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Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.

BACKGROUND: In 1995, the World Bank launched an African Programme for Onchocerciasis Control to eliminate Onchocerca volvulus disease from 19 African countries by means of community-based ivermectin treatment (CBIT). Several cases of encephalopathy have been reported after ivermectin in people heavily infected with microfilariae of Loa loa (loiasis). We assessed the incidence of serious events in an area where onchocerciasis and loiasis are both endemic. METHODS: Ivermectin (at 150 micrograms/kg) was given to 17877 people living in the Lékié area of Cameroon. 50 microL samples of capillary blood were taken during the daytime before treatment from all adults (aged > or = 15 years), and the numbers of L loa and Mansonella perstans microfilariae in them were counted. Patients were monitored for 7 days after treatment. Adverse reactions were classified as mild, marked, or serious. Serious reactions were defined as those associated with a functional impairment that required at least a week of full-time assistance to undertake normal activities. We calculated the relative risk of developing marked or serious reactions for increasing L loa microfilarial loads. Risk factors for serious reactions were identified and assessed with a logistic regression model. FINDINGS: 20 patients (0-11%) developed serious reactions without neurological signs but associated with a functional impairment lasting more than a week. Two other patients were in coma for 2-3 days, associated with L loa microfilariae in cerebrospinal fluid. Occurrence of serious reactions was related to the intensity of pretreatment L loa microfilaraemia. The relative risk of developing marked or serious reactions was significantly higher when the L loa load exceeded 8000 microfilariae/mL; for serious reactions, the risk is very high (odds ratio > 1000) for loads above 50000 microfilariae/mL. INTERPRETATION: Epidemiological surveys aimed at assessing the intensity of infection with L loa microfilariae should be done before ivermectin is distributed for onchocerciasis control in areas where loiasis is endemic. In communities at risk, monitoring procedures should be established and adhered to during CBIT so that people developing serious reactions may receive appropriate treatment.

Adolescent↗

Specific serodiagnosis with adult Onchocerca volvulus antigen in an enzyme-linked immunosorbent assay.

The cross-reactivity of the blood from onchocerciasis, loiasis, and dipetalonemiasis was tested by a micro-ELISA technique, utilizing adult Onchocerca volvulus antigen and blood samples taken on filter paper. The average ELISA values (OD at 500 nm) were as follows: 0.58 in persons with O. volvulus microfilariae (n = 81), 0.49 in microfilariae-negatives from the same endemic area (n = 39), 0.15 in dipetalonemiasis (n = 27), and 0.25 in loiasis (n = 12), while those of 65 Dipetalonema perstans-negative people were markedly low (average 0.14) and that of 22 Loa loa-negatives, 0.22, respectively. This ELISA could successfully differentiate onchocerciasis from dipetalonemiasis and loiasis.

Adolescent↗

Longitudinal survey of Loa loa filariasis in southern Cameroon: long-term stability and factors influencing individual microfilarial status.

A longitudinal, one-year survey of Loa loa infection was carried out in an endemic area of southern Cameroon. Parasitologic samplings (calibrated thick blood smears) were performed every two months to study the evolution of loiasis infection at both the population and the individual level. The mean number of measurements by subject was 3.8 (range 1-6). At the population level, prevalence of infection and microfilarial load were found to be very stable over time. This observation is consistent with the existence of an important reserve of parasitic material available for vectors and the maintenance of high levels of transmission. At the individual level, both the microfilarial status (microfilaremic/nonmicrofilaremic) and the level of parasitemia showed a remarkable stability over time. Age was the relevant factor that influenced the individual microfilarial status in the whole population. When only microfilaremic individuals were taken into account, age did not influence the level of microfilaremia, suggesting that loiasis could be considered as a noncumulative disease. The stability of individual microfilarial status and the pattern of infection variations observed with age support the view that genetic factors might be involved in host defense mechanisms against loiasis infection.

Adolescent↗

Rapid assessment method for prevalence and intensity of Loa loa infection.

OBJECTIVE: To assess the validity of observations on eye worm and Calabar swellings for the rapid assessment of the prevalence and intensity of loiasis at the community level. METHOD: A total of 12895 individuals over the age of 15 years living in 102 communities in Cameroon and Nigeria took part in the study. A standardized questionnaire was administered to participants from whom finger-prick blood samples were collected and examined for Loa loa microfilariae. Rapid assessments of the prevalence and intensity of loiasis were made on the basis of a history of eye worm or Calabar swellings. FINDINGS: There was a strong correlation between the indices of the rapid assessment procedures and the parasitological indices of L. loa endemicity. The rapid assessment indices were effective in diagnosing high-risk communities (sensitivity 94-100%; specificity 66-92%). The highest sensitivity (100%) and specificity (92%) were obtained with a rapid assessment procedure based on a history of eye worm lasting 1-7 days together with confirmation by the guided recognition of a photograph of adult L. loa in the eye. CONCLUSION: Rapid assessment of the prevalence and intensity of loiasis at the community level can be achieved using a procedure based on the history of eye worm lasting 1-7 days together with confirmation by the guided recognition of a photograph of an adult L. loa in the eye.

Adolescent↗

Loa loa macrofilariasis in the eyelid: case report of the first periocular subcutaneous manifestation in Germany.

PURPOSE: We report a case of periocular subcutaneous macrofilariasis as an initial sign of a systemic Loa loa infection. METHODS: Thorough history, eye examination and surgical intervention. Parasitological and serological analysis. RESULTS: A periocular adult Loa loa worm was extracted from the left upper eyelid in an African student living in Germany after presenting to our department with intermittent attacks of painful lid swelling. Four weeks later he presented with Calabar swellings in his arms without serological evidence of microfilaria and was treated with diethylcarbamazine. CONCLUSION: Due to increasing migration of populations to Europe rare manifestations of ocular loiasis are becoming more common. Intermittent painful eyelid swelling in patients who visited or have lived in Africa should always raise the suspicion of systemic loiasis.

Adult↗

OvGalBP, a filarial antigen with homology to vertebrate galactoside-binding proteins.

The increased incidence of "allergic" symptomatology and clinical complications seen in non-endemic individuals with loiasis, as compared to natives of endemic areas, is thought to reflect a heightened immune response to filarial antigens. To identify antigens involved in this hyperresponsiveness, a cDNA library constructed from adult female RNA from the related filarial parasite, Onchocerca volvulus, was screened with serum from a North American who acquired loiasis in West Africa. Sequence analysis of one of the identified clones, OvGalBP, revealed significant homology to the vertebrate S-type lectins, a family of thiol-dependent, metal-independent galactoside binding lectins, which includes an IgE-binding protein thought to be involved in IgE regulation. The 1100-bp insert of OvGalBP contains the entire protein coding region and has a 3' poly(A) tail. The two amino acid consensus sequences (WGxExR and HFNPRF) found in all of the S-type lectins are present. Purified recombinant protein expressed as a fusion with glutathione-S-transferase (OvGalBP-GST) was recognized by sera from a majority of filaria-infected patients but not by putatively immune individuals from an endemic area or by unexposed endemic and non-endemic controls. Interestingly, OvGalBP-GST specifically bound IgE (and not IgG) in a lactose-inhibitable manner, suggesting a potential role for this protein in the pathophysiology of human filarial infection.

Amino Acid Sequence↗

First case of ivermectin-induced severe hepatitis.

Loiasis, caused by the filarial parasite Loa loa, is endemic in West and Central Africa. Ivermectin has been shown to be an effective treatment of loiasis. We report the case of a 20-year-old woman originally from Cameroon who was infected by the L. loa parasite and developed severe hepatitis, identified 1 month after a single dose of ivermectin. Liver biopsy showed intralobular inflammatory infiltrates, confluent necrosis and apoptosis, compatible with drug-induced liver disease. To our knowledge, this is the first case of ivermectin-induced severe liver disease published in the literature.

Adult↗

Reduced Loa loa microfilaria count ten to twelve months after a single dose of ivermectin.

The action of a single dose of ivermectin (200 micrograms/kg) on 71 Gabonese patients with Loa loa microfilariae in the peripheral blood, and living in areas highly endemic for loiasis, has been evaluated. Ten to 12 months after treatment, 43 patients (63%) had no circulating microfilaria and the geometric mean peripheral blood microfilaria count had decreased by 88.6% (P < 0.02). Thus, a single annual dose of ivermectin can markedly reduce loiasis transmission.

Adolescent↗

Structure of the microfilarial reservoir of Loa loa in the human host and its implications for monitoring the progr,ammes of Community-Directed Treatment with Ivermectin carried out in Africa.

This paper describes the structure of the microfilarial reservoir of Loa loa in an endemic population of central Cameroon. The possible effects of age and sex on the prevalence and intensity of microfilaraemia have been explored. Logistic analysis showed that the prevalence of microfilaraemia increased significantly with age, reaching 60 % in the oldest males. This result suggests that the figure commonly reported, according to which only one third of the infected individuals were microfilaraemic, should be reconsidered; in addition, as part of surveys of loiasis, crude microfilaraemia prevalence values should be replaced by adjusted ones. The intensity of infection did not show any age-specific change. As a result, even if the oldest members of the male population are clearly the most at risk of developing post-ivermectin serious adverse reactions, especially Loa-encephalopathy, the other members of the population are not risk-free. Therefore, in those areas where the African Programme for Onchocerciasis Control is undertaking regular mass distributions of ivermectin for onchocerciasis control, and where loiasis is co-endemic, no subpopulation should be excluded from surveillance and monitoring during community directed treatments with ivermectin.

Adolescent↗

Effect of diethylcarbamazine on adult Loa in monkeys.

The effect of diethylcarbamazine citrate (DEC) treatment (43-150 mg kg-1 daily for 12-21 days) on adult Loa worms in five drills (Mandrillus leucophaeus) is described. In individual monkeys, between one-third and all of the adult worms survived the treatment, and most of the surviving females were still producing live microfilariae. These experiments provide direct evidence which may explain the common clinical experience that single courses of DEC do not always succeed in eliminating the signs and symptoms of loiasis in humans. Further work on the chemotherapy of loiasis in monkeys, using DEC and other filaricides, might improve the treatment of this disease.

Animals↗

Loa loa infection as a cause of migratory angioedema: report of three cases from the Texas Medical Center.

Loa loa is a filarial parasite that is endemic in West and Central Africa. Expatriates infected with L. loa commonly develop characteristic migratory angioedema called Calabar swellings. We describe three patients who presented with classical Calabar swellings for whom the diagnosis of loiasis was delayed. Unusual features that were present included a leukocytoclastic vasculitis seen on skin biopsy (case 1), a relatively short exposure to an area of endemicity (cases 1 and 3), and a normal eosinophil count on initial evaluation (cases 2 and 3). We discuss the characteristic clinical manifestations of, pathological findings of, and therapy for loiasis. With the increased frequency of international travel, L. loa infection must be considered in the differential diagnosis for patients with migratory angioedema, urticarial vasculitis, or eosinophilia.

Adult↗

Loa loa infection in temporary residents of endemic regions: recognition of a hyperresponsive syndrome with characteristic clinical manifestations.

Loiasis in residents of endemic areas is generally manifested by microfilaremia, episodic angioedema, periocular migration of adult worms, modest eosinophilia, and variable antibody levels. In 20 temporary residents who acquired loiasis in West Africa, however, the clinical presentations were markedly different. Only three of the 20 had detectable microfilaremia. Furthermore, these patients often showed a state of marked immunological hyperresponsiveness manifested by very high titers of antibody to filariae, increased levels of serum IgE, and profound hypereosinophilia--to levels greater than 3,000/mm3 in 18 of the 20. These patients were also notable for the increased severity, frequency, and pruritic nature of their angioedema. Also, significant complications occurred in seven of the 20; one patient developed endomyocardial fibrosis and six, renal disease after treatment with diethylcarbamazine. Thirteen of the 20 developed subcutaneous nodules; adult parasites were recovered from three of five of these patients who underwent biopsy. All of the patients responded to therapy with diminution of their clinical symptoms and decreases in levels of eosinophils, IgE, and antibody to filariae.

Adult↗

[Cutaneous filariasis Loa Loa: 26 moroccan cases of importation].

INTRODUCTION: Loa Loa filariasis or loiasis is a subcutaneous and bloody vectorial parasitosis. It is endemic in forest and swamp areas of west and central Africa. PATIENTS AND METHODS: We reviewed 26 moroccan cases of importation. All patients had visited Equatorial Guinea. Transient and migratory edema with pruritus were described in all cases and seen in 5 cases. A history of eyeworm was reported in 13 patients and subcutaneous migration of adult Loa Loa in 19 patients. Other features including fever and asthenia were reported in 11 patients. Microfilaremia was positive in 8 patients and eosinophilia was present in 22 patients. Fifteen patients were treated with diethylcarbamazine alone and 9 patients with ivermectin and diethylcarbamazine. Two patients were treated with ivermectin alone. Relapses were noted in 8 cases. No visceral complications were noted excepting one case of terminal hematury. DISCUSSION: Loiasis is a filarial infection of man that occurs exclusively in central and West Africa. The most common symptoms being pruritus with temporary, localised edema, subcutaneous and subconjonctival eye passage of the adult worm, fever and fatigue. The biologic diagnosis of loaisis is made on peripheral microfilariae, filarial serology and eosinophil count. Travel and visits endemic areas were at the origin of the emergence of this pathology in Morocco. Filarial Loa Loa infection should be treated with diethylcarbamazine and/or ivermectin.

Adult↗

[Hyperendemic loaiasis in the Tikar plain, shrub savanna region of Cameroon].

A survey on filariasis was conducted in the south-western part of the Adamaoua Province (Cameroon). In the Bankim district, located in the Tikar plain, the 10 surveyed villages were all hyperendemic for loiasis. The prevalence of microfilaraemia in adults exceeded 50% in four communities, and 5.4% of the adults had microfilarial loads above 30,000 microfilariae per ml blood. In the Banyo district, which is contiguous but located on the Adamaoua Plateau, five of the six villages examined were hypoendemic for loiasis. The considerable levels of endemicity recorded in the Tikar Plain, a region of pre-forest shrub savanna, are probably due to the presence of forest-galleries, favourable to the biology of Chrysops. Regarding onchocerciasis, the most affected villages were located south of the Tikar Plain, near the Mbam River. The low prevalence of hydroceles suggests that lymphatic filariasis is not endemic in this study area.

Adolescent↗

[Filarial meningoencephalitis: discussion of a case].

Loiasis treatment by diethylcarbamazine (DEC) may be complicated by a meningoencephalitis that is often fatal. Following one case, four others have been reviewed in the literature and the therapeutic approach in resuscitation departments discussed. Until the discovery of other less-dangerous microfilaricidal or macrofilaricidal drugs, we raise the question of the opportunity to treat loiasis by DEC, while many authors consider it as a simple nuisance.

Adult↗

Identification of a surface antigen on Loa loa microfilariae the recognition of which correlates with the amicrofilaremic state in man.

Filarial infections induce a spectrum of disease in their natural hosts, and by correlating immunity found in individuals with their disease pattern, one may delineate non-pathogenic, protective mechanisms. Loa loa is causal of mild to moderate pathology, and it is unique among the human filaria in that adult worms are occasionally visible during subconjunctival migration. To study immune mechanisms controlling microfilaremia, sera from 15 subjects with amicrofilaremic occult loiasis (OL) were compared with sera from 10 subjects with microfilaremic loiasis (ML) microfilaremia, (greater than 4000/ml) for their reactions with living microfilariae (mf). An IFA was first used to detect antibodies able to bind to the surface of living L. loa mf. ML subjects either did not react (7/10) or reacted only very weakly (3/10). Highly reactive sera were found only in OL subjects; 7/15 gave very bright fluorescence, 5/15 gave moderate reactions, and 3/15 were negative. Most of these antibodies were of the IgG class. Sera from all subjects were also reacted with living mf in an antibody-dependent cellular adherence test using normal leukocytes. Sera that were strongly positive in IFA showed strong adherence and IFA-negative sera were non-reactive. To identify the Ag involved, mf were surface iodinated, detergent-extracted Ag were immunoprecipitated, and Mr was determined on SDS-PAGE. Several OL sera, all highly reactive in the above tests, precipitated a 23-kDa molecule with which all ML sea failed to react. Sera from a mandrill experimentally infected with L. loa also precipitated the 23-kDa Ag when taken post-patency. In conclusion, it appears that certain people who control L. loa microfilaremia have high levels of IgG antibodies that bind to a surface Ag of 23 kDa and are able to mediate cellular adherence.

Adhesiveness↗

[Hypotheses on the dynamic ecology of Loa infections].

In the light of the known data about epidemiological cycles of human and simian loiasis in Africa, and the eventual relationships between these infections, a hypothetical schema is presented, giving a whole view of the dynamic ecology of the Loa systems. This schema involves a primitive simian savannah cycle, from which, the filaria passing from monkey to man, a human savannah cycle, and then the classical human forest cycle are developed. The primitive savannah cycle could also be at the origin of simian forest cycles, but the exchanges between monkeys and man seem very unlikely inside the forest. Between the factors favouring the passage from one cycle to another,. the bush fires could have played are important role. Finally, the main factors of the geographical distribution of human loiasis are discussed.

Africa, Central↗

High levels of parasite-specific IgG4 in the absence of microfilaremia in Loa loa infection.

The specificity of IgG4 as marker of infection has been investigated. The study was based on two well defined clinical groups: amicrofilaremic individuals with verified ocular passage of adult worms of Loa loa, and microfilaremic patients. Both groups were compared to Africans not exposed to loiasis infection and to Europeans. The study revealed that there is no significant difference in the level of parasite-specific IgG4 between individuals with occult infection (i.e. amicrofilaraemic, but infected) and microfilaremic individuals, but there is a significant difference between L. loa infected individuals and Mansonella perstans exposed people. IgG4 of individuals exposed to L. loa infection recognised specific antigens in the molecular weight range 12-30 kDa. We conclude that the elevated level of filarial-specific IgG4 is therefore not dependent upon the presence of circulating microfilariae and that serology using homologous L. loa low molecular weight antigens, can facilitate specific diagnosis of occult loiasis in an endemic area with mixed filarial infections.

Animals↗