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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↗

Effect of a single dose (600 mg) of albendazole on Loa loa microfilaraemia.

The problem of Loa-encephalopathy, which may occur after ivermectin treatment of patients harbouring high Loa microfilarial loads, might be solved if one could find a treatment regimen bringing about a significant but progressive decrease in the Loa microfilaraemia. A trial was performed in Central Cameroon, whose aim was to follow up for 10 months, and to compare the changes in the Loa microfilarial loads in two groups of patients, one treated with a single dose (600 mg) of albendazole (Alben, SmithKline Beecham) given with fatty food, and the other treated with mebendazole (100 mg, twice a day, generic tablets) at a fasting state. The microfilarial loads remained stable in the mebendazole group, whereas a significant decrease in microfilaraemia was recorded in the albendazole group (initial median load: 230 microfilariae per 50 microliters; median load ten months after: 84 microfilariae per 50 microliters). This should encourage further trials to evaluate the effects and the safety of two- or three-day albendazole regimens in patients infected with Loa loa.

Adolescent↗

[Loa loa infection of the eye -- a case series].

BACKGROUND: With increasing migration tropical diseases such as Loa loa infections are becoming more frequent in Europe. While the ocular diagnosis is usually straight forward, systemic work-up and treatment requires an interdisciplinary approach. We review the diagnostic and therapeutic work-up of ocular Loa loa infections based on a series of 4 cases that presented between 1998 and 2004. HISTORY AND SIGNS: The first symptoms in all cases were ocular irritations occurring 2 months to 8 years after a trip to West Africa. One case presented with a swollen upper eyelid without a visible worm. In three patients microfilariae were detected in the blood. THERAPY AND OUTCOME: In two cases visible subconjunctival worms could be removed under the slit lamp. Three cases required systemic treatment as inpatients while one case could be observed without systemic treatment. All 4 cases had a favourable outcome with complete eradication of the disease. CONCLUSION: Surgical removal of adult Loa loa worms from the subconjunctival space only improves the ocular symptoms. An interdisciplinary approach (ophthalmology, infectious disease and parasitology) for a systemic work-up and treatment is usually required.

Adolescent↗

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↗

Loa loa microfilariae aspirated during oocyte retrieval.

Loa loa is a filarial parasite which is mainly confined to West and Central Africa. Although considered as mildly pathogenic for people living in endemic areas, its appearance in other places might be a cause for concern. We report here the unusual finding of Loa loa microfilariae in the follicular aspirate of a 35-year-old black women during oocyte retrieval for in-vitro fertilization. Most likely these microfilariae were aspirated, along with follicular fluid, from the small blood vessels around the ovarian follicles, which are frequently lacerated during ovarian puncture. Despite the spectacular microscopic view of vigorous moving worms trapped on the cumulus cells, the presence of Loa loa microfilariae does not seem to prevent fertilization and cleavage completely.

Adult↗

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↗

Species-specific sequence in the repeat 3 region of the gene encoding a putative Loa loa allergen: a diagnostic tool for occult loiasis.

A polymerase chain reaction (PCR)-based method to detect Loa loa DNA in the blood lysate of infected individuals is described. A set of primers was designed to amplify the repeat 3 sequence (15r3) of the gene encoding a putative L. loa allergen. The qualitative PCR was carried out using blood lysates from subjects from an L. loaendemic area of Gabon where loiasis exists sympatrically with Mansonella perstans, and from individuals from a loiasis-free area in Togo infected concomitantly with M. perstans and Onchocerca volvulus. No specific amplification was observed after ethidium bromide staining of a gel containing M. perstans and O. volvulus control samples. In contrast, a 396-basepair (bp) DNA was detected in all L. loa microfilaremic individuals and in seven of the 20 L. loa amicrofilaremic subjects diagnosed by leukoconcentration. Qualitative Southern blots carried out at high stringency (65 degrees C) using 15r3 oligonucleotide probe revealed hybridization only with L. loa samples (5 of 5 microfilaremic individuals and 15 of 20 amicrofilaremic individuals), confirming the results obtained with ethidium bromide staining of PCR products. We conclude that this 396-bp sequence could be used as a species-specific diagnostic tool for occult loiasis in an endemic area with concurrent filarial infections.

Allergens↗

Subconjunctival Loa Loa worm: case report.

A 38-year old Ghanaian suddenly had the sensation of a foreign body in his right eye. Slit-lamp examination revealed a transparent worm underneath the conjunctiva. With topical anesthesia, the complete worm, 3.5 cm long, was removed surgically. A microbiological analysis at the Institute of Tropical Medicine confirmed the diagnosis of Loa Loa. Laboratory tests showed negative blood eosinophilia, positive blood film examination for microfilariae and positive results for filarial serology. The postoperative treatment consisted of progressive doses of di-ethyl-carbamazine (50-->100-->200 mg/d). A subconjunctival Loa Loa worm is rare in Belgium and usually occurs in immigrants or travellers returning from Tropical (Equatorial) West and Central Africa. Our patient visited Nigeria in 1985 and Ivory Coast in 1986. Those regions are highly endemic for Loa Loa.

Adult↗

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↗

Genetic heterogeneity in Loa loa parasites from southern Cameroon: A preliminary study.

Ivermectin (or Mectizan trade mark ) is widely used by onchocerciasis and lymphatic filariasis control programs worldwide. Generally, Mectizan trade mark is both safe and well tolerated. An exception to this general pattern is in some areas co-endemic for Onchocerca volvulus and Loa loa, where a number of severe adverse reactions to Mectizan trade mark have been noted in L. loa infected individuals. The vast majority of these severe adverse events have occurred in Southern Cameroon. This suggested the hypothesis that the parasites endemic to Southern Cameroon might form a distinct population that exhibited a phenotype of eliciting severe adverse reactions in Loa-infected individuals upon Mectizan trade mark exposure. To test this hypothesis, the DNA sequences of three potentially polymorphic loci were compared among L. loa parasites from Southern Cameroon and other endemic foci in Sub-Saharan Africa. Analysis of these data suggested that parasites from Southern Cameroon were at least as genetically diverse as those from other foci. Furthermore, no polymorphisms were noted that were unique to and shared among the parasite isolates from Southern Cameroon. Although a limited number of parasite isolates were tested, these results do not appear to support the hypothesis that L. loa parasites from Southern Cameroon represent a unique, genetically isolated population.

Journal Article↗

[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↗

Satellite mapping of Loa loa prevalence in relation to ivermectin use in west and central Africa.

For many years, ivermectin has been widely distributed throughout west Africa for the safe and effective control of onchocerclasis. However, recent events in Loa-loa-endemic areas of Cameroon, where severe adverse reactions have occurred, now constrain the public-health use of this drug in the forest habitat of the L. loa vector. We have created a model of L. loa prevalence to identify areas where high endemicity may be associated with the occurrence of such reactions. The model results have been mapped and the areas of overlap between high L. loa prevalence and planned ivermectin distribution for onchocerciasis control identified.

Africa↗

High levels of parasite-specific IgG1 correlate with the amicrofilaremic state in Loa loa infection.

To investigate the mechanisms of protective immunity operating in Loa loa infection, 56 persons from a L. ioa-endemic village in southeast Gabon were examined over a 7-year period. The level of L. loa-specific IgG subclasses in defined parasitologic groups was compared by use of ELISA with either adult, microfilarial, or third-stage larval (L3) antigens of L. loa. With all antigen preparations, IgG1 levels were significantly higher in amicrofilaremic persons than in persons with high or low levels of microfilariae. Moreover, there was a significant negative correlation between IgG1 levels to L3 antigen and the density of microfilariae (Spearman's r(s) = -.701; P < .01). There was no correlation between density of microfilariae and levels of other IgG subclasses or of IgE. These data indicate that IgG1 may play a role in the effector mechanism(s) involved in resistance against L. loa and suggest that L3 antigens may be important in eliciting protective responses.

Adult↗

Age of appearance of IgG, IgM, and IgE antibodies specific for Loa loa in Gabonese children.

IgG, IgM, and IgE antibodies against the filaria Loa loa were measured in umbilical cord blood and in blood from young Gabonese children by an ELISA technique using a homologous metabolic antigen. For children in eight consecutive age groups and adults the percentage of the population positive for each of the antibody classes was determined. The number of children with maternal IgG decreased until one year of age when new synthesis began to become apparent. IgM antibodies were detected only after six months, probably indicating an early infancy as opposed to a fetal infection. The percentage of individuals positive for IgM or IgE reached a peak between two and three years old, followed by a slight decline. Over half of the individuals over one year of age had IgM antibody against L. loa, indicating long-term synthesis of this class of immunoglobulin in many people. In the first two years of life, IgE antibodies were usually accompanied by L. loa-specific IgM. This specific IgE did not appear to trigger the synthesis of nonspecific IgE. By the age of two, 95% of the population had some antibodies against L. loa and by five the percentage of individuals positive for each antibody class had reached adult levels.

Adult↗

Antibody-dependent cell-mediated immune reactions to Loa loa microfilariae in amicrofilaraemic subjects.

Antibody-mediated mechanisms that could be important in controlling microfilaraemia in Loa loa infected amicrofilaraemic adults (mf-ve) were studied. These subjects were selected as having a verified ocular passage of an adult L. loa but being amicrofilaraemic and without recent diethylcarbamazine treatment. Sera from 37 mf-ve subjects were compared to 14 sera from heavily (greater than 4000 mf/ml) infected subjects (mf+ve) and 9 sera from Caucasian control subjects for their reactions with L. loa mf (mf). Many mf-ve sera (22/37) were strongly positive in immunofluorescence (IFAT) on living mf. Mf+ve sera were negative, or only weakly positive, and Caucasian sera were negative. Clinical signs were not significantly different between IFAT reactive and non-reactive mf-ve subjects. Approximately half of the IFAT positive, mf-ve sera were also able to agglutinate mf; no other sera were active in this test. Titres ranged from log2 3-6 and in most cases, 9/11, the agglutination reaction was mercaptoethanol-sensitive. Antibody-dependent cellular adherence was studied using mf and leukocytes from uninfected donors. Using cryopreserved mf many heat-inactivated mf-ve sera gave strong reactions with obvious adherence by 4 h and few motile mf remained by 16 h but when fresh mf were employed these reactions were weak. However, addition of complement to many (10/11) mf-ve sera considerably enhanced adherence to fresh mf. The effect of various treatments on the complement source indicated a role for both the classical and alternative pathways. The cells attached to mf were mainly neutrophils (83%) with some eosinophils (15%) and few mononuclear cells (2%). The common occurrence of antibodies able to mediate complement-dependent adherence of polymorphonuclear leukocytes to L. loa mf in the sera of mf-ve subjects may indicate that such a mechanism is important in controlling microfilaraemia in vivo.

Adult↗