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



We 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.



The 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.



Our 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.
MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. christian.bottomley@lshtm.ac.uk.
Christian
C
Bottomley
Department of Statistical Science, University College London, Gower Street, London, WC1E 6BT, UK.
Valerie
V
Isham
Cátedra de Salud Pública. Facultad de Medicina (Escuela Luis Razetti), Universidad Central de Venezuela, Caracas, Venezuela.
Sarai
S
Vivas-Martínez
UNICEF/UNDP/World Bank/WHO, Special Programme for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.
Annette C
AC
Kuesel
Department of Microbiology, University of Ghana Medical School, Accra, Ghana.
Simon K
SK
Attah
University of Health and Allied Sciences Research Centre (UHASRC) Hohoe, Volta Region, Ghana.
Nicholas O
NO
Opoku
Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, 310 E 67th St, New York, NY, 10065, USA.
Sara
S
Lustigman
London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, School of Public Health, Faculty of Medicine (St Mary's campus), Norfolk Place, London, W2 1PG, UK.
Martin
M
Walker
London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, School of Public Health, Faculty of Medicine (St Mary's campus), Norfolk Place, London, W2 1PG, UK.
Maria-Gloria
MG
Basáñez
D000818:Animals; D002163:Cameroon / Q000453:epidemiology; D005260:Female; D005869:Ghana / Q000453:epidemiology; D006166:Guatemala / Q000453:epidemiology; D006801:Humans; D007559:Ivermectin / Q000627:therapeutic use; D058069:Neglected Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D017181:Onchocerca volvulus / Q000302:isolation & purification*; D009855:Onchocerciasis / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D011159:Population Surveillance; D012680:Sensitivity and Specificity; D012867:Skin / Q000469:parasitology*; D014687:Venezuela / Q000453:epidemiology
D007559:Ivermectin
Diagnostics; Elimination; Ivermectin; Onchocerciasis; Prevalence; Sensitivity; Skin snips; Surveillance