Estimating helminth burdens using sibship reconstruction

Abstract

Background Sibship reconstruction is a form of parentage analysis that can be used to identify the number of helminth parental genotypes infecting individual hosts using genetic data on only their offspring. This has the potential to be used for estimating individual worm burdens when adult parasites are otherwise inaccessible, the case for many of the most globally important human helminthiases and neglected tropical diseases. Yet methods of inferring worm burdens from sibship reconstruction data on numbers of unique parental genotypes are lacking, limiting the method’s scope of application. Results We developed a novel statistical method for estimating female worm burdens from data on the number of unique female parental genotypes derived from sibship reconstruction. We illustrate the approach using genotypic data on Schistosoma mansoni (miracidial) offspring collected from schoolchildren in Tanzania. We show how the bias and precision of worm burden estimates critically depends on the number of sampled offspring and we discuss strategies for obtaining sufficient sample sizes and for incorporating judiciously formulated prior information to improve the accuracy of estimates. Conclusions This work provides a novel approach for estimating individual-level worm burdens using genetic data on helminth offspring. This represents a step towards a wider scope of application of parentage analysis techniques. We discuss how the method could be used to assist in the interpretation of monitoring and evaluation data collected during mass drug administration programmes targeting human helminthiases and to help resolve outstanding questions on key population biological processes that govern the transmission dynamics of these neglected tropical diseases.

Parasite Population Genetic Contributions to the Schistosomiasis Consortium for Operational Research and Evaluation within Sub-Saharan Africa

“…Although this could potentially reflect species differences between S. haematobium and S. mansoni , consistent with their contrasting mean daily egg output per adult worm, it is important to acknowledge that the aforementioned Tanzanian S. mansoni populations represented a true pretreatment baseline population, 44 whereas these Zanzibar S. haematobium populations had been subjected to many previous treatments, over several years, with PZQ before the start of the SCORE/ZEST program. 62 Indeed, within these Zanzibarian S. haematobium populations, there was evidence of density dependence within individuals in relation to host age and gender (and, hence, also infection intensity profiles), consistent with that previously documented through population genetic analyses for both S. mansoni in Tanzania 31 , 47 and S. haematobium in Mali. 44 Furthermore, population genetic and statistical analyses did indicate inherent differences in schistosome fecundity levels by site across both islands, frequently consistent with those shehias that went on to be classed as nonresponder hotspot sites.…”

“…This raises fundamental and unresolved questions on the population biology of schistosomes that could play a key role in shaping the transmission dynamics of the parasite and its potential response or resilience to the treatment. 31 , 32 …”

“… 32 It is thus likely that different reproductive outputs could affect the results of statistical models used to estimate female worm burdens from miracidial offspring data using parentage analysis. 31 Similarly, sibship reconstruction is a form of parentage analysis that can be used to identify the number of helminth parental genotypes infecting individual hosts using genetic data on only their offspring. However, methods for inferring worm burdens from sibship reconstruction data on numbers of unique parental genotypes were lacking, limiting the method’s scope of application.…”

“…However, methods for inferring worm burdens from sibship reconstruction data on numbers of unique parental genotypes were lacking, limiting the method’s scope of application. Therefore, to proceed with our SCORE population genetic analyses, further statistical methods for estimating female worm burdens from data on the unique number of distinct female parental genotypes derived from sibship reconstruction were developed 31 and applied to both the S. haematobium and S. mansoni SCORE datasets to produce more robust measures on the within-host parasite populations present.…”

“…This indicated there was a relaxation of the density-dependent inhibition on schistosome fecundity following treatment with PZQ among these S. mansoni populations. 31 Furthermore, it highlighted how the continued high EPG infection intensity levels observed after PZQ treatment could have, without the added value of population genetic analyses, been erroneously otherwise interpreted as evidence of, for instance, either lack of treatment coverage and/or reduced drug efficacies if measured only through standard monitoring and evaluation parasitological protocols. Nevertheless, it must also be emphasized that where interventions, through reductions in size of the parasite population, relax density-dependent inhibition in parasite fecundity, as observed here, this can also subsequently lead to increased reproduction rates in drug-resistant or reduced-susceptibility parasites that survive treatment.…”