Pathology Of Onchocerciasis Flashcards
What is Onchocerciasis and what causes it?
Onchocerciasis is a parasitic disease caused by Onchocerca volvulus
What is Onchocerca volvulus?
How is it transmitted?
What is the major risk factors?
What habitat can it be seen in?
Onchocerca volvulus is a filarial nematode that is the leading cause of preventable blindness in sub Saharan Africa
It is transmitted by repeated bites of infected blackflies (Simuliumspp.).
The major risk factor for onchocerciasis is residing or having extended visit time in areas where blackflies are endemic.
The vector’s habitat is near ‘fast moving water’ so there is higher incidence of human disease near the rivers accounting for the name river blindness given to this disease.
How does one get infected with the parasite?
- It is important to note that it often takes more than one blackfly bite to get infected with onchocerciasis.
- The most serious and debilitating outcomes associated with the condition typically happen after years of repeated exposure to the parasite.
- The more infections a person experiences throughout their lifetime, the more likely the damage done to the eyes and skin becomes permanent or leads to blindness and disfigurement.
EPIDEMIOLOGY
Onchocercainfections are found in tropical climates. The main burden is in 31 countries in sub-Saharan Africa.
The parasite is also found in limited areas in South America and in Yemen in the Middle East.
Four countries have been verified by the World Health Organization (WHO) as free from onchocerciasis: Colombia, Ecuador, Mexico, and Guatemala.
Colombia was the first country of the world receiving the verification of the elimination of onchocerciasis in 2013, followed by Ecuador in 2014, Mexico in 2015, and Guatemala in 2016.
Globally, it is estimated that there are 18 million people infected and 270,000 blinded by onchocerciasis
LIFE CYCLE
- During a blood meal, an infected blackfly (genusSimulium) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite woundin subcutaneous tissues
- The larvae develops into adult filariae, which commonly reside in nodules in subcutaneous connective tissues
- Some nodules may contain numerous male and female worms. Adults can live in the nodules for approximately 15 years
- Adult worms mate and the female worms lay eggs which develop into microfilariae
- A blackfly ingests the microfilariae during a blood meal
- After ingestion, the microfilariae migrate from the blackfly’s midgut through the hemocoel to the thoracic muscles
- There the microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae
- The larvae molts twice inside the fly before reaching the infective stage
- The third-stage infective larvae migrate to the blackfly’s proboscisand can infect another human when the fly takes a blood meal
Specifications and measurements
- Females measure 33 to 50 cm in length and 270 to 400 µm in diameter, while males measure 19 to 42 mm by 130 to 210 µm.
- In the subcutaneous nodules, the female worms are capable of producing microfilariae for approximately 9 years.
- The microfilaria measures 220 to 360 µm by 5 to 9 µm and is unsheathed, it has a life span that may reach 2 years.
- Microfilariae are occasionally found in peripheral blood, urine, and sputum but are typically found in the skin and in the lymphatics of connective tissues
PATHOGENESIS
The disease attributed to onchocerciasis is primarily due to inflammation induced by the microfilaria death.
Adult O. volvulus parasites mate in the dermis where they are surrounded by a mixed infiltrate of host cells that produce a characteristic subcutaneous nodule (onchocercoma)
Inseminated females produce microfilariae which accumulates in the skin and can disseminate to the eye chambers
Wolbachia is a symbiotic bacteria that is required for the fertility of filarial species. Symbiotic wolbachia infect filarial nematodes and contribute to the pathogenesis of the disease. They are required for nematode development and reproduction
Antibiotics that eradicate wolbachia impair nematode survival and fertility.
MORPHOLOGY
Onchocerca volvulus causes chronic, itchy dermatitis with focal darkening or loss of pigment and scaling, referred to as leopard, lizard, or elephant skin.
Foci of epidermal atrophy and elastic fibre breakdown may alternate with areas of hyperkeratosis, hyperpigmentation with pigment incontinence, dermal atrophy, and fibrosis.
The subcutaneous onchocercoma is composed of a fibrous capsule surrounding adult worms and a mixed chronicinflammatory infiltrate that includes fibrin, neutrophils, eosinophils, lymphocytes, and giant cells.
Overhanging skin may develop, especially in the groin, as a result of the destruction of the elastic tissue
The progressive eye lesions begin with punctate keratitis along with small, fluffy opacities of the cornea caused by degenerating microfilariae.
This is followed by a sclerosing keratitis that opacifies the cornea. Keratitis is sometimes accentuated by treatment with anti filarial drugs (Mazzotti reaction).
Microfilariae in the anterior chamber cause iridocyclitis and glaucoma, whereas involvement of the choroid and retina results in atrophy and loss of vision.
Mazotti Reaction
The Mazzotti reaction, first described in 1948, is a symptom complex seen in patients after undergoing treatment of onchocerciasis with the medicationdiethylcarbamazine(DEC).
Mazzotti reactions can be life-threatening, and are characterized by symptoms and signs that occur within seven days of treatment of microfilariasis. They include:
Fever
Urticaria
Swollen and tender lymph nodes
Tachycardia
Hypotension
Arthralgia
Edema
Abdominal pain
DIAGNOSIS
Skin snip Microscopy:
Onchocerciasis is usually diagnosed by the finding of microfilariae in skin snips. Microfilariae ofOnchocercado not exhibit any form of periodicity and skin snips may be collected at any time.
Skin snips should be thin enough to include the outer part of the dermal papillae but not so thick as to produce bleeding.
Skin snips should be placed immediately in normal saline or distilled water, just enough to cover the specimen.
Microfilariae tend to emerge more rapidly in saline, however in either medium the microfilariae typically emerge in 30-60 min and can be seen in wet mount preparations
For a definitive diagnosis, allow the wet mount to dry, fix in methanol, and stain with Giemsa or hematoxylin-and-eosin.
Typically six snips are taken from different areas of the body. Polymerase chain reaction (PCR) of the skin snip can allow for diagnosis if the larvae are not visualized.
Biopsy:
Onchocerciasis can also be diagnosed in patients with nodules in the skin, the nodule can be surgically removed (biopsy) and examined for adult worms.
Slit-lamp examination:
Infections in the eye can be diagnosed with a slit-lamp examination of the anterior part of the eye where the larvae, or the lesions they cause, are visible.
Antibody tests:
Antibody tests have been developed to test for infection, they can detect if the body has responded to an onchocerciasis infection. These tests cannot distinguish between past and current infections, so they are not as useful in people who lived in areas where the parasite exists, but they are useful in visitors to these areas. Some of the tests are general tests for infection with any filarial parasite and some are more specific for onchocerciasis.
TREATMENT
Because most of the pathogenesis of onchocerciasis is secondary to microfilariae, the goal of therapy is to eliminate the microfilaria stage of disease to improve symptoms, to prevent progression of eye lesions, and to interrupt disease transmission.
People who are found to be infected withO. volvulusshould be treated in order to prevent long-term skin damage and blindness. The recommended treatment is Ivermectin, which will need to be given every 6 months for the life span of the adult worms (i.e., 10–15 years) or for as long as the infected person has evidence of skin or eye infection.
Ivermectin kills the larvae and prevents them from causing damage but it does not kill the adults.
There is a promising treatment using doxycycline that kills the adult worms by killing theWolbachiabacteria on which the adult worms depends on in order to survive.
Before any treatment is begun, it is necessary to make sure that the individual is not also infected withLoa loa, another filarial parasite found in central Africa that is sometimes found in the same areas whereO. volvulusis found, becauseLoa loacan be responsible for severe side effects to the medications used to treat onchocerciasis.
Most clinicians recommend that subcutaneous nodules should be excised, if possible, thereby removing the adult worms that may reproduce more microfilariae over time
PREVENTION AND CONTROL
There are no vaccines or medications available to prevent becoming infected withO. volvulus.
The best prevention efforts include personal protection measures against biting insects. This includes:
Wearing insect repellant such as N,N-Diethyl-meta-toluamide (DEET) on exposed skin
Wearing long sleeves and long pants during the day when blackflies bite
Wearing permethrin- treated clothing.
Vector Control:Spraying the flies’ breeding sites with insecticide can disrupt the life cycle of the parasite and stop new infections from happening in the area.
Mass Treatment Programs
Life Cycle
- During a blood meal, an infected blackfly transmits filarial larvae onto the skin of the human host, where the larvae enter the bite wound.
- The larvae migrate to subcutaneous tissues.
- There, the larvae develop into adult filariae, which commonly reside in subcutaneous nodules for up to about 15 years.
- After mating, female worms produce unsheathed microfilariae, which are typically present in the skin and the lymphatics of connective tissues but are occasionally present in peripheral blood, urine, and sputum.
- A blackfly ingests the microfilariae during a blood meal.
- After ingestion, the microfilariae penetrate the blackfly’s midgut and migrate to the thoracic muscles.
7–8. There, the microfilariae go through 3 stages (L1-L3) of larval development.
- Larvae migrate to the blackfly’s proboscis and can infect another human when the fly takes a blood meal.
