Chagas disease
Target product profile for Chagas disease
Chagas disease
Target product profile for Chagas disease
DNDi aims to develop an oral, age-adapted shorter-course treatment for Chagas disease that is safer and more effective than current options, for use in all regions and in both chronic and acute patients, including during pregnancy.
Target product profile for Chagas disease
| Ideal | Acceptable | |
|---|---|---|
| Target population | Chronic and acute | Chronic |
| Geographic distribution | All regions | All regions |
| Efficacy | Superiority to benznidazole standard dose in acute and chronic phases of disease (parasitological cure) | Non inferior to benznidazole standard dose* (parasitological cure) |
| Safety/tolerability | Superiority to benznidazole* in the frequency of definitive treatment discontinuations for medical indication (clinical and laboratory) ** No genotoxicity; no teratogenicity; no pro-arrhythmic potential | Superiority to benznidazole* in the frequency of definitive treatment discontinuations for medical indication (clinical and laboratory) ** No genotoxicity**; no pro-arrhythmic potential |
| Contraindications | No contraindications | Pregnancy |
| Drug-drug interactions | No clinically significant interactions | No clinically significant interactions with anti-arrythmic and anticoagulant drugs |
| Formulation | Oral Age-adapted | Oral/parenteral (suitable for point-of-care) *** Age-adapted |
| Stability | 5 years, climatic zone IV | 3 years, climatic zone IV |
| Treatment regimen | <30 days | Oral: any duration Parenteral: <7 days |
| Cost | Lowest possible | Current treatments |
* As per WHO recommendation
** No genotoxicity is a condition only for NCEs
*** Need for parenteral treatment for severe disease
Target product profile for a test for early assessment of treatment response in Chagas disease patients
Source: Target product profile for a test for the early assessment of treatment efficacy in Chagas disease patients: An expert consensus. Alonso-Padilla J, Abril M, Alarco´n de Noya B, Almeida IC, Angheben A, Araujo Jorge T, et al. PLoS Negl Trop Dis. 2020;14(4): e0008035. https://doi.org/10.1371/ journal.pntd.0008035
| Ideal | Acceptable | Comments | |
|---|---|---|---|
| Scope | |||
| Goal of test or intended use | To be used as an endpoint in clinical trials evaluating new anti–T. cruzi treatments or regimens. | To guide the management of Chagas disease patients post-treatment. | Objective: Develop a test to determine if a patient treated for Chagas disease has successfully responded to treatment, which is simple to perform and can be used as early as possible. |
| The target population to be tested | Treated patients in the acute phase of infection (all types*). Treated patients in the chronic phase of infection >1 year of age (all clinical forms**). | Treated patients in the chronic phase of infection >1 year of age, with an indeterminate clinical form or early tissue damage involvement (e.g., Kuschnir scale grades 0 – 1). | *Congenital, oral, reactivation upon immune-suppression, vector-transmitted ** Indeterminate, cardiac, digestive, and cardio-digestive |
| Level of implementation in the healthcare system | Healthcare structures with low-complexity laboratory facilities (i.e., equipped at most with an ELISA* reader). | Healthcare structures (same level where treatment is provided) with middle-to-high-level laboratory facilities (i.e., those with a quality-control programme installed). | Here, the ideal conditions for the test would better suit the acceptable scenario (daily clinical management rather than clinical trial). Clinical trials are well funded and rely on well-equipped facilities to run the required tests, whereas in most endemic settings it is common to have poorly equipped facilities. |
| Intended end-users | Healthcare workers with no laboratory skills | Healthcare workers with laboratory training. | Here, the ideal conditions for the test would better suit the acceptable scenario (daily clinical management rather than CT). |
| Performance | |||
| Diagnostic sensitivity (Se) | Sensitivity equal or better than 95%, so that the test should be able to detect more than 95% of the patients in whom the treatment was efficacious. | Sensitivity equal or better than 60%, so that the test should be able to detect more than 60% of the patients in whom the treatment was efficacious. | Sensitivity for Chagas disease therapeutic efficacy (as defined above) means correctly identifying subjects in whom the treatment was efficacious. The sensitivity threshold established for each scenario should be included in the 95% CI. |
| Diagnostic specificity (Sp) | 100% | More than 90% | Specificity for Chagas disease therapeutic efficacy (as defined above) means correctly identifying subjects who failed to respond to the treatment, so that they can be managed accordingly. The specificity threshold established for each scenario should be included in the 95% CI. |
| Geographic working range | Pan-T. cruzi test | Test works in a particular region but not in all | Eco-epidemiological geographic differences observed in Chagas disease are associated with the distribution of discrete typing units. In the ideal use-case scenario, the test should be universal, i.e., capable of detecting all human-infecting lineages. In the acceptable use-case scenario, the test should work in at least one of the regions defined by Miles et al.1 |
| Operational characteristics | |||
| Type of test | Single biomarker-based test | Single or multiple biomarker-based test | |
| Type of analysis | Qualitative | Semi-quantitative or quantitative | |
| Format | Easy-to-use rapid test (e.g., lateral-flow immuno-chromatographic strip format) | Lab-based test (e.g., ELISA*-type assay) | |
| Reading system | Visual – no instrument required | Electronic-reader device required. Portable device preferred | Again, the ideal conditions for the test would better suit the acceptable scenario than the ideal one (daily clinical management rather than clinical trial setting). |
| Manual preparation of samples (steps needed after obtaining sample) | Maximum one step; precise volume control and timing may be required. | Several steps; precise volume control and timing required | |
| Reagent integration and storage | All reagents should be contained in a single device. Reagent distribution and storage without cold chain. | External reagents may be needed and if required, should be included in the test kit, preferably presented in a ready-to-mix, ready-to-use format. Reagent distribution and storage without cold chain. | All reagents and/or components of the kit must be available commercially |
| Time to results (excluding sample collection) | Less than 3 hours | Less than 24 hours | |
| Type of specimen | Capillary whole blood (finger prick sample), saliva and/or urine | Whole blood extracted by venous puncture | If blood samples are needed, finger prick samples would be preferred to venous extraction of blood. However, it must be considered that volumes larger than 50 μL will require venous puncture. It must also be considered that tests involving the use of sera will require a centrifugation step to segregate it from other blood components. This will require the availability of a centrifuge, which might not be the case in low-complexity laboratories. |
| Sample volume | Maximum volume by finger prick for rapid tests can be ~50 μl | Maximum volume: 5 ml in adults, 1 ml in children | |
| Number of samples | A maximum of two samples: one pre-treatment and one post-treatment | A maximum of three samples: one pre-treatment and up to two post-treatment | |
| Timing of sampling (of the first post-treatment sample) | Sampling within 6 months of treatment | Sampling within 24 months of treatment | |
| Power requirements | None (instrument free), minimal portable equipment, or minimum requirements (battery operated or electricity for a short time) | Standard operating currents with built-in uninterruptable power supply for utilization in locations with variable power | The fewer the infrastructure requirements (i.e., power, water, skills), the more likely it is that this test can be adopted at lower levels, such as in the community or in primary healthcare facilities. |
| Maintenance | No maintenance or minimal maintenance required by technically trained personnel or remote support | Preventative maintenance once a year or after running >1000 samples; only simple tools and minimal expertise required; include maintenance alert. Mean time to failure of at least 18 months. | A maintenance alert and records on duration of use are essential to ensuring proper functionality in settings where it is unlikely that the device will always be handled by the same person. It is essential that only simple tools and minimal expertise are necessary to carry out maintenance, given the number of devices likely to be in use. |
| Calibration | None required | Remote or auto-calibration | |
| Operating temperature | Between 5 and 50˚C at up to 90% relative humidity | Between 5 and 40˚C at up to 70% relative humidity | High environmental temperatures and high relative humidity are often present in countries where Chagas disease is endemic. |
| Operating altitude | Any altitude (up to 5000 m) | Up to 4000 m | High environmental temperatures and high relative humidity are often present in countries where Chagas disease is endemic. |
| Additional supplies (not included in the kit) | None. If required, supplies should be included in the test kit in a ready to use format. | If required, supplies should be easy to obtain, and preferably presented in a ready-to-use format | In the case of molecular biomarkers, the inclusion of low-cost equipment for nucleic acid extraction from collected samples should be considered. Otherwise, the sensitivity of the test might be compromised. |
| Internal quality control | Internal full-process positive controls and negative controls | Internal full-process positive controls. In the case of molecular methods, negative controls would be also mandatory. | In addition to EQA* |
| Training & education needs | Less than 5 days of training | Less than 6 weeks of training; laboratory personnel (biochemists, microbiologists) | Low training and education needs are desirable, but this will depend on the type of test (e.g., rapid diagnostic tests may require less training than laboratory-based assays). An EQA* to survey the process and training should be included at least once a year. |
* ELISA=enzyme-linked immunosorbent assay; EQA=external quality assessment
1The molecular epidemiology and phylogeography of Trypanosoma cruzi and parallel research on Leishmania: Looking back and to the future. Miles MA, Llewellyn MS, Lewis MD, Yeo M, Baleela R, Fitzpatrick S, Gaunt MW, Mauricio IL Parasitology 2009; 136:1509–1528
Making medical history for neglected patients
We develop urgently needed treatments for neglected patients and ensure they’re affordable, available, and adapted to the communities who need them
Stay connected
Get our latest news, personal stories, research articles, and job opportunities.
