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PubMed1999

Population biology of human onchocerciasis.

Human onchocerciasis (river blindness) is the filarial infection caused by Onchocerca volvulus and transmitted among people through the bites of the Simulium vector. Some 86 million people around the world are at risk of acquiring the nematode, with 18 million people infected and 600,000 visually impaired, half of them partially or totally blind. 99% of cases occur in tropical Africa; scattered foci exist in Latin America. Until recently control programmes, in operation since 1975, have consisted of antivectorial measures. With the introduction of ivermectin in 1988, safe and effective chemotherapy is now available. With the original Onchocerciasis Control Programme of West Africa coming to an end, both the new African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas, rely heavily on ivermectin self-sustained mass delivery. In consequence, the need for understanding the processes regulating parasite abundance in human and simuliid populations is of utmost importance. We present a simple mathematical framework built around recent analyses of exposure- and density-dependent processes operating, respectively, within the human and vector hosts. An expression for the basic reproductive ratio, R0, is derived and related to the minimum vector density required for parasite persistence in localities of West Africa in general and northern Cameroon in particular. Model outputs suggest that constraints acting against parasite establishment in both humans and vectors are necessary to reproduce field observations, but those in humans may not fully protect against reinfection. Analyses of host age-profiles of infection prevalence, intensity, and aggregation for increasing levels of endemicity and intensity of transmission in the Vina valley of northern Cameroon are in agreement with these results and discussed in light of novel work on onchocerciasis immunology.

Adolescent↗

PubMed1992

Musculo-skeletal pain (MSP) in onchocerciasis: a potential in the rapid low cost epidemiological survey and in the assessment of impact of ivermectin treatment on a community.

The diagnostic potential of musculo-skeletal pain (MSP) in the rapid assessment of onchocerciasis of morbidity and of the impact of ivermectin treatment in a community is brought to picture. The clinical impression is that MSP is a common, early, chronic important symptom of onchocerciasis. With a significant association with onchocerciasis, MSP has the potential of being an important operational diagnostic clue in the detection of onchocerciasis. It has the advantage of being easily recognizable, and therefore can be applied by primary health care workers. MPS is proved to cause the greatest morbidity, particularly among working farmers in areas where the forest strain of O. volvulus is predominant. Thus, onchocerciasis is contributing more than was perhaps realized to the reduced output of work from farmers. However, MPS, a parasitic rheumatism, is proved to be eminently susceptible to treatment by DEC.

Humans↗

PubMed1996

Elevated serum angiotensin-converting enzyme activity in onchocerciasis.

Our objective was to measure serum angiotensin-converting enzyme (ACE) activity in patients with onchocerciasis. Serum ACE activity is commonly used in the diagnosis and follow-up of patients with sarcoidosis. However, serum ACE activity can also be elevated in a number of other granulomatous disorders. In onchocerciasis, a parasitic disease affecting millions of people in Africa and Central and South America, granulomatous tissue around adult worms has been identified, yet raised serum ACE activity has not been reported so far. We measured serum ACE activity in serum samples from 42 onchocerciasis patients and 39 endemic controls previously enrolled in two studies concerning the side effects after invermectin treatment in Sierra Leone, West Africa. The mean ACE activity in the patient group was 53.8 units/liter (S.D. 19.8) compared with 35.2 units/liter (S.D. 14.0) in the control group (p < 0.0001). Nine of 42 patients had elevated ACE activity (mean of the endemic controls +/- 2 S.D.) compared with 1 of 39 controls (p = 0.01). Sensitivity and specificity of elevated ACE in serum from onchocerciasis patients from Sierra Leone was 21 and 97%, respectively. ACE activity was not related to the microfilarial skin load or development of side effects after ivermectin treatment. Serum ACE activity can be elevated in onchocerciasis. Clinicians should be aware of this phenomenon when determining serum ACE activity in persons from endemic areas.

Adult↗

PubMed1991

Detailed epidemiological mapping of three onchocerciasis foci in West Africa.

Detailed epidemiological mapping of three isolated foci of hyperendemic blinding onchocerciasis was undertaken in three West African countries as part of community trials of ivermectin, a new microfilaricide for the treatment of human onchocerciasis. The results show that the geographical distribution of the prevalence and intensity of onchocerciasis infection in the community can be very different from what was expected on the basis of demographic and entomological information. The technique of detailed epidemiological mapping is an important tool for the identification of target populations for large scale ivermectin treatment of onchocerciasis. It is being used extensively in the Onchocerciasis Control Programme in West Africa.

Africa, Western↗

PubMed1995

Differences in eosinophil and neutrophil chemotactic responses in sowda and generalized form of onchocerciasis.

Extravasation of host's leukocytes from blood vessels into inflammatory tissues represents a prerequisite for a subsequent interaction with invaded parasites. The migratory responses of eosinophilic and neutrophilic granulocytes in the polar forms of the filarial infection onchocerciasis were investigated. The hyporeactive, generalized form, the chronic hyperreactive (sowda) form and persons without signs of onchocerciasis from a hypoendemic area for onchocerciasis were compared. Eosinophils from sowda patients responded more strongly to the inflammatory mediator platelet-activating factor (PAF) than those from generalized patients and persons without onchocerciasis. The most significant differences were found between the sowda group and a subgroup of the generalized form with 16-80 microfilariae/mg skin (P<0.05) while patients with low microfilarial density exhibited chemotactic responses similar to the sowda group. In contrast to the strong eosinophil response, neutrophils from sowda patients appeared unreactive to PAF and the tripeptide activator formyl-methionyl-leucyl-phenylalanine (fMLP), thereby differing from both other groups. Laboratory data confirmed a state of hyperreactivity in sowda patients similarly found in generalized patients with low microfilarial density and contrasting with those with a microfilarial density of 16-80 mf/mg. The results revealed an inverse chemotactic responsiveness of eosinophil and neutrophil granulocytes in sowda patients and strengthened the observation of a spectrum of host's responsiveness in onchocerciasis.

Adolescent↗

PubMedDate not supplied

Serum-dependent interaction of granulocytes with Onchocerca volvulus microfilariae in generalized and chronic hyper-reactive onchocerciasis and its modulation by diethylcarbamazine.

The adherence and cytotoxicity of granulocytes to microfilariae of Onchocerca volvulus were examined in vitro. Reactivity and modulation by diethylcarbamazine of isolated eosinophilic and neutrophilic granulocytes from patients with generalized and chronic hyper-reactive onchocerciasis (sowda or localized form) from endemic foci in Liberia were evaluated under varying serum conditions. In the presence of pooled sera from patients with generalized onchocerciasis granulocytes from both polar groups of patients exhibited similar adherence rates, whereas immobilization rates were higher for eosinophils than for neutrophils. In localized onchocerciasis, the use of autologous serum resulted in a significant decrease in adherence and immobilization rates for both eosinophils and neutrophils. After preincubation of eosinophils, but not of microfilariae, with diethylcarbamazine autologous serum-mediated adherence and cytotoxicity were enhanced to rates similar to those found with pooled serum from individuals with generalized onchocerciasis. These results suggest that granulocytes from both forms of onchocerciasis did not differ with respect to their anti-parasitic reactivity and that antibodies as well as additional serum factors appear to contribute to the functional activity of these effector cells. The findings indicate that predominantly eosinophils, compared to neutrophils, damage the larvae of O. volvulus and support earlier observations which suggest that diethylcarbamazine influences the effector cells rather than the parasite itself.

Adolescent↗

PubMedDate not supplied

Co-endemicity of loiasis and onchocerciasis in the South West Province of Cameroon: implications for mass treatment with ivermectin.

Encephalopathy has been reported in Cameroon in individuals heavily infected with Loa loa microfilariae who were treated with ivermectin against onchocerciasis. Prior to the initiation of the community-directed treatment of onchocerciasis with ivermectin (CDTI) in the South West Province of Cameroon, an epidemiological survey of loiasis was conducted (in July 1998-July 1999) to ascertain the intensity of the disease. Thick blood films were made from 1228 blood samples collected during the day. Rapid epidemiological assessment (REA) of onchocerciasis was conducted among 614 individuals in the Upper Bayang area. Sixteen percent of the population examined were carriers of L. loa microfilariae. More males (20.1%) than females (12.4%) were infected. The community mean microfilaraemias of the different villages were low (< 1100 mf/mL). However, 1 person was found harbouring 174,000 mf/mL of blood and 1% of the study population (12) had microfilaraemia > 8100 mf/mL. Results of the REA of onchocerciasis show that 31.3% of the population investigated in the Upper Bayang area have this disease. These findings show that loiasis and onchocerciasis are co-endemic in the area, but the risk of developing encephalopathy after taking ivermectin is small.

Adolescent↗

PubMed1998

High incidence of epilepsy related to onchocerciasis in West Uganda.

The incidence of epilepsy was assessed in an onchocerciasis endemic area in West Uganda over a period of 4 years. A high overall crude incidence rate of 215 per 100000 person-years was found (age-adjusted: 156 per 100000 person-years) and the incidence in zones of high onchocerciasis endemicity was significantly higher than in low endemic zones (age adjusted rates: 232 per 100000 person-years versus 77 per 100000 person-years; Yates corrected chi2: P < 0.01). The data constitute a baseline for an ongoing intervention study on the effects of onchocerciasis control on epilepsy incidence in the study area. If a causal relationship between onchocerciasis and epilepsy can be confirmed, this would have significant implications for the concept of morbidity due to onchocerciasis and for the prevention of epilepsy in the endemic areas.

Adolescent↗

PubMed2003

Integrated community-directed treatment for the control of onchocerciasis, schistosomiasis and intestinal helminths infections in Uganda: advantages and disadvantages.

Onchocerciasis is co-endemic with schistosomiasis and intestinal helminths infections, which are all diseases of the rural and the poorest communities in Africa. Community-directed treatment (ComDT) for the control of onchocerciasis is the only functional health approach in most of these communities and the strategy has proven to be effective for onchocerciasis control. This study was conducted to assess the feasibility of integrating ComDT with ivermectin for the control of onchocerciasis, and with praziquantel (PZQ) and mebendazole (MBD) for the control of schistosomiasis and intestinal helminths infections in children aged 5-14 years, and to assess advantages and disadvantages of the integrated ComDT over the routine ComDT and the school-based treatment approach. Integrated ComDT achieved higher treatment coverage (85%) for PZQ and MBD than the school-based treatment approach (79%) among children aged 5-14 years (P = 0.03). There were more reported adverse reactions after treatment with a combination of PZQ and MBD in the school-based treatment approach (33%) than for the combination of ivermectin and MBD on day 1 and PZQ on day 2 in the integrated ComDT (18%). However, all adverse reactions were mild (headache, nausea/vomiting and abdominal pain). The integrated ComDT also achieved higher ivermectin treatment coverage for all ages (81.3%) than routine ComDT (77.2%) (P = 0.0003). To achieve even better coverage for PZQ and MBD among the targeted high risk groups, integrated ComDT should treat all age groups in areas where the prevalence of schistosomiasis and intestinal helminths infections is >50%. This would minimize the shortage of the drugs targeted to treat the high risk groups, as the non-targeted groups, will inevitably demand and receive the treatment from the distributors. The results of this study show that PZQ and MBD treatment for the control of schistosomiasis and intestinal helminths, respectively, can be integrated with ivermectin treatment for the control of onchocerciasis without negatively affecting ivermectin treatment coverage.

Adolescent↗

PubMed2000

Humoral responses to a secretory Onchocerca volvulus protein: differences in the pattern of antibody isotypes to recombinant Ov20/OvS1 in generalized and hyperreactive onchocerciasis.

The Onchocerca volvulus secretory protein Ov20/OvS1 represents a dominant antigen expressed in the infective larvae, microfilariae and adult stages of the parasite. The humoral responses to this protein have not yet been analysed in the polar clinical and immunological forms of onchocerciasis. Analysis by ELISA of class and subclass antibodies to Ov20/OvS1 in persons with the generalized or the hyperreactive form of onchocerciasis revealed similar strong responses of IgG1, IgG4 and IgM antibody levels in both forms of onchocerciasis and significant differences were observed in the IgE and IgA antibody classes. Computation of the ratios of antibodies showed that persons with the generalized form exhibited significantly higher ratios of IgG4 to IgG1, IgG4 to IgE, and IgM to IgE than patients with the hyperreactive form. To investigate the isotype recognition of antigenic sites on Ov20/OvS1 protein, three recombinantly expressed fragments (F1-3) of Ov20/OvS1 were probed using sera which strongly reacted with intact recombinant Ov20/OvS1. Epitope(s) on F1 comprising amino acid residues 1-63 were significantly recognized by IgG1 and IgE, while IgM recognized epitopes on all three fragments. The strongest reaction of IgM occurred with epitope(s) formed by residues 108-171 (F3). In contrast, IgG4 type antibodies were not reactive with either of the three OvS1 fragments, but they reacted with intact Ov20/OvS1 protein. Generalized onchocerciasis, unable to eliminate microfilariae, and hyperreactive onchocerciasis, with a high potency to eliminate or to reduce parasite loads, can be distinguished by a distinct pattern of isotype responses to Ov20/OvS1.

Animals↗

PubMed2000

A health club for a community school in south-eastern Nigeria: influence on adult perception of onchocerciasis and compliance with community-based ivermectin therapy.

The impact of a school health club on adult perception of onchocerciasis and compliance with ivermectin was evaluated in an onchocerciasis-endemic community in southeastern Nigeria. Venous blood was collected from each of 26, 32 and 124 randomly selected subjects during ivermectin distribution programmes in 1995 1996 and 1997 respectively. Ivermectin concentrations were measured in the samples. Data was also collected from 334 and 319 randomly selected household heads or their representatives (aged 24 to 65 years) before and after health talks by schoolchildren, using interviewer-administered questionnaires. There was an increasing number of subjects who participated in control programmes (116 in 1995, 437 in 1996 and 2055 in 1997). Compliance with ivermectin treatment was low (53.9%) in 1995 but increased dramatically (90.1%) in 1997. A significant proportion (chi2 = 108.7, df = 1, P < 0.0001) of respondents knew about onchocerciasis after health education, predominantly from health workers (64.5%) before the tests and children (92.3%) after. Knowledge and beliefs about causative agents (chi2 = 266.4, df = 5, P < 0.0001), diagnostic method (chi2 = 207.4, df = 3, P < 0.0001), prevention (chi2 = 67.0, df = 4, P < 0.0001) of onchocerciasis and the effectiveness of ivermectin (chi2 = 40.4, df = 1, P < 0.0001) also differed significantly between the periods before and after tests. The school health club increased adult knowledge about onchocerciasis and its treatment. Schoolchildren could therefore supplement the information, education and communication (IEC) aspect of health care delivery in a community through such health clubs.

Adult↗

PubMed1998

A method to determine the coverage of ivermectin distribution in onchocerciasis-control programmes.

Onchocerciasis is a human filarial infection responsible for an estimated 750,000 blind and severely visually disabled people. In some African countries, this disease represents the main cause of blindness, with considerable socio-economic impact on the affected communities. Since the introduction of ivermectin as a microfilaricidal agent, there is hope that visual loss from onchocerciasis can be eliminated through community-based ivermectin-distribution programmes. The African Programme for Onchocerciasis Control (APOC) has now been initiated, by the World Health Organization and World Bank, to distribute ivermectin in 19 African countries where onchocerciasis is endemic. Estimates of ivermectin coverage in distribution programmes for onchocerciasis control have so far been based on the number of treatments given, in any one year, to a target population. There is a need for a standardized method to evaluate, measure and monitor coverage over time. In April 1996, a cluster random-sampling method was used to calculate coverage with ivermectin in an urban population of 30,000 people in the Central African Republic. The method was adapted from that used to determine coverage by the WHO Expanded Programme on Immunization. It proved to be inexpensive and easy to perform, requiring only local equipment and personnel. The method used and results obtained in Bossangoa and the potential use of the technique in other distribution programmes are discussed.

Adult↗

PubMed2004

Incidence of blindness during the Onchocerciasis control programme in western Africa, 1971-2002.

BACKGROUND: Infection with Onchocerca volvulus is associated with the prevalence of severe visual impairment and blindness. However, longitudinal studies of the incidence of blindness caused by onchocerciasis are scarce. METHODS: The relationship, at the individual level, between infection with O. volvulus microfilariae and bilateral blindness was examined, by use of data collected, during the Onchocerciasis Control Programme in western Africa (OCP), from 2315 villages in 11 countries. The data were analyzed by Poisson maximum-likelihood techniques with adjustment for overdispersion. RESULTS: A total of 297,756 persons were eligible for follow-up in the cohort, and, during 1971-2001, these persons accumulated 367,788 person-years of follow-up without blindness. A total of 673 bilateral cases of blindness occurred during this period; 29.7% were caused by onchocerciasis. After ivermectin therapy was introduced (during 1988-2001), only 19.6% of cases were caused by onchocerciasis. The incidence of blindness was significantly and positively associated with increasing microfilarial burden (P<.001). Overall, female subjects had an ~40% lower risk of becoming blind than did male subjects (P<.001). After an initially high incidence of blindness at the beginning of the OCP, the rate of blindness from causes other than onchocerciasis remained approximately constant during follow-up. CONCLUSIONS: We demonstrate, in a comprehensive data set and in both sexes, a direct relationship between microfilarial load and the incidence of blindness.

Adolescent↗

PubMed1987

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↗

PubMed2005

Development and evaluation of an antigen detection dipstick assay for the diagnosis of human onchocerciasis.

To improve on the diagnosis of onchocerciasis, especially light infections, we developed and evaluated an oncho-dipstick test based on the detection of Onchocerca volvulus specific antigens in urine and tears. The test was able to detect as little as 25 ng/ml of parasite specific antigens in samples and took as little as 3 h. Evaluation of the assay on 456 residents of an onchocerciasis hyperendermic area in Cameroon resulted in 408 (89.5%) positives in urine and 374 (82%) positives in tears. The prevalence of onchocerciasis in the study area, as determined by Rapid Epidemiological Mapping of Onchocerciasis (REMO) and skin snip methods, was 52 and 36.8%, respectively. The sensitivity of the oncho-dipstick assay was 100% in urine and 92% in tears; its specificity was 100% in both. Concordance between urine and tear test results from the same individuals was 87%. The test strips were sufficiently reactive when left at room temperature for up to 8 months. The test would be useful for laboratory diagnosis of onchocerciasis in low transmission zones and to ascertain successful treatment of patients in experimental drug studies.

Animals↗

PubMed2007

Evaluation of the diethylcarbamazine patch to evaluate onchocerciasis endemicity in Central Africa.

OBJECTIVE: As part of a baseline data collection for assessing the impact of the African Programme for Onchocerciasis Control, to evaluate the diethylcarbamazine (DEC) patch test in determining the endemicity of onchocerciasis. METHOD: A total of 226 untreated children aged 3-5, living in four selected endemic foci, in Cameroon, Gabon and Central African Republic, were tested. Observed graded skin reactions to the patch were analysed and compared with the prevalence of onchocercal nodules and reactive skin disease in the corresponding community. RESULTS: The proportion of children who tested positive ranged from 25.0% to 77.1%. The values were closely correlated with the prevalence of nodules, i.e. the level of endemicity for onchocerciasis. CONCLUSION: The DEC patch test, which has been so far used only in West African foci of onchocerciasis, can also constitute a valuable tool to evaluate the levels of endemicity of onchocerciasis in Central Africa, and to follow-up the intensity of transmission of Onchocerca volvulus.

Cameroon↗

PubMed1993

Preliminary evaluation of recombinant Onchocerca volvulus antigens for serodiagnosis of onchocerciasis.

Serodiagnostic assays for onchocerciasis based on native antigens are hampered by the scarcity of antigen, and they suffer from poor specificity. The present study was designed to evaluate the diagnostic utility of recently described recombinant Onchocerca volvulus antigens OC 3.6 and OC 9.3 in enzyme immunoassays. The recombinant proteins were expressed as glutathione S-transferase fusions and were tested in several enzyme immunoassay formats to measure immunoglobulin G (IgG) and IgG4 antibodies with sera from patients with onchocerciasis in Nigeria and with various types of control sera. The best results were obtained by measuring IgG4 antibodies to the fusion proteins. Forty of 42 (95%) serum specimens from patients with onchocerciasis were reactive with OC 3.6; the reactivity with OC 9.3 was 81%. Results obtained with sera from experimentally infected chimpanzees suggest that OC 3.6 might be especially useful for detecting prepatent infections in humans, while OC 9.3 mainly detects mature, patent infections. Sera from individuals in Nigeria and the United States residing in areas nonendemic for onchocerciasis were uniformly nonreactive with these antigens in IgG and IgG4 assays, as were sera from patients with bancroftian filariasis, brugian filariasis, loiasis, ascariasis, schistomiasis, and dracunculiasis. These results suggest that enzyme immunoassays based on the recombinant antigens OC 3.6 and OC 9.3 are useful for the diagnosis of onchocerciasis.

Animals↗

PubMed1991

Molecular cloning and characterization of recombinant parasite antigens for immunodiagnosis of onchocerciasis.

Immunological cross-reactivity among nematodes has hampered the development of specific serodiagnostic assays for onchocerciasis. In the present study, an Onchocerca volvulus adult worm complementary DNA expression library was differentially screened with human sera from patients infected with O. volvulus and with an omnibus anti-nematode serum pool comprised of sera from patients infected with Brugia malayi, Loa loa, Wuchereria bancrofti, Mansonella perstans, Strongyloides stercoralis, Ancylostoma duodenale, Ascaris lumbricoides, and Dracunculus medinensis. Seven Onchocerca-specific clones were identified and screened with individual onchocerciasis patient sera. Additional studies were performed to characterize the most immunoreactive clones, OC 3.6 and OC 9.3. OC 3.6 produced a 152-kD beta-galactosidase fusion protein that was recognized in dot-immunoblots by 54 of 55 sera from onchocerciasis patients (98%). The OC 3.6 DNA insert is 996 bp long with an open reading frame of 627 bp and a 369-bp untranslated 3' end. OC 3.6 is closely related to a previously reported clone (OV 33-3), but it differs from that clone at both the 5' and 3' ends. OC 9.3 contained a novel 565-bp insert and produced a 138-kD fusion protein that was recognized by 46 of 55 sera from onchocerciasis patients (83%). Additional studies are in progress to develop and evaluate immunodiagnostic tests for onchocerciasis based on measurement of antibodies to these promising recombinant antigens.

Amino Acid Sequence↗