Dept. Medical Parasitology and Infection Biology Molecular Parasitology-Epidemiology Unit The need for mobile devices for rapid diagnosis of febrile or infectious diseases in resource-poor countries 2016 Healthcare IT News, HIMSS Media Hans-Peter Beck Seoul, 14 July 2016
Innovative mobile devices for resource limited settings? 3 examples: Prevention of over-prescription of inappropriate drugs leading to drug resistance Improvement of the management of childhood illness Identification of the unknow infectious reservoir for strategies to control or eliminate malaria Possible product development and product profile 25 July 2016 2
Diagnosis of febrile illness in children 1005 children in Tanzania with febrile symptoms enrolled with 1225 diagnoses. recruited in Amana District Hospital (Dar es Salaam, area of low malaria endemicity, 1 to 4% point prevalence, 2.5 % Pf. of all febrile episodes). recruited in St. Francis Designated District Hospital (Ifakara, Kilombero District, intermediate endemicity, 7% of febrile patients had parasitemia). All children were treated according to the standard health facility procedures Samples from all children were collected and diagnostically analyzed by state-of-the-art technologies. For each sample the most appropriate method of detection of pathogens (bacteria, viruses, parasites) was used for each acute febrile episode (> 25 000 laboratory tests (RT-PCR, serology, culture, microscopy)) D'Acremont V et al. N Engl J Med 2014;370:809-817.
Diagnosis of febrile illness in children Overlap among disease types and pathogen types in 1005 febrile children. Panel A: diseases diagnosed by state-of-the-art technology Panel B: final diagnoses at the health facility D'Acremont V et al. N Engl J Med 2014;370:809-817.
Most common diagnoses by age Correct diagnosis and treatment would prevent over-prescription of inappropriate drugs leading to drug resistance D'Acremont V et al. N Engl J Med 2014;370:809-817.
Improvement of the management of childhood illness ALMANACH ALgorithm for the MANAgement of CHildhood illnesses using mobile technology A project implemented by Swiss TPH in collaboration with ICRC and PMU 25 July 2016 7
Aim: to improve quality of out-patient department (OPD) consultations and prevent drug resistance Method: develop and implement a mobile device-based medical algorithm (running on Android smartphones and tablets) Beneficiaries: Background In 2015, 16 000 children worldwide under the age of five died every day despite of available cost-effective interventions (WHO) The impact of the Integrated Management of Childhood Illness (IMCI, WHO) has been less successful due to limited acceptance and poor adherence Children aged between 2 months and 5 years 25 July 2016 8
What is ALMANACH? Improved IMCI support on Android Tailored to local settings and validated by authorities No simple focus on syndromes but focused on few meaningful clinical examinations and laboratory investigations. Support rational use of drugs, especially antibiotics. Hands-on training sessions for health workers. 25 July 2016 9
Medical algorithm in the application Example: - The user interface is designed for user-friendliness and ease of navigation - The application guides the user through the steps of the medical algorithm - Upon completion, the collected data is sent to the server for monitoring and evaluation analysis 25 July 2016 10
ALMANACH in Tanzania Control standard care Study ALMANACH Prescribed Antimalarials 7% 4% Prescribed Antibiotics 84% 15% Children cured on Day 7 92% 97% Shao et al, New Algorithm for Managing Childhood Illness Using Mobile Technology (ALMANACH): A Controlled Non- Inferiority Study on Clinical Outcome and Antibiotic Use in Tanzania, PLOS One, 2015 25 July 2016 11
The unknown infectious reservoir of submicroscopic malaria parasites Shrinking the malaria map 25 July 2016 12
Malaria in Korea North Korea: approx. 10 000 cases in 2014 25 July 2016 13
Sub-microscopical parasitemia Solomon Island Microscopy prevalence: 2.7% (17% Pf, 18 % febrile; 82% Pv, 2.8% febrile) ~0.15% detected as febrile cases at health posts. PCR prevalence: 8.7% Harris I, Sharrock WW, Bain LM, Gray KA, Bobogare A, Boaz L, Lilley K, Krause D, Vallely A, Johnson ML, Gatton ML, Shanks GD, Cheng Q. 2010 A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting. Malaria Journal 2010, 9:254 Ethiopia Microscopy prevalence: 3.7% RDT 6.9% PCR prevalence: 19.2% Golassa L, Enweji N, Erko B, Aseffa A, Swedberg G. 2013. Detection of a substantial number of submicroscopic Plasmodium falciparum infections by polymerase chain reaction: a potential threat to malaria control and diagnosis in Ethiopia Malaria Journal 12:352 25 July 2016 14
Parasitemia by RDT and PCR On average, microscopy captured 87% (95% confidence interval = 74 102%) of rapid diagnostic test-positive infections. Lindsey W. et al. 2015 Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies. Nature 528, S86 S93 25 July 2016 15
Diagnostic tools are needed Point-of-care devices are needed for: Non-malarial fevers Rapid diagnosis of viral diseases Detection (and quantification) of bacterial infections Highly sensitive detection of parasitic diseases with emphasis on malaria Detection of drug resistance associated SNPs Envisaged applications: to improve diagnosis/health in general to avoid unneccessary antibiotic and malaria treatment diagnosis to use for malaria surveillance and control to monitor effects of drugs/vaccines in clincial trials for molecular-epidemiological research 25 July 2016 17
Diagnostic tools are needed robust (and to be run on car batteries/mobile devices) cheap (at least consumables) linked to mobile technology highly sensitive (in some instances, e.g. malaria) easy-to-perform at point of care multiplexed assays possible for parallelization adaptable to various diagnostic assays 25 July 2016 18
Examples of already available tools Used for Ebola detection, identification and phylogenetic studies Oxford nanopores provides devices with nanoscale holes through which an ionic current passes through. When biological molecules (e.g. DNA, RNA) passes through the changes in current are measured. The information about the change in current can be used to identify these molecules (DNA strand sequencing). The whole assay is powered and run by a laptop computer. (https://www.nanoporetech.com) Quick J et al. 2016. Real-time, portable genome sequencing for Ebola surveillance. Nature. 2016; 530 (7589):228-32. 25 July 2016 19
Examples of already available tools FilmArray multiplex PCR system Closed pouches store all reagents for cell lysis, DNA/RNA extraction and purification, amplification, and detection. Turnaround time: 1hr Hands-on: 2 min all-in-one assay commercially available Piralla A, et al. 2014 FilmArray respiratory panel performance in respiratory samples from neonatal care units. Diagn Microbiol Infect Dis. Jun;79(2):183-6.
Examples of already available tools prevalence Nm1 (sensitivity/ Cellscope (sensitivity/ (microscopy) specificity) specificity) Diagnosis: S. haematobium 39.8 91.7/99.5 50/99.5 S. mansoni 5.3 81.1/97.1 35.6/100 Giardia intestinalis 20.7 84.0/100 n.d. Entamoeba histolytica/ E. dispar 4.9 83.3/100 n.d. Coulibaly JT. et al. 2016 Accuracy of Mobile Phone and Handheld Light Microscopy for the Diagnosis of Schistosomiasis and Intestinal Protozoa Infections in Côte d Ivoire. PLoS Negl Trop Dis 10(6): e0004768.
Korean innovations Noul, Korea Nanonbiosys/Korea Seegene, Korea Quantamatrix, Korea 25 July 2016 22
Conclusion Control of infectious diseases relies on high quality diagnosis Diagnosis is often of low quality and of poor sensitivity Diagnosis is often not available or affordable at peripheral health facilities No easy to use POC tests are available Hardly any link to mobile technology Urgent need for affordable and reliable devices 25 July 2016 23
Thank you for your attention 25 July 2016 24