Growth and development failure (failure to thrive) due to parasitic infections

Lisawati Susanto & Taniawati Supali Department of Parasitology, Faculty of Medicine, University of Indonesia

Definition
is a description applied to children whose current weight or rate of weight gain is significantly below that of other children of similar age and sex. height or weight less than the third to fifth percentiles for age on more than one occasion.

Failure to thrive
In general, the rate of change in weight and height may be more important than the actual measurements. It is important to determine whether failure to thrive results from medical problems or factors in the environment, such as abuse or neglect.

Etiology of failure to thrive

Chromosome abnormalities, such as Down syndrome and Turner syndrome Abnormalities in the gastrointestinal system, which may result in malabsorption or absence of digestive enzyme, resulting inadequate nutrition. Abnormalities of the endocrine system, such as growth hormone deficiency Damage to the brain or central nervous system, which may cause feeding difficulties Anemia

Some parasites within their life cycle pass through gastrointestinal system

Giardia lamblia Ascaris lumbricoides Hookworms

Parasitic infection and failure to thrive

Chronic parasitic infections may cause disturbances on food absorption in the GI tract system effecting the host nutrition.

Parasitic infection and failure to thrive

In general parasitic infections could be divided into two classifications: helminthes (metazoa) and protozoa Helminthes: Ascaris lumbricoides, hook worm Protozoa: Giardia lamblia

Class Nematoda

Species
Ascaris lumbricoides Hookworms

Infective stage
Mature egg Filariform larva

Protozoa

Giardia lambia

Cyst

Risk factors
Defecation habits Geophagia (eating soil) Cultural differences relating to personal and food hygiene Inadequate sanitation Poor socio-economic conditions Occupation such as farmer, mining labour

Ascaris lumbricoides
Ascariasis is a disease caused by Ascaris lumbricoides (round worm), which is the most prevalent intestinal worm infection in the world. The adult worm lives in the lumen of small intestine Eggs are found in the soil, infection occurs when a person accidentally ingests (swallow) infective eggs.

Ascariasis
Route of infection:
Children/Human become infected after touching their mouth with their hands contaminated with eggs from soil or other contaminated surfaces

Life cycle of A. lumbricoides

Human ingested embryonated egg. In the stomach, larvae hatch from the eggs. and are carried via the hepatic portal vein, then systemic circulation to the lungs, mature in the lungs (10 -14 days), penetrate the alveolar walls, ascend the bronchial tree to the throat, and are swallowed. Once swallowed, they reach the intestines and develop into adults worms. Adult female worms lay eggs that are then passed in feces; this cycle will take between 2 3 months

Eggs are passed in the stool. Unfertilized eggs may be ingested but not infective.

Pathogenesis
Heavy infection children with malnutrition Acute inflammatory response Proinflammatory Monokines (IL-1, IL-6, TNF-) Appetite Loss of protein raise resting energy expenditure

Pathogenesis
Adult worms in the small intestine

Direct competition with the host for nutrients

Ascaris lumbricoides
Adult worms
secreting

Protease inhibitors & anti-trypsine

Interfering host digestion

Enable to ingest the meal before host absorption

Ascaris lumbricoides
Adult worms Abnormalities of small intestine Changes in the absorption of fat and xylose

Symptoms of ascariasis

Commonly infected persons: No symptoms Immature worms enter the small intestine and mature into adult worms. - abdominal symptoms: abdominal discomfort-fullness, malabsorption.

Ascariasis
Complications: Adult worms move to bile duct and interfere the lipid digestion. Heavy infection in children:
loss of appetite and insufficient absorption of digested foods can occur as a large number of parasites take nourishment from the hosts body Nutritional deficiencies

Diagnosis
Eggs stage in stool examination

Adult worms in stool or vomit

Treatment
Drug of choice: Albendazole - 400 mg (single dose) Mebendazole - 500 mg (single dose) Pyrantel pamoat - 10 mg/kg BW (single dose)

Prevention
Sanitary disposal of feces through the implementation of latrines Health education: personal hygiene and food hygiene

Hookworm
There are two species of hookworm which infect human
Ancylostoma duodenale Necator americanus

Hookworm
Disease:
Ancylostomiasis Necatoriasis

Route of infection: Ancylostoma duodenale : oral, percutaneous Necator americanus : percutaneous

Filariform larva (infective stage)

Hookworm
Hookworm eggs require warm, moist, shaded soil to hatch into larvae. These barely visible larvae penetrate the skin (often through bare feet), are carried to the lungs, go through the respiratory tract to the mouth, are swallowed, and eventually reach the small intestine. This journey takes about a week. In the small intestine, the larvae develop into half-inch-long worms, attach themselves to the intestinal wall, and suck blood. The adult worms produce thousands of eggs. These eggs are passed in the feces (stool). If the eggs contaminate soil and conditions are right, they will hatch, molt, and develop into infective larvae again after 5 to 10 days.

Hookworm
Worms live in the small intestine by attaching to the mucose via the buccal capsule. Worms feed on host mucosa and blood. Worms change position of attachment site every 4 6 hours in response to tissue depletion and or the onset of local inflammation. (The blood is still coming out from the old attachment site for several day)

Pathogenesis
The adult worms move several times a day to different attachment sites in the intestinal mucosa. The worms eat villous tissue and also suck blood directly from their site of attachment to the intestinal mucosa and submucosa. The worms secrete an anticoagulant that blocks the action of host factor Xa and VII a/tissue factors. Blood loss continues after the worms move to a new location.

Pathogenesis
The combination of constant blood loss due to hookworm infection and poor iron intake in the diet results in iron deficiency anaemia. The severity of iron-deficiency anemia depends upon the species of hookworms in the intestine (A. duodenale ingests 4-5 times more blood each day than N. americanus)

Pathogenesis
Adult worms Suck host blood from the capillaries of Intestinal mucosa Secrete anti-coagulant
blocking factors Xa dan VII a

Loss of blood plasma & Its constituents

Blood lost

Hypoproteinemia

Anaemia

Hookworms and host blood loss

Necator americanus Ancylostoma duodenale 0.15 (0.05-0.30) 0.20(0.14-0.26) 5 (4-7)

Intestinal blood loss in ml per worm per day, mean (range) Number (range) of worms causing a blood loss of 1 ml/day Blood loss (ml/day) per 1000 epg stool Iron loss (mg/day) per 1000 epg stool

0.03 (0.01-0.04) 0.04 (0.02-0.07) 25 (14-50)

1.3 (0.82-2.24)

2.2 (1.54-2.86)

0.45

0.76

Hookworm
Head of A. duodenale Head of N. americanus

Heavy infection with hookworm can create serious health problems for newborns, children, pregnant women, and persons who are malnourished.

Symptoms
aHookworms

on the bowel mucosa

Heavy infection can cause anemia, abdominal pain, diarrhea, loss of appetite, and weight loss. When children are continuously infected by many worms, the loss of iron and protein can retard growth and mental development, sometimes irreversibly. Anaemia in Children can impair their educational performance.

Diagnosis
The examination of stool sample for the presence of eggs is the most reliable means of diagnosis. The recommended procedure is the KatoKatz technique which is able to count the number of eggs to determine intensity of infection Egg counts express as EPG (eggs per gram of faeces)
Egg

Rhabditiform larva

Treatment
Drug of choice:
Albendazole 400 mg (single dose) Mebendazole -100 mg (twice a day for 3 consecutive days)

Prevention
Sanitary disposal of feces through the implementation of latrines Health education: personal hygiene and food hygiene Encouraging use of shoes or other footwear (hookworms).

Giardia lamblia
(Giardiasis)
Zoonosis Host: animal and human

Trophozoite

Cyst

Life cycle of G.lamblia

Giardia lamblia exists in two forms, an active form called a trophozoite, and an inactive form called a cyst. The active trophozoite attaches to the lining of the small intestine with a sucker and is responsible for causing the signs and symptoms of giardiasis. The trophozoite cannot live long outside of the body, therefore it cannot spread the infection to others. The inactive cyst, on the other hand, can exist for prolonged periods outside the body. When it is ingested, stomach acid activates the cyst, and the cyst develops into the diseasecausing trophozoite. It takes ingestion of only ten cysts to cause infection. Trophozoites are important not only because they cause disease, they also produce cysts that exit the body in faeces and spread infection to others.

Pathogenesis
The mucosal and luminal factors involved in the pathogenesis.
The mucosal factors : The intestinal mucosa is damaged by the attachment of trophozoites on the epithelial brush border. Absorptive activities are blocked due to the trophozoites "blanketing" the intestinal mucosa and causing functional mucosal obstruction and interference in absorption of fats and fat-soluble vitamins. The luminal factors : The increased number of anaerobic & aerobic bacteria in the small intestine leads to the deconjugation of bile salts. The bile salts are then taken up by the trophozoites stimulating parasite growth. The consumption of host bile salts in chronic infection deplete the bile salt pool and thus contribute to fat malabsorption.

Pathogenesis
Immunologic mechanisms may also play a role since individuals with decreased gamma globulin levels have a higher prevalence of infection and reinfection.

Clinical presentation
The clinical presentation of the disease is influenced by the host's immune response to the parasite and the parasite load in the small intestine.

Symptoms
10-25 cysts are capable of causing clinical disease. Symptoms of giardiasis normally begin 1 to 2 weeks (average 7 days) after becoming infected.

Symptoms
Commonly no symptoms at all. Diarrhea:
Stools become malodorous, mushy, and greasy. Watery diarrhea may alternate with soft stools or even constipation.

Flatulence Steatorrhea Stomach cramps Nausea. These symptoms may lead to weight loss and dehydration.

Symptoms
These symptoms may lead to weight loss. Weight loss occurs in more than 50% of patients and averages 10 pounds per person. Chronic illness may occur with adults presenting with long-standing malabsorption syndrome and children with failure to thrive.

Symptoms
The disease is more prevalent in children. The symptoms of giardiasis cause dehydration due to diarrhea, therefore drink plenty of fluids .

Laboratory examination
Stool examination
Trophozoites may be found in fresh, watery stools. Cysts are passed in soft and formed stools.

Laboratory examinations
Stool antigen detection
ELISA to detect giardia specific antigen 65 kDa (GSA-65)

ELISA Results

Other tests
Detection of trophozoites in duodenal fluid can be done by String test / Entero test.

Treatment
Metronidazole 3 x 250 750 mg for 7 10 days Tinidazole: 2 g- single dose

Prevention
Washing hand after defecation. Chlorination, sedimentation, and filtration methods to purify public water supplies. Drinking water can be purified by using filtration (pore size, <1 mm) or by briskly boiling water for at least 5 minutes.