Effectiveness of single-dose albendazole against soil-transmitted helminth infection in children: A longitudinal study in a tribal dominated district of Odisha, India

Study design and setting

The present study was carried among children (1-15 yr) from a 18 different clusters/villages of Nabarangpur district, a tribal-dominated district of Odisha. Using the multi-stage sampling method, three out of 10 blocks in the district were randomly selected. Six clusters/villages were selected from each block i.e a total of 18 clusters were selected using the probability proportional to size (PPS) method. From each cluster, 80 or more children were randomly selected and recruited under the study with support from local health administration and frontline health care providers through house-to-house visits.

Sample size

Considering the reported prevalence of STH infection in India at 13.3 per cent⁵, confidence level of 95 per cent, absolute precision of 2.5 per cent and design effect of 1.5, the desired sample size was estimated to be 1063. Assuming a 20 per cent non-response rate, the sample size was estimated at 1329 and rounded up to 1400. To ensure adequate representation, 18 clusters were selected, targeting to recruit 80 participants (children aged 1–15 yr) per cluster. Children were eligible if they were permanent residents of the selected clusters and their parents or guardians provided written informed consent. Children were excluded if they were absent during the household survey, if consent was not obtained, or if they had received anti-helminthic treatment within the three months preceding data collection.

Stool sample collection and investigation for STH

Morning stool samples were collected from study participants. Routine microscopic examination was conducted to identify the presence of STH infections. For each positive sample, two aliquots were prepared for further analysis. The first aliquot was used for the quantitative identification of helminth eggs using the standard Kato-Katz thick smear technique, while the second aliquot was stored for future investigation.

A small quantity of collected fresh stool sample was filled in the template that was placed on the slide using a spatula. The template was removed after the known amount of excrement settled on the slide. The sample was covered with a cellophane strip that has been soaked in 3 per cent Methylene blue solution. Then it was lightly pressed to distribute the sample equally on the slide and left for 30 min to set. Slides were examined under the microscope in the laboratory. The infection rate of STHs was determined by calculating the average number of eggs per Kato-Katz slide, which was then multiplied by 24 to estimate the number of eggs per gram (EPG) of stool. All results were documented, and the infection intensities were categorized according to World Health Organization (WHO) thresholds into light, moderate, and heavy infections⁸.

Drug administration and follow up

The identified STH-positive children were administered with single dose anthelmintic drug albendazole 400 mg (tablet Noworm) and syrup to the children below 5 yr supervised by the trained anganwadi workers across the three blocks of Nabarangpur simultaneously. The children were kept under observation for a minimum of 2 h and were asked to report if any side effects were observed.

Following treatment, stool samples were collected from each participant at 14-day intervals for three consecutive follow ups (D14, D28 and D42). These samples were examined in the laboratory using the same techniques as at baseline to detect the presence of parasite eggs. This systematic monitoring aimed to assess both the immediate and sustained effects of albendazole on parasite clearance. All findings, including any side effects and changes in egg counts, were meticulously recorded for further analysis to evaluate treatment effectiveness and resistance development.

Data management and analysis

All collected data were entered into the statistical software R (version 4.4.1) for analysis, using modules based on the WHO child growth standards for descriptive statistics and to evaluate the effectiveness of albendazole. The fecal egg count reduction rate (FECRR) was calculated for each participant using a standard formula⁹. The average cure rate (CR) and egg reduction rate (ERR) among children infected with STH were determined using the Kato-Katz smear technique following the administration of tablet albendazole at 14-day intervals over three treatment cycles.

$\begin{array}{c}\text{FECRR}\%=\text{1}00\text{X}\\ \text{[1}-\text{(Arithmetic mean of follow up faecal egg count}\\ /\text{arithmetic mean baseline faecal egg count)]}\end{array}$

$\begin{array}{c}\text{CR}\%=\text{1}00\text{X}(\text{Number of negative children after treatment}\\ /\text{total no}.\text{ of positive before treatment})\end{array}$

$\text{Number needed to treat }\left(\text{NNT}\right)=\text{1}/\text{cure rate}$

Participant flow

A total of 1246 stool samples were collected from 1489 enrolled children in Nabarangpur district (drop out 16.3%). Of these, 203 were positive for STH infection and were administered a single 400 mg dose of albendazole. Follow-up stool samples were collected at 14, 28, and 42 days post-treatment. The flow of participants through enrolment, baseline positivity, and follow-up is shown in figure 1.

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Fig. 1.

Flow of participant through enrolment, baseline and follow up. STH, soil transmitted helminth.

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The status for prevalence of soil-transmitted helminth (STH) positivity cases and in three different study sites of Nabarangpur district is depicted in figure 2.

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Fig. 2.

Prevalence of Soil transmitted helminth (STH) positive cases in Nabarangapur District, Odisha, India. Source: QGIS 3.4 (open source software). The figure is generated by the authors only for this study and is not adopted from any literature source.

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Baseline characteristics

Mean age of 203 children positive for STH infection was 5.5 (±1.4) yr, and 50 per cent were boys. For analysis, age was grouped into 1–5 yr (pre-school age) and 6–15 yr (school-going age). Baseline average egg counts across socio-demographic groups are presented in table I. Higher baseline burdens were observed among older children, males, those from Nabarangpur block, children attending school, those living in kutcha houses, and children practicing open defecation.

Primary and secondary outcomes

Based on the number of helminthic eggs, the severity of the illness was assessed. Egg counts between 1-4999, 5000–49999, and ≥50000 were deemed to be mild, moderate, and severe respectively, for A. lumbricoides. Egg counts for hookworm were classified as mild, moderate, or severe based on egg counts between 1 and 1999, 2000–3999, and ≥4000, respectively¹⁰. Species-specific treatment responses are summarized in table II. A. duodenale was the most prevalent species (67.4%), followed by A. lumbricoides (32.0%), with one mixed infection. For A. lumbricoides, the FECRR was 96.2 per cent (meeting the WHO threshold of ≥95%), while the CR was 66.7 per cent (below the WHO-recommended ≥95%). For A. duodenale, the FECRR was 93.8 per cent (meeting the WHO threshold of ≥90%), but the CR was only 52.9 per cent. The single mixed infection showed a FECRR of 93.9 per cent and a CR of 0 per cent.

Trends in egg count reduction from baseline to days 14, 28, and 42 are shown in table III. Both age groups demonstrated significant declines, with higher baseline counts in older children. Girls had higher baseline egg counts than boys, though both sexes showed significant reductions (P= 0.025). Geographic differences were evident, with children from Nabarangpur block having the highest baseline counts, and significant reductions were observed across all blocks (P = 0.001). Schooling status was not significantly associated with reductions, although children without schooling had the highest baseline values.

Additional analyses

The impact of socio-demographic factors on egg count reduction is illustrated in figure 3 and supplementary figures 1, 2 and 3. Repeated measures ANOVA showed no significant effect of schooling (P=0.479), though children without schooling had higher baseline counts (Supplementary Fig. 1). Gender had a significant effect (P=0.025), with girls showing higher counts at all time points (Supplementary Fig.2). Tribal status did not significantly influence reductions (P=0.307) (Supplementary Fig. 3). Geography significantly interacted with time (P=0.001), with all blocks showing significant reductions, and Nabarangpur block having the highest baseline burden.

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Fig. 3.

Impact of socio-demographic factors on egg count reduction.

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