Day 8: filariasis, nematodes (intestinal and tissue).

Day 8:

Today’s talk started off with a talk on filariasis, a parasitic disease caused by roundworms. They are spread by mosquitoes and black flies. They are divided into 3 groups: lymphatic, (W. bancrofti, Brugia malayi and Brugia timori),  subcutaneous filariasis (loa loa, mansonella streptocerca, and onchocerca), and serous cavity filariasis (mansonella perstans, M. Ozzardi and Dirofilaria immitis is also listed here).

Lymphatic filariasis, although caused by 3 organisms, is 90% caused by W. bancrofti.  It is transmitted  by several mosquitoes but primarily culex (species quinquefasciatus), interestingly, it makes its way to the mouth of the mosquito and then gets deposited onto the skin surface, where the filariform larvae will then invade the host.  This being contrasted to malaria which is directly injected, hence the transmission is less efficient.

Clinical features can very from asymptomatic without any microfilaria in the blood, asymptomatic WITH microfilaria in the blood, filarial fever, tropical pulmonary eosinophilia (in where only antigen test is positive), and chronic lymphatic pathology. Symptoms can occur after a year and up to 15 years! Symptoms can be episodic occurring several times a year.

Two presentations worth mentioning are acute filarial lymphangitis (AFL) and acute dermatolymphangioadenitis (ADLA). AFL is a reaction often due to death of the adult worm – causing circumscribed inflammatory nodule or cord, it is mild but can get secondarily infected. ADLA is intense inflammation resembling cellulitis, more systemically ill, stasis of lymph can predispose for bacterial infection. An episode can last a week but lead to damage of lymphatics/fibrosis and progression to elephantiasis.  ADLA is more common in endemic regions

Other than chronic lymphedema, other features related to rupture of lymphatics, chylous ascites, chyluria, chylous diarrhea, hydrocoele

Brugia causes pretty similar disease in Asia but is thought to be more mild and usually limited to below the knees.

Diagnosis: can be tricky, and need to look for microfilaria in the blood around midnight, because that is when they come out, clever because that’s when it’s mosquito comes out to (hopefully) pick it up. However, very sensitive an specific rapid tests have been developed which have largely replaced midnight blood sampling (if available). Patient will often have eosinophilia.

Treatment can get complicated because for two reasons: DEC, although the drug of choice, can precipitate encephalopathy if loa loa is present at high levels, and a Mazzotti reaction if onchocerca is present.

Treatment:

1.     If no Loa Loa, and no onchocerciasis, DEC 6 mg/kg for 1-12 days, which is weird.

2.     If co-infection with onchocerciasis, give doxycycline 200 mg/day x 4 weeks, ivermectin (thus often avoided if from Africa)

3.     If loa loa at high levels, can give doxycycline first

Often re-treatment with DEC every 6-12 months as necessary.

Also, combo of albendazole and ivermectin may suppress microfilaria, but will not affect adult worms. A trial in India showed great success with doxy (200 mg/kg) and albendazole 400 mg daily x 7 days with 99% 1 year eradication

Loa Loa:

Can present as migratory swellings that can stay for a week (a differential which includes gnathostomiasis, dirofilaria immitis (dog heart worm), fasciola gigantica and even paragonimus). The classic associated of an adult worm crossing one’s eye is apparently more common for people living in the endemic region (vs the migratory calabar swellings one would more often see in a traveler returning back with that infection).

It is endemic to western Africa only, thus is not a differential for migratory swellings in someone who has not been to Africa. It is transmitted by the Chrysops (also known as mango fly) in tropical forests in Africa. The larvae migrate subcutaneously, maturing into 3-7 cm long over a year. They can survive for more than 15 years. Adult worms will produce microfilariae which can remain in blood for 2 years. Most symptoms are related to migration of adult worm (urticarial, arthralgia, migration of worm across eye). Encephalopathy has been associated with high microfilaria particular in the context of treatment, also patients can develop pulmonary infiltrates, proteinuria, and endomyocardial fibrosis, possibly associated with hypereosinophilia. Unlike W. Bancrofti which appears at night in the blood, this occurs during the day most often. It is a sheathed microfilaria (as are Brugia, and W. Bangrofti) – my mnemonic for this being “Branded With Love”.

Treatment is typically with DEC 2mg/kg po TID x 7-10 days, it affects both adult worms and microfilaria. This can be repeated every 2-3 months. Also, if unable to assess for onchocerca, a single dose of Ivermectin can be given to reduce the risk of Mazzotti reaction if co-infected with onchocerca (but would avoid if microfilaria from loa loa is >2500 Mf/mL. Other than plasmapheresis to filter out high levels, albendazole for a few weeks prior to DEC can be done to reduce microfilaria load.

Onchocerca is a subcutaneous filariasis (in the same category as loa loa and Mansonella streptocerca). Known as River blindness for causing blindness of people living near a river and getting infected from black flies (simulian). The adult worm can be up to 40 cm long, and form subcutaneous nodules where they produce microfilariae, that migrates through the skin and eye. The adult worm can lives for over 10 years.

The simulian breed in fresh water and bite those near by. The adult worm often cause few symptoms, but it is rather dying microfilaria and their endosymbiotic wolbachia which trigger innate immune system cause clinical disease. Two skin manifestation (acute popular onchodermatitis – APOD) had intensely itchy, popular lesions +/- edema. Chronic popular onchoderamtitis is similar with hyperpigmented papules. The classic hanging groin is due to premature aging of skin.

Painless subcutaneous nodules may be palpable over bony prominences, which represent adult worms that have arrested and incased in fibrous tissues. In Africa nodules are found below the waste, whereas in the Americas they are found over the head.

Eye disease can develop with itching and redness, late disease can cause blindness. Microfilariae have been identified in all ocular tissues except he lens. There have been two eye disease described, one in the savannah which has been shown to have high wolbachia DNA to nematode ratio compared to infection from rain forest strains.

Diagnosis: Typically skin snips are diagnostic, often microfilaria cannot be seen in blood. A rapid diagnostic test exists which has 100% sensitivity, varying degrees of specificity to other parasites. Classically people would use a Mazzotti test with DEC to look for reaction to assess the disease, a modified version Mazzotti, the DEC patch test is safer.

Treatment: Ivermectin is the drug of choice, it kills microfilariae by immobilizing them, killing them slowly unlike DEC. It has little effect on adult worms. Thus patients can be treated with ivermectin alone yearly for at least 14 years. Doxycyline can be used to kill adult worms. (Note DEC works on all stages of filariasis)

Intestinal nematodes: Overall mortality low but morbidity high . Dr. Libman brought up interesting studies commenting on cons and some pros of having parasites. For the most part, if you can avoid ingestion of stool or stepping on stool, you can avoid geohelmiths

Some highlights:

Pinworms: infection worldwide, scotch tape test is best (although unkown sensitivity) at night or first thing in the morning is optimal timing, trial of treatment is reasonable (often treat family members). Don’t do stool O&P.

Trichuria: Fun fact: T suis has been used in inflammatory bowel disease. Dysentery from disease can cause rectal prolapse (classic association). Eggs in stool have classic football shaped appearance. Single dose of mebendazole can be given but CDC suggests 3 days for most infections. They grow to 3-5 cm in length, adults life ~ 1 year, often found along with ascaris.

Ascaris: aka round worm, this can get large and cause obstruction, vomited up during pregnancy. Associated with seasonal loefflers syndrome in Saudi Arabia where it migrates through lungs, associated with eosinophilia pneumonia (of note, this migration to the lungs and eosinophilia has also been associated with hook worm and strongyloides.

Hookworms: Anclostoma duodenale (lives up to 5 years), necator americanus (lives up to 1 year). Reason for regular deworming, migration is through the skin and gets through the lungs then intestines.  Vaccinations underway! Not to be confused with dog or cat hookwork – ancylostoma braziliense which is associated with CLM and is not able to migrate through the body.

Strongyloides: Similar lifecycle to hookworm where filariform larvae migrate through skin. Classic rash is larva curens (moves very quickly compared to CLM), can cause diffuse rash, cause of PPI resistant GERD in tropics. Associated with HTLV-1. One of two reasons to order &P on sputum (paragonimiasis is another). Low threshold to do serology for it when patient planned for immunosuppression.  Treat with ivermectin x 2 doses, for severe infection with ileus give SC dosing (usually this is given by vets to animals). Suspect with recurrent gram negative sepsis and gram negative meningitis.

TISSUE nematodes:

Dr. Coyle from Albert Einstein gave us a run down of tissue nematodes. Started off with toxocara canis –  which is present in a dog (puppies are the main culprit) cat, it excretes eggs in feces, which can be picked up by a child and ingested. These eggs rarely develop into adults in humans

Visceral larva migrans: high eosinophilia and fever, pneumonitis, LAD, HSM, diagnosis is made by ELISA. In children pneumonitis with hepatitis + eosinophilia, but can affect just about any organ. Many cuteanoues manifestations have been described.

Ocular larva migrans: a larva invades the eye causing granulomatous reaction, this can cause choriodoretinits with mass lesion and be mistaken for retinoblastoma. Serology is usually negative, antibody detection is vitreous fluid is more sensitive. Generally treated with steroids.

Covert toxo is a term used for serology positive patients, typically with no symptoms. Although this parasite cannot replicate in humans, larvae cannot replicate or grow in humans, but can remain alive for 7 years per uptodate.

Dr. Coyle presented a child with eosinophilia and liver lesions, biopsy of the liver showed toxocara. Prevention of this: avoid kids playing in poo, deworm your pets regularly.

Gnathostomiasis: parasitic infection from undercooked fish, classically in SE Asia but also South America. Can present as migratory swellings (like loa loa, dirofilaria and fasciola gigantica), also intra-vitreal worms have been seen. Associated with eosinophilia and multi system disease. Treated with albendazole for 21 days. One of the 3 common causes of eosinophilic meninigitis (others being angyiostrongylous and balisyscaris). Best test is an immunoblot test to look for a specific band, after treatment, would usually follow eosinophilia. Swellings/rash can be present for years after initial infection. Also to suspect with SAH and eosinophilia.

Baylisascaris procynosis – poor outcome if in CNS, can cause OLM like toxocara, no proven therapy.

A case of migratory nodule in a Philipino women that was dirofilaria repens. Diagnosed when worm removed from eye.

Trichinosis: uncooked bear meat or pork, peri-orbtial edema, eosinophilia with increase ck.

Calcified larvae in tissue.

Anasikiasis: case of a man who ate a bunch of raw salmon he bought form the supermarket. This organisms is killed when frozen (as is mandatory for raw fish from sushi restaurants, but not if you were to buy it raw from a supermarket). Acute symptoms after a meal are common, it can be associated with intestinal perforation. Patient’s can also get urticarial and anaphylaxis to a reaction to the parasite.

The areas of highest prevalence are Scandinavia (from cod livers), Japan (after eating sashimi), the Netherlands (by eating infected fermented herrings (maatjes)), Spain (from eating anchovies and other fish marinated in escabeche), and along the Pacific coast of South America (from eating ceviche)