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PubMed1993

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↗
PubMed2000

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↗
PubMed2001

[Entomologic study of loaiasis transmission in the Lekie area (Cameroon)].

A number of cases of Loa encephalopathy have been recorded after ivermectin treatment in the Lekie Division, an area of degraded forest located in central Cameroon. An entomological study was carried out in a village of this region between May 1999 and April 2000 to determine whether the high microfilarial loads of Loa found in the population, which can exceed 10,000 microfilariae per ml of blood, were related to high densities of vector populations. The Chrysops collected at 10 catching stations, using hand nets, by persons standing by a wood fire, were dissected to evaluate their level of infection with Loa. The vectorial densities were three-fold higher in the forest stations than in those located near the habitations (2307 and 725 bites per man per year, respectively). These values are lower than those reported from similar studies in Cameroon, Congo and Gabon. Measurement of Chrysops densities does not seem to be an appropriate tool to evaluate the level of endemicity of loiasis, and to delineate the areas where there is a risk of post-ivermectin Loa encephalopathies.

Animals↗
PubMed1985

In vitro parasite antigen-induced antibody responses in human helminth infections.

Helminth parasites characteristically induce vigorous antibody responses in human infections, but the immunoregulatory mechanisms determining the level of these responses are not at all understood. To investigate these mechanisms, peripheral blood mononuclear cells were obtained from 10 patients with parasitic helminth infections (three with schistosomiasis, three with onchocerciasis, and four with loiasis), along with six normal controls. These cells were then cultured in vitro and the capacity of the cells to respond to a specific parasite antigenic stimulus was examined by measuring the amount of parasite-specific antibody produced. Parasite antigen alone, without exogenous mitogen, induced an IgG anti-parasite antibody response in vitro. Optimal responses were obtained at extremely low antigen concentrations--concentrations at which little if any polyclonal immunoglobulin production occurred. Additionally, the in vitro induction of parasite-specific antibody was antigen dose-dependent, requiring much lower antigen concentrations than those necessary to induce lymphocyte blastogenesis. Antibody production was shown to require the cooperative interaction of B and T cells. These studies demonstrate that in vitro responses to antigens from naturally acquired parasitic infections, like those in individuals postimmunization, can be utilized to dissect the cellular and humoral factors that regulate antibody production to naturally acquired human pathogens.

Adult↗
PubMed1989

Clinical and biological study of Loa loa filariasis in Congolese.

Clinical and biological evaluations were carried out on 84 Congolese patients with parasitologically confirmed Loa loa filariasis (without concurrent infection with other filariae) and on 98 controls without filariasis. On the patients, 72 presented with microfilaremia; another 12 with negative blood tests were seen towards the end of an episode of subconjunctival migration of the adult worm. The incidence and severity of the clinical signs depended upon the method of recruitment. The 3 most common signs were pruritus and edema (both occurring in successive acute episodes affecting mainly the hands and forearms) and subconjunctival migration of adult filariae. Papulovesicular eruptions were located mainly on the arms. Headaches and arthralgia were noted more frequently than in the controls. No relation was found between the ABO blood groups and loiasis. Eosinophilia (higher in patients with symptoms) and raised serum IgE levels were found in nearly all patients and were strongly marked in approximately 66%. A positive correlation was observed between these 2 parameters. Fluorescent antibody levels (adult filaria Dipetalonema viteae antigen) were comparatively low in patients with microfilaremia.

ABO Blood-Group System↗
PubMed1989

[Loa loa filariasis: cause of severe eosinophilia].

Two cases of very high hypereosinophilia (28,160 and 11,232/mm3) observed in congolese patients are presented. Although microfilaraemia was not detectable, loiasis was diagnosed, given the clinical manifestations, epidemiological data, history of sub-conjunctival migration of the adult worm (in one case), spectacular recovery (clinical and biological) after treatment with diethylcarbamazine. This "allergic form" of filariasis is often considered unusual in indigenous subjects.

Adult↗
PubMed1985

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↗
PubMed1993

[Value of filariopheresis in the treatment of Loa loa filariasis].

To prevent the side effects as encephalitis, related with diethylcarbamazine treatment in loiasis, an exchange blood transfusion was proposed. To avoid the disadvantage of this heavy technique, the authors are proposing filariopheresis to trap the microfilariae using cytapheresis technique and filtration. They obtained a medium 75 p. cent microfilariae extraction: 55-70 p. cent by cytapheresis and 5-20 p. cent by filtration. The number of blood cells must be supervised as an important decrease of the platelets may occur temporary. This simple and not expensive technique is efficient, but diethylcarbamazine treatment must be instituted very quickly after filariopheresis session. Furthermore, the millions of microfilariae collected can provide useful antigen for immuno-parasitological tests.

Adult↗
PubMed1994

Brugia malayi: the diagnostic potential of recombinant excretory/secretory antigens.

The diagnostic potential of recombinant E/S antigens of the lymphatic filaria Brugia malayi was investigated by Western blot. A cDNA expression library was constructed using B. malayi male adult worm mRNA, and E/S recombinants were identified with a rabbit antiserum raised against E/S products collected in vitro from B. malayi male and female adult worms. Two of these recombinants, Bm12 and Bm14L, were studied after subcloning the cDNA inserts in an Escherichia coli plasmid expression and purification vector, obtaining the inserts' nucleotide sequence, and purifying the expressed proteins. By homology of their deduced amino acid sequence with that of previously identified proteins, Bm12 was identified as the B. malayi gp 15/400 antigen, and Bm14 as a member of the hsp90 family of heat shock proteins. The antigenic cross-reactivity of the purified recombinant proteins was assessed with 28 serum samples from patients infected with Ascaris, Trichuris, or hookworm, and also with a few samples from patients with onchocerciasis and loiasis. For Bm12, the specificity for all of the intestinal helminthiasis together was 75%. Bm14L, on the other hand, cross-reacted with all of the ascariasis serum samples with which it was tested. Presence of antibodies cross-reactive with B. malayi was confirmed in all of these serum samples by examining their antibody reactivity with Western blots of extracts of whole B. malayi adult worms. A semiquantitative (+ or -) assessment of the sensitivity of Bm12 for antibody detection was performed using 6 serum samples from patients with chronic filariasis and 24 samples from patients with microfilaremia. All of these serum samples contained anti-Bm12 antibody (sensitivity of 100%). Finally, the ability of Bm12 to detect antibody before the onset of patency was established with a longitudinal collection of serum samples obtained from 2 African green vervets (Cercopithecus aethiops) and 3 rhesus macaques (Macaca mulatta), all of which were infected with B. malayi. Anti-Bm12 antibodies were detectable in all animals between 4 and 11 weeks before patency.

Amino Acid Sequence↗
PubMed1977

Man-biting species of Chrysops meigen, Culicoides latreille and Simulium latreille in Ethiopia, with discussion of their vector potentialities.

Human filariasis and its vectors are little known in Ethiopia. Wuchereia bancrofti is confined to the western lowlands and cannot be the aetiological agent of elephantiasis in the highlands. Onchocerca volvulus is widespread in the south-western highlands. Loa loa and Dipetalonema perstans are reported here for the first time and appear to be uncommon. Studies were conducted in 1973, mostly near Jimma in Kaffa Province, on potential vectors of all but the first of these parasites. Among Simuliidae, the only blackflies of apparent medical importance were S. woodi ethiopiense and a possibly new member of the S. damnosum complex. The former is less seasonal and much less numerous than the latter, but may be more widespread and important along smaller and higher streams. Onchocerca larvae were recovered from "damnosum", but not from the small number (46) of ethiopiense examined. In August, at the height of the rainy season, the biting-rate of ethiopiense at 1,710 m altitude on the Gilgil Ghibe river reached 9.5/man-hour at 10-1100 hours and about 12/man-hour at 14-1600 hours. At the same time and place, the attack of "damnosum" reached a midday climax of about 1,800/man-hour; this peak could be delayed or suppressed by rain. Another possibly anthropophilic blackfly, S. dentulosum, tended to become most common in December afer the rainy season had passed, but proved incompetent to bite man successfully. The only feasible loiasis vector found in Ethiopia was Chrysops streptobalius; however, this tabanid was not closely associated with man. Up to 34/man-day were caught in watermeadows by the Gojeb river (altitude 1,160 m) in October. Man-biting species of Ceratopogonidae in various parts of Ethiopia were Culicoides fulvithorax, C. grahamii, C. kingi and C. milnei. The first two of these were anthropophilic in lowlands, but apparently not so in highlands. C. milnei was extremely abundant biting man highlands. C. milnei was extremely abundant biting man and domestic animals both indoors and outdg cycle was irregular, usually displaying a succession of ill-define nocturnal peaks; sometimes it attacked in daylight. Up to 35,000 C. milnei per trap-night were caught in light traps. Most of the females entering light traps in a stable were already engorged with blood. It seemed very likely that C. milnei would prove to be of veterinary importance. No firm indication was obtained as to what may transmit D. perstans in Ethiopia.

Animals↗
PubMed2000

Effects of environmental change on emerging parasitic diseases.

Ecological disturbances exert an influence on the emergence and proliferation of malaria and zoonotic parasitic diseases, including, Leishmaniasis, cryptosporidiosis, giardiasis, trypanosomiasis, schistosomiasis, filariasis, onchocerciasis, and loiasis. Each environmental change, whether occurring as a natural phenomenon or through human intervention, changes the ecological balance and context within which disease hosts or vectors and parasites breed, develop, and transmit disease. Each species occupies a particular ecological niche and vector species sub-populations are distinct behaviourally and genetically as they adapt to man-made environments. Most zoonotic parasites display three distinct life cycles: sylvatic, zoonotic, and anthroponotic. In adapting to changed environmental conditions, including reduced non-human population and increased human population, some vectors display conversion from a primarily zoophyllic to primarily anthrophyllic orientation. Deforestation and ensuing changes in landuse, human settlement, commercial development, road construction, water control systems (dams, canals, irrigation systems, reservoirs), and climate, singly, and in combination have been accompanied by global increases in morbidity and mortality from emergent parasitic disease. The replacement of forests with crop farming, ranching, and raising small animals can create supportive habitats for parasites and their host vectors. When the land use of deforested areas changes, the pattern of human settlement is altered and habitat fragmentation may provide opportunities for exchange and transmission of parasites to the heretofore uninfected humans. Construction of water control projects can lead to shifts in such vector populations as snails and mosquitoes and their parasites. Construction of roads in previously inaccessible forested areas can lead to erosion, and stagnant ponds by blocking the flow of streams when the water rises during the rainy season. The combined effects of environmentally detrimental changes in local land use and alterations in global climate disrupt the natural ecosystem and can increase the risk of transmission of parasitic diseases to the human population.

Animals↗
PubMedDate not supplied

Efficacy of single dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.

In a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mg alone or in combination with ivermectin (iver) 400 micrograms/kg or diethylcarbamazine citrate (DEC) 6 mg/kg was compared with a single dose of the combination DEC 6 mg/kg and iver 400 micrograms/kg over a period of 15 months after treatment. All but one subject, with 67 microfilariae (mf)/mL, had pre-treatment counts > 100 mf/mL. All 4 treatments significantly reduced mf counts, but alb/iver was the most effective regimen for clearing mf from night blood: 9 of 13 subjects (69%) were amicrofilaraemic by membrane filtration 15 months after treatment compared to one of 12 (8%), 3 of 11 (27%), and 3 of 10 (30%) in the groups treated with alb, alb/DEC, and DEC/iver, respectively. Filarial antigen tests suggested that all 4 treatments had significant activity against adult W. bancrofti; alb/DEC had the greatest activity according to this test, with antigen levels decreasing by 77% 15 months after therapy. All 4 regimens were well tolerated and clinically safe, although mild, self-limited systemic reactions were observed in all treatment groups. These results suggest that alb/iver is a safe and effective single dose regimen for suppression of microfilaraemia in bancroftian filariasis that could be considered for control programmes. Additional benefits of this combination are its potent, broad spectrum activity against intestinal helminths and potential relative safety in areas of Africa where DEC cannot be used for filariasis control because of co-endemicity with onchocerciasis or loiasis.

Adolescent↗
PubMed2003

Diagnosis of human filariases (except onchocerciasis).

The traditional method of diagnosing filarial infections is to examine blood or skin samples for microfilariae and for many this is still the standard procedure. However, since the present global campaign to eliminate lymphatic filariasis new diagnostic tools have emerged like PCR, antigen detection using finger-prick blood taken during the day and ultrasound to visualize adult worms. The last two can be applied in endemic countries with limited resources and enable the detection of early infections. As well as their value in control schemes, the latter is particularly important for the individual since recent research has shown that damage is usually caused long before symptoms appear. The usefulness in different situations and the advantages and disadvantages of the various new tools for diagnosis of lymphatic filariasis are discussed. For loiasis, immunodiagnostic methods have not been very successful but repetitive DNA sequences in the Loa genome have been found to be species specific. Techniques based on them are particularly useful for diagnosing cases of occult infection without microfilaraemia. There have been no advances in the diagnosis of Mansonella perstans but both immunodiagnostic and PCR tests show promise in differentiating M. streptocerca, and the latter in differentiating M.ozzardi, from Onchocerca. In addition to the human filariae, the dog parasites Dirofilaria immitis and D. repens can also occur in humans but do not produce microfilariae in them. ELISAs and PCR probes have been devised and can usefully differentiate between pulmonary dirofilariasis and lung cancer.

Animals↗
PubMed2001

[New indications of ivermectin].

INTRODUCTION: Ivermectin is a semi-synthetic derivative of a family of macrocyclic lactones. This drug has a broad-spectrum anti-parasitic effect against various nematodes and ectoparasites. CURRENT KNOWLEDGE AND KEY-POINTS: Onchocerciasis and lymphatic filariasis are common indications. More recently ivermectin has been recommended in the treatment of strongyloidiasis and scabies. FUTURE PROSPECTS AND PROJECTS: Promising results have been shown in the treatment of ascariasis, cutaneous larva migrans, loiasis and head lice.

Antiparasitic Agents↗
PubMed2000

Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations.

Repeated, single, oral doses of combinations of ivermectin, diethylcarbamazine (DEC) or albendazole are recognized as important tools for parasite control in lymphatic filariasis. In order to assess the effects of re-treatment using these combinations in Brugia malayi infections, 40 asymptomatic microfilaraemics were re-treated at the end of the first year, with an additional, single, dose of the combination they had previously received. They were then followed-up for another year. The subjects, of both sexes and aged 14-70 years, each received a two-drug combination: ivermectin (200 micrograms/kg) with DEC (6 mg/kg); ivermectin (200 micrograms/kg) with albendazole (400 mg); or DEC (6 mg/kg) with albendazole (400 mg). The kinetics of microfilarial clearance were similar to that seen during the first treatment, the members of the two groups given DEC having less intense microfilaraemias, 1 year after the re-treatment, than those given ivermectin with albendazole (P < 0.001 for each comparison). At this time, the two DEC groups also had a higher proportion of amicrofilaraemic individuals (22 of 26) than the ivermectin + albendazole group (three of nine). There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment. In countries such as India, where there is no co-endemicity of onchocerciasis or loiasis, the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole. Where there is no access to ivermectin, transmission control must be based on DEC alone or in combination with albendazole.

Adolescent↗
PubMed1997

Comparison of the use of skin scarification and skin biopsies to determine the prevalence and intensity of Onchocerca volvulus infection.

Two methods for the detection of Onchocerca volvulus microfilariae in the skin were compared in a population-based survey in Gatete, Murama and Jerama, three 'collines' (administrative units) in Burundi. Of the 513 subjects examined, each by both methods, 131 (25.5%) were found positive by skin scarification and 119 (23.2%) by membrane filtration of the fluid in which two skin snips had been incubated. Whilst the sensitivity of the two methods was similar (90% for scarifications and 82% for skin snips), more microfilariae were found by scarification than by biopsy (with geometric mean numbers of 9.1 and 4.1, respectively). Also, more of the cases with infections of low intensity (i.e. < or = 5 microfilariae detected) were found by scarification than by skin snipping (77.9% v. 60.3%; P = 0.06). The endemicity of onchocerciasis and age- and sex-specific prevalences and intensities of infection could be determined equally well using either method. The shortcomings of past comparisons between scarification and skin-snip methods are discussed. Skin scarification has many advantages for the detection of infected individuals in rural health centres and for use in population-based surveys. It may also be helpful when mixed filarial infections are present (especially where onchocerciasis and loiasis co-occur).

Adolescent↗
PubMed1999

Treatment of the microfilaraemia of asymptomatic brugian filariasis with single doses of ivermectin, diethylcarbamazine or albendazole, in various combinations.

Several new chemotherapeutic tools are now available for the control of lymphatic filariasis. Combinations of single doses of antifilarial drugs are generally superior to single drugs. The efficacy and safety of albendazole in combination with diethylcarbamazine (DEC) or ivermectin, for the treatment of Brugia malayi infection, were investigated, for the first time, in an open, hospital-based study. Fifty-one asymptomatic microfilaraemics (with 108-4034 microfilariae/ml; median = 531) of both sexes and aged 14-70 years were randomly allocated to receive single-dose treatments of ivermectin (200 micrograms/kg) with diethylcarbamazine (DEC; 6 mg/kg), ivermectin (200 micrograms/kg) with albendazole (400 mg), DEC (6 mg/kg) with albendazole (400 mg), or albendazole (400 mg) alone. Albendazole alone had no effect on the microfilarial levels at the 1-year follow-up but both groups given DEC had significantly lower microfilaraemias (P < 0.015 and P < 0.02) than that given ivermectin with albendazole. Overall, 47%-64% of those given DEC but only 14% of those given ivermectin with albendazole appeared to be amicrofilaraemic 1 year post-treatment. The adverse reactions seen in the study were mild, transient and qualitatively similar to those seen earlier with ivermectin and DEC. The combination of DEC and albendazole, both well tested drugs, offers a new option for countries such as India where there is no onchocerciasis or loiasis and where ivermectin may not be immediately available. The direct and indirect effects of albendazole on intestinal helminths would be additional benefits.

Adolescent↗
PubMed2001

Comparative analysis of natural killer cell activity, lymphoproliferation and lymphocyte surface antigen expression in nonhuman primates housed at the CIRMF Primate Center, Gabon.

Six different species of nonhuman primates housed at the CIRMF Primate Center, cynomolgus monkeys (Macaca fascicularis), rhesus monkeys (Macaca mulatta), mandrills (Mandrillus sphinx), vervets (Cercopithecus aethiops pygerythrus), chimpanzees (Pan troglodyte) and baboons (Papio hamadryas), were evaluated for their natural killer cell activity and for the ability of their peripheral blood mononuclear cells to proliferate in response to known mitogens (concanavalin A, phytohemagglutinin and staphylococcal enterotoxin A) and to react with a panel of mouse monoclonal antibodies directed against human leukocyte surface antigens. Basic information on normal immune functions in these primates is important because of their use as experimental animal models for the study of human diseases such as acquired immunodeficiency syndrome (AIDS), hepatitis, loiasis and malaria.

Animals↗