Lecture 8 - Nematodes: Onchocerciasis Filariasis Flashcards

1
Q

More than 180 million estimated to have at least one of the human filariases ⇒ Long term suffering & hardship.

Name three important nematode infections.

A
  1. Lymphatic filariasis
  2. Onchocerciasis
  3. Loiasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Pathology causes and treatment filariasis:

What is the treament targeted on? Why?

How is pathology caused?

Why is it important to have ‘care in treatment’?

A

New treatments against the bacterial symbionths (Wolbachia) of microfilaria, because adult worms live for ~17 years and are relatively unresponsive to anti-helminth agents.

Pathology due to dying worms, their bacterial symbionths and secondary bacterial infections.

Care in treatment, because killing all the worms at once may provoke irreversible immune responses.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the difference in clinical course between those living in endemic regions and travellers?

A

Infection is usually asymptomatic, and disease generally occurs only after prolonged exposure and accumulation of worms. - those living in endemic regions.

Travellers may develop severe disease at lower levels of exposure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Vectors determine filarial distribution:

  • Wuchereria bancrofti -
  • Brugia malayi -
  • Onchocerca volvulus -
  • Loa loa -
A
  • Wuchereria bancrofti - GLOBAL (anopheles, culex, aedes)
  • Brugia malayi - SE Asia/India
  • Onchocerca volvulus - Africa/Americas (blackflies, simulium)
  • Loa loa - Africa (tabanid flies)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Adult female Onchocerca volvulus (40 cm) live in humans’ subcutaneous tissue, sometimes coiled within fibrous nodules, where they produce microfilariae (350 μm).

  • Where can microfilariae migrate to?
  • When do microfilariae develop further? When taken up by blackflies, how long does it take for them to be transmitted into another person?
  • How long do microfilariae live?
A

The microfilariae migrate through the skin and often into the eyes.

Microfilariae only develop further if they are taken up by biting blackflies of the genus Simulium. These flies can transmit infection after a week or more and deposit infective larvae as they bite another person.

Microfilariae live for about 1 year and adults 12 year on average.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Life cycle Onchcerca volvulus:

Start with blackfly (g. Simulium) taking a blood meal and parasites penetrating skin and end with blackfly midgut/thoracic muscle/proboscis stage.

A
  1. Blackfly takes a blood meal and third stage larvae penetrate skin wound. In subcutaneous tissue larvae develop into adults and commonly reside in fibrous nodules.
  2. Female filariae produce microfilariae. The microfilariae are sheathed and are commonly found in skin and lymphatic tissues.
  3. Blackfly ingests microfilariae and they will migrate from the midgut (and lose sheaths) to thoracic muscles via the hemocoel.
  4. There the microfilariae develop into first stage larvae and subsequently into third-stage larvae.
  5. The third stage larvae migrate to blackfly’s proboscis and can infect other humans when blackfly feeds again.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Onchocerciasis (River Blindness) - Onchocerca volvulus.

How is pathology is caused.​

A

Pathology is due to immune reaction to dead and dying microfilariae and Wolbachia symbionths.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How is “leopard skin” caused in ‘late onchocerciasis’?

A

Intense itching -> healing leads to depigmentation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are clinical features of Onchocerciasis (River Blindness)?

A
  • May be asymptomatic
  • Skin manifestations
  • Subcutaneous nodules
  • Eye disease
  • General health
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

River Blindness:

Why do adult worms cause few symptoms? How does pathology arises in onchocerciasis?

A

Adult worms cause few symptoms, because they evade the host immune response.

Pathology immune reaction to dead and dying microfilariae and Wolbachia symbionts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

A clinical feature in onchocerciasis is “general health”. How is general health affected?

A

Skin disease may be socially stigmatizing and medication may cause economic loss. Unrelenting itch may result in chronic sleep disturbance and depression. Blind people in village communities have a shortened lifespan.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Skin manifestations are:

  • Acute papular onchodermatitis (APOD) - intensely …, papular …, sometimes oedema.
  • Chronic papular onchodermatitis (CPOD) - larger, itchy, … papules (Sowda).
  • … onchodermatitis - discrete itchy, hyperpigmented papulnodular plaques, often lymphadenopathy.
  • Excoriation and … bacterial infection - due to relentless itching. … depigmentation (leopard skin).
  • Skin atrophy and depigmentation - loss of … cause wrinkled skin, with inguinal lymphadenopathy -> …. .
A
  • Acute papular onchodermatitis (APOD) - intensely itchy, papular rash, sometimes oedema.
  • Chronic papular onchodermatitis (CPOD) - larger, pruritic, hyperpigmented papules (Sowda).
  • Lichenified onchodermatitis - discrete pruritic, hyperpigmented papulnodular plaques, often lymphadenopathy.
  • Excoriation and secondary bacterial infection - due to relentless itching. Patchy depigmentation (leopard skin).
  • Skin atrophy and depigmentation - loss of elasticity cause wrinkled skin, with inguinal lymphadenopathy -> hanging groin.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Eye disease in onchocerciasis (River blindness):

  1. Describe the difference between early disease (3) and late disease.
  2. How does ‘snowflake’ opacity appear?
  3. How is pannus formed?
  4. Widespread chorioretinitis with pigmentary changes is often accompanied by optic nerve atrophy, what is the result of this?
A
  1. Early disease - itching, redness and excess lachrymation.
    1. Late disease - varying degrees of vision loss and eventually blindness.
  2. ‘Snowflake’ opacity - due to reactions to death of microfilariae.
  3. Pannus forms as blood vessels invade the cornea and covering pupil can cause blindness.
  4. Optic nerve atrophy - affecting central vision - tunnel vision.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is Onchocerciasis (River Blindness) diagnosed?

A
  1. Skin snipping
  2. Punch biopsy
  3. Slit lamp (look for microfilariae in anterior chamber of eye)
  4. Rapid diagnostic tests (LIPS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are African programma challenges in Onchocerciasis?

A
  • Civil strife and conflict
  • Insufficient health infrastructure, resources
  • Political commitment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Onchocerciasis Control Programmes - OCP:

Control operations were initially based on killing the … of the blackfly vectors. This was achieved by weekly aerial spraying of … over fast-flowing … and streams – the breeding sites of the … . Spraying continued for at least 14 years to break the life-cycle of the parasite.

… treatment was added to the control operations following the donation of Mectizan® by Merck 1989.

A

Control operations were initially based on killing the larvae of the blackfly vectors. This was achieved by weekly aerial spraying of insecticide over fast-flowing rivers and streams – the breeding sites of the blackflies. Spraying continued for at least 14 years to break the life-cycle of the parasite.

Ivermectin treatment was added to the control operations following the donation of Mectizan® by Merck 1989.

17
Q

Treatment of Onchocerciasis (River Blindness):

Currently doxycycline 100 mg 6 weeks and dose of ivermectin 150ug/kg on completing doxy. Ivermectin kills microfilariae by … them, so that they are carried away from their usual locations via the … .

  • Why is Ivermectin succesful?
  • Why is doxycyclin used?
A

Ivermectin kills microfilariae by immobilizing them, so that they are carried away from their usual locations via the lymphatics.

  • Ivermectin is less immediate and less likely to provoke irreversible inflammatory responses.
  • Doxycyclin kills endosymbiotic Wolbachia in filariae, resulting in slow, and therefore less pathogenic, death of parasite.
18
Q

APOC (African Programme for … Control) - remarkable impact on population health in Africa between 1995 and 2010.

Impact is predicted to … during the subsequent five years of programme.

APOC is highly … public health programme.

A

APOC (African Programma for Onchocerciasis Control) - remarkable impact on population health in Africa between 1995 and 2010.

Impact is predicted to double during the subsequent five years of program.

APOC is highly cost-effective public health programme.

19
Q

Bancroftian filariasis:

  • Central & … America, Africa, …, Pacific
  • Common in … areas
  • Transmitted by Culex, Anopheles and sometimes Aedes.
  • Main urban vector is … quinquefasciatus

Brugian filariasis:

  • … and South East Asia
  • Mainly in … areas
  • Major vectors are night-biting … .
A

Bancroftian filariasis:

  • Central & South America, Africa, Asia, Pacific
  • Common in urban areas
  • Transmitted by Culex, Anopheles and sometimes Aedes.
  • Main urban vector is Culex quinquefasciatus

Brugian filariasis:

  • India and South East Asia
  • Mainly in rural areas
  • Major vectors are night-biting Mansonia.
20
Q

Lymphatic filariasis versus Onchocerciasis:

Adults live in …

Female produce … microfilariae a day.

Adults average age.

Microfilariae are sheathed/unsheathed

A

Lymphatic filariasis: adults live in lymphatic vessels. Female produce 10’000 sheathed microfilariae a day. Average age adults is 15 years.

Onchocerciasis: adults live in fibrous nodules in subcutaneous tissue. Female produce 1000 unsheathed microfilariae a day. Average age adults is 10 years.

21
Q

Life cycle Lymphatic filariasis:

Start with moquito blood meal and third stage larvae, mention thoracic muscles, and end with mosquito proboscis.

A
  1. Infected mosquito takes a blood meal and third stage larvae penetrate skin wound. They reside in lymphatic tissue.
  2. Female filariae produce microfilariae. The microfilariae are sheathed and migrate to blood and lymph vessels.
  3. Mosquito ingests microfilariae, which lose their sheaths after ingestion and move to thoracic muscles.
  4. There the microfilariae develop into first stage larvae and subsequently into third stage larvae.
  5. The third stage larvae migrate to mosquito’s proboscis and can infect other humans when mosquito feeds again.
22
Q

Bacroftian filariasis clinical effects:

  • Acute filarial fever without …, fever, pain.
  • Acute filarial lymphangitis - occurs following death of … worm
  • Acute dermatolymphangioadenitis:
    • Local … associated with secondary … infection, impaired lymphatic flow > limb oedema and eventually … .
    • Bacteria may enter through breaks in skin. … of lymph provides excellent conditions for rapid … .
  • Chronic Lymphatic filariasis - lymphatic … > lymphoedema and eventually elephantiasis.
A
  • Acute filarial fever without lymphadenitis, fever, pain.
  • Acute filarial lymphangitis - occurs following death of adult worm
  • Acute dermatolymphangioadenitis:
    • Local inflammation associated with secondary bacterial infection, impaired lymphatic flow > limb oedema and eventually elephantiasis.
    • Bacteria may enter through breaks in skin. Stasis of lymph provides excellent conditions for rapid growth.
  • Chronic Lymphatic filariasis - lymphatic obstruction > lymphoedema and eventually elephantiasis.
23
Q

Major advance in treatment of filariasis Wolbachia symbiont: much of inflammatory component of filariasis is because of bacterium.

  • Bacteria are necessary … to larval development in mosquito.
  • These bacteria produce … molecules.
  • When microfilariae …, bacteria are released and interact with human immune system > … response associated with onchocerciasis.
  • Antibiotic treatment to eliminate Wolbachia from the microfilariae causes … in blindness among chronically infected even without clearance of … .
A
  • Bacteria are necessary catalysts to larval development in mosquito.
  • These bacteria produce proinflammatory molecules.
  • When microfilariae die, bacteria are released and interact with human immune system > inflammatory response associated with onchocerciasis.
  • Antibiotic treatment to eliminate Wolbachia from the microfilariae causes reduction in blindness among chronically infected even without clearance of helminths.
24
Q

Where is Wolbachia present in Brugia malayi (brugian filariasis)?

Why is Wolbachia present in helminths?

A

Location: lateral cords and ovaries.

Wolbachia is essential for growth, development, embryogenesis, and survival.

25
Q

In areas where microfilaridermia persists after … ivermectin treatment, targeting of … in O. volvulus is effective in clearing … and in … killing of adult worms.

A

In areas where microfilaridermia persists after repeated ivermectin treatment, targeting of Wolbachia in O. volvulus is effective in clearing microfilariae and in enhanced killing of adult worms.

Target Wolbachia by using doxycyclin.

26
Q
  • Loa loa is transmitted by … flies of genus Chrysops and causes … . Larvae migrate … . Females produce microfilariae, which … appear in peripheral blood and can survive for up to … years.
  • Symptoms are mainly caused by … worms and include urticaria, pruritis, arthralgia and malaise. … migration causes intense eye-pain and inflammation. Trauma to … adult worm, mostly on extremities, may provoke a localized inflammatory reaction (… swelling).
A
  • Loa loa is transmitted by red flies of genus Chrysops and causes loiasis. Larvae migrate subcutaneously. Females produce microfilariae, which periodically appear in peripheral blood and can survive for up to two years.
  • Symptoms are mainly caused by adult worms and include urticaria, pruritis, arthralgia and malaise. Subconjunctial migration causes intense eye-pain and inflammation. Trauma to migrating adult worm, mostly on extremities, may provoke a localized inflammatory reaction (Calabar swelling).
27
Q

How is Loiasis diagnosed and treated?

A

Incidental findings of calcified worms on X-ray. Peripheral blood microfilaraemia shows characteristic sheathed microfilariae.

Treatment: DEC in combination with ivermectin.