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.

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 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 [1,4-6].

It is estimated that at least 90% of those affected and requiring treatment for schistosomiasis live in Africa [4]. In this region, there are two major species of Schistosoma; the first is the S. haematobium which inhabits the vesicular and pelvic venous plexus of the bladder and causes urogenital schistosomiasis and the second is S. mansoni which is more often in the inferior mesenteric veins draining the large intestine and causes intestinal schistosomiasis [4,6]. In addition, the former has been reported in the Middle East and Corsica, while the latter has a wider distribution in the Middle East, the Caribbean, Brazil, Venezuela and Suriname [4]. The pathologies associated with both species vary depending on factors not limited to the severity of infection, migration of the worms through the organs and body tissues and inflammatory responses to the presence of the eggs laid by the adults [4,7,8]. Intestinal schistosomiasis can result in symptoms such as abdominal pain, diarrhea, blood in the stool, and in more severe cases, enlargement of the liver and spleen, a condition known as hepatosplenomegaly [4,9]. However, haematuria, which is classified as the passage of visible or invisible blood in urine is a common sign of urogenital schistosomiasis [4]. Other complicated pathologies may include fibrosis of the bladder and ureter, kidney damage and in more advanced cases cancer of the bladder [4]. Urogenital schistosomiasis may become more complex in females in a condition known as female genital schistosomiasis (FGS), which may present with symptoms such as genital lesions, vaginal bleeding, pain during sexual intercourse and infertility [10-12]. 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 [13-15].

Children under 15years of age remains 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], with 36 states and 774 local government areas (LGAs). About 708 LGAs had been mapped by the Federal Ministry of Health (FMoH), with 608 of them being endemic [16]. Since 2009, treatment with praziquantel commenced in 27 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, was among the states in mapped for schistosomiasis in 2010 and subsequently in 2014 [16,17]. The state is located in the northeastern region of the country, and has 16 LGAs. 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 A and Takum B 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 (>75%) in the last 5 rounds of mass drug administration (MDA) [17]. In August 2020, during the COVID-19 pandemic, an outbreak of schistosomiasis was reported in both children and adults across eleven communities in Takum (Barki Lissan, Liji, Takpa, Shibong Igbang, Lukpo, Kashimbila, Birama, Bibbi, Bawuro, Gamga and Mamga) (Fig 1). These communities were not part of the communities mapped in 2014, which calls for urgent public health action. The study was therefore conducted to (1) re-assess the prevalence of schistosomiasis in these communities; (2) document the status of water, sanitation and hygiene (WASH) resources; (3) identify risk factors promoting the transmission of schistosomiasis (4) treat the entire population and create awareness about schistosomiasis and (5) provide recommendations to improve program planning and implementation. In this paper, we, therefore, summarize the findings from the epidemiological study conducted and the programmatic actions implemented in line with the global target of eliminating schistosomiasis.

Fig 1

Samples of bloody urine collected during study procedures.

Source: The authors took this picture on using their camera with the permission of the participants. Permission: The authors give permission to re-use this image.

Methodology

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 km2 (Fig 2) [17]. 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 [17].

Fig 2

Map of Taraba State showing the study LGA.

Source: The authors using their primary data in ArcGIS software created this map. Permission: The authors give permission to re-use this map.

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 eleven communities that reported schistosomiasis outbreak in the LGA. The five study communities (Barkin lissa, Birama, Gamga, Shibong and Takpa) were randomly selected using the paper ballot approach out of the eleven communities. After selection, the severity of the outbreak reported to the district health officer was re-examined, and compared among selected communities and those that were not selected. Replacements were done where necessary to ensure a balance of priority. Preliminary advocacy visits were made to the NTD control unit closer to the selected communities (i.e., ward level), prior to the epidemiological investigation. The study was conducted in September, 2020, and 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

As an initial step, the total population of school-aged children and adults in the communities were extracted from the 2020 village census register obtained from the NTDs control department in the LGA. A total of 6,012 persons comprising 2531 children and 3481 adults were enumerated. As a further step, a sample-size was determined using the formula; and , as described by Lwanga et al [18], where ns is the required sample size and N is the target population. We assumed a prevalence (p) of 50% since there are no previous baseline data on schistosomiasis in the five communities, a relative precision (d) of 5% and a confidence level of 95% which corresponds to a z score of 1.96. The minimum sample size determined, therefore, was 362 i.e., an average of 72 persons per community. However, the recruitment of participants extended beyond the estimated sample size, considering the aim of identifying factors associated with the outbreak.

For the selection of study participants, we employed a total sampling methodology, following the method previously described by [19]. Community sensitization and advocacy visits were made to the community leaders and other stakeholders. This was followed by mobilization of eligible community members to participate in the study using town announcers Only residents of the community, who are above age of 5 years, can provide consent or assent, and has lived within the community in the last 3 months were recruited into the study. Enrollment of participants and collection of samples took place at a central point in the community, provided by the community leader. This point has a secluded space for administering study questionnaires and sorting of samples before transporting them to the laboratory. The number of consenting participants varied across the communities, hence giving an unequal number of persons recruited.

Questionnaire administration

A simple standardized questionnaire was used to collect participants’ details (S1 Appendix). The questionnaire tool which has four different sections; demographic, WASH, water contact practice and laboratory results, was first designed in English language (S1 Appendix), translated to Hausa language (S2 Appendix), piloted and designed as an electronic data from. Prior to administration of questionnaire, recruited participants who had completed informed consent or assent forms were assigned unique identification number. The demographic section of the questionnaire captured the name, sex, age and unique identification number of the participant. Participants unique identification number was used to allocate a pre-labeled sterile stool and urine specimen bottle. Furthermore, the WASH section captured information about participants’ access to water, sanitation and hygiene facilities. The water contact practice section was used to document the range of water contact activities the participants performed in the last three months, while the laboratory section 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 conducted in Hausa language and 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. All eligible and non-eligible participants were treated with 400mg/kg of praziquantel as an immediate benefit of the research investigation. In addition to this, incentives such as bar soaps and bisquits were given to reinforce positive hygiene behaviors and stimulate community integration during a tensed situation which the pandemic has presented. These incentives were provided in a non-coercive manner, ensuring they do not influence the decision of the community members to participate or decline participation in the research.

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. Data on socio-demographic characteristics and water contact behavior were considered as independent variable, while prevalence of infection was considered as dependent variable. Data obtained were first subjected to descriptive statistics including frequencies and cross-tabulations, then followed by Pearson chi-square statistics to test for associations between the variables. Variables that were associated with infection were considered significant only when P <0.05. Subsequently, variables were also subjected to univariate analyses i.e., logistic regression, to estimate the magnitude of association between infection data and other variables. Potential risk factors were entered into the model as covariates using bidirectional stepwise entry method. Reference category was formulated for categorical variables before analysis and observations with missing values for any variable were excluded from the analysis. Predictive index in the model is represented as Exp(B) which is the odds-ratio (OR). A 95% confidence interval (CI) was calculated for the OR, and values were considered statistically significant when the CI does not include 1 and the P < 0.05.

Result

Demographic characteristics of study participants

A total of 432 community residents from five communities; Barkin lissa (97, 22.5%), Birama (71, 16.4%), Gamga (76, 17.6%), Shibong (96, 22.2%) and Takpa (92, 21.3%) were enrolled into this study. The majority of the participants were males (218, 50.5%), compared to females (214, 49.5%), and there was a significant difference in the gender distribution across the communities (p = 0.00). By age category, the majority of the participants were between age 5 and 10 (152, 35.2%), followed by those above 21 years (130, 30.1%), 11–16 years (112, 25.9%) and 17–20 years (38, 8.8%). There were also significant differences between the age category of participants across the study communities (p = 0.02) (Table 1).

Table 1

Demographic characteristics of the study population.

	Communities
	Barkin Lissa (n = 97)	Birama (n = 71)	Gamga (n = 76)	Shibong (n = 96)	Takpa n = 92)	Total (n = 432)	X2, df, pvalue
Sex
Female	36(37.1)	43(60.6)	44(57.9)	39(40.6)	52(56.5)	214(49.5)	16.412, 4, 0.00
Male	61(62.9)	28(39.4)	32(42.1)	57(59.4)	40(43.5)	218(50.5)
Age group in years
5–10	31(32.0)	32(45.1)	27(35.5)	28(29.2)	34(37.0)	152(35.2)	23.595,12, 0.02
11–16	26(26.8)	17(23.9)	22(28.9)	32(33.3)	15(16.3)	112(25.9)
17–20	16(16.5)	1(1.4)	4(5.3)	8(8.3)	9(9.8)	38(8.8)
>21	24(24.7)	21(29.6)	23(30.3)	28(29.2)	34(37.0)	130(30.1)

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 (Figs 3 and 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) (Fig 3).

Table 2

Prevalence of schistosomiasis among the study participants.

		S. haematobium		S. mansoni		S haematobium +S. mansoni
Communities	NE	NI	95% CI	NI	95% CI	NI	95% CI
Barki Lissa	97	49	50.5 (40.5–60.5)c	6	6.2 (1.4–10.9) a	49(50.5)	50.5 (40.6–60.5) c
Birama	71	18	25.4 (15.2–35.4)b	33	46.5 (34.9–58.1) b	41(57.7)	57.7 (46.3–69.2) c
Gamga	76	12	15.8 (7.6–23.9) b	0	-	12(15.8)	15.8 (7.6–23.9) b
Shibong	96	30	31.3 (21.9–40.5) b	2	2.1(-0.78–4.94) a	32(33.3)	33.3 (23.9–42.8) b
Takpa	92	16	17.4 (9.6–25.1) b	0	-	16(17.4)	17.4 (9.6–25.1) b
Total	432	125	28.9 (24.7–33.2) b	41	9.5 (6.73–12.3)a	150(34.7)	34.7 (30.3–39.2) b

NE: Number Examined; NI: Number Infected; CI: Confidence Interval.

Categories of Endemicity

aLow endemicity when prevalence is between 1–9.9%.

bModerate endemicity when prevalence is between 10–49.9%.

cHigh endemicity when prevalence is above 50%.

Fig 3

Prevalence of schistosomiasis by sex among the study participants.

Source: The authors using their primary data to create this chart in Microsoft Excel software. Permission: The authors give permission to re-use this map.

Fig 4

Prevalence of schistosomiasis by age among the study participants.

Source: The authors using their primary data to create this chart in Microsoft Excel software. Permission: The authors give permission to re-use this map.

Access to water, sanitation and hygiene (WASH) facilities and prevalence of schistosomiasis

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. 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).

Table 3

Access to water, sanitation and hygiene (WASH) facilities and prevalence of schistosomiasis.

Characteristic	Frequency (%)	Positives (%)	Negatives (%)	X2, df, pvalue	OR (95% CI)		p-value
	N = 432	N = 150 (34.7)	N = 282 (65.3)
Water supply facilities
Handpump/Borehole	28(6.5)	12(42.9)	16(57.1)	21.235, 6, 0.00	1	-
Unprotected Dug well	1(0.2)	1(100.00)	0(0.0)		3.96(0.14–105.6)	0.41
Protected Dug well	6(1.4)	2(33.3)	4(66.7)		0.67 (0.10–4.26)	0.67
Surface Water (River)	102(23.6)	17(16.7)	85(83.3)		0.27(0.1–0.66)	0.00*
Rainwater collection	3(0.7)	1(33.3)	2(66.7)		0.67(0.05–8.24)	0.75
Sachet/Pure water	4(0.9)	2(50.0)	2(50.0)		1.33(0.16–10.86)	0.78
None	288(66.7)	115(39.9)	173(60.1)		0.88(0.40–1.94)	0.76
Toilet facilities
Flush toilet	10(2.3)	6 (60.0)	4 (40)	13.59, 4, 0.01	1		-
Pit latrine without slab	12(2.8)	8(66.7)	4 (33.3)		1.33(0.23–7.62)		0.32
Pit latrine with slab	22(5.1)	12(54.5)	10 (45.5)		0.80 (0.17–3.65)		0.77
VI-Pit latrine	13(3.0)	5 (38.5)	8 (61.5)		0.42 (0.08–2.25)		0.31
None	375(86.8)	119(31.7)	256 (68.3)		0.31(0.09–1.12)		0.07
Handwashing facilities
Water and Soap	223(51.6)	75 (33.6)	148 (66.4)	0.24, 1, 0.62	1	-
None	209(48.4)	75 (35.9)	134 (64.1)		1.1(0.74–1.64)	0.62

X2: Chi-square value; df: degree of freedom; OR: Odd ratio; CI: Confidence interval; * significant difference exist at 95%; VI-Pit Latrine: Ventilated Improved Pit Latrine.

Water contact behavior among the study participants

Out of the six water contact practices investigated, fishing (43, 10%) was the least common practice in the study areas. However, the majority of the participants engage in activities such as bathing (419, 97%), washing of clothes (357, 82.6%), fetching water (358, 82.9%), playing in river (193, 44.7%) and swimming (214, 49.5%). Infections were significantly associated with playing and swimming activities with increased odds of 1.50 (95% CI: 1.01–2.25) and 1.55 (95% CI: 1.04–2.31), respectively. (Table 4).

Table 4

Water contact activities and prevalence of schistosomiasis.

Water Contact Activities	Frequency (%)	Positives (%)	Negatives (%)	X2, df, pvalue	OR (95%CI)	pvalue
	N = 432	N = 150 (34.7)	N = 282 (65.3)
Bathing
No	13(3.0)	2 (0.5)	11 (2.5)		1
Yes	419(97.0)	148 (34.4)	271 (62.7)	2.21, 1, 0.14	3.00(0.66–13.7)	0.15
Washing
No	75(17.4)	27 (6.3)	48 (11.1)		1
Yes	357(|82.6)	123 (28.5)	234 (54.2)	0.06,1, 0.79	0.93(0.56–1.57)	0.79
Fishing
No	389(90.0)	132 (30.6)	257 (59.5)		1
Yes	43(10.0)	18 (4.2)	25 (5.8)	1.074,1,0.30	1.40(0.73–2.66)	0.85
Fetching Water
No	74 (17.1)	27 (6.3)	47 ((10.9)		1
Yes	358(82.9)	123 (28.5)	235 (54.4)	0.12, 1, 0.73	0.91(0.54–1.53)	0.73
Playing
No	239(55.3)	73 (16.9)	166 (38.4)		1
Yes	193(44.7)	77 (17.8)	116 (26.9)	4.12, 1, 0.04	1.50(1.01–2.25)	0.04*
Swimming
No	218(50.5)	65 (15.0)	153 (35.4)		1
Yes	214(49.5)	85 (19.7)	129 (29.9)	4.67,1,0.03	1.55(1.04–2.31)	0.03*

X2: Chi-square value; df: degree of freedom; OR: Odd ratio; CI: Confidence interval; * significant difference at 95%.

Treatment data

A total 3,580 person were treated across the study communities. More persons were treated in Shibong (n = 1,057), followed by Birama (n = 1,044), Barki Lisa (n = 634), Gamga (n = 632) and Takpa (n = 213). Furthermore, treated males (n = 1912) were more than treated females (n = 1668), and treated persons above aged 15 (n = 2,436) were more than school-aged children between age 5 and 14 (n = 1124) (Table 5).

Table 5

Praziquantel treatment data across the study communities.

	Treatment data
	5–14 years			15 years and above			Total treated
Communities	Male	Female	Total	Male	Female	Total	Male	Female	Total
Barki Lissa	134	129	263	188	183	371	322	312	634
Birama	143	122	265	494	285	779	637	407	1,044
Gamga	103	68	171	231	230	461	334	298	632
Shibong	186	145	311	328	398	726	514	543	1,057
Takpa	56	58	114	49	50	99	105	108	213
Total	622	522	1124	1290	1146	2436	1912	1668	3580

Discussion

Since 2014, Takum LGA has benefitted from three biennial rounds of MDA targeted at school-aged children. In these years, the therapeutic coverage was optimal, surpassing the 75% national targets [17], as such, the outbreak of schistosomiasis in this area was unexpected. Furthermore, with the advent of COVID-19, MDA program was paused in 2020 across endemic countries, owing to the fact that mass gatherings during trainings and administration of medicines may increase the transmissibility of the virus [20]. The shifts in policies to non-pharmaceutical interventions including closure of schools and restrictions placed on public gatherings and movements therefore impacted on the response time of the epidemiology team during this outbreak. Nevertheless, the team arrested the outbreak through mass treatment of all eligible persons above age 5 in concordance with the standard operating guidelines stipulated for resuming MDA amid COVID-19 pandemic [21]. 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 schistosomiasis 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 [19]. Until now, Takum was classified to be a low endemic LGA, 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 program focused on schistosomiasis [22-24]. 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 [23,25]. 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 [23].

Swimming and playing are risk factors that are common among male young school-aged children [26,27]. 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 [28]. 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 [29].

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 (3) predominant risky behavior of swimming and playing among the young children which might have been compounded by the lockdown imposed from the pandemic, and (4) availability of a pool of viable intermediate snail host at the river sites. These concerns, therefore, reflect gaps that need to be addressed in line with the goal of eliminating schistosomiasis by 2030.

It is therefore imperative to consider; (1) investments in effort targeted at reclassifying the LGA as highly endemic, and adjusting the MDA thresholds from the biennial cycle to an annual cycle (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 re-classify the LGA as highly endemic, and adjust the MDA thresholds from the biennial cycle to an annual cycle. 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 might 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 recruitment of participants.

Questionnaire for the study in English Language.

(DOCX)

Click here for additional data file.

Questionnaire for the study in Hausa Language.

(DOCX)

Click here for additional data file.

13 Oct 2021

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Additional Editor Comments:

This is the study beneficial for public health control programs in the context of the COVID 19 pandemic.

In addition to the comments of two reviewers, authors should add the following to improve scientific integrity:

1. The reported number of cases of COVID-19 in the study area which impeded the schistosomiasis control program activities.

2. The total population of school-aged children and the adult population in the study area

3. Specific computation of sample size and comprehensive sampling procedure among the target population and to include the sampling strategy related to mitigation of selection bias.

4. Comprehensive description of the simple logistic regression procedure in the data management and data analysis section.

5. To add 95% confidence intervals for prevalence ratios in Table 2.

6. Both unadjusted and adjusted odds should be included in Tables 3 and 4.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: No

**********

5. Review Comments to the Author

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Reviewer #1: The manuscript is well written. The edits are very few such as italicizing Schistosoma and just minimal grammatical lapses and better sentence construction. My only major question is the sample size, how it was computed and what proportion of the computed sample size is represented by the number of actual respondents.

Reviewer #2: I would advice you look at the gap and discuss your results with the information there-in.

The paper is addressing a key issue in public health i.e An outbreak of schistosomiasis in Takum LGA in Northeastern Nigeria. However, the paper has some shortfalls and I suggest you consider the following:

1. The methodology needs some clarification, administration of drugs to people was larger than the sample surveyed. The use of error bar seems misleading and needed to be re-address

2. Though the paper was well presented, however, some aspect needed for follow a chronological order so as to have free flow when reading the paper if accepted for publication.

3. The gap which was identified needed to be filled through right discussion on good implementation research

4. The discussion needs to be aligned to the key results of the study and avoid reference to stuff that was note presented in the results.

5. The present manuscript requires editing for grammar, spelling errors and further concision.

**********

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Reviewer #1: No

Reviewer #2: Yes: Opeyemi G. Oso

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Submitted filename: REVIEWERS REPORT.docx

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Submitted filename: PONE-D-21-30831_reviewer_new-1.pdf

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25 Oct 2021

Editor Comments:

This is the study beneficial for public health control programs in the context of the COVID 19 pandemic.

In addition to the comments of two reviewers, authors should add the following to improve scientific integrity:

C1. The reported number of cases of COVID-19 in the study area which impeded the schistosomiasis control program activities.

R1: Thank you very much for the comments. The data on the number of cases of COVID-19 in Nigeria is reported at the district level (i.e., LGA). The total number of cases in Takum LGA as at the time of the outbreak (September) was 5, and this was recorded in June, as such there were no new cases since June till September. However, what impeded the schistosomiasis control activities is not the number of cases, but the concerns that such program which are characterized by mass gatherings, door to door movements, and administration of medicines to residents, has a strong potential to contribute to COVID-19 transmission. As such, the WHO mandated that all mass treatment programs should be ceased until recently.

We have now modified the beginning paragraphs of our discussion line to address this issue. We added 2 new references to support this line of discussion.

20 Warren, L. Community directed treatment for Neglected Tropical Diseases in a post COVID-19 lockdown world. 2020. Retrieved from https://end.org/community-directed-treatment-for-neglected-tropical-diseases-in-a-post-COVID-19-lockdown-world/

21 Molyneux D, Bush S, Bannerman R, Downs P, Shu'aibu J, et al. Neglected tropical diseases activities in Africa in the COVID-19 era: the need for a "hybrid" approach in COVID-endemic times. Infect Dis Poverty. 2021;10(1):1.

We appreciate you for raising this very important issue. Please see the modified lines in the discussion below.

Discussion

Since 2014, Takum LGA has benefitted from three biennial rounds of MDA targeted at school-aged children. In these years, the therapeutic coverage was optimal, surpassing the 75% national targets [17], as such, the outbreak of schistosomiasis in this area was unexpected. Furthermore, with the advent of COVID-19, MDA program was paused in 2020 across endemic countries, owing to the fact that mass gatherings during trainings and administration of medicines may increase the transmissibility of the virus [20]. The shifts in policies to non-pharmaceutical interventions including closure of schools and restrictions placed on public gatherings and movements therefore impacted on the response time of the epidemiology team during this outbreak. Nevertheless, the team arrested the outbreak through mass treatment of all eligible persons above age 5 in concordance with the standard operating guidelines stipulated for resuming MDA amid COVID-19 pandemic [21] 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.

C2: The total population of school-aged children and the adult population in the study area

R2: Thank you very much for this comment, we have now included the population of the school-aged children and the adult population. We have also described extensively how we used these figures to estimate the sample size.

Please see below

Sample size determination and selection of study participants

As an initial step, the total population of school-aged children and adults in the communities were extracted from the 2020 village census register obtained from the NTDs control department in the LGA. A total of 6,012 persons comprising 2531 children and 3481 adults were enumerated. As a further step, a sample-size was determined using the formula; n_s=n/(1+(n/N) ) and n= (z^2 p(1-p))/d^2 , as described by Lwanga et al [18], where ns is the required sample size and N is the target population. We assumed a prevalence (p) of 50% since there are no previous baseline data on schistosomiasis in the five communities, a relative precision (d) of 5% and a confidence level of 95% which corresponds to a z score of 1.96. The minimum sample size determined, therefore, was 362 i.e., an average of 72 persons per community. However, the recruitment of participants extended beyond the estimated sample size, considering the aim of identifying factors associated with the outbreak.

C3: Specific computation of sample size and comprehensive sampling procedure among the target population and to include the sampling strategy related to mitigation of selection bias.

R3: Thank you very much for your very valuable comment, which has improved the quality of our manuscript. We have now provided very explicit details on how the sample-size were estimated and how the participants were recruited.

Please find below

Sample size determination and selection of study participants

As an initial step, the total population of school-aged children and adults in the communities were extracted from the 2020 village census register obtained from the NTDs control department in the LGA. A total of 6,012 persons comprising 2531 children and 3481 adults were enumerated. As a further step, a sample-size was determined using the formula; n_s=n/(1+(n/N) ) and n= (z^2 p(1-p))/d^2 , as described by Lwanga et al [18], where ns is the required sample size and N is the target population. We assumed a prevalence (p) of 50% since there are no previous baseline data on schistosomiasis in the five communities, a relative precision (d) of 5% and a confidence level of 95% which corresponds to a z score of 1.96. The minimum sample size determined, therefore, was 362 i.e., an average of 72 persons per community. However, the recruitment of participants extended beyond the estimated sample size, considering the aim of identifying factors associated with the outbreak.

For the selection of study participants, we employed a total sampling methodology, following the method previously described by [19]. Community sensitization and advocacy visits were made to the community leaders and other stakeholders. This was followed by mobilization of eligible community members using town announcers to participate in the study. Only residents of the community, who are above age of 5 years, can provide consent or assent, and has lived within the community in the last 3 months were recruited into the study. Enrollment of participants and collection of samples took place at a central point in the community, provided by the community leader. This point has a secluded space for administering study questionnaires and sorting of samples before transporting them to the laboratory. The number of consenting participants varied across the communities, hence giving an unequal number of persons recruited.

C4: Comprehensive description of the simple logistic regression procedure in the data management and data analysis section.

R4: Thank you very much editor. We have reworked this section to provide more comprehensive description of the logistic regression.

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. Data on socio-demographic characteristics and water contact behavior were considered as independent variable, while prevalence of infection was considered as dependent variable. Data were first subjected to descriptive statistics including frequencies and cross-tabulations, then followed by Pearson chi-square statistics to test for associations between the variables. Variables that were associated with infection were considered significant only when P <0.05. Subsequently, variables were subjected to univariate analyses i.e., logistic regression, to estimate the magnitude of association between infection data and other variables. Potential risk factors were entered into the model as covariates using bidirectional stepwise entry method. Reference category was formulated for categorical variables before analysis and observations with missing values for any variable were excluded from the analysis. Predictive index in the model is represented as Exp(𝐵) which is the odd-ratio (OR). A 95% confidence interval (CI) was calculated for the OR, and values were considered statistically significant when the CI does not include 1 and the P < 0.05.

C5: To add 95% confidence intervals for prevalence ratios in Table 2.

R5: Thank you very much for this comment, which has improved our manuscript. The 95% confidence intervals have been included in Table 2. We are very grateful for the comment.

C6: Both unadjusted and adjusted odds should be included in Tables 3 and 4.

R6: We limited our analyses to univariate analyses, because the variables were not significant in the multivariate model. Thank you very much for your comments.

Reviewer #1:

C1: The manuscript is well written. The edits are very few such as italicizing Schistosoma and just minimal grammatical lapses and better sentence construction. My only major question is the sample size, how it was computed and what proportion of the computed sample size is represented by the number of actual respondents.

R1: Thank you very much for your very valuable comment, which has improved the quality of our manuscript. We have worked through the manuscript and corrected the grammatical errors, and where possible, we constructed several sentences. Please find them as highlight in the tracked version of the manuscript.

Also, we have now provided very explicit detail on how the sample-size were estimated and how the participants were recruited.

Please find below

Sample size determination and selection of study participants

As an initial step, the total population of school-aged children and adults in the communities were extracted from the 2020 village census register obtained from the NTDs control department in the LGA. A total of 6,012 persons comprising 2531 children and 3481 adults were enumerated. As a further step, a sample-size was determined using the formula; n_s=n/(1+(n/N) ) and n= (z^2 p(1-p))/d^2 , as described by Lwanga et al [18], where ns is the required sample size and N is the target population. We assumed a prevalence (p) of 50% since there are no previous baseline data on schistosomiasis in the five communities, a relative precision (d) of 5% and a confidence level of 95% which corresponds to a z score of 1.96. The minimum sample size determined, therefore, was 362 i.e., an average of 72 persons per community. However, the recruitment of participants extended beyond the estimated sample size, considering the aim of identifying factors associated with the outbreak.

For the selection of study participants, we employed a total sampling methodology, following the method previously described by [19]. Community sensitization and advocacy visits were made to the community leaders and other stakeholders. This was followed by mobilization of eligible community members using town announcers to participate in the study. Only residents of the community, who are above age of 5 years, can provide consent or assent, and has lived within the community in the last 3 months were recruited into the study. Enrollment of participants and collection of samples took place at a central point in the community, provided by the community leader. This point has a secluded space for administering study questionnaires and sorting of samples before transporting them to the laboratory. The number of consenting participants varied across the communities, hence giving an unequal number of persons recruited.

REVIEWER’S REPORT.

Summary

The paper is addressing a key issue in public health i.e., An outbreak of schistosomiasis in Takum LGA in Northeastern Nigeria. However, the paper has some shortfalls and I suggest you consider the following:

C1: The methodology needs some clarification, administration of drugs to people was larger than the sample surveyed. The use of error bar seems misleading and needed to be re-address

R1: Thank you very much for the valuable comments. Foremost, we explained within the manuscript that the epidemiological team responded to the outbreak by implementing mass administration of praziquantel to all eligible persons in the communities through the usual door-door preventive chemotherapy approach as recommended by the WHO. This approach doesn’t require prior diagnosis of infection before administration of tablets. Prior to the COVID-19 pandemic, this treatment is planned biennially (twice in a year) by the LGA NTD unit, but was ceased due to the COVID-19 pandemic. However, because of the outbreak reported, it became imperative to resume treatment in this area, which coincided with the time the epidemiological investigation was conducted. For this reason, the number of persons treated were larger in number than those surveyed in the study.

Secondly, for the figures, we used standard deviation to illustrate the margin between the individual infection data. The authors prefer to use this metric in place of standard error which measures the accuracy of estimations.

C2: Though the paper was well presented, however, some aspect needed for follow a chronological order so as to have free flow when reading the paper if accepted for publication.

R2: Thank you very much for this valuable comment. We have revised this section to allow more thoughtful flow. We really appreciate the reviewer for pointing this out. We have revised several parts of the manuscripts to allow more chronological flow.

C3: The gap which was identified needed to be filled through right discussion on good implementation research

R3: Under the recommendation paragraphs and conclusion remarks, we have re-emphasized how to address the gaps that was identified. This comment was also addressed under the more specific comments raised by the reviewer (C25)

C4: The discussion needs to be aligned to the key results of the study and avoid reference to stuff that was note presented in the results.

R4: Thank you for this comment. We really appreciate your inputs. We have also addressed this comment under the more specific comments raised by the reviewer (C22 and C24)

C5: The present manuscript requires editing for grammar, spelling errors and further concision.

R5: We take this opportunity to appreciate the reviewer for the invaluable comments. We have worked through the manuscript and have corrected the grammar, spelling errors and deleted some unnecessary sentences

Other comments

C1: Line 2. Abstract, kindly recast, there cannot be an outbreak of haematuria, it is just one of the symptoms of schistosomiasis

R1: Thank you very much for this valuable comment. We think PloS ONE goes with the American style.

C2; Page 2, keyword on hematuria, Please, be consistent with the choice of your English, it's either you go with American style of British.

R2: Thank you very much for this comment.

C3: Page 10, Line 3 under Introduction, "one of the major and most.." please, kindly recast, it is seems ambiguous!

R3: Thank you very much for this comment. We have revised it to “one of the most”

C4; Page 11, Line 1, For haematuria as a sign of the infection, most times, visible blood is noticed, you know?

R4: Thank you very much for this comment. We have revised the word symptom to sign. We thank you for this valuable addition.

C5: Page 22, Paragraph 2, Line 1, what is the unit of your age here?

R5: Thank you very much for this comment. We have revised it to “Children under 15 years of age….

C6: Page 22, Paragraph 2, Line 8 "LGA" is appearing for the first here, yet, you had only "government areas" here.?????

R6: Thank you very much for this comment. We have revised it to “local government areas….

C7: Page 22, Paragraph 2, Line 13, I would suggest, you allow your information to flow in a chronological order.

R7: Thank you very much for this valuable comment. We have revised it to allow more thoughtful flow. Please see the revised text below:

Nigeria is one of the schistosomiasis endemic countries in Africa [1], with 36 states and 774 local government areas (LGAs). About 708 LGAs had been mapped by the Federal Ministry of Health (FMoH), with 608 of them being endemic [16]. Since 2009, treatment with praziquantel commenced in 27 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, was among the states in mapped for schistosomiasis in 2010 and subsequently in 2014 [16,17]. The state is located in the northeastern region of the country, and has 16 LGAs.

C8: Page 12, Line 3, how many Takum community/LGA do you have in that LGA???

R8: Thank you very much for this valuable comment. We have highlighted this and revised accordingly. We have 2 different communities with the name Takum A and Takum B. Thanks for pointing this out.

C9: : Page 12, Line 7, ????

R9: Thank you very much for this valuable comment. We have highlighted this and revised accordingly. We have replaced the word hematuria with schistosomiasis

C10: Page 12, Line 11, Kindly correct your error here!!!!!

R10: Thank you very much for pointing out this error. We have deleted the repeated word.

C11: Page 13, under study area, Are you the first to carry out an investigation in that LGA? If your answer is NO. kindly, provide the reference for the coordinate provided here!!!!

R11: Thank you very much for this. We have provided a reference to support the description of the study area.

C12: Page 13, Line 4, under study design, kindly recast, this sentence is ambiguous!!!!!!!

R12: Thank you very much for pointing this out. We have reworked the sentence to provide more clarity

Please see below

The five study communities (Barkin lissa, Birama, Gamga, Shibong and Takpa) were randomly selected using the paper ballot approach out of the eleven communities.

C13; Page 13, Line 9, under study design, Again, you sentences should be in chronological order. I didn't find these statement easy to read.

R13: Thank you very much for pointing this out. We have reworked the sentence to provide more clarity

Please see below

Preliminary advocacy visits were made to the NTD control unit closer to the selected communities (i.e., ward level), prior to the epidemiological investigation

C14; Page 13, Line 3, under sample size, You invited all members of the community for the study, yet, you stated before that you had a method of choosing who to participate????? OR

does the study involved a purposive method????

R14: Thank you very much for your very valuable comment, which has improved the quality of our manuscript. We have now provided very explicit details on how the sample-size were estimated and how the participants were recruited.

Please find below

Sample size determination and selection of study participants

As an initial step, the total population of school-aged children and adults in the communities were extracted from the 2020 village census register obtained from the NTDs control department in the LGA. A total of 6,012 persons comprising 2531 children and 3481 adults were enumerated. As a further step, a sample-size was determined using the formula; n_s=n/(1+(n/N) ) and n= (z^2 p(1-p))/d^2 , as described by Lwanga et al [18], where ns is the required sample size and N is the target population. We assumed a prevalence (p) of 50% since there are no previous baseline data on schistosomiasis in the five communities, a relative precision (d) of 5% and a confidence level of 95% which corresponds to z score 1.96. The minimum sample size determined, therefore, was 362 i.e., an average of 72 persons per community. However, the recruitment of participants extended beyond the estimated sample size, considering the aim of identifying factors associated with the outbreak.

For the selection of study participants, we employed a total sampling methodology, following the method previously described by [19]. Community sensitization and advocacy visits were made to the community leaders and other stakeholders. This was followed by mobilization of eligible community members to participate in the study using town announcers. Only residents of the community, who are above age of 5 years, can provide consent or assent, and has lived within the community in the last 3 months were recruited into the study. Enrollment of participants and collection of samples took place at a central point in the community, provided by the community leader. This point has a secluded space for administering study questionnaires and sorting of samples before transporting them to the laboratory. The number of consenting participants varied across the communities, hence giving roughly an unequal number of persons recruited.

C15: Page 16, Line 5, Giving of these incentives looks as if you used those items to entice them for the study which it seems not ethical, if you had provided this information to your ethical review committee, maybe, it may have been spotted and provide necessary advice!!!!!!!!

R15: Thank you very much for your comments. These incentives were not used to entice the participants, as they were given even to those that refused to participate in the study but visited the collection point. This information was provided in our letter of request, it was highlighted that the immediate benefits from the study would be provision of treatment to all eligible members of the communities, and incentives such as bar soaps to reinforce positive hygiene behaviors and bisquits to stimulate community integration especially during a tensed situation which the pandemic has presented. As such we guided the time of introduction of the incentives, ensuring it is non-coercive and doesn’t influence their participation in the research

Thank you very much for this valuable comment, and we have added some lines to support the sentence.

Please see below

All eligible and non-eligible participants were treated with 400mg/kg of praziquantel as an immediate benefit of the research investigation. In addition to this, incentives such as bar soaps and bisquits were given to reinforce positive hygiene behaviors and stimulate community integration during a tensed situation which the pandemic has presented. These incentives were provided in a non-coercive manner, ensuring they do not influence the decision of the community members to participate or decline participation in the research

C16: Page 16, Line 12, under parasitological assessment, Did you divide the infection into categories????

R16: Yes the infection were divided into categories. One category for S. haematobium and the other for S. mansoni. Thank you for your comment.

C17: Page 16, Line 2, under treatment, The use of your "all" is confusing. do you mean all infected individual or all communities members who came for the test?

R17: Thank you very much for your comment. Yes we treated all eligible members of the community, irrespective of their participation in the study. This followed the routine guidelines for implementing MDA in the country. Door to door visitation was made and praziquantel was administered to every member of the community.

We have improved our text to highlight this.

C18: Page 18, under results, Line 4, What is the basis for checking for the significant difference here????

R18: Thank you for your comments here. Really there is no major basis here other than the fact that it gives prior information that the distribution of participants varied significantly by gender across the communities. Which is quite typical of most cross-sectional epidemiological studies. But we don’t think it add much value to the paper, or reduces it. But we would love to retain them if the reviewers don’t mind.

C19: Page 20, title,????

R19: Thank you very much for your comment. We really appreciate it

C20: Page 20, Line 1, under treatment data, 432 participated in the investigation, you treated 3,580 people. How do you explain the rationale for this action? Did you just treat people without conducting an appropriate test?

R20: Thank you very much for the valuable comments. Foremost, we explained within the manuscript that the epidemiological team responded to the outbreak by implementing mass administration of praziquantel to all eligible persons in the communities through the usual door-door preventive chemotherapy approach as recommended by the WHO. This approach doesn’t require prior diagnosis of infection before administration of tablets. Prior to the COVID-19 pandemic, this treatment is planned annually (once in a year) by the LGA NTD unit, but was ceased due to the COVID-19 pandemic. However, because of the outbreak reported, it became imperative to resume treatment in this area, which coincided with the time the epidemiological investigation was conducted. For this reason, the number of persons treated were larger in number than those surveyed in the study.

C21: Page 20, line 3, under treatment data, Please what was the rationale for this????

R21: Thank you very much for your comments. The response to this comment has been provided above. We really appreciate your contributions.

C22: Page 21, Line 2, under discussion, This statement is not convincing enough!!!!

R22: Thank you very much for pointing this to us. This really improved the flow of our text. We have modified the text, and added a reference to support our statement here.

Please see below

Since 2014, Takum LGA has benefitted from three biennial rounds of MDA, which targeted 75% of its school-aged children. In these years, the therapeutic coverage were optimal, surpassing the 75% national targets, as such, the outbreak of urogenital schistosomiasis was unexpected [17].

C23: Page 21, Paragraph 2, line 1, ????????

R23: Thank you very much, we have improved the text, and changed the word from hematuria to schistosomiasis.

C24: Page 21, Paragraph 2, Line 4, You are discussing what you did not show in your result, why???

R24: Thank you very much for this observation. We have provided the results been presented here on Table 2. Now with your comments we found it necessary to improve the table and also include a footnote with thte table to describe the categories of endemicity based on prevalence value. We take this time to thank you once more for the valuable comments.

Please see below

C25: Page 23, Line 1, under conclusion, since you identified a gap in the implementation of drug delivery by FMoH and other for the treatment of the disease, I thought you will focus more on how to address right implementation of drug delivery but little or nothing is said about it in this conclusion and recommendation.

R25: Thank you very much once again for this very valuable comment. We have now adjusted the recommendation and conclusion lines, to buttress these points. Thanks.

Please see below

Under recommendations:

It is therefore imperative to consider; (1) investments in effort targeted at reclassifying the LGA as highly endemic, and adjusting the MDA thresholds from the biennial cycle to an annual cycle

Under conclusions:

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 re-classify the LGA as highly endemic, and adjust the MDA thresholds from the biennial cycle to an annual cycle

C26: Figure 2: Your error bar looks misleading, if you use standard error data for your error bar, I don't think you will have this high error bar for your data!!!!

R26: Thank you so much for all your wonderful comments, which were really helpful. For the figures, we used standard deviation to illustrate the margin between the individual infection data. The authors prefer to use this metric in place of standard error which measures the accuracy of estimations.

Submitted filename: Response to Reviewer 2 comments.docx

Click here for additional data file.

26 Dec 2021

27 Dec 2021

C1: They did a good job by updating the manuscript, I really commend them. However, I will encourage the authors to look into the error bars in figure 3 and 4, the error bars are too high giving the impression that there are so meny errors assosiated with the data collected. Thank you.

R1: Thank you very much for your very valuable comment, which has improved the quality of our manuscript. We agree completely with you. We have re-worked the error-bars using percentage error bars, because both SE and SD error bars were too high after trying them. We have provided new figures showing these new error bars. We take this opportunity to appreciate the reviewers and editor for the great efforts on our manuscript.

Submitted filename: Response to Reviewer 2 Commnets.docx

Click here for additional data file.

28 Dec 2021

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

PONE-D-21-30831R2

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12 Jan 2022

PONE-D-21-30831R2

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

Dear Dr. Mogaji:

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