Schistosomiasis outbreak during COVID-19 pandemic in Takum, Northeast Nigeria: Analysis of infection status and associated risk factors

Background Mass drug administration for schistosomiasis started in 2014 across Taraba State. Surprisingly in 2020, an outbreak of schistosomiasis was reported in Takum local government area. This epidemiological investigation therefore assessed the current status of infection, analyzed associated risk factors and arrested the outbreak through community sensitization activities and mass treatment of 3,580 persons with praziquantel tablets. Methods Epidemiological assessment involving parasitological analysis of stool and urine samples were conducted among 432 consenting participants in five communities. Samples were processed using Kato-Katz and urine filtration techniques. Participants data on demography, water contact behavior and access to water, sanitation and hygiene facilities were obtained using standardized questionnaires. Data were analysed using SPSS 20.0 and significance level was set at 95%. Results An overall prevalence of 34.7% was observed, with 150 participants infected with both species of Schistosoma parasite. By communities, prevalence was higher in Birama (57.7%), Barkin Lissa (50.5%) and Shibong (33.3%). By species’, S. haematobium infection was significantly higher than S. mansoni (28.9% vs 9.5%), with higher proportion of younger males infected (p<0.05). The condition of WASH is deplorable. About 87% had no latrines, 67% had no access to improved source of potable water and 23.6% relied on the river as their main source of water. Infections was significantly associated with water contact behaviors like playing in water (OR:1.50, 95% CI: 1.01–2.25) and swimming (OR:1.55, 95% CI: 1.04–2.31). Conclusion It is important to reclassify the treatment needs of Takum LGA based on the findings of this study. Furthermore, efforts targeted at improving access to WASH, reducing snail population, improving health education and strengthening surveillance systems to identify schistosomiasis hotspots will be a step in the right direction

Ethical clearance for this study was obtained from the Taraba State Ministry of Health ethics review board. A pre-survey contact/advocacy meeting was made to each selected study community to obtain consent from community leaders and other major stakeholders after explaining the objectives of the research to them. This was followed by community mobilization and sensitization using town announcers to communicate the objectives of our visit to community members. Sensitization was done in all religious and public places like schools and market squares to promote participation.
Community members willing to participate in the study completed written consent forms on the day of sample collection. Assent forms was completed in cases where the willing member is below 16 years of age. In this case, parents or any legal guardian were asked to accompany minors under age 16 to the sample collection site, to provide additional consents. The method of consent assertion was through thumbprint on already printed informed consent forms (ICFs).

Methods
Epidemiological assessment involving parasitological analysis of stool and urine samples were conducted among 432 consenting participants in five communities. Samples were processed using Kato-Katz and urine filtration techniques. Participants data on demography, water contact behaviour and access to water, sanitation and hygiene facilities were obtained using standardized questionnaires. Data were analysed using SPSS 20.0 and significance level was set at 95%.
About 87% had no latrines, 67% had no access to improved source of potable water and 23.6% relied on the river as their main source of water. Infections was significantly

Introduction
Schistosomiasis is an acute and chronic parasitic disease, caused by a water-borne trematode of the genus Schistosoma. Owing to the burden associated with this disease, the World Health Organization (WHO) classified it as one of the major and most common neglected tropical diseases (NTDs) requiring public health attention [1] Schistosomiasis is as well a focal disease [2], with a wide geographic distribution [3,4].
Currently, over 206 million people in 78 countries are affected with about 24,000 deaths and 2.5 million disability-adjusted life years (DALYs) [3]. The disease thrives in tropical and subtropical regions, especially among rural and marginalized urban populations without access to water, sanitation and hygiene (WASH) facilities [1,[4][5][6].
It is estimated that at least 90% of those affected and requiring treatment for intercourse and infertility [10][11][12]. The pathologies are worsened among children because of the developing immunity, with already established evidence on anemia, stunting, protein-energy malnutrition, school absenteeism and reduced cognition [13][14][15].
Children below age 15 remain the most vulnerable and represent the target group for most control interventions [5]. Ongoing elimination effort involves mass drug administration (MDA) of praziquantel to school-aged children between age 5 and 14 years in endemic areas following already established guidelines [5]. Since 2010, the WHO has coordinated the annual distribution of 250 million praziquantel donated by Merck and co. to several endemic countries with about 95.3 million people treated in 2019 [3]. Nigeria is one of the schistosomiasis endemic countries in Africa [1]. Of the 774 government areas (LGAs), about 708 LGAs had been mapped by the Federal Ministry of Health (FMoH), with 608 of them being endemic [16]. Treatment commenced since 2009 in Taraba and other 26 states with the support of WHO, UNICEF and partner organizations such as Mission to save the helpless (MITOSATH), Sightsavers, AMEN foundation among others [16]. Taraba is one of the 36 states in Nigeria, located in the northeastern region.
The state has 16 administrative units, referred to as local government areas (LGAs). All the LGAs were mapped for schistosomiasis in 2010 and subsequently in 2014 by the FMoH and other supporting partners [16,17]. During the mapping phase, a total of 80 schools was surveyed (5 schools per LGAs) with urine and stool examination from 3,936 school-aged children [17]. Takum was one of the LGAs mapped, with a low prevalence of 4% across the five schools examined in Sufa, Gboko, Kwambai, Takum and Takum communities. The LGA was then classified to be of low endemicity, and benefitted from biennial treatment strategy targeted at school-aged children since 2014 [17]. The therapeutic coverage in this LGA was optimal in the last 5 rounds of mass drug administration (MDA). In August 2020, during the COVID-19 pandemic, an outbreak of hematuria was reported in both children and adults across eleven communities in Takum

Ethical statement and considerations
Ethical clearance for this study was obtained from the Taraba State Ministry of Health ethics review board. A pre-survey contact/advocacy meeting was made to each selected study community to obtain consent from community leaders and other major stakeholders after explaining the objectives of the research to them. This was followed by community mobilization and sensitization using town announcers to communicate the objectives of our visit to community members. Sensitization was done in all religious and public places like schools and market squares to promote participation. Community members willing to participate in the study completed written consent forms on the day of sample collection.
Assent forms was completed in cases where the willing member is below 16 years of age.
In this case, parents or any legal guardian were asked to accompany minors under age 16 to the sample collection site, to provide additional consents. The method of consent assertion was through thumbprint on already printed informed consent forms (ICFs).

Study area
This study was carried out in five communities located in Takum LGA, Taraba state, Northeastern, Nigeria. Takum is one of the 16 LGAs in Taraba state, with an approximate land area of 2,503 km 2 (Figure 2). The climate of the area is tropical with vegetation characterized by a typical Guinea savannah interspersed with gallery forest. The annual rainfall ranges between 1,200mm and 2,000mm annually, while the average temperature is between 28 and 32°C reaching a peak at 37 °C in March and April. In addition, the area has several ponds, streams and rivers, which provides conducive environment for farming and fishing occupation, as well as sites for other recreational activities such as bathing, swimming, and washing of clothes.

Study design and selection of communities
This study employed a cross-sectional sampling design involving questionnaire administration and sample collection in five communities out of the 11 communities that reported hematuria outbreak in the LGA. These communities (Barkin lissa, Birama, Gamga, Shibong and Takpa) were randomly selected using a balloting method. After selection, the severity of the outbreak reported to the district health officer was reexamined, and compared among selected schools and those that were not selected.
Replacements were done where necessary to ensure a balance of priority. Preliminary contacts with the sub-district coordinator NTD unit, serving each ward were made in advance, before visiting the communities. The epidemiological study which was conducted in September, 2020, involved 4 distinct phases; (1) advocacy and sensitization; (2) questionnaire administration; (3) sample collection and laboratory examination and (4) treatment of all persons.

Sample size determination and selection of study participants
This study employed a total sampling methodology, following the method previously described by [18]. In brief, considering the fact that the study aimed to investigate the factors associated with the outbreak, all members of the community were mobilized and invited to participate in the study. Mobilization occurred using town announcers, and a sampling spot, at the center of the community was given to the research team for field process. This area has a secluded space for administering the questionnaire and sorting of samples before transportation to the laboratory.

Questionnaire administration
In this study, four separate data collection forms were used. The first, which is the demographic form was used to capture the name, sex and age of participants. The form was also used to assign a unique identification number. The details on this form were used to recruit the participant into the study after completing the consent form.
Participants unique identification number was used to allocate a pre-labeled sterile stool and urine specimen bottle. Furthermore, the WASH form was used to capture information about participants' access to water, sanitation and hygiene facilities. This was also accompanied by a water contact practice form, which was used to document the range of water contact activities the participants performed in the last three months. The last form is the laboratory assessment form, which was used to document the findings from the laboratory assessment of the urine and stool specimen. Before data collection, research assistants were trained on how to capture data electronically using Kobo collect tool and LINKS system on smartphones. All data were collected electronically and transferred to a remote backup server immediately after each interview. All interviews were held in confidence in a private space, except when the interviewee is a minor and needs the assistance of a legal guardian or a parent.

Collection of stool and urine samples
Participants were provided with two sterile specimens bottle, pre-labeled with their unique identification number, an applicator stick, a plain sheet of paper and a tissue paper to clean their anus. Participants were instructed to defecate on the plain sheet of paper and use the applicator stick to transfer a fresh portion into the first bottle. Furthermore, they were instructed to provide approximately 10ml of urine in the second bottle. Samples bottled were retrieved within 1 hour of distribution, and all study participants were provided with soap and water to wash their hands appropriately. In addition, the children were provided incentives like biscuits, while the adults were provided with bar soap.
Participants were also treated with 400mg/kg of praziquantel.

Parasitological assessment of stool and urine samples
All collected stool and urine samples were sorted and transported for processing within 2hours of collection to the Parasitology laboratory located in Takum General Hospital.
The urine filtration method was employed to identify S. haematobium eggs. In brief, 10ml of urine sample was vigorously shaken and passed through a Nytrel filter with a 40 µm mesh size. The filter was then placed on a clean microscopic slide and viewed under the microscope using the x10 and x40 objective lens in search of an egg with a characteristic terminal spine. For each slide, the fields were re-examined and eggs were re-counted by another microscopist for quality assurance. Similarly, stool specimens were processed using the Kato-Katz technique. Two thick smears were prepared from a single stool sample and allowed to clear for 30 minutes before microscopic examination for S. mansoni. The fields were also re-examined and counter-check by another microscopist.
For both urine and stool specimens, a participant is considered infected, if there is an egg count recorded on both sheets of the two microscopists who examined the smears.

Treatment of all consenting persons and sensitization about schistosomiasis
Following field procedures, the NTD unit at the sub-district level performed a door to door administration of praziquantel (400mg/kg) to all persons in the community. During their visits, they sensitized the household members about schistosomiasis and the need to avoid contact with the river. They also emphasized prompt reporting of symptoms such as bloody urine to the nearest health center. The field team was supervised by a team comprising the NTD coordinators from the FMoH, the state and the LGA.

Data management and analysis
Data obtained were downloaded from the remote server by the biostatistician, and imported into Microsoft Excel for sorting before analysis in SPSS 20.0 software.
Descriptive statistics including frequencies and percentages were used to describe the variables, while Chi-square statistics and logistics regression was used to estimate association and the magnitude of association between the prevalence data and other variables. A significant level was set at 95%.

Prevalence of schistosomiasis among the study participants
Of the 432 participants examined, a total of 150 (34.7%) were infected with both species of Schistosoma parasite; 125 (28.9%) for S. haematobium, and 41 (9.5%) for S. mansoni.
Prevalence level varies across the communities, with the highest recorded in Birama (57.7%), followed by Barkin Lissa (50.5%), Shibong (33.3%), Takpa (17.4%) and Gamga (15.8%). (Table 2). Prevalence was higher among males and children below age 16 ( Figure 3, 4). By species' prevalence, S. haematobium infection was significantly higher among males (P<0.05), but there was no significant difference in the proportion of males or females infected with S. mansoni (p>0.05) (Figure 3). Table 3 shows the status of water supply, sanitation and hygiene (WASH) facilities. The majority of the study participants (288, 66.7%) had no regular source of potable water supply, while a high percentage of them relied on the river as their main source of water supply (102, 23.6%). Only 6.5% of the participants had access to the handpump borehole.

Access to water, sanitation and hygiene (WASH) facilities and prevalence of schistosomiasis
Furthermore, the majority of the participants had no latrines (375, 86.8%) and over 40% of them had no handwashing facilities. Of all the WASH variables examined, only access to river was significantly associated with reduced odds of infection (OR:0.27; 95% CI: 0.1-0.66).

Discussion
The outbreak of urogenital schistosomiasis was unexpected in Takum LGA, considering the optimal records of therapeutic coverage for praziquantel MDA since 2014. Due to the pandemic, the response to this outbreak involved a lot of processes, which made it more challenging since MDA had ceased, with schools closed and restrictions to public gatherings and movements. Nevertheless, the epidemiological team responded swiftly and arrested the outbreak through mass treatment of all individuals above age 5 in concordance with the standard operating guidelines stipulated for resuming MDA amid COVID-19 pandemic. It is therefore necessary to present the learnings from the epidemiological analysis of the outbreak, more importantly, the current status of infection, associated risk factors and recommendations to forestall future occurrence.
The prevalence reported in this study corroborates with the hematuria outbreak, with two of the communities having an overall prevalence above 50%, another had a prevalence above 30% and two communities had their prevalence between 16 and 17%. The moderate prevalence (<50%) recorded in the other three communities could be attributed to the fact that targeted administration of Praziquantel was carried out before the arrival of the epidemiological team. Also, on an aggregated basis, the pattern of infection across the communities might have been masked, since the prevalence across these five communities is 34.7%. This aggregation could misinform program actions targeted at eliminating the disease [18]. Until now, Takum was classified to be a low endemic LGA since 2014 and had been receiving biennial treatment [17]. This outbreak and our prevalence reports, therefore, highlight the need to re-classify the LGA for annual treatment, and also support the ongoing discussion on precision mapping and disaggregation of data during planning and implementation of MDA [2]. This becomes very important considering the focality of schistosomiasis, and the complex life cycle involving a mixture of human behavior and availability of snail intermediate host in conducive water bodies.
WASH has been advocated severally as a complementary tool to ongoing MDA programme focused on schistosomiasis [19][20][21]. Surprisingly, the odds of infection reduced among those who regard the river as their source of drinking water. The collection of water for drinking has been reported as a relatively less important pathway of infection because it involves immersion of small areas of the body and for relatively short durations unlike other activities like bathing, swimming or playing [20,22]. To support this submission, our results show that other water contact activities such as playing and swimming, which would require more contact time with the river were significantly associated with increased odds of infection, with those who visit the river to swim or play been twice more exposed than those who do not. This finding conforms with earlier reports of [20].
Swimming and playing are risk factors that are common among male young school-aged children ] 23,24]. Our findings also support this as the majority of those infected participants in our study were young male children below age 15. It is possible that the primary source of this outbreak might be from a segment of these young population who got in contact with the water body via swimming or playing, urinated in the process around the peak periods, thus supporting the transmission of schistosomiasis. This thought is in line with a similar outbreak reported in Zimbabwe [25]. This segment of the population might have been heavily infected and under-treated because of the previous misclassification of the LGA on treatment basis. On the other hand, the closure of schools during the pandemic era supports clustering and more contact hours between young school-aged children at river sites, from different communities and could also be another pathway of contamination of river sites [26].
Notwithstanding, the epidemiological risk analysis has raised the following substantial concerns that could have supported the outbreak; (i) lack of baseline mapping in the study communities which calls for more refined approaches such as precision mapping, (2) misclassification of the LGA based on treatment needs which resulted in undertreatment It is therefore imperative to consider; (1) investments in effort targeted at reclassifying the LGA and adjusting the treatment thresholds (2) strengthening surveillance system to identify hot-spots such as areas with high reportage of hematuria, (3) investments in the epidemiological mapping of infections when resources allow, (4) continuous sensitization of young children, most especially as schools have resumed on the dangers of excessive recreational activities at the river site is important, and (5) investments in efforts targeted at reducing the snail population in the river body associated with these communities.

Conclusion
Until now, Takum was classified to be a low endemic LGA and had been receiving biennial treatment. This outbreak and our prevalence reports highlight the need to reclassify the LGA and adjust the treatment thresholds. In addition, our findings support the ongoing discussion on precision mapping and disaggregation of data during planning and implementation. Swimming and playing in rivers were the most potent risk factor supporting the transmission of schistosomiasis. Strengthening available surveillance systems to identify hotspots and investments in efforts targeted at improving health education of children and reducing snail population will be a step in the right direction

Limitation of the study
Although participation was voluntary, some participants may be afraid to join the study because of their perception of the pandemic. As such, we cannot ignore the impact the COVID-19 pandemic had on participant recruitment which might have affected our sample size in each of the communities. Ethical clearance for this study was obtained from the Taraba State Ministry of Health ethics review board. A pre-survey contact/advocacy meeting was made to each selected study community to obtain consent from community leaders and other major stakeholders after explaining the objectives of the research to them. This was followed by community mobilization and sensitization using town announcers to communicate the objectives of our visit to community members. Sensitization was done in all religious and public places like schools and market squares to promote participation. Community members willing to participate in the study completed written consent forms on the day of sample collection.

List of abbreviations
Assent forms was completed in cases where the willing member is below 16 years of age.
In this case, parents or any legal guardian were asked to accompany minors under age 16 to the sample collection site, to provide additional consents. The method of consent assertion was through thumbprint on already printed informed consent forms (ICFs).

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.     Permission: The authors give permission to re-use this map.