Intestinal Helminthiasis in

Pregnancy
Immunologic Perspective,
Implications to Treatment &
Impact to Public Health

Objectives
Describe the immune response of pregnant
women
Determine the effects of helminthiasis to the
health of a pregnant woman and her fetus
Identify the current strategies of treatment of
helminthiasis and the outcomes in pregnancy

Gestational Immunity
Gestation is a unique physiologic state that
carries with it several immunologic
consequences and results in changing
susceptibility to various diseases.

Adegnika, 2007

Gestational Immunology
Paradox of
Pregnancy
a lack of antigen
stimulation of maternal
lymphocytes, since the
fetal trophoblast cells
do not express major
histocompatibility
complex (MHC) Ia
antigens
Medawar, 1953; Veenstra van Nieuwenhoven

T cells in pregnancy
the numbers of Tc lymphocytes and Th
lymphocytes may or may not differ in pregnant
women versus non-pregnant women
pregnancy is a Th2 phenomenon probably due
to hormonal influences and placental
interference

Matthiesen et al., 1996; Luppi et al., 2002; Coulam et al., 1983;Veenstra van Nieuwenhoven et
al., 2002; Wegmann et al., 1993

Other immune cells

the number of peripheral NK cells is decreased
in pregnant women as compared with nonpregnant women
the granulocytes and monocytes is activated
during pregnancy
studies on dendritic cells in peripheral blood
in pregnant women are inconclusive

Watanabe et al., 1997; Kuhnert et al., 1998; Veenstra van Nieuwenhoven et al., 2002; Sacks et
al., 1998; Germain et al., 2002; Williams et al., 2002

The Bottomline
cell-mediated immune response of the
maternal specific immune system is relatively
suppressed
the CMI suppression seems to be
compensated for by an activation of the
innate immune response

Immune Response to Intestinal

Helminths
chronic but generally asymptomatic infections
although helminth infections induce strong
Th2 responses, parasitic worms may survive in
their mammalian hosts by switching off
inflammatory immune responses and inducing
a tolerant response to parasite antigens

Zaconne et al., 2006

Cellular interactions in the immune response to helminths.

Maizels R et al. JEM 2009;206:2059-2066

2009 Maizels et al.

Immune Response to Intestinal

Helminths
infection with helminths can be beneficial to
the host, as the Th2 and T reg cell responses
that develop in response to helminths can
suppress allergic and autoimmune responses
worm therapy
that helminth infections benefit the hosti.e.,
by dampening potentially damaging
inflammationthey also blunt responses to
vaccines
Wilson and Maizels, 2004; Maizels et al., 2009

Immune Response to Intestinal

Helminths
intestinal helminths are known to elicit a
strong systemic Th2 response or to upregulate Treg activity, which are normally
associated with a weakened Th1 immunity

Cooper et al., 2000; Bentwich et al., 1996; Kalinkovich et al., 1998; Borkow et al., 2000; Borkow
et al., 2004; Bentwich et al., 1995; Bentwich et al., 1995

Immune Response to Intestinal

Helminths
several mechanisms have been proposed to
explain the anti-inflammatory effects of
helminth infections, including the production
of IL-10 and transforming growth factor beta
(TGF-) by regulatory T cells, production of
IgG4 isotype blocking antibodies, and
suppression of mast cells, basophils, and
eosinophils

Akdis, 2008; Cooper, 2009

Cycle of Parasitic Adverse Events

Steketee, 2003

Helminthiasis and Pregnancy

Helminthiasis is infestation of the human body
with parasitic worms and it is estimated to affect
44 million pregnancies, globally, each year

Haider et al., 2009

Helminthiasis and Pregnancy

in Lambarn, Gabon, the prevalence of
intestinal helminths was 66% (n=58) in the
pregnant participants and 36% (n=32) in the
non-pregnant controls
pregnancy status was an independent risk
factor for being infected with intestinal
helminths (AOR and 95% CI: 3.0 [1.4-5.9])

Adegnika, 2007

Helminthiasis and Pregnancy

Primiparous and young women (<21 years of
age) had a significantly higher prevalence of
helminth infections

Adegnika, 2007

Helminthiasis and Pregnancy

a hookworm infection was associated with a
lower mid upper arm circumference (adjusted
mean decrease 0.7 cm, 95% CI 0.31.2 cm).
hookworm infections with an egg count of
1000/ gram feces (11 women) were associated
with lower hemoglobin (adjusted mean
decrease 1.5 g/dl, 95% CI 0.32.7)

van Eijk et al., 2009

Helminthiasis and Pregnancy

Contradicting results:
geohelminth infections were not associated with
clinical symptoms, or low body mass index

van Eijk et al., 2009

Helminthiasis and Pregnancy

no significant changes in the prevalence of any of
the common helminth species during the course
of pregnancy or between the pregnant and
control groups
no evidence that the density of helminth eggs in
the stool samples differed between sample times
or between the pregnant and control groups
the study therefore supports the hypothesis that
pregnancy does not influence the course of
human infection with helminths.
Herter et al., 2007

Parasitic Burden

Anemia
Nutrient deficiency
Low pregnancy weight gain
Intrauterine growth retardation
Low birth weight
Pregnancy loss
Effects in lactation
Impact with co-parasitism

Anemia
intestinal helminthiasis is associated with blood
loss and decreased supply of nutrients for
erythropoiesis, resulting in iron deficiency
anaemia
over 50% of the pregnant women in low- and
middle-income countries suffer from iron
deficiency anaemia
though iron deficiency anaemia is multifactorial,
hook worm infestation is a major contributory
cause in women of reproductive age in endemic
areas
Haider et al., 2009

Anemia
impact of intestinal helminth infections on
anaemia during pregnancy is aggravated by
low nutritional status of subjects whose
staple foods, such as rice, cassava and maize
are poor sources of folate and iron

Ayoya et al., 2006; Pasricha et al., 2008; Brooker et al., 2008; Fleming, 1982

Anemia
data on the epidemiology of iron deficiency
anaemia in East Africa and elsewhere point to
the important contribution of hookworms to
this condition
in Kathmandu, Nepal, hookworm infection
was associated with severe but not moderate
anaemia among women receiving antenatal
care
Ayoya et al., 2006; Stoltzfus et al., 1997; Bondevik et al., 2000; Ayoya et al., 2006; Stoltzfus et al.,
1997; WHO, 1993

Anemia
hookworm infection causes mechanical
laceration and enzymatic damage to the
mucosa of the small intestine leading to
approximately 0.05 mL/d of blood loss per
adult Necator americanus and approximately
0.25 mL/d per adult Ancyclostoma duodenale
The hypochromic microcytic anemia follows
chronic infection within 35 months after
exposure
Torlesse et al., 2001; Macleod, 1988

Nutrient Deficiency
The gastrointestinal blood loss, malabsorption
and appetite inhibition (Cline et al., 1984) may
further aggravate the iron, zinc and proteinenergy deficiencies and the anemia of
pregnancy

Torlesse et al., 2001

Low Pregnancy Weight Gain

Intervention studies suggest that even
relatively light hookworm infections may
decrease fetal growth and weight gain in
pregnancy

Torlesse et al., 2001

Intrauterine Growth Retardation &

Low Birth Weight
helminth infection results of this are low
pregnancy weight gain and intrauterine
growth retardation (IUGR), followed by low
birth weight (LBW), with its associated greater
risks of infection and higher perinatal
mortality rates

Rodriguez-Morales et al., 2006

Effects in Lactation
Lactating rats experience a breakdown of
immunity to parasites, i.e. they carry larger worm
burdens after re-infection compared to their nonlactating
counterparts. Feeding high-protein foods to
lactating rats results in reduced worm burdens.
This could be attributed to changes in
gastrointestinal
environment or to overcoming effects of nutrient
scarcity on host immunity.

Co-infection with Malaria

some studies have failed to find any
relationship between geohelminth infection
and malaria others have shown an increased
incidence of P. falciparum malaria in presence
of geohelminths
Ascaris lumbricoides infections were linked to
severe P. falciparum malaria in Senegal but
they have more often been associated with a
beneficial effect on malaria
Shapiro et al., 2005; Boel et al., 2010; Nacher et al., 2002; Sokhna et al., 2004; Spiegel et al.,
2003; Specht et al., 2007; Brutus et al., 2006; Le Hesran et al., 2004; Nacher et al., 2000; Brutus
et al., 2007; Nacher et al., 2001; Murray et al., 1978

Co-infection with Malaria

women in their second and third pregnancies
who were diagnosed with one particular type
of worm infection (Ascaris lumbricoides) were
less likely to have malaria than other women
in their second or third pregnancies who did
not have this type of worm infection (OR 0.4,
95% CI 0.20.8)

van Eijk et al., 2009

Co-infection with Malaria

Several immunological hypotheses, including
modulation of T-helper or dendritic cell
responses and cytokine induction, have been
proposed to explain these helminthplasmodium interactions

Pharmacologic Therapy
Albendazole
Inhibits microtubule synthesis
Larvicidal and ovicidal
Safety in pregnancy has not been established

Mebendazole
Inhibits micrtubule synthesis
Teratogenic

Katzung et al., 2008

Pharmacologic Therapy
Pyrantel pamoate
Not effective against migratory stages in the
tissues or against ova
Neuromuscular blocking agent
experience in pregnant is limited

Katzung et al., 2008

Pharmacologic Therapy
Ivermectin
Intensifying GABA (-aminobutyric acid)-mediated
transmission of signals in peripheral nerves
contraindicated in pregnancy

Piperazine
Blocking acetylcholine at the myoneural junction
Not to be given to women during pregnancy

(Katzung et al., 2008)

Pharmacologic Therapy
The specific and very effective treatment with
albendazole, mebendazole, ivermectin and
praziquantel has embryo-, fetotoxic, mutagenic
and teratogenic potential. Therefore, it should
be delayed until after delivery.

Bialek et al., 1999

Public Health Concerns

provision of deworming service as part of the
pre-natal package of basic or comprehensive
emergency obstetric and neonatal care
albendazole or mebendazole may be offered to
pregnant women in the 2nd and 3rd trimesters of
pregnancy and to lactating women in preventive
chemotherapy interventions targeting areas
where the prevalence of any soil-transmitted
helminth infection (ascariasis, trichuriasis and
hookworm infection) exceeds 20%
DOH, 2009; WHO, 2006

Public Health Concerns

Larocque, 2006

Public Health Concerns

In the present study, deworming with
albendazole or praziquantel during the second
or third trimester of pregnancy effectively
treated susceptible infections but had no
overall effect on maternal anemia, birth
weight, perinatal mortality, or congenital
anomalies.

Public Health Concerns

single dose of antihelminth along with iron
supplementation throughout the second and third
trimester of pregnancy was not associated with any
impact on maternal anaemia in the third trimester as
compared to iron supplementation alone (RR 0.76; 95%
CI 0.39 to 1.45, random-effects (2 studies, n = 1017)).
No impact was found for the outcomes of low
birthweight (RR 0.94; 95% CI 0.61 to 1.42 (1study; n =
950)), perinatal mortality (RR 1.10; 95% CI 0.55 to 2.22
(2 studies, n = 1089)) and preterm birth (RR 0.85; 95%
CI 0.38 to 1.87 (1 study, n = 984))

Future Directions
further knowledge is required to identify the
components that are needed to establish a full
program effort;
evaluate new and alternative antimalarial drugs;
evaluate the combined benefit of a package of
interventions addressing malaria (with
intermittent preventive treatment and
insecticide-treated bed nets), anemia (with iron
and folate supplements) and intestinal helminths
(with an antihelminth drug)

Future Directions
identify when and where vitamin A and zinc
supplements should be part of this package so
that public health officials can provide clear,
implementable recommendations addressing
safety, efficacy and cost-effectiveness of these
interventions
determine the link between infection and
poor nutritional and pregnancy outcomes and
the public health extent of the problem;

Future Directions
establish the appropriate public health
interventions if these studies demonstrate
that the disease extent and burden merit a
public health approach
evaluate and update case diagnosis and
management options so that individuals can
be well managed for their specific infection
and disease