Comparison of coproprevalence and seroprevalence to guide decision-making in national soil-transmitted helminthiasis control programs: Ethiopia as a case study

Abstract

Background: WHO recommends periodical assessment of the prevalence of any soil-transmitted helminth (STH) infections to adapt the frequency of mass drug administration targeting STHs. Today, detection of eggs in stool smears (Kato-Katz thick smear) remains the diagnostic standard. However, stool examination (coprology) has important operational drawbacks and impedes integrated surveys of multiple neglected tropical diseases. Therefore, the aim of the present study was to assess the potential of applying serology instead of coprology in STH control program decision-making.

Methodology: An antibody-ELISA based on extract of Ascaris lung stage larvae (AsLungL3-ELISA) was applied in ongoing monitoring activities of the Ethiopian national control program against schistosomiasis and soil-transmitted helminthiasis. Blood and stool samples were collected from over 6,700 students (median age: 11) from 63 schools in 33 woredas (districts) across the country. Stool samples of two consecutive days were analyzed applying duplicate Kato-Katz thick smear.

Principal findings: On woreda level, qualitative (seroprevalence) and quantitative (mean optical density ratio) serology results were highly correlated, and hence seroprevalence was chosen as parameter. For 85% of the woredas, prevalence based on serology was higher than those based on coprology. The results suggested cross-reactivity of the AsLungL3-ELISA with Trichuris. When extrapolating the WHO coproprevalence thresholds, there was a moderate agreement (weighted κ = 0.43) in program decision-making. Using the same threshold values would predominantly lead to a higher frequency of drug administration.

Significance: This is the first time that serology for soil-transmitted helminthiasis is applied on such large scale, thereby embedded in a control program context. The results underscore that serology holds promise as a tool to monitor STH control programs. Further research should focus on the optimization of the diagnostic assay and the refinement of serology-specific program decision-making thresholds.

Fig 1. Coproprevalence and seroprevalence of STHs per woreda.

The coproprevalence (any STH, Ascaris, Trichuris and hookworm) was calculated as the proportion of students for whom eggs in the stool were detected by Kato-Katz thick smear. The seroprevalence (AsLungL3-ELISA) was defined as the proportion of students with an optical density ratio (ODr) on the AsLungL3-ELISA above the diagnostic cutoff. Nstud: number of students per woreda, Nsch: number of schools per woreda. Samples were collected in woredas of the following 7 regional states: Amhara (woredas 332–342), Oromia (woredas 400–466), Benishangul-Gumuz (woredas 662 & 669), SNNPR (771–788), Gambella (woreda 881), Tigray (woreda 903) and Harari (woreda 991).

Fig 2. Correlation between seroprevalence and mean optical density ratio on woreda level.

The size of the dots indicates the number of screened students per woreda. ODr: optical density ratio (ODr = (OD of sample–OD of negative control)/(OD of positive control–OD of negative control)).

Fig 3. Correlation between coproprevalence and seroprevalence on woreda level.

Panel A shows the correlation between Ascaris coproprevalence and seroprevalence, including Trichuris prevalence of the woredas as indicated by their color. Panel B displays the correlation between Trichuris coproprevalence and seroprevalence, showing Ascaris coproprevalence by color scale. The WHO coproprevalence thresholds for program decision-making regarding the frequency of drug administration are indicated in red on the x-axis [15]. The size of the dots indicates the number of screened students per woreda.

Fig 4. Program decision-making based on any STH coproprevalence and seroprevalence.

Classification based on the program decision tree endorsed by the WHO during the implementation phase of a control program (prevalence ≥ 50%: 3x MDA/year; 50% > prevalence ≥ 20%: maintain MDA frequency; 20% > prevalence ≥ 10%: 1x MDA/year; 10% > prevalence ≥ 2%: 1x MDA/2 years; prevalence < 2%: no MDA) [15]. The WHO coproprevalence thresholds are indicated in red on the x-axis. The same thresholds were extrapolated to the seroprevalence data due to a lack of evidence-based alternatives. The size of the dots indicates the number of screened students per woreda. The percentage of woredas ranked in a certain category is shown in the left bottom corner.