Diagnosis of O. volvulus infection via skin exposure to diethylcarbamazine: clinical evaluation of a transdermal delivery technology-based patch

Awadzi, K.; Opoku, Nicholas; Attah, Simon K.; Lazdins-Helds, Janis K.; Kuesel, Annette C.

doi:10.1186/s13071-015-1122-9

Cited by 12 publications

(12 citation statements)

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“…MDA combined with vector control has been successful in reducing transmission to elimination in the Americas [ 6 – 8 ]. Similar trends have been observed in foci in Africa resulting from large-scale implementation of vector control and MDA by the Onchocerciasis Control Program (OCP) and the African Program for Onchocerciasis Control (APOC) [ 9 – 13 ].…”

Section: Introductionmentioning

confidence: 53%

“…Screening tests using skin snip samples is challenging to implement at large scale due to the relatively labor-intensive nature of the process, the invasiveness, and as local disease burden decreases, a lowered acceptability from the community to be subjected to this process. A transdermal patch that delivers diethylcarbamazine as a local microfilaricide that induces a local skin reaction (a Mazzotti reaction) also can be used as a marker for infection [ 13 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of age-dependent trends in Ov16 IgG4 seroprevalence to onchocerciasis

et al. 2016

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BackgroundDiagnostics provide a means to measure progress toward disease elimination. Many countries in Africa are approaching elimination of onchocerciasis after successful implementation of mass drug administration programs as well as vector control. An understanding of how markers for infection such as skin snip microfilaria and Onchocerca volvulus-specific seroconversion perform in near-elimination settings informs how to best use these markers.MethodsAll-age participants from 35 villages in Togo were surveyed in 2013 and 2014 for skin snip Onchocerca volvulus microfilaria and IgG4 antibody response by enzyme-linked immunosorbent assay (ELISA) to the Onchocerca volvulus-specific antigen Ov16. A Gaussian mixture model applying the expectation-maximization (EM) algorithm was used to determine seropositivity from Ov16 ELISA data. For a subset of participants (n = 434), polymerase chain reaction (PCR) was performed on the skin snips taken during surveillance.ResultsWithin the 2,005 participants for which there was Ov16 ELISA data, O. volvulus microfilaremia prevalence and Ov16 seroprevalence were, 2.5 and 19.7 %, respectively, in the total population, and 1.6 and 3.6 % in children under 11. In the subset of 434 specimens for which ELISA, PCR, and microscopy data were generated, it was found that in children under 11 years of age, the anti-Ov16 IgG4 antibody response demonstrate a sensitivity and specificity of 80 and 97 %, respectively, against active infections as determined by combined PCR and microscopy on skin snips. Further analysis was performed in 34 of the 35 villages surveyed. These villages were stratified by all-age seroprevalence into three clusters: < 15 %; 15–20 %; and > 20 %. Age-dependence of seroprevalence for each cluster was best reflected by a two-phase force-of-infection (FOI) catalytic model. In all clusters, the lower of the two phases of FOI was associated with a younger age group, as reflected by the seroconversion rates for each phase. The age at which transition from lower to higher seroconversion, between the two phases of FOI, was found to be highest (older) for the cluster of villages with < 15 % seroprevalence and lowest (younger) for the cluster with the highest all-age seroprevalence.ConclusionsThe anti-Ov16 IgG4 antibody response is an accurate marker for active infection in children under 11 years of age in this population. Applying Ov16 surveillance to a broader age range provides additional valuable information for understanding progression toward elimination and can inform where targeted augmented interventions may be needed. Clustering of villages by all-age sero-surveillance allowed application of a biphasic FOI model to differentiate seroconversion rates for different age groups within the village cluster categories.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1623-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Analysis of age-dependent trends in Ov16 IgG4 seroprevalence to onchocerciasis

et al. 2016

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“…Ideally test-and-treat strategies and surveillance should be implemented using tests that are less invasive than the skin snip method. The DEC-patch test ([ 15 – 18 , 20 ] and see also [ 70 – 72 ]), and Ov-16 serology [ 73 , 74 ] are two possible alternatives. The DEC patch test consists of applying diethylcarbamazine citrate topically to a 6 cm 2 area of skin.…”

Section: Discussionmentioning

confidence: 99%

Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings

et al. 2016

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BackgroundThe African Programme for Onchocerciasis Control has proposed provisional thresholds for the prevalence of microfilariae in humans and of L3 larvae in blackflies, below which mass drug administration (MDA) with ivermectin can be stopped and surveillance started. Skin snips are currently the gold standard test for detecting patent Onchocerca volvulus infection, and the World Health Organization recommends their use to monitor progress of treatment programmes (but not to verify elimination). However, if they are used (in transition and in parallel to Ov-16 serology), sampling protocols should be designed to demonstrate that programmatic goals have been reached. The sensitivity of skin snips is key to the design of such protocols.MethodsWe develop a mathematical model for the number of microfilariae in a skin snip and parameterise it using data from Guatemala, Venezuela, Ghana and Cameroon collected before the start of ivermectin treatment programmes. We use the model to estimate sensitivity as a function of time since last treatment, number of snips taken, microfilarial aggregation and female worm fertility after exposure to 10 annual rounds of ivermectin treatment.ResultsThe sensitivity of the skin snip method increases with time after treatment, with most of the increase occurring between 0 and 5 years. One year after the last treatment, the sensitivity of two skin snips taken from an individual infected with a single fertile female worm is 31 % if there is no permanent effect of multiple ivermectin treatments on fertility; 18 % if there is a 7 % reduction per treatment, and 0.6 % if there is a 35 % reduction. At 5 years, the corresponding sensitivities are 76 %, 62 % and 4.7 %. The sensitivity improves significantly if 4 skin snips are taken: in the absence of a permanent effect of ivermectin, the sensitivity of 4 skin snips is 53 % 1 year and 94 % 5 years after the last treatment.ConclusionsOur model supports the timelines proposed by APOC for post-MDA follow-up and surveillance surveys every 3–5 years. Two skin snips from the iliac region have reasonable sensitivity to detect residual infection, but the sensitivity can be significantly improved by taking 4 snips. The costs and benefits of using four versus two snips should be evaluated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1605-3) contains supplementary material, which is available to authorized users.

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“…A ready-to-use diethylcarbamazine containing patch, called the LTS-2 patch, has recently been developed, and Awadzi et al 96 have demonstrated that its safety, tolerability, and ability to detect infections are comparable to those of the diethylcarbamazine patch. 96 were present in serum pools from patients infected with other filariae.…”

Section: P0310mentioning

confidence: 99%

Targeting Human Onchocerciasis: Recent Advances Beyond Ivermectin

Sainas

Dosio

Boschi

et al. 2018

Annual Reports in Medicinal Chemistry

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The Parasite and Its Life Cycle 1.2 Clinical Presentation 2. Drugs and Drug Combinations in Clinical or Preclinical Evaluations 2.1 Diethylcarbamazine (DEC) 2.2 Ivermectin 2.3 Benzimidazole Drugs 2.4 Doxycycline 2.5 Rifampicin 2.6 Emodepside 2.7 Combination Therapy 3. Recent Advances Beyond Ivermectin 3.1 Searching for Chemodiversity within Natural Sources 3.2 The Repositioning of Closantel: Targeting OvCHT1 Chitinase 3.3 Studies on New Therapeutic O. volvus Targets 4. Methodologies for Onchocerciasis Diagnosis 4.1 Clinical Examination 4.2 Microscopic Identification of Microfilariae in Skin Snips 4.3 Nucleic Acid-Based Molecular Assays 4.4 Diethylcarbamazine Patch Test 4.5 Antibody Diagnostic Tests 5. Conclusions References

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Diagnosis of O. volvulus infection via skin exposure to diethylcarbamazine: clinical evaluation of a transdermal delivery technology-based patch

Cited by 12 publications

References 31 publications

Analysis of age-dependent trends in Ov16 IgG4 seroprevalence to onchocerciasis

Analysis of age-dependent trends in Ov16 IgG4 seroprevalence to onchocerciasis

Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings

Targeting Human Onchocerciasis: Recent Advances Beyond Ivermectin

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