Hookworms

Megbaru A

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 Introduction
• Hookworm infection in humans is caused by
– Necator americanus & Ancylostoma duodenale
• is one of the most common chronic infections
• ~ 740 million cases in the tropics & subtropics
• Hookworm infection occurs predominantly among
impoverished people
– pre-1949 China :“sick man of Asia”
• high prevalence and intensity of infection with
hookworm

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Transmission pattern and epidemiology

• Greatest number of hookworm cases

– Asia & sub-Saharan Africa
• N. americanus is more common
• A. duodenale is more geographically restricted
• Geographical overlap (mixed infection)
• 3 species of zoonotic hookworm
– A. ceylanicum (dogs and cats)
– A. caninum (dogs)- human eosinophilic enteritis
– A. braziliense-causes cutaneous larva migrans
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 Transmission pattern and epidemiology
• Higher HW transmission
– sandy soils , Moisture, To
• Age
– more common in adults
– child targeted deworming
programs???
– Exposure differences
– Transmission
• fields vs near houses
• Gender ???
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 Transmission pattern cont’d

• Impact of a treatment program directed at either

– Children/ adults/whole population
• Depends on
i) Potential contamination from a population group
– Egg output
– Behavior (defecation sites favoring parasite survival)
• Children are more indiscriminate (more contamination)
• Adults deposit feces in sites more conducive to larval
dev’t
ii) Mixing patterns b/n children and adults
• Relative probabilities of the members of one group being
infected with infective stages that come originally from the
same or d/t group
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 Mixing pattern
 3 models (impact of de-worming programs)
• Model 1: One transmission site (random mixing
model)
– Adults and children get infected from the same
transmission site (equal probability of infection)
• Model 2: Separate transmission site (no mixing
model)
– Different & unconnected transmission sites
• Model 3: Two sites (restricted mixing model)
– 2 transmission sites
– One of the groups use both sites
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Figure 1. Flow charts to show the mixing structure
of the models used
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Figure 2.Results of simulation of a hookworm control program treating children
only. The mean worm burden for each group (adults solid line, children dotted
line) is plotted over time. (a) Random mixing model (b) No mixing model (c)
Restricted mixing model 8
 Mixing pattern cont’d
 Treatment of children only
• Random mixing model
– moderate reduction in mean worm burden in children
– a small reduction in adults
• No mixing model
– a much larger reduction in child worm burden
– no change in the adult worm burden
• Restricted mixing model
– virtually no reduction in mean worm burden in the adults
• b/c transmission continues to occur at the second site
– reduction for children is considerably less than for the no mixing
model
• continued presence of heavily infected adults
 this model shows the lowest overall reduction in mean worm burden

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Figure 3. Results of simulation of a hookworm control programme treating
adults only. The mean worm burden for each group (adults solid line, children
dotted line) is plotted over time. a. Random mixing model. b. No mixing model.
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c. Restricted mixing model
 Mixing pattern cont’d
Treatment of adults only
• higher initial worm burdens
• higher contamination rates
• the impact of treating adults will lead to greater reductions in overall
mean worm burden
• less variation in the trajectory of the mean worm burden curve for
adults between the models
– Lesser epidemiological importance of children
• random mixing
– a small reduction in the worm burden of children and the overall
reduction is greater for this case compared with the no mixing
case

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Figure 4. Results of simulation of a hookworm control programme treating
children and adults. The mean worm burden for each group (adults solid
line, children dotted line) is plotted over time. 4a. Random mixing model. 4b.
No mixing model. 4c. Restricted mixing model 12
 Mixing pattern cont’d
• Treatment of both groups
– increased reduction in overall mean worm burden
– no mixing model
• sum of the child & adult targeted treatment programs
– the overall reduction in mean worm burden is almost
exactly equal for random mixing and no mixing
– However, when there is no mixing, the reduction in
children is larger and the reduction in adults is smaller
• greater epidemiological importance of adults
• In the presence of adults, the child group experiences
higher infection rates

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 Worm characteristics

1. Habit and Habitat

• The adult worms live in the jejunum
– Duodenum(less often)
– ileum (rarely)
• Hookworms flourish under primitive conditions;
– Barefooted society
– Miners
– poor sanitation
– open defecation

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 Hookworms cont’d
Morphology
(i) Shape, size and color
• Adult worms are small and cylindrical in shape
• Sexes are separate
• adult females:
– 10 to 13 mm (A. duodenale)
– 9 to 11 mm (N. americanus)
• adult males:
– 8 to 11 mm (A. duodenale)
– 7 to 9 mm (N. americanus)
• Freshly passed worm, reddish brown ( ingested b/d)
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 Morphology cont’d

• Adult worm (A. duodenale)

– curved (dorsal concave & ventral
convex)
– Anterior end is bent dorsally in the
direction of body curvature
– Mouth is not at the tip but directed
dorsally
– Prominent buccal capsule (6 teeth;
4 hook-like teeth ventrally, and 2
knob-like dorsally)
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 Ancylostoma doudenale cont’d

• Male Worm
• Posterior end
– Round copulatory bursa
• 3 lobes; 1 dorsal and 2 lateral
• the lobes are supported by 13 fleshy
chitinous rays, 5 each in lateral lobes
and 3 in dorsal lobe:
– The pattern of the rays helps Spp
identification
– 2 long retractile bristle-like
copulatory spicules

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 Ancylostoma doudenale cont’d
• Female worm (A. duodenale)
– Conoid hind with a
subterminal ventral anus
– vulva opens ventrally
– vagina situated behind the
middle of the body
• leads to coiled ovarian tubes
– copulating pair presents a Y-
shaped appearance
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 Hookworm morphology cont’d
• Necator Americanus
• Morphology
– The anterior end is bent in a direction
opposite to the body curvature
– smaller buccal capsule with 2 pairs of
semilunar cutting plates
– long, conical & wide copulatory bursa
– copulatory spicules are fused at the
ends to form a barbed tip
– Vulva is placed anterior
to middle of the body

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 A. Adult female (AD— anterior curvature
uniform with body curve; NA anterior
curvature in opposite direction to body
curve
– Vulva opens at junction of middle and
posterior thirds in AD; in (NA) it opens a
little in front of the middle;
A B. Buccal capsule, AD 2 pairs of hook-Iike
teeth ventrally and a dental plate with
median cleft dorsally; (NA) has two pairs
B of semilunar cutting plates
C. Copulatory bursa (AD), the dorsal ray
(D.R.) is single with a split end, making a
total of 13 rays; (NA) has a paired dorsal
C ray, making a total of 14 rays. Copulatory
spicules (C.S.) separate in (ancylostoma);
they are fused at the tip in (necator)
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 Morphology
• Eggs
– Oval or elliptical, 60 μm x40 μm.
– Colorless, not bile stained
– Surrounded by a thin transparent hyaline shell membrane
– unsegmented ovum when released
– ovum develops down the intestine
– When passed in feces, the egg contains a segmented
ovum, usually with 4 or 8 blastomeres
– There is a clear space between the segmented ovum and
the egg shell

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Eggs

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 Hookworms cont’d
3. Digestive System
• Consists of
– Mouth
– buccal capsule
– muscular pharynx
– oesophageal bulb
– intestine, rectum and cloaca in male but an anus in female
– glands connected with the digestive system
• oesophageal gland (secretes a chemical to prevent the
clotting of blood )

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 Hookworms cont’d
4. Reproductive Organs
• Sexes are separate
• sexual dimorphism is well distinct
• Male reproductive organs
– a single, tubular testis twisted around the intestine
– vas deferens
– seminal vesicle
– ejaculatory duct which opens into the cloaca

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 Reproductive organs cont’d`
• Female reproductive organs
– 2 highly twisted tubules (ovaries)
– oviducts
– seminal receptacles
– muscular uterus
– vagina which opens out by vulva/gonopore

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Life History

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 Life history cont’d
• Copulation and Fertilization:
– Copulation occurs in the intestine of the host
• Egg Laying:
– The female worm lays eggs in the intestine of
the host
– pass out with faeces
– On an average nearly 9,000-25,000 eggs/
day/worm

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 Life history cont’d
• Development in Soil:
– favourable conditions (moisture, oxygen and temperature
(about 68-85°F)
– embryo develops into a rhabditiform larva (250 µm)
– larva hatches out of the egg in the soil (48 hours)
– feeds on bacteria and other debris & molts twice(3rd & 5th
day)
– develops into a filariform larva (500 to 600 µm)
– non feeding stage (alive for several wks)
– time from eggs to filiform larvae (8 -10 days)

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 Life history cont’d
• Infection to New Host:
– filiform larvae penetrate the skin
– oral spears to penetrates the soft skin of the feet and hands,
through hair follicles
• Migration and development:
– From subcutaneous tissues, the larvae enter into the lymphatic’s
and small venules
– pass through the lymphatic-vascular system into the venous
circulation
– are carried through the right heart into the pulmonary capillaries
– break through the capillary walls to enter into the alveolar spaces

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Life history cont’d

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Skin penetration and tissue migration
• Penetration of the skin by L3
– chemical process
– mediated by proteolytic enzymes (aspartic proteases
(APRs APR Na-APR-1 )
• degrade the connective tissue substrates
– collagen, fibronectin, laminin, and elastin
– Hyalurnidase
• Degrade hyaluronic acid
– major component of the extracellular matrix
– Metalloprotease (Ac-MTP-1)
• aids larval migration through the skin and other tissues
by degrading fibronectin, laminin, and collagen
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Nutrient acquisition by hookworms
• Blood-feeding
– Attachment to intestinal mucosa by teeth/cutting plates
– mechanical disruption of mucosal plug lodged within the
worm’s buccal capsule
• metalloprotease Ac-MTP-2
– anticoagulant peptides (NAPs)
• facilitate ingestion of blood released from ruptured
capillaries
• Adu NAP4:
– inhibit factors VIIa/tissue factor complex
– factors Xa and Xia

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 Nutrient acquisition cont’d
• Hgb digestion
– Aspartic proteases
• Na-APR-1 and Ac-APR-17 cleave the intact Hgb tetramer
at many sites
• allows further proteolysis of globin fragments by other
proteases
– Cysteine proteases
• Ac-CP-2 & Na-CP-3 degrade intact hemoglobin
– Metalloproteases
• (Na-MEP-1) hydrolyzes host globin fragments after
cleavage by Na-APR-1
– Glutathione-S-transferases (GSTs)
• detoxify oxidative iron contained in heme and hematin
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 Immune responses to hookworms
• Sophisticated life cycle
– antigenic challenge occurs at numerous anatomic sites
• skin, lungs and intestinal mucosa
– Different mRNA and protein profiles of different developmental
stages
– In addition, hookworms secrete immunomodulatory molecules
• Loosely fits the typical of gastrointestinal nematodes in the types of
immune response
– Ab isotypes and subclasses & cellular responses (Th2) immune
response
• Elevated levels of parasite-specific and total IgE
– accompanied by eosinophilia
» systemic and localised to the lungs and around the
sites of attachment in the gut
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 Immune responses cont’d
• Protection against gastrointestinal
nematodes is usually mediated by Th2
responses
– IL-4 and IL-5 play prominent roles
• hookworm infections exhibit some of
the hallmark features of Th2 responses
(IgE & local & systemic eosinophilia)
• Immunity fails to protect most infected
people
– cross-regulatory mechanisms
– Associations between anti-ES IgG
levels and parasite burden in
younger hosts have been reported
– the association reverses in older
hosts
• Profound cellular
hyporesponsiveness in chronic HW
infection
– successful removal of parasite
load by anthelminthic therapy
– Older pts (>40y.o) no restoration
of cellular proliferation (to
hookworm antigens) ~ 12
months
– 3 months after treatment in
younger pts (<39 y.o)
• Moreover, cellular proliferation to
non-hookworm antigens was also
blunted in the older cohorts –
patients (P40 y.o.)
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Immune responses cont’d

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 Clinical presentation

• Early symptoms
– 1-2 weeks of cutaneous infection
• local irritation (ground itch)
–intensely pruritic, erythematous, or
vesicular rash
–severity is proportionate to the
number of infecting larvae
–distinguished from a creeping eruption
( A braziliense)
Ground itch

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 Clinical presentation cont’d

• Cough and wheezing

– 1 week after exposure
– larval migration through the lungs
– Pulmonary symptoms are uncommon and usually
mild, except in severe infections
– In rare cases, severe infections may give rise to
Löffler syndrome
• paroxysmal attacks of cough
• Dyspnea, little or no fever, and eosinophilic pulmonary
infiltrates
 Clinical presentation cont’d

• Migration of the worms into GIT

– GI discomfort secondary to irritation
– mature worms in the jejunum
• diarrhea, vague abdominal pain, colic, flatulence,
nausea, or anorexia
• Wakana syndrome
– in people infected with a large burden of A
duodenale through oral ingestion
– resembles an immediate-type hypersensitivity reaction
• pharyngeal itching, hoarseness, nausea, vomiting,
cough, dyspnea, and eosinophilia
 Clinical presentation cont’d
•Late symptoms
–Moderate-to-heavy infections=significant b/d loss
•Melena
•Exhausted iron reserves + history of poor iron intake → anemia 
–Severe iron-deficiency anemia 
•lassitude, headache, palpitations, exertional dyspnea, syncope, or
edema
•perverted taste and pica
•Deficits in physical and intellectual growth
•Eosinophilic enteritis
–repeated episodes of abdominal pain
–may mimic appendicitis or intestinal perforation
Hookworm anemia

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 Clinical presentation cont’d

• Complications (heavy parasitism)

– acute gastrointestinal hemorrhage
– severe acute anemia
– congestive heart failure
– children with chronic infection perform poorly
in school
• chronic iron-deficiency anemia
• missed learning opportunities
– stunted growth
 Diagnosis cont’d
• Stool
– Occult blood
– Charcot-leyden crystals
• Stool culture
– Harada Mori method
• Blood
– Eosinphilia
– Microcytic hypochromic anaemia

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 Eggs: Hookworms vs Trichostrongylus
Hookworms
•colorless with a thin shell
which appears
microscopically as a black line
around the ovum
• Oval in shape (65x40µm)
•Contains an ovum which
appears segmented (usually
4–8 cell stage)
Trichostrogylus
•Longer and thinner than
a hookworm egg (85-115
µm in length
•More pointed at one or
both ends
• Usually appears more
segmented

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Eggs: Hookworms vs Trichostrongylus

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 Larvae:Hookworms vs Strongyloides
Strongyloides Hookworm
2nd small buccal capsule large buccal capsule
stage Large genital Small genital
larva primordium primordium
3rd Esophagus extends to Esophagus extends to
stage approximately approximately
larva 40% of the total length 25% of the total length

No sheath Sheath present

Tail forked Tail pointed

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Rhabiditiform Larvae:Hookworms vs
Strongyloides

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 Prevention and control
– Prevention of soil pollution with feces
– Proper disposal of night soil and use of
sanitary latrines
– Use of footwear
– Gloves
– Treatment

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