Sudan-savanna and rain-forest onchocerciasis in West Africa: an epidemiological problem (author's transl)

A Sudan-savanna and a rain forest onchocerciasis have been described in West Africa. These two patterns of onchocerciasis have in common many epidemiological features but in hyperendemic areas there is a very essential difference between the two. In savanna the prevalence of serious ocular lesions and blindness due to onchocerciasis are much higher than in forest. Therefore attempting to explain these differences five groups of factors (or working hypothesis) are reviewed: --factors related to the vectors; --onchocerca-simulium couples; --different Onchocerca volvulus strains; --factors related to the human-host; --other varied factors: nutritional factors, concomitant ocular infections, luminousness of savanna, periods of transmission... A critical examination of these hypothesis brings to the conclusion that according to our present knowledge the main difference between savanna and rain-forest onchocerciasis may be due to degrees in pathogenicity of different strains of O. volvulus but these hypothesis have not been proved formally. More the part of concomitant factors (co-factors), themselves related to bioclimactic zones must not be ruled out.     

Seasonal variation in the microfilarial skin density of Onchocerca volvulus and in the biting activity of Simulium spp. in Guatemala

The density of Onchocerca volvulus microfilariae in the skin of 11 carriers was examined by carrying out a monthly examination in a single endemic area of Guatemalan onchocerciasis. The results obtained suggested the possibility of a seasonal variation in the microfilarial skin density. Almost all of the volunteers participating had shown a peak concentration of microfilariae in September, followed by August or October. The highest biting densities of Simulium ochraceum, the principal vector of onchocerciasis in Guatemala, occurred from September to the following January. It thus appears that the seasonal variation in the microfilarial density may correspond, to some extent, with the biting activity of the vector, S. ochraceum, and/or with climatic changes in the area.     

The use of an Onchocerca volvulus microfilarial antigen skin test in an epidemiological survey of onchocerciasis in Guatemala

Onchocerca volvulus microfilariae obtained from onchocercal nodules were used as antigenic material for a skin test. This antigen is as specific as those previously employed in skin tests, detecting 85·2% of the persons with positive diagnostic signs of onchocerciasis in endemic areas. A low rate of false positives was found in the control group in non-endemic areas. The positive rate of reactions in the persons without positive signs in the endemic areas might be due to the presences of cases not detected as a result of palpation for nodules and two skin biopsies. In the examination of the residents of several populations, a close correlation was found between the positive rates of skin tests and the presence of infection. From these findings, we conclude that the skin test using the microfilarial antigen is a suitable procedure for the diagnosis of onchocerciasis. The skin test could also be useful as an epidemiological tool in assessing the effectiveness of control programmes.     

Microfilaruria in onchocerciasis. A clinical and epidemiological follow-up study in the Republic of Chad

Microfilariae of O. volvulus were recovered from the urine of 11% of the residents of a village in the Republic of Chad where onchocerciasis was holoendemic. A follow-up study of the same population 3 years after the original investigation revealed that microfilaruria was still present and that living microfilariae of O. volvulus could be recovered from small urine samples obtained by high catherization of the ureters. Radiological changes consistent with chronic pyelitis were found in 4 out of 14 persons with microfilaruria who were examined by retrograde pyelography. The recovery of microfilariae in the urine was associated with the intensity of the infection, as determined by counts of microfilariae in skin snips and the number of onchocercomata. A systematic comparison for differences between onchocerciasis patients with and without microfilaruria revealed that the microfilaruria patients had a low weight: height ratio, deficient antibody responses in indirect haemagglutination tests with O. volvulus antigen, elevated serum aminotransferase levels, and reduced systolic blood pressure.     

Onchocerciasis in Kenya 9, 11 and 18 years after elimination of the vector

Elimination of the onchocerciasis vector Simulium neavei through larvicidal operations in focal areas of Kenya in 1946, 1953, and 1955 achieved complete interruption of transmission. Since no treatment was administered to the infected population, the areas provided an opportunity for studying the natural course of the infection in man in the absence of reinfection, with particular emphasis on its average duration and the effect of duration of exposure to the infection. In a follow-up survey conducted in 1964 in four focal areas, approximately 2000 people were examined parasitologically and clinically; slightly over half this group were also given a thorough ophthalmological examination. The results showed that, 11 years after interruption of transmission, live Onchocerca volvulus adults were present in nodules and microfilariae were present in the skin; after 18 years, however, microfilariae were no longer found in the skin. Assuming that in hyperendemic areas parasites are acquired until shortly before interruption of transmission, it can thus be postulated that O. volvulus worms lose their reproductive potentiality after 16 years or possibly earlier. A comparison of recent microfilarial rates with adjusted rates found in earlier surveys seems to indicate that the onchocercal infection, after interruption of transmission, follows a straight regression line, theoretically reaching zero after about 13-17 years.     

Studies on onchocerciasis in the United Cameroon Republic. I. Comparison of populations with and without Onchocerca volvulus

The results of an onchocerciasis survey of total populations aged 5 years and over in 22 village groups in Cameroon rain-forest and savanna are reported. Using standardized techniques the same observers examined skin and eye lesions in 2,678 persons infected with O. volvulus, and compared them with lesions in 1,156 persons in whom the parasite was not detected.     

Epidemiological studies on onchocerciasis by means of a new field technique.

A new membrane filter concentration technique for the detection and quantification of Onchocerca volvulus microfilariae in skin snips was compared for sensitivity and efficiency with a widely used “standard” technique. A field study was carried out in five villages in an onchocerciasis focus north-east of the town of Sokodé, Mô river valley, Togo. Use of the new technique resulted in a substantial rise in the observed prevalence and density of microfilariae.     

Mixing of Schistosoma haematobium strains in Ghana.

In Ghana, Schistosoma haematobium exists as two strains, one transmitted by Bulinus rohlfsi and the other by B. globosus. In Anyaboni, a resettlement town, where the field station of the UNDP/WHO Schistosomiasis Research and Control Project is located, the residents contract the ”rohlfsi” strain of the parasite from the Volta Lake and the ”globosus” strain from a stream near the town. The present studies indicate that there is mixing of the two parasite strains on a community and an individual basis. In Anyaboni, the parasite developed well in both B. rohlfsi and B. globosus. In another village 25 km from Accra, where B. globosus was the only vector, the parasite developed well in B. globosus but was refractory in B. rohlfsi. In a village near the Volta Lake where B. rohlfsi was the sole vector, the parasite developed well in B. rohlfsi but was refractory in B. globosus. However, complete separation of the two strains is uncommon in Ghana because extensive mixing has already occurred owing to migration of people and snails.     

Onchocerciasis in Zambia: report of O. volvulus in a child and its differentiation from O. dukei in cattle

We report the finding of Onchocerca volvulus in a child in Zambia. This is the first such documented case in an indigenous person and represents perhaps the southernmost limit of the known occurrence of human onchocerciasis in Africa. The specific diagnosis was confirmed by the morphology of the adult worms and microfilariae in tissue sections. O. volvulus was differentiated from O. dukei, a similar species found in cattle from the same geographical locality, to exclude a zoonosis.     

DNA vaccine encoding the moonlighting protein Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) leads to partial protection in a mouse model of human filariasis

River blindness, caused by the filarial parasite Onchocerca volvulus, is a major socio-economic and public health problem in Sub-Saharan Africa. In January 2015, The Onchocerciasis Vaccine for Africa (TOVA) Initiative has been launched with the aim of providing new tools to complement mass drug administration (MDA) of ivermectin, thereby promoting elimination of onchocerciasis in Africa. In this context we here present Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) as a possible DNA vaccine candidate. We report that in a laboratory model for filariasis, immunization with Ov-GAPDH led to a significant reduction of adult worm load and microfilaraemia in BALB/c mice after challenge infection with the filarial parasite Litomosoides sigmodontis. Mice were either vaccinated with Ov-GAPDH.DNA plasmid (Ov-pGAPDH.DNA) alone or in combination with recombinantly expressed Ov-GAPDH protein (Ov-rGAPDH). During the following challenge infection of immunized and control mice with L. sigmodontis, those formulations which included the DNA plasmid, led to a significant reduction of adult worm loads (up to 57% median reduction) and microfilaraemia (up to 94% reduction) in immunized animals. In a further experiment, immunization with a mixture of four overlapping, synthetic Ov-GAPDH peptides (Ov-GAPDHpept), with alum as adjuvant, did not significantly reduce worm loads. Our results indicate that DNA vaccination with Ov-GAPDH has protective potential against filarial challenge infection in the mouse model. This suggests a transfer of the approach into the cattle Onchocerca ochengi model, where it is possible to investigate the effects of this vaccination in the context of a natural host–parasite relationship.     

The effects of drugs on Onchocerca volvulus. 4. Trials of melarsonyl potassium

The effects of the arsenical drug melarsonyl potassium on Onchocerca volvulus were investigated in patients in Cameroon infected with the Cameroon forest and Sudan savanna strains of the parasite. Two intramuscular dosage schedules were tested: the first comprised 4 consecutive daily doses of 200 mg repeated once after a 10-14 day interval, i.e., 2 (4×200 mg). The second was a single dose schedule at 7.1 mg/kg—10 mg/kg, with a maximum of 500 mg.     

Prevalence of depigmentation of the shins: a simple and cheap way to screen for severe endemic onchocerciasis in Africa.

The prevalence of skin depigmentation in the pretibial region is closely correlated in the adult Congolese population with conventional indices (microfilarial index, mean microfilarial density, cyst index) for the evaluation of endemic onchocerciasis. Individuals over 15 years of age in endemic villages who had a microfilarial index of 80-90%, had a cystic index of 60-70% and a pretibial depigmentation index about 20% (30-40% for individuals aged > 50 years). Thus, in Africa, this new evaluation index offers a simple, noninvasive, quick and cheap way to identify areas where the level of endemic onchocerciasis is probably high and which are likely to benefit from an anti-onchocerciasis campaign.     

Variation in delayed hypersensitivity in onchocerciasis

Soluble antigen preparations were made from Onchocerca volvulus adults recovered from subcutaneous nodules, and from Necator americanus third-stage larvae. Intradermal skin tests were carried out on a total of 100 individuals clinically classified as having either the generalized form of onchocerciasis (86 cases), or the localized sowda form (14 cases). 91 of the people studied produced immediate reactions to the onchocercal antigen, but only those with sowda showed delayed reactions, though one person with generalized disease showed a doubtful delayed reaction. Reactions to N. americanus antigen, both immediate and delayed, were seen in both forms of the disease.The lack of delayed skin reaction in the generalized form of onchocerciasis is discussed, and a comparison is made with other diseases. Preliminary evidence for the existence of a true spectrum of clinical and immunological forms of onchocerciasis is suggested by one case in this study.     

Enzymes of entamoeba histolytica

In spite of extensive studies of the pathogenic activities of Entamoeba histolytica upon animal hosts by many investigators, the factors that govern the pathogenesis of the parasite are still largely unknown. Attempts have been made to determine the factors concerned in the pathogenicity of certain strains of E. histolytica from the aspect of parasite itself and from the point of view of its interaction with the host. The enzyme content of the trophozoites of the amoebae examined has been studied in detail, both in the living organism and in its extracts. The total patterns of proteolytic enzymes and of certain other enzymes were determined to establish whether it was possible to define the invasiveness of the various strains of E. histolytica already established as pathogenic by other workers or in our laboratories. It was found impossible to distinguish clearly between the so-called ”pathogenic” and ”non-pathogenic” strains of E. histolytica by such means.     

Mating, blood feeding, and oviposition of Simulium damnosum Theobald in the laboratory

The development of suitable techniques for colonizing the vectors of human onchocerciasis in the laboratory would facilitate critical studies on many aspects of their biology. Progress towards this end, however, has until now been prevented by the fact that no African simuliid had been induced to mate in captivity. The main vector of human onchocerciasis in Africa is Simulium damnosum, which exists in a number of different forms, some but not all of which bite man. During the present investigations one form of S. damnosum, the “Kibwezi” form, was successfully induced to mate, to blood-feed, and to lay viable eggs in the laboratory. The methods described should be tested on other forms of S. damnosum, especially the anthropophilic forms responsible for the transmission of Onchocerca volvulus.     

The effects of drugs on Onchocerca volvulus. 2. The antimonial preparations TWSb and MSbE

Antimonial preparations (Pentostam, Neostibosan, stibophen, and tartar emetic) have occasionally been used in the treatment of onchocerciasis without very promising results. The advent of the preparations TWSb (stibocaptate) and MSbE (Friedheim) of allegedly reduced toxicity made it desirable to test them against Onchocerca volvulus.     

Relationship between onchocerciasis and epilepsy: a matched case-control study in the Mbam Valley,Republic of Cameroon

Studies conducted during the past 10 years to investigate the possible relationship between onchocerciasis and epilepsy have led to contradictory results. In 1991-92 and 2001 we investigated 14 villages in central Cameroon to evaluate the relationship, at the community level, between the prevalence of epilepsy and the endemicity level of onchocerciasis. A case-control study compared the microfilarial loads of 72 epileptic and 72 non-epileptic individuals, matched according to sex, age, and village of residence. The prevalence of epilepsy and the community microfilarial load (CMFL) were closely related (P < 0.02), and the case-control study demonstrated that the microfilarial loads (microfilariae per snip) in the epileptic group (arithmetic mean = 288, median = 216) were significantly higher (P < 10(-4)) than in the control group (arithmetic mean = 141, median = 63). The results strongly support the existence of a link between onchocerciasis and epilepsy. The fact that such a relationship has not been found recently in some other West and Central African areas is probably due to the lowered endemicity of onchocerciasis following vector- and ivermectin-related control measures applied over the past 5-25 years. The socio-economic and demographic impact of onchocerciasis-related epilepsy should be evaluated, and taken into account as part of all onchocerciasis control programmes.     

Experiments on the chemoprophylaxis of Onchocerca volvulus infection

Previous work on monkeys and on human volunteers led to the development of a schedule of diethylcarbamazine dosage suitable for the chemoprophylaxis of loiasis. In several parts of Africa where this chemoprophylaxis is practised against Loa loa, infections with Onchocerca volvulus are also common. Attempts were therefore made to determine whether diethylcarbamazine has any prophylactic action against the latter parasite by making use of chimpanzees exposed to experimental infections, and also by using biopsy techniques to study the fate of infective larvae inoculated into volunteers.