The neglected cestode infection: Epidemiology of Hymenolepis nana infection among children in rural Yemen

The cestode Hymenolepis nana, commonly known as the dwarf tapeworm, is the most prevalent cestode in humans, infecting over 75 million people worldwide (King, 2010). Infections occurs most commonly among children in the tropics and subtropics, particularly in underprivileged rural communities lacking sanitation and safe drinking water, with a prevalence as high as 55 % (Macnish, 2001; Thompson, 2015). Hymenolepis nana is known to infect humans through ingestion of eggs in food or water contaminated with faeces from infected humans or rodents. It can also be acquired by accidental ingestion of arthropods (usually flour beetles and fleas that serve as intermediate hosts) containing the cysticercoid stages, which then develop into adult worms in the gastrointestinal tract (Galan-Puchades, 2015). Moreover, H. nana is the only cestode that can be transmitted directly from person to person as well as autoinfection (endogenous autoinfection) commonly occurs, a feature that may have implications in the prognosis of infection among immunocompromised patients (Lucas et al., 1979; Olson et al., 2003).

Infection with H. nana, called hymenolepiasis, is most often asymptomatic, but heavy infections may cause abdominal pain, diarrhoea, nausea, vomiting, loss of appetite, anal itching, and weakness (Mirdha and Samantray, 2002; Cabada et al., 2016). Moreover, headache, dizziness, sleep, and behaviour disturbances are frequently reported (O’Dempsey, 2011). Furthermore, H. nana infection may cause serious disseminated disease and death, particularly among immunocompromised individuals, such as AIDS patients and malnourished children (Lucas et al., 1979; Olson et al., 2003; Muehlenbachs et al., 2015; Amer et al., 2018). Nevertheless, despite several reports on H. nana infections among children in different countries, data on clinical relevance and morbidity caused by H. nana are not convincing. Currently the drug of choice for H. nana infection is praziquantel, administered as a single dose (Schenone, 1980; O’Dempsey, 2011).

In Yemen, a Middle Eastern country, approximately 19 million people (70 % of the population) live below the poverty line and are food insecure (UNOCHA, 2019). Moreover, there is a severe lack of sanitation and less than 25 % of the population have access to clean drinking water (Oxfam, 2015). Due to the current widespread civil war, over 55 % of the country’s health facilities are totally destroyed, underground water in all Yemeni cities is contaminated with sewage, and the substandard sewage treatment plants are not functioning, putting the entire population at great risk of many infectious diseases (Gavlak, 2015; Al-Mekhlafi, 2018). For instance, since 2015, there have been deadly outbreaks of cholera, dengue, leishmaniasis, and diphtheria (Al-Mekhlafi, 2018; El Bcheraoui et al., 2018; Alghazali et al., 2019).

With regards to intestinal parasites, many studies have reported on the prevalence of different intestinal parasitic infections in Yemen, including soil-transmitted helminth (STH), Giardia, Entamoeba, and Cryptosporidium infections (Azazy et al., 2002; Alyousefi et al., 2011; Al-Mekhlafi et al., 2016; Alsubaie et al., 2016; Al-Areqi et al., 2017; Al-Mekhlafi, 2017). A few of those studies have included the occurrence of H. nana infection in the parasitological assessment, and have reported a prevalence rate ranging between 5 % and 13 %. However, the data on the distribution of H. nana infection in Yemen is limited. Moreover, data on the associated risk factors and potential impact of infection on the health and nutritional status of infected individuals is not available. Therefore, the current study was carried out among rural communities in Yemen to determine the prevalence and distribution as well as the associated risk factors of H. nana infection.

All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional ethical committee and with the 1964 Helsinki declaration and its later amendments.

The study protocol was approved by the Medical Ethics Committee of the University of Malaya Medical Centre (Ref. No. 201411-805). Moreover, permission to commence sampling and data collection was also obtained from the respective health office of each governorate. A written and signed or thumb-printed informed consent was obtained from the parents for their participation as well as on behalf of their children.

The current study is the first to provide information on the epidemiology of H. nana in Yemen. The findings revealed a relatively high prevalence (15.5 %) of H. nana infection among rural children in Taiz and Almahweet governorates. Moreover, this is the highest prevalence reported in Yemen and the Middle East region. Previous studies among primary schoolchildren in different governorates in Yemen reported prevalence rates between 2.3 % and 13 % (Raja’a et al., 2000; Azazy et al., 2002; Raja’a and Mubarak, 2006; Al-Haddad and Baswaid, 2010; Al-Mekhlafi et al., 2016; Alsubaie et al., 2016; Alwabr and Al-Moayed, 2016). The highest prevalence reported before the current study was 13 % among children aged 5 – 18 years in Ibb governorate, which borders Taiz (Raja’a et al., 2000) followed by 12.2 % reported among 320 children aged 6 – 16 years in Hajjah governorate, which borders Almahweet (Alharbi et al., 2019). This variation in the prevalence of H. nana could be attributed to the different areas and populations studied as well as to the methods utilised for stool examination. A much lower prevalence rate (0.9 – 1.4 %) was reported among participants aged 2 – 80 years attending hospitals and clinics in Sana’a City and Taiz governorate (Alyousefi et al., 2011; Al-Harazi, 2016). The higher prevalence reported by the current study may also be explained by the devastating ongoing civil war in Yemen that has led to approximately 55 % of healthcare facilities being totally non-functioning (Gavlak, 2015; UNOCHA, 2019). Moreover, mass drug administration (MDA), the key strategy for controlling schistosomiasis and STH infections in Yemen, has been largely interrupted due to the war (Al-Mekhlafi et al., 2018).

A much lower prevalence of H. nana infection is commonly reported worldwide (Oliveira et al., 2015; Asai et al., 2016; Spinicci et al., 2018; Periago et al., 2018; von Huth et al., 2019). However, a similar prevalence (17.4 %) has been reported among children aged 3 – 16 years in the highlands of Peru (Cabada et al., 2016). In contrast, a higher prevalence rate has been reported in different countries around the world. For instance, 25.8 % in 602 children aged 7 – 11 years in western Tajikistan (Matthys et al., 2011), 27.5 % (195/708) in 708 children aged 8 – 16 years in Nepal (Shrestha et al., 2018), 28.3 % in 405 children aged less than 13 years in Ethiopia (Amare et al., 2013), 33 % among 500 preschool children of displaced communities in Khartoum, Sudan (Abdel Hamid et al., 2015), 50 % in 150 cases of phlyctenular eye disease in Egypt (Hussein and Nasr, 1991) and 55 % among the aboriginal community in northwestern Australia (Reynoldson et al., 1997).

With regards to the risk factors of H. nana infection, the current study identified age below 6 years, presence of other family members infected with H. nana, highlands residency, living in a house without toilet facilities, not washing hands after defecation, and not washing vegetables before consumption as the significant risk factors. Interestingly, the current study revealed a significantly higher prevalence of H. nana infection among preschool-aged children (below 6 years) compared to older children. This is inconsistent with previous studies conducted in Zimbabwe (Mason and Patterson, 1994) and Peru (Cabada et al., 2016).

Currently, studies specifically among preschool children in Yemen are not available. However, a linear association between the prevalence of intestinal parasites and age is well documented. For instance, it is commonly reported that older children aged 10 years and above are more likely to contract infections from the environment (Cabada et al., 2016; Al-Mekhlafi et al., 2019). However, the nature and extent of the association might be different for some parasites, specifically H. nana and E. vermicularis because these can be transmitted directly from human to human and through auto-reinfection. The acquisition of H. nana infection can also be linked to the presence of other family members infected with H. nana, which the current study also identified as a risk factor of H. nana. This association might be attributed to the horizontal transmission (intrafamily transmission) of intestinal parasitic infections among family members. For instance, in poor communities an infected mother could transmit H. nana by preparing food for her family members, and infected children could also transmit the parasite to their siblings. These suppositions are consistent with previous studies on H. nana and other intestinal parasites such as Giardia, Entamoeba and STH in Yemen and elsewhere (Mason and Patterson, 1994; Elyana et al., 2016; Al-Areeqi et al., 2017; Al-Mekhlafi, 2017)

The higher prevalence of H. nana among preschool children may have an important implication for the schistosomiasis and STH infections control programmes in Yemen and other countries that are endemic for Schistosoma and H. nana infections. These programmes cover only schoolchildren, whereas preschool-aged children and non-enrolled school-aged children, particularly girls, are not offered treatment (Oshish et al., 2011; Faust et al., 2020). In such circumstances, preschool children will continue serving as a source of infection within endemic communities, and other age groups will be reinfected within a short period of time. Therefore, it is vital to include preschool-aged children in MDA with praziquantel to improve the control of schistosomiasis and other intestinal parasitic infections (including H. nana) (Soares Magalhães et al., 2013; Asai et al., 2016). However, the absence of paediatric formulations of praziquantel hampers the routine treatment of preschool-aged children. Hence, the need for a paediatric formulation of praziquantel is pressing, and efforts are being undertaken to make it available by 2020 (Coulibaly et al., 2017; Fenwick, 2017). Indeed, the Pediatric Praziquantel Consortium, an international partnership, was established in 2012 with the goal of developing a pediatric-friendly praziquantel orally dispersible tablet formulation and obtaining regulatory approval of its use for treating schistosomiasis in children aged from 3 months to 6 years (https://www.pediatricpraziquantelconsortium.org/) Two paediatric clinical trials (Phase I and II) have been conducted in sub-Saharan Africa in the frame of the Consortium’s project, and the Phase III trials of safety and efficacy of the developed formulation are ongoing (N’Goran et al., 2019; Faust et al., 2020).

In the current study, H. nana infection was found to be significantly higher among children residing in the highlands (Almahweet). These children had three times the odds of acquiring H. nana compared to their peers residing in coastal/foothill areas (Taiz). While the underlying reasons for such association remain unexplained, a similar topographical variation in H. nana prevalence has been reported in Peru where prevalence rates of 17.4 % and 7.6 % were found among children in coastal and highlands areas, respectively (Cabada et al., 2016; Vilchez Barreto et al., 2017). This suggests that further studies are needed on the impact of environmental and meteorological factors on the prevalence and distribution of H. nana.

It is also well documented that intestinal parasitic infections are particularly common in children living in underprivileged areas where poverty prevails and where sanitation and an improved water supply are lacking (Vaz Nery et al., 2019). In the current study, living in a house without functioning toilet facilities doubled the odds of children acquiring a H. nana infection. This is in agreement with previous studies in Mexico (Martinez-Barbabosa et al., 2010) and Peru (Vilchez Barreto et al., 2017). These two studies (Martinez-Barbabosa et al., 2010; Vilchez Barreto et al., 2017), as well as studies conducted in Kyrgyzstan (Steinmann et al., 2010) and Tajikistan (Matthys et al., 2011), have also identified the lack of an improved water supply in the household as a significant risk factor of H. nana; an association that was not reported in the current study.

Personal hygiene practices play a crucial role in the transmission of intestinal parasitic infections (Gungoren et al., 2007). The current study found that children who did not wash their hands after defecation and those who did not wash vegetables before consumption were approximately twice as likely to be infected with H. nana compared with children who practised good personal hygiene. This is consistent with previous reports on intestinal parasitic infections (Gulliver et al., 2014; Elyana et al., 2016; Al-Areeqi et al., 2017; Al-Mekhlafi, 2017). Thus, the findings of the current clearly speak to the imperative need for improved sanitation, water and hygiene (WASH) facilities in the rural communities of Yemen. Hymenolepis nana is the only cestode that does not necessarily require an intermediate host for its transmission from person to person. Infected individuals who do not wash their hands with soap after defecation may transmit infective eggs of H. nana to others by a variety of means including shaking hands and processing food. A previous randomised controlled trial showed that frequent handwashing with soap significantly decreased the H. nana reinfection rate among schoolchildren (Mahmud et al., 2015). Similarly, a systematic review of studies on the parasitic contamination of fruits and vegetables processed for human consumption showed that H. nana was among the most commonly reported parasites (Karshima et al., 2018).

Although H. nana infection is usually asymptomatic, it has been associated with gastrointestinal symptoms among children. The current study found a significant association between H. nana infection and abdominal pain and anal itching as well as dizziness. Although skin manifestations such as pruritus ani (anal itching) are rare in H. nana infection, a significant association between H. nana infection and anal itching was reported among the studied children. A previous study in Peru showed that H. nana infection is significantly associated with diarrhoea, jaundice, and headache (Cabada et al., 2016). Likewise, H. nana-infected Sudanese children have been found to have a nine-fold higher risk of diarrhoea compared with uninfected children (Abdel Hamid et al., 2015). Moreover, H. nana infection has been identified as a significant predictor of malnutrition and anaemia (Mohammad and Hegazi, 2007; Oliveira et al., 2015; Spinicci et al., 2018). Thus, further studies are warranted on the burden and clinical profile of H. nana infection among children in rural Yemen.

It should be noted that the current study has limitations that should be considered when interpreting the findings. Firstly, a cross-sectional study design was used for this study, which limited the ability to infer causality between H. nana infection and explanatory variables. Secondly, a single faecal sample was collected from each child instead of the ideal three consecutive days of sample, which would have enhanced the sensitivity of parasite diagnosis (Hall, 1981). Thus, the prevalence of H. nana infection reported in the current study might have been underestimated.

In conclusion, this study revealed a high prevalence of H. nana infection among children in rural Yemen, particularly among preschool-aged children. Therefore, preschool-aged children should be included in the national schistosomiasis and STH control programme. In addition to periodic MDA, the control programme should focus on providing health education on hygienic practices, the introduction of adequate WASH facilities and screening and treating other infected family members. These measures are crucial because they will help to significantly reduce the prevalence of H. nana and other intestinal parasites among rural communities in Yemen. Also, further investigations are required to evaluate the true public health burden and the clinical profile of H. nana infection in these communities in order to guide future control efforts against intestinal parasites.