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

Abstract

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.

Skin snips have no role in programmatic evaluations for onchocerciasis elimination: a reply to Bottomley et al.

“…Another is for PCR confirmation of a suspected patent infection in a person who is Ov16 positive, as noted in the WHO Guidelines. Regardless, given these core mitigating factors noted above, we believe that Bottomley et al [1] erred in calling for the use of skin-snipping as a method to determine whether to stop MDA and as a post-MDA surveillance procedure. The 2016 WHO Guidelines for the verification of elimination of onchocerciasis state emphatically that the use of skin snips is to be avoided as a means to determine whether or not to stop MDA, and to monitor post-MDA status as a lead up to verification of interruption of transmission.…”

“…We read with interest the recent article by Bottomley et al [1] and were surprised that the authors concluded that skin snips have utilitarian value in evaluating the efficacy of onchocerciasis elimination programs three years after final mass drug administration (MDA). We strongly disagree that skin snips would have any practical utility in this or any other operational scenario in assessing whether to stop MDA or in post MDA transmission elimination monitoring.…”

“…The replacement of the Poisson model by the negative binomial model is generally done because it is believed that the data is subject to over dispersion. A critical observation made by Bottomley et al [1] is that the chances that a skin snip contains no microfilariae are increased. It would seem reasonable that as an elimination program proceeds and the number of microfilariae decreases, that large numbers of zero snips will be detected in persons actually infected (and infectious to flies; see, for example, Davies et al [2]).…”

“…Skin-snipping is often painful and not well tolerated by a sizeable segment of the target population. Bottomley et al [1] cite three papers in which population sampling was complicated by rejection of skin-snipping, yet the authors fail to mention this in their paper. For example, Ozoh et al [7] stated that “… the procedure [skin-snipping] is invasive and may cause secondary bacterial or viral infections.…”

“…In at least six cases, entire villages refused to participate in post MDA surveillance activities involving skin snips [9]. Further, given these precedents, to double the number of snips per person (four instead of two) in order to increase the sensitivity of the model (as recommended by Bottomley et al [1]) would be a non-starter in virtually every MDA post-surveillance setting.…”