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[Onchocerciasis in travelers to the tropics].

Two men, aged 54 and 31 years respectively, developed an itching skin rash 18 and 6 months respectively after returning from a trip to Africa, the former also recurrent conjunctivitis. Two years and 6 months, respectively, passed from the time of first symptoms until the diagnosis of onchocerciasis was made. Both patients had an eosinophilia (10.5 and 19%) and specific antibodies against Onchocerca volvulus. Microfilaria were demonstrated in the skin of the younger man. The other one had bilateral corneal infiltrates. Both patients were treated with a single dose of ivermectin, 150 micrograms/kg. Within several months, the clinical symptoms and eosinophilia disappeared and the antibody titres decreased.

Adult↗

[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.

Adolescent↗

Immunological studies on onchocerciasis in Sierra Leone. 1. Pretreatment baseline data.

Cellular immune responses were tested in vitro using peripheral blood mononuclear cells from 203 individuals resident in an area of Sierra Leone where onchocerciasis is hyperendemic, and 32 individuals (Gambians) with no history of contact with Onchocerca volvulus. Mean reactivity to the mitogen, Concanavalin A, did not differ between these two groups, but responses to PPD were markedly lower in those with onchocerciasis. Proliferative responses to adult female O. volvulus antigen in the latter group were generally low although elevated reactivity was found in certain sub-groups. Higher responses were evident in infected 10-14 year olds, and there was an association between elevated reactivity to O. volvulus antigens and acute reactive dermatological signs, with individuals in the latter group also carrying higher dermal microfilarial loads. A sub-group presenting with lymphadenopathy showed the strongest associations of these three parameters. These results suggested the requirement for a threshold density of dermal microfilariae for induction of acute reactivity. The presence of immunosuppressive factors in soluble O. volvulus antigen was indicated by the ability to suppress, at low concentrations, the cellular responses to PPD of a proportion of individuals.

Adolescent↗

The Wellcome Trust lecture. Inflammatory responses to filarial connective tissue parasites.

The inflammatory responses to lymphatic filariae and to Onchocerca volvulus are reviewed with particular attention to evolutionary biology; inflammatory host spectrum; non-specific components; immunoregulation; immune evasion versus immunomodulation; chronic tissue damage and scarring and disease models. Basic principles of pathogenesis are emphasized, comparisons drawn with schistosome infection, and critical items of missing information are highlighted.

Animals↗

Microepidemiology of onchocerciasis in Guatemala: dispersal and survival of Simulium ochraceum.

Wild Simulium ochraceum females, both blood engorged and non-blood engorged, were collected from human volunteers infected with Onchocerca volvulus, marked with fluorescent dyes, and released from the same locality as they were collected during February and March 1989. A small hyperendemic village located within 0.5 km of streams supporting large populations of S. ochraceum larvae served as the site for both collection and release of adult females. Fifteen sites for the recapture of flies were located within this same village, within two other villages located 1.0 and 3.7 km from it, and at other places spaced approximately 0.25-3.5 km within a coffee agroecosystem. Flies from both groups were recaptured at distances ranging to 3.5 km from the point of release. Non-blood-engorged flies, however, exhibited a greater tendency to disperse away from the release site. Of the total number of blood-engorged flies recaptured, 51.9% were collected at the release point, 25.7% at 1.0 km, and 1.6% at 3.3-3.5 km. The corresponding percentages for non-blood-engorged flies were 26.9%, 40.4%, and 4.4%, respectively. No flies from either group were recaptured at the most distant site, a large village that was 3.7 km away. Marked flies from both groups were recaptured 12-14 days after release, which was sufficient time for the development of infective O. volvulus larvae. A survival rate (4.7%) of marked, blood-engorged flies over the second and third gonotrophic cycles was estimated from the slope of the regression line of the log number of flies recaptured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antibody responses in forest and savanna onchocerciasis in Ivory Coast.

Three foci of onchocerciasis transmission (two forest and one savanna, respectively) in the Republic of Ivory Coast were chosen for a comparative analysis of Onchocerca volvulus antigens and of patients' antibody responses. Clear differences between frequency and intensity of ocular pathology existed between the forest foci and the savanna focus. We found heterogeneity of SDS-PAGE-separated components of female worms with respect to the mobility of three protein bands of the 100 KD region and to the ability of an 80 KD band to bind horseradish peroxidase. These variations were clearly not associated with the degree of ocular pathology. No differences in the composition of worm antigens were detected by immunoblotting. A variable with a possible relation to ocular pathology was the antibody response of patients: individuals from the savanna focus, where a high degree of ocular pathology is observed, tended to have a stronger and more differentiated IgG antibody response against O. volvulus antigens than patients from the forest foci. However, no antigens specifically recognized by patients from either forest or savanna were detected.

Adolescent↗

Man-biting species of Chrysops meigen, Culicoides latreille and Simulium latreille in Ethiopia, with discussion of their vector potentialities.

Human filariasis and its vectors are little known in Ethiopia. Wuchereia bancrofti is confined to the western lowlands and cannot be the aetiological agent of elephantiasis in the highlands. Onchocerca volvulus is widespread in the south-western highlands. Loa loa and Dipetalonema perstans are reported here for the first time and appear to be uncommon. Studies were conducted in 1973, mostly near Jimma in Kaffa Province, on potential vectors of all but the first of these parasites. Among Simuliidae, the only blackflies of apparent medical importance were S. woodi ethiopiense and a possibly new member of the S. damnosum complex. The former is less seasonal and much less numerous than the latter, but may be more widespread and important along smaller and higher streams. Onchocerca larvae were recovered from "damnosum", but not from the small number (46) of ethiopiense examined. In August, at the height of the rainy season, the biting-rate of ethiopiense at 1,710 m altitude on the Gilgil Ghibe river reached 9.5/man-hour at 10-1100 hours and about 12/man-hour at 14-1600 hours. At the same time and place, the attack of "damnosum" reached a midday climax of about 1,800/man-hour; this peak could be delayed or suppressed by rain. Another possibly anthropophilic blackfly, S. dentulosum, tended to become most common in December afer the rainy season had passed, but proved incompetent to bite man successfully. The only feasible loiasis vector found in Ethiopia was Chrysops streptobalius; however, this tabanid was not closely associated with man. Up to 34/man-day were caught in watermeadows by the Gojeb river (altitude 1,160 m) in October. Man-biting species of Ceratopogonidae in various parts of Ethiopia were Culicoides fulvithorax, C. grahamii, C. kingi and C. milnei. The first two of these were anthropophilic in lowlands, but apparently not so in highlands. C. milnei was extremely abundant biting man highlands. C. milnei was extremely abundant biting man and domestic animals both indoors and outdg cycle was irregular, usually displaying a succession of ill-define nocturnal peaks; sometimes it attacked in daylight. Up to 35,000 C. milnei per trap-night were caught in light traps. Most of the females entering light traps in a stable were already engorged with blood. It seemed very likely that C. milnei would prove to be of veterinary importance. No firm indication was obtained as to what may transmit D. perstans in Ethiopia.

Animals↗

Some unsolved problems in the epidemiology of onchocerciasis.

The descriptive epidemiology of onchocerciasis is well understood in the major foci of infection; a great stimulus to epidemiological research has been the implementation of the first control programme, which led to the eradication of infection in Kenya and, more recently, the vast Onchocerciasis Control Programme in the Volta River Basin of West Africa. However, there are still significant gaps in epidemiological knowledge which hamper the planning of future control programmes and the evaluation of current programmes. The four most important unsolved problems are: the refinement of field diagnostic techniques to identify skin microfilariae at the ultra-low densities that will become common in the late stages of vector-control campaigns; the definitive identification of Onchocerca volvulus infective larvae in Simulium species; strain analysis in the field of microfilariae from humans and of developing stages from Simulium, to determine their potential for ocular pathogenicity; determination of the lifespan, or maximum fecundity span, of adult female O. volvulus after the interruption of transmission. Three other unsolved problems are of enormous interest epidemiologically, although less urgent in practical importance. They are the identification of factors causing severe disease as opposed to heavy infection; the effects of seasonal as opposed to perennial transmission; and the importance of transplacental transmission of microfilariae or soluble antigens.

Africa↗

Metrifonate in onchocerciasis and lymphatic filariasis.

Metrifonate, in doses of 10 mg/kg for 3 consecutive days, demonstrated partial microfilaricidal activity against Onchocerca volvulus in humans. Higher doses were not investigated because of the toxic reactions obtained and the absence of monitoring of the blood cholinesterase levels. Spaced doses of 10 mg/kg every 2 weeks or once monthly up to 3 doses showed neither micro- nor macrofilaricidal activity against Wuchereria bancrofti.

Adolescent↗

Changes in antibody profile after treatment of human onchocerciasis.

To define the changes in antibody response to Onchocerca volvulus antigens after treatment of patients with onchocerciasis, IgG and IgE antibodies were examined quantitatively and qualitatively in 21 patients and 3 control individuals before and sequentially for 14 days after treatment with diethylcarbamazine. The quantitative levels of IgE and IgG responses (both polyclonal and O. volvulus-specific) remained essentially unchanged for all patients, but 9 of the 21 patients showed intensified responses to one or more parasite-specific antigens, and 8 of 21 developed antibodies to previously undetected antigens. There was a significant correlation between the intensities of infection and the development of newly recognized anti-O. volvulus antibodies. These studies demonstrate that O. volvulus-specific IgE and IgG antibody responses are, at least transiently, enhanced by treatment with diethylcarbamazine and that after treatment, parasites possibly release antigens previously hidden from the host's immune response.

Adolescent↗

Diagnosis and extirpation of nodules in human onchocerciasis.

The clinical search for onchocercal nodules, and their preferred sites on the body in different geographic areas are described and illustrated. The differential diagnosis of onchocercomata is discussed and figures on the frequency of false diagnoses are reported. The prevalence of adult Onchocerca volvulus in relation to the endemicity of infection, the age and sex of the patients, the localisation of nodules on the body, and the measures used to control onchocerciasis are discussed. Recommendations are made on the selection of patients for different medical studies. The technique of nodulectomy and the equipment needed are described.

Animals↗

Studies on the biology of Simuliidae (Diptera) at the Santiago onchocerciasis focus in Ecuador, with special reference to the vectors and disease transmission.

A survey showed the presence of seven simuliid species in the onchocerciasis focus in Ecuador Simulium exiguum and S. quadrivittatum were the two most common anthropophilic species and were shown to be both experimental and natural vectors of Onchocerca volvulus. S. antillarum only occasionally bit man. Observations were made on the biology of the two vector species and it was evident that S. exiguum was the primary vector of onchocerciasis in the rainy season. The relevance of these findings to the epidemiology and control of onchocerciasis in Ecuador are discussed.

Animals↗

Thirty-month follow-up of sub-optimal responders to multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana.

The pathogenesis of the sub-optimal response of Onchocerca volvulus to ivermectin was investigated in a 30-month follow-up of 28 individuals who, in a previous study, had been found to show a sub-optimal (N = 15) or adequate response (N = 13) to multiple treatments with the drug. Verbal informed consent was obtained before each subject was given a general clinical and ocular examination. Skin snips were taken from both iliac crests and both calves. Seventeen nodule carriers were hospitalized for nodulectomy. Adult worms were harvested, embryogrammes were constructed and all developmental stages were counted; degenerate, stretched microfilariae were noted separately. All the subjects were in good general health and all except one had received at least one additional treatment with ivermectin since the earlier study. A large proportion of the adult female worms in 10 out of the 11 sub-optimal responders who were nodule carriers were in full embryonic production but most of the stretched microfilariae they carried were degenerate. This picture is similar to that found in adult worms exposed to the first dose of ivermectin. In one subject who had no viable worms in his nodules, the existence of occult but actively reproductive worms was inferred from the high level of microfilaridermia observed less than 12 months after treatment. These observations confirm the existence of populations of adult female O. volvulus that respond poorly to repeated doses of ivermectin. The use of suramin in the treatment of the sub-optimal responders is discussed.

Adult↗

Microfilariae in the cerebrospinal fluid, and neurological complications, during treatment of onchocerciasis with diethylcarbamazine.

Microfilariae of Onchocerca volvulus were found in the cerebrospinal fluid (CSF) of 5/8 heavily infected onchocerciasis patients. During treatment with diethylcarbamazine citrate 10/11 patients showed increased numbers of 0. volvulus microfilariae in the CSF. Patients with concentrations of 8-31 mf/ml CSF developed severe vertigo, and some other neurological manifestations, during treatment. A hypothesis is put forward to account for this clinical piciture, and its importance in relation to the treatment of onchocerciasis is discussed.

Arachnoid↗

Variations in host responses and the pathogenesis of human onchocerciasis.

Different immune responses to Onchocerca volvulus cause considerable variation in clinical manifestations of human onchocerciasis. Onchocercal lesions result from inflammatory reactions involving immunologic mechanisms; the role of the immune system in pathogenesis is emphasized by the phenomena accompanying accelerated worm destruction during microfilaricidal chemotherapy (e.g., eosinophilia, changes in total immunoglobulin level, and anaphylactic symptoms). Although most pathologic changes are associated with the microfilarial stage, the extent to which circulating antibodies are directed against antigens in the adult worm or its uterine constituents is unknown. Microfilarial destruction can be mediated by antibody to the surface-associated antigens of the worms and enhanced by complement; a correlation exists between the presence of these antibodies and punctate keratitis. Heterogeneous immunologic components are associated with the surface of dermal and nodular microfilariae in vivo. Preliminary findings indicate that the level of O. volvulus-specific immune complexes is inversely proportional to the microfilarial load. To monitor a patient's clinical status and immunologic response, a quantitative system dividing symptoms into those associated with active responses to the microfilariae and those representing long-term consequences of these reactions is suggested.

Antibody Formation↗

The status of Simulium oyapockense and S. limbatum as vectors of human onchocerciasis in Brazilian Amazonia.

In an attempt to explain the current distribution of onchocerciasis in the forests of northern Brazil (Moraes et al., 1979, 1986), and its potential for dispersal to other areas, this study compares the vector status of Simulium oyapockense Floch and Abonnenc, 1946 in both a hypoendemic and an onchocerciasis free area with that of S. limbatum Knab, 1915 in the latter area. Both species allowed the full development of Onchocerca volvulus (Leuckart) to the infective L3 stage after experimental infection with microfilariae. Their vector competence was significantly lower than for other efficient vector species in South America and Africa because of the lethal effect of the cibarial armature on ingested microfilariae. The low vector capacity of S. oyapockense, together with the low prevalence and intensity of infection of O. volvulus, probably explains why onchocerciasis has not significantly increased in intensity over the last 10 years in the hypoendemic part of the Amazonian focus. Omnipresence of both vector species in the adjacent savanna region, however, could facilitate the spread of onchocerciasis if human population movements continue from the hyperendemic part of the onchocerciasis focus.

Animals↗

Anthropophily, zoophily and roles in onchocerciasis transmission of the Djodji form of Simulium sanctipauli and S. squamosum in a forest zone of Togo.

Adult female Simulium damnosum s.l. were caught at human and cattle bait at Djodji in Togo. Two members of the Simulium damnosum complex, the Djodji form of S. sanctipauli (74.9% of the total catch) and S. squamosum (25.1%), were identified and both were mainly anthropophilic. Although each species was also recorded feeding on cattle or turkey baits, most flies which were caught at animal baits did not take blood from them. Flies caught unfed at the cattle bait tended to be larger and have higher parous rates than those caught on man. S. sanctipauli flies were on average larger than S. squamosum but the sizes of both species varied seasonally. Infections with Onchocerca volvulus were found in both species. The infection rates varied seasonally with the highest levels occurring in the wet season. The Djodji form of S. sanctipauli is potentially a much more efficient vector (162 L3/1000 biting flies) than both S. squamosum (48 L3/1000 biting flies) and the S. sanctipauli s.l. found in the Cote d'Ivoire.

Animals↗

A semi-automated system of intrathoracic injection for the large-scale production of Onchocerca lienalis infective larvae.

Intrathoracic injection of Onchocerca lienalis microfilariae (mf) into Simulium ornatum sl. is a highly efficient procedure for routine production of infective stage larvae (L3). This bovine parasite provides a useful analogue of Onchocerca volvulus from man, which presents far greater difficulties for L3 production outside endemic areas of onchocerciasis. Using novel systems for the infection and caging of adult blackflies in the laboratory, mean yields of 10.1-38.6 L3 per fly have been regularly obtained. Cyclical maintenance of either the parasite or vector is not a requirement for the success of this approach. An automated device has been developed to control deliveries of mf inoculations, that permits an experienced operator to perform injections at a rate of approximately 200 flies an hour. Mass recoveries of larvae by Baermann extraction appeared to be highly efficient, contrasting an earlier report on the application of this method to Onchocerca L3. Typical performance of these techniques in routine use over a period of time is illustrated with data on 18,000 inoculated blackflies, which yielded over 100,000 L3. Viability of the L3 obtained by the procedures described was confirmed by successful transmission of patent infections to laboratory-reared calves.

Animals↗