Therapeutic efficacy of albendazole against soil-transmitted helminthiasis in children measured by five diagnostic methods

Abstract

Background: Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz.

Methods: An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy.

Principal findings and conclusions: The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance.

Trial registration: ClinicalTrials.gov NCT03465488.

Conflict of interest statement

The FECPAKG2 technology was produced and distributed by Techion Group Ltd, of which ET is an employee and GM is managing director. Both hold stocks in Techion Group Ltd. The Mini-FLOTAC device is a commercial product distributed by GC, LR and MPM through the University of Napoli Federico II. However, their affiliations did not play any role in the preparation and submission of this manuscript. All other authors declared that they have no competing interests.

Figures

Fig 1. Number of subjects withheld at recruitment, baseline and follow-up, and for statistical data analysis.

FECs: fecal egg counts expressed in eggs per gram of stool (EPG), 2x KK: duplicate Kato-Katz.

Fig 2. The individual drug efficacy of albendazole against Ascaris lumbricoides, measured by five diagnostic methods.

The upper three bar plots illustrate the different classifications of individual albendazole efficacy for A. lumbricoides detected in the study population (n = 441; Ethiopia: 137, Lao PDR: 111, Pemba (Tanzania): 193) in each of the 3 countries using 5 different diagnostic methods (single (1x KK) and duplicate Kato-Katz (2x KK), Mini-FLOTAC (MF), FECPAKG2 (FP) and qPCR). The bars represent the number of cases. The color of the bars reflects the individual egg or genome equivalent reduction rate (i(G)ERR). The bottom three bar plots represent the classification of the i(G)ERRs for A. lumbricoides for those individuals for which i(G)ERR data was available for all five diagnostic methods (n = 258; Ethiopia: 80, Lao PDR: 50, Pemba (Tanzania): 128).

Fig 3. The individual drug efficacy of albendazole against Trichuris trichiura, measured by five diagnostic methods.

The upper three bar plots illustrate the different classifications of individual albendazole efficacy for T. trichiura detected in the study population (n = 456; Ethiopia: 106, Lao PDR: 105, Pemba (Tanzania): 245) in each of the 3 countries using 5 different diagnostic methods (single (1x KK) and duplicate Kato-Katz (2x KK), Mini-FLOTAC (MF), FECPAKG2 (FP) and qPCR). The bars represent the number of cases. The color of the bars reflects the individual egg or genome equivalent reduction rate (i(G)ERR). The bottom three bar plots represent the classification of the i(G)ERRs for T. trichiura for those individuals for which i(G)ERR data was available for all five diagnostic methods (n = 256; Ethiopia: 21, Lao PDR: 29, Pemba (Tanzania): 206).

Fig 4. The individual drug efficacy of albendazole against hookworm, measured by five diagnostic methods.

The upper three bar plots illustrate the different classifications of individual ALB efficacy for hookworm detected in the study population (n = 457; Ethiopia: 90, Lao PDR: 228, Pemba, Tanzania: 139) in each of the 3 countries using 5 different diagnostic methods (single (1x KK) and duplicate Kato-Katz (2x KK), Mini-FLOTAC (MF), FECPAKG2 (FP) and qPCR). The bars represent the number of cases. The color of the bars reflects the individual egg or genome equivalent reduction rate (i(G)ERR). The bottom three bar plots represent the classification of the i(G)ERRs for hookworm for those individuals for which i(G)ERR data was available for all five diagnostic methods (n = 256; Ethiopia: 34, Lao PDR: 166, Pemba, Tanzania: 56).