National mapping of schistosomiasis, soil-transmitted helminthiasis and anaemia in Yemen: Towards better national control and elimination.

BACKGROUND: Schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) are known to be endemic in Yemen. However, the distribution of both diseases had not previously been assessed by a well-structured national mapping study covering all governorates. The main aim of this study was, therefore, to map the prevalence of SCH and STH in Yemen in order to better inform implementation of effective national control and elimination interventions. The assessment of the distribution of anaemia was also included as a well-known consequence of infection with both SCH and STH. Secondarily, the study aimed to provide a broad indication of the impact of large-scale treatment on the distribution of infection. METHODOLOGY AND PRINCIPAL
FINDINGS: To achive these aims, 80,432 children (10-14 years old) from 2,664 schools in 332 of Yemen's 333 districts were included, in 2014, into this national cross-sectional survey. Countrywide, 63.3% (210/332) and 75.6% (251/332) of districts were found to be endemic for SCH and STH respectively. More districts were affected by intestinal than urogenital SCH (54.2% and 31.6% respectively). SCH infection was mostly mild and moderate, with no districts reporting high infection. One quarter (24.4%) of Yemeni districts had high or moderate levels of Ascaris lumbricoides infection. Infection with Trichuris trichiura was the second most common STH (44.9% of districts infected) after A. lumbricoides (68.1%). Hookworm was the least prevalent STH (9.0%). Anaemia was prevalent in 96.4% of districts; it represented a severe public health problem (prevalence ≥ 40%) in 26.5% of districts, and a mild to moderate problem in two thirds of the districts (33.7% and 36.1% respectively).
CONCLUSION: This study provided the first comprehensive mapping of SCH, STH, and anaemia across the country. This formed the basis for evaluating and continuing the national control and elimination programme for these neglected tropical diseases in Yemen.

1. Introduction

Schistosomiasis (SCH; also known as Bilharzia), and Soil-Transmitted Helminthiasis (STH) are classified by the World Health Organization (WHO) as neglected tropical diseases (NTDs). Both are widely distributed parasitic diseases that infect hundreds of millions of people worldwide; particularly those who have limited access to safe water, sanitation services, and health facilities. Children of school age typically harbour the highest levels of infection [1-3].

Historical records suggest that SCH is endemic in Yemen with an estimated burden of at least three million cases nationwide at the end of the 20th century [4]. In Yemen, SCH is caused by Schistosoma mansoni and S. haematobium, digenetic blood trematodes that result in intestinal and urogenital infections, respectively, due to their characteristic oviposition sites. The clinical manifestations of intestinal SCH include blood in the stool, diarrhoea, abdominal pain, ascites, and complications related to chronic damage to the liver and kidneys. Urogenital SCH is associated with blood in urine, bladder and ureter fibrosis, damage to the female reproductive tract (female genital SCH), bladder cancer, and increased risk of HIV transmission [5, 6].

Before large-scale control programmes commenced in Yemen in 2009, over half a million individuals were reportedly suffering from significant clinical morbidity, including hepatosplenomegaly in more serious cases and anaemia, stunting, and poor cognitive development, particularly in young children [4, 7]. The common STH infections—hookworm, Ascaris lumbricoides and Trichuris trichiura—are also thought to be highly prevalent in Yemen, and are often detected as co-infections with SCH [4, 8]. There had been several historical surveys conducted at the sub-national level in Yemen. For example, Nagi and colleagues demonstrated that both urogenital and intestinal SCH were highly prevalent in Taiz governorate and Khamer district [4, 8]. Another cross-sectional study estimated the prevalence of intestinal parasites among schoolchildren in one remote district, Sahar [9]. However, no national survey had been implemented before the one described in this paper.

Until 2008, treatment against SCH and STH was sporadic, at local scale, and dependent on demand at health facilities and local private pharmacies, in addition to targeting schools in high endemic areas associated with on-the-spot parasitological investigation and treatment. In 2008, a national scale treatment programme against SCH and STH was formulated, led by the Yemen Ministry of Public Health and Population (MoPHP), with funding from the World Bank (WB) and The END Fund, and technical support from the Schistosomiasis Control Initiative (SCI) and the WHO [10]. This programme treated approximately two million school-aged children in its first year (2008) via preventive chemotherapy using the anthelminthic drug praziquantel (PZQ), to which albendazole (ALB) or mebendazole (MEB) were added for STH. Later in 2010, the programme was expanded to include both schools and communities nationwide. Based on historical records, in 2008 the programme started targeting the areas known to be of the highest risk of infection. At the beginning of the programme, epidemiological mapping was undertaken to identify SCH endemic districts across the country with the purpose of stratifying them according to level of risk to start treatment [10]. This was conducted in 2010 and aimed to estimate SCH prevalence using a geospatial model that combined parasitological surveys that sampled students from 108 schools in 27 districts and relevant ecological co-variates. However, the parasitological surveys were selected from only nine (of 23) Yemeni governorates and following a different methodology to the current study, making direct comparisons difficult.

As per the WHO recommendations [11] re-assessment should be implemented after five to six rounds of treatment to determine the progress and thus the next phase of such a large-scale deworming programme. Accordingly, the Yemen MoPHP, supported by the World Bank, the END Fund, WHO, and the SCI, conducted a nationwide prevalence mapping (PM) survey in 2014. This paper presents the findings.

The PM aimed to assess the epidemiology of SCH (S. mansoni and/or S. haematobium) and STH across all 23 Yemeni governorates following three years of implementation of control interventions by the Yemen national SCH control programme (NSCP). A national ’Yemen Prevalence Mapping Protocol’ [12], targeting school-aged children according to WHO guidelines [11], was prepared by the SCI, and applied to the PM survey, with an overall purpose of informing the future national control approach.

The PM survey also included measuring haemoglobin concentration in the same school-aged children, as part of an integrated survey, in what proved to be the first nationwide anaemia prevalence survey in this population group. In 2013, the Yemen National Health and Demographic Survey (YNHDS) had assessed prevalence of anaemia only among children under five years of age and women in reproductive age (15–49 years old) [13]. Anaemia is a known sequela of various infections prevalent in the country, including SCH, STH, and malaria [14, 15]. The high rates of undernutrition (stunting and wasting) among children, especially in rural populations, [13] makes the countrywide assessment of anaemia crucial.

Accordingly, this nationwide mapping survey was implemented to achieve the objectives of: (1) identifying district-level prevalence of SCH and STH to guide future mass treatment interventions; (2) estimating the level of anaemia prevalence among school-aged children in Yemen in order to make a case for action; (3) evaluating the progress the programme had made against SCH compared to the situation in 2010 and to potentially shift from an objective of control to elimination. However, we note that the 2010 and 2014 surveys used different methodologies which hinders making direct comparisons between them. This article discusses the methods and main findings of this PM survey.

2. Methods

2.1. Ethics statement

Ethical approval was granted by the Imperial College Ethical Review Board and the ethics committee at the Yemeni MoPHP. Permission to collect data was obtained from governorate and district health and education officials and school managers. Detailed information was provided to parents and the communities in advance, via governorate and district health and education officials, to ensure acceptability of the survey and testing.

Permission to access schools was obtained from the local education authorities. School head-teachers, as gatekeepers, informed all teachers, pupils and their parents/guardians about the study, then individual and independent informed consents were obtained from all participants. Permission was obtained from parents/guardians regarding their child’s involvement in the survey. Schools applied an opt-out approach, which is commonly utilised for obtaining consent in school-based research [16-19]: head teachers of all sampled schools contacted parents/guardians to inform them about the survey and asked them to inform the school if they did not permit their child to participate in the survey. Additionally, children were encouraged to discuss their contribution in the study with their parents/guardians before participating in the survey. Moreover, children were asked for their own permission to participate in the study. As recommended in the literature on conducting research in children [17-20], children who refused to participate or whose parents/guardian refused permission were excluded from this study.

All procedures followed during the study were in accordance with the ethical standards of the Helsinki Declaration (1964, 2008) of the World Medical Association. All individuals found to be infected with SCH were provided praziquantel (40 mg/kg body weight).

2.2. Study design

A countrywide cross-sectional school-based survey was conducted in 2,664 schools in 332 health districts between February to May 2014. Yemen is divided into 23 governorates (the first administrative unit) which are then further subdivided into 333 districts. Only one district (Wald Rabi’ district from Al Bayda’ governorate) was excluded from this survey because of its unstable security situation.

The mapping strategy was formulated following WHO guidelines [11, 21]. The recommended sample of 200–250 school-aged children to be drawn from each ecologically homogenous area within the country was applied to each district; this was done with the purpose of having a finer representation of the burden and distribution of schistosomiasis across Yemen, and also to reflect the fact that the district is considered the ‘implementation unit’ at which it is logistically feasible to tailor the treatment strategies effectively [22].

2.3. Study population and sampling

Eighty thousand four hundred and thirty-two children aged 10 to 14 years were selected from 2,664 schools, following WHO guidelines for evaluating helminth control programmes [11]. The sample size was calculated using EPI Info-7 statistical package [23] using 50.0% as the expected prevalence of SCH and a 0.75% error margin, to ensure a sufficient sample [22]. In each district eight schools were selected using simple random methods, amongst schools that were functioning and included sufficient numbers of both male and female students, as the WHO guideline requests [11, 21]. At least 35 children were selected, using simple random methods, per school to make a total of 280 children sampled per district [12] as per the WHO guideline [11, 21].

2.4. Data collection

Data were collected by parasitological technicians (n = 125) forming 25 teams (5 parasitological technicians per team) that were recruited and trained on sample collection techniques and precautionary measures at Sana’a University under the guidance of professors from the Department of Parasitology. The teams were given a manual for field data collection to remind them of the training content. Targeted districts were allocated to each team based on logistics and feasibility.

Upon arrival at each school, teams randomly selected students after informed written consent was obtained from school headteachers, and oral assent was received from the children. Each student was provided with empty stool and urine containers and instructed on how to collect a sufficient amount of each sample. Stool samples collected from each student were tested for the presence of S. mansoni and the STHs (Ascaris, Trichuris and hookworm) using the Kato-Katz method [24, 25]. Urine samples were tested for S. haematobium with a two-step method that employed urine filtration and haematuria reagent strips (Hemastix dipsticks) in order to increase the specificity of testing and minimize false-positive results due to potential samples contamination with blood from menstruation or other infections [24, 25]. In order to determine the prevalence and severity of anaemia, the haemoglobin concentration was assessed using HemoCue and the cut off point for identifying the anaemia was adapted to the altitude of each school, following the international guidelines [26-28]. The coordinates and altitude of all sampled schools were recorded with a Global Positioning System (GPS) (eTrex, Garmin International, Kansas, U.S.A) at arrival and at departure. All data and information collected were noted on prepared case report forms.

For quality assurance, supervisory field visits were conducted throughout the data collection period, to ensure the teams followed the correct methodology and processes during sampling. Additional random sub-samples (10%) of Kato-Katz slides from each school were re-examined by a second member of the team blinded to the initial results. Results for the two readings of the slides were compared for any discrepancy [10]. Moreover, weekly progress reports and results were collected and monitored by supervisors at Sana’a University, the manager of the control programme and the SCI.

2.5. Data analysis

Data on paper case report forms were entered into Microsoft Excel and sent via email to the university team in Sana’a along with the original hard copies. The results were then cross-checked before being sent to the SCI. Cleaning and consistency checks were conducted, and average prevalence of infection with S. mansoni, S. haematobium, A. lumbricoides, T. trichiura, hookworm as well as prevalence of mild, moderate, and severe anaemia were calculated, along with crude confidence intervals at governorate and district level. Robust 95% confidence intervals (CIs) were generated using the statistical software R 3.1.1 (R Foundation for Statistical Computing, Vienna, Austria) with the R ‘survey’ package (T. Lumley (2012) "survey: analysis of complex survey samples". R package version 3.28–2). District-level CIs were calculated accounting for clustering at the school-level, where each child was not considered an independent data point with the assumption that children from the same school would show less heterogeneity than those from different schools.

Maps of the prevalence of infection by district and governorate level were developed using QGIS 2.4.0-Chugiak (Open-Source Geospatial Foundation Project). The geographical information system (GIS) data for Yemen was obtained from the DIVA-GIS database (www.diva-gis.org/gdata) and the Yemen MoPHP (http://www.mophp-ye.org/english/data.html). Yemeni districts were classified into high, moderate, or low risk categories for SCH and STH based on the cut-offs detailed in Tables 1 and 2 respectively [11, 12]. Each district was also further classified by the upper boundary of the 95% confidence intervals, where districts with borderline prevalence rates or upper limits that overlap could be identified and warrant more attention from the control programme. Additional maps of the estimated number of infected cases in the country were developed using the MoPHP population data and calculated prevalence rates. In this map, the population size [29], was projected to expected levels in 2014 based on medium-variant projections by the United Nations and MoPHP [30].

Table 1

Classification of the risk for schistosomiasis based on the WHO cut-off values of district-level prevalence.

Category *	Thresholds for any form of schistosomiasis
High-risk	≥50%
Moderate-risk	≥10% and <50%
Low-risk	<10%

* Categories and cut-off values listed based on WHO guidelines [11].

Table 2

Classification of the risk for STHs based on the WHO cut-off values of district-level prevalence.

Category *	Cumulative prevalence of all STH	The % of moderate/heavy intensity infections
High-risk	≥50%	≥10%
Moderate-risk	≥20% and <50%	<10%
Low-risk	<20%	<10%

* Categories and cut-off values listed based on WHO guidelines [11].

Following WHO recommendations, data on haemoglobin concentrations were used to classify cases of anaemia into mild, moderate, or severe categories as shown in Table 3. Haemoglobin concentrations were adjusted for altitude, with the assumption that communities living at high altitude (>1000m above sea level) have generally higher haemoglobin concentrations than those living at lower altitudes [31].

Table 3

Classification of anaemia severity at sea level based on measured haemoglobin concentrations by age group.

Age group		Non-Anaemia* (g/L)	Anaemia* (g/L)
			Mild	Moderate	Severe
6–59 months		≥110	100–109	70–99	<70
5–11 years		≥115	110–114	80–109	<80
12–14 years		≥120	110–119
≥15 years	Girls**	≥120	110–119
	Boys	≥130	110–129

*WHO recommended anaemia cut-offs for measured haemoglobin levels [31–33].

** Non-pregnant girls.

To identify the public health significance of anaemia, the district-level prevalence of anaemia was used to classify districts into severe (≥40%), moderate (20.0–39.9%), mild (5.0–19.9%), or non-anaemic (≤4.9%) categories, as outlined by the WHO [32].

3. Results

This study included a total of 80,432 children aged 10–14 years drawn from 2,664 schools in 332 districts from all the Yemeni governorates. Approximately 61% of the samples were male due to poor compliance among female students in various schools. The mean age of participants was 12.5 (inter-quartile range (IQR): 9–11.5 years). All participants were screened for all parasites and anaemia.

3.1. Distribution of infection

Of the 332 districts, 63.3% (n = 210) were found to be endemic above the treatment threshold for SCH and 75.6% (n = 251) for STH. This equates to approximately 286,114 infected pupils and 5,510,818 of the general population warranting MDA for SCH or STH. These numbers were calculated based on the UN population projection in 2014 [30]. The guideline for controlling SCH recommends treating school-aged children in districts with low or moderate infection and all populations (school-aged children and adults) in districts with high infection. The Yemen target population was decided on the basis of SCH epidemiology, with ALB/MEB added to the same population.

3.1.1 Prevalence of schistosomiasis

Fig 1A and 1B describe the point prevalence of intestinal (S. mansoni) and urogenital (S. haematobium) SCH infection per district. The findings identified that 31.6% and 54.2% of Yemeni districts were endemic for S. haematobium and S. mansoni respectively. More districts were affected by intestinal (n = 180) than urogenital (n = 105) SCH. As Table 4 demonstrates, more than half (54.2%) of the Yemeni districts were classified as having either low (48.2%) or moderate (6.0%) risk for intestinal SCH infection. Additionally, about a third (31.6%) of districts were classified as having either low (31.3%) or moderate (0.3%) risk for urogenital SCH infection. In 2014, no district had high risk of either urogenital or intestinal SCH as the prevalence of any SCH was less than 50% in all districts.

Fig 1

District-level prevalence maps of schistosomiasis infection in Yemen, 2014.

(A) Intestinal (Schistosoma mansoni) and (B) Urogenital (S. haematobium) schistosomiasis. These figures were created for this manuscript in QGIS using open source data from DIVA-GIS for the base layers. (DIVA-GIS-http://www.diva-gis.org/gdata).

Table 4

The distribution of districts according to risk category for schistosomiasis and soil-transmitted helminth, Yemen, 2014.

Risk category	The proportion of districts (Number)
	S. mansoni	S. haematobium*	Ascaris		Trichuris		Hookworm
			Based on Point Prevalence**	Based on Upper 95% CI***	Based on Point Prevalence**	Based on Upper 95% CI ***	Based on Point Prevalence**	Based on Upper 95% CI***
High	0	0	0.6% (2)	2.7% (9)	0	0.9% (3)	0	0
Moderate	6.0% (20)	0.3% (1)	11.4% (38)	21.7% (72)	1.5% (5)	3.9% (13)	0	0.3% (1)
Low	48.2% (160)	31.3% (104)	56.0% (186)	43.7% (145)	43.4% (144)	40.1% (133)	9.0% (30)	8.7% (29)
Uninfected	45.8% (152)	68.4% (227)	31.9% (106)		55.1% (183)		91.0% (302)

* Classification based on WHO recommended thresholds (≥50% High-risk, ≥ 10% and <50% Moderate-risk and <10% Low-risk).

** Classification based on WHO recommended thresholds (≥50% High-risk, ≥20% and <50% Moderate-risk and <20% Low-risk) [11]. Districts were classified based on the point prevalence of each STH separately by district.

***Districts were classified based on the upper boundary of the 95% confidence interval calculated for the prevalence of each STH by district.

Fig 2A and 2B demonstrate the point prevalence of any SCH infection at the governorate and district level. No districts had more than 50% of its population of school-aged children infected by any SCH, so none were classified as having high risk of SCH infection. There was no significant sex difference in the prevalence of SCH.

Fig 2

Prevalence of any schistosomiasis (intestinal or urogenital) infection in Yemen, 2014.

The maps depict any schistosomiasis prevalence at (A) Governorate and (B) District level. These figures were created for this manuscript in QGIS using open source data from DIVA-GIS for the base layers. (DIVA-GIS-http://www.diva-gis.org/gdata).

3.1.2 Prevalence of Soil-transmitted Helminthiasis

The findings showed that three-quarters (75.6%) of the Yemeni districts were endemic for any STH infection (n = 251). Fig 3A describes the district-level point prevalence of STH in each Yemeni district. More districts were affected by Ascariasis (n = 226) and Trichuriasis (n = 149) than by hookworm infections (n = 30). Table 4 provides the number of districts affected by each species, and species-specific maps are provided in the supplementary information.

Fig 3

District-level point prevalence of soil-transmitted helminthaisis infection in Yemen, 2014.

The maps depict (A) any soil-transmitted helminth infection and (B) Ascaris lumbricoides infection. These figures were created for this manuscript in QGIS using open source data from DIVA-GIS for the base layers. (DIVA-GIS-http://www.diva-gis.org/gdata).

About two-thirds (65.4%) of the Yemeni districts were classified as having either low or moderate risk of Ascaris infection. Fig 3B shows the district-level point prevalence of Ascaris infection at the district level. About a fifth (21.7%) of Yemeni districts have Ascaris infections among 20%-50% of schoolchildren. Based on the WHO classification [12, 21], nine districts are in the high-risk category, with more than 50% of schoolchildren infected with Ascaris (Table 4). Trichuriasis was the second most common STH: 133 districts (40.1%) were classified as having low levels of Trichuris, while sixteen (4.8%) had either high or moderate infection. For both Ascaris and Trichuris, these districts tended to be poor and rural, with agriculture as the main source of income. Infection was higher in females than males. Hookworm was the least prevalent STH in Yemen, with only 9.0% of districts with infections, all of which were classified under the low-risk category except one moderate-risk district, indicating that the prevalence was less than 20% among schoolchildren (Table 4).

3.2. Prevalence and severity of Anaemia

Anaemia is prevalent among schoolchildren in 96.4% of the Yemeni districts. Fig 4 demonstrates the severity of anaemia at the district and governorate levels. Only 12 districts have anaemia in less than 5% of schoolchildren. These districts tended to be urban and had the highest income.

Fig 4

Prevalence maps of the public health significance of anaemia in Yemen, 2014.

The maps display anaemia severity nationwide at (A) the governorate level and (B) the district level. These figures were created for this manuscript in QGIS using open-source data from DIVA-GIS for the base layers. (DIVA-GIS-http://www.diva-gis.org/gdata).

Anaemia is a severe public health problem in over a quarter (26.5%) of Yemeni districts as more than 40% of schoolchildren in these districts had anaemia. Over a third of Yemeni districts (36.1%) had anaemia in 20–40% of schoolchildren, indicating a moderate public health problem based on the WHO classification [31-33]. As shown in Table 5 below, only one third (33.7%) of districts have anaemia in less than one-fifth of schoolchildren and thus have mild prevalence of anaemia. Lack of historical district-level anaemia data limited our ability to estimate the impact of the programme on anaemia. There was no significant sex difference in the prevalence of anaemia (31.0% and 30.1% among females and males, respectively).

Table 5

District-level distribution of anaemia in Yemen, 2014.

Category (prevalence [%])	Number of districts	% of districts
No anaemia (≤ 4.9)	12	3.6%
Mild (5.0–19.9)	112	33.7%
Moderate (20.0–39.9)	120	36.1%
Severe (≥ 40)	88	26.5%

4. Discussion

This study identified that 63.3% and 75.6% of Yemeni districts are endemic above treatment thresholds for SCH and STH respectively. This represents a reduction in the number of districts estimated to harbour any SCH infection and, importantly, those with high and medium levels of infection compared to 2010 when SCH was known or suspected to be endemic in 82.6% (275/333) of Yemeni districts and STH infection was suspected in all 333 districts [34, 35]. Based on a threshold of ≥40% for SCH, 51 districts were classified as high risk in 2010 compared to the 2014 survey where none of the districts reported SCH prevalence of more than 40%. However, it was noted that if a more conservative high-risk cut-off of ≥30% is utilised, three districts will fall into the high risk category in 2014 [36].

However, it is important to explain that the two surveys used different methodological approaches which restricts the ability to conduct direct comparisons. The 2010 survey included demographic and ecological data from 41,381 mapped villages, including village population, number of houses, number of families, male and female population, and age. The data were combined in a geospatial model with relevant ecological covariates (rivers and other water sources, rainfall, temperature, population distribution, land cover and altitude) to map the risk of helminth transmission and infection across the country with the purpose of stratifying districts according to level of risk [10]. The 2010 survey also employed a GIS-based implementation planning kit. This supported the planning process for every village, sub-district (ozla), treatment point, working team, district, and province in Yemen. The kit automated the calculation of the targeted population subgroups for treatment, the required drug amounts, and the operational and social mobilization costs at all levels. The population estimation was based on 2004 population figures for 333 districts [10].

Despite the difference in the methods used, the findings highlight a reduction in the burden of both SCH and STH across the country after implementing the national intervention activities by the NSCP. SCH control was sporadic until 2008, when the five-year national NSCP was initiated to treat over two million school-aged children via preventive chemotherapy using anthelminthic drugs. Following the first three years of programme implementation, nine rounds of treatment were conducted with 45 million PZQ tablets and 18 million ALB tablets distributed to 13 million people. MDA was conducted using a combination of fixed and temporary sites (schools, mosques, health facilities) and mobile teams. This approach has been demonstrated to be effective in reaching the programme’s key target groups of enrolled and non-enrolled school-aged children, and adults in 275 out of 333 districts based on data from 2010. In the most affected districts, individuals have received up to three doses of PZQ once per year. Much of the east of the country is effectively SCH-free (Fig 1A and 1B), with much lighter infection in many other places. However, more interventions need to be implemented in other districts, especially in the western districts (Fig 2B), toward better national control.

There was no evidence of any changes in environmental health interventions aimed at improving sanitation and safe water supply provision which could have contributed to reductions in helminth infections. Treatment alone is unlikely to lead to elimination of SCH or STH infections which is thought to also require health education, improved access to safe water, and adequate sanitation facilities in order to stop open defecation and improve personal hygiene practices [1–3, 11]; absence of these interventions could lead to infection morbidity recrudescence [37-40]. For example, lack of access to handwashing facilities in schools and in the community are likely to promote STH transmission [39, 40]. It is recommended to involve the private sector and NGOs in implementing these activities, as historically they have shown effectiveness in supporting and sustaining similar activities in other low and middle-income countries [39, 41–43].

This study also identified that anaemia is prevalent among schoolchildren in almost all Yemeni districts. Anaemia is a severe public health problem in over a quarter of districts and a moderate public health problem in a further third. Anaemia is a known sequela of various infections prevalent in the country, including SCH, STH, and malaria [14, 15] and is known to be correlated with the high rates of undernutrition (stunting and wasting) among children, especially in rural populations [13]. Few subnational studies have indicated that the prevalence of anaemia among Yemeni children under five years old range from 20.0% to 73.5% and suggest that it is more prevalent among those who have worm infestations [44, 45]. However, none of the previous national surveys had assessed the prevalence of anaemia among schoolchildren [12]. The Yemen National Health and Demographic Survey regularly assess anaemia among children under five and women of reproductive age. Lack of district anaemia data from 2010 precluded any estimation of the impact of the NSCP on the prevalence of anaemia. A Master’s thesis conducted in 2018 explored the prevalence of intestinal SCH and its effect on nutritional status and anaemia among schoolchildren in two districts in Sana’a Governorate [46]. The study demonstrated that the highly focal distribution of intestinal SCH was related to prevalence of wasting and stunting in early adolescents. Anaemia is still a moderate public health problem in early female adolescents. Underweight and wasting were identified to be high among adolescent school-aged children in two governorates endemic with SCH [9, 45]. Evidence from other contexts suggest that anthelminthic treatments are effective in improving haemoglobin levels and reducing the prevalence of anaemia and undernutrition in general [42, 47].

The findings of this PM survey signal that SCH distribution is much reduced compared to the 2010 estimates. This stimulated asking questions about the possibility of shifting the programme objectives toward elimination of transmission rather than just control, in line with the WHO 2020 and 2025 goals [37, 38, 48] and the global target [47, 49, 50]. However, the end of the programme grants as well as the political instability in the country and the huge disruption since the eruption of the conflict in 2015, which affected all sectors including education and health, are major challenges toward implementation of large-scale programmes, and hence of achieving the ambitious target of elimination of SCH in Yemen.

WHO recommends using school-based sampling to estimate the distribution of helminth infections [11, 21] and school-based deworming interventions have been demonstrated to reduce the burden of helminth infections [51]. Rapid diagnostic tests can play a role in improving the efficiency of diagnosis in field settings, particularly where access to laboratory equipment is constrained [52, 53]. However, given the continuing instability, school-based monitoring and deworming is incredibly challenging. As UNICEF reported in mid-2021, the conflict in Yemen has pushed almost two million children out of school and meant that two-thirds of Yemeni teachers have been without salaries for more than four years [54]. Children were forced to leave schools due to insecurity, school destruction, or to help families with income generation and household tasks [55]. In addition, these challenges necessitated a change in funding approach so that MDAs are an output-based payment for those Yemeni teachers. Such status affects the quality of drug distribution, consequently, MDAs reverted from a large scale into a small scale covering mainly the high and meso endemic districts on alternative years. Even though the MDA campaigns have continued to cover the enrolled and the non-enrolled school-aged children through fixed and community-based treatment, pre-campaign impact evaluation studies have completely ceased since 2015. Consequently, there have not been any more regular parasitological assessment surveys including anaemia and anthropometric measurements on school-aged children [56]. These are clear barriers to controlling SCH and STH and improving anaemia and other health challenges in Yemen.

5. Conclusions and recommendations

This study provided a comprehensive mapping of SCH, STH, and anaemia in Yemen. Anaemia was identified as a severe or moderate public health problem in at least a quarter and a third, respectively, of Yemeni districts. This reinforces the need for interventions to reduce the burden of anaemia across the country. Although malnutrition and helminth infections are the most suspected causes of anaemia, confirmatory research is needed in this regard.

The results show reduced levels of both SCH and STH infections across all Yemen districts compared to a previous survey in 2010 after implementing national intervention activities. However, this status cannot be guaranteed after ending of the programme grant and the political instability in the country due to the war which has been ongoing since 2014. There is a need to restore the programme’s full functioning capacity to protect gains in infection levels and prevent recrudescence of infection. Without comprehensive community awareness, behaviour change interventions, and significant improvement of the provision of safe water and adequate sanitary facilities, it will be challenging to interrupt the SCH and STH transmission cycle and eliminate these infections across the country. Combating the burden of STH and SCH and their consequences requires a holistic intervention approach that should involve different stakeholders including community members and local authorities.

Although the distribution of infection will undoubtedly have changed somewhat since this survey was conducted in 2014, these data provide a strong platform and most recent disease distribution data for planning a sustained national control and elimination programme when the security situation allows. Future studies should also explore the impact of the programme on anaemia as well as nutritional status and educational achievement of children. This would enhance appropriate resource allocation for controlling neglected tropical diseases and their sequelae in Yemen.

Point prevalence map of Trichuris infection in Yemen, 2014.

This figure was created for this manuscript in QGIS using open-source data from DIVA-GIS for the base layers. (DIVA-GIS-http://www.diva-gis.org/gdata).

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Click here for additional data file.

Point prevalence map of Hookworm infection in Yemen, 2014.

This figure was created for this manuscript in QGIS using open-source data from DIVA-GIS for the base layers. (DIVA-GIS-http://www.diva-gis.org/gdata).

(TIF)

Click here for additional data file.

28 Jun 2021

Dear Dr Annuzaili,

Thank you very much for submitting your manuscript " National Mapping of Schistosomiasis, Soil-Transmitted Helminthiasis and Anemia  in Yemen: Towards Better National Control and Elimination " for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Alberto Novaes Ramos Jr

Associate Editor

PLOS Neglected Tropical Diseases

Marco Coral-Almeida

Deputy Editor

PLOS Neglected Tropical Diseases

***********************

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: see summary and general comments

Reviewer #2: Find my comments attached

Reviewer #3: See general comments.

Reviewer #4: See attached

--------------------

Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: see summary and general comments

Reviewer #2: Find my comments attached

Reviewer #3: See general comments.

Reviewer #4: See attached

--------------------

Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: see summary and general comments

Reviewer #2: Find my comments attached

Reviewer #3: See general comments.

Reviewer #4: See attached

--------------------

Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: (No Response)

Reviewer #2: (No Response)

Reviewer #3: Minor Comments:

1) Lines 109-11: When were the 45 million tablets distributed to 13 million people? After the 2014 survey? Between 2010 and 2014?

2) Line 256: for clarity, please define “endemic”.

3) Lines 260-262: were there districts that warranted STH treatment that did not require PZQ treatment? Were they treated?

4) Fig. 3: as above, were data comparable for 2010 and 2014?

5) Lines 290-291: “About a fifth (22%) of Yemeni districts have Ascaris infections among 20%-40% of school children.” Fig. 4 uses the WHO thresholds of 20 and 50%. These numbers should agree.

Reviewer #4: See attached

--------------------

Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: The article is important since is documenting the epidemiological situation od Schistosomiasis and STH infection in Yemen in 2014, is well written and in my opinion merits publication.

I have only minor changes to request:

1- one point is not completely clear: the author mention that the one conducted in 2014 wass the first national survey conducted in Yemen but then in figure compare the endemicity in 2010 and 2014; so 2010 data are present? If not how the classification of each district in the different classes of endemicity was done?

2- In line 386-388 the authors mention the programme was successful in control the SCH related morbidity but do not provided an indicator for that claim.

The morbidity of SCH (and STH infections) is measured by WHO as the prevalence of infections of moderate heavy intensity (as infection of light intensity are causing minimal morbidity) it would therefore be important (if the data are available) to report the prevalence of infection of moderate/ heavy intensity for SCH (and STH)(and present it in a map.

This will provide a clear idea of the morbidity due to these infection present in Yemen in 2014.

Reviewer #2: Find my comments attached

Reviewer #3: In this manuscript, Johari and colleagues report the results of a large scale mapping exercise for schistosomiasis and soil transmitted helminths that was conducted in Yemen in 2014. The impressive scale of the survey– more than 80,000 children tested – makes these data especially noteworthy. It is a pity that there was such a delay in the reporting of this information and that the war has undermined the country’s ability to provide MDA.

I have a few concerns about this paper. First, as noted in the discussion, the authors are trying to make the case that the 2014 survey results document “substantial and significant reduction in the burden of both SCH and STH.” However, except for the information presented in Fig. 3, the reader has no access to information about the 2010 survey: how extensive was it, were the same districts tested, were the same age groups? I did not see these results referenced. If the comparison of the 2010 and 2014 results is a central conclusion of the paper, more information should be provided about the 2010 survey.

I don’t understand why this paper is using thresholds for SCH that are different from those used by WHO. I understand the desire to be more conservative, but the programmatic decision can be made separately from the presentation of the data here.

Given the scale of the tragedy that has unfolded in Yemen, I think it is important for the paper to refer to this more specifically. Are children in school? Is MDA ongoing anywhere? How has the disruption in services affected children in terms of their growth and anemia status? Are the “gains” being reversed?

Reviewer #4: See attached

--------------------

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Reviewer #1: No

Reviewer #2: Yes: Jean T. Coulibaly

Reviewer #3: No

Reviewer #4: No

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Submitted filename: Reviewer Comment (24 6 2021).docx

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Submitted filename: Manuscript Review.docx

Click here for additional data file.

30 Aug 2021

Submitted filename: Cover Letter.docx

Click here for additional data file.

4 Oct 2021

Dear Dr Annuzaili,

Thank you very much for submitting your manuscript "National Mapping of Schistosomiasis, Soil-Transmitted Helminthiasis and Anemia  in Yemen: Towards Better National Control and Elimination" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Alberto Novaes Ramos Jr

Associate Editor

PLOS Neglected Tropical Diseases

Marco Coral-Almeida

Deputy Editor

PLOS Neglected Tropical Diseases

***********************

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #3: (No Response)

Reviewer #4: The authors have satisfactorily addressed the my original comments in regard to methods with the exception of the use of baseline (please see my comments in the summary/general comments section below).

--------------------

Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #3: See below

Reviewer #4: The authors have satisfactorily addressed the my original comments in regard to results.

--------------------

Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #3: See below

Reviewer #4: (No Response)

--------------------

Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #3: Minor Comments:

1) Lines 121-22: The authors have now provided the years when the 45 million tablets distributed to 13 million people; however, it’s hard to understand how these numbers relate to the number of years of treatment and coverage.

2) Line 204-205: “The results were then cross-checked before being to the SCI.” A word is missing here.

Reviewer #4: I suggest moving the newly added figures in the discussion section to the supplementary folder. The discussion is not the place for presenting this data visually.

--------------------

Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #3: In this manuscript, Johari and colleagues report the results of a large scale mapping exercise for schistosomiasis and soil transmitted helminths that was conducted in 2014. The scale of this survey was impressive – more than 80,000 children tested – makes these data especially noteworthy. It is a pity that there was such a delay in the reporting of this information and that the war has undermined the ability to provide MDA.

I still have a few concerns about this paper. First, as noted in the discussion, the authors are trying to make the case that the 2014 survey results document “substantial and significant reduction in the burden of both SCH and STH.” Despite some additions to the text, the reader still doesn’t have access to the 2010 survey results or even an adequate description of the methodology. If the comparison of the 2010 and 2014 results is a central conclusion of the paper, more information should be provided about the 2010 survey.

I don’t understand why this paper is using thresholds for SCH that are different from those used by WHO. I understand the desire to be more conservative, but the programmatic decision can be made separately from what is reported here.

Given the scale of the tragedy that has unfolded in Yemen, I think it is important for the paper to refer to this more specifically. Are children in school? Is MDA ongoing anywhere? How has the disruption in services impacted children in terms of their growth and anemia status? Are the “gains” being reversed?

Reviewer #4: The authors have done well to address all the reviewer comments so thoroughly. Although I agree with the authors response to my comment (#3) regarding the use of previous mapping data to highlight the progress made, I still disagree with the use of the term 'baseline' for this earlier data. I strongly suggest avoiding the use of baseline and follow up as it suggests a very different type of analysis than what has been presented in this manuscript. Rather, the data could be referred to by the year, e.g., 2010 survey and 2014 survey.

--------------------

PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: No

Reviewer #4: No

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

3 Dec 2021

Submitted filename: Cover Letter_ 1 Dec 2021.docx

Click here for additional data file.

14 Dec 2021

Dear Dr Annuzaili,

We are pleased to inform you that your manuscript 'National Mapping of Schistosomiasis, Soil-Transmitted Helminthiasis and Anemia  in Yemen: Towards Better National Control and Elimination' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Alberto Novaes Ramos Jr

Associate Editor

PLOS Neglected Tropical Diseases

Marco Coral-Almeida

Deputy Editor

PLOS Neglected Tropical Diseases

***********************************************************

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: objective of the study is clear and method well explained

Reviewer #3: (No Response)

**********

Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: Results are well reported

Reviewer #3: (No Response)

**********

Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: The conclusions are supported by the data resented

Reviewer #3: (No Response)

**********

Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: (No Response)

Reviewer #3: (No Response)

**********

Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: I think the paper report important epidemiological data on schistosomiasis and STH and should be published in the present form.

Reviewer #3: (No Response)

**********

PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: No

15 Feb 2022

Submitted filename: Cover Letter_ 1 Dec 2021.docx

Click here for additional data file.

17 Feb 2022

Dear Dr Annuzaili,

We are pleased to inform you that your manuscript 'National Mapping of Schistosomiasis, Soil-Transmitted Helminthiasis and Anaemia  in Yemen: Towards Better National Control and Elimination' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Alberto Novaes Ramos Jr

Associate Editor

PLOS Neglected Tropical Diseases

Marco Coral-Almeida

Deputy Editor

PLOS Neglected Tropical Diseases

***********************************************************

The authors have included in the revised version of the manuscript an updated ethics statement. These adjustments satisfactorily address the ethical issues previously indicated.

4 Mar 2022

Dear Dr Annuzaili,

We are delighted to inform you that your manuscript, " National Mapping of Schistosomiasis, Soil-Transmitted Helminthiasis and Anaemia  in Yemen: Towards Better National Control and Elimination ," has been formally accepted for publication in PLOS Neglected Tropical Diseases.

We have now passed your article onto the PLOS Production Department who will complete the rest of the publication process. All authors will receive a confirmation email upon publication.

The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any scientific or type-setting errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Note: Proofs for Front Matter articles (Editorial, Viewpoint, Symposium, Review, etc...) are generated on a different schedule and may not be made available as quickly.

Soon after your final files are uploaded, the early version of your manuscript will be published online unless you opted out of this process. The date of the early version will be your article's publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers.

Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases