Plasma-derived parasitic microRNAs have insufficient concentrations to be used as diagnostic biomarker for detection of Onchocerca volvulus infection or treatment monitoring using LNA-based RT-qPCR

Lagatie, Ole; Debrah, Linda Batsa; Debrah, Alex; Stuyver, Lieven

doi:10.1007/s00436-017-5382-5

Cited by 28 publications

(23 citation statements)

References 36 publications

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“…Recent research has also produced assays to detect potentially viable adult worms such as specific metabolites produced by female worms [ 56 , 57 ] and detection of parasite microRNA in the blood [ 58 , 59 ] though the latter may not be present in sufficient concentration to act as a biomarker for infection [ 60 ].…”

Section: New Diagnosticsmentioning

confidence: 99%

Onchodermatitis: Where Are We Now?

Murdoch

2018

TropicalMed

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Onchocerciasis causes debilitating pruritus and rashes as well as visual impairment and blindness. Prior to control measures, eye disease was particularly prominent in savanna areas of sub-Saharan Africa whilst skin disease was more common across rainforest regions of tropical Africa. Mass drug distribution with ivermectin is changing the global scene of onchocerciasis. There has been successful progressive elimination in Central and Southern American countries and the World Health Organization has set a target for elimination in Africa of 2025. This literature review was conducted to examine progress regarding onchocercal skin disease. PubMed searches were performed using keywords ‘onchocerciasis’, ‘onchodermatitis’ and ‘onchocercal skin disease’ over the past eight years. Articles in English, or with an English abstract, were assessed for relevance, including any pertinent references within the articles. Recent progress in awareness of, understanding and treatment of onchocercal skin disease is reviewed with particular emphasis on publications within the past five years. The global burden of onchodermatitis is progressively reducing and is no longer seen in children in many formerly endemic foci.

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Section: New Diagnosticsmentioning

confidence: 99%

Onchodermatitis: Where Are We Now?

Murdoch

2018

TropicalMed

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“…While miR-71 and lin-4 have previously been detected in host fluids and linked to several filarial worms, including O. volvulus, O. ochengi, L. loa, L. sigmodontis, Dirofilaria immitis and Brugia pahangi, as well as helminth extracellular exosomes and vesicles 37,40,41,50 , they were not reliable markers for O. volvulus infection. The very low proportion of miRNA-positive samples is likely related to the locality of O. volvulus adult and larval stages in the host.…”

Section: Discussionmentioning

confidence: 90%

“…A recent study investigated circulating cel-miR-71-5p and bma-lin-4, as well as 15 other putative O. volvulus miR-NAs, using RT-qPCR 40 . This study also highlighted that levels of extracellular parasite-derived miRNAs are very low, if at all detectable.…”

Section: Discussionmentioning

confidence: 99%

“…perstans co-infections by eliminating samples from patients infected with other mf species, although we acknowledge there could be occult infections. The study by Lagatie et al 40 also highlighted inadequate specificity as a concern due to the detection of worm-derived miRNAs in uninfected samples, as well discrepancy in miRNA qPCR melt curves. By comparison, our study validated worm miRNA assays with relevant biological reference species, and the melt curve for the assays was consistent when tested with O. ochengi, L. loa and patient plasma cDNA.…”

Section: Discussionmentioning

confidence: 99%

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The insufficiency of circulating miRNA and DNA as diagnostic tools or as biomarkers of treatment efficacy for Onchocerca volvulus

Macfarlane

Quek

Pionnier

et al. 2020

Sci Rep

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Skin snip evaluation for onchocerciasis has insufficient sensitivity when skin microfilarial (mf) densities are low, such as following ivermectin treatment. Mf density is suitable for assessing microfilaricidal efficacy but only serves as an indirect indicator of macrofilaricidal activity. We assessed circulating nucleic acids from Onchocerca volvulus as an alternative to skin snips. We screened a plasma sample set of infected individuals followed up at four, 12 and 21 months after microfilaricidal (ivermectin, n = four), macrofilaricidal (doxycycline, n = nine), or combination treatment (n = five). Two parasite-derived miRNAs, cel-miR-71-5p and bma-lin-4, and O-150 repeat DNA were assessed. Highly abundant DNA repeat families identified in the O. volvulus genome were also evaluated. miRNAs were detected in two of 72 plasma samples (2.8%) and two of 47 samples (4.3%) with microfilaridermia using RT-qPCR. O-150 DNA was detected in eight (44.4%) baseline samples by qPCR and the number of positives declined post-treatment. One doxycycline-treated individual remained O-150 positive. However, only 11 (23.4%) samples with microfilaridermia were qPCR-positive. Analysis by qPCR showed novel DNA repeat families were comparatively less abundant than the O-150 repeat. Circulating parasite-derived nucleic acids are therefore insufficient as diagnostic tools or as biomarkers of treatment efficacy for O. volvulus. Onchocerciasis, or "river blindness" is a parasitic disease caused by the filarial worm Onchocerca volvulus. Over 100 million people are at risk of infection, of which 99% reside in 31 sub-Saharan African countries endemic for onchocerciasis 1,2. In Africa, the standard elimination strategy consists of annual mass drug administration (MDA) with ivermectin (Mectizan; IVM). IVM kills microfilariae (mf) in the skin and is used in MDA programmes, which aim to reduce disease burden and block transmission to black fly vectors (Simulium spp.) 3. A specific and sensitive diagnostic test is needed for onchocerciasis 'end-game' scenarios, both to verify elimination and to detect cases when endemicity levels no longer justify MDA 4. High sensitivity is required for O. volvulus hypoendemic areas to detect low mf densities, as well as occult and amicrofilaridermic infections, and to monitor infection recrudescence 5. High specificity is also required to discriminate between closely related filarial nematodes with overlapping geographic distributions. This is particularly relevant in areas co-endemic for O. volvulus and the filarial worm Loa loa, such as in "hypoendemic hotspots" 6 , where IVM treatment can cause serious adverse events (SAEs) when L. loa microfilaraemia is high (>30,000 mf/ml) 7. In these areas, alternative strategies with drugs that are safe to use with loiasis will be required to meet elimination targets 8. Alternative 'test and (not) treat' (TaNT) approaches, Loa-first and Oncho-first, can be used to identify and exclude people at risk of SAEs or those not infected with onchocerciasis 9. While the new rapid Loa...

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“…There has been further development of infection assays using parasite-specific metabolites that are produced by the female worms, including a neurotransmitter excreted in host urine 92 and microRNAs in the peripheral blood. 93 , 94 All these showed promise, but the neurotransmitter detection system was unsuitable for large-scale use and the parasite microRNA may not be present in sufficient concentration for easy detection. 95…”

Section: Diagnostic Tools In the Onchocerciasis Elimination Eramentioning

confidence: 99%

<p>Onchocerciasis Elimination: Progress and Challenges</p>

Lakwo¹,

Oguttu²,

Ukety

et al. 2020

RRTM

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Onchocerciasis is a parasitic infection caused by the filarial nematode Onchocerca volvulus and transmitted through the bites of black flies of the genus Similium that breed in rivers and streams. The impact of mass treatment with ivermectin and supplemented by vector control in some countries has changed the global scene of onchocerciasis. There has been reported progress made in elimination of onchocerciasis in central and southern American countries and in some localities in Africa. The target for elimination in the Americas has been set at 2022 while for 12 countries in Africa this is expected in 2030. This review was conducted to examine the current status of onchocerciasis elimination at the global level and report on progress made. Literature searches were made through PubMed, articles in English or English abstracts, reports and any other relevant articles related to the subject. The global burden of onchocerciasis is progressively reducing and is no longer a public health problem in some regions. However, programs are challenged with a range of issues: cross-border transmission, diagnostic tools, Loa loa co-endemicity, limited workforce in entomology and maintaining enthusiasm among community drug distributors. More concerted effort using appropriate tools is required to overcome the challenges.

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Plasma-derived parasitic microRNAs have insufficient concentrations to be used as diagnostic biomarker for detection of Onchocerca volvulus infection or treatment monitoring using LNA-based RT-qPCR

Cited by 28 publications

References 36 publications

Onchodermatitis: Where Are We Now?

Onchodermatitis: Where Are We Now?

The insufficiency of circulating miRNA and DNA as diagnostic tools or as biomarkers of treatment efficacy for Onchocerca volvulus

<p>Onchocerciasis Elimination: Progress and Challenges</p>

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