Onchocerciasis

Overview

• Introduction
• Epidemiology
• Lifecycle
• Morphology
• Vector
• Pathogenesis
• Clinical presentation
• Diagnosis
• Management
• Prevention and control
• Control Programmes

Introduction

• Also known as River blindness. Second most common infectious cause of preventable blindness after trachoma.
• It is caused by a parasitic tissue nematode of the subcutaneous system called Onchocerca voluvulus along with Loa loa and Dracunculus medinensis
• Bite of an infected insect vector, S imulium spp . Typically S. damnosum
• Occupational risk to farmers, fishermen, road construction workers etc. who spend time around
• infested streams.

Epidemiology

• Currently, onchocerciasis is endemic to 31 African countries, toYemen, and in localized foci in Brazil and Venezuela.
• Globally, at least 18 million individuals have onchocerciasis , 99% of whom reside in Africa.
• The World Health Organization (WHO) estimates that 750,000people are blind or have reduced vision as a result of the disease.
• In July 2016, Guatemala became the fourth country in the worldafter Colombia (2013), Ecuador (2014), and Mexico (2015) to be verified free of onchocerciasis
• Onchocerciasis does not have a sexual, age or racial predilection.
• For an unclear reason, the symptoms caused by O volvulus infection appear to differ from region to region. 
• Onchodermatitis is more common in forested areas, while blindness is more common in savanna areas.
• Some evidence has suggested that genetic variation in the host may explain part of this geographic specificity Transplacental transmission of microfilariae may occur.

In Nigeria

• The provisional estimates had suggested that 7-10 million Nigerians are infected with Onchocerca volvulus , approximately 40 million are at risk of the disease and 120,000 cases of onchocerciasis related blindness.
• A cross sectional study was carried out in the Okigwe Local Government Area, Imo State, Nigeria involving 1024 individuals recorded an onchocerciasis prevalence of 37%.
  

Onchocerciasis Life Cycle

Life Cycle of Onchociasis in Humans

Morphology

Microfilariae

• Microfilariae of Onchocerca volvulus are unsheathed and measure 300 315 µm in length. The tail tapers to a point and is often sharply bent. 
• The nuclei do not extend to the tip of the tail.
• Microfilariae typically reside in the skin and subcut . tissues but may invade the eye or be found in blood or urine during heavy infections.
• The gravid female worm releases about 1,000 microfilariae (L1) per day over a 9 to 14 year period.

Vector

• Black fly Simulium spp.spp.) are obligate intermediate hosts of O. volvulus which breed in fast flowing rivers. Simulium damnosum and S. neavei in Africa; S . callidum S. ochraceum and S. metallicum in the Americas.
• The aquatic larvae require swift flowing streams or highly oxygenated waters for their development, a critical epidemiologic factor in the role of these flies as disease vectors. 
• Mature adults can disperse tens or hundreds of kilometers from their breeding grounds in fresh flowing water.
• They are hump backed and typically possess black or dark gray, with short (1.5 to 6.0mm ), broad, gauzy wings, stout antennae and legs, and rather short mouthparts that are adapted for sucking blood. 
• Compound eyes are well separated above the antennae.
  

Vectors

Pathogenesis

• Dead microfilariae
• Recognition of FB
• Activation of naïve T cells are activated into TH2 cells: IL4,5,13, Interferon gamma (in chronic disease)
• Eosinophils , mast cells, intense itching
• Mixed inflammatory infiltrates (neutrophils, Monocytes, Plasma cells,Giant cells and Fibroblasts) make the onchocercoma
• Destruction of melanocytes and elastic tissues
  

Features of Onchocerciasis

Clinical Presentation of Onchocerciasis

Both dermal and ocular manifestations are thought to occur when the parasites die and initiate an inflammatory response.

Eye lesions

Conjuctivitis

 sclerosing keratitis

 corneal neovascularisation and

 opacification which progresses to blindness

Skin lesions

 Pruritus

 subcutaneous nodules

 diffuse onchodermatitis

onchocercomata (subcutaneous nodules ) and

lymphadenopathies.

In its extreme form, skin atrophy may cause drooping of the inguinal skin termed hanging

groin.

Skin Manifestations in Onchocerciasis

• Skin nodules ( Onchocercoma )
• Spotted depigmentation (Leopard’s skin’)
• Inflammatory dermatitis (intense irritation, raised papules and alteration in the pigmentation).
• The skin loses its elasticity wrinkling (‘elephant skin’), patient look more aged.
• 'Sowda'  (Black severe allergic response, only one limb , with darkening of the groin area --‘hanging groin’/enlarged groin lymph nodes

Skin Changes in Onchocerciasis

    Diagnosis of Onchocerciasis

• Skin snip biopsy: Gold standard . This technique yields high specificity (100%) in experienced hands but low sensitivity ( 50%) in early stages of infection.
• Sclerocorneal biopsy punch or by elevating a small cone of skin (3 mm in diameter) with a needle and shaving it off with a scalpel.
• Approximately 2 mg of tissue is obtained and incubated in normal saline at room temperature for 24 hours to allow the microfilariae (larvae) to emerge and be identified microscopically.
• The sites for the skin snip are usually over bony prominences such as the iliac crest, the scapula, and the lower extremities. Six snips provide the most diagnostic sensitivity.
• Microfilariae of Onchocerca do not exhibit any form of periodicity and skin snips may be collected at any time.
• Surgical removal and examination of nodules onchocercomata ) for adult nematodes
• Onchocerca specific serologic tests such as the OV 16 antigen antibody test and the OV luciferase immunoprecipitation system (LIPS) assay, but these are currently only available in the research
• Slit lamp eye exam can be used to visualize microfilariae in individuals with eye disease
• PCR: Performing polymerase chain reaction (PCR) of the skin snip can increase the sensitivity in these two situations, though this is not commercially available.

A. Microfilariae of O. volvulus from a skin nodule of a patient from Zambia, stained with hematoxylin and eosin (H&E). Image taken at 1000x oil magnification. B. Microfilariae of O. volvulus seen in the anterior chamber of the eye

C. Gravid onchocerca volvulus with uterus containing eggs and larvae. D. Adult onchocerca volvulus contained within Onchocercomas of the skin

Mazzoti Test

• Mazzoti test elicits localized cutaneous reactions (pruritus, maculopapular eruptions, dermal edema) in response to dying microfilariae following test dosing with a single oral dose of 25 to 50 mg of diethylcarbamazine (DEC ).
• Intense pruritus develops within a few hours. The itching can be severe and may be accompanied by erythema, edema, and papules; it usually subsides within a few days but is discouraged due to severe adverse reactions
• More recently, a patch test using DEC, which decreases risk, has been used.

DEC Patch Test

Treatment/Medication of Onchocerciasis

Invermectin

• Drug of choice
• Ivermectin is microfilaricidal , it does sterilize the females.
• 150mcg/kg orally in one dose every 6 months.
• Adverse reactions are less compared with DEC.
• WHO recommends treating onchocerciasis with Ivermectin at least once yearly for between 10 to 15 years.
• Where O. volvulus co exists with Loa loa , treatment strategies have to be adjusted. Treatment of individuals with high levels of L. loa in the blood can sometimes result in severe adverse events
• such as toxic encephalopathy.

Diethylcarbamazine

• Very effective against microfilaria Microfilaricidal
• Dose 6 mg/Kg/ 12 days
• Recent dosage 6 mg/Kg single dose
• Adverse reactions are mostly due to the rapid destruction of mf which is characterised by fever, nausea, myalgia, sore throat, cough, headache
• Diethylcarbamazine accelerates the development of onchocercal blindness

Doxycycline

• It has been shown in studies to kill Wolbachia , an endosymbiotic rickettsia like bacterium that appears to be required for the survival of the O. volvulus macrofilariae and for embryogenesis.
• Interrupts microfilarial embryogenesis.
• Treatment with a 6 week course of doxycycline has been shown to kill more than 60% of the adult female worms and to sterilize 80 to 90% of the females 20 months after treatment.
• 200 mg orally daily for 6 weeks.

Others

• Moxidectin is an antiparasitic drug that was approved by the FDA in June 2018 to treat onchocerciasis in patients aged 12 years or older. 
• It is closely related to Ivermectin but yields a more sustained reduction in microfilarial levels.
• Surgical Care
• Nodulectomy can result in cure only if excision eliminates all adult worms. Thus, this is not a practical choice in patients with multiple nodules or in patients in whom nodules are not clinically evident.
• OCCUPATIONAL REHABILITATION

PREVENTION AND CONTROL

• Destruction of Simulium larvae by application of insecticides (drip feed methods in small river /
• aerial spraying of larger rivers
• Avoiding Simulium bites (covering the body)
• Identifying infected persons (nodules on head or ocular symptoms which may go blind)
• Mass distribution of Ivermectin

• There is no vaccine or medication to prevent infection with O. volvulus
• In 2015 an international consortium launched a new global initiative, known as TOVA The Onchocerciasis Vaccine for Africa with the goal of evaluating and pursuing vaccine development as a complementary control tool.
• Between 1974 and 2002, Onchocerciasis Control Programme (OCP ) WA: spraying of insecticides against blackfly larvae (vector control) by helicopters and airplanes. This has been supplemented by large scale distribution of Ivermectin since 1989.
• The OCP relieved 40 million people from infection, prevented blindness in 600 000 people, and ensured that 18 million children were born free from the threat of the disease and blindness.
• Abandoned arable land were reclaimed for settlement and agricultural production, capable of feeding 17 million people annually.
  
• On October 21, 1987, Merck and Company agreed to donate Mectizan ® “for as long as it might be needed” for control programs.
• The African Programme for Onchocerciasis Control (APOC) was launched in 1995 with the objective of controlling onchocerciasis in the remaining endemic countries in Africa and closed at the end of 2015 after beginning the transition to onchocerciasis elimination.
• In APOC’s final year, more than 119 million people were treated with Ivermectin , and many countries had greatly decreased the morbidity associated with onchocerciasis . More than 800,000 people in Uganda and 120,000 people in Sudan no longer required Ivermectin by the time that APOC closed.

• The Expanded Special Project for the Elimination of Neglected Tropical Diseases in Africa (ESPEN), which has replaced APOC, will initially focus on several priority countries to support their neglected tropical diseases (NTDs) programmes , including their onchocerciasis programmes , and will create a pool of experts that can provide technical assistance to all member countries. ESPEN, like OCP and APOC, is housed in the WHO Regional Office for Africa.

Salient Details of Onchocerciasis

References

1.Rabiu MM, Gudlavalleti MVS, Gilbert CE, Sivasubramaniam S, Kyari F, Abubakar

T. Ecological determinants of blindness in Nigeria: The Nigeria national blindness and

visual impairment survey. South African Med J . 2011;101(1):53 58.

doi:10.1167/iovs.09 3507.

2.Osei Atweneboana MY, Eng JK, Boakye DA, Gyapong JO, Prichard RK.

Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in

endemic communities in Ghana: a two phase epidemiological study. Lancet .

2007;369(9578):2021 2029. doi:10.1016/S0140 6736(07)60942 8.

3.Uttah EC. Onchocerciasis in the upper imo river basin, nigeria : Prevalence and

comparative study of waist and shoulder snips from mesoendemic Communities. Iran J

Parasitol . 2010;5(2):33 41.

4.WHO. Onchocerciasis . http://www.who.int/news room/fact

sheets/detail/onchocerciasis accessed 26 th September 2018

5.CDC. Onchocerciasis . https://www.cdc.gov/dpdx/onchocerciasis/index.html

accessed 26 th September 2018

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