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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↗

Effect of attraction factors on the sampling of Chrysops silacea and C. dimidiata (Diptera: Tabanidae), vectors of Loa loa (Filaroidea: Onchocercidae) filariasis.

The effects of fire and human host density on Chrysops silacea and C. dimidiata abundance and age structure was evaluated at sites of Loa loa filariasis transmission in the Congo rain forest. Fire increased the catch of C. silacea 8.5-fold at ground level and 5-fold in the canopy, but did not modify the catch size of C. dimidiata. Catch size increased 2-fold when a pygmy camp located near the collecting station was inhabited. The presence of fire did not alter the parity and Loa loa infection rates in the populations.

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↗

Differential recognition of Loa loa antigens by sera of human subjects from a loiasis endemic zone.

Somatic antigens of Loa loa adult worms with molecular weights of 15-180 kDa were identified by Western blot analysis using sera from 3 categories of parasitologically and clinically defined subjects from a loiasis endemic zone. Sera of occult, amicrofilaremic (OL), and 'resistant' individuals with no clinical signs of infection (R) reacted with an antigen of 160 kDa; sera of highly microfilaremic individuals (ML) did not. ML sera strongly reacted with an antigen of 18 kDa which was recognized only weakly or not at all by OL and R sera. At higher dilutions, OL sera only reacted with antigens at 23 and 160 kDa and ML sera reacted with antigens at 18 and 23 kDa, whereas R sera reacted with antigens at 23, 42, 54, 70, 100, and 160 kDa. These data suggested that R sera contained a higher concentration of antibodies which reacted with denatured, nitrocellulose-bound antigens. The IgG4 isotype predominated for all groups of sera, while IgG3 antibody responses were observed only with R sera. IgG1 antibodies were seen in all groups but reacted with fewer antigens than IgG4 antibodies, and no IgG2 antibody responses were detected. Sera against Brugia malayi, Wuchereria bancrofti, Onchocerca volvulus, and Dirofilaria immitis cross-reacted with somatic antigens greater than 70 kDa, whereas none reacted with Loa loa antigens less than 23 kDa.

Animals↗

Microfilarial densities, hematologic changes, and serum antibody levels in Loa loa-infected rhesus monkeys (Macaca mulatta).

To better define Loa loa infection in the rhesus monkey and assess the potential usefulness of this host as a model for studies of human loiasis, 12 monkeys (four splenectomized and eight nonsplenectomized) were inoculated with L. loa infective larvae. Microfilaremia and hematologic changes as well as parasite-specific antibody were assessed as a function of time in these animals. Eleven of 12 inoculated monkeys became microfilaremic. Splenectomized animals had moderate (250-1,000) to low (< 250) numbers of microfilariae per milliliter (mf/ml), whereas the mf/ml in nonsplenectomized animals varied from high (> 1,000) to low. A significant increase in total leukocyte and lymphocyte numbers was seen in animals with moderate-to-low mf/ml but not in animals with high mf/ml mainly because of variations between animals in the latter group, rather than a direct consequence of increased mf numbers. All infected animals developed an eosinophilia before patency, suggesting the adult worms most likely contribute to this phenomenon. As the infection progressed, the eosinophil numbers decreased significantly. Although splenectomized animals overall had slightly higher numbers of total leukocytes (lymphocytes and eosinophils), these hematologic changes as a function of time were not significantly different from those in nonsplenectomized animals. Parasite-specific IgG antibody was increased significantly before patency in all animals and with the exception of the one amicrofilaremic animal, it decreased after patency. This study shows that splenectomy of rhesus monkeys prior to L. loa inoculation does not enhance the microfilarial density nor does it adversely affect eosinophilia or antibody production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ocular findings after ivermectin treatment of patients with high Loa loa microfilaremia.

Hemorrhages in the palpebral conjunctiva (HPCs) have been recorded in patients living in an area endemic for loiasis who developed serious reactions after ivermectin treatment. A study was designed to evaluate the frequency of these lesions, and to identify risk factors associated with their appearance. The conjunctivae of 1,682 patients who complained of reactions were systematically examined. HPCs were found in 41 patients. The initial mean Loa loa microfilaremia in the individuals with HPCs was 14,900 microfilariae (mf) per mL, as compared with 14.5 mf/mL in the other patients. Mansonella perstans microfilaremia and male gender were also associated with HPCs. Post-treatment fundus examinations were performed on 37 patients, and a close relationship was found between the occurrence of HPCs and the presence of retinal lesions. The vascular pathological processes leading to the ocular lesions may be similar to those which occur at the cerebral level in patients harboring high L. loa microfilaremia who develop neurologic troubles after ivermectin treatment. Retinal lesions may represent a special feature of the Loa-related encephalopathies useful for differential diagnosis, and the HPCs may be useful as an alarm sign to identify those individuals who might develop serious reactions after ivermectin treatment.

Adolescent↗

Loa-loa microfilaremia in the Nigerian population.

In about half of 1026 Nigerians infected with Loa loa, the microfilaria levels were low, less than 8% had more than 1000 microfilariae in 50 cumm blood. The length range of 445 microfilariae obtained from 39 infected people was 156.8 to 308.7 micron with a mean of 236.4 micron, or microgram; smaller than in the Kumba strain of Cameroon. The persistence of a rather high number of microfilariae in the peripheral blood of four patients till 22 hours was discussed in relation to the importance of Mansonia africana mosquitoes as a vector of Loa loa.

Adult↗

Loa loa: development and course of patency in experimentally-infected primates.

Loa loa infections were studied in baboons, rhesus and patas monkeys. Animals were infected either by s.c. injection of third-stage larvae (L 3) or by surgical implantation of juvenile worms of known age, sex and number. Microfilaremia was first detected in baboons at 140 days following inoculation of L 3 and at 142 days and 143 days in patas and rhesus monkeys, respectively; the mean prepatent period was 151 days in baboons, 149 days in patas monkeys and 169 days in rhesus monkeys. The primary wave of microfilariae (mf) was suppressed by the spleen in all three primate species. In baboons, the initial wave of mf lasted from 11 to 46 weeks (mean: 22 weeks), whereas in patas monkeys it persisted for 47 to 60 weeks, and in rhesus monkeys for 1 to 2 years. Gross and microscopical changes in the spleen were noted in all three primate species and consisted of numerous granulomata in the red pulp underlying the capsule. A resurgence of mf was observed following splenectomy in all three species of monkeys. Postsplenectomy levels of microfilaremia typically exceeded presplenectomy levels. One pair of worms was sufficient to produce patent infections in monkeys for extended periods of time. However, levels of microfilaremia were lower than in monkeys which received 75 and 200 to 300 L 3, although some overlap in microfilaremias between groups did occur. Overall, there was no proportional relationship between levels of microfilaremia and numbers of adult worms recovered from monkeys at necropsy. It was observed that, in the primate host, Loa is a long-lived parasite. Living worms were recovered from the tissues as long as 9 years after inoculation and there was no reason to doubt that patency would have persisted for some time into the future. Adult worms were frequently observed moving freely in the subcutaneous tissues of the primate hosts, although no instance of Calabar swellings or the presence of worms in or around the eye were ever recorded. The primate model of loiasis is an especially useful system because of the predictability of the behavior of the parasite. In most regards, the behavior of L. loa in the primate host is comparable to observations on the parasi e in man.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Etiological study of low fertility in eastern Gaboon. III. Filarial endemicity (Loa loa, D. perstans). Prevalence of microfilariae in hydroceles (author's transl)].

During an inquiry performed in Gaboon the prevalence of hydroceles had led to puncture systematically every vaginal flow. 68 fluids were so collected at the end of the inquiry. Subsequently the statistical analysis of the results in men seems to suggest a correlation between microfilaremia (Loa loa and D. perstans) and the prevalence of hydroceles. Microfilariae were found in 77% according to the following distribution: Loa loa seldom diagnosed in this kind of flow were detected in 10%; D. perstans although never reported so far in hydrocele fluids appeared to be present in 62%. O. volvulus more currently referred to in hydrocele liquids were scarcely traced.

Adult↗

Development and larval morphology of Loa loa in experimental primate hosts.

Experimental infections with Loa loa were established in laboratory primates by inoculation of third-stage larvae recovered from either Chrysops silacea infected after engorging on a human volunteer with loiasis, or Chrysops atlanticus infected after blood feeding on experimentally infected primates. The third molt occurred at 16 to 20 days postinoculation of infective larvae, and the fourth at about 50 days. Early larval development was characterized by rapid growth and marked differentiation of the reproductive systems. Differences in the body's growth rate between the sexes were seen as early as 30 days and was especially marked by 60 days. Females grew more rapidly, and for a longer time than males. Males reach maximum size by 120 days, females not until about 300 days. Female worms were inseminated prior to day 90 developing eggs filled the uteri by 120 days, and microfilariae appeared in the peripheral blood at approximately 150 days. Morphological features of the larval and adult stages of human Loa loa are described.

Animals↗

Loa loa and Mansonella perstans filariasis in the Chaillu mountains, Congo: parasitological prevalence.

1934 Bantus and 379 Pygmies were investigated for Loa loa and Mansonella perstans filariasis in 7 villages in the Chaillu forest of the Congo. Bantus were more frequently infected with L. loa than Pygmies (18.9% of microfilariae carriers compared with 10.6%). In individuals over 30 years of age, males were more frequently infected than females. Microfilarial densities increased until the age of 20 years and then remained stable. Parasite load was not significantly different in the two ethnic groups. For mansonelliasis, the microfilarial rate was higher in the Pygmies (67.5% compared with 22.0%) and males of the 2 groups were more frequently infected than females. Microfilarial load was also higher in Pygmies than in Bantus (mean microfilarial densities (MfD 50) 13 and 2 respectively). In the Pygmy group, MfD 50 for M. perstans increased with age whereas it remained stable in the Bantus. 53.8% of the 249 questioned persons had experienced worm migration under the conjunctiva. Both ethnic groups were equally exposed to the vectors of L. loa and reasons for the difference in prevalence of microfilaria carriers are discussed. For mansonelliasis increased contact with vectors may explain the higher degree of infestation observed in Pygmies. Other filariases were infrequent in (Mansonella streptocerca), or absent from (Onchocerca volvulus and Wuchereria bancrofti), the study area.

Adolescent↗

Ocular Loa Loa with cryoprobe extraction of subconjunctival worm.

A healthy 27-year-old West African man presented to the emergency room at the Massachusetts Eye and Ear Infirmary complaining of a moving foreign body sensation in his right eye. He had experienced recurrent episodes of subconjunctival Loa Loa, a parasite endemic in Africa. A cryoprobe was successfully used for extraction of a large adult worm. Strategies for the removal of subconjunctival worms are presented. The systemic and ocular manifestations of Loa Loa are reviewed and a discussion of complications of medical management follows.

Adolescent↗

[Retinal hemorrhages after ivermectin treatment for onchocerciasis in a patient with Loa loa microfilaremia].

A case of retinal hemorrhages with special features and degradation of the general condition is reported in a 27-year-old female patient, following the ingestion of ivermectin for the treatment of onchocerciasis. The patient was infested by both Onchocerca volvulus and Loa loa. A bilateral peripheral temporal location of the retinal lesions was observed. The role of L. loa microfilarial load in the occurrence of the retinal lesions as well as the transient character of the lesions are discussed, based on the clinical observation and with reference to the literature. The authors call for setting up a rapid therapeutic system to take care of serious adverse reactions following treatment with ivermectin in areas with a high prevalence of L. loa infestation.

Adult↗

Thrombosis of the ulnar veins--an unusual manifestation of Loa loa filariasis.

A 49-y-old male, who had travelled in Central Africa, was admitted to hospital with oedema of the right forearm. He was diagnosed as having thrombosis of the ulnar veins. Subsequently eosinophilia and positive serology for filariae established the aetiologic agent as Loa loa. The patient received antithrombotic and antiparasitic therapy. This is, to our knowledge, the first reported case of thrombosis of the ulnar veins associated with Loa loa.

Africa↗

Transmission intensity affects both antigen-specific and nonspecific T-cell proliferative responses in Loa loa infection.

T-cell proliferative responses were studied in two villages in Gabon with different levels of Loa loa transmission. The first village (Okoumbi) had an annual transmission potential (ATP) of approximately 9,000 infective larvae (L3)/person/year (high transmission village), while the second village (Ndjokaye) had an ATP of approximately 1,000 L3/person/year (low transmission village). Proliferation and cytokine assays were performed on peripheral blood mononuclear cells (PBMC) from individuals aged 18 years and over using either mitogens (concanavalin A or phytohemagglutinin), antigens (purified protein derivative [PPD], irrelevant antigen), or soluble extracts of L3, microfilariae, or adult L. loa. PBMC from individuals in the low transmission village responded better to stimulation with adult antigen and to PPD than did PBMC from individuals in the high transmission village (P = 0.0031 and P = 0.0012, respectively). These data suggest that high levels of transmission of L. loa depress both specific and nonspecific T-cell proliferative responses in infected humans.

Adult↗

Loa loa encephalopathy temporally related to ivermectin administration reported from onchocerciasis mass treatment programs from 1989 to 2001: implications for the future.

Of the 207 Serious Adverse Events (SAEs) following treatment with Mectizan(R) (ivermectin, Merck, Sharpe & Dohme) that were reported from 1989 to 2001 through the passive SAE surveillance system required of all onchocerciasis mass treatment programs, 65 were cases of 'Probable' or 'Possible' Loa loa Encephalopathy temporally Related to treatment with Mectizan(R) (PLERM).A retrospective analysis of these 65 PLERM cases revealed that 97% were from southern Cameroon, 85% were male and 93% were being treated with ivermectin for the first time. The mean time to onset of symptoms was 1.7 days (95% CI: 1.3, 2.2) but the mean time to receiving medical attention after the onset of symptoms was 2.0 days (95% CI: 1.5, 2.6). Hospitalization was reported in 53 cases with a mean duration of 27.5 days (95% CI: 13.3, 41.6, n = 35). Clinical outcome was reported in 34 cases: 64.7% recovered fully, 11.8% had partial neurologic deficit and 23.5% died. For the 32 cases where quantitative L. loa data were reported, the arithmetic means with 95% confidence intervals were for 1) peripheral blood: pre-treatment - 164,250 mf/ml (79,537, 248,963; n = 4); post-treatment within 1 month - 3926 mf/ml (2,128, 5,725; n = 21) and within 5 to 6 months - 7800 mf/ml (3417, 12,183; n = 7); and for 2) cerebrospinal fluid: 32 mf/ml (7, 37; n = 10) within 1 month post-treatment.Pending further research on practical methods to exclude individuals with high intensity L. loa infection from onchocerciasis mass treatment programs, more emphasis should be placed on surveillance and monitoring to ensure early recognition, referral and management of SAEs, during the first 2 years when majority of the population is presumably naïve to ivermectin.

Journal Article↗

Loa loa: experimental infection in two species of African primates.

Four species of primates, baboon (Papio anubis), patas monkeys (Erythrocebus patas), green monkey (Cercopithecus aethiops) and chimpanzee (Pan troglodytes) were inoculated with third-stage larvae of a human strain of Loa loa from Cameroon, West African. The baboon and patas monkeys developed patent infections after 135 to 148 days; the green monkeys and chimpanzee did not. In each animal which became patent, microfilaremia rose rapidly to high levels. In the baboon, but not in the patas monkeys, there was a suppression of microfilaremia during the 4th month of patency. After splenectomy, microfilariae reappeared in the peripheral blood in large numbers. In both baboon and patas monkeys, the microfilariae of Loa loa maintain the diurnal periodicity so characteristic of their behavior in man.

Animals↗