Diagnostic services for tuberculosis (TB) are not sufficiently accessible in low-resource settings, where most cases occur, which was aggravated by the COVID-19 pandemic. Early diagnosis of... Show moreDiagnostic services for tuberculosis (TB) are not sufficiently accessible in low-resource settings, where most cases occur, which was aggravated by the COVID-19 pandemic. Early diagnosis of pulmonary TB can reduce transmission. Current TB-diagnostics rely on detection of Mycobacterium tuberculosis (Mtb) in sputum requiring costly, time-consuming methods, and trained staff. In this study, quantitative lateral flow (LF) assays were used to measure levels of seven host proteins in sera from pre-COVID-19 TB patients diagnosed in Europe and latently Mtb-infected individuals (LTBI), and from COVID-19 patients and healthy controls. Analysis of host proteins showed significantly lower levels in LTBI versus TB (AUC:0 center dot 94) and discriminated healthy individuals from COVID-19 patients (0 center dot 99) and severe COVID-19 from TB. Importantly, these host proteins allowed treatment monitoring of both respiratory diseases. This study demonstrates the potential of non-sputum LF assays as adjunct diagnostics and treatment moni-toring for COVID-19 and TB based on quantitative detection of multiple host biomarkers. Show less
To date there is only one single drug with modest efficacy and no vaccine available to protect from schistosomiasis. Here, Amaral et al. characterize the self-cure process of rhesus macaques... Show moreTo date there is only one single drug with modest efficacy and no vaccine available to protect from schistosomiasis. Here, Amaral et al. characterize the self-cure process of rhesus macaques following primary infection and secondary challenge with Schistosoma mansoni to inform future vaccine development studies.The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine. Show less
Hooij, A. van; Fat, E.M.T.K.; Jong, D. de; Khatun, M.; Soren, S.; Chowdhury, A.; ... ; Corstjens, P.L.A.M. 2021
To end the decade-long, obstinately stagnant number of new leprosy cases, there is an urgent need for field-applicable diagnostic tools that detect infection with Mycobacterium leprae, leprosy's... Show moreTo end the decade-long, obstinately stagnant number of new leprosy cases, there is an urgent need for field-applicable diagnostic tools that detect infection with Mycobacterium leprae, leprosy's etiologic agent. Since immunity against M. leprae is characterized by humoral and cellular markers, we developed a lateral flow test measuring multiple host proteins based on six previously identified biomarkers for various leprosy phenotypes. This multi-biomarker test (MBT) demonstrated feasibility of quantitative detection of six host serum proteins simultaneously, jointly allowing discrimination of patients with multibacillary and paucibacillary leprosy from control individuals in high and low leprosy endemic areas. Pilot testing of fingerstick blood showed similar MBT performance in point-of-care (POC) settings as observed for plasma and serum. Thus, this newly developed prototype MBT measures six biomarkers covering immunity against M. leprae across the leprosy spectrum. The MBT thereby provides the basis for immunodiagnostic POC tests for leprosy with potential for other (infectious) diseases as well. Show less
Corstjens, P.L.A.M.; Hooij, A. van; Fat, E.M.T.K.; Alam, K.; Vrolijk, L.B.; Dlamini, S.; ... ; Geluk, A. 2019
Acute inflammatory reactions represent the major cause of irreversible neuropathy in leprosy. These tissue-destroying episodes have considerable overlap with acute immunological complications ... Show moreAcute inflammatory reactions represent the major cause of irreversible neuropathy in leprosy. These tissue-destroying episodes have considerable overlap with acute immunological complications (flares) in several chronic (autoimmune) diseases that similarly warrant early detection. However, the lack of diagnostic tests impedes early diagnosis of these reactions. Here, we evaluated a user-friendly multiplex lateral flow assay for the simultaneous detection of IP-10 and anti-phenolic glycolipid I antibodies for longitudinally monitoring early onset and treatment of leprosy reactions. Show less
