1. Introduction
Soil-transmitted helminth (STH) infections are the most common infections of neglected tropical diseases (NTDs) worldwide, primarily affecting the poorest and most deprived communities [
1]. STHs are endemic in the tropical and sub-tropical regions, with the highest burdens occurring in sub-Saharan Africa, the Americas, China, and East Asia [
2]. More than 1.5 billion or 24% of the world’s population suffer from one or more STH infections [
1]. The most common species of STH that infect people are the roundworm (
Ascaris lumbricoides), the whipworm (
Trichirus trichiura), and various species of hookworms (
Necator americanus Ancylostoma duodenale and
Ancylostoma ceylanicum) [
1].
Ascaris and
Trichirus infections are transmitted through contaminated food and water, whereas hookworms are transmitted by skin penetration [
3]. Children are by far the most disproportionately affected by STH, and infected children are usually malnourished and anemic because of the resultant nutritional deficiency. Over 568 million school-age children live in areas where these parasites are intensively transmitted [
1]. Numerous studies have indicated that poor water, sanitation, and hygiene (WASH) put children at higher risk of STH infections [
3,
4]. STH infection contributes to delayed intellectual development, diminished physical fitness, growth retardation, and cognition [
5].
To reduce the morbidity of schistosomiasis and STH, in May 2001, the World Health Assembly endorsed a resolution for regular treatment of high-risk groups, particularly school-age children, through mass drug administration (MDA) of anthelmintics [
6]. Large-scale preventive chemotherapy (PC) (also called deworming) through periodic mass administration of single-dose albendazole 400 mg or mebendazole 500 mg to at-risk population is WHO’s core intervention strategy to control morbidity [
7]. The WHO intervention program targets to eliminate STH as a public health problem (defined as a reduction in prevalence to <1% of moderate or high-intensity infection) by 2020 [
8]. Although the WHO intervention strategy recommends PC to all at-risk groups, NTD programs in many endemic countries, including Rwanda, provides MDA to pre-school children (Pre-SAC) and school-aged children (SAC), while adults-at-risk are not considered and may serve as a source of infection to treated children [
9].
Following the WHO recommendations, school-based MDA has been initiated in many endemic countries, including Rwanda. The national NTD control program in Rwanda was established in 2007. The first MDA was delivered in 2008 after the initial disease mapping pre-intervention survey that revealed that >65% of children had intestinal worms with high levels of multiple parasite coinfection [
10]. Although Rwanda achieved about 100% coverage of albendazole and praziquantel MDA, mostly targeting school-aged children in 2008–2010, the transmission of
Schistosoma mansoni (S. mansoni) and STHs continued as reported by a follow-up survey [
9]. The mapping report of 2014 revealed that the average STHs prevalence in all districts was 45.2% compared to 65.8% that was reported by the pre-intervention mapping in 2008; this shows a decrease in the prevalence of 20.6% countrywide [
11]. However, no assessment was done on the effectiveness of long-term interventions in controlling morbidity. Continued surveillance after a decade of program implementation is important to assess the STH control program’s impact and determine the next steps [
12]. As the milestone of WHO target to eliminate STH as a public health problem in 2020 is due, surveillance data assessing the impact of long-term PC in reducing the disease burden is critical for evidence-based decision making. The aim of the study was to investigate the prevalence, infection intensities, and factors associated with STH among school children in four rural districts in the western province of Rwanda.
3. Discussion
This cross-sectional study investigated the prevalence, intensity, and associated risk factors for STH infections (ascariasis, trichuriasis and hookworms) among school children 5–15 years old attending eight primary schools in four rural districts in the Western province of Rwanda. The study districts (Rusizi, Nyamasheke, Rubavu, and Rutsiro) lay on the belt of lake Kivu (
Figure 4), which is among the most STH endemic region in Rwanda. The main findings of the study include; (i) a high overall prevalence (77.7%) of STH infection, though prevalence significantly varies between study districts (ranging from 54% to 92%), and between study schools (ranging from 54% to 93%), (ii)
T. trichiura (66.8%) was the most prevalent STH parasite species followed by
A. lumbricoides (49.9%), and hookworms (1.9%), (iii) a high prevalence of multiple parasite coinfection (>50%) mostly with
T.trichiura and
A. lumbricoides, (iv) stunting, male sex, living district, school, and schistosomiasis coinfection were significant predictors of STH infection, (v) stunting and living district were significant predictors of high infection intensity, particularly for
T. trichiura and
A. lumbricoides infections. To our knowledge, this is the most extensive study to evaluate the status and predictors of STH infections after long-term implementation of multiple rounds of MDA in Rwanda and sub-Saharan Africa at large.
The study findings revealed that 32% of the children were stunted, which is in line with Rwanda Demographic and Health Survey’s national data, reporting 38% of children were stunted in 2015 [
15]. A recent study from Tanzania [
16] reported that 29% of schoolchildren were stunted. Our result indicates a significant correlation between stunting with having STH infection, regardless of parasite species involved (
Table 2). Stunting was also a predictor of high infection intensity (high number of eggs counts/gram of stool), particularly for infection by
A. lumbricoides and
T. trichiura. Similar findings were reported from Uganda and Kenya, which revealed that children affected by STH are usually malnourished and anemic because of nutritional deficiency [
17,
18]. Stunting due to STH infection may contribute to delayed intellectual development, diminished physical fitness, growth retardation, and cognition [
5,
19]. The high prevalence of coinfection between
T. trichiura and
A. lumbricoides (49.3%) found in this study is consistent with a recent report that most of the dual STH infections observed in Ethiopia involve
A. lumbricoides and
T. trichiura [
20]. In line with the report from Ethiopia [
20], we also found a significant correlation between schistosomiasis and STH coinfection (
Table 4). Our study revealed that sex, district, school, stunting, and schistosomiasis coinfection as significant predictors of STH infection.
Large-scale targeted preventive chemotherapy or deworming to at all risk-population is WHO’s core intervention strategy to control morbidity and eliminate STHs as a public health problem [
8]. In 2008, the Rwandan national NTD program conducted pre-intervention disease mapping. The baseline survey reported that STH and schistosomiasis infection was a significant public health problem in Rwanda, where more than 65% of children had intestinal worms with high levels of multiple parasite coinfection prevalence [
10]. Since 2008, Rwanda’s national NTD program has been implementing a targeted school-based biannual deworming program with albendazole and an annual deworming for praziquantel in all areas with a moderate-to-high prevalence rate of STH and schistosomiasis infections. Early follow-up surveys indicated that despite Rwanda achieved about 100% coverage of MDA during 2008–2010, the transmission of STHs continued [
9]. The mapping report of 2014 revealed STH prevalence of 45.2% STH infection countrywide, which is a decrease by 20.6% from the 65.8% pre-intervention mapping report in 2008 [
11].
The current study was conducted after ten years (in 2019) nationwide implementation of MDA in Rwanda, with >68.8 million and >3.2 million treatments delivered to children against STH and schistosomiasis, respectively [
21]. The overall STH infection prevalence (77.7%) and the high multiple parasite infection prevalence (>50%) observed in this study indicate that STH infection remains a significant public health problem in Rwanda, despite a decade of preventive chemotherapy with nearly 100% coverage. This study can serve as a proxy to assess the impact of a 10-year preventive chemotherapy implementation to control and eliminate STH infection in the 4 study districts. Apparently, despite biannual MDA for years, the burden of STH infection, in particular
T. trichiura infection, remain the same in Rubavu and paradoxically increasing in Ruszi district (
Figure 2 and
Figure 3). Nevertheless, the applied standard single-dose albendazole 400 mg preventative chemotherapy has successfully lowered the burden of hookworm infection and slightly reduced
A. lumbricoides infection, but with no significant impact on
T. trichiura infection. The significant decrease in hookworm infection prevalence rate over time compared to
A. lumbricoides and
T. trichiura could be due to variations in albendazole efficacy against the three parasite species. A systematic review and meta-analysis study reported the highest efficacy of albendazole against hookworm infection and a significant reduction in the efficacy of albendazole against
T. trichiura over the past two decades [
22]. Lack of efficacy of albendazole or mebendazole against
T. trichiura is also reported previously [
23,
24]. A randomized clinical trial that investigated the efficacy of 200 mg, 400 mg, 600 mg of albendazole or placebo in pre-school children, and 400 mg, 600 mg, 800 mg of albendazole or placebo in school children reported that low efficacy against
T. trichiura in both study populations and by all studied doses [
25]. Search for other alternative treatment against
T. trichiura infection is ongoing, including albendazole combination therapy with oxantel pamoate [
26] or with moxidectin [
27] but so far with limited success. On the other hand, reduced efficacy of albendazole against
A. lumbricoides in Rwandan school children is reported previously [
28]. Available reports, including ours, highlight that to eliminate STH as a public health problem in endemic regions, new drugs or alternative treatment regimens, particularly for
A. lumbricoides and
T. trichiura is urgently needed.
The study findings indicate that residence districts and schools are significant predictors of STH infection. The most affected districts were the Rubavu and Ruszi districts, where 91.8% and 88.6% of the children were infected by one or more STH species. Rambo and Rubona schools were the most affected, where 93% and 91% of the children were infected by at least one or more STH species (
Table 2). A recent study conducted in Nkombo Island in the western province of Rwanda revealed a higher overall prevalence of STH (95.2%) infection, and the prevalence for
T. trichiura, A. lumbricoides, and hookworm being 92.9%, 35.7%, and 11.6% for respectively [
29] This further highlights a similar trend in STH species with the current study finding (prevalence of 67% for
T. trichiura, 50% for
A. lumbricoides, and 1.9% for hookworm). Available reports, including ours, indicate a considerable burden of STH in the western province of Rwanda.
The WHO intervention program set a goal to eliminate STH as a public health problem by 2020. For operation purposes, WHO defines STH infection as a public health problem when the prevalence of moderate or high-intensity in at-risk populations is >1% [
8]. Although most children had light intensity infection, the overall prevalence of moderate or high-intensity infection for
T. trichiura and
Ascaris lumbricoides in our study was 7.1% and 13.9%, respectively (
Table 1). This indicates that Rwanda is far from achieving the intended WHO target to eliminate STH as a public health problem by 2020. It is well recognized that the WHO intervention strategy and implementation of the global NTD program have contributed to reducing the disease burden. However, the long-term intervention measures taken so far by many endemic countries in sub-Saharan Africa, including Rwanda, have not managed to control and eliminate STH and other NTDs as a public health problem by 2020 [
16,
20,
30,
31]. Several factors may have contributed to this shortcoming [
32]. With respect to STH infections, apart from increasing MDA coverage, adequate access to clean water, sanitation, and hygiene are vital to reduce the risk of parasite exposure and halt transmission [
33,
34]. In 2015, WHO recommended a global plan to better integrate water, sanitation, and hygiene (WASH) services with four other public health interventions to accelerate progress in eliminating and eradicating neglected tropical diseases (NTDs) by 2020 [
35]. Although many endemic countries managed to achieve high MDA coverage, limited coordination with the water, sanitation, and hygiene (WASH) sector in many endemic countries remains challenging [
32]. Recognizing this challenge, Rwanda revised its Neglected Tropical Diseases Strategic Plan 2019–2024 and set a goal to make Rwanda free from NTDs as a public health problem by 2024 through the implementation of WHO-recommended public health strategies for prevention and control of NTDs [
21]. Recent expert review projects that with sustained program implementation, the global elimination of STH infections as a public health problem might be achieved by 2030 [
36].
The other contributing factor for the high prevalence of STH in our study could be the reduced effectiveness of albendazole in killing STHs. The large-scale repeated use of anthelminthic drugs and repeated drug exposure may increase the likelihood of the targeted parasite developing resistance. Lack of impact of repeated mass albendazole chemotherapy in preventing
T. trichiura transmission observed in this study, and the reduced efficacy of albendazole against
A. lumbricoides in Rwandan school children reported previously [
28] is a concern. Drug resistance should be suspected if high-frequency anthelminthic treatment with high-coverage is found to have less than the expected effect on the target parasite [
37]. After four years of implementing PC programs for schistosomiasis and soil-transmitted helminthiases, anthelminthic drug efficacy assessment is recommended [
37]. As the current mass STH control programs, rely almost exclusively on few available benzimidazole anthelmintics, regular surveillance and monitoring of drug efficacy are essential for early detection of parasite resistance so that mitigation strategies such as combination therapy to prolong the effectiveness of the existing anthelmintic drugs, and intensify the search for new anthelmintic drugs or intervention measures [
38].
This study has some limitation. Although we used Kato-Katz, the most widely used diagnostic method recommended by WHO for epidemiologic surveys and anthelminthic drug efficacy studies against schistosomiasis and STH [
37,
39], its sensitivity decreases in low prevalence and low-intensity settings [
40]. Low sensitivity of Kato-Katz for detection of hookworm infection may be related to rapid degeneration of delicate hookworm eggs with time [
41]. To overcome this limitation, fresh fecal samples were processed and read onsite at each study school within one hour of sample collection. In addition, the current study was done in a similar set-up using the same diagnostic method (Kato-Katz) used previously by the national NTD program during the 2008 and 2014 STH mapping. Therefore the significant decline in hookworm prevalence in this study compared to the mapping data in 2008 and 2014 (
Figure 3) could possibly be due to repeated preventive chemotherapy, since albendazole displays highest efficacy rate against hookworm than
A. lumbricoides and
T. trichiura [
22]. Use of Kato-Katz method for STH screening is useful to define infection intensity according to the WHO threshold [
13]. The prevalence of moderate or heavy infection intensities in at-risk population can serve as a surrogate marker to assess the impact of preventive chemotherapy in eliminating STH as a public health problem [
8]. As our study was done in a resource-limited setting with relatively higher infection prevalence and intensity, we consider that our finding is valid despite using the less sensitive Kato-Katz technique. Nevertheless, the observed light intensity-infection prevalence in this study could possibly be increased by using a more sensitive molecular diagnostics methods such as quantitative polymerase chain reaction (qPCR).