17th June 2024

Nematode infections – Filarial disease

There are several important types of filarial disease. All are caused by nematode worms and are transmitted by diverse insect vectors.

Onchocerciasis

Onchocerca volvulus is the causative nematode in onchocerciasis, or “river blindness”. It is a major cause of preventable blindness across Central Africa. There is also some endemicity across Central and South America. Simulium blackflies allow passage of the larval stage into the subcutaneous tissue, where adult female worms mature over a period of around one year, before producing microfilariae for up to 15 years if left untreated. Dying microfilariae cause the signs and symptoms of onchocerciasis, which include depigmented skin lesions and gradual loss of sight as microfilariae die within various parts of the eye. Diagnosis can be made by microscopy and direct visualisation of microfilariae, with PCR being used on the sample if visualisation is not possible. Microfilariae can also be observed on slit lamp examination of the eye. Diethylcarbamazine (DEC) causes rapid death of microfilariae and can lead to the Mazzotti reaction, a life-threatening immunological reaction characterised by fever, hypotension, urticaria, and lymphadenopathy. This phenomenon can be exploited for diagnostic purposes, using small patches to invoke a localised immune response. Ivermectin is microfilaricidal, however is less likely to cause the Mazzotti reaction as its mechanism of action is slower. Wolbachia is an endosymbiotic bacterium found within all the filarial species we will discuss, except for Loa loa. It is, therefore, a useful target in treating adult worms. Doxycycline causes Wolbachia death and is therefore useful as an agent against adult worms (macrofilaricidal).

Loiasis

Loiasis, caused by Loa loa, is transmitted by the Chrysops fly, which resides in the rainforests of West and Central Africa. As in onchocerciasis, adult female worms develop in the subcutaneous tissue and begin to produce microfilariae after several months. Again, the adult worms may be viable for over a decade. Microfilariae are found in various bodily fluids. As the Chrysops fly is a day biter, evolution has dictated that the microfilariae are most likely to be found in the blood during this time in order to complete the lifecycle. Migration of the adult worm causes most signs and symptoms. It can be visible in the patient’s eye at times, usually causing transient local inflammation without permanent damage to sight. Calabar swellings are skin swellings associated with adult worm migration through the subcutaneous tissue. Diagnosis can be clinical, or microfilariae can be found on blood films taken from the patient during the daytime. DEC kills both adult worms and microfilariae but must be used with caution in areas where onchocerciasis is endemic. Ivermectin treatment prior to DEC administration will reduce the chance of the Mazzotti reaction on patients with both diseases. Unfortunately, treatment with both agents can precipitate encephalopathy due to rapid microfilarial death. If microfilarial load is high in blood samples, then prior treatment with albendazole (which limits the production of viable microfilaria) and concurrent use of steroids may reduce the likelihood of treatment-related encephalopathy. As there is no Wolbachia endosymbiosis, doxycycline is not effective.

Lymphatic filariasis

Lymphatic filariasis, often caused by Wuchereria bancrofti, is prevalent across much of the tropics and subtropics. The infective process is similar to other filarial disease, with mosquitos acting as the vectors. However, the adult worms reside within the lymphatics rather than subcutaneous tissue. Microfilarial death within the pulmonary capillaries may cause a syndrome called tropical pulmonary eosinophilia, characterised by an asthma-like clinical picture, with low-grade fever and eosinophilia. Chest X rays may be normal or demonstrate a reticulonodular or miliary appearance. Chronic lymphatic filariasis is associated with lymphoedema due to lymphatic obstruction, causing disfiguring leg and scrotal swelling. A blood film obtained during the night has the best chance of identifying microfilaria. Ultrasound may show adult worms. Serological tests are also available. Ideally, lymphatic filariasis is treated with DEC. However, this may precipitate the Mazzotti reaction or encephalopathy if there is concurrent infection with Onchocerca volvulus or Loa loa, respectively. Albendazole and ivermectin combination therapy may also be used. Doxycycline can be useful as there is Wolbachia endosymbiosis. Mass drug administration in areas of high helminth endemicity is a viable public health intervention, though the complex overlap of filarial diseases in certain regions and reactions to specific treatments makes this challenging.