A short History of Onchocerciasis

by Guido Kluxen
Discovery of the microfilariae
In 1874, John ONeill, a British naval surgeon attached to HMS Decoy at Cape Coast Castle in the
Gold Coast (Ghana) became intrigued by an irritating and intractable skin disease somewhat
resembling scabies which afflicted many people living in parts of the West Coast of Africa. He
determined to look for the cause of this peculiar condition, which was known locally as craw-craw,
by studying a number of patients in Addah Fort Hospital under the care of Dr. Thompson of the
Glover Expedition. The condition was characterized by papules, vesicles and pustules. ONeill
examined the contents of pustules and vesicles under a microscope but found nothing other than
leucocytes. When he turned his attention to papules, success attended his efforts for he found an
organism which he had no doubt, was the cause of the complaint. He reported his observations in
1875.
When specimen were examined in a drop of water under a microscope, microfilariae that were
easily detectable by virtue of their violent contortions were often seen: At the head, or blunted
extremity, two small dots are noticed, but their nature could not be determined (Fig. 1) (ONeill
1875).

Fig. 1:
Unsheathed microfilariae from craw-craw
of ONeill at the Gold Coast, Ghana (Original from The Lancet 1875).
Discovery of the adult worm
In 1890, an unnamed German doctor working in the Gold Coast (Ghana), West Africa, removed two
tumours, each about the size of a pigeons eggs, one from the scalp and the other from the chest,
from two of the local inhabitants. On examining the specimens, he found that they contained worms
and sent them to Rudolf Leuckart in Germany for identification. Both tumours contained several
female and male worms, the former being about 6-70 mm in length and the latter about half that

size; they were coiled together to form a ball which was very difficult to unravel. The mass of worms
was situated in a cavity which contained fluid laden with embryos. Leuckart did not publish news of
this discovery, but informed Patrick Manson in a personal communication. It was left to Manson to
publish a skimpy notice of the parasite, with due to acknowledgement to Leuckart, in a chapter he
wrote on skin diseases in the tropics for Davidsons book Hygiene and disease of warm climates.
The section on this parasite was labelled Filaria volvulxus, the latter apparently being a
mistranscription of volvulus (from the Latin volvo, volvere = to roll or turn round); whether this
was Leuckarts or Mansons designation was not indicated in the text, but was presumably intended
to draw attention to the twisted and coiled intertwining of the worms.

Fig. 2: Rudolf Leuckart (1822-1898), zoologist and helminthologist in Leipzig, Germany,

discovered Onchocerca volvulus
Onchocerca volvulus:
"The twisting hook-tail"
Leuckart had also sent Manson a histological section containing a fragment of the uterus of one of
the worms, Manson remarked: I did not see represented in the embryo of Filaria volvulus the
sheath. Professor Leuckart makes the same remark.
The name Onchocerca was derived from a combination of the Greek word ONCHOS meaning
hook and KERKOS; CERCOS meaning tail (Railliet and Henry 1910).
Symptomentrias according to Robles
The first persons to mention ocular onchocerciasis were Rodolfo Robles and Pacheco-Luna in
Guatemala in 1915/1916. Ophthalmic symptoms and signs were marked in the Triassic, also known
as Morbus Robles: 1. Filarial worm infection of an adult Onchocerca in America, 2. Erisipela de la
costa, red skin inflammation of the coast, a skin disease located on the face, 3. Conjunctivitis and

iritis of the anterior segment of the eye (Pacheco Luna 1918).

In 1915, Robles was consulted by a women concerning recurrent erysipelas of the face which was
accompanied by fever, a burning sensation, pruritus and poor vision (Fig. 4), but he did not know
the cause. Afterwards he saw a boy with the same features: Oedema of the eyelids, the forehead, and
the superior lip. On his forehead was a tumour the size of a cherry. It was this lump that Robles
excised and first discovered the adult Onchocerca in the Americas and later remarked: I
understood then that the erysipelas lesions surely were due to the presence of this parasite
(Robles 1917).
In the coffee-producing districts, having altitudes between 2,500 to 5,000 feet, over 95 percent of
the population in an area of volcanoes are Indians who are especially exposed to the bites of
Simuliidae and an infection with onchocerciasis.

Fig. 3: Rodolfo Robles discovered onchocerciasis

of the Americas in Guatemala

Fig. 4: In 1915, Rodolfo Robles was consulted by this women

with an erysipelas of the face as the reason was still unknown.
Brumpt gave a detailed description of the parasite (Brumpt 1919), and after comparing it with the
specimens collected by him in the Congo, decided that it was a different species which he named O.
caecutiens to indicate that the parasite caused blindness (from the Latin caecus = blind). But the
two were morphologically indistinguishable and there was no consistent difference existing between
them.

Fig. 5: mile Brumpt (1877-1951)

It was the itching and consequent scratching which led to the rediscovery by Montpellier and
Lacroix (1920) of microfilariae in the integument which were the same as ONeills parasites. But
Brumpt could not believe it (Brumpt 1920). In the middle of the 1920s, it was becoming clear that
the unsheathed microfilariae obtained from O. volvulus adults were indeed the same microfilariae
seen in the skin. Finally, despite the reservations of some sceptics such as Brumpt, it seemed certain
in retrospect that the filariae seen in the skin 50 years earlier by ONeill were indeed O. volvulus
microfilariae.
Montpellier and Lacroix constantly found microfilariae in the dermal layer of the skin examining
members of native troops in Africa suffering with a form of itch or craw-craw. They concluded that
the craw-craw described by ONeill is a dermal manifestation of onchocerciasis termed gle
filarienne (Fig. 6).

Fig. 6: Gle filarienne (Original from Montpellier and Lacroix 1920)

Fig. 7: Donald Breadalbane Blacklock (1879-1955), born in Scotland .

Simulium damnosum Theobald:
Mode of transmission of onchocerciasis
In 1923, the Briton, Donald Breadalbane Blacklock, began to investigate the mode of transmission
of onchocerciasis in Sierra Leone. Since the microfiariae were not in the blood but in the skin, he
postulated that any arthropode capable of transmitting the worms must be able to damage the skin
and dislodge the larvae in its efforts to reach blood. Accordingly, he first looked at the Congo floor
maggot, Auchmeromyia luteola, which was common in the houses, but no signs of the parasites
were found. In 1923/24, he observed that the blackfly prophetically named Simulium damnosum by
Theobald in 1903 (Theobald 1903) was biting viciously and in great numbers near the streams
supplying several of the villages in an endemic area of onchocerciasis. Furthermore, he noticed that
the insect was slow in drawing blood, which reinforced his idea that it must be inflicting severe
damage. He therefore caught 100 specimens and examined them for larvae, but finding nothing,
abandoned the search temporarily. In 1925, he resumed this operation at another village, this time
with success. 780 flies were captured while biting randomly selected boys and 2.6 % of the insects
contained larvae morphologically identical with O.volvulus microfilariae. Thereupon, he submitted
two men who were known to have O.volvulus microfilariae in their skin, but were not infected with
any other filarial parasite, to the flies and found that 17 % of Simuliidae contained microfilariae.
When flies were permitted to bite only on a 4 inch band around the patients body, this area
including nodules near the trochanters, 80 % of the insects became infected. The development of
the L3-larvae in the fly is demonstrated in Blacklocks original figure (Fig. 8). Only the female was
found biting, and the biting habit is diurnal (Blacklock 1926/1927).

Fig. 8: Diagram to illustrate the development of O. volvulus larvae in the tissues of Simulium
damnosum (Blacklock 1927). I = Larva from infected skin, II = larva in mid-gut, III = larva in
thoracic muscles (early stage), IV = Larva in thoracic muscles (late stage), V = Larva in head and
labium, A = Antenna, B.C. = Blood coagulum, T.M. = Thoracic muscles, L = Labium, L.e. =
Labrum-epipharynx, H. = Hypopharynx, M. = Mandible, Mx. = Maxilla, Mx.P. = Maxillary palp.
The infective stage larvae (V) are now termed L3 larvae, and stage-I-larvae are now termed
microfilariae.

Fig. 9: Simulium damnosum Theobald (Photo: Hj. Trojan)

The observations of Hissette radically changed the way
of looking at onchocerciasis
The early investigators of onchocerciasis from 1874-1930 in Africa made no mention at all of a
concomitant severe eye disease. Publications of the observations in Central America by Rodolfo
Robles and mile Brumpt in 1917/1919 prompted some specialists in tropical medicine to look for
eye disease associated with African onchocerciasis. However, there did not seem to be any eye
disease leading to blindness (Flleborn 1924). Only Ouzilleau and his colleagues recorded in 1921
that one of the 16 infected persons of 27 inhabitants they had found in a village near Brazzaville had
keratitis. Blacklock (1927) reported that he could find no evidence of eye disease in patients with
onchocerciasis in Sierra Leone.
It was not until 1930/1931 that Jean Hissette reported that 20% of patients with onchocerciasis
were blind in an onchocerciasis focus on the Sankuru River in the Belgian Congo, and that 50% of
the villagers suffered from eye troubles. Two years later, he found a second focus with the same
pathology on the Ule River. Hissette described the pathomechanism of this blindness in a long
paper in 1932 and in addition to a description of anterior eye disease, he drew attention to an
association with chororetinitis. Two years later the Harvard African Expedition to the Belgian
Congo under Richard Pearson Strong with five American colleagues was organized at Belgiums
expense. His members had to check Dr. Jean Hissettes reports because there were doubts about his
findings. Confronted by this commission in the form of the Harvard African Expedition, Hissette
traveled once more to the Sankuru with the Americans as the seventh member of the expedition and
showed them "his" river blindness patients. The Americans finally confirmed all the observations on
river blindness caused by onchocerciasis in the American Journal of Tropical Medicine (Strong
1938) that had already been communicated by Hissette (1932).

Fig. 10: Riverblind people from the Sankuru Region 1930

Fig. 11: Microfilariae of Onchocerca volvulus in the Chorioidea of an enucleated eye from the
Sankuru River 1931 (Original histology by Jean Hissette, microfilariae are black and stretched)

Fig. 12: The Sankuru River Region and Ule River Region of the Belgian Congo
Hissettes findings prompted renewed efforts to find ocular complications of onchocerciasis in other
parts of Africa, now known as river blindness. In 1944, Harold Ridley found that slightly more than
one third of patients with onchocerciasis in a region of the Gold Coast (Ghana) had evidence of
either anterior or posterior disease of the eye, with nearly half of them being blind or nearly blind.
Ridleys monograph Ocular onchocerciasis (1945) was of considerable success in river blindness
research.
The numerical distribution of microfilariae of Onchocerca volvulus in the skin of man follows a clear
pattern which is related to the distribution and severity of the skin and eye lesions. For the eye
changes and blindness this is especially the region of the head and neck (Kershaw et al. 1954).
Choyce (1958) confirmed that the scared fundus, hitherto thought to be due to onchocerciasis, was
identical with the chorioidal sclerosis described by Sorsby (1939). This could be the fact in
Bonjongo, Cameroons where he found such changes indistinguishable for him. Sorsbys chorioidal
sclerosis is a genetic disease transmitted in a dominant fashion. No evidence was found of vitamin A
deficiency as a cause of chorioretinitis in onchocerciasis (Woodruff et al. 1963).
Onchocerca volvulus has not been transmitted experimentally to humans by infected flies, but
epidemiological evidence suggests that the prepatent period is between 3 to 18 months. The adult

worms may live for 15 years and are capable of producing microfilariae for up to ten years (Roberts
et al. 1967), while microfilariae may persist for from 6 months to 3 years (Duke 1968).
On October 21, 1987, Merck officials (MSD Merck Sharp & Dohme) said that they would be donating
their drug Ivermectin to affected areas for as long as it might be needed. Diethylcarbamazine and
suramin caused severe side effects in so many individuals. Ivermectin can be given as a tablet on a
once a year basis and has minimal side effects. The drug is distributed by Merck, in close
collaboration with WHO, an independent committee of experts in tropical medicine, The World
Bank, The Carter Centre in Atlanta, Georgia/USA, and about a dozen NGDOs (non-governmental
developing organizations) in several different countries.
Most of the evidence supporting a role for Wolbachia in the pathogenesis of filarial diseases stems
from adverse reactions in infected individuals. For example, systemic treatment of onchocerciasis
patients with diethylcarbamazine (DEC) causes rapid death of the microfilariae in the skin and eyes,
resulting often severe post treatment side effect the so called Mazzotti reaction. The severity of the
Mazzotti reaction is dependent on the number of microfilariae containing Wolbachia in the skin
and eyes (Hoerauf and Pfarr 2007). And this was also the fact when Hissette induced the erysipelas
in a little 12 year old boy at the Ule in 1933 (Hissette 1933, Kluxen 2011) by needling his head
nodules and killing the worms in it. Reactions include fever, headache, dizziness, myalgia,
arthralgia, tachycardia, ciliary injection, severe pruritus, enlargement of lymph nodes and erysipelas
of the coast.
While alive, the microfilariae appear to cause little or no inflammation, even being in the anterior
chamber. However, when they die, either by natural attrition or after chemotherapy, the host
response to degenerating worms can result in ocular inflammation (keratitis, uveitis, chorioretinitis,
optic neuritis) that causes progressive loss of vision. Blindness therefore tends to occur in adulthood
after many years of infection.