Impact of a national deworming campaign on the prevalence of soil-transmitted helminthiasis in Uganda (2004-2016): Implications for national control programs

Background Soil-transmitted Helminths and Anemia potentially reduce and retard cognitive and physical growth in school-age children with great implications for national control programs in Africa. After 13 years of deworming and limited health education campaigns, a study was undertaken to evaluate the impact of deworming interventions on the prevalence and intensity of soil-transmitted helminthic infections in school-age children in Uganda. Methodology A cross-sectional study was carried out in six regions of Uganda, where two districts were randomly selected per region based on the ecological zones in the country. Included in the study were the districts; Mpigi and Nakasongola from the Central; Nakapiripirit and Kotido from Karamoja; Arua and Yumbe from West Nile; Gulu and Alebtong from the North; Kaliro and Mbale from the East; Hoima and Bundibugyo in the West. Five schools were randomly selected from each district and in each school 50 children aged 6–14 years were randomly selected. Stool samples were taken each child and examined for the presence of helminthic infections. A short pretested questionnaire was administered to each participant to obtain their knowledge, attitude, and practice relating to STH infections, their control. General observations were made on environmental sanitation in the schools. The location of each school was geo-referenced using a GPS machine (Garmin®GPSMAP62, Garmin Ltd, Southampton, UK). Results In total, 4,285 children were assessed including 719(16.82%) from central region, 718(16.80%) from eastern region, 719 (16.82%) from northern region, 689 (18.82%) from Karamoja region, 717(16.77%) from West Nile region and 723(16.91%) from western region. The average age of the children was 12.6 years with a standard deviation, SD 1.8 years and the minimum age was 6 years and upper age limit of 12 years. The percentage of boys (50.1%) and girls (49.9%) was comparable. 8.8% (95% CI; 8.0–9.7) were infected with at least any one STH species. Hookworm was the most prevalent (7.7%; 95% CI; 6.9–8.5) followed by whipworms (Trichuris trichiura) (1.3%; 95% CI; 1.0–1.7) and roundworms (Ascaris lumbricoides) (0.5%; 95% CI; 0.3–0.7). Some children had Schistosoma mansoni, 13.0% (95% CI; 12.0–14.0). All the children knew what soil transmitted helminths were (62.8%, 95% CI: 61.3–64.2) and most common knowledge of information were from; home (39%, 95% CI: 37.1–40.8), media (radio& newspaper)(11%, 95% CI: 9.8–12.2), school(65.7%, 95% CI: 63.9–67.5) and friends(11.5%, 95% CI: 10.3–12.7). Majority were aware of how one gets infected with soil transmitted helminths through; eating contaminated food (77.5%, 95% CI: 76.0–79.1), walking barefoot (59.6%, 95% CI: 57.8–61.5), drinking contaminated water (52.9%, 95% CI: 51.0–54.8), playing in dirty places (21.8%, 95% CI: 20.2–23.3) and dirty hands (2.3%, 95% CI: 1.7–2.9). Conclusion Semi-annual deworming campaigns have proved effective in significantly reducing helminthic infections in most of the districts in Uganda. Regular evaluations are vital to assess impact of the interventions and guide programme implementation. Our data shows that the prevalence of infection has been reduced to a level where STH morbidity is no longer of public health importance in most districts surveyed.


Conclusion
Semi-annual deworming campaigns have proved effective in significantly reducing helminthic infections in most of the districts in Uganda. Regular evaluations are vital to assess impact of the interventions and guide programme implementation. Our data shows that the prevalence of infection has been reduced to a level where STH morbidity is no longer of public health importance in most districts surveyed.

Introduction
Soil-transmitted Helminthic infections pose a great and often a silent burden of morbidity and mortality on poor populations in developing countries. The most common helminths infections are caused by roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura), and hookworms (Necator americanus and Ancylostoma duodenal). Worldwide estimates suggest that A. lumbricoides infects 1.221 billion people, T. trichiura, 795 million, and hookworms, 740 million [1].Between 1998 and 2003, the Vector Control Division of the MOH mapped schistosomiasis and soil-transmitted helminthiasis (STH) using the Kato Katz method [2]. The derived map, based on 23,627 individuals in 271 schools situated in 46 of the then 56 (82%) districts showed that STH prevalence was quite high, the prevalence of infection being over 60% in 35, of the 46 districts [3]. A.lumbricoides and T.trichiura were greatest in the south western districts with prevalence generally above 80%. Moderate prevalence occurred in selected central and eastern districts and there was a near absence of transmission in the northern districts [4]. By contrast, hookworm was homogeneously distributed throughout the country, exceeding 60% to 85% of the schools surveyed, but again the prevalence was quite low in the Karamoja region [4]. Thus according to WHO guidelines [5], virtually all districts in Uganda had a prevalence of any worm generally above 50% and the whole country fell into the category targeted for twice yearly treatment. A deworming campaign was initiated in 18 of the then 56 districts in 2003 by MoH supported by Schistosomiasis Control Initiative (SCI) but was scaled up to the national level in 2004 [6]. Deworming activities are done once or twice a year mainly targeting PSAC and SAC but is also provided in antenatal clinics to expectant mothers. However, where LF is endemic the whole population receives albendazole as part of the LF treatment regimen with ivermectin and this given during one of the twice yearly deworming campaign.

Prevalence and intensity of STH infections in school children
In terms of the disease burden in school-age populations in developing countries including Uganda [7], intestinal helminths infections rank first among the causes of all communicable and non-communicable diseases [8]. Field studies of Schistosomes and the major intestinal nematodes Trichuris trichiura and Ascaris lumbricoides repeatedly demonstrate that the intensity and prevalence of infection exhibit marked dependency on host age [9]. Peak levels of infection typically occur in hosts aged between 10 and 14 years in endemically infected communities [10]. Age-dependent patterns of infection prevalence are generally similar among the major helminth species, exhibiting a rise in childhood to a relatively stable asymptote in adulthood [11]. Epidemiological studies of STH infections have shown that the prevalence and intensity of infection are highest among children 4-15 years of age [3]. For the vast part of Uganda, a uniform treatment strategy involving school-based (for school age children) and community-based treatment (for under-fives) is implemented twice yearly during the child health days in April and October. However, in schistosomiasis high-risk villages and in lymphatic filariasis (LF) endemic districts, the first round of mass drug administration (MDA) targets the whole population while the second round of treatment is limited to under-fives and school-age children. No study has been done to assess the impact of school-based deworming which has been ongoing since 2004. Program monitoring has been limited to reported treatment coverage, but the reports have never been validated and it is possible that the data are exaggerated.

Morbidity and burden of STH
Soil-transmitted helminths frequently cause chronic and debilitating diseases, mainly in infants, preschool and school-aged children, adolescent girls and pregnant women [12][13]. Global burden is typically expressed in DALYs estimated as high as 39 million, similar to malaria or tuberculosis [11,14]. Globally an estimated 807-1221 million people are infected with A.lumbricoides, 604-795 million with T.trichiura, 576-740 million with hookworms [12,15]. Concurrent infections with multiple helminth species are common [16][17][18][19] a known cause of malnutrition, intestinal obstruction, biliary colic and pancreatitis [20]. T.trichiura infections can induce Trichuris dysentery syndrome, whose symptoms include rectal prolapse, anemia, and clubbing of fingers [21]. Hookworm is implicated as the causative factor in more than 50% of cases of iron deficiency anemia in Asia and Africa [22].
Generally, infections with STH have a negative impact on pregnancy and birth outcomes, hamper children's cognitive and physical development [23][24], resulting in reduced work capacity, and therefore compromise the social and economic development of communities and entire nations [11,25]. An infection level of A.lumbricoides and T.trichiura are highest in children aged between 5 and 14 years [14]with decline in frequency and intensity in adulthood [26]. This age dependency might be due to changes in exposure and/or acquired immunity [10] and morbidity associated with the number of worms harbored [27].
The aim of this study was to evaluate the impact of a national deworming campaign on the prevalence and intensity of soil-transmitted helminthic infections in Uganda.

Study area
The selection criteria for the districts was based on the six regions in which two districts were selected per region with Central region (Mpigi and Nakasongola), Karamoja region(Nakapiripirit and Kotido), West Nile region (Arua and Yumbe), Northern Region (Alebtong and Gulu),Eastern region (Mbale and Kaliro) and Western region (Bundibugyo and Hoima). The Fig 1 below shows the list districts that were selected for the surveys.

Study design
The study was descriptive and cross-sectional. The major objective of the study was to assess the impact of deworming on STH and guided by the following objectives: 1. to determine the prevalence of all STH species infection among school-age children in identified districts 2. to compare the prevalence of infection before and after interventions 3. To examine the current water and sanitation conditions in schools and relate the parameters to the current prevalence of infection

Selection of study population and data collection
From each district, five schools were randomly selected. In each of the selected schools, children aged 6-14 years (30 boys and 30 girls) were randomly selected, whereas, in communities, 60 participants aged 5 years and above were selected and conducted during June-July 2016 period.

Laboratory methods
Duplicate Kato-Katz thick smears [2] were prepared in the field upon receipt of the fecalsamples and were read under a microscope within 60 minutes of slide preparation to determine hookworm ova. To avoid inter-observer errors, the two slides from one specimen were read by different technicians. For quality control, 10% sub-sample of the slides was re-read by an experienced technician. There was no significant difference between the technicians' readings and those of the sampled slides.

Measurement of haemoglobin levels
Haemoglobin (Hb) levels were measured using finger prick blood taken from each child for the assessment of Hb as proxy to measuring anaemia levels. The Hb was measured in the field using a portable hamoglobinometer (HemoCue Hb301, LTD Angelholm, Sweden). Determination of anaemia levels followed WHO references defined as: Hb< 115 g/L for children 5-11 years; Hb<120 g/L for children 12-14 years; Hb<120 g/L for non-pregnant women ! 15 years; Hb<110 g/L for pregnant women; Hb<130 g/L for men ! 15 years [28][29].

Measuring knowledge, attitude, and practice
A short pretested questionnaire was administered to each participant to obtain their knowledge, attitudes, and practices relating to infection and control of STH. General observations were made on the sanitations of their environments. Observations were made on school and community environment including availability and conditions of latrines and hand washing facilities. Coordinates of each school were taken using a GPS machine (GarminGPSMAP62, Garmin Ltd, Southhampton, UK).

Treatment and ethical approval
All children found positive for intestinal schistosomiasis (egg-patency) were treated with praziquantel (Distocide, Shin Poong Pharmaceuticals, Seoul Republic of Korea) at 40 mg/kg body weight. Regardless of infection status, a tablet of albendazole (400mg) was given to each child for soil-transmitted helminthiasis. This study was approved by the Ugandan National Council of Science and Technology and formed part of the monitoring and surveillance activities of the Ugandan National Bilharzia & Worm Control Programme. Permission from school authorities was sought and children consented before participation in the study.

Data analysis
A descriptive analysis of the data on prevalence and intensity of infection from the national registry of the Ministry of Health in 2004 was done and compared with the recent study for the selected districts. Besides the analysis of frequency and proportion distributions, the geographic locations of prevalence and intensity of infection data points for school-age children were mapped, as this was useful to visualize gaps in data. The database was made with MS-Excel 2013 and the analysis with STATAVersion10. All the data were double entered into the computer using excel programme by different clerks. The impact on the intensity of infection was determined using student's T-test. Binary logistic regression analysis was utilized to determine WASH factors as associated with STH infections. Multivariable models for infection with each type of infection was adjusted for gender, residence in a treatment area, playing barefoot; and reported the presence of latrine and any other purported risk factor under study. None overlapping 95% confidence intervals and p-values <0.05 were considered as significant levels.

Results
Overall data were collected from a total of 4,275 children including 719(16.8%) from central region, 718(16.8%) from eastern region, 719 (16.8%) from northern region, 689 (18.1%) from Karamoja region, 717(16.7%) from West Nile region and 723(16.9%) from western region. The average age of the children was 12.6 years with a standard deviation, SD 1.8 years and the minimum age was 6 years and upper age limit of 12 years. The percentage of boys (50.2%) and girls (49.9%) was comparable as shown below in Table 1. Table 2 above summarizes the prevalence and intensities of infection by the district. Generally, the pattern of Soil-transmitted helminths (STH) varied markedly with an overall 8.8%, (95% CI; 8.0-9.7) infected with at least any one STH species. The most common soil-transmitted helminths were hookworms (7.7% 95% CI; 6.9-8.5), Trichuris trichiura (1.3%, 95% CI; 1.0-1.7) and Ascaris lumbricoides (0.5%; 95% CI; 0.3-0.7) respectively. The highest prevalence infection was observed in Bundibugyo district with the prevalence of 24.9% [20.5-29.4   The prevalence of light intensities of infections for Ascaris lumbricoides varied from 0.0% to 100% with an overall 86.4% while the prevalence of moderate intensities of infections ranged from 0.0% to 100% with an overall 13.6%. There were no individuals observed with heavy intensities of infection. The prevalence of light intensities of infections for Trichuris trichiura infections ranged from 0.0% to 100% with an overall 98.3% while Mpigi district recorded 4.2% prevalence for moderate intensities of infections. There were no individuals observed with heavy intensities of infection.

Comparison of prevalence of STH infection at baseline in 2004 and 2016
Overall, the study results show that the prevalence of STH was generally high at baseline (2002) Fig 2A. Comparison of Hookworm infection. Overall, the results show that the prevalence of Hookworm infections was generally high at baseline in 2002 compared to over a decade of Deworming campaign in Uganda that achieved a significant reduction. However, there was a significant increase in Hookworm prevalence in Mpigi (4.9% vs. 11.6%) and Kaliro (16.4% vs.

Treatment coverage over the years for STH
Mass drug administration (MDA) is the mainstay of morbidity control for schistosomiasis and soil-transmitted helminths (STHs) [5]; hookworm, roundworm, and whipworm are the three main species of STHs that infect humans. MDA is the delivery of free single-treatment preventive chemotherapies at regular intervals to endemic populations. STHs are treated with albendazole (ALB) or mebendazole (MBZ). Repeated annual or biannual treatments are necessary mainly due to susceptibility to reinfection after treatment [30][31]. The central challenges identified by the WHO to increase MDA coverage are sustaining financial support for MDA, improving monitoring and evaluation, expanding local administrative capacity, and increasing access to preventive chemotherapies during MDA [32].
Implemented by districts using school teachers and volunteers known as Village Health Teams (VHTs) and Healthcare workers during Child Days plus (CDP) with the aim to control morbidity. The delivery strategy is through mass annual anthelmintic treatment targeted at school-aged children and high-risk groups in the endemic areas using Albendazole (ALB) /Mebendazole (MBZ) to treat STH infection [33][34]. Generally, there has been a tremendous improvement in the STH worm burden over the years. However, there is still a challenge to STH elimination as some districts continue to register lower MDA coverage than recommended >75% by WHO as indicated in Fig 3 below.

Discussion
Generally, there was a significant reduction in the worm burden throughout the country, although, this could be attributed to regular deworming and improved sanitation over the years. A national deworming program was initiated in 2003 by the Ugandan Ministry of Health (MOH) with support from the Schistosomiasis Control Initiative (SCI) and later scaled-up to the national level in 2005 [6]. A uniform strategy involving school-based and community directed implementation has been implemented in Uganda twice yearly in April and October. However, in Schistosomiasis high-risk villages and in lymphatic filariasis (LF) endemic districts, the first round of mass drug administration (MDA) targets the whole population while the second round of treatment is limited to under-fives and school-age children.
Integrating disease control programs can result in improved cost-effectiveness and resource efficiency where endemic populations overlap and more so where MDA and disease-specific requirements are similar. In most communities, the environmental Health Division of MoH has been running a sanitation program and this has contributed to improved sanitation and promotion of safe water supply provision. This is believed to have contributed to reduction in STH infections. Disease diagnosis is very challenging in a rural context where resources may not be adequate but very important for monitoring program progress in the context of integrated control as programs move towards elimination strategy of 2020. Integrated NTD activities can result in improved cost-effectiveness and resource efficiency, where endemic populations overlap and particularly where MDA and disease-specific assessment requirements are somewhat similar. This study has shown that deworming campaigns in Uganda has achieved significant reduction in disease prevalence for STH over the years for example; Significant reductions were observed in prevalence of Hookworm infections in districts that implement MDA for LF Impact of deworming in Uganda alone for example; Bundibugyo (56.8% vs. 27.7%), Mbale (54.1% vs. 6.9%), Kotido (24.7% vs. 0.3%) and Nakapiripirit (12.2% Vs.3.9%). However, there was an increase in STH prevalence observed for Kaliro (16.4% vs. 21.9%) compared to districts that don't have LF. It is interesting to note that children who attended school had a lower risk of STH infection, probably because they were more likely to be dewormed than their counterparts that did not attend school and secondly children in schools are congregated resulting into higher treatment impact in schoolbased deworming. This was observed in similar studies [35].
For districts that are endemic for Lymphatic Filariasis and Onchocerciasis, mass treatment using IVM has been on-going. The use of Ivermectin in the treatment of Onchocerciasis has contributed significantly in the reduction of the burden of soil-transmitted helminths for all districts surveyed in this study except for Mpigi which is neither Lymphatic Filariasis (LF) nor Onchocerciasis program supported district. A number studies [35][36] have shown similar observations where deworming significantly reduces worm burden.
The same study further points out that 17.7% had any type of anaemia, 4.8% had moderate and only 0.6% had severe anaemia and studies have by [37] proved that Antihelminthic treatments are very effective means of improving hemoglobin(Hb) levels although may not be specific to iron deficient anaemia [38]. Our study findings show that awareness and knowledge about soil transmitted helminths has increased unlike in studies by [39] where they observed low awareness and knowledge information among participants for STH.

Challenge to elimination of STH morbidity in Uganda
The target for STH in Uganda is control whereby we aim at eliminating the associated morbidity to levels of no public health importance (WHO 2012 Roadmap for NTDs Implementation towards 2020). Treatment and limited health education alone cannot sustain STH morbidity elimination. The high reproductive capacity of soil transmitted helminthes means that in the absence of additional interventions, transmission cannot be interrupted even if the infection intensity is greatly reduced [40] and this can lead to morbidity recrudescence. There is need for stable provision and use of adequate sanitation facilities to end open defecation, improved personal and food hygiene behavior and access to clean water [41].The Uganda sanitation and water supply have made substantial progress since 1990s especially in urban centers (http://en. wikipedia.0rg/wiki/water). The government with support from multilateral and bilateral agencies, NGOs and the private sector has been vigorously supporting programmes aimed at improving safe water supply for now over 3 decades. In early 1990s, only 10% of urban dwellers were supplied with safe water but the figure had risen to 81% by 2006. However, most households and schools rural areas in Uganda still have inadequate sanitation and safe water supply. When the whole population estimated at 37.5 million people is considered, access to safe water was still just 62% [42] and has improved a little since then.
Despite efforts punt into improving sanitation, it has been accorded low priority with little resources and inadequate collaboration and coordination among stakeholders [43]. According to Ministry of Health records, the national average toilet coverage is still at around 68% but it varies; 80% in urban areas, 60% in rural areas and about 40% in slums [43]. However, latrine coverage in some communities can be as low as 10% especially in fish landing villages [44]. In some rural areas like Karamoja and the Lake Victoria Islands, superstitions against using toilets result in extensive open air defecation [43]. There is almost complete absence of hand washing facilities [43][44] and all these factors promote STH transmission.

Conclusions
The situation as it is today shows reduced levels of STH morbidity. This status cannot be guaranteed unless sanitation issues are well addressed. Without significantly improving WASH, it will be difficult to interrupt STH transmission in most parts of the country. It is also necessary to prioritize operational research agenda that includes NTD monitoring within the local government health sector. Nationally, there is need to monitor STH programme every 5 years to guide the MoH on feasible interventions. Routine evaluations should not be limited to impact on infection rates but should also aim at evaluating impact of the programme on nutrition and educational achievements. This would leverage proper resource allocation and utilization. Combating the burden of STH requires a holistic approach and it should be a responsibility of all stakeholders including the affected communities.