Pregnancy, Children and Inter-Relating Factors Affected by Geohelminthiasis

*Asher John Mohan, Neeraj Upmanyu and Silviya Sarah Lal*

## **Abstract**

A life-threatening parasitic infection arising in evolving countries, principally prevalent in children below 5 years and pregnant women, has led to the growing interest for understanding the condition acknowledged as geohelminthiasis. Decreased cell-mediated immunity (a necessity in fetal retention) leading to a compromised immunological response is what makes pregnant women more prone to the infection thereby increasing the risk of maternal anemia, preterm deliveries and stillbirths based on reports. An outcome of geohelminthiasis on children is its deteriorative effect on cognition. This chapter highlights the relationship between the helminthic infection with respect to pregnant women and children additionally focusing on other associated factors such as poverty, hygiene, etc. that further contribute to the decline in quality of life in developing countries.

**Keywords:** geohelminthiasis, cell-mediated immunity, cognition, pregnancy, parasitic infection

### **1. Introduction**

The general term used to describe a worm is referred to as a "helminth." These invertebrates fall under two categories, namely flatworms or Platyhelminthes (flukes and tapeworms) and roundworms or Nematoda [1, 2]. They either survive in aquatic and terrestrial environments as parasites or free of a host. Out of the various types, intestinal nematodes or soil-transmitted helminths (STH) also known as "Geohelminths" are the most common worldwide. The World Health Organization (WHO) claims that 1.5 billion people worldwide, constituting to 24% of the world's population, are infected by STH; with wide distributions in the Sub-Saharan Africa, America, China and East Asia in tropical and subtropical regions [3].

The major infection of STH originates from the attack of *Ascaris lumbricoides* (commonly called the large intestinal roundworm or the common roundworm) and *Trichuris trichiura* (whipworm) [4, 5]. Hookworm (Ancylostomatidae) affliction is also another most common chronic infection found in humans that contribute to STH [6].

Children are the frequent victims to an STH attack as many of them are school aged, living in areas of extensive disease transmission; requiring treatment interventions and preventive measures [7]. Secondary victims of this infection are pregnant women reported every year, among which 44 million are estimated to be affected globally [8]. Improvements in potable water services, drainage, sanitary food control,

#### *Helminthiasis*

living quarters, individual and community anti-vector action are a few conceptualizations that can be implemented for the eradication of this infectious outbreak [9].

The central focus of this chapter is to gain insight into as to how aspects of childhood and pregnancy are concomitant to geohelminthiasis, along with various other inter-relating factors such as poverty, hygiene, etc.; that cause a drop in the quality of life in developing countries.

### **2. Immune responses to STH**

Preclinical data from animals suggest that th2 (T-helper) cells are triggered by cytokine release along with immunoglobulin E (IgE) of the host immune system aiding in the elimination of helminthic burdens [10, 11]. However, the innate and adaptive immunity are often markedly found to remain suppressed. This indicates that immune responses triggered due to a helminthic infection could result in host protection responses against microbial pathogens to be antagonized [12, 13]. Recent findings of the involvement of macrophages referred to as alternatively activated macrophages can also be a contributing factor leading to an inflammatory response when in contact with a helminth [14].

### **3. Children and geohelminthiasis**

School children of countries affected by this epidemic, were found to exhibit the greatest incidence and severity of the outbreak. No ill effects (with respect to morbidity) were thought to be experienced by children with light infections. However, recent evidences oppose this traditional notion with reports of slight or minimal intensity outbreaks having significant decrement in the development and growth of children [15]. Information regarding as to how various factors affect geohelminthiasis in children is discussed below.

#### **3.1 Nutrition**

Nutrition plays a key role as a target for the alleviation of helminthic infections. Several surroundings of the developing world are impacted by malnutrition and helminthic infection, both as their main or supplementary factors governing mortality [16]. Impaired digestion, malabsorption, diminution in food consumption and poor growth rates are often noted in children who endure this helminthic incursion [17]. Recent studies also depict the fact that malnutrition is in direct proportion to the intensity of the pathogen Ascaris [18]. Other factors governing infection scale include the extent of nutritional deficiency and concurrent prominence of single or multiple infections and single or multiple nutritional deficiencies [19]. Increased loss of endogenic protein paired with the distress of energy and mineral metabolism are the mechanisms by which an intestinal nematode reduces feed intake by the host. Better nutrition can improve the rate of adult worm rejection via an approach of diet consumption rich in metabolizable proteins [20].

The improvement of the nutritional status of school children would be an essential remedy for disease alleviation [21, 22].

#### **3.2 Environment**

The environmental variables attributing to the risk of this parasitic outbreak cannot be avoided as a correlation between this aspect and disease condition is of high prevalence.

**13**

*Pregnancy, Children and Inter-Relating Factors Affected by Geohelminthiasis*

not exposed to drugs and the possibility of underdosing [24].

classrooms can be taken into consideration for disease management [23].

Since the primary mode of therapy includes the use of anti-helminthics, development of resistance due to their administration is a crucial factor governing geohelminthiasis. The known variables that add value to an anti-helminthic resistance are medication frequency, refuge or the percentage in the parasite population

Another causative factor in children leading to intestinal obstruction observed was prior anti-helminthic treatment [25]. Although specific IgE antibodies are believed to participate in the protection against helminthic infection, the polyclonal stimulation of IgE caused by helminthic parasites could be the sole reason for re-infection [26]. In a follow-up investigation concerning growth retarded children where anti-helminthic therapy was discontinued after successful alleviation; the extent of re-infection was found to dramatically increase which could pose diffi-

The negative influence of STH infections on cognitive processes, notably in school children; has been deduced by researchers since 1900. Prolonged anemia and toxemia were factors accountable for the substantial increase in the degree of cognitive delay with respect to the level of infection. However, clarification remains to be produced regarding the mechanism by which worms impact cognition. Certain postulates comprise of malnutrition and fatigue in children troubled from the infection as consequences of diminished cognition. Reports of medication reversing this adverse effect are also at large and very much essential for effective control of

Helminthic infections are suggested to be extremely damaging, with detrimental effects on maternal anemia and birth outcomes in cases of pregnancy, with a total

A characteristic feature of pregnancy is the successful retention of the fetus due to hormonal, dietary and immunological changes occurring during the period [33]. This is a unique illustration of how the body adjusts to a destructive immune response during pregnancy [34]. Therefore, studies have clearly defined the characteristic of pregnancy as immune modulation and not its suppression. In other words, an alteration to the immune system contributes to differential responses not merely on the basis of microorganisms but on the basis of stage of pregnancy [35]. Although the periparturic immunosuppression involvement remains unclear, one of the proposed mechanism depicts the avoidance of particular processes of host immune defense by the parasitic helminth [36, 37]. The resemblance between the immune reactions to helminths and pregnant females may be a sign

global impact on pregnancies estimated to be 44 million [31, 32].

**4.1 Probable mechanism of susceptibility to STH in pregnancy**

Recent studies of various schools reporting the presence of certain other influential environmental factors governing the infection such an inadequate water supply, requirement of regular water/sanitation maintenance regimes and overcrowding in

*DOI: http://dx.doi.org/10.5772/intechopen.86925*

**3.3 Anti-helminthic treatment in children**

culty in the quality of life of the concerned [27].

**3.4 Cognition**

the disease [28–30].

**4. Pregnancy and geohelminthiasis**

Recent studies of various schools reporting the presence of certain other influential environmental factors governing the infection such an inadequate water supply, requirement of regular water/sanitation maintenance regimes and overcrowding in classrooms can be taken into consideration for disease management [23].

## **3.3 Anti-helminthic treatment in children**

Since the primary mode of therapy includes the use of anti-helminthics, development of resistance due to their administration is a crucial factor governing geohelminthiasis. The known variables that add value to an anti-helminthic resistance are medication frequency, refuge or the percentage in the parasite population not exposed to drugs and the possibility of underdosing [24].

Another causative factor in children leading to intestinal obstruction observed was prior anti-helminthic treatment [25]. Although specific IgE antibodies are believed to participate in the protection against helminthic infection, the polyclonal stimulation of IgE caused by helminthic parasites could be the sole reason for re-infection [26]. In a follow-up investigation concerning growth retarded children where anti-helminthic therapy was discontinued after successful alleviation; the extent of re-infection was found to dramatically increase which could pose difficulty in the quality of life of the concerned [27].

### **3.4 Cognition**

*Helminthiasis*

of life in developing countries.

**2. Immune responses to STH**

when in contact with a helminth [14].

**3. Children and geohelminthiasis**

sis in children is discussed below.

of diet consumption rich in metabolizable proteins [20].

essential remedy for disease alleviation [21, 22].

**3.1 Nutrition**

living quarters, individual and community anti-vector action are a few conceptualizations that can be implemented for the eradication of this infectious outbreak [9].

The central focus of this chapter is to gain insight into as to how aspects of childhood and pregnancy are concomitant to geohelminthiasis, along with various other inter-relating factors such as poverty, hygiene, etc.; that cause a drop in the quality

Preclinical data from animals suggest that th2 (T-helper) cells are triggered by cytokine release along with immunoglobulin E (IgE) of the host immune system aiding in the elimination of helminthic burdens [10, 11]. However, the innate and adaptive immunity are often markedly found to remain suppressed. This indicates that immune responses triggered due to a helminthic infection could result in host protection responses against microbial pathogens to be antagonized [12, 13]. Recent findings of the involvement of macrophages referred to as alternatively activated macrophages can also be a contributing factor leading to an inflammatory response

School children of countries affected by this epidemic, were found to exhibit the greatest incidence and severity of the outbreak. No ill effects (with respect to morbidity) were thought to be experienced by children with light infections. However, recent evidences oppose this traditional notion with reports of slight or minimal intensity outbreaks having significant decrement in the development and growth of children [15]. Information regarding as to how various factors affect geohelminthia-

Nutrition plays a key role as a target for the alleviation of helminthic infections. Several surroundings of the developing world are impacted by malnutrition and helminthic infection, both as their main or supplementary factors governing mortality [16]. Impaired digestion, malabsorption, diminution in food consumption and poor growth rates are often noted in children who endure this helminthic incursion [17]. Recent studies also depict the fact that malnutrition is in direct proportion to the intensity of the pathogen Ascaris [18]. Other factors governing infection scale include the extent of nutritional deficiency and concurrent prominence of single or multiple infections and single or multiple nutritional deficiencies [19]. Increased loss of endogenic protein paired with the distress of energy and mineral metabolism are the mechanisms by which an intestinal nematode reduces feed intake by the host. Better nutrition can improve the rate of adult worm rejection via an approach

The improvement of the nutritional status of school children would be an

The environmental variables attributing to the risk of this parasitic outbreak cannot be avoided as a correlation between this aspect and disease condition is of high prevalence.

**12**

**3.2 Environment**

The negative influence of STH infections on cognitive processes, notably in school children; has been deduced by researchers since 1900. Prolonged anemia and toxemia were factors accountable for the substantial increase in the degree of cognitive delay with respect to the level of infection. However, clarification remains to be produced regarding the mechanism by which worms impact cognition. Certain postulates comprise of malnutrition and fatigue in children troubled from the infection as consequences of diminished cognition. Reports of medication reversing this adverse effect are also at large and very much essential for effective control of the disease [28–30].

## **4. Pregnancy and geohelminthiasis**

Helminthic infections are suggested to be extremely damaging, with detrimental effects on maternal anemia and birth outcomes in cases of pregnancy, with a total global impact on pregnancies estimated to be 44 million [31, 32].

#### **4.1 Probable mechanism of susceptibility to STH in pregnancy**

A characteristic feature of pregnancy is the successful retention of the fetus due to hormonal, dietary and immunological changes occurring during the period [33]. This is a unique illustration of how the body adjusts to a destructive immune response during pregnancy [34]. Therefore, studies have clearly defined the characteristic of pregnancy as immune modulation and not its suppression. In other words, an alteration to the immune system contributes to differential responses not merely on the basis of microorganisms but on the basis of stage of pregnancy [35].

Although the periparturic immunosuppression involvement remains unclear, one of the proposed mechanism depicts the avoidance of particular processes of host immune defense by the parasitic helminth [36, 37]. The resemblance between the immune reactions to helminths and pregnant females may be a sign

#### *Helminthiasis*

that tolerance may be invoked by analogous mechanisms (i.e., type 2 responses). Another suggestion has been that helminths may have undergone self-adaptation in order to combat immune responses from the mother by utilizing the similarity in mechanisms as used by a human fetus [38]. These could have been some among the many reasons a pregnant mother's susceptibility to helminthic attack is widespread.

The WHO reports that far more than half of the pregnant females in emerging economies have concerns pertaining to iron deficiency anemia, which could be a result of an elevated metabolic requisite for iron during childbirth coupled with poor nutrition. This iron STH related deficiency has been concomitant to augmented mortality rate, premature birth and low birth weights during the period of pregnancy [39, 40].

#### **4.2 Co-infection**

Considering pregnancy, the susceptibility to co-infections cannot be ignored due to immunological modulations associated with the stage. Data indicating the exhibition of higher prevalence of *Trichuris trichiura*, followed by an *Ascaris lumbricoides* infection were found in cases of pregnancy; where attacks of a single infection was found to be at a higher percent than that of co-infections [41]. Considering co-infections associated with pregnancy related STH, it was found that the malarial parasite *Plasmodium falciparum* co-existed with hookworms, when compared to roundworms and whipworms [42, 43].

#### **4.3 Geophagy (soil eating)**

Another causal component for STH diseases is geophagy that is practiced among some African females. While the exact reason remains a mystery, some beliefs such as curing heartburn and alleviating morning sickness are still at large [44]. Adequate data indicates that geophagy can be associated with enhanced anemic peril and reduced hemoglobin amounts [45]. Geophagy in lactating mothers resulted in reinfection and hence was advised for immediate interventions to tackle disease transmission [46].

#### **4.4 Maternal anemia**

The greater the severity of hookworm infestations, the greater was the percentage of blood loss or anemia observed in pregnant women from an endemic area survey [47]. During pregnancy, the hookworm, in particular, was considered to be the source of mild associative anemia while the other STH's were involved in mild deficiencies of iron [48, 49]. A current connection between co-infection and anemia, as reported in the latest studies indicate that the latter is not a sole companion of helminthic attack alone [50].

Since there is an additional relationship between anemia and birth outcomes (increased risk of preterm birth or low birth weight), a helminthic outbreak could also be affiliated to the second during pregnancy [51]. All the above findings indicate that the association of anemia due to STH can be debilitating in case of pregnant women.

#### **4.5 Birth outcomes**

The reason for the problem of low birth weight was the exposition to an attack of hookworm resulting in intrauterine growth retardation especially in cases of HIV infected subjects [52]. A lower prevalence of low birth weight was the end result of

**15**

*Pregnancy, Children and Inter-Relating Factors Affected by Geohelminthiasis*

factor contributing to the development of such illnesses [55, 56].

options are a must to curb disease morbidity [59].

**6. Other inter-relating factors**

ing to an attack of STH [60–63].

**7. Conclusion**

periodic anti-helminthics and the weekly iron folic acid supplements before pregnancy [53]. Another birth outcome experienced was the premature birth. Similar to the case of maternal anemia, the co-existence of other infections with STH brought

Although helminthic infections are difficult for kids and for pregnant females, the asymptomatic stage in an helminthic infection was found act as a guard keeper against immunological syndromes [54]. An unusual, inflammatory bowel disease (characterized by chronic gastrointestinal inflammation) hygiene hypothesis suggests a lack of exposure to intestinal helminths as an important environmental

The possibility of predisposition to Crohn's disease (an inflammatory idiopathic

All the above discussed variables associated with children and pregnant women are also dependent on conditions of on geographical circumstances, poverty and bad hygiene. The STH assault is restricted to rural regions of tropics, especially in coastal regions; where temperature, humidity and soil type are appropriate for development and growth. Exposure to larval eggs in farming areas where individuals expose their skin to the hot and humid soil is what aids in disease transmission. Sandy soils provide better growth conditions for these worms when compared to clayey soils. An important adverse link between socioeconomic status and incidence or severity of helminthic disease can also attribute towards the spread of STH. It was found that the prevalence of disease was less in cases of higher income groups. Bad sanitation or hygiene due to the lack of income is also an associated factor lead-

Geohelminthiasis or soil-transmitted helminthiasis is recognized as a lifethreatening parasitic outbreak in developing nations, predominantly in kids under 5 years of age and pregnant females and has resulted to increased concern. Reports of nutrition, environment, resistance to treatment and cognition were the associative parameters found in children, whereas in the condition of pregnancy existence of co-infections, geophagy, maternal anemia and birth outcomes were found to be the inter-relating variables to STH. The avoidance of particular processes of host immune defense and self-adaptation to combat immune responses from the mother by utilizing the similarity in mechanisms as used by a human fetus were the proposed mechanisms by which pregnant women are more prone to the attack. All the associative parameters discussed above were found to increase disease burden. Tackling these factors is therefore a must for achieving an improved quality of life.

bowel disease, most often involving the ileum, colon and in certain cases; the esophagus) due to lack of exposure to helminthic parasites as per data of a certain study [57, 58]. A similar small cross-sectional study showed the prevalence of STH to have beneficial effects in patients with type 2 diabetes (insulin resistant). However, this may seem to be damaging in areas where helminthic treatment

*DOI: http://dx.doi.org/10.5772/intechopen.86925*

about a greater negative birth outcomes.

**5. Present beneficial hypotheses**

periodic anti-helminthics and the weekly iron folic acid supplements before pregnancy [53]. Another birth outcome experienced was the premature birth. Similar to the case of maternal anemia, the co-existence of other infections with STH brought about a greater negative birth outcomes.

## **5. Present beneficial hypotheses**

*Helminthiasis*

pregnancy [39, 40].

roundworms and whipworms [42, 43].

**4.3 Geophagy (soil eating)**

disease transmission [46].

of helminthic attack alone [50].

**4.4 Maternal anemia**

pregnant women.

**4.5 Birth outcomes**

**4.2 Co-infection**

that tolerance may be invoked by analogous mechanisms (i.e., type 2 responses). Another suggestion has been that helminths may have undergone self-adaptation in order to combat immune responses from the mother by utilizing the similarity in mechanisms as used by a human fetus [38]. These could have been some among the many reasons a pregnant mother's susceptibility to helminthic attack is widespread. The WHO reports that far more than half of the pregnant females in emerging economies have concerns pertaining to iron deficiency anemia, which could be a result of an elevated metabolic requisite for iron during childbirth coupled with poor nutrition. This iron STH related deficiency has been concomitant to augmented mortality rate, premature birth and low birth weights during the period of

Considering pregnancy, the susceptibility to co-infections cannot be ignored due to immunological modulations associated with the stage. Data indicating the exhibition of higher prevalence of *Trichuris trichiura*, followed by an *Ascaris lumbricoides* infection were found in cases of pregnancy; where attacks of a single infection was found to be at a higher percent than that of co-infections [41]. Considering co-infections associated with pregnancy related STH, it was found that the malarial parasite *Plasmodium falciparum* co-existed with hookworms, when compared to

Another causal component for STH diseases is geophagy that is practiced among

The greater the severity of hookworm infestations, the greater was the percentage of blood loss or anemia observed in pregnant women from an endemic area survey [47]. During pregnancy, the hookworm, in particular, was considered to be the source of mild associative anemia while the other STH's were involved in mild deficiencies of iron [48, 49]. A current connection between co-infection and anemia, as reported in the latest studies indicate that the latter is not a sole companion

Since there is an additional relationship between anemia and birth outcomes (increased risk of preterm birth or low birth weight), a helminthic outbreak could also be affiliated to the second during pregnancy [51]. All the above findings indicate that the association of anemia due to STH can be debilitating in case of

The reason for the problem of low birth weight was the exposition to an attack of hookworm resulting in intrauterine growth retardation especially in cases of HIV infected subjects [52]. A lower prevalence of low birth weight was the end result of

some African females. While the exact reason remains a mystery, some beliefs such as curing heartburn and alleviating morning sickness are still at large [44]. Adequate data indicates that geophagy can be associated with enhanced anemic peril and reduced hemoglobin amounts [45]. Geophagy in lactating mothers resulted in reinfection and hence was advised for immediate interventions to tackle

**14**

Although helminthic infections are difficult for kids and for pregnant females, the asymptomatic stage in an helminthic infection was found act as a guard keeper against immunological syndromes [54]. An unusual, inflammatory bowel disease (characterized by chronic gastrointestinal inflammation) hygiene hypothesis suggests a lack of exposure to intestinal helminths as an important environmental factor contributing to the development of such illnesses [55, 56].

The possibility of predisposition to Crohn's disease (an inflammatory idiopathic bowel disease, most often involving the ileum, colon and in certain cases; the esophagus) due to lack of exposure to helminthic parasites as per data of a certain study [57, 58]. A similar small cross-sectional study showed the prevalence of STH to have beneficial effects in patients with type 2 diabetes (insulin resistant). However, this may seem to be damaging in areas where helminthic treatment options are a must to curb disease morbidity [59].

## **6. Other inter-relating factors**

All the above discussed variables associated with children and pregnant women are also dependent on conditions of on geographical circumstances, poverty and bad hygiene. The STH assault is restricted to rural regions of tropics, especially in coastal regions; where temperature, humidity and soil type are appropriate for development and growth. Exposure to larval eggs in farming areas where individuals expose their skin to the hot and humid soil is what aids in disease transmission. Sandy soils provide better growth conditions for these worms when compared to clayey soils. An important adverse link between socioeconomic status and incidence or severity of helminthic disease can also attribute towards the spread of STH. It was found that the prevalence of disease was less in cases of higher income groups. Bad sanitation or hygiene due to the lack of income is also an associated factor leading to an attack of STH [60–63].

## **7. Conclusion**

Geohelminthiasis or soil-transmitted helminthiasis is recognized as a lifethreatening parasitic outbreak in developing nations, predominantly in kids under 5 years of age and pregnant females and has resulted to increased concern. Reports of nutrition, environment, resistance to treatment and cognition were the associative parameters found in children, whereas in the condition of pregnancy existence of co-infections, geophagy, maternal anemia and birth outcomes were found to be the inter-relating variables to STH. The avoidance of particular processes of host immune defense and self-adaptation to combat immune responses from the mother by utilizing the similarity in mechanisms as used by a human fetus were the proposed mechanisms by which pregnant women are more prone to the attack. All the associative parameters discussed above were found to increase disease burden. Tackling these factors is therefore a must for achieving an improved quality of life.

### *Helminthiasis*

Although recent or upcoming beneficial hypotheses could play an important role in the eradication of associative diseases, the same benefit could have least highlighting phenomena when poverty is involved. Improvements in hygiene and improved access to anti-helminthic drugs are some of the factors that could establish a better alleviating status for the disease attack. Further researches/studies and proper awareness among groups where the disease is endemic is however still a requisite for both devising and strategizing to fight against the disease.

## **Acknowledgements**

The authors would like to express their gratitude to People's University, Bhanpur, Bhopal, for providing the necessary environment for completion of this chapter.

## **Conflict of interest**

We the authors would like to declare that there is no conflict of interest based on the information produced.

## **Author details**

Asher John Mohan1 \*, Neeraj Upmanyu1 and Silviya Sarah Lal<sup>2</sup>

1 School of Pharmacy and Research, Affiliated to People's University, Bhopal, India

2 Indian Institute of Science Education and Research (IISER), Bhopal, India

\*Address all correspondence to: asherjohnmohan@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**17**

*Pregnancy, Children and Inter-Relating Factors Affected by Geohelminthiasis*

[7] Karshima SN. Prevalence and distribution of soil-transmitted helminth infections in Nigerian

[8] Salam RA, Haider BA,

Humayun Q, Bhutta ZA. Effect of administration of antihelminthics for soil-transmitted helminths during pregnancy. Cochrane Database of Systematic Reviews. 2015;**6**:CD005547

[9] Kumate J. Infectious diseases in the 21st century. Archives of Medical

[10] Maynard CL, Weaver CT. Effector CD4+ T cells in the intestines. In: Mestecky J, Strober W, Russell MW, Kelsall BL, Cheroutre H, Lambrecht BN, editors. Mucosal Immunology. 4th ed. Boston: Academic Press; 2015. pp. 721-732. Available from: http://www. sciencedirect.com/science/article/pii/

Research. 1997;**28**(2):155-161

B9780124158474000343

B9780323357623000214

2009;**126**(1):18-27

[11] Carty SA, Riese MJ, Koretzky GA. T-Cell Immunity. In: Hoffman R, Benz EJ, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, et al., editors. Hematology. 9th ed. Elsevier; 2018. p. 221-239. DOI: 10.1016/C2013-0- 23355-9. Available from: http://www. sciencedirect.com/science/article/pii/

[12] Jackson JA, Friberg IM, Little S, Bradley JE. Review series on helminths, immune modulation and the hygiene hypothesis: Immunity against helminths and immunological phenomena in modern human populations:

Coevolutionary legacies? Immunology.

[13] Salgame P, Yap GS, Gause WC. Effect of helminth-induced immunity on infections with microbial

2018;**7**(1):69

children: A systematic review and metaanalysis. Infectious Diseases of Poverty.

*DOI: http://dx.doi.org/10.5772/intechopen.86925*

[1] Castro GA. Helminths: Structure,

Medical Microbiology. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Available from: http://www.ncbi.nlm.nih.gov/

[2] Wakelin D. Helminths: Pathogenesis and defenses. In: Baron S, editor. Medical Microbiology. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Available from: http://www.ncbi.nlm.

classification, growth, and development. In: Baron S, editor.

nih.gov/books/NBK8191/

[3] Soil-Transmitted Helminth Infections. 2019. Available from: https://www.who.int/ news-room/fact-sheets/detail/ soil-transmitted-helminth-infections

[4] Walker M, Hall A, Basáñez M-G. Ascaris lumbricoides: New epidemiological insights and

B9780123969781000070

T, Ryan ET, editors. Hunter's Tropical Medicine and Emerging Infectious Disease. 9th ed. London: W.B. Saunders; 2013. pp. 797- 803. Available from: http://www. sciencedirect.com/science/article/pii/

B9781416043904001077

2004;**58**:197-288

[6] Brooker S, Bethony J, Hotez PJ. Human hookworm infection in the 21st century. Advances in Parasitology.

mathematical approaches. In: Holland C, editor. Ascaris: The Neglected

Parasite. Amsterdam: Elsevier; 2013. pp. 155-201. Available from: http://www. sciencedirect.com/science/article/pii/

[5] Bundy DA, Cooper ES, Brooker S. Nematodes limited to the intestinal tract (*Enterobius vermicularis*, *Trichuris trichiura*, *Capillaria philippinensis* and *Trichostrongylus* spp.). In: Magill AJ, Hill DR, Solomon

**References**

books/NBK8282/

*Pregnancy, Children and Inter-Relating Factors Affected by Geohelminthiasis DOI: http://dx.doi.org/10.5772/intechopen.86925*

## **References**

*Helminthiasis*

**Acknowledgements**

**Conflict of interest**

**Author details**

Asher John Mohan1

the information produced.

Although recent or upcoming beneficial hypotheses could play an important role in the eradication of associative diseases, the same benefit could have least highlighting phenomena when poverty is involved. Improvements in hygiene and improved access to anti-helminthic drugs are some of the factors that could establish a better alleviating status for the disease attack. Further researches/studies and proper awareness among groups where the disease is endemic is however still a requisite for

The authors would like to express their gratitude to People's University, Bhanpur,

We the authors would like to declare that there is no conflict of interest based on

and Silviya Sarah Lal<sup>2</sup>

1 School of Pharmacy and Research, Affiliated to People's University, Bhopal, India

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 Indian Institute of Science Education and Research (IISER), Bhopal, India

Bhopal, for providing the necessary environment for completion of this chapter.

both devising and strategizing to fight against the disease.

\*, Neeraj Upmanyu1

\*Address all correspondence to: asherjohnmohan@gmail.com

provided the original work is properly cited.

**16**

[1] Castro GA. Helminths: Structure, classification, growth, and development. In: Baron S, editor. Medical Microbiology. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Available from: http://www.ncbi.nlm.nih.gov/ books/NBK8282/

[2] Wakelin D. Helminths: Pathogenesis and defenses. In: Baron S, editor. Medical Microbiology. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Available from: http://www.ncbi.nlm. nih.gov/books/NBK8191/

[3] Soil-Transmitted Helminth Infections. 2019. Available from: https://www.who.int/ news-room/fact-sheets/detail/ soil-transmitted-helminth-infections

[4] Walker M, Hall A, Basáñez M-G. Ascaris lumbricoides: New epidemiological insights and mathematical approaches. In: Holland C, editor. Ascaris: The Neglected Parasite. Amsterdam: Elsevier; 2013. pp. 155-201. Available from: http://www. sciencedirect.com/science/article/pii/ B9780123969781000070

[5] Bundy DA, Cooper ES, Brooker S. Nematodes limited to the intestinal tract (*Enterobius vermicularis*, *Trichuris trichiura*, *Capillaria philippinensis* and *Trichostrongylus* spp.). In: Magill AJ, Hill DR, Solomon T, Ryan ET, editors. Hunter's Tropical Medicine and Emerging Infectious Disease. 9th ed. London: W.B. Saunders; 2013. pp. 797- 803. Available from: http://www. sciencedirect.com/science/article/pii/ B9781416043904001077

[6] Brooker S, Bethony J, Hotez PJ. Human hookworm infection in the 21st century. Advances in Parasitology. 2004;**58**:197-288

[7] Karshima SN. Prevalence and distribution of soil-transmitted helminth infections in Nigerian children: A systematic review and metaanalysis. Infectious Diseases of Poverty. 2018;**7**(1):69

[8] Salam RA, Haider BA, Humayun Q, Bhutta ZA. Effect of administration of antihelminthics for soil-transmitted helminths during pregnancy. Cochrane Database of Systematic Reviews. 2015;**6**:CD005547

[9] Kumate J. Infectious diseases in the 21st century. Archives of Medical Research. 1997;**28**(2):155-161

[10] Maynard CL, Weaver CT. Effector CD4+ T cells in the intestines. In: Mestecky J, Strober W, Russell MW, Kelsall BL, Cheroutre H, Lambrecht BN, editors. Mucosal Immunology. 4th ed. Boston: Academic Press; 2015. pp. 721-732. Available from: http://www. sciencedirect.com/science/article/pii/ B9780124158474000343

[11] Carty SA, Riese MJ, Koretzky GA. T-Cell Immunity. In: Hoffman R, Benz EJ, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, et al., editors. Hematology. 9th ed. Elsevier; 2018. p. 221-239. DOI: 10.1016/C2013-0- 23355-9. Available from: http://www. sciencedirect.com/science/article/pii/ B9780323357623000214

[12] Jackson JA, Friberg IM, Little S, Bradley JE. Review series on helminths, immune modulation and the hygiene hypothesis: Immunity against helminths and immunological phenomena in modern human populations: Coevolutionary legacies? Immunology. 2009;**126**(1):18-27

[13] Salgame P, Yap GS, Gause WC. Effect of helminth-induced immunity on infections with microbial pathogens. Nature Immunology. 2013;**14**(11):1118-1126

[14] Kreider T, Anthony RM, Urban JF, Gause WC. Alternatively activated macrophages in helminth infections. Current Opinion in Immunology. 2007 Aug;**19**(4):448-453

[15] Zulkifli A, Anuar AK, Atiya A, Yano A. The prevalence of malnutrition and geo-helminth infections among primary schoolchildren in rural kelantan. The Southeast Asian Journal of Tropical Medicine and Public Health. 2000;**31**(2):7

[16] Bundy DAP, Golden MHN. The impact of host nutrition on gastrointestinal helminth populations. Parasitology. 1987;**95**(3):623-635

[17] Crompton DWT, Nesheim MC. Nutritional impact of intestinal helminthiasis during the human life cycle. Annual Review of Nutrition. 2002;**22**(1):35-59

[18] Yamamoto R, Nagai N, Kawabata M, Leon WU, Ninomiya R, Koizumi N. Effect of intestinal helminthiasis on nutritional status of schoolchildren. The Southeast Asian Journal of Tropical Medicine and Public Health. 2000;**31**(4):7

[19] Koski KG, Scott ME. Gastrointestinal nematodes, nutrition and immunity: Breaking the negative spiral. Annual Review of Nutrition. 2001;**21**(1):297-321

[20] Van Houtert MFJ, Sykes AR. Implications of nutrition for the ability of ruminants to withstand gastrointestinal nematode infections. International Journal for Parasitology. 1996;**26**(11):1151-1167

[21] Jemaneh L. Schistosomiasis mansoni and geo-helminthiasis in school children in the Dembia plains, Northwest Ethiopia. The Ethiopian Journal of

Health Development. 1998;**12**(3):1-11. Available from: https://www.ejhd.org/ index.php/ejhd/article/view/984

[22] Tulu B, Taye S, Zenebe Y, Amsalu E. Intestinal parasitic infections and nutritional status among primary school children in Delo-mena District, South Eastern Ethiopia. Iranian Journal of Parasitology. 2016;**11**(4):549-558

[23] Hughes RG, Sharp DS, Hughes MC, Akauola S, Heinsbroek P, Velayudhan R, et al. Environmental influences on helminthiasis and nutritional status among Pacific schoolchildren. International Journal of Environmental Health Research. 2004;**14**(3):163-177

[24] Vercruysse J, Albonico M, Behnke JM, Kotze AC, Prichard RK, McCarthy JS, et al. Is anthelmintic resistance a concern for the control of human soiltransmitted helminths? International Journal for Parasitology: Drugs and Drug Resistance. 2011;**1**(1):14-27

[25] Anthelmintics as a Risk Factor in Intestinal Obstruction by *Ascaris lumbricoides* in children - Abstract - Europe PMC. 2019. Available from: https://europepmc.org/abstract/ med/11757415

[26] Hagel I, Lynch NR, Prisco MCD, Rojas E, Pérez M, Alvarez N. Ascaris reinfection of slum children: Relation with the IgE response. Clinical and Experimental Immunology. 1993;**94**(1):80-83

[27] Hagel I. Helminthic infection and anthropometric indicators in children from a tropical slum: Ascaris reinfection after anthelmintic treatment. Journal of Tropical Pediatrics. 1999;**45**(4):215-220

[28] Nokes C, Grantham-McGregor SM, Sawyer AW, Cooper ES, Bundy DAP. Parasitic helminth infection and cognitive function in school children. Proceedings of the Royal Society of London B. 1992;**247**(1319):77-81

**19**

*Pregnancy, Children and Inter-Relating Factors Affected by Geohelminthiasis*

immunoevasive strategy? Trends in Parasitology. 2005;**21**(6):273-277

[38] Blackwell AD. Helminth infection during pregnancy: Insights from evolutionary ecology. International

Journal of Women's Health.

[39] Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao S. Hookworm Infection. The New England Journal of Medicine.

factors (malaria and intestinal helminthiasis) in Lubumbashi. Santé

[40] Kalenga MK, Nyembo MK, Nshimba M, Foidart JM. Anemia and associated

[41] Njeru A, Mutuku F, Muriu S. Status of soil-transmitted helminthiasis among pregnant women attending antenatal clinic in Kilifi county hospital, Kenya.

[42] Hillier SD, Booth M, Muhangi L, Nkurunziza P, Khihembo M, Kakande M, et al. *Plasmodium falciparum* and helminth coinfection in a semiurban population of pregnant women in Uganda. The Journal of Infectious Diseases. 2008;**198**(6):920-927

[43] Ndibazza J, Webb EL, Lule S, Mpairwe H, Akello M, Oduru G, et al. Associations between maternal helminth and malaria infections in pregnancy and clinical malaria in the offspring: A birth cohort in Entebbe, Uganda. The Journal of Infectious Diseases. 2013;**208**(12):2007-2016

[44] Geophagy: "Soil-Eating" as an Addictive Behaviour.

ScienceDaily. 2019. Available from: https://www.sciencedaily.com/ releases/2016/12/161205085943.htm

[45] Kawai K, Saathoff E, Antelman G, Msamanga G, Fawzi WW. Geophagy (soil-eating) in relation to anemia and

2016;**8**:651-661

2004;**351**(8):799-807

Publique;**15**(4):413-421

bioRxiv. 2019;**1**:613570

*DOI: http://dx.doi.org/10.5772/intechopen.86925*

[30] Mcgarvey ST, Olveda RM, Acosta LP, Kurtis JD, Bellinger DC, Langdon GC, et al. Helminth infection and cognitive impairment among filipino children. The American Journal of Tropical Medicine and Hygiene.

[31] Brooker S, Hotez PJ, Bundy DAP. Hookworm-related anaemia among pregnant women: A systematic review. PLoS Neglected Tropical Diseases. 2008;**2**(9). Available from: https://www.ncbi.nlm.nih.gov/pmc/

[32] Haider BA, Humayun Q, Bhutta ZA. Effect of administration of antihelminthics for soil transmitted helminths during pregnancy. Cochrane Database of Systematic Reviews.

[33] Mpairwe H, Tweyongyere R, Elliott A. Pregnancy and helminth infections. Parasite Immunology.

[34] Guleria I, Sayegh MH. Maternal acceptance of the fetus: True human tolerance. The Journal of Immunology.

[35] Mor G, Cardenas I. The immune system in pregnancy: A unique complexity. American Journal of Reproductive Immunology.

[36] Lloyd S. Effect of pregnancy and lactation upon infection. Veterinary Immunology and Immunopathology.

[37] Mulcahy G, O'Neill S, Fanning J, McCarthy E, Sekiya M. Tissue migration by parasitic helminths—An

[29] Nokes C, Bundy DAP. Does helminth infection affect mental processing and educational achievement? Parasitology Today.

1994;**10**(1):14-18

2005;**72**(5):540-548

articles/PMC2553481/

2009;**2**:CD005547

2014;**36**(8):328-337

2007;**178**(6):3345-3351

2010;**63**(6):425-433

1983;**4**(1-2):153-176

*Pregnancy, Children and Inter-Relating Factors Affected by Geohelminthiasis DOI: http://dx.doi.org/10.5772/intechopen.86925*

[29] Nokes C, Bundy DAP. Does helminth infection affect mental processing and educational achievement? Parasitology Today. 1994;**10**(1):14-18

*Helminthiasis*

pathogens. Nature Immunology.

Health Development. 1998;**12**(3):1-11. Available from: https://www.ejhd.org/ index.php/ejhd/article/view/984

[22] Tulu B, Taye S, Zenebe Y, Amsalu E. Intestinal parasitic infections and nutritional status among primary school children in Delo-mena District, South Eastern Ethiopia. Iranian Journal of Parasitology. 2016;**11**(4):549-558

[23] Hughes RG, Sharp DS, Hughes MC, Akauola S, Heinsbroek P, Velayudhan R, et al. Environmental influences on helminthiasis and nutritional status among Pacific schoolchildren. International Journal of Environmental Health Research. 2004;**14**(3):163-177

[24] Vercruysse J, Albonico M, Behnke JM, Kotze AC, Prichard RK, McCarthy JS, et al. Is anthelmintic resistance a concern for the control of human soiltransmitted helminths? International Journal for Parasitology: Drugs and Drug Resistance. 2011;**1**(1):14-27

[25] Anthelmintics as a Risk Factor in Intestinal Obstruction by *Ascaris lumbricoides* in children - Abstract - Europe PMC. 2019. Available from: https://europepmc.org/abstract/

[26] Hagel I, Lynch NR, Prisco MCD, Rojas E, Pérez M, Alvarez N. Ascaris reinfection of slum children: Relation with the IgE response. Clinical and Experimental Immunology.

[27] Hagel I. Helminthic infection and anthropometric indicators in children from a tropical slum: Ascaris reinfection after anthelmintic treatment. Journal of Tropical Pediatrics. 1999;**45**(4):215-220

[28] Nokes C, Grantham-McGregor SM, Sawyer AW, Cooper ES, Bundy DAP. Parasitic helminth infection and cognitive function in school children. Proceedings of the Royal Society of London B. 1992;**247**(1319):77-81

med/11757415

1993;**94**(1):80-83

[14] Kreider T, Anthony RM, Urban JF, Gause WC. Alternatively activated macrophages in helminth infections. Current Opinion in Immunology. 2007

[15] Zulkifli A, Anuar AK, Atiya A, Yano A. The prevalence of malnutrition and geo-helminth infections among primary schoolchildren in rural kelantan. The Southeast Asian Journal of Tropical Medicine and Public Health.

[16] Bundy DAP, Golden MHN. The impact of host nutrition on gastrointestinal helminth populations. Parasitology. 1987;**95**(3):623-635

[17] Crompton DWT, Nesheim MC. Nutritional impact of intestinal helminthiasis during the human life cycle. Annual Review of Nutrition.

[18] Yamamoto R, Nagai N, Kawabata M, Leon WU, Ninomiya R, Koizumi N. Effect of intestinal helminthiasis on nutritional status of schoolchildren. The Southeast Asian Journal of Tropical Medicine and Public Health.

Gastrointestinal nematodes, nutrition and immunity: Breaking the negative spiral. Annual Review of Nutrition.

[21] Jemaneh L. Schistosomiasis mansoni and geo-helminthiasis in school children

[20] Van Houtert MFJ, Sykes AR. Implications of nutrition for the ability of ruminants to withstand gastrointestinal nematode infections. International Journal for Parasitology.

in the Dembia plains, Northwest Ethiopia. The Ethiopian Journal of

2013;**14**(11):1118-1126

Aug;**19**(4):448-453

2000;**31**(2):7

2002;**22**(1):35-59

2000;**31**(4):7

[19] Koski KG, Scott ME.

2001;**21**(1):297-321

1996;**26**(11):1151-1167

**18**

[30] Mcgarvey ST, Olveda RM, Acosta LP, Kurtis JD, Bellinger DC, Langdon GC, et al. Helminth infection and cognitive impairment among filipino children. The American Journal of Tropical Medicine and Hygiene. 2005;**72**(5):540-548

[31] Brooker S, Hotez PJ, Bundy DAP. Hookworm-related anaemia among pregnant women: A systematic review. PLoS Neglected Tropical Diseases. 2008;**2**(9). Available from: https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC2553481/

[32] Haider BA, Humayun Q, Bhutta ZA. Effect of administration of antihelminthics for soil transmitted helminths during pregnancy. Cochrane Database of Systematic Reviews. 2009;**2**:CD005547

[33] Mpairwe H, Tweyongyere R, Elliott A. Pregnancy and helminth infections. Parasite Immunology. 2014;**36**(8):328-337

[34] Guleria I, Sayegh MH. Maternal acceptance of the fetus: True human tolerance. The Journal of Immunology. 2007;**178**(6):3345-3351

[35] Mor G, Cardenas I. The immune system in pregnancy: A unique complexity. American Journal of Reproductive Immunology. 2010;**63**(6):425-433

[36] Lloyd S. Effect of pregnancy and lactation upon infection. Veterinary Immunology and Immunopathology. 1983;**4**(1-2):153-176

[37] Mulcahy G, O'Neill S, Fanning J, McCarthy E, Sekiya M. Tissue migration by parasitic helminths—An immunoevasive strategy? Trends in Parasitology. 2005;**21**(6):273-277

[38] Blackwell AD. Helminth infection during pregnancy: Insights from evolutionary ecology. International Journal of Women's Health. 2016;**8**:651-661

[39] Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao S. Hookworm Infection. The New England Journal of Medicine. 2004;**351**(8):799-807

[40] Kalenga MK, Nyembo MK, Nshimba M, Foidart JM. Anemia and associated factors (malaria and intestinal helminthiasis) in Lubumbashi. Santé Publique;**15**(4):413-421

[41] Njeru A, Mutuku F, Muriu S. Status of soil-transmitted helminthiasis among pregnant women attending antenatal clinic in Kilifi county hospital, Kenya. bioRxiv. 2019;**1**:613570

[42] Hillier SD, Booth M, Muhangi L, Nkurunziza P, Khihembo M, Kakande M, et al. *Plasmodium falciparum* and helminth coinfection in a semiurban population of pregnant women in Uganda. The Journal of Infectious Diseases. 2008;**198**(6):920-927

[43] Ndibazza J, Webb EL, Lule S, Mpairwe H, Akello M, Oduru G, et al. Associations between maternal helminth and malaria infections in pregnancy and clinical malaria in the offspring: A birth cohort in Entebbe, Uganda. The Journal of Infectious Diseases. 2013;**208**(12):2007-2016

[44] Geophagy: "Soil-Eating" as an Addictive Behaviour. ScienceDaily. 2019. Available from: https://www.sciencedaily.com/ releases/2016/12/161205085943.htm

[45] Kawai K, Saathoff E, Antelman G, Msamanga G, Fawzi WW. Geophagy (soil-eating) in relation to anemia and

helminth infection among HIV–Infected pregnant women in Tanzania. The American Journal of Tropical Medicine and Hygiene. 2009;**80**(1):36-43

[46] Luoba AI, Geissler PW, Estambale B, Ouma JH, Alusala D, Ayah R, et al. Earth-eating and reinfection with intestinal helminths among pregnant and lactating women in western Kenya. Tropical Medicine and International Health. 2005;**10**(3):220-227

[47] Larocque R, Casapia M, Gotuzzo E, Gyorkos TW. Relationship between intensity of soil-transmitted helminth infections and anemia during pregnancy. The American Journal of Tropical Medicine and Hygiene. 2005;**73**(4):783-789

[48] Fuseinisup G, Edohsup D, Kalifasup BG, Hamidsup A-W, Knight D. Parasitic infections and anaemia during pregnancy in the Kassena-Nankana district of Northern Ghana. JPHE. 2010;**2**(3):48-52

[49] Gyorkos TW, Gilbert NL, Larocque R, Casapía M. Trichuris and hookworm infections associated with anaemia during pregnancy. Tropical Medicine & International Health. 2011;**16**(4):531-537

[50] Naing C, Whittaker MA, Nyunt-Wai V, Reid SA, Wong SF, Mak JW, et al. Malaria and soil-transmitted intestinal helminth co-infection and its effect on anemia: A meta-analysis. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2013;**107**(11):672-683

[51] Bánhidy F, Ács N, Puhó EH, Czeizel AE. Iron deficiency anemia: Pregnancy outcomes with or without iron supplementation. Nutrition. 2011;**27**(1):65-72

[52] Eiríksdóttir VH, Ásgeirsdóttir TL, Bjarnadóttir RI, Kaestner R, Cnattingius S, Valdimarsdóttir UA. Low birth weight, small for gestational age and preterm births before and after the economic collapse in Iceland: A population based cohort study. PLoS One. 2013;**8**(12):e80499

[53] Passerini L, Casey GJ, Biggs BA, Cong DT, Phu LB, Phuc TQ, et al. Increased birth weight associated with regular pre-pregnancy deworming and weekly iron-folic acid supplementation for Vietnamese women. PLoS Neglected Tropical Diseases. 2012;**6**(4):e1608

[54] McSorley HJ, Maizels RM. Helminth infections and host immune regulation. Clinical Microbiology Reviews. 2012;**25**(4):585-608

[55] Weinstock JV, Elliott DE. Helminths and the IBD hygiene hypothesis. Inflammatory Bowel Diseases. 2009;**15**(1):128-133

[56] Fusunyan RD, Sanderson IR. Inflammatory bowel disease. In: Delves PJ, editor. Encyclopedia of Immunology. 2nd ed. Oxford: Elsevier; 1998. pp. 1375-1381. Available from: http://www. sciencedirect.com/science/article/pii/ B0122267656003625

[57] Moskaluk CA. Esophagus. In: Weidner N, Cote RJ, Suster S, Weiss LM, editors. Modern Surgical Pathology. 2nd ed. Philadelphia: W.B. Saunders; 2009. pp. 637-672. Available from: http:// www.sciencedirect.com/science/article/ pii/B9781416039662000205

[58] Elliott DE, Urban JF, Argo CK, Weinstock JV. Does the failure to acquire helminthic parasites predispose to Crohn's disease? The FASEB Journal. 2000;**14**(12):1848-1855

[59] Wiria AE, Hamid F, Wammes LJ, Prasetyani MA, Dekkers OM, May L, et al. Infection with soil-transmitted helminths is associated with increased insulin sensitivity. PLoS One. 2015;**10**(6):e0127746

**21**

*Pregnancy, Children and Inter-Relating Factors Affected by Geohelminthiasis*

*DOI: http://dx.doi.org/10.5772/intechopen.86925*

[60] Hotez P. Hookworm and poverty. Annals of the New York Academy of Sciences. 2008;**1136**(1):38-44

[61] Holland CV, Taren DL, Crompton DWT, Nesheim MC, Sanjur D, Barbeau

I, et al. Intestinal helminthiases in relation to the socioeconomic environment of Panamanian children.

Social Science and Medicine.

Health. 2005;**10**(1):42-57

[62] Raso G, Utzinger J, Silué KD, Ouattara M, Yapi A, Toty A, et al. Disparities in parasitic infections, perceived ill health and access to health care among poorer and less poor schoolchildren of rural Côte d'Ivoire. Tropical Medicine and International

[63] Olsen A, Samuelsen H, Onyango-Ouma W. A study of risk factors for intestinal helminth infections using epidemiological and anthropological approaches. Journal of Biosocial Science. 2001;**33**(4):569-584

1988;**26**(2):209-213

*Pregnancy, Children and Inter-Relating Factors Affected by Geohelminthiasis DOI: http://dx.doi.org/10.5772/intechopen.86925*

[60] Hotez P. Hookworm and poverty. Annals of the New York Academy of Sciences. 2008;**1136**(1):38-44

*Helminthiasis*

helminth infection among HIV–Infected pregnant women in Tanzania. The American Journal of Tropical Medicine

birth weight, small for gestational age and preterm births before and after the economic collapse in Iceland: A population based cohort study. PLoS

[53] Passerini L, Casey GJ, Biggs BA, Cong DT, Phu LB, Phuc TQ, et al. Increased birth weight associated with regular pre-pregnancy deworming and weekly iron-folic acid supplementation for Vietnamese women. PLoS Neglected Tropical Diseases. 2012;**6**(4):e1608

[54] McSorley HJ, Maizels RM. Helminth infections and host immune regulation.

[55] Weinstock JV, Elliott DE. Helminths

Clinical Microbiology Reviews.

and the IBD hygiene hypothesis. Inflammatory Bowel Diseases.

[56] Fusunyan RD, Sanderson IR. Inflammatory bowel disease. In: Delves PJ, editor. Encyclopedia of Immunology. 2nd ed. Oxford: Elsevier; 1998. pp. 1375-1381. Available from: http://www. sciencedirect.com/science/article/pii/

[57] Moskaluk CA. Esophagus. In: Weidner N, Cote RJ, Suster S, Weiss LM, editors. Modern Surgical Pathology. 2nd ed. Philadelphia: W.B. Saunders; 2009. pp. 637-672. Available from: http:// www.sciencedirect.com/science/article/

pii/B9781416039662000205

2000;**14**(12):1848-1855

2015;**10**(6):e0127746

[58] Elliott DE, Urban JF, Argo CK, Weinstock JV. Does the failure to acquire helminthic parasites predispose to Crohn's disease? The FASEB Journal.

[59] Wiria AE, Hamid F, Wammes LJ, Prasetyani MA, Dekkers OM, May L, et al. Infection with soil-transmitted helminths is associated with increased

insulin sensitivity. PLoS One.

2012;**25**(4):585-608

2009;**15**(1):128-133

B0122267656003625

One. 2013;**8**(12):e80499

[46] Luoba AI, Geissler PW, Estambale B, Ouma JH, Alusala D, Ayah R, et al. Earth-eating and reinfection with intestinal helminths among pregnant and lactating women in western Kenya. Tropical Medicine and International

[47] Larocque R, Casapia M, Gotuzzo E, Gyorkos TW. Relationship between intensity of soil-transmitted helminth

[48] Fuseinisup G, Edohsup D, Kalifasup

Parasitic infections and anaemia during pregnancy in the Kassena-Nankana district of Northern Ghana. JPHE.

[49] Gyorkos TW, Gilbert NL, Larocque R, Casapía M. Trichuris and hookworm infections associated with anaemia during pregnancy. Tropical Medicine & International Health. 2011;**16**(4):531-537

[50] Naing C, Whittaker MA, Nyunt-Wai V, Reid SA, Wong SF, Mak JW, et al. Malaria and soil-transmitted intestinal helminth co-infection and its effect on anemia: A meta-analysis. Transactions of the Royal Society of Tropical Medicine and Hygiene.

and Hygiene. 2009;**80**(1):36-43

Health. 2005;**10**(3):220-227

infections and anemia during pregnancy. The American Journal of Tropical Medicine and Hygiene.

BG, Hamidsup A-W, Knight D.

2005;**73**(4):783-789

2010;**2**(3):48-52

2013;**107**(11):672-683

2011;**27**(1):65-72

[51] Bánhidy F, Ács N, Puhó EH, Czeizel AE. Iron deficiency anemia: Pregnancy outcomes with or without iron supplementation. Nutrition.

[52] Eiríksdóttir VH, Ásgeirsdóttir TL, Bjarnadóttir RI, Kaestner R,

Cnattingius S, Valdimarsdóttir UA. Low

**20**

[61] Holland CV, Taren DL, Crompton DWT, Nesheim MC, Sanjur D, Barbeau I, et al. Intestinal helminthiases in relation to the socioeconomic environment of Panamanian children. Social Science and Medicine. 1988;**26**(2):209-213

[62] Raso G, Utzinger J, Silué KD, Ouattara M, Yapi A, Toty A, et al. Disparities in parasitic infections, perceived ill health and access to health care among poorer and less poor schoolchildren of rural Côte d'Ivoire. Tropical Medicine and International Health. 2005;**10**(1):42-57

[63] Olsen A, Samuelsen H, Onyango-Ouma W. A study of risk factors for intestinal helminth infections using epidemiological and anthropological approaches. Journal of Biosocial Science. 2001;**33**(4):569-584

**23**

**Chapter 3**

**Abstract**

**1. Introduction**

**2. Epidemiology**

increasing fetal loss.

*Richard R. Roach*

Soil-Transmitted Helminths

treatment failure and new therapeutic approaches.

**Keywords:** helminths, *Ascaris*, *Trichuris*, hookworm

resulted in research, long tardy, for these diseases.

Helminths currently affect over 2 billion people worldwide with a quarter of the world's population infected at some time in their lives. Sobering statistics from the WHO March 2008 report that 80% of the "Bottom Billion" impoverished population of the world have *Ascaris*, 60% have *Trichuris*, and 57% have hookworms. This would only be a problem of pharmacologic distribution if not for an additional report demonstrating that several new studies reported to the WHO claim a 50% failure rate clearing *Trichuris* and 90% failure rate clearing hookworm. These parasitic infections pose a challenge to tropical physicians who have considered mebendazole and albendazole as adequate treatments for children. This is even more of a challenge for physicians in temperate climates who may be less familiar with these medications. This article presents the recent data and the approach to

Intestinal parasites cause substantial morbidity and mortality, particularly in children in whom they have detrimental effects on growth and cognitive performance. Parasitic infestation leads to deformity and long-term disabilities and often stigmatizes the child. Parasitized pregnant women are anemic, have increased fetal wastage, and have low birth weight newborns. Though tropical diseases affect a large proportion of the world's population, less than 1% of new drug development over the past 30 years focused on tropical diseases. Recent philanthropic interest has

There are three soil-transmitted helminth infections, *Ascaris lumbricoides*, hookworm (*Ancylostoma duodenale* and *Necator americanus*), and *Trichuris trichiura*, labeled by the WHO as the "Unholy Trinity." They are ubiquitous in tropical climates and even temperate rural areas in poverty-stricken communities with poor sanitation (see **Table 1**). *Ascaris* and *Trichuris* increase in prevalence from infancy to puberty and then decrease in adulthood. In contrast, hookworm, the leading cause of anemia throughout the world, continues to increase through life, not reaching a plateau until age 40. This characteristic has a profound effect on women of childbearing age and is associated with small-for-gestation newborns as well as

## **Chapter 3** Soil-Transmitted Helminths

*Richard R. Roach*

## **Abstract**

Helminths currently affect over 2 billion people worldwide with a quarter of the world's population infected at some time in their lives. Sobering statistics from the WHO March 2008 report that 80% of the "Bottom Billion" impoverished population of the world have *Ascaris*, 60% have *Trichuris*, and 57% have hookworms. This would only be a problem of pharmacologic distribution if not for an additional report demonstrating that several new studies reported to the WHO claim a 50% failure rate clearing *Trichuris* and 90% failure rate clearing hookworm. These parasitic infections pose a challenge to tropical physicians who have considered mebendazole and albendazole as adequate treatments for children. This is even more of a challenge for physicians in temperate climates who may be less familiar with these medications. This article presents the recent data and the approach to treatment failure and new therapeutic approaches.

**Keywords:** helminths, *Ascaris*, *Trichuris*, hookworm

## **1. Introduction**

Intestinal parasites cause substantial morbidity and mortality, particularly in children in whom they have detrimental effects on growth and cognitive performance. Parasitic infestation leads to deformity and long-term disabilities and often stigmatizes the child. Parasitized pregnant women are anemic, have increased fetal wastage, and have low birth weight newborns. Though tropical diseases affect a large proportion of the world's population, less than 1% of new drug development over the past 30 years focused on tropical diseases. Recent philanthropic interest has resulted in research, long tardy, for these diseases.

## **2. Epidemiology**

There are three soil-transmitted helminth infections, *Ascaris lumbricoides*, hookworm (*Ancylostoma duodenale* and *Necator americanus*), and *Trichuris trichiura*, labeled by the WHO as the "Unholy Trinity." They are ubiquitous in tropical climates and even temperate rural areas in poverty-stricken communities with poor sanitation (see **Table 1**). *Ascaris* and *Trichuris* increase in prevalence from infancy to puberty and then decrease in adulthood. In contrast, hookworm, the leading cause of anemia throughout the world, continues to increase through life, not reaching a plateau until age 40. This characteristic has a profound effect on women of childbearing age and is associated with small-for-gestation newborns as well as increasing fetal loss.


#### **Table 1.**

*Impact of soil-transmitted helminths [2].*

### **3. Management**

The WHO has classified parasitic infestation by egg intensity to clarify symptomatic and asymptomatic infestations (see **Table 2**). Children with light worm loads are often asymptomatic, but children form the greatest population of the heavy intensity group. Even children considered asymptomatic may have subtle differences in learning and intellectual achievement [1].

The clinical presentation relates to parasite migration in the skin, viscera, and gastrointestinal tract. *Trichuris* and *Ascaris* are a result of fecal-oral ingestion. Wheezing, dyspnea, nonproductive cough, fever, bloody sputum, chest x-ray infiltrates, and systemic eosinophilia result during pulmonary vascular migration. Once swallowed the larvae mature, and their migration in the gut causes abdominal pain, distention, and malabsorption.

If adult *Ascaris* migrate into the biliary tree, then pancreatitis, cholangitis, and cholecystitis result. Hepatic abscesses and appendicitis may result from *Ascaris* migration. In younger children, heavy loads of worms can cause partial or complete bowel obstruction in the ileum. Swelling of Peyer's patches leads to an increased risk of intussusception and volvulus. Unrecognized obstruction may eventually cause bowel infarction and perforation with resulting peritonitis.

*Trichuris* may infect any part of the colon, but the parasite prefers the cecum. Eggs release the larvae in the small intestine, and the worms mature in the colon where they tunnel into the mucosa, causing inflammation. Heavy infestation causes a dysentery syndrome severe enough that it may result in rectal prolapse. Impaired growth and anemia are the consequences of chronic infestation.

Hookworm infects through skin penetration. Itching erythematous rash from multiple skin penetrations causes severe pruritus of the skin, usually on the feet or hands. The larvae use the pulmonary vasculature to access the bronchial secretions and then, when swallowed, mature into adults in the gastrointestinal tract. Bronchial migration presents as clinical pneumonitis but may be mistaken for asthma. Pulmonary symptoms are seldom as dramatic as with *Ascaris*. The significant sequelae of infection relate to intestinal blood loss. As few as 40 worms can reduce the hemoglobin below 11 g/dl. Heavy infestations lead to loss of protein with resulting loss of plasma osmotic pressure and anasarca.

Helminth infestations cause anemia and malnutrition, growth stunting, and cognitive deficits, associated with poor school attendance and performance. Since this occurs in an impoverished area where the diet has limited resource to protein, the consequences of the poor child's limited diet magnifies the malnutrition. If this occurs in a malaria area, the anemia caused by helminths exaggerates the anemia of malaria.

**25**

**Table 3.**

*\*In children 1–2 years old, use 200 mg.*

*Treatment of soil-transmitted helminth infections [6].*

*Soil-Transmitted Helminths*

*Epg: eggs per gram of feces.*

**Table 2.**

**4. Treatment**

*DOI: http://dx.doi.org/10.5772/intechopen.87143*

*Soil-transmitted helminth infection intensity [3].*

area, the risks of malaria increase the infant mortality.

worms increases the risk of a bowel obstruction.

**Infection Drug Dose** *Ascariasis* Albendazole\* 400 mg once

*Hookworm* Albendazole\* 400 mg once

This is especially crucial for women of childbearing age, since infected women were 2.6 times more likely to have preterm deliveries and 3.5 times more likely to have small-for-gestational age infants. If the woman lives in a malaria-endemic

**Intensity** *Ascaris Hookworms Trichuris* Light 1–4999 epg 1–1999 epg 1–999 epg Moderate 5000–49,999 epg 2000–3999 epg 1000–9999 epg Heavy ≥50,000 epg ≥4000 epg ≥10,000 epg

There are four medications currently available to treat soil-transmitted helminth

The most important aspect of treatment is efficacy. Cure rates and egg reduction rates are high for all four drugs when treating *Ascaris* (see **Table 4**). Nevertheless, recent studies have documented ineffective and inconsistent treatment of *Trichuris* and hookworm, whether *Ancylostoma duodenale* or *Necator americanus*. The concern is drug resistance, despite lack of previous investigation. Researchers presumed that the drugs were effective in the past because they were effective with the other

Mebendazole 100 mg twice daily × 3 days or 500 mg once

Levamisole 2.5 mg/kg once, repeat after 7 days for heavy infection

Pyrantel pamoate 11 mg/kg (max 1 g) × 3 days

Mebendazole 100 mg twice daily × 3 days Pyrantel pamoate 11 mg/kg (max 1 g) × 3 days

*Trichuris* Mebendazole 100 mg twice daily × 3 days or 500 mg once Albendazole\* 400 mg × 3 days

Levamisole 2.5 mg/kg once

infections (see **Table 3**). Benzimidazoles impede the microtubular system, in particular β-tubulin, in the worm. Since this is not a host system, patients tolerate these drugs with minimal side effects. Very few patients report nausea, vomiting, and headache, but allergic reactions with fever are rare. Levamisole and pyrantel pamoate are nicotinic acetylcholine receptor agonists, which paralyze the worms and precipitate their expulsion. Gastrointestinal symptoms, headache, dizziness, fever, and rash are usually mild and self-limited. However, a bulk of paralyzed


#### **Table 2.**

*Helminthiasis*

**Disease Global** 

**prevalence (millions) [1]**

**Population at risk (billions)**

**3. Management**

*Impact of soil-transmitted helminths [2].*

**Table 1.**

The WHO has classified parasitic infestation by egg intensity to clarify symptomatic and asymptomatic infestations (see **Table 2**). Children with light worm loads are often asymptomatic, but children form the greatest population of the heavy intensity group. Even children considered asymptomatic may have subtle

*Ascariasis* 807 4.2 1.8–10.5 School-age children *Trichuriasis* 604 3.2 1.8–6.4 School-age children *Hookworm* 576 3.2 1.5–22.1 School-age children, women

**Estimated global disease burden (disability-adjusted life years in millions)**

**Vulnerable population**

of reproductive age

The clinical presentation relates to parasite migration in the skin, viscera, and gastrointestinal tract. *Trichuris* and *Ascaris* are a result of fecal-oral ingestion. Wheezing, dyspnea, nonproductive cough, fever, bloody sputum, chest x-ray infiltrates, and systemic eosinophilia result during pulmonary vascular migration. Once swallowed the larvae mature, and their migration in the gut causes abdominal

If adult *Ascaris* migrate into the biliary tree, then pancreatitis, cholangitis, and cholecystitis result. Hepatic abscesses and appendicitis may result from *Ascaris* migration. In younger children, heavy loads of worms can cause partial or complete bowel obstruction in the ileum. Swelling of Peyer's patches leads to an increased risk of intussusception and volvulus. Unrecognized obstruction may eventually cause

*Trichuris* may infect any part of the colon, but the parasite prefers the cecum. Eggs release the larvae in the small intestine, and the worms mature in the colon where they tunnel into the mucosa, causing inflammation. Heavy infestation causes a dysentery syndrome severe enough that it may result in rectal prolapse. Impaired

Hookworm infects through skin penetration. Itching erythematous rash from multiple skin penetrations causes severe pruritus of the skin, usually on the feet or hands. The larvae use the pulmonary vasculature to access the bronchial secretions and then, when swallowed, mature into adults in the gastrointestinal tract. Bronchial migration presents as clinical pneumonitis but may be mistaken for asthma. Pulmonary symptoms are seldom as dramatic as with *Ascaris*. The significant sequelae of infection relate to intestinal blood loss. As few as 40 worms can reduce the hemoglobin below 11 g/dl. Heavy infestations lead to loss of protein with

Helminth infestations cause anemia and malnutrition, growth stunting, and cognitive deficits, associated with poor school attendance and performance. Since this occurs in an impoverished area where the diet has limited resource to protein, the consequences of the poor child's limited diet magnifies the malnutrition. If this occurs in a malaria area, the anemia caused by helminths exaggerates the

differences in learning and intellectual achievement [1].

bowel infarction and perforation with resulting peritonitis.

growth and anemia are the consequences of chronic infestation.

resulting loss of plasma osmotic pressure and anasarca.

pain, distention, and malabsorption.

**24**

anemia of malaria.

*Soil-transmitted helminth infection intensity [3].*

This is especially crucial for women of childbearing age, since infected women were 2.6 times more likely to have preterm deliveries and 3.5 times more likely to have small-for-gestational age infants. If the woman lives in a malaria-endemic area, the risks of malaria increase the infant mortality.

## **4. Treatment**

There are four medications currently available to treat soil-transmitted helminth infections (see **Table 3**). Benzimidazoles impede the microtubular system, in particular β-tubulin, in the worm. Since this is not a host system, patients tolerate these drugs with minimal side effects. Very few patients report nausea, vomiting, and headache, but allergic reactions with fever are rare. Levamisole and pyrantel pamoate are nicotinic acetylcholine receptor agonists, which paralyze the worms and precipitate their expulsion. Gastrointestinal symptoms, headache, dizziness, fever, and rash are usually mild and self-limited. However, a bulk of paralyzed worms increases the risk of a bowel obstruction.

The most important aspect of treatment is efficacy. Cure rates and egg reduction rates are high for all four drugs when treating *Ascaris* (see **Table 4**). Nevertheless, recent studies have documented ineffective and inconsistent treatment of *Trichuris* and hookworm, whether *Ancylostoma duodenale* or *Necator americanus*. The concern is drug resistance, despite lack of previous investigation. Researchers presumed that the drugs were effective in the past because they were effective with the other


#### **Table 3.**

*Treatment of soil-transmitted helminth infections [6].*


#### **Table 4.**

*Efficacy of single- and multiple-dose anthelminthic drugs against common soil-transmitted helminth infections [4].*

helminths. Recent studies by veterinarians tested efficacy in mass drug administration to animals in endemic areas. Such studies presumed human efficacy. Subsequent studies done in adults excluded children and pregnant women, the most at-risk populations.

**27**

infestations.

*Soil-Transmitted Helminths*

pyrantel in pregnancy [2].

**5. Prevention**

*DOI: http://dx.doi.org/10.5772/intechopen.87143*

**6. Future research and treatment**

imidazoles and showed no advantage in humans.

of herd treatment.

assessment of benefit/risk ratio. The WHO does recommend treatment of hookworm in pregnancy due to the adverse effect of anemia which is greater than the risk of the medication [2]. Limited studies show no congenital anomalies or perinatal mortality with the use of albendazole, mebendazole, or ivermectin, although use in the first trimester is still discouraged. Studies have yet to focus on levamisole and

Because of the large burden of disease, prevention needs to be the foremost consideration in improving community health. Sanitation, access to a clean source of water, and careful food preparation limit fecal-oral contamination. Careful disposal of feces decreases exposure to helminthic eggs, and footwear limits hookworm exposure.

The other approach has been to limit morbidity through periodic treatment. The school system has been the logical institution for community treatment. Many studies have employed deworming schoolchildren on an annual basis, while others have focused on women of reproductive age. One recent study focused on community versus schoolchildren treatment justified a strategy that involves the entire community [3]. Community treatment in several studies documents the requirement to reach at least 75% of the at-risk population. Governments willing to institute such programs recognize the cost of \$0.02 USD. Several pharmaceutical companies made the drugs affordable. One example, a study done in Zanzibar, examined the coadministration of ivermectin, albendazole, and praziquantel in 5055 children and

adults. This mass drug administration benefitted the entire community.

Considering the high prevalence of soil-transmitted helminths and the established resistance, there is a need for other treatment options. This has provoked enthusiasm for vaccines and drugs with novel mechanisms of action. Unfortunately, there has been little financial incentive for developing human vaccines and novel drugs for poverty-stricken areas, but veterinary medicine has the financial incentive

The nicotinic acetylcholine receptor is unique to helminths and nematodes, although it appears to be a malaria parasite receptor as well. Since this receptor does not exist in humans, a medication to block this receptor should be effective and well tolerated. A vaccine with an antibody against this receptor seems a logical potential step for research. Tribendimidine is an L-type nicotinic acetylcholine receptor agonist. It is very effective in animals. Clinical trial in humans resulted in approval in China in 2004. Despite the difference in chemical structure and the hypothesized receptor agonist effect, it proved to have the same mechanism of action as benz-

Monepantel is a nicotinic acetylcholine receptor agonist. It is highly effective and licensed for sheep. Researchers initiated studies in humans. It does appear to have a unique mechanism of action since in animals it has been effective in multidrug resistant nematode infections it may also be effective in humans with resistant

Developing a vaccine requires an antigen. Developers have struggled with which antigen to use that will allow a sufficient and effective antigenic response. Vaccines developed for soil-transmitted helminths are effective in newborn animals. A vaccine to the hookworm antigen, Na-ASP-2, is effective in dogs [4]. Vaccinated

Currently, research established benzimidazoles as safe for children greater than 1 year of age. Teratogenic potential seen in animal studies requires careful

#### *Soil-Transmitted Helminths DOI: http://dx.doi.org/10.5772/intechopen.87143*

assessment of benefit/risk ratio. The WHO does recommend treatment of hookworm in pregnancy due to the adverse effect of anemia which is greater than the risk of the medication [2]. Limited studies show no congenital anomalies or perinatal mortality with the use of albendazole, mebendazole, or ivermectin, although use in the first trimester is still discouraged. Studies have yet to focus on levamisole and pyrantel in pregnancy [2].

## **5. Prevention**

*Helminthiasis*

**26**

**Table 4.**

at-risk populations.

helminths. Recent studies by veterinarians tested efficacy in mass drug administration to animals in endemic areas. Such studies presumed human efficacy. Subsequent studies done in adults excluded children and pregnant women, the most

*Efficacy of single- and multiple-dose anthelminthic drugs against common soil-transmitted helminth infections [4].*

Currently, research established benzimidazoles as safe for children greater than 1 year of age. Teratogenic potential seen in animal studies requires careful

Because of the large burden of disease, prevention needs to be the foremost consideration in improving community health. Sanitation, access to a clean source of water, and careful food preparation limit fecal-oral contamination. Careful disposal of feces decreases exposure to helminthic eggs, and footwear limits hookworm exposure.

The other approach has been to limit morbidity through periodic treatment. The school system has been the logical institution for community treatment. Many studies have employed deworming schoolchildren on an annual basis, while others have focused on women of reproductive age. One recent study focused on community versus schoolchildren treatment justified a strategy that involves the entire community [3]. Community treatment in several studies documents the requirement to reach at least 75% of the at-risk population. Governments willing to institute such programs recognize the cost of \$0.02 USD. Several pharmaceutical companies made the drugs affordable. One example, a study done in Zanzibar, examined the coadministration of ivermectin, albendazole, and praziquantel in 5055 children and adults. This mass drug administration benefitted the entire community.

## **6. Future research and treatment**

Considering the high prevalence of soil-transmitted helminths and the established resistance, there is a need for other treatment options. This has provoked enthusiasm for vaccines and drugs with novel mechanisms of action. Unfortunately, there has been little financial incentive for developing human vaccines and novel drugs for poverty-stricken areas, but veterinary medicine has the financial incentive of herd treatment.

The nicotinic acetylcholine receptor is unique to helminths and nematodes, although it appears to be a malaria parasite receptor as well. Since this receptor does not exist in humans, a medication to block this receptor should be effective and well tolerated. A vaccine with an antibody against this receptor seems a logical potential step for research. Tribendimidine is an L-type nicotinic acetylcholine receptor agonist. It is very effective in animals. Clinical trial in humans resulted in approval in China in 2004. Despite the difference in chemical structure and the hypothesized receptor agonist effect, it proved to have the same mechanism of action as benzimidazoles and showed no advantage in humans.

Monepantel is a nicotinic acetylcholine receptor agonist. It is highly effective and licensed for sheep. Researchers initiated studies in humans. It does appear to have a unique mechanism of action since in animals it has been effective in multidrug resistant nematode infections it may also be effective in humans with resistant infestations.

Developing a vaccine requires an antigen. Developers have struggled with which antigen to use that will allow a sufficient and effective antigenic response. Vaccines developed for soil-transmitted helminths are effective in newborn animals. A vaccine to the hookworm antigen, Na-ASP-2, is effective in dogs [4]. Vaccinated

### *Helminthiasis*

while still puppies, they were resistant to hookworm infection. This success led to a limited phase 1 trial in Brazil. Unfortunately, 30% of the patients developed urticaria, and one patient developed anaphylaxis. These reactions stopped the trial. Speculation as to the cause of this intense reaction led to the hypothesis that the study patients had antibodies to the antigen because of previous exposure from residing in an endemic area. Like the puppies, the requirement must to vaccinate human subjects prior to antigenic exposure [5].

## **7. Conclusions**

Helminth infections are a common problem. Presumed effectiveness of drugs is a deficient hypothesis. The available medications are not as effective as once thought. The trials of mass treatment of schoolchildren do not exterminate the source of infection or resolve the community exposure. New medication research is essential, especially for *Trichuris*. Novel treatments such as vaccines may be on the horizon, but safety concerns for humans with previous exposure is an important immunologic problem. Sanitation is still the most important community solution. The recent disaster in Port-au-Prince, Haiti, demonstrated that without sewer systems and potable water, we humans are indeed a vulnerable species.

## **Author details**

Richard R. Roach Internal Medicine Department, Western Michigan University School of Medicine, Kalamazoo, MI, USA

\*Address all correspondence to: richard.roach@med.wmich.edu

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**29**

*Soil-Transmitted Helminths*

2007;**357**(10):1018-1027

S1471-4922(02)02386-3

helminths in Kenya: A cluster-

2019;**393**(10185):2039-2050

[2] Allen HE, Crompton DW, de Silva N, LoVerde PT, Olds GR. New policies for using anthelmintics in high risk groups. Trends in Parasitology. 2002;**18**(9):381-382. DOI: 10.1016/

**References**

*DOI: http://dx.doi.org/10.5772/intechopen.87143*

[1] Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD, et al. Control of neglected tropical diseases. The New England Journal of Medicine.

[3] Pullan RL, Halliday KE, Oswald WE, Ncgari C, et al. Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted

randomised controlled trial. The Lancet.

[4] Keiser J, Utzinger J. The drugs we have and the drugs we need against major helminth infections. In: Xiao-Nong Zhou RBRO, Jürg U, editors. Advances in Parasitology. Vol. 73. Academic Press; 2010. pp. 197-230

[5] Lemoine JF, Desormeaux AM, Monestime F, Fayette CR, et al.

2016;**10**(10):e0004954

2001;**87**(2):413-418

Controlling neglected tropical diseases in Haiti: Implementation strategies and evidence of their success. PLOS Neglected Tropical Diseases.

[6] Muchiri EM, et al. A comparative study of different albendazole and mebendazole regimens for the treatment of intestinal infections in school children of Usigu Division, western Kenya. Journal of Parasitology. *Soil-Transmitted Helminths DOI: http://dx.doi.org/10.5772/intechopen.87143*

## **References**

*Helminthiasis*

**7. Conclusions**

while still puppies, they were resistant to hookworm infection. This success led to a limited phase 1 trial in Brazil. Unfortunately, 30% of the patients developed urticaria, and one patient developed anaphylaxis. These reactions stopped the trial. Speculation as to the cause of this intense reaction led to the hypothesis that the study patients had antibodies to the antigen because of previous exposure from residing in an endemic area. Like the puppies, the requirement must to vaccinate

Helminth infections are a common problem. Presumed effectiveness of drugs is a deficient hypothesis. The available medications are not as effective as once thought. The trials of mass treatment of schoolchildren do not exterminate the source of infection or resolve the community exposure. New medication research is essential, especially for *Trichuris*. Novel treatments such as vaccines may be on the horizon, but safety concerns for humans with previous exposure is an important immunologic problem. Sanitation is still the most important community solution. The recent disaster in Port-au-Prince, Haiti, demonstrated that without sewer

Internal Medicine Department, Western Michigan University School of Medicine,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: richard.roach@med.wmich.edu

provided the original work is properly cited.

systems and potable water, we humans are indeed a vulnerable species.

human subjects prior to antigenic exposure [5].

**28**

**Author details**

Richard R. Roach

Kalamazoo, MI, USA

[1] Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD, et al. Control of neglected tropical diseases. The New England Journal of Medicine. 2007;**357**(10):1018-1027

[2] Allen HE, Crompton DW, de Silva N, LoVerde PT, Olds GR. New policies for using anthelmintics in high risk groups. Trends in Parasitology. 2002;**18**(9):381-382. DOI: 10.1016/ S1471-4922(02)02386-3

[3] Pullan RL, Halliday KE, Oswald WE, Ncgari C, et al. Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: A clusterrandomised controlled trial. The Lancet. 2019;**393**(10185):2039-2050

[4] Keiser J, Utzinger J. The drugs we have and the drugs we need against major helminth infections. In: Xiao-Nong Zhou RBRO, Jürg U, editors. Advances in Parasitology. Vol. 73. Academic Press; 2010. pp. 197-230

[5] Lemoine JF, Desormeaux AM, Monestime F, Fayette CR, et al. Controlling neglected tropical diseases in Haiti: Implementation strategies and evidence of their success. PLOS Neglected Tropical Diseases. 2016;**10**(10):e0004954

[6] Muchiri EM, et al. A comparative study of different albendazole and mebendazole regimens for the treatment of intestinal infections in school children of Usigu Division, western Kenya. Journal of Parasitology. 2001;**87**(2):413-418

Section 3

Nematodes Infections

31

Section 3
