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Relationship of Intestinal Parasites, H. Pylori Infection with Anemia or Iron Status Among School age Children in Rural Bangladesh

Ahmed S Rahman, Shafiqul A Sarker, Tahmeed Ahmed, Rafiqul Islam, Mohammad A Wahed, David A Sack

Ahmed S Rahman, Shafiqul A Sarker, Tahmeed Ahmed, Mohammad A Wahed, Centre for Nutrition and Food Security; International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b); Mohakhali, Dhaka1212, Bangladesh
Rafiqul Islam, School of Medicine and Public Health, University of Newcastle, Australia
David A Sack, Johns Hopkins University Bloomberg School of Public Health. Baltimore, Maryland, the United States

Correspondence to: Ahmed S Rahman, PhD, Centre for Nutrition and Food Security; International Centre for Diarrhoeal Diseases Research, Bangladesh; Mohakhali, Dhaka-1212,
Bangladesh. ashafiq@icddrb.org
Telephone:+880-2-9840523-32
Fax:+880-2-9885657
Received: May 20, 2013
Revised: July 17, 2013
Accepted: July 20, 2013
Published online: September 21, 2013

ABSTRACT

AIM: To investigate an association of intestinal parasites or Helicobacter pylori infection with hemoglobin, anemia or iron status among rural school aged children in Bangladesh.

METHODS: Data and specimens from a controlled trial among children aged 6-15 years old to assess the nutritional impact of fortified flour were used to carry out this additional analysis on factors which effect anemia. Stool samples from 310 children were collected at the end of the trial and were tested for Helicobacter pylori stool antigen and intestinal parasites. Data on hematological parameters were obtained from endline measurements of the trial.

RESULTS: The overall prevalence of parasitic infection was 84% among children with the highest prevalence for Ascaris (71%) followed by Trichuris (67%) and Hookworm (31%). The prevalence of Helicobacter pylori infection was 39.7%. A total of 26.8% children were anemic, while low iron status as defined by a low serum ferritin (<20 μg/L) or elevated transferrin receptor (>5.0 mg/L) respectively was present in 18% and 11% of the children. No statistically significant association was found between Helicobacter pylori or any intestinal parasites and hemoglobin concentration, anemia or iron status among the children. However, there was a significant association between low hemoglobin concentration and low iron status based on serum ferritin (Coefficient: -0.28, 95% CI -0.54, -0.03) or transferrin receptor level (Coefficient: -0.89, 95% CI -1.18, -0.59) as well as anemia and low iron status based on serum transferrin receptor (OR 3.57; p<0.01).

CONCLUSION: Our results are in line with other studies from developing countries that showed no significant association between intestinal parasites or Helicobacter pylori infection and anemia, hemoglobin or iron status.

Key words: Anemia; Helicobacter pylori; intestinal parasites; school age children; rural Bangladesh

© 2013 The Authors. Published by ACT Publishing Group Ltd.

Rahman AS, Sarker SA, Ahmed T, Islam R, Wahed ma, Sack DA. Relationship of Intestinal Parasites, H. Pylori Infection with Anemia or Iron Status Among School age Children in Rural Bangladesh. Journal of Gastroenterology and Hepatology Research 2013; 2(9): 769-773 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/480

Introduction

Anemia is still a major public health problem in many developing countries. The World Health Organization (WHO) Global Database on Anemia for 1993-2005 showed that 25% or 1.62 billion people globally suffer from anemia with the highest number of 315.4 million in South-East Asia region[1]. Iron deficiency anemia (IDA) during pregnancy increases the risk of death in mothers and neonates during perinatal period. Globally, more than 115000 maternal deaths and 591000 perinatal deaths per year are attributable to anemia[2]. Evidence indicates that IDA delay psychomotor development and impairs cognitive performance in children as well as reduces work capacity and productivity in adult life[3]. In Bangladesh, over one third of the school-age children (5-11 years) or adolescents (12-19 years) were anemic, some of which is due to iron deficiency[4].

Low dietary intake of bioavalable iron is assumed to be a major cause of anemia in the developing world. Dietary iron consumed in resource poor areas is predominantly non-heme iron of plant origin, containing high amounts of inhibitors of iron absorption such as phytate[5]. In addition to low iron bioavailability from the diet, the high prevalence of infections and other nutritional deficiencies in developing countries can also contribute to the development of anemia. The WHO estimated that there were 1billion cases of Ascaris lumbricoides, and half a billion cases of Trichuris trichiura infection worldwide[6]. Blood loss caused by gastrointestinal parasites, such as hookworm, is considered to be an important contributing factor in the development of poor iron status leading to iron deficiency anemia[7]. More recently, another common infection, Helicobacter pylori, has been discussed in the etiology of anemia and IDA[8-11].

H. pylori is a common gastrointestinal pathogen world-wide with a very high prevalence in many developing countries. For example, data from India shows that the frequency of H. pylori infection can be more than 80% by age 20 years[12], and a study in Bangladesh reported an overall 68% prevalence of H. pylori infection in infants and children[13]. Once established, H. pylori infection is thought to persist life resulting in chronic gastritis, which is a risk factor for development of atrophic gastritis, reduced gastric acid output[14], and gastric cancer[15]. Gastric acid is considered to be one of the most important luminal factors necessary for optimal non-heme iron absorption[16]. Thus, it is possible that H. pylori infections can result in a reduced ability to absorb iron due to gastric atrophy and achlorhydria, or due to a more transient hypochlorhydria during active infections. Both mechanisms would result in an increased susceptibility to IDA. Pervasive occult gastrointestinal bleeding as a result of chronic active gastritis has also been considered as a cause for iron deficiency anemia in H. pylori infected subjects[17]. Besides its involvement in the etiology of IDA, infection with H. pylori has been reported to be linked with therapeutic failure of oral iron therapy in children and adolescent girls with IDA[18, 19].

Food fortification with micronutrients is one strategy to address nutritional deficiencies in populations with access to fortified food products. We conducted a double-blind controlled trial during 2002 in a rural area of Bangladesh to investigate the efficacy of wheat flour chapatti (round flat bread) fortified with multiple micronutrients including vitamin A and iron in improving vitamin A and anemia or iron status in healthy, school aged children, many of whom had subclinical anemia[20]. Unfortunately the hemoglobin and iron status of those receiving the fortified product did not improve. Because of this lack of improvement, we assessed the potential role of other factors which could reduce the effectiveness of the fortified food, namely coinfection with intestinal parasites and/or H. pylori. Thus the primary objective of this exploratory study was to investigate an association of intestinal parasites or H. pylori infection with hemoglobin, anemia or iron status among school aged rural Bangladeshi children who participated in the chapatti fortification trial for the total duration of 6 months. Secondarily, this study also explored the relationship between iron status with hemoglobin and anemia status among school aged children. Younger children were not included in this study because younger children receive vitamin A capsules regularly through national programs.

METHODS

Design, setting and study population

This cross-sectional study was carried out in October 2002 in Mirsarai, a rural sub-district in the district of Chittagong located in the south-eastern part of Bangladesh, among children 6-15 years of age (n=334) who participated for 6 months in the efficacy trial of wheat flour chapatti. In the trial, either unfortified or fortified wheat flour was provided to clusters for families to prepare chapattis to the children each day. The fortified flour had added multiple micronutrients including vitamin A, 3030 μg retinol equivalent as retinyl palmitate and 66 mg hydrogen reduced elemental iron per Kg of flour. Children inthe efficacy trial, were enrolled from 43 Baris (clusters, composed of ~5-6 households per Bari), randomly selected from the total list of Baris (n=4875) in the study area. Stool samples were collected from 310 children from 42 Baris at the end of the efficacy trial and investigated for H. pylori antigen and intestinal parasites.

In the present study, data on hemoglobin concentration, serum ferritin and transferrin receptor concentrations and child characteristics were obtained from final measurements of the efficacy trial. A child was considered anemic when the hemoglobin level was lower than 120 g/L and 115 g/L for 12-15 and 6-11 years old children respectively. They were considered to have low iron status when serum ferritin level was lower than 20 µg/L or serum transferrin receptor level >5 mg/L.

Ethical approval

The study was approved by the institutional review board of International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b). Before enrolment in the study, a written informed consent was obtained from parents and assent from children more than 8 years old.

Screening of Helicobacter pylori infected children

A qualitative enzyme immunoassay test for H. pylori stool antigen (HpSA) was used for the detection of H. pylori antigens in stool (Premier Platinum HpSA, Meridian Diagnostic Inc, Cincinnati, Ohio, USA). The test was found to be highly sensitive (95%) and specific (95%) against the conventional urea breath test (UBT) and gastric mucosal biopsy[21,22]. Stool samples were transported to Dhaka and the tests was carried out according to the manufacterer’s direction at the icddr, b laboratory.

Screening for ova/parasite

Stool parasites were detected by the formalin-ether concentration technique[23]. A day before the stool sample collection, a container was distributed to the mothers/caretakers, and they were instructed on how to collect a stool sample and to make sure the specimen was not contaminated with soil or dirt. The specimens were taken within an hour after collection to the research station at Mirsarai where 1.0 to 1.5 g sample was preserved in 9 mL of 10% formalin and kept in room temperature. The samples were transported to the Parasitology Laboratory of icddr, b at Dhaka where they were examined by experienced technicians for the detection of Ascaris lumbricoides, Trichuris trichiura and hookworm.

Statistical analysis

Data were entered into SPSS version 10.0 (SPSS Inc., Chicago IL, USA) and analyzed using STATA version 12.0 (Stata Corporation, 4905 Lakeway Drive, College Station, Texas, USA). Univariate analysis was used to find the mean and prevalence of selected variables along with confidence intervals. Body weight and height measurements were converted to height-for-age z-score using WHO AnthroPlus 2007, v 1.0 software. To explain an association of intestinal parasites or H. pylori infection with anemia, hemoglobin or iron status indicators; and association of iron status indicators with anemia and hemoglobin concentration, regression analyses were done with adjustment of child’s sex and age. All the analyses were performed considering the cluster (Bari) effect. The level of significance was set at p value <0.05.

RESULTS

After the completion of the trial, of the 334 children, stool samples were collected from 310 (93%) children. Characteristics of the study children are presented in table 1. The mean hemoglobin concentration was 12.28 g/dL and 26.8% of the children were anemic where as, 18% and 11% children had low iron status based on serum ferritin and transferrin receptor level respectively.

Table 2 shows the prevalence of intestinal parasites and H. pylori infection among the children. The overall prevalence of parasitic infection was almost 84% with the highest prevalence for Ascaris (71%) followed by Trichuris (67%). Hookworm infection was present in 31% of the children. Thirty nine percent of the children were infected with H. pylori infection.

Tables 3 and 4 show the results of regression analyses. There was no statistically significant association between infection with any of the intestinal parasites or H. pylori infection and anemia (Table 3), hemoglobin concentration (data not shown) or low iron status (Table 4). However, a statistically significant association was found between low hemoglobin concentration and low iron status based on both serum ferritin (Coefficient: -0.28, 95% CI -0.54, -0.03; p < 0.05) and transferrin receptor level (Coefficient: -0.89, 95% CI -1.18, -0.59; p < 0.01). Also, the odds of anemia was significantly higher for children with low iron status based on transferrin receptor level (Table 3).

DISCUSSION

The prevalence of both anemia and parasitic infection was high among children in this rural setting of Bangladesh. In the present study, we found an association of low hemoglobin with low iron status based on both serum ferritin and transferrin receptor level and anemia with low iron status based on serum transferrin receptor however, could not detect an association of parasitic infection with anemia, hemoglobin or iron status.

Our results differ with other studies that reported a significant association of intestinal parasites such as, Ascaris[24], Trichuris[24-26], and hookworm[27-29], with anemia or low iron status. The results also partly contradict with the previous study conducted in Bangladesh among school children that reported a significant impact of hookworm but not Ascaris on iron status[28].

A growing body of evidence supports a clinically significant influence of H. pylori infection on body iron stores. Despite studies supporting the role of H. pylori infection in the development of iron deficiency anemia[30-33], some studies from developing countries failed to find such an association[34-36]. A recent report from Bangladesh also concluded that H. pylori was neither a cause of IDA, iron deficiency nor a reason for treatment failure of iron supplementation in young Bangladeshi children[37]. Our results are in line with these studies that documented no statistically significant association of H. pylori infection with anemia or low iron status[34-37].

Overall, our results suggested that the presence of anemia and low iron status in rural Bangladeshi children might be contributed by many factors together. Populations in less developed countries are frequently susceptible to deficiency of various micronutrients needed for hemoglobin synthesis other than iron. These may include folic acid, vitamin B12, vitamin A and low protein intake from poor quality diet. Therefore, apart from geohelminth infections and H. pylori; other infections, inadequate bio-available iron, folic acid, vitamin B12, vitamin A as well as low protein intake from poor quality diet might have contributed to the development of anemia or low iron status among these children. Thus the role of H. pylori in IDA is less likely to be obvious in less developed countries in contrast to other populations which have shown a link with H. pylori infection and anemia/IDA.

In this study most children were younger when compared to other studies where the patients were adolescent or adults in whom the histological damage in the stomach likely to be more pronounced. The observed lack of an effect in iron absorption by H. pylori as observed in young Bangladeshi children[36], supports the notion that H. pylori has no link with IDA/ anemia may also be related to the presence of subclinical infection by other organism competing with for iron uptake resulting the role of H. pylori less overt in causing IDA or anemia in underprivileged population.

CONCLUSION

The present study showed no significant association of intestinal parasites or H. pylori infection with hemoglobin, anemia or iron status in rural Bangladeshi school aged children with high burden of the infection and supports other studies from developing countries with similar findings.

ACKNOWLEDGMENTS

This study was supported by grants from icddr, b core research funds. The authors are grateful to all the study participants. Dr. Ahmed S Rahman was involved in the study concept, design, conduction, data analyses, and writing of the manuscript; Drs. Shafiqul A Sarker, Tahmeed Ahmed and David A Sack, and Mohammad A Wahed were involved in the study concept, design and writing of the manuscript; and Dr. Rafiqul Islam was involved in analyses and manuscript writing. None of the authors has any conflict of interest or any financial interest.

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Peer reviewers: Petar Ivanovski MD, PhD, Associate Professor of Pediatrics, subspecialist of hematology, General Pediatrics, University Children`s Hospital Medical Faculty University of Belgrade, 10 Tirshova str. 11000, Belgrade, Serbia.

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