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Onchocerciasis in West Africa after 2002: a challenge to take up.

Initially planned for a 20 year life time, the Onchocerciasis Control Programme in West Africa (OCP) will have finally continued its activities for nearly three decades (vector control alone from 1975 to 1989, then vector control and/or therapeutic treatment until 2002). Although onchocerciasis is no longer a problem of public health importance nor an obstacle to socio-economic development in the OCP area, the control of this filariasis is not over because OCP never aimed at eradication, neither of the parasite (Onchocerca volvulus), nor of its vector (Simulium damnosum s.l.). In 2003, the eleven Participating countries of OCP will take over the responsibility of carrying out the residual activities of monitoring and the control of this disease. This mission is of great importance because any recrudescence of the transmission could lead in the long run to the reappearance of the clinical signs of onchocerciasis, if not its most serious manifestations. For epidemiological and operational reasons, and given the disparity in national health policies and infrastructures, the capacities of the countries to take over the residual activities of monitoring and control of onchocerciasis are very unequal. Indeed, the interventions to be carried out are very different from one country to another and the process of integrating the residual activities into the national health systems is not taking place at the same pace. This inequality among the countries vis-a-vis the challenges to be met does not, however, prejudge the epidemiological situation after 2002 whose evolution will also depend on the effectiveness of the provisions made before that date by OCP, then after 2002, by the Regional Office for Africa of the World Health Organization which is currently setting up a sub-regional multidisease surveillance centre.

Africa, Western↗

The distribution of the Simulium damnosum complex in Sierra Leone and its relation to onchocerciasis.

Because of the paucity of literature concerning onchocerciasis and its vectors in Sierra Leone, new information of the geographical distribution of the Simulium damnosum complex is presented in the context of a comprehensive review of what is known generally about S. damnosum s.l. in Sierra Leone, and how the data relate to the transmission of onchocerciasis. Neither biting adults nor breeding sites have been found on the coastal plain and Freetown peninsula, and these area seem to be free from infestation. Throughout the rest of the country S. damnosum s.l. breeds extensively in all the major river systems. The close proximity of the major rivers to one another facilitates inter-river migration, and ensures that most villages are well within the fly's dispersal range. In accordance with this, onchocerciasis is widespread throughout Sierra Leone and vector biting has been recorded away from riverine breeding sites. Seven cytospecies have been recorded in Sierra Leone but of these S. sirbanum and S. damnosum s.str. are rare outside the far north, in the narrow savanna belt. Simulium squamosum and S. yahense are widely distributed, although S. squamosum is somewhat less common than S. yahense which unexpectedly occurs in large rivers of the forest and savanna as well as small forest streams. Simulium sanctipauli has been found in the south-east of the country, where the forest is most dense, whereas S. soubrense occurs farther north. A new species referred to as S. soubrense 'B' is restricted to the south and west of the country. Over most of Sierra Leone onchocerciasis shows a 'forest' epidemiology and is transmitted by 'forest' vector cytospecies. However, data from the narrow savanna belt in the extreme north are sparse.

Animals↗

A rapid mapping technique for the prevalence and distribution of onchocerciasis: a Cameroon case study.

A rapid and cheap method for mapping the endemicity levels of onchocerciasis in both forest and savanna areas, where the vectors are members of the Simulium damnosum complex, is described. The selection of the study communities is based on a general understanding of the vectors' ecology and biassed towards those at highest risk of onchocerciasis, although there must be adequate geographical coverage. In a case study in Cameroon, prevalences were determined, using the non-invasive nodule palpation technique, in samples, each of 30-50 adult males, from 49 villages in six study areas in Cameroon. The method proved effective in the rapid mapping of onchocerciasis distribution in all areas studied, in which the distribution patterns varied from the classical linear to diffuse, and in one area with an anomalous distribution. The method should prove of value in the design of national onchocerciasis control programmes.

Adult↗

Drastic reduction of populations of Simulium sirbanum (Diptera: Simuliidae) in central Sierra Leone after 5 years of larviciding operations by the Onchocerciasis Control Programme.

The major vectors of the blinding form of human onchocerciasis in West Africa are two blackfly species, Simulium sirbanum and Simulium damnosum s.s. (Diptera: Simuliidae), identified at the adult stage as the 'savanna group' of the Simulium damnosum complex. In 1988, in the central part of Sierra Leone, the average daily biting rate (females/man/day) by savanna blackflies (mostly S. sirbanum) during the peak of the dry season (April-May) was 59.9, making up 69.1% of total captures on average. There was evidence of a strong long-range immigration of adult females of S. sirbanum through eastern Guinea in the dry season, with a reverse movement towards Guinea in the rainy season. Therefore, in 1989, the World Health Organization's Onchocerciasis Control Programme (OCP) extended its vector control operations from central West Africa to rivers of central and northern Sierra Leone, and to rivers of eastern Guinea. Four years of efficient larviciding drastically reduced adult populations of S. sirbanum in Sierra Leone. In the peak of the dry seasons of 1993 and 1994, the average biting rate by savanna blackflies in central Sierra Leone had dropped to 1.0, making up only 4.3% of total captures on average. Yearly biting rates by S. sirbanum in central Sierra Leone were therefore reduced to 2% of their pre-intervention levels. Based on larval samples, the S. sirbanum has been replaced by two forest species, S. leonense in the south and S. squamosum in the north. Since 1992, it has been possible to calculate accurate transmission rates for blinding onchocerciasis, based on DNA-probe identifications. From 1993, the risk of transmission has not only been reduced by vector control but also by mass distribution of ivermectin to rural communities. In terms of control strategy, the authors conclude that larviciding operations could be alleviated in central Sierra Leone without increasing the risk of blinding onchocerciasis transmission, as long as the migration of S. sirbanum through eastern Guinea and northern Sierra Leone is prevented.

Animals↗

A rapid-format antibody card test for diagnosis of onchocerciasis.

Improved methods are needed for field diagnosis of onchocerciasis, to support efforts aimed at elimination of the disease. A rapid-format card test was evaluated that detects IgG4 antibodies to recombinant Onchocerca volvulus antigen Ov16 with serum samples from patients with onchocerciasis and with various types of control serum samples. The sensitivity of the test with serum samples from 106 microfilariae-positive subjects was 90.6%. The test was equally sensitive with serum samples obtained from patients in Africa and Latin America. Specificity was excellent; positive tests were observed for 2 of 38 serum samples from patients with other filarial infections and for 1 of 23 serum samples from patients with nonfilarial helminth infections. The 3 "false-positive" serum samples were from West Africans who could have been coinfected with onchocerciasis. No positive tests were observed with nonendemic serum samples from normal adults, patients with autoimmune disorders, or patients with the hyper-IgE syndrome. This new test holds great promise as a simple tool for diagnosis of onchocerciasis.

Adult↗

Dermatological survey of onchocerciasis in Guatemala.

A comprehensive survey of onchocerciasis was performed on 1259 inhabitants in San Vicente Pacaya and the surrounding area. The total number of inhabitants examined was 1259, 763 males and 496 females. An examination of microfilarial density was carried out by the skin snip method. There were 610 microfilarial positives (50.4%) out of 1211 persons, 448 males (60.9%), and 162 females (34.1%). Nodules were examined by palpation, and there were 404 (32.8%) positives for nodule out of 1232 persons, 299 males (40.3%), and 105 females (21.4%). Eczematous dermatitis was seen in 149 persons, the generalized type in 13, and other types in 136. Depigmentation on the lower extremities was seen in 290 persons, the severity was graded from 0 to 4, and grade 1 depigmentation was seen in 91; grade 2, in 143; grade 3, in 52 and grade 4 in 4 persons out of 1159 individuals examined. The positives for lymphadenopathy (above grade 2) were 464 (41.2%) out of 1127 individuals. Itching was seen in 129 (18.3%) of 705 individuals examined by the inquiry card method. The correlation between skin changes and onchocerciasis was also analyzed. Those individuals who were microfilarial positive in the skin snip and eyes, and who had palpable nodules were defined as being onchocerciasis patients. There was a high frequency of eczematous dermatitis, depigmentation on the lower extremities and lymphadenopathy in the onchocerciasis infected group, compared with the non-infected group, but there was no difference in the rate of itching between them. Hanging groin, elephantiasis and "erisipela de la costa" were not seen in this endemic area, and the degree of skin changes was slight, compared with that reported in Africa thus far.

Adolescent↗

Associations between clinical disease, circulating antibodies and C1q-binding immune complexes in human onchocerciasis.

Onchocerciasis is a disease where often there are high levels of serum antibodies and high parasitic loads. The role of immune complexes in the development of the disease is investigated here by studying non-specific and Onchocerca volvulus specific immune complex levels, as well as the antibody concentrations, in the sera of 372 people living in either Southern (199) or Northern (173) Sudan; sera from Sudanese individuals (31) and Caucasians (21) living outside the onchocerciasis endemic area were also tested. The levels of non-specific immune complexes (NS-IC) in these sera were measured by a solid phase radio-immunoassay and those of O. volvulus-specific immune complexes (OV-IC) by an assay measuring antibody-excess complexes using C1q-coated plates. The concentrations of O. volvulus IgG antibodies were measured by ELISA. Immune complex and antibody levels of the serum donors were compared with regard to their clinical status due to onchocerciasis. These clinical changes were classified according to onchocercal lesions related to either the active destruction of microfilariae (acute changes), or the long term tissue alterations (chronic changes). Data was analysed using the Odds Ratio method. A negative association between microfilarial load and immune complex level was found, with the higher levels of OV-IC present in patients with the lower levels of dermal microfilariae (i.e., less than 10 mf/mg). Significant associations between immune complex levels and the severity of onchocercal disease were also found. Levels of OV-IC specific immune complexes were higher in infected individuals carrying dermal onchocercal lesions than in those without such clinical changes; there was no apparent relationship between these levels and the presence of ocular lesions. OV-IC levels varied considerably within each age group and from age to age. A weak positive association was detected between microfilarial load and parasite-specific IgG antibody concentration in the sera. On average younger individuals (less than 25 years) had the higher antibody levels with a gradual reduction in mean concentrations with age. The significance of these serological findings in terms of the pathogenesis of onchocerciasis is discussed.

Age Factors↗

Farm land size and onchocerciasis status of peasant farmers in south-western Nigeria.

Concern is being raised about the economic impact of the non-blinding strain of onchocerciasis, since half of those affected with onchocerciasis in Africa live in the forest zones where the non-blinding form is prevalent. WHO's TDR programme has embarked on multi-country studies on the social and economic effects of onchocercal skin disease (OSD). Baseline data from one site, the Ibarapa Local Government Area of Oyo State, Nigeria, is presented here. Farmers were screened for signs and symptoms of onchocerciasis including palpable nodules, reactive skin lesions and self-reported severe itching. Those having two or more of these conditions were classified as having severe OSD. A matching group of farmers without any of the signs or symptoms formed a control group. Women in the area either did not farm or held only one small plot. Land size comparisons were undertaken with 51 pairs of male farmers matched for age and location within 23 small hamlets bordering the Ogun River. Farmers with OSD had significantly less farmland under cultivation (9117 m2) than those with no OSD (13850 m2). The farmers with OSD did not appear to have alternative income strategies to compensate and, consequently, they had a lower value of personal wealth indicators (e.g. iron sheet roofing, motorcycle) than those without OSD. One can conclude that although the effect of forest strain onchocerciasis is less dramatic than of the blinding from, the disease poses an important economic threat in the region.

Adolescent↗

Canine ocular onchocerciasis in the United States: two new cases and a review of the literature.

Since 1991, 53 cases of canine ocular onchocerciasis have been reported in the literature worldwide, 43 of these were from Greece, five from Hungary, and five from the western United States. Information on the histopathologic features of canine ocular onchocerciasis is limited. We describe the histopathologic features of canine ocular onchocerciasis in two dogs from California that presented clinically with firm episcleral nodules and uveitis unilaterally. Pertinent literature and pathogenesis are reviewed; recognizable clinical features and treatment are discussed. The cases presented were diagnosed via histopathology of the enucleated globes and episcleral granulomas at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). Positive identification of adult Onchocerca within episcleral granulomas was made based on light-microscopy features. Histopathologic examination of both globes revealed episcleral parasites surrounded by granulomas containing few to moderate numbers of eosinophils. Other sequelae, in both cases, included lymphoplasmacytic uveitis, preiridal fibrovascular membranes, peripheral anterior synechiae, retinal degeneration, and optic nerve head cupping. Both male and female worms were present, as were in utero microfilariae in both cases. Worms in both cases were tentatively identified as Onchocerca lienalis. Ocular onchocerciasis should be a differential consideration in cases of canine conjunctival nodules or periorbital swelling, particularly in dogs from the western United States.

Animals↗

Impact of mass treatment of onchocerciasis with ivermectin on the transmission of infection.

Onchocerciasis is a major blinding disease that, until recently, has been essentially untreatable. Ivermectin is a safe and effective drug for the mass treatment of onchocerciasis and when used on an individual basis, it reduces the ability of the treated person to transmit Onchocerca volvulus infection. In the present study, the effect of community-based ivermectin treatment on the degree of transmission within the community was assessed by determining the incidence of new infection in children. Ivermectin was distributed annually on three occasions to the eligible members of a population of approximately 14,000 people living on a rubber plantation in a forest area endemic for onchocerciasis. After 2 years, the prevalence of infection in 5-year-old children decreased by 21%. The annual incidence in an uninfected cohort of children decreased by 35% and, after age-specific adjustment, the reduction in incidence in 7- to 12-year-old children was 45%. Thus, community-based distribution of ivermectin led to a significant reduction in incidence of new infection. These findings suggest that ivermectin can be important in reducing the transmission of onchocerciasis.

Child↗

Visual field defects in onchocerciasis.

Lesions in the posterior segment of the eye in onchocerciasis may give visual field defects, but so far no detailed investigation has been done to determine the functional visual loss. Examination of the visual fields in 18 selected cases of onchocerciasis by means of a tangent screen test revealed important visual field defects associated with lesions in the posterior segment of the eye. Involvement of the optic nerve seemed to be important, giving rise to severely constricted visual fields. Cases of postneuritic optic atrophy showed a very uniform pattern of almost completely constricted visual fields, with only 5 to 10 degree central rest spared. Papillitis gave a similar severe constriction of the visual fields. The pattern of visual fields associated with optic neuropathy in onchocerciasis indicates that a progressive lesion of the optic nerve from the periphery may be responsible for the loss of vision. The visual field defects in onchocerciasis constitute a serious handicap, which must be taken into consideration when estimating the socioeconomic importance of the disease.

Adolescent↗

Ocular manifestations of onchocerciasis in a rain forest area of west Africa.

The epidemiology and natural history of onchocerciasis and its ocular complications in rain forest areas are poorly understood. The present study was conducted on a rubber plantation in a hyperendemic area in the rain forest of Liberia, West Africa, where 800 persons were examined. The prevalence of infection was 84% overall 29% had intraocular microfilariae, and 2.4% were blind in one or both eyes. Onchocerciasis was the cause of all binocular blindness and one-third of all visual impairment. Over half of the visual impairment caused by onchocerciasis was due to posterior segment diseases. Chorioretinal changes were present in 75% of people, and included intraretinal pigment clumping in 52% and retinal pigment epithelium atrophy in 32%. Atrophy of the retinal pigment epithelium was associated with increasing age and severity of infection. Intraretinal pigment was strongly associated with anterior uveitis. There was a strong correlation between uveitis and the inflammatory chorioretinal sequelae: retinitis, intraretinal pigment, subretinal fibrosis, and optic neuropathy. These findings indicate that considerable visual impairment associated with rain forest onchocerciasis is common and is due largely to chorioretinal disease.

Adolescent↗

Onchocerciasis in Ecuador: ocular findings in Onchocerca volvulus infected individuals.

Little is known of the epidemiology and clinical picture of ocular onchocerciasis in South America. A survey of onchocercal eye disease was performed in the hyperendemic area of a rain forest focus of onchocerciasis in Esmeraldas Province in Ecuador. A total of 785 skin snip positive individuals from black and Chachi Amerindian communities were examined. The blindness rate attributable to onchocerciasis was 0.4%, and 8.2% were visually impaired. Onchocercal ocular lesions were seen in a high proportion of the study group: 33.6% had punctate keratitis, microfilariae in the anterior chamber and cornea were seen in 28.9% and 33.5% respectively, iridocyclitis was seen in 1.5%, optic atrophy in 5.1%, and chorioretinopathy in 28.0%. Sclerosing keratitis was not seen. The prevalence of all ocular lesions increased with age. Punctate keratitis was strongly associated with microfilarial counts in the cornea and chorioretinopathy was correlated with infection intensities in the cornea and anterior chamber. Chachi Amerindians had higher anterior chamber microfilarial counts and a greater prevalence of punctate keratitis than blacks though blacks had a greater prevalence of iridocyclitis and optic nerve disease. The pattern of ocular disease resembled rain forest onchocerciasis in west Africa with few severe ocular lesions in the anterior segment and all blinding lesions attributable to posterior segment disease.

Adolescent↗

Review of epidemiological studies searching for a relationship between onchocerciasis and epilepsy.

A review and a meta-analysis of the available epidemiological literature for evidence of an association between onchocerciasis infection and epilepsy were carried out. We used EMBASE (1974-2002), MEDLINE (1966-2002), and PASCAL (1987-2002) databases and relevant journals and bibliographies. We limited our analysis to the epidemiological studies, where the status regarding onchocerciasis infection and epilepsy was available for each subject. Nine African studies were included. The common relative risk estimated by the random-effects model was 1.21 (95% CI 0.99-1.47; p = 0.06). The meta-analysis did not show any difference according to the onchocerciasis endemicity level and the African areas. Our results do not allow to conclude for an association between Onchocerca volvulus infection and epilepsy. However, the results are nearly significant. Further research is needed in this neglected subject, in particular for the better understanding of the neurological pathogenicity in onchocerciasis.

Brain Diseases↗

The achievements and challenges of the African Programme for Onchocerciasis Control (APOC).

The main strategy of APOC, of community-directed treatment with ivermectin (CDTI), has enabled the programme to reach, empower and bring relief to remote and under-served, onchocerciasis-endemic communities. With CDTI, geographical and therapeutic coverages have increased substantially, in most areas, to the levels required to eliminate onchocerciasis as a public-health problem. Over 20 million people received treatment in 2000. APOC has also made effective use of the combination of the rapid epidemiological mapping of onchocerciasis (REMO) and geographical information systems (GIS), to provide information on the geographical distribution and prevalence of the disease. This has led to improvements in the identification of CDTI-priority areas, and in the estimates of the numbers of people to be treated. A unique public-private-sector partnership has been at the heart of APOC's relative success. Through efficient capacity-building, the programme's operations have positively influenced and strengthened the health services of participating countries. These laudable achievements notwithstanding, APOC faces many challenges during the second phase of its operations, when the full impact of the programme is expected to be felt. Notable among these challenges are the sustainability of CDTI, the strategy's effective integration into the healthcare system, and the full exploitation of its potential as an entry point for other health programmes. The channels created for CDTI, could, for example, help efforts to eliminate lymphatic filariasis (which will feature on the agenda of many participating countries during APOC's Phase 2). However, these other programmes need to be executed without compromising the onchocerciasis-control programme itself. Success in meeting these challenges will depend on the continued, wholehearted commitment of all the partners involved, particularly that of the governments of the participating countries.

Africa↗

Onchocerciasis: the clinical and epidemiological burden of skin disease in Africa.

An attempt was made to assess the true public-health importance of onchocercal skin disease throughout the African region and hence provide an objective basis for the rational planning of onchocerciasis control in the area. The seven collaborative centres that participated in the study (three in Nigeria and one each in Ghana, Cameroon, Tanzania and Uganda) were all in areas of rainforest or savannah-forest mosaic where onchocercal blindness is not common. A cross-sectional dermatological survey was undertaken at each site following a standard protocol. At each site, the aim was to examine at least 750 individuals aged 5 years and living in highly endemic communities and 220-250 individuals aged 5 years and living in a hypo-endemic (control) community. Overall, there were 5459 and 1451 subjects from hyper-and hypo-endemic communities, respectively. In the highly endemic communities, the prevalence of itching increased with age until 20 years and then plateaued, affecting 42% of the population aged 20 years. There was a strong correlation between the prevalence of itching and the level of endemicity (as measured by the prevalence of nodules; r=0.75; P<0.001). The results of a multivariate logistic regression analysis showed that, at the individual level, the presence of onchocercal reactive skin lesions (acute papular onchodermatitis, chronic papular onchodermatitis and/or lichenified onchodermatitis) was the most important risk factor for pruritus, with an odds ratio (OR) of 18.3 and 95% confidence interval (CI) of 15.19-22.04, followed by the presence of palpable onchocercal nodules (OR=4.63; CI=4.05-5.29). In contrast, non-onchocercal skin disease contributed very little to pruritus in the study communities (OR=1.29; CI=1.1-1.51). Onchocercal skin lesions affected 28% of the population in the endemic villages. The commonest type was chronic papular onchodermatitis (13%), followed by depigmentation (10%) and acute papular onchodermatitis (7%). The highest correlation with endemicity was seen for the prevalence of any onchocercal skin lesion and/or pruritus combined (r=0.8; P<0.001). Cutaneous onchocerciasis was found to be a common problem in many endemic areas in Africa which do not have high levels of onchocercal blindness. These findings, together with recent observations that onchocercal skin disease can have major, adverse, psycho-social and socio-economic effects, justify the inclusion of regions with onchocercal skin disease in control programmes based on ivermectin distribution. On the basis of these findings, the World Health Organization launched a control programme for onchocerciasis, the African Programme for Onchocerciasis Control (APOC), that covers 17 endemic countries in Africa.

Adolescent↗

Mass treatment of onchocerciasis with ivermectin: should people with epilepsy and/or growth-retardation syndromes be excluded?

In many areas of Africa where human onchocerciasis is endemic there are now programmes for mass treatment with ivermectin (Mectizan), to eliminate the disease as a public-health problem. To determine whether those with epilepsy and/or growth-retardation syndromes (GRS) should be excluded from such mass drug administrations, literature searches of the standard biomedical databases were performed for all relevant articles published in English or French before January 2003. Cross-referencing and the retrieving of articles recommended by experts completed the search. The literature review revealed that there is insufficient evidence for an association between onchocerciasis and epilepsy or GRS. Since ivermectin does not normally cross the blood-brain barrier, the drug is unlikely to have direct pro- or anti-convulsive activity. Furthermore, an estimated 1-2 million epileptics in Africa have been treated with ivermectin, in onchocerciasis-control programmes, without any reports of serious adverse events (SAE) to the passive surveillance system for such events. As there are few data on the prevalence of GRS in Africa, it is difficult to estimate the number of GRS cases who have been treated with ivermectin or the incidence of ivermectin-related SAE among such cases. Epileptics should not be excluded from mass treatments with ivermectin unless they are actively seizing or postictal. Although those with GRS associated with chronic wasting, with or without epilepsy, should be excluded, they should be eligible for clinic-based treatment if the diagnosis of onchocerciasis is confirmed and the benefits of treatment are deemed to outweigh any potential risks.

Africa↗

Analysis of aqueous humour in ocular onchocerciasis.

The development of an onchocercal chorioretinopathy from the first detectable signs to a full blown oncho fundus is not fully understood. We investigated the intraocular humoral immune response against Onchocerca volvulus, human S-antigen, IRBP and crude retinal extract (using an ELISA) by examining paired aqueous humour and serum samples obtained from onchocerciasis patients (without [n = 10] and with ocular symptoms [n = 8]) and endemic controls [n = 14] from Sierra Leone (West Africa). A local intraocular anti-retinal IgG antibody production could not be demonstrated in onchocerciasis patients, whether they had ocular symptoms or not. A significantly higher level of O. volvulus antibodies and IgG was measured in the aqueous of onchocerciasis patients with ocular involvement, as compared to patients without ocular symptoms (Mann-Whitney ranksum test; p less than 0.001 and p less than 0.02 respectively). Since interleukin-6 (IL-6) plays an essential role in the differentiation of B cells into immunoglobulin producing plasma cells, we therefore measured this cytokine in paired aqueous and serum samples. Elevated IL-6 levels were found in the aqueous of two out of eight onchocerciasis patients tested. In view of these findings it seems improbable that retinal autoimmunity is a major factor in the pathogenesis of onchocercal chorioretinopathy. The high intraocular levels of antibodies against the parasite suggest a direct involvement of the parasite in the pathogenesis of onchocercal chorioretinopathy.

Adult↗