaniasis LAMP EIKEN CHEMICAL VL CE mark (no mechanism) Offers a promising alternative to current methods, which are invasive and/or unreliable in some epidemiological contexts and in HIV co-infected populations
MGIT liquid culture Becton, Dickinson and Company TB CE mark 2007 Rapid liquid culture for diagnosis of TB and drug-susceptibility delivers results 3–4 weeks vs >6–8 weeks using conventional methods for identifying multi-drug resistant TB

More sensitive than smear-based tests, especially important for case detection in patients with low numbers of TB bacteria in their sputum, such as children and people coinfected with HIV

MTB rapid speciation TAUNS Laboratories; SD/Alere (now Abbott) TB CE mark 2007 Simple, accurate strip test to allow rapid TB confirmation in both liquid and solid culture within 15 minutes

Easier and faster than traditional biochemistry tests or phenotyping

Detects the MPB 64 antigen, specific to M. tuberculosis complex strains, without sample processing or additional equipment

iLED fluorescent microscope ZEISS TB and HAT CE mark 2009 Durable, affordable, easy-to-operate, energy-efficient LED-based fluorescence microscope, specifically adapted for implementation in resource-poor settings

The lamp has a lifespan of 10,000–50,000 hours; can be used for both FM and LM, and provides bright, clear images

Initially trialed for use in TB microscopy centres, now also used in the diagnostic algorithm for HAT, along with a specific concentrating and staining method

Cross-disease platform with potential also for malaria and leishmaniasis

TrueNat/TrueLab (TB and Rif) MolBio (Bigtec) TB CE mark 2018 Chip-based nucleic acid amplification test to diagnose TB

Works in combination with an automated sample preparation instrument (Trueprep)

This system and its assays have been developed in a BRICS country (India)

A competitor to Xpert, the system will be deployable at the lower levels of the healthcare system