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A patient with a filarial infection due to Loa loa and renal failure was treated with a modified regimen of diethylcarbamazine while receiving hemodialysis. Infection with Loa loa may be associated with glomerulonephritis due to immunologically mediated injury. Serum immune complexes were elevated in our patient, and a kidney biopsy specimen revealed globally sclerosed glomeruli. As gauged by the clearance of the microfilaremia, the treatment regimen proved safe and effective.
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A 40-yr-old West African man presented acutely with pleural effusion. Cytologic evaluation of the pleural fluid revealed Loa loa microfilariae. No additional etiology for the pleural effusion could be identified, and antifilarial treatment with diethylcarbamazine led to a rapid resolution of the patient's symptoms and pulmonary abnormalities. Loa loa must be considered as a treatable cause of eosinophilic pleural effusions in persons from endemic areas of West and Central Africa.
No microfilariae are detectable in a significant percentage of those infected with the filarial worm Loa loa. While the probability of an infected individual becoming microfilaraemic is known to increase with age, the mechanisms underlying this trend are not well understood. Epidemiological data from an endemic village in central Cameroon were therefore explored, in an attempt to determine if, after taking into account any history of filaricidal treatment, the presence of Loa microfilaraemia in an individual was related to his/her gender, age, and/or exposure to the human-infective larvae of the parasite. An index of exposure, based on the monthly transmission potentials of the Chrysops in each of the main types of vegetation in a village and on the activity schedule of each inhabitant of the village, was developed. The results of the data analysis confirm that the acquisition of microfilaraemia is gender-dependent (males generally being more likely to be microfilaraemic than females), and indicate that, in males, a high level of exposure to infective larvae determines the shift from amicrofilaraemic to microfilaraemic status. They also indicate that filaricidal treatments have a long-lasting suppressive effect on Loa microfilaraemia, an observation that may have important implications for any strategy to limit the risk of Loa-associated encephalopathy following ivermectin treatment.
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In March 1981, a 32-year-old male naturalist involved with collecting mammals for study was found to have an unexpected eosinophilia. Serum parasitic screening done at the Centers for Disease Control showed filarial titer by indirect hemagglutination of 1:1,024 and of 1:40 by bentonite flocculation. His travel history disclosed 3 months spent in Cameroon in 1978. He also gave a history of intermittent arm swelling for at least a year. Peripheral blood, collected repeatedly at mid-day and midnight and tested for microfilariae by the Knott technique, was negative. He was begun empirically on diethylcarbamazine, and on day 11 of treatment he removed a worm, identified as a male Loa loa, from his leg. He completed treatment without difficulty and has done well.
Two clinical studies were carried out in Gabon, Africa to evaluate the efficacy, safety, and tolerability of ivermectin in the treatment of patients with Loa loa infection. In the first study, 35 patients received single oral doses of ivermectin, 5-200 mcg/kg body weight. Blood microfilariae levels did not decrease after a single oral 5, 10, 30, or 50 mcg/kg dose of ivermectin, but levels did decrease after doses of 100, 150, and 200 mcg/kg. The most efficacious dose was 200 mcg/kg; mean blood microfilariae levels decreased to 12% of mean pretreatment values by day 15 and remained decreased for 28 days. A second study evaluated the safety and efficacy of ivermectin in patients with multifilarial infections. All 17 patients had concomitant Loa loa and O. volvulus infection. M. perstans affected 5 of the patients. Sixteen patients also had infections due to intestinal nematodes. The patients each received single oral doses of 200 mcg/kg ivermectin. Ten days later, the mean Loa loa blood microfilariae level had decreased to 20% of the mean pretreatment level. O. volvulus dermal microfilariae densities were reduced to 2% of the pretreatment levels. A minimal increase in blood microfilaria levels was observed on day 28. In contrast, dermal microfilariae levels remained near zero for the duration of the study. Intestinal infection due to Ascaris was eradicated in all of the affected patients by day 23; efficacy against Trichuris and hookworm infections, however, was poor. All patients tolerated ivermectin well including those with multiple infections.
Five cases of encephalitis following treatment with diethylcarbamazine (DEC) were observed in Congolese patients with Loa loa filariasis. Two cases had a fatal outcome and one resulted in severe sequelae. The notable fact was that this complication occurred in three patients hospitalized before treatment began, with whom particularly strict therapeutic precautions were taken, i.e., initial dose less than 10 mg of DEC, very gradual dose increases, and associated anti-allergic treatment. This type of drug-induced complication may not be that uncommon in highly endemic regions. It occurs primarily, but not exclusively, in subjects presenting with a high microfilarial load. The relationship between the occurrence of encephalitis and the decrease in microfilaremia is evident. The pathophysiological mechanisms are discussed in the light of these observations and the few other comments on this subject published in the literature.
A study was carried out in southeastern Gabon to evaluate the tolerance and efficacy of single high doses of ivermectin in 31 Loa loa-infected subjects with low-to-moderate parasitemia (7-7,700 microfilaria/ml). The first group of 16 subjects received 300 micrograms/kg of ivermectin and, seven days later, a second group of 15 received 400 micrograms/kg. Complete clinical and biological monitoring was carried out during the first 10 days post-treatment and again after one and three months. All subjects continued with their usual activities during the study. The clinical tolerance of treatment was very good, and except in one case, only mild adverse reactions were observed, with pruritus being the most common symptom. There were no significant changes in blood or urine function test results or in hematologic results, except for a pronounced eosinophil reaction. The 400 micrograms/kg dose of ivermectin equaled or surpassed in tolerance that of 300 micrograms/kg dose. After treatment, L. loa microfilaremia decreased rapidly to less than 9% of the pretreatment value by day 10. This decrease was enhanced with the 400 micrograms/kg dose, although differences between the two groups diminished slightly with time. At 100 days post-treatment, the microfilaremia was still at less than 10% of the initial values in the two groups, which may indicate an effect of ivermectin on the adult worms.
One hundred nine Gabonese patients infected with Loa loa microfilariae were treated with ivermectin (200 microg/kg of body weight) at the Parasitology, Mycology and Tropical Medicine Department (Faculte de Medecine et des Sciences de la Sante, Libreville, Gabon). Each was given one dose per month for six consecutive months. The peripheral blood microfilaria (mf) count before and after each dose showed an average decrease in the microfilaremia of 87.3% (short-term-single dose). An annual single-dose mass treatment with 200 microg/kg of ivermectin was sufficient to control the parasite in populations with low (< 400/ml) L. loa mf counts. One month after the sixth dose (short-term-multiple doses), the average microfilaremia rate had decreased by 99.2% compared with the initial infection (35 patients). Samples were taken from 28 patients one month after the first dose and one month after the sixth dose. The average mf count decreased by 96.4% after the first dose and by 99.6% after the sixth dose (average residual mf counts = 13.7 and 1.5 mf/ml, respectively). The mf count after the sixth dose was only 11.2% of the count after the first dose. The low mf count persisted for more than six months after the sixth treatment (long-term-multiple doses). Thus, mass treatment with multiple doses is more appropriate for areas where the blood mf count is very high. These results show that the number of the annual treatments used in mass chemotherapy with ivermectin can be adapted to each population to provide efficient protection.
Specific IgG subclasses were investigated in two villages (Okoumbi and Ndjokaye) in southeast Gabon with different Loa loa transmission intensities of approximately 9,000 and 1,300 infective larvae (L3) per person per year, respectively. IgG subclasses were measured by an enzyme-linked immunosorbent assay (ELISA) using extracts of L. loa L3, microfilariae (MF), or adult worms. Levels of L3-specific IgG3 were significantly higher in the village with low transmission (Ndjokaye) (P = 0.006). In contrast, MF-specific IgG2 was significantly higher in Okoumbi than in Ndjokaye (P = 0.0009). In the high-transmission village (Okoumbi), levels of both MF- and adult-specific IgG4 were significantly increased in MF carriers compared with amicrofilaremic subjects (P = 0.0015 and P = 0.003, respectively), while levels of L3- and MF-specific IgG1 were significantly higher in amicrofilaremic individuals compared with MF carriers (P = 0.04 and P = 0.03, respectively). Furthermore, among microfilaremic individuals, the level of the specific IgG1 subclass was much lower in Okoumbi than in Ndjokaye (P = 0.036). These results suggest that the expression of antigen-specific IgG3 and IgG2 is more likely to vary with transmission intensity, whereas antigen-specific IgG4 and IgG1 varies with adult worm and MF burden.