Deworming program for women of reproductive age implemented through national iron folate supplementation program reduces prevalence of anemia: evidence from a community trial in rural Bangladesh

Introduction

Anemia, defined as a hemoglobin concentration below average for the age and sex of the individual is one of the major public health problems in the world. Globally, 1.74 billion are suffering from anemia¹ and its consequences which include, decrease in cognitive and motor development^2–5, loss of economic productivity^6,7 and increased risk of low birth weight, still birth, pre term delivery and prolonged labor for pregnant women^8–10. Children and women of reproductive age (WRA, 15–49 years) are most vulnerable to the consequences of anemia evident from the reported prevalence of 47.4% and 30% for children under 5 and WRAs respectively. Additionally, 42% pregnant women are suffering from anemia. Most of this anemia burden is from low and middle income countries (LMICs) in Africa and Asia¹¹. In Bangladesh, the demographic and health survey 2011 reported that, 51% of 6–59 months old children and 42% of women aged 15–49 years are anemic¹². The government of Bangladesh (GoB) has identified these age groups as high-risk groups and committed to take necessary steps to reduce the burden of anemia among them.

Anemia can be caused by different factors such as deficiency of nutrients including iron, folic acid, vitamin B 12 and vitamin A as well as different types of infections such as soil transmitted helminths, schistosomiasis and malaria¹³. Chronic infections like soil transmitted helminth (STH) infection are an important cause of anemia in tropical and sub-tropical countries, where ecological conditions of these regions allow larval development and poverty, poor water, sanitation and infrastructure to exacerbate this condition by facilitating the spread of the infection. Globally, species of intestinal nematodes that are most important for anemia are Round worm (Ascaris lumbricoides), Whip worm (Trichuris trichiuria) and Hook worm (Ankylostoma duodenale and Necator americanus). These parasites infect humans through contact with parasite eggs or larvae, grow as adult worms and then, can live for years in the human gastrointestinal tract causing chronic infections. Hookworm, which can cause chronic blood loss are the major helminth species responsible for causing anemia. All the helminths cause injury to the mucosa of the small intestine, causing malabsorption and gastrointestinal losses of nutrients such as iron and folic acid resulting in anemia¹⁴.

STHs, though causing anemia, can have serious impacts on health such as, impairment of growth and physical fitness. STH burden also have adverse effects on the future economy and productivity of a country. Studies show that, STH infection causes a reduction in income which can be reversed by deworming^15,16.

The government of Bangladesh (GoB) has taken steps to reduce the burden of helminth infection through the conduction of school-based deworming campaigns twice a year among school children aged 5–12 years since 2007. In this mass drug administration (MDA) campaign, a single dose of Albendazole 400mg tablet is administered to every primary school child irrespective of their infection status. This campaign has seen remarkable success considering the prevalence of decreasing from 80% to 16%¹⁷. However, there is no such campaign for women of reproductive age, who constitute a larger portion of the population and are also more at risk of anemia due to physiological reasons. Due to lack of any nation-wide data on the prevalence of STH infection, the high prevalence of anemia among WRAs in this country indicates that STH infection is also high among this age group.

In absence of any mass deworming program for the WRAs, we conducted a community trial to see the effect of regular deworming on WRAs conducted through an existing government health care delivery system in the rural setting of Bangladesh. We hypothesized that, regular deworming of WRAs would result in reduction of prevalence of anemia among them.

Methods

Results

The study area contained 4789 women aged 15–49 years. Among them, 2438 lived in the intervention arm and the rest (2351) lived in the control arm. Four hundred and fifty-nine WRAs in the intervention arm and 460 WRAs in the control arm comprised the sample for the baseline survey. After two rounds of deworming an end line survey was conducted where 412 and 411 WRAs were enrolled from intervention and control arms respectively (Figure 1). Mean (±SD) age of the participants was 28.93±9.04 and 30.94±9.68 for baseline and end line survey respectively. Socio demographic characteristics of the survey participants are provided in Table 1. The full dataset can be found under Underlying data²⁰.

Figure 1. Study flow chart.

Our intervention period lasted from December 2015 to July 2016, during which we conducted two rounds of deworming four months apart. During the first round, that lasted from December 2015 to March 2016, 82% (2001 out of 2441) women of reproductive age in the intervention arm voluntary attended the community clinics for the deworming drug. During the second round which lasted from April 2016 to July 2016, the compliance rate slightly reduced to 79% (1938 out of 2441).

For hemoglobin concentration, we were able to collect 459 and 460 capillary blood samples during the baseline survey. One participant enrolled in the baseline survey refused to provide capillary blood sample. The prevalence of anemia was 63.6% and 65.7% in the intervention and control arm respectively during the baseline survey. The mean hemoglobin level was 11.5±1.23 and 11.5±1.26 in the control and intervention arm respectively without any statistically significant difference. After two rounds of the deworming program the mean hemoglobin had significantly increased in the intervention arm (11.9±1.26) compared to the control arm (11.5±1.09). During the endline survey, we were able to collect 820 capillary blood samples from 823 enrolled participants, and 3 participants refused to provide blood samples. Prevalence of anemia during the endline survey was also significantly different between the intervention (47.6%) and control arm (63.7%). However, no significant difference in BMI was seen between the intervention and control arm, as a result of the intervention. Details are provided in Table 2.

For measuring the burden of STH infection, we were able to collect 918 stool samples during the baseline survey (out of 919 enrolled participant) and 822 stool samples (from 823 enrolled participants). The species of STH with highest prevalence was Ascaris lumbricoides with the baseline prevalence of 17.9% and 24.1% in the intervention and control arm respectively. After the intervention, the prevalence of A. lumbricoides as well as other species reduced significantly (Figure 2). The intensity of the infection which is expressed as mean eggs per gram also decreased in the intervention arm compared to the control arm (Table 3).

Figure 2. Change in prevalence of different helminths species at baseline and endline in two arms.

The crude difference in differences (DID) calculation was carried out to observe the effect of the intervention package on reduction of anemia and STH infection prevalence at both community and individual level. Table 4 and Table 5 show the level of protection against anemia and STH conferred by our intervention package at both individual and community level. The intervention package reduced anemia by 14% and 11% at community and individual level respectively. Similarly, STH infection were reduced by 16% and 17% respectively.

Discussion

In the absence of any GoB adopted regular deworming program for WRA, we conducted a community trial to test the efficacy of such programs implemented through an existing iron folic acid supplementation program. The successful implementation of our program yielded reduction in prevalence of anemia and STH infection by 14% and 16% respectively.

WHO recommends regular deworming of adolescent as well as WRAs where prevalence of STH is over 20%²¹. While the recommendation is a single dose of Albendazole, we opted for providing the medicine for three successive days, accounting for infection with T. trichiura, as per CDC guideline¹⁸. After the treatment of 2 rounds of deworming, 4 months apart, along with weekly iron folic acid supplementation, prevalence of anemia decreased from 63.6% during baseline to 47.6% during endline, indicating a 25% reduction from baseline. Similar results were observed in a large community trial in Vietnam that showed, from baseline anemia prevalence of 38%, regular deworming and weekly IFA supplementation reduced anemia prevalence to 26% in 3 months²², 19% in 12 months²³, 18% in 54 months²⁴ and 14% in 72 months²⁵ indicating 28%, 50%, 52% and 63% reduction from baseline in 3, 12, 54 and 72 months respectively. Although, our intervention for 8 months yielded lower reduction than the program in Vietnam, it could be simply due to the sheer difference in population size (5,000 compared to 52, 000). Our program also increased mean Hb concentration by 3g/L in the intervention arm which was similar to the 3.5 g/L of the Vietnam study after 3 months²². Another randomized control trial in Peru failed to demonstrate any effect of single dose deworming administered in the post-partum period on maternal anemia after 6 months, although there was significant reduction in risk of STH infection in intervention arm²⁶. This might be due to the fact that, deworming alone has little to no impact on anemia²⁷. However, coupled with IFA supplementation, this culminates in an effective reduction of anemia among WRAs.

Our intervention effective reduced the overall and species-specific prevalence of STH as well as the infection burden expressed as the mean of eggs per gram (EPG). A number of studies^22–25 of similar design in Vietnam looking at the reduction of STH infection reported similar results. Although, in contrast to these studies we did not observe a high prevalence of hookworm infection during the baseline survey in our study, probably due to decreased sensitivity of one sample test especially for hookworms²⁸, the overall decrease in STH infection shows resemblance to these studies. The Vietnamese studies reported a reduction of hookworm prevalence from 76% at baseline to 57%, 30%, 22% and 11% and 10% after 3, 12, 30, 54 and 72 months respectively. At the same time infection with A. lumbricoides and T. trichiura was also reduced from 19% and 29% at baseline respectively to 1.4% and 2.3% to endline respectively^22–25. The Peruvian study also experienced a significant decrease in risk of infection from all STH species. The study showed single dose albendazole confers decreased risk of infection by 50% for Ascaris, 40% for Trichuris and 90% for hookworm infection²⁶. The lowest risk reduction in Trichuris justifies the requirement of multiple doses for complete elimination.

It is well known that, in spite of their efficacy, the protection conferred by preventive chemotherapy is very short lived. A meta-analysis showed that within six months after treatment 68% become re-infected with Ascaris, 67% with Trichuris, and 55% with hookworm²⁹. This requires arrangement of deworming campaigns at regular intervals. Bangladesh has seen a lot of success in deworming school children through school-based mass deworming programs. However, reaching adolescent girls and WRAs for such campaigns is a tangible challenge recognized by WHO²¹. Therefore, our utilization of the existing healthcare system of distributing IFA among such populations is undoubtedly a novel solution. The health setups we have used for this project serve 6000–8000 of the population in the rural area and our project showed that, this setup can be effectively used to piggyback this important public health campaign that results in reduction in anemia and STH burden among WRAs. The fact that drug distribution was carried out by the existing government healthcare workforce indicates the sustainability of this approach. Our program enjoyed encouraging compliance in the first round which reduced a little during the second round. However, studies in similar context have shown increased compliance of 76% and 72% in 54 and 72 months respectively to weekly iron-folate supplementation (WIFS) as well as 95% and 85% to preceding deworming drug administrations in 54 and 72 months respectively^24,25. This indicates that same level of compliance can be replicated in the context of Bangladesh. Such campaigns would also be cost effective to reduce helminth burden in the community as proved by cost effectiveness analysis of the Vietnamese program³⁰.

This study was conducted in a small community of a sub-district in Bangladesh where homogeneity of the population was very prominent. The timeline of the intervention was only 14 months. So the long term effect of the intervention could not be estimated through this project.

Our study clearly showed that existing health setups can be utilized effectively to incorporate a deworming campaign for WRAs and thus scale up of the national deworming program for successful elimination of STH. Future endeavors should focus on replicating the same efficacy in a large-scale trial, determining the cost effectiveness and exploring the barriers to compliance to the program. The efforts would yield valuable evidence and, together with the evidence from the present study, would encourage policy makers to incorporate the program of deworming WRAs into national policy that would lead to successful elimination of STH in Bangladesh and similar contexts.