Chapter Six - The Role of More Sensitive Helminth Diagnostics in Mass Drug Administration Campaigns: Elimination and Health Impacts

https://doi.org/10.1016/bs.apar.2016.08.005Get rights and content

Abstract

Diagnostics play a crucial role in determining treatment protocols and evaluating success of mass drug administration (MDA) programmes used to control soil-transmitted helminths (STHs). The current diagnostic, Kato-Katz, relies on inexpensive, reusable materials and can be used in the field, but only trained microscopists can read slides. This diagnostic always underestimates the true prevalence of infection, and the accuracy worsens as the true prevalence falls.

We investigate how more sensitive diagnostics would impact on the management and life cycle of MDA programmes, including number of mass treatment rounds, health impact, number of unnecessary treatments and probability of elimination. We use an individual-based model of STH transmission within the current World Health Organization (WHO) treatment guidelines which records individual disability-adjusted life years (DALY) lost. We focus on Ascaris lumbricoides due to the availability of high-quality data on existing diagnostics.

We show that the effect of improving the sensitivity of diagnostics is principally determined by the precontrol prevalence in the community. Communities at low true prevalence (<30%) and high true prevalence (>70%) do not benefit greatly from improved diagnostics. Communities with intermediate prevalence benefit greatly from increased chemotherapy application, both in terms of reduced DALY loss and increased probability of elimination. Our results suggest that programmes should be extended beyond school-age children, especially in high prevalence communities. Finally, we argue against using apparent or measured prevalence as an uncorrected proxy for true prevalence.

Introduction

Over 1 billion children are at risk of soil-transmitted helminth (STH) infections globally (Pullan and Brooker, 2012). High burdens of the worms causative of these infections have been shown to be associated with health impacts, although the health impact of lower burden infections have proved more difficult to identify and quantify (Holland et al., 2013). It was estimated that in 2010, 1.45 billion people were infected with at least one species of soil-transmitted helminths (STHs), resulting in a burden of 5.18 million disability-adjusted life years (DALYs) (Pullan et al., 2014). Mass drug administration (MDA) has been shown to be a cost-effective way of reducing the burden of infection when compared to selective treatment of those with the highest burdens (Guyatt et al., 1993, Holland et al., 1996, Turner et al., 2015b). This has led to a global initiative to provide MDA to 600 million children annually through the donation of albendazole and mebendazole by major pharmaceutical companies (WHO, 2012).

Recently, mass treatment for STHs has been under scrutiny, as there are very few high-quality trials that evaluate the health impact of such programmes, and they have not been powered to detect the impact in highly burdened individuals (Campbell et al., 2016). This debate is on-going, and is occurring in parallel with a discussion about whether limiting morbidity rather than true elimination is the correct goal for these programmes (Anderson et al., 2015, Brooker et al., 2015).

Treatment guidelines for MDA are generally based on a pretreatment estimate of prevalence, with high levels of prevalence leading to more frequent or more intensive treatment programmes (WHO, 2011a). Treatment frequency is modified in response to changes in prevalence during the programme (see below and Table 1). For STHs, prevalence is most commonly evaluated using a diagnostic technique called Kato-Katz (Kato and Miura, 1954, Katz et al., 1972). This involves obtaining a stool sample, taking a scoop from this sample, spreading it on a slide and counting the number of observable eggs in this part of the stool sample under a microscope. It is relatively inexpensive in terms of a one-off investment in microscopes and the possibility of reusing slides, but demands large amounts of technician time and requires that the diagnostic team comes to the field, as eggs, particularly hookworm eggs, degrade very quickly. The identification and targetting of high burden individuals, although potentially effective (Anderson and Medley, 1985), is not a cost-effective strategy to reduce morbidity, largely because of this high resource requirement and the inaccuracy of Kato-Katz for individual diagnoses (Asaolu et al., 1991, Guyatt et al., 1993, Holland et al., 1996). Were the costs of treatment much higher, then targetted treatment would be more cost-effective, but MDA has a much lower cost per individual treated than it costs to diagnose high burdens.

As investment in the control of STHs increases, and some programmes move towards an elimination target, there have been calls for more sensitive diagnostics (Bergquist et al., 2009). New tools, such as polymerase chain reaction (PCR), are being developed to detect both eggs and worms in faeces (Easton et al., 2016, Mejia et al., 2013) but careful consideration of their long-term impact needs to be exercised prior to large-scale investment in their development and deployment. For other neglected tropical diseases, such as lymphatic filariasis, onchocerciasis, visceral leishmaniasis and sleeping sickness (McCarthy et al., 2012), new diagnostics have made both surveys and treatment of these diseases significantly easier. The opportunities for STH infections to see similar gains will depend on the characteristics of the diagnostic, in terms of sensitivity and specificity at different intensities, as well as cost and a well-developed use case. The prevalence measured by a diagnostic will always be the apparent prevalence, and not the true prevalence, of infection, but is the only source of information to manage and evaluate MDA programmes. Here we focus on the potential impact on improving treatment decisions and resulting health impact of a more sensitive diagnostic with different characteristics using mathematical models of transmission and health impact.

Modelling of STHs is the most efficient approach to evaluating the impact of potential diagnostics at a population level. We develop a new, individual-based mathematical model specifically to predict the impact of new, more sensitive diagnostics on the outcome of MDA programmes.

The analyses we present concentrate on Ascaris lumbricoides, which remains the most prevalent and persistent of the soil-transmitted nematodes. The worm's comparatively large size, migratory pathway through the tissues and allergenicity further enhance its public health significance (Holland, 2013). The implications of larval migration remain particularly cryptic but consequences include both liver and lung inflammation and disease. Pulmonary symptoms, described as Loeffler syndrome, range from debilitating to lethal, particularly in children (Holland et al., 2013). Despite these characteristics, Ascaris lumbricoides is comparatively neglected in comparison to the other members of the soil-transmitted nematodes, Trichuris and hookworm, and this is, in part, explained by the lack of an accessible animal model to mimic human infection.

The genus Ascaris is composed of two species: Ascaris lumbricoides and Ascaris suum, which have been described as parasitic to humans and pigs respectively. However, these species are morphologically very similar and there is evidence of cross-transmission and hybridization between species (Criscione et al., 2007b), so that, in areas with transmission opportunities between humans and pigs, there is the possibility that both species are present in humans (Criscione, 2013). Throughout this chapter we refer to Ascaris without clearly defining the species, although in most cases this will be A. lumbricoides. We use the species name when we wish to be specific.

Infectious disease epidemiology and public health rely on accurate diagnostic data in order to inform both treatment decisions and the evaluation of interventions. All diagnostic tests have sensitivity (i.e. probability of detecting a true positive) and specificity (i.e. probability of detecting a true negative), so that the determination of the presence of infection in an individual contains some error. At an individual level, test results can be used to make clinical decisions. At a population level, individual measures can be combined to produce assessments of the health of populations, provide information on which to base intervention decisions and to monitor and evaluate intervention outcomes. When diagnostics are being developed, evaluated and adapted for use, the criteria for clinical (individual-level) use frequently dominates, although the requirements for population-level use might be different (in terms of sensitivity, specificity, cost etc.).

For STHs, the current diagnostics are based on microscopic detection of infectious stages (eggs) as they leave the host in faeces (Bergquist et al., 2009). The number of eggs per gram of faeces (epg) varies from 0 to many thousands even from the same host collected at the same time (Hall, 1982). For example, Hall (1981) undertook a focussed study upon 10 people infected with STHs and recorded mean egg counts of Ascaris lumbricoides over five consecutive days; the results demonstrated considerable variability: 76, 21, 485, 1093 and 200 epg respectively. Note that these are means of 10 individuals, and individual variability is much higher. Consequently, these diagnostics are ineffective in clinical decision-making in the absence of clinical signs and symptoms, i.e. it is not possible to use them to screen a population to decide which individuals should receive treatment. Additionally, the current diagnostic tests for STHs are relatively intrusive, expensive and labour intensive. However, the consequent results are only used to assess the prevalence of infection in a community and to inform public health interventions.

A range of diagnostic tests are currently available and include direct microscopy of faecal smears (WHO, 1994), the Kato-Katz method (Katz et al., 1972), the formol-ether concentration technique (Allen and Ridley, 1970), the McMaster method (Anon, 1986, Levecke et al., 2011), FLOTAC (Cringoli et al., 2010) and mini-FLOTAC (Barda et al., 2013). A diagnostic test needs to be accurate, sensitive and easy to use. Currently the most utilized test for population-based assessments is the Kato-Katz method; its advantages include speed of processing, no need for a centrifuge and the ability to detect the eggs of both intestinal nematodes and schistosomes. It is also the diagnostic test recommended by the World Health Organization (1994) based upon duplicate slides.

It is important to note that there is no gold standard for STH diagnostics, meaning that sensitivity can only be assessed relative to other imperfect diagnostics, such as worm expulsion. Whilst advanced statistical analyses can compensate and correct for the lack of “truth”, their major role is to quantify the diagnostic uncertainty. A recent, useful meta-analysis, utilizing Bayesian latent class analysis, compared a range of diagnostic tests for the detection of Ascaris, Trichuris trichiura and hookworm species (Nikolay et al., 2014). The authors used data, mainly from schoolchildren, from a range of 12 countries, some of which included both low- and high-intensity settings. FLOTAC was found to be the most sensitive diagnostic test with values of 79.7% for Ascaris, 91% for Trichuris and 92.4% for hookworm. However, FLOTAC has a number of practical limitations as a diagnostic method including relatively low throughput and the need for a centrifuge. A comparison of the sensitivity of the Kato-Katz method (64.6% for Ascaris, 84.8% for Trichuris and 63% for hookworm) with the formol-ether concentration technique (Ascaris 56.9%, Trichuris 81.2% and hookworm 53%) revealed that Kato-Katz performed better. However, when low- and high-intensity settings were compared, sensitivity was reduced markedly at low intensities for Kato-Katz (Ascaris high 97% versus low 55.2%, Trichuris 95.3% versus 79.8% and hookworm 74% versus 52.6%). For the formol-ether concentration technique, only data from low intensity settings were available with sensitivity of 51.3% for Ascaris, 21.5% for Trichuris and 38.9% for hookworm.

In a recent diagnostic advance, Easton et al. (2016) described the assessment of a multiparallel qPCR for the detection of eight parasites (including Ascaris, Trichuris, Necator americanus and Ancylostoma duodenale) in comparison to the 2-stool, 2-slide Kato-Katz approach. Molecular diagnosis was revealed to be more sensitive than Kato-Katz for Ascaris (98% versus 70%) and N. americanus (98% versus 32%). The authors concluded that Kato-Katz might be insensitive when infection intensities are low after repeated rounds of treatment.

These concerns are also reflected in the observations of Manser et al. (2016) that highlighted how differences in methodology between laboratories may influence the sensitivity of egg recovery. Using the Ridley-Allen concentration method (referred to as the formol-ether concentration method above) as an example, the authors collected questionnaire-based data to compare factors such as mode of preservation, sieve pore size, solvent, centrifugal force and time and concluded that variation in such approaches, influenced parasite recovery especially if intensity was low.

Recently, Vlaminck et al. (2016) utilized an enzyme-linked immunosorbent assay (ELISA) test measuring IgG4 antibodies to Ascaris suum haemoglobin (AsHb) developed in pigs, to assess changes in antibody rates in humans after MDA. While the ELISA was not sensitive for detecting all Ascaris-infected individuals, the percentage of seropositive individuals declined rapidly after treatment and reductions in antibody levels reflected decreases in mean intensity of infection at the level of the community and within different age groups. The authors concluded that this Ascaris-specific ELISA could be potentially useful for assessing the extent of Ascaris transmission and the impact of treatment in endemic communities.

In the case of schistosomiasis, stool examination by the Kato-Katz method is regarded as the optimum method for the detection of eggs despite the known limitations when intensity of infection is low (Speich et al., 2013). There has been increasing interest in diagnosis of schistosomiasis (which is blood-dwelling) through detection of an antigen or immunological response. Lamberton et al. (2014) compared a single antigen test to up to six Kato-Katz smears, and concluded that, posttreatment when prevalence is reduced, the antigen test is more sensitive. In a large-scale study conducted in seven Chinese villages, Zhou et al. (2011), compared the performance and utility of three immunoassays – an indirect haemagglutination assay (IHA_JX), an enzyme linked immunosorbent assay (ELISA_SZ) and a dot immunogold filtration assay (DIGFA_SH) for the detection of seropositivity in Schistosoma japonicum infected subjects. ELISA_SZ performed significantly better in terms of sensitivity especially in subgroups with very low infection intensities and the authors concluded that this assay could be used to guide selective chemotherapy in low and moderate endemic regions whereas IHA_JX would be a useful diagnostic tool for surveillance and certification of elimination.

Taken together, these pieces of evidence suggest a significant degree of uncertainty with respect to the sensitivity of existing diagnostic methods based upon the analysis of faecal material for the presence of soil-transmitted helminth and schistosome eggs especially if the intensity of infection is low. It is therefore important to recognize that the true prevalence of infection with intestinal nematodes and schistosomes cannot be assessed. Virtually all previous modelling has been based on equating the apparent (test) prevalence with the true prevalence. In terms of understanding the population dynamics of STHs and the impact of interventions, addressing the issue of the relationship between apparent and true prevalence is critical. To our knowledge the impact of different diagnostics has not been considered previously in models of STHs to assess the real (rather than apparent) impact of interventions.

Helminth populations within individuals (i.e. adult worms) can be killed or sterilized by application of anthelmintic chemotherapy. Given current diagnostics and the weak relationship between egg output and worm burden (Walker et al., 2013, Wilson et al., 2014), the infection status of individuals cannot be accurately ascertained. Consequently, given the relative low cost of treatment, the most cost-effective approach is to target groups with highest prevalence, curing the most heavily infected and relying on indirect effects to reduce prevalence to the whole community (Anderson and Medley, 1985, Chan et al., 1994b, Medley et al., 1993). The questions then become who to treat, and how often. Currently, for Ascaris lumbricoides, Trichuris trichiura and the schistosomes, school-age children (SAC) are targetted partly because current diagnostics indicate that they carry the heaviest burdens of infection, partly because the costs of treatment and monitoring are lower, and partly because compliance will be higher ensuring a high coverage (i.e. the proportion of the target group receiving treatment). School-based deworming is a cost-effective way of reaching school-aged children in areas where enrolment is high, and has been shown to be a cost-effective way of reducing anaemia in some settings (Brooker et al., 2008, Guyatt et al., 2001). However, it is becoming increasingly recognized that targetting SAC has limitations for hookworm infections, which are more often skewed towards adults for heavily infected communities and where attendance at school-based deworming is poor (Anderson et al., 2015, Truscott et al., 2014, Truscott et al., 2015, Turner et al., 2015a).

In January 2012, the World Health Organization (WHO), international donors, governments and pharmaceutical companies, committed to ‘sustain, expand and extend drug access programmes to ensure the necessary supply of drugs and other interventions to help control [these infections] by 2020’as part of The London Declaration on Neglected Tropical Diseases (Uniting to Combat Neglected Tropical Diseases, 2012). The aim of scaling up treatment programmes against STHs is to limit the burden of morbidity in school-aged children (WHO, 2012). Modelling analyses such as this will be important in identifying progress made towards the London Declaration goals (Deribe, 2016).

Although the current aim according to the Declaration is to control infection and disease due to STHs, it is increasingly recognized that elimination of infection is the only sustainable target. Control of disease is defined as reduction in disease burden that requires continued treatment and intervention (Dowdle, 1998, Dowdle and Hopkins, 1998). Elimination of infection does not necessarily require continued intervention and treatment, although there will still be some interventions required to ensure that infection is not reintroduced from areas and populations in which infection has not been eliminated (Molyneux et al., 2004). Indefinite control of soil-transmitted helminthiases through periodic MDA is vulnerable to both donor fatigue (resulting in costs of drugs increasing) and continued substantial costs of drug delivery (Uniting to Combat Neglected Tropical Diseases, 2012). The longer soil-transmitted helminth populations are exposed to anthelmintics, the more likely it is for drug resistance to emerge, and the more likely that helminth populations will adapt to periodic culling (Leignel and Cabaret, 2001). Consequently, in this analysis, we consider both the reduction in disease (measured as DALYs saved) and the probability of elimination of infection, as key outcomes of our model.

Sampling and treatment are conducted according to WHO Guidelines (WHO, 2011a). Every 5 years, 200–250 SAC from a number of schools should be sampled and assessed using a recognized diagnostic. The prevalence of infection amongst SAC informs the decision for the following 5-year treatment programme, according to Table 1. Note that there is a slight logical inconsistency in this framework, in that a population with a prevalence of STHs <20% at first survey will receive no treatment initially, but will then have biennial (once every 2 years) or annual treatment at subsequent decision points if it has the same prevalence. This is assuming that the population is resurveyed every 5 years. The key point is that the decisions taken are based on estimated (apparent) prevalence, so the accuracy of the estimate will have a large effect on outcome, particularly at the boundaries between treatment frequencies.

Modelling of macroparasites, and helminth infections in particular, began in earnest during the 1970s (Anderson and May, 1985, Basáñez et al., 2012b, Truscott et al., 2016). The basic frameworks contain two principal populations: within-host helminths (the adult, reproductive stage), and the free-living infectious stage (Anderson and May, 1982). The key to understanding helminth population dynamics is that adult stages are not distributed randomly among hosts, but are highly clumped. The majority of hosts harbour no worms or only a few worms and a small proportion of hosts harbour most of the worms, and are more heavily infected.

The distribution of parasites between hosts matters for two reasons. First, the parasites are dioecious so that production of fertilized eggs depends on the presence of both sexes, but female parasites also experience a density-dependent depression of fecundity, both of which are determined by the parasite distribution (Churcher et al., 2005, Medley and Anderson, 1985, Walker et al., 2009, Wilson et al., 2014). This creates a nonlinear effect as infections with small numbers of worms (the majority) are likely to be single sex and nonfertile, but the per worm egg output decreases as worm burden increases. Second, the clinical and health impact of infection is largely determined by the burden of parasites an individual harbours (Crompton and Nesheim, 2002, Hotez and Kamath, 2009). The highly overdispersed distribution of parasites between hosts was initially included in models as a simple negative binomial distribution, which provides a good empirical description (Anderson and May, 1985). However, the administration of anthelmintics disrupts this distribution, and subsequent modelling approaches were developed that allowed the distribution of parasites to vary dynamically as a consequence of the processes of treatment and reinfection (Anderson and Medley, 1985, Chan et al., 1994b, Chan et al., 1996, Medley et al., 1993). The models used, belonging to the current generation, are direct descendants of these earlier models (Anderson et al., 2014, Truscott et al., 2014, 2016).

If models are to include a dynamic distribution of parasites, then they must include the mechanisms by which they are generated. From a modelling viewpoint, there is a continuum of possibilities for generation of such distributions (Anderson and Medley, 1985). At one end of the continuum, hosts with unusually high (low) burdens are predisposed to that level of infection (Schad and Anderson, 1985), ultimately through genetic or behavioural traits that are temporally consistent. Individual propensity for high (low) burdens might also be due to exposure through household conditions and composition, as long as these are relatively constant (Haswell-Elkins et al., 1989, Walker et al., 2011). The opposite end of the continuum is that hosts with unusually high (low) burdens are just unlucky (lucky), i.e. high burdens occur when a host by chance becomes heavily infected with a massive influx of infection and this is a relatively rare event. The reality is likely to be somewhere between the two extremes: hosts with high burdens are somewhat predisposed to such burdens, but unlucky to have them at this point (Anderson and Medley, 1985, Holland, 2009).

In order to be able to compare health outcomes of different interventions, public health decision-makers need a measure of health burden that is not cause- or location-specific. The disability-adjusted life year (DALY) is a metric, which captures both years of life lost from premature death (YLLs) and years of life lived with disability (YLDs) into a composite estimate. The disability weights used to estimate the YLD are a quantification of the severity of health loss associated with each disease sequel. These range from 0 to 1, with 0 being equivalent to perfect health and 1 being equivalent to death. In other words one DALY can be thought of as one lost year of ‘healthy’ life (Murray and Lopez, 1996).

In early attempts to estimate the global burden of disease, soil-transmitted helminthiases were ranked as a major cause of healthy life lost, because, even though the per individual impact was low, the population at risk was large and young (Brooker, 2010, Chan, 1997, Chan et al., 1994c). The impacts of childhood infection included an impairment of cognition which was immediate, although the loss of education and intellectual development lasted throughout life (Albonico and Kvalsig, 2013). More recently, the estimates of the health consequences of infection of individuals have been questioned. Cochrane reviews (Taylor-Robinson et al., 2015) of the available randomized controlled trials of STH deworming identified little support for any cognitive/educational benefits and contrasting evidence regarding the nutritional benefits. However, it should be noted that if the impact is highly nonlinearly related to worm burden, then the (high) benefits to a (small) minority of people may be being diluted in community evaluations, where the majority will suffer little or no burden. Critics of these reviews have argued that many of the included trials suffer from a number of methodological shortcomings that may bias the results, and that better-designed studies are required in this area (Brooker and Pullan, 2013, Campbell et al., 2016, de Silva et al., 2015, Montresor et al., 2015).

In should also be noted that reanalyses of the Miguel and Kremer (2004) study in Kenya found less promising outcomes which reignited the debate over the WHO's recommendation of mass- treatment of STHs – although many of the benefits of STH deworming were still significant in the reanalysis (Aiken et al., 2015, Davey et al., 2015, Miguel and Kremer, 2004).

In order to investigate the impact of novel diagnostics, we have adapted a model for Ascaris lumbricoides, a soil-transmitted helminth, largely based on previous models (Anderson and Medley, 1985, Chan et al., 1994b, Medley, 1989). The model gives results for individual communities treated by MDA using different diagnostic profiles. The research reported here also contributed to an assessment of current and future diagnostics for soil-transmitted helminthiases and schistosomiasis (PATH, 2016).

We first describe the diagnostic profiles that we have considered, and demonstrate the influence that these have on estimation of prevalence. We then briefly describe the model framework, the process by which we convert model results into measures of disease, especially DALY losses and likelihood of elimination. As decisions about MDA programmes are often taken at national or regional levels (i.e. for multiple communities), we consider how community results can be combined into national results. Finally we draw conclusions and comment on the outcomes and processes.

Section snippets

Modelling Diagnostics

The diagnostic profiles we develop are defined as the relationship between the true numbers of worms harboured, and the ability of the diagnostic to detect at least one worm. We use original field data for Ascaris to estimate a fitted profile of sensitivity as number of worms varies, and then propose the diagnostic performance characteristics of worse and better diagnostics. As the fitted diagnostic is based on data gathered in research projects, we assume that the sensitivity of diagnostics

Modelling Transmission Dynamics

In this section we give a brief description of the assumptions behind the individual-based, stochastic transmission dynamic model used to evaluate programme outcomes with different diagnostic sensitivities. The most novel aspect of the model is the inclusion of continuous measurement of health outcomes of infection. The model is simulated in Matlab (2015), and the code is freely available at https://github.com/GrahamMedley/HelSim.

The model is a discrete time, individual-based simulation: the

Results

We present the results in four sections. First, we show dynamic patterns of true prevalence and cumulative DALY losses in all the different community circumstances considered. Second, we consider the time-dependent probability of elimination of infection. Third, we consider incremental results (i.e. how many DALYs are saved for an increase in diagnostic sensitivity). Finally, we show the results combined into a country, India, as an example of how community level results are likely to combine.

Discussion

Observations on a population of parasitic helminths cannot be made directly, but rely on indirect assessment, and we have considered methods of assessment of the infection status of individual hosts (i.e. infected or uninfected). These methods currently rely on detection of eggs in faeces, although other tests are under consideration. The accuracy of these tests at the individual level depends on the intensity of the infection of the host, and the accuracy of the test at the population level

Acknowledgements

All authors acknowledge PATH for supporting this work through a grant from the Bill and Melinda Gates Foundation. We thank Dr Rachel Pullan for access to country level prevalence data and discussions.

References (109)

  • H.L. Guyatt et al.

    A population dynamic approach to the cost-effectiveness analysis of mass anthelmintic treatment: effects of treatment frequency on Ascaris infection

    Trans. R Soc. Trop. Med. Hyg.

    (1993)
  • A. Hall

    Quantitative variability of nematode egg counts in faeces: a study among rural Kenyans

    Trans. R Soc. Trop. Med. Hyg.

    (1981)
  • A. Hall et al.

    Geographical variation in Ascaris lumbricoides fecundity and its implications for helminth control

    Parasitol. Today

    (2000)
  • G.F. Medley et al.

    Density-dependent fecundity inSchistosoma mansoni infections in man

    Trans. R Soc. Trop. Med. Hyg.

    (1985)
  • D.H. Molyneux et al.

    Disease eradication, elimination and control: the need for accurate and consistent usage

    Trends Parasitol.

    (2004)
  • B. Nikolay et al.

    Sensitivity of diagnostic tests for human soil-transmitted helminth infections: a meta-analysis in the absence of a true gold standard

    Int. J. Parasitol.

    (2014)
  • L.S. Stephenson et al.

    Relationships between Ascaris infection and growth of malnourished preschool children in Kenya

    Am. J. Clin. Nutr.

    (1980)
  • A.M. Aiken et al.

    Reanalysis of health and educational impacts of a school-based deworming programme in western Kenya: a pure replication

    Int. J. Epidemiol.

    (2015)
  • M. Albonico et al.

    Effects of geohelminth infection on neurological development

    Handb. Clin. Neurol.

    (2013)
  • A.V. Allen et al.

    Further observations on the formol-ether concentration technique for faecal parasites

    J. Clin. Pathol.

    (1970)
  • R.M. Anderson et al.

    Population dynamics of human helminth infections: control by chemotherapy

    Nature

    (1982)
  • R.M. Anderson et al.

    Community control of helminth infections of man by mass and selective chemotherapy

    Parasitology

    (1985)
  • R.M. Anderson et al.

    The coverage and frequency of mass drug administration required to eliminate persistent transmission of soil-transmitted helminths

    Philos. Trans. R. Soc. Lond. B Biol. Sci.

    (2014)
  • R.M. Anderson et al.

    Should the goal for the treatment of soil-transmitted helminth (STH) infections be changed from morbidity control in children to community-wide transmission elimination?

    PLoS Negl. Trop. Dis.

    (2015)
  • Anon: Ministry of Agriculture Fisheries and Food

    Manual of Veterinary Parasitological Laboratory Techniques

    (1986)
  • S.O. Asaolu et al.

    Community control of Ascaris lumbricoides in rural Oyo State, Nigeria: mass, targeted and selective treatment with levamisole

    Parasitology

    (1991)
  • B.D. Barda et al.

    Mini-FLOTAC, an innovative direct diagnostic technique for intestinal parasitic infections: experience from the field

    PLoS Negl. Trop. Dis.

    (2013)
  • M.G. Basáñez et al.

    A research agenda for helminth diseases of humans: modelling for control and elimination

    PLoS Negl. Trop. Dis.

    (2012)
  • C. Bottomley et al.

    Modelling neglected tropical diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings

    Parasites Vectors

    (2016)
  • S.J. Brooker et al.

    The Global Atlas of Helminth Infection: mapping the way forward in neglected tropical disease control

    PLoS Negl. Trop. Dis.

    (2010)
  • S.J. Brooker et al.

    Cost and cost-effectiveness of nationwide school-based helminth control in Uganda: intra-country variation and effects of scaling-up

    Health Policy Plan

    (2008)
  • D.A.P. Bundy et al.

    Intestinal Nematode Infections, in Global Epidemiology of Infectious Disease, WHO

    (2004)
  • S.J. Campbell et al.

    Complexities and perplexities: a critical appraisal of the evidence for soil-transmitted helminth infection-related morbidity

    PLoS. Negl. Trop. Dis.

    (2016)
  • M.S. Chan et al.

    The development and validation of an age-structured model for the evaluation of disease control strategies for intestinal helminths

    Parasitology

    (1994)
  • M.S. Chan et al.

    Dynamic models of schistosomiasis morbidity

    Am. J. Trop. Med. Hyg.

    (1996)
  • M.S. Chan et al.

    The evaluation of potential global morbidity attributable to intestinal nematode infections

    Parasitology

    (1994)
  • T.S. Churcher et al.

    Density dependence and overdispersion in the transmission of helminth parasites

    Parasitology

    (2005)
  • G. Cringoli et al.

    FLOTAC: new multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans

    Nat. Protoc.

    (2010)
  • C.D. Criscione

    Genetic epidemiology of Ascaris: cross-transmission between humans and pigs, focal transmission, and effective population size

  • C.D. Criscione et al.

    Microsatellite markers for the human nematode parasite Ascaris lumbricoides: development and assessment of utility

    J. Parasitol.

    (2007)
  • C.D. Criscione et al.

    Disentangling hybridization and host colonization in parasitic roundworms of humans and pigs

    Proc. R. Soc. Ser. B

    (2007)
  • D.W.T. Crompton et al.

    Nutritional impact of intestinal helminthiasis during the human life cycle

    Annu. Rev. Nutr.

    (2002)
  • C. Davey et al.

    Re-analysis of health and educational impacts of a school-based deworming programme in western Kenya: a statistical replication of a cluster quasi-randomized stepped-wedge trial

    Int. J. Epidemiol.

    (2015)
  • S.J. De Vlas et al.

    Validation of a chart to estimate true Schistosoma mansoni prevalences from simple egg counts

    Parasitology

    (1997)
  • W.R. Dowdle

    The principles of disease elimination and eradication

    Bull. World Health Organ.

    (1998)
  • W.R. Dowdle et al.

    The Eradication of Infectious Diseases

    (1998)
  • A.V. Easton et al.

    Multiparallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming

    Parasites Vectors

    (2016)
  • R.M. Flueckiger et al.

    Integrating data and resources on neglected tropical diseases for better planning: the NTD mapping tool (NTDmap.org)

    PLoS Negl. Trop. Dis.

    (2015)
  • J.E. Forrester et al.

    Measurement of Ascaris lumbricoides infection intensity and the dynamics of expulsion following treatment with mebendazole

    Parasitology

    (1990)
  • H.L. Guyatt et al.

    Evaluation of efficacy of school-based anthelmintic treatments against anaemia in children in the United Republic of Tanzania

    Bull. World Health Organ.

    (2001)
  • Cited by (32)

    • Assessment of cetyl-trimethyl-ammonium bromide (CTAB) based method for the extraction of soil-transmitted helminth DNAs from stools for molecular dagnostic of soil-transmitted helminthiasis

      2023, Journal of Microbiological Methods
      Citation Excerpt :

      The use of CTAB-based may have some epidemiological impacts in the control of soil-transmitted helminthiasis. Indeed, through health impact modeling, Medley et al. (2016) reported that improving diagnostic methods may increase the probability of disease elimination by optimizing the frequency of mass drug administration (MDA). This could also improve the disability adjusted life years (DALYs) and to some extent, could lead to earlier decision of stopping MDA.

    • How qPCR complements the WHO roadmap (2021–2030) for soil-transmitted helminths

      2021, Trends in Parasitology
      Citation Excerpt :

      Thus, the sustainable control or elimination of STHs must address current limitations in the use and implementation of diagnostic methods. WHO defines STH elimination when the prevalence of moderate to heavy infections is <2% [6–8]. Although the diagnostic tool(s) to be used to define this prevalence threshold are yet to be defined, a 3-year cycle of review and revision of the new WHO roadmap could accommodate these needs.

    • Quantitative PCR-Based Diagnosis of Soil-Transmitted Helminth Infections: Faecal or Fickle?

      2019, Trends in Parasitology
      Citation Excerpt :

      Mapping endemic geographies and evaluating an intervention programme would likely require a less sensitive test. Accuracy and sensitivity are more important when programmatic efforts focus on assessing the success of mass drug administration (MDA), post-MDA surveillance, or move towards the breakpoint of transmission [41]. Here, qPCR remains a strong candidate as the diagnostic technique of choice as long as the breakpoint of transmission has been sufficiently characterized epidemiologically for each of the helminths being monitored (e.g., biomarker clearance post-MDA) [42–44].

    • A comparison of helminth infections as assessed through coprological analysis and adult worm burdens in a wild host

      2018, International Journal for Parasitology: Parasites and Wildlife
      Citation Excerpt :

      There is, however, a consensus, irrespective of host species, that the accuracy of faecal egg and larval counts for diagnosing helminth infection is restricted because of several factors that include, but are not limited to, their absence when only male or female worms are present, variation in the methodologies employed in diagnostic procedure including faecal sample collection (Seivwright et al., 2004), variation in the abundance of eggs or larvae produced by the worms (Hudson, 1986; Shaw and Moss, 1989) and the influence of density-dependent factors (Keymer and Slater, 1987; Schad and Anderson, 1985; Tompkins and Hudson, 1999). In a recent analysis, utilizing both chemo-expelled Ascaris adult worms collected from children and egg production assessed by the formyl-ether concentration method (Holland et al., 1989), we were able to model the effects of improved diagnostic sensitivity and how that might impact upon the assessment of the success of large-scale control programmes for soil-transmitted helminths (Medley et al., 2016). In contrast, the present study, utilises similar data from a wild host, the European badger (Meles meles), providing support for the wider applicability of scientific findings from wildlife health surveillance as an important component of the one health concept (Daszak et al., 2000; Akdesir et al., 2018).

    View all citing articles on Scopus
    View full text