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[Study of the distribution of human filariasis in West Province of Cameroon].

A clinical and parasitological survey of onchocerciasis and loiasis has been carried out in 38 communities in the West Province of Cameroon prior to the implementation of a mass ivermectin treatment. The highest endemicity levels of onchocerciasis were recorded in the villages located at an altitude below 1400 m, and whose inhabitants go down to the valleys for agricultural activities. Conversely, low endemicity levels were recorded in the most populated part of the study area, which is located at an altitude above 1400 m; in the latter communities, the residents cultivate the high ground not far from their houses and are thus less exposed to transmission of onchocerciasis. Despite relatively low microfilarial loads, the prevalences of nodules were fairly high; this demonstrates that in some epidemiological situations the latter indicator gives an erroneous indication of the intensity of infection in the population. The prevalence of loiasis is very low in most of the villages of the study area.

Agriculture↗

The Mectizan Donation Program - highlights from 2005.

Through the Mectizan Donation Program, Merck & Co., Inc. has donated Mectizan (ivermectin, MSD) for the treatment of onchocerciasis worldwide since 1987. Mectizan has also been donated for the elimination of lymphatic filariasis (LF) since 1998 in African countries and in Yemen where onchocerciasis and LF are co-endemic; for LF elimination programs, Mectizan is co-administered with albendazole, which is donated by GlaxoSmithKline. The Mectizan Donation Program works in collaboration with the Mectizan Expert Committee/Albendazole Coordination, its scientific advisory committee. In 2005, a total of 62,201,310 treatments of Mectizan for onchocerciasis were approved for delivery via mass treatment programs in Africa, Latin America, and Yemen. Seventy-seven percent and 20% of these treatments for onchocerciasis were for countries included in the African Programme for Onchocerciasis Control (APOC) and the former-Onchocerciasis Control Programme in West Africa (OCP), respectively. The remaining 3% of treatments approved were for the six onchocerciasis endemic countries in Latin America, where mass treatment is carried out twice-yearly with the goal of completely eliminating morbidity and eventually transmission of infection, and for Yemen. All 33 onchocerciasis endemic countries where mass treatment with Mectizan is indicated have ongoing mass treatment programs. In 2005, 42,052,583 treatments of co-administered albendazole and Mectizan were approved for national Programs to Eliminate LF (PELFs) in Africa and Yemen. There are ongoing PELFs using albendazole and Mectizan in nine African countries and Yemen; these represent 35% of the total number of countries expected to require the co-administration of these two chemotherapeutic agents for LF elimination. In Africa, the expansion of existing PELFs and the initiation of new ones have been hampered by lack of resources, technical difficulties with the mapping of LF endemicity, and the co-endemicity of LF and loiasis. Included in this review are recommendations recently put forward for the co-administration of albendazole and Mectizan in areas endemic for LF, loiasis, and onchocerciasis.

Journal Article↗

A possible case of spontaneous Loa loa encephalopathy associated with a glomerulopathy.

It is well known that renal and neurological complications may occur after antifilarial treatment of patients infected with Loa loa. Conversely, spontaneous cases of visceral complications of loiasis have been rarely reported. A 31-year-old Congolese male patient who had not received any antifilarial drug developed oedema of the lower limbs, and then transient swellings of upper limbs. Two months after, he developed troubles of consciousness within several hours. At hospital, the patient was comatose with mild signs of localization. Laboratory tests and an abdominal echography revealed a chronic renal failure due to a glomerulopathy. Three weeks after admission, Loa microfilariae were found in the cerebrospinal fluid, and a calibrated blood smear revealed a Loa microfilaraemia of 74,200 microfilariae per ml. The level of consciousness of the patient improved spontaneously, without any specific treatment, but several days after becoming completely lucid, the patient died suddenly, from an undetermined cause. Unfortunately, no biopsy or autopsy could be performed. The role of Loa loa in the development of the renal and neurological troubles of this patient is questionable. But the fact that such troubles, which are known complications of Loa infection, were found concomitantly in a person harbouring a very high microfilarial load suggests that they might have been caused by the filarial parasite. In areas endemic for loiasis, examinations for a Loa infection should be systematically performed in patients presenting an encephalopathy or a glomerulopathy.

Journal Article↗

Frequency analysis of IgE-secreting B lymphocytes in persons with normal or elevated serum IgE levels.

The immunoregulatory mechanisms that determine the high serum IgE antibody levels in disorders such as helminth parasite infections and the hyper-IgE recurrent infection syndrome (HIE) remain poorly understood. To assess whether elevated serum IgE levels result from an increased number of B lymphocytes committed to IgE production, the proportion of IgE-producing B lymphocytes was determined by a filter immunoplaque assay using PBMC from persons with a broad range of serum IgE levels that included normal persons (n = 9) and patients with loiasis (n = 12), tropical pulmonary eosinophilia (TPE) (n = 6), lymphatic filariasis (n = 28), and HIE (n = 8). PBMC from these persons were assessed for production of in vitro IgE. The geometric mean number of IgE-secreting cells in 10(5) B lymphocytes in PBMC was 0.42 (range 0-2.2) in normal persons, 5.6 (range 0.1-35.5) among patients with loiasis, 9.4 (range 0-53.2) among patients with lymphatic filariasis, 52 (range 31.5-115) among patients with TPE, and 218 (range 56-1404) among patients with HIE. When all study subjects were grouped, there were significant correlations with serum IgE levels (r2 = 0.78; p less than 0.0001) and net spontaneous in vitro IgE production (r2 = 0.8; p less than 0.0001). Estimates of the amount of IgE production per B lymphocyte were similar among normal persons, patients with filarial infections, and patients with TPE (geometric means of 134, 96, and 141 pg/ml/cell, respectively); in contrast, for HIE patients, IgE production by individual B cells was significantly lower (geometric mean 28 pg/ml/cell; p less than 0.001). These observations demonstrate that clonal expansion of IgE-producing B lymphocytes is a major mechanism underlying the elevated serum IgE levels seen in persons with hyper-IgE states.

Adolescent↗

Epidemiology of concomitant infections due to Loa loa, Mansonella perstans, and Onchocerca volvulus in rain forest villages of Cameroon.

An epidemiological survey was conducted in 16 remote villages of the rain forest of southern Cameroon to ascertain the prevalence and intensity of three species of filariae: Loa loa, Onchocerca volvulus, and Mansonella perstans. We examined 1458 individuals for blood-dwelling microfilariae and 1255 of these were also for the presence of palpable nodules. All the villages surveyed were found highly endemic for onchocerciasis and mansonellosis with prevalence ranging from 28.44% to 87.17% for O. volvulus and 52.48% to 100% for M. perstans. The intensities of infection were also found high for M. perstans with arithmetic means of microfilaremia ranging from 280.94 to 4947.57 mf/ml. The loiasis prevalence was relatively low with value from 2.22% to 19.23%. Males were found more infected than females for the three species of filariae, and the prevalence and intensities of microfilaremia vary differently in males and females at different ages. The three species of filariae displayed different degrees of association in the inhabitants with a low prevalence of co-occurrence between L. loa/O. volvulus and between L. loa/M. perstans. In contrast, there was a high prevalence of co-occurrence between M. perstans and O. volvulus. The implications of the co-occurrence of the three species of filariae in the populations of these remote villages on the intervention programs based on mass treatment with mectizan are discussed.

Adolescent↗

No evidence of Wolbachia endosymbiosis with Loa loa and Mansonella perstans.

Endosymbiotic Wolbachia bacteria from different filarial species, including major pathogens of humans such as Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus, seem to play an important role in the development, viability and fertility of these worms. Wolbachia trigger inflammatory host responses as well as adverse reactions against standard treatment regimens and are therefore under investigation as novel treatment targets. We investigated whether Wolbachia are also endosymbiotic in Loa loa and Mansonella perstans. In both male and female adult L. loa, we found no evidence of bacteria by light or transmission electron microscopy. Furthermore, Wolbachia-specific PCR was negative in both L. loa and M. perstans microfilariae. The absence of Wolbachia in both filarial species therefore discourages the use of antibiotics as an adjunct or alternative approach to current treatment concepts for both loiasis and mansonelliasis perstans.

Animals↗

Identification and specificity of a 38 kDa Loa loa antigenic fraction in sera from high-microfilaraemic Gabonese patients.

Circulating antigens isolated from sera of three high-microfilaraemic ( Loa loa) Gabonese patients were fractionated by gel filtration. A major component (38 kDa) was identified after SDS-PAGE and immunoblotting using sera of amicrofilaraemic patients with high level of antimicrofilariae Loa loa antibodies. The 38 kDa fraction was not found in the sera of parasitised patients or healthy controls. We looked for the 38 kDa antigen in the various stages of the filarial life cycle and found it in extracts of Loa loa microfilariae but not in somatic extracts of Loa loa male and female adult worms. This fraction could be used as a diagnostic marker in loiasis for amicrofilaraemic patients.

Animals↗

Filariasis due to Loa loa and Mansonella perstans: distribution in the region of Okondja, Haut-Ogooué Province, Gabon, with parasitological and serological follow-up over one year.

The prevalence of Loa loa and Mansonella perstans filariasis has been determined in 6 rural villages in eastern Gabon. Between 18.9 and 27.2% of people carry L. loa microfilariae with an overall microfilarial rate of 25.1%. The microfilarial rate for M. perstans was more variable, between 33.3 and 62.2% (average 49.1%). No significant difference was seen in the microfilarial rate with age over 15 years for either parasite, but men were infected more frequently than women. Anti-L. loa antibody titres were measured, using a homologous microfilarial antigen in ELISA. Taking the parasitological and immunological evaluations together, only 10% of the sample population appear to be free of these filarial infections. L. loa and M. perstans microfilaraemia and corresponding serology were also investigated twice in 150 people at a one-year interval. 99.1% of the cases who had no circulating L. loa microfilaria in March 1984 still did not show any 12 months later. Similarly, 97.1% of the untreated, microfilaraemic cases still harboured this parasite a year later. The same was not observed for M. perstans, since microfilariae appeared or disappeared in 26.7% of the cases. This suggests different dynamics for the two filarial infections. Variation in individual anti-L. loa antibody titres was low. The possibility of a genetic influence on the expression of loiasis is discussed.

Adolescent↗

Microfilarial distribution of Loa loa in the human host: population dynamics and epidemiological implications.

Severe adverse events (SAEs) following ivermectin treatment may occur in people harbouring high Loa loa microfilarial (mf) densities. In the context of mass ivermectin distribution for onchocerciasis control in Africa, it is crucial to define precisely the geographical distribution of L. loa in relation to that of Onchocerca volvulus and predict the prevalence of heavy infections. To this end, we analysed the distribution of mf loads in 4183 individuals living in 36 villages of central Cameroon. Mf loads were assessed quantitatively by calibrated blood smears, collected prior to ivermectin distribution. We explored the pattern of L. loa mf aggregation by fitting the (zero-truncated) negative binomial distribution and estimating its overdispersion parameter k by maximum likelihood. The value of k varied around 0.3 independently of mf intensity, host age, village and endemicity level. Based on these results, we developed a semi-empirical model to predict the prevalence of heavy L. loa mf loads in a community given its overall mf prevalence. If validated at the continental scale and linked to predictive spatial models of loiasis distribution, this approach would be particularly useful for optimizing the identification of areas at risk of SAEs and providing estimates of populations at risk in localities where L. loa and O. volvulus are co-endemic.

Adolescent↗

Blastogenic responses, interleukin-2 production and interleukin-2 receptor expression on CD4+ and CD8+ lymphocytes in rhesus monkeys experimentally inoculated with Loa loa.

To better understand cellular responses in loiasis infection, in vitro blastogenesis of peripheral blood mononuclear cells (PBMC) to filarial antigen was assessed in 12 Loa loa-inoculated rhesus monkeys over a two-year period. Cellular reactivity to antigen was observed between 10-35 weeks postinoculation (WPI), but had declined by week 50. The roles of interleukin-2 (IL-2) and IL-2 receptor (IL-2R) expression of CD4+ and CD8+ T cells in regulating the response to antigen were examined during the initial (57 WPI) and late (92 WPI) time points of the observed diminished reactivity to antigen. The levels of IL-2 in antigen cultures at both time points were not significantly different from those in unstimulated cultures. Also, exogenous IL-2 partially reversed the PBMC response to antigen. The percentages of CD4+ and CD8+ T cells expressing IL-2R in antigen cultures at 57 WPI were not different from those of control animals. Likewise at 92 WPI, the percentage of CD4+ T cells expressing IL-2R in antigen cultures, were not increased above those of control animals. In contrast, the percentage of CD8+ T cells expressing IL-2R in antigen cultures were significantly increased above those of control animals (P < 0.0001), coinciding with an increase in CD8+ T cells numbers in these cultures. The data show that factors besides IL-2; and probably an imbalance in the percentages of CD4+ and CD8+ T cells bearing IL-2R in antigen cultures, may contribute to the diminished reactivity to antigen in L. loa-inoculated rhesus monkeys.

Animals↗

Relationships between the prevalence and intensity of Loa loa infection in the Central province of Cameroon.

Ivermectin treatment may induce marked adverse effects in those harbouring > 8000 Loa microfilariae (mff)/ml of blood, individuals with > 30 000 Loa mff/ml being at risk of developing serious neurological reactions. It is thus necessary to delineate the geographical areas where such responses may occur. To determine if the simple measure of prevalence of Loa microfilaraemia would be appropriate to identify the communities at risk, the relationships between prevalence and intensity of Loa microfilaraemia were investigated in 67 villages in Cameroon. The prevalence recorded in the adult population was found to be closely related to each of the indicators of infection intensity investigated. For example, when the prevalences of Loa microfilaraemia in adults were 20%, 30% and 40%, approximately 5%, 9% and 16% of the adults had microfilarial loads exceeding 8000 mff/ml, respectively; the corresponding percentages of adults with > 30 000 mff/ml were about 1%, 3% and 5%-6%. Thus it seems that, in areas where loiasis is co-endemic, the monitoring procedure during large-scale ivermectin treatments for the control of onchocerciasis only needs to be strengthened in those communities where the prevalence of Loa microfilaraemia in adults exceeds 20%.

Adolescent↗

The host preferences of Chrysops silacea and C. dimidiata (Diptera: Tabanidae) in an endemic area of Loa loa in the Congo.

The analysis of 404 blood meals from Chrysops silacea and C. dimidiata which had been collected in the forests of the Chaillu mountains (People's Republic of the Congo) has demonstrated for the first time that both species also feed on non-human hosts. For both species the feeding patterns are fairly similar. However, man remains the main host in 89-90% of the cases. C. silacea and C. dimidiata took 6 and 4% respectively of their blood meals from hippopotamuses, 2 and 0% from rodents, 2 and 4% from wild ruminants, and 0.8 and 0.7% from monitor lizards. Whenever a differentiation has been made between the different members of the primates, only meals from humans but not from chimpanzees or baboons have been detected. The results may provide an explanation for the distinct barrier between the simian and human loiasis infections. They also give evidence for the ability of both vectors to travel over prolonged distances.

Animals↗

Prevalences of Loa loa microfilaraemia throughout the area endemic for the infection.

Several cases of encephalopathy recorded in Cameroon since 1991 were in patients with very high, coincident, Loa loa microfilaraemias who had been treated with ivermectin for onchocerciasis. There was thus an urgent need to identify those areas where loiasis is hyperendemic, and where specific monitoring procedures should be developed if large-scale ivermectin treatment of onchocerciasis is to be implemented. In the present review, the available data on Loa endemicity are detailed and maps showing the prevalence of Loa microfilaraemia throughout the area endemic for the infection are presented. By superimposing these maps on those which show where onchocerciasis is meso- or hyper-endemic, it is now possible to identify several areas, in south-eastern Nigeria, southern and central Cameroon, the south of the Central African Republic, Equatorial Guinea, Gabon, and the north and west of the Democratic Republic of the Congo (ex-Zaire), where ivermectin treatment, although indicated, is most likely to lead to adverse reactions because of L. loa infections. Additional surveys, to delineate the areas highly infected with L. loa more accurately, are required.

Adolescent↗

Detection of circulating antigens in Gabonese patients with Loa loa filariasis.

Circulating antigens were detected in sera of Gabonese patients with Loa loa filarial infection by co-electrosyneresis (Co-ES). The serum samples selected for this study were exposed to rabbit hyperimmune antifilarial antisera and human immune antisera: specific arcs were observed in 35/60 filarial patients, of whom 24/47 were microfilaraemic and 11/13 amicofilaraemic. The identity of rabbit hyperimmune antisera and loiasial immune sera was confirmed by the continuity of precipitation arcs. These preliminary studies were carried out to develop diagnostic tools for loiasis and to study the physiopathology of immune complexes.

Animals↗

Effects of a 3-day regimen of albendazole (800 mg daily) on Loa loa microfilaraemia.

The encephalopathy that sometimes develops after ivermectin treatment in patients with high Loa microfilaraemias is probably related to a massive effect of the drug on the Loa microfilariae. A trial was therefore conducted to evaluate whether a course of albendazole would bring about a slower decrease in the Loa microfilaraemia, and thus could be used as a mass 'clearing' treatment, before the distribution of ivermectin in areas where onchocerciasis and loiasis are co-endemic. The Loa microfilarial loads were followed monthly for 9 months in two groups of subjects, one treated with albendazole (400 mg twice a day for 3 days), and the other with vitamin (B(1), B(6) and B(12)) tablets. There were no significant between-group differences in the microfilarial loads at any of the examination rounds. During the follow-up period, there was also no significant change in the overall loads among those treated with albendazole, although the counts in those with high initial microfilaraemias (>8000 microfilariae/ml) tended to decrease progressively during the first 3 months. Further trials should now be performed, to evaluate the effects on Loa loa of two courses of albendazole given 2-3 months apart.

Adolescent↗

The migration and localization of Loa loa infective and fourth-stage larvae in normal and immunosuppressed rodents.

The migration and localization of the human filarial parasite Loa loa in laboratory mice (BALB/c and Swiss) and jirds (Meriones unguiculatus) was investigated. The rodents, either left immunocompetent or immunosuppressed with hydrocortisone, were each inoculated subcutaneously or intraperitoneally with 50 or 200 infective, third-stage larvae (L(3)) of L. loa. Groups of the rodents were killed at various times post-infection, up to day 40, to enable histological studies and permit developing larvae to be recovered. Larvae survived and developed for only 1 week in the immunocompetent rodents but for a mean of 3 weeks in the immunosuppressed. Most of the larvae were found in the subcutaneous tissues (81.9%), peritoneal cavity (14.9%), pleural cavity (1.8%) or the lungs and heart (1.3%) and none was detected in the spleen, kidney, intestine, liver or pancreas. Localization of the larvae appeared unaffected by the site of inoculation, the rodent species or strain, or the dose of L(3) used. The recovery of larvae (as a percentage of the number inoculated) was better among the rodents inoculated with 50 L(3) each than among those given four times as many L(3). The results of the histological studies not only confirmed the presence of larvae in the subcutaneous tissue (72.5%), muscles (11.7%) and peritoneal and pleural cavities (7.8%) of the infected rodents but also revealed worms in the lymphatic vessels of the mesentery and spinal cord (7.3%). These results indicate that most L. loa L(3) inoculated into a mammalian host localize in the cutaneous sites and that only a small proportion of them might migrate, using the lymphatic system, into the internal organs. The observation of migrating L. loa larvae in the lymphatic vessel of the meningeal envelope of the spinal cord, albeit in an experimental host, may explain why, in areas where human loiasis is endemic, neurological manifestations occasionally occur in those with L. loa infections.

Animals↗

Loa loa in the anterior chamber of the eye: a case report.

An unusual case of loiasis from Assam is reported here. Loa loa is a subcutaneous filarial parasite of man and is transmitted to humans by chrysops flies. The patient presented with foreign body sensation and visual disturbances of the right eye. Examination revealed a white coiled structure in the cornea. Routine blood and other investigations were within normal limits. A live adult worm was extracted and identity was confirmed by microscopy to be Loa loa. Patient was treated with diethylcarbamazine and steroid. We found this case interesting as the worm was present in the anterior chamber--an unusual site and there were no other positive findings besides the lone worm.

Animals↗

Transmission indices of Loa loa in the Chaillu Mountains, Congo.

A longitudinal entomological survey of the vectors of loiasis was conducted in the Missama area (Lekoumou region) in the Congo from September 1987 to August 1989. The principal catching site was a palm grove surrounded by forest 3 km from the village. Landing/biting densities of Chrysops were measured by standardized fly catches lasting 11 hr carried out twice a month. Vector landing densities were also assessed in the Bantu and Pygmy villages and in the fields. Populations of Chrysops from the palm grove were examined 6 times a month for infection with the infective stage of Loa loa. Chrysops silacea was the predominate vector except at the beginning of the rainy season, when C. dimidiata was the prevailing species. Chrysops were caught throughout rainy season, from October to June. The host-seeking activity of C. silacea was greatest in the middle of this season (February), but occurred sooner (October) for C. dimidiata. The following variables associated with transmission were calculated from our observations in the palm grove (the first figure corresponds to the first year of the study and the figure in parentheses corresponds to the second year). It was calculated that 2.658 (2.185) C. silacea and 1.412 (1.182) C. dimidiata could bite a person in the palm grove per year, including an average of 14.4 (12.7) infective C. silacea and 9.8 (7.2) infective C. dimidiata. The percentage of all dissected flies with third stage larvae in the head and the mean number of larvae in the head/infective fly were 0.57% and 10.1 +/- 6.8 for C. silacea and 0.66% and 11.2 +/- 6.5 for C. dimidiata, respectively. The estimated annual transmission potentials were 171.1 (102.9) for C. silacea and 116.1 (73.8) for C. dimidiata. In the palm grove, transmission was ensured by 2 effective vectors during the rainy season (October to May). Although the annual biting rate for both species was twice as low in the village as in the forest, our data suggest that effective transmission occurs there also.

Animals↗