Malaria is a life-threatening parasitic disease killing more than 400 thousands people every year, 61% of which are children aged under 5 years old. The fight against malaria demands billions of USD each year representing an unbearable burden which exasperate the already difficult economic situation of most of the malaria endemic countries. Despite many efforts have been put into the research of antimalarial drugs and prevention methods, the onset of drug resistance and the mosquito habits adaptations risk of putting them in jeopardy. In this ongoing struggle, diagnostic tools represent a fundamental guidance for a prompt and proper treatment of the disease, helping to reduce the mortality rate and counteracting the occurrence of adaptations of the parasite to antimalarials. The panorama of currently diagnostic methods sees three main techniques: microscopy examination, rapid diagnostic test and polymerase chain reaction based diagnosis. Their cost, complexity and time requirements, however, are not always adequate to allow a wide spread to support the constant need. It is precisely to face this lack that the World Health Organization itself calls for development of low cost, easy to use and reliable new diagnostic techniques. The developed innovative system here presented is aimed to support this request by proposing a panplasmodic, quantitative, easy to use, rapid and potentially low cost diagnostic tools. The name of the project itself, Tid Mekii, the name of the malaria in Cameroon language, highlights its aim and purpose to provide a rapid and valid alternative up to the actual devices and methods while ensuring a low cost to guarantee its wide spread in the poorest endemic countries. The technique relies on the selective magnetophoretic attraction and consequent electrical impedance detection and quantification of malaria infected red blood cells (iRBCs). The tests performed with the device demonstrate its capability of detecting and quantify both hemozoin crystals (HCs), i.e. the malaria pigment, and iRBCs concentrations down to, respectively, 104 HCs/ul and 10 iRBCs/ul in less than 10 minutes. The possibility to perform a follow up of the treatment and discriminating between different stages of the disease has emerged although further dedicated investigations are required to confirm said features. A preclinical validation have been carried out at Hopital Saint Luc of Mbalmayo, Cameroon, Africa on 108 suspected malaria patients. The outcomes of this study show the absence of false negatives (100% sensitivity) but few false positives occurrences (65.5% specificity). However, the high inter-patient differences in blood properties prevented an accurate quantification of the parasitaemia. These results prove the possibility of the developed instrument and technique to become a reliable and useful diagnostic tool up to the task of competing with currently available ones and providing a valid alternative to them. The idea and the device here presented have been the subject of two social patent applications in which the inventors give up any revenues deriving from its exploitation which should be reinvested for social purposes.
La malaria è una malattia parassitaria pericolosa per la vita che causa oltre 400 mila morti ogni anno, il 61% delle quali sono bambini di età inferiore ai 5 anni. La lotta contro la malaria richiede miliardi di dollari ogni anno, rappresentando un onere insopportabile che esaspera la già difficile situazione economica della maggior parte dei paesi in cui la malaria è endemica. Nonostante siano stati fatti molti sforzi nella ricerca di farmaci antimalarici e metodi di prevenzione, l'insorgenza di resistenza ai farmaci e di adattamenti nelle abitudini delle zanzare rischiano di renderli vani. In questa perpetua lotta, gli strumenti diagnostici rappresentano una guida fondamentale per un trattamento tempestivo e adeguato della malattia, contribuendo a ridurre il tasso di mortalità e contrastando il verificarsi di adattamenti del parassita agli antimalarici. Il panorama dei metodi diagnostici attuale vede tre tecniche principali: indagine al microscopico, test diagnostico rapido e diagnosi basata sulla reazione a catena della polimerasi. I loro costi, complessità e requisiti di tempo, tuttavia, non sono sempre adeguati per consentirne un'ampia diffusione e per supportare il bisogno costante. È proprio per affrontare questa mancanza che la stessa Organizzazione Mondiale della Sanità richiede lo sviluppo di nuove tecniche diagnostiche a basso costo, facili da usare e affidabili. L'innovativo sistema sviluppato, qui presentato, mira a supportare questa richiesta proponendo strumenti diagnostici panplasmodici, quantitativi, facili da usare, rapidi e potenzialmente a basso costo. Il nome stesso del progetto, Tid Mekii, il nome della malaria in lingua camerunense, mette in luce l'obiettivo e lo scopo di fornire un'alternativa rapida e valida ai metodi attuali, garantendo nel contempo un basso costo per garantire la sua ampia diffusione nei paesi endemici più poveri. La tecnica si basa sull'attrazione magnetoforetica selettiva e sulla conseguente rilevazione e quantificazione impedenziometrica dei globuli rossi infetti da malaria (iRBC). I test eseguiti con il dispositivo dimostrano una capacità di rilevazione e quantificazione sia di cristalli di emozoina (HC), ovvero il pigmento della malaria, sia di iRBC fino a concentrazioni pari a, rispettivamente, 104 HC / ul e 10 iRBC / ul, in meno di 10 minuti. La possibilità di eseguire un follow-up del trattamento e discriminare tra le diverse fasi della malattia è stata dimostrata, sebbene sia necessario un ulteriore studio dedicate per confermare detta funzionalità. Una convalida preclinica è stata effettuata presso Hopital Saint Luc di Mbalmayo, Camerun, Africa su 108 pazienti sospetti malarici. I risultati di questo studio mostrano l'assenza di falsi negativi (sensibilità del 100%) e la presenza di pochi falsi positivi (specificità del 65,5%). Tuttavia, le elevate differenze inter-pazienti nelle proprietà del sangue hanno impedito un'accurata quantificazione della parassitemia. Questi risultati dimostrano la possibilità che lo strumento e la tecnica sviluppati diventino un utile e valido dispositivo diagnostico in grado di competere con quelli attualmente disponibili e fornire una valida alternativa ad essi. L'idea e il dispositivo qui presentati sono stati oggetto di due domande di brevetto sociale in cui gli inventori rinunciano a qualsiasi ricavo derivante dal suo sfruttamento il quale deve essere reinvestito a scopi sociali.
Tid Mekii : a rapid and quantitative diagnostic system for malaria
GIACOMETTI, MARCO
2019/2020
Abstract
Malaria is a life-threatening parasitic disease killing more than 400 thousands people every year, 61% of which are children aged under 5 years old. The fight against malaria demands billions of USD each year representing an unbearable burden which exasperate the already difficult economic situation of most of the malaria endemic countries. Despite many efforts have been put into the research of antimalarial drugs and prevention methods, the onset of drug resistance and the mosquito habits adaptations risk of putting them in jeopardy. In this ongoing struggle, diagnostic tools represent a fundamental guidance for a prompt and proper treatment of the disease, helping to reduce the mortality rate and counteracting the occurrence of adaptations of the parasite to antimalarials. The panorama of currently diagnostic methods sees three main techniques: microscopy examination, rapid diagnostic test and polymerase chain reaction based diagnosis. Their cost, complexity and time requirements, however, are not always adequate to allow a wide spread to support the constant need. It is precisely to face this lack that the World Health Organization itself calls for development of low cost, easy to use and reliable new diagnostic techniques. The developed innovative system here presented is aimed to support this request by proposing a panplasmodic, quantitative, easy to use, rapid and potentially low cost diagnostic tools. The name of the project itself, Tid Mekii, the name of the malaria in Cameroon language, highlights its aim and purpose to provide a rapid and valid alternative up to the actual devices and methods while ensuring a low cost to guarantee its wide spread in the poorest endemic countries. The technique relies on the selective magnetophoretic attraction and consequent electrical impedance detection and quantification of malaria infected red blood cells (iRBCs). The tests performed with the device demonstrate its capability of detecting and quantify both hemozoin crystals (HCs), i.e. the malaria pigment, and iRBCs concentrations down to, respectively, 104 HCs/ul and 10 iRBCs/ul in less than 10 minutes. The possibility to perform a follow up of the treatment and discriminating between different stages of the disease has emerged although further dedicated investigations are required to confirm said features. A preclinical validation have been carried out at Hopital Saint Luc of Mbalmayo, Cameroon, Africa on 108 suspected malaria patients. The outcomes of this study show the absence of false negatives (100% sensitivity) but few false positives occurrences (65.5% specificity). However, the high inter-patient differences in blood properties prevented an accurate quantification of the parasitaemia. These results prove the possibility of the developed instrument and technique to become a reliable and useful diagnostic tool up to the task of competing with currently available ones and providing a valid alternative to them. The idea and the device here presented have been the subject of two social patent applications in which the inventors give up any revenues deriving from its exploitation which should be reinvested for social purposes.| File | Dimensione | Formato | |
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https://hdl.handle.net/10589/164249