Diagnostic tools developed
Diagnostic test | Commercial partner(s) | WHO recommended | Description |
Line probe assays (LPA) | |||
LPA for first-line TB drugs (1st generation) | Hain Lifescience (now Bruker) | 2008 | 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 TB drugs (2nd generation) | Hain Lifescience (now Bruker); NIPRO Corporation | 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 TB drugs | Hain Lifescience (now Bruker) | 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 (now Danaher) | 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 (now Danaher) | 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 (now Danaher) | 2017; PQ | Decentralized hepatitis C RNA confirmatory test, considered a point-of-care test with whole blood cartridge |
Xpert Ebola | Cepheid (now Danaher) | 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 (now Danaher) | 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 (now Danaher) | 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 | – | 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) | 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) | 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) | (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) | 2016; PQ | 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 (Fever/malaria) | SD Biosensor | – | 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 Co. Ltd. | 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 Co. Ltd. | 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 Co. Ltd. | – | 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 Co. Ltd. | (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 Co. Ltd. | (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 |
Others | |||
MGIT liquid culture (TB & MDR-TB) |
Becton, Dickinson and Company | 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) | 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 | 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 Labs) | 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 |