Clinical picture,epidemiology and outcome of <Emphasis Type="Italic">Loa</Emphasis>-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon

In August 2002, 65 cases of Loa-associated neurological Serious Adverse Events were reported after ivermectin treatment. The first signs, occurring within the 12-24 hours following treatment, included fatigue, generalized arthralgia, and sometimes agitation, mutism, and incontinence. Disorders of consciousness, including coma, generally appeared between 24 and 72 hours, and showed a rapid variation with time. The most frequent objective neurological signs were extrapyramidal. The patients presented with haemorrhages of the conjunctiva and of the retina. Biological examinations showed a massive Loa microfilaruria, the passage of Loa microfilariae into the cerebrospinal fluid, haematuria, and an increase in the C-reactive protein, all of which have been correlated with the high intensity of the initial Loa microfilaraemia. Eosinophil counts decreased dramatically within the first 24 hours, and then rose again rapidly. Electroencephalograms suggested the existence of a diffuse pathological process within the first weeks; the abnormalities disappearing after 3-6 months. Death may occur when patients are not properly managed, i.e. in the absence of good nursing. However, some patients who recovered showed sequelae such as aphasia, episodic amnesia, or extrapyramidal signs. The main risk factor for these encephalopathies is the intensity of the initial Loa microfilaraemia. The disorders of consciousness may occur when there are >50,000 Loa microfilariae per ml. The possible roles of co-factors, such as Loa strains, genetic predisposition of individuals, co-infestations with other parasites, or alcohol consumption, seem to be minor but they should be considered. The mechanisms of the post-ivermectin Loa-related encephalopathies should be investigated to improve the management of patients developing the condition.     

The effect of Brugia pahangi infection on survival of susceptible and refractory species of the Aedes scutellaris complex

Life table statistics were used to examine the survival functions of filarial susceptible and refractory species of the Aedes scutellaris (Walker) group of mosquitoes, following infection with high and moderate doses of Brugia pahangi (Buckley & Edeson). Survivorship curves and hazard function curves were generated, and the median survival times and the proportions of mosquitoes surviving beyond the extrinsic incubation period of the parasite were determined. In the susceptible populations of Aedes polynesiensis Marks, Ae. pseudoscutellaris (Theobald) and Ae.tabu Ramalingam & Belkin a dose-response relationship was detected between parasite load and mortality. This relationship was characterized by a significant reduction in the proportions of infected female mosquitoes surviving at days 1 and 9 postinfection, reduction in the median survival times and an increase in the hazard rates as the infectious dose increased. The survival of the refractory species, Ae.alcasidi Huang and Ae.katherinensis Woodhill was not significantly affected by the infection. A positive correlation between microfilaraemia in the vertebrate host and parasite load in the susceptible mosquito populations was also observed. Regression analysis of the number of parasites recovered from susceptible mosquitoes at the time of death showed that mosquitoes at highest risk of dying harboured from 11.6 to 19.4 infective larvae when fed on a gerbil with sixty-five microfilariae per 20 microliters blood; this resulted in 34.4-40.2% mortality by day 9 postinfection. A mean number of 32.6-46.9 infective larvae was observed when these populations were exposed to a gerbil with a microfilaraemia of 150 mf/20 microliters and resulted in 72.8% to 80% mortality in these populations. Viable infective larvae were recovered from infected mosquitoes up to 50 days postinfection.     

Mapping the distribution of Loa loa in Cameroon in support of the African Programme for Onchocerciasis Control

BACKGROUND: Loa loa has recently emerged as a filarial worm of significant public health importance as a consequence of its impact on the African Programme for Onchocerciasis Control (APOC). Severe, sometimes fatal, encephalopathic reactions to ivermectin (the drug of choice for onchocerciasis control) have occurred in some individuals with high Loa loa microfilarial counts. Since high density of Loa loa microfilariae is known to be associated with high prevalence rates, a distribution map of the latter may determine areas where severe reactions might occur. The aim of the study was to identify variables which were significantly associated with the presence of a Loa microfilaraemia in the subjects examined, and to develop a spatial model predicting the prevalence of the Loa microfilaraemia. METHODS: Epidemiological data were collected from 14,225 individuals living in 94 villages in Cameroon, and analysed in conjunction with environmental data. A series of logistic regression models (multivariate analysis) was developed to describe variation in the prevalence of Loa loa microfilaraemia using individual level co-variates (age, sex, microl of blood taken for examination) and village level environmental co-variates (including altitude and satellite-derived vegetation indices). RESULTS: A spatial model of Loa loa prevalence was created within a geographical information system. The model was then validated using an independent data set on Loa loa distribution. When considering both data sets as a whole, and a prevalence threshold of 20%, the sensitivity and the specificity of the model were 81.7 and 69.4%, respectively. CONCLUSIONS: The model developed has proven very useful in defining the areas at risk of post-ivermectin Loa-related severe adverse events. It is now routinely used by APOC when projects of community-directed treatment with ivermectin are examined.     

Encephalopathy in a patient with loiasis treated with albendazole: A case report

BackgroundLoiasis is a vector-borne parasitic infection endemic across many areas of Central and West Africa. Its treatment is tricky due to the risk of serious neurologic adverse events occurring after the administration of microfilaricidal drugs, like diethylcarbamazine or ivermectin, in subjects with high pre-treatment microfilarial load. Albendazole is currently recommended to slowly reduce microfilaremia before curative regimen is prescribed.Case presentationWe report the case of a 25-year-old man from Guinea-Conakry who was incidentally diagnosed with highly microfilaremic Loa loa infection. A three weeks regimen of albendazole was prescribed. Minor neurologic side effects occurred after two weeks of administration, while serious encephalopathy developed one week later. Clinical and electroencephalographic features of the patient resembled those of an immune-mediated encephalitis. After exclusion of other causes of encephalopathy, treatment-related Loa loa encephalopathy induced by albendazole was suspected. Corticosteroid treatment was administered and the patient recovered.DiscussionOur case confirms that Loa loa treatment-related encephalopathy may occur even during albendazole treatment. The clinical and electroencephalographic similarities between Loa loa albendazole-related encephalopathy and immune-mediated encephalitis suggest the possibility of an underlying inflammation-based pathogenesis. Although corticosteroid administration is not recommended in Loa loa ivermectin-induced encephalopathy, in this case of Loa loa albendazole-induced encephalopathy it may have played a therapeutic role.     

A controlled prospective trial of the prophylactic effect of a single dose of ivermectin against Onchocerca volvulus

A clinical trial was conducted in Cameroon in order to evaluate in humans the possible effect of a single dose of ivermectin (150 micrograms per kg) on the pre-adult stages of Onchocerca volvulus. The incidence of the skin microfilariae was measured in two groups of patients who initially had negative biopsies, and who were subsequently treated, immediately after the seasonal peak of transmission of O. volvulus, either with a combination of ivermectin + ferrous sulphate, or with ferrous sulphate alone. One year after the treatment, i.e. 14 months after the start of the transmission period, the proportion of patients with positive skin biopsies, and their mean microfilarial loads, did not differ significantly between the two groups. Thus a single dose of ivermectin does not seem to have any perceptible prophylactic effect against O. volvulus.     

A comparative study of different albendazole and mebendazole regimens for the treatment of intestinal infections in school children of Usigu Division, western Kenya

A clinical trial to compare the effectiveness of 4- and 6-mo repeated treatment with albendazole 600 mg (Zentel, SmithKline Beecham) or mebendazole 600 mg (Vermox, Janssen) on geohelminth infections was carried out on children in 6 primary schools; the study included 1,186 children, ages 4 to 19 yr. Kato-Katz examination was performed on stool samples before and after treatment. Overall, albendazole produced better cure rates and egg reduction rates for geohelminths. The cure rates for albendazole were 92.4% for hookworm infection, 83.5% for Ascaris lumbricoides, and 67.8% for Trichuris trichiura. Mebendazole given either 2 or 3 times in a year had cure rates of 50 and 55.0% (respectively) for hookworm, 79.6 and 97.5% for A. lumbricoides, and 60.6 and 68.3% for T. trichiura infection. The geometric mean intensity of hookworm eggs per gram (epg) of stool decreased by 96.7% after albendazole treatment compared with 66.3 and 85.1%, respectively, for 2 or 3 doses of mebendazole (P < 0.05) over the same period. Reductions in epg for A. lumbricoides and T. trichiura were comparable for both drugs. Our results indicate that treatment with albendazole at a 6-mo interval was more effective than mebendazole regimens and may be the best choice for use in the control of the 3 geohelminths.     

Studies with Brugia pahangi. 16. Precipitation antibody in infected cats detected by counterimmunoelectrophoresis

In cats infected with normal, or irradiated, infective (L3) larvae of Brugia pahangi counterimmunoelectrophoresis revealed the presence of antibody to soluble antigens derived from microfilariae, adults and infective larvae of the same parasite. Infected cats with a persistently high to moderate microfilaraemia gave positive precipitin reactions to L3, microfilarial and adult worm antigens. Cats which had become amicrofilaraemic had antibody to L3 and microfilarial antigens but not to adult worm antigen. Serum from cats inoculated with irradiated L3 larvae produced a precipitin reaction only to the L3 antigen.     

Studies on the Malayan forest rat filaria, Breinlia booliati: periodicity and microfilaraemic patterns during the course of infection.

Breinlia booliati exhibited nocturnal subperiodicity in its natural host, Rattus sabanus in contrast to experimentally infected laboratory-reared albine rats which showed irregular fluctuations of microfilariae throughout the 24 hour cycle. All the infected albino rats showed a prepatent period between 11-14 weeks postinoculation. Three patterns of microfilaraemia were discerned during the course of infection 38/49 rats displayed a single peak, 4/49 displayed 2 peaks about 12-15 weeks apart and 7/49 showed a sustained high plateau-like pattern of microfilaraemia. Cortisone had no effect on microfilarial levels when administered to rats near postpatency and some at postpatency.     

The effect of sodium bicarbonate on a single dose of diethylcarbamazine therapy in patients with bancroftian filariasis in Kenya

An attempt was made to examine the effect of a combination of diethylcarbamazine citrate (DEC-C) and sodium bicarbonate (NaHCO₃) on the pharmacokinetics of diethylcarbamazine (DEC), side-reactions and reduction of the microfilarial density of patients with Wuchereria bancrofti infection at a hospital in Nairobi, Kenya. The microfilariae carriers received DEC-C at 6 mg/kg or 3 mg/kg with or without NaHCO₃ at 75 mg/kg body weight. The patients treated with a combination of drugs showed alkaline urine for 4 h post-treatment, while patients treated with DEC-C alone showed acidic urine. Although no significant difference was detected in the DEC half-life value and other pharmacokinetic parameters between patients treated with DEC-C (6 mg/kg) plus NaHCO₃ (75 mg/kg) and those treated with DEC-C (6 mg/kg) alone, the general tendency was that in patients receiving NaHCO₃ the first-order elimination rate constant decreased and serum elimination half-life and area under the serum concentration-time curve values increased. There was a significant difference between the mean values of the first-order absorption rate constant, the first-order elimination rate constant, and the time to maximum serum concentrations for the patients receiving DEC-C at 3 mg/kg plus NaHCO₃ at 75 mg/kg and those for the group receiving DEC-C at 6 mg/kg alone. There was no difference in frequency and severity of the side-reactions between patients receiving DEC-C at 6 mg/kg plus NaHCO₃ at 75 mg/kg, DEC-C at 3 mg/kg plus NaHCO₃ at 75 mg/kg, and DEC-C at 6 mg/kg alone. During the initial 5 days post-treatment, there was no significant difference in reduction of microfilarial density among these three groups. In the field, an attempt was made to examine the possibility of increased antifilarial effect using a combination of DEC-C and NaHCO₃. The patients were examined for microfilariae, given DEC-C at 6 mg/kg with or without NaHCO₃ at 75 mg/kg, and examined for microfilariae again 1 year later. Although the cure rate was the same among the groups, the percentage reduction in microfilarial density of the patients receiving DEC-C plus NaHCO₃ was significantly greater than those of patients receiving DEC-C alone. A combination of DEC-C with NaHCO₃ will be of practical value in a single dose of DEC-C for the mass-treatment of bancroftian filariasis.     

Dipetalonema vitae: survival of adult females and microfilarial release in both a chemically defined and serum-supplemented medium

Studies were conducted on survival and microfilarial release of afult Dipetalonema viteae in culture, using worms of various ages derived from jirds. In chemically defined NI medium (a 1:1 mixture of NCTC 135 and Iscove's modified Dulbecco's medium) under a gas phase of 5% CO2 in nitrogen (pO2 of medium approximately 40 mm Hg), the peak of microfilarial release of several thougsand microfilariae per female per 24 hr occurred at approximately day 10. Thereafter, microfilarial release declined and generally ended about 1 mo after the start of culture. The adult females moved actively for about 50 days or more and survived up to 82 days in NI medium alone. The females in NI medium supplemented with fetal bovine serum showed serpentine movement for approximately 2 mo. Some of the worms survived more than 83 days. The total number of microfilariae deposited in culture by D. viteae increased as adult females grew in size (volume) over time. Microfilarial deposition continued to increase after worms reached maximum size, deposition reaching a plateau between approximately 300 and 400 days of age. Thereafter, microfilarial deposition decreased as females continued to age. Addition of fetal bovine serum to the NI medium increased the number of microfilariae released and extended the period of release.     

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind,Randomized, Placebo-Controlled Trial

BackgroundLoiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely.MethodologySixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001–50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment.

Principal Findings

None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively.

Conclusions/ Significance

The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas.     

Antifilarial effect of Zingiber officinale on Dirofilaria immitis

Dogs, naturally infected with Dirofilaria immitis, were treated with the residues of the alcoholic extracts of the rhizomes of Zingiber officinale (ginger). Twelve subcutaneous injections of the extract given at 100 mg/kg reduced microfilarial concentration in blood by a maximum of 98%. Fifty five days after the last injection there was 83% reduction in microfilarial concentration suggesting partial destruction of adult worms. Half of the treated dogs showed some lethargy at the beginning of treatment possibly due to the mass annihilation of microfilariae in blood.     

Poor efficacy of albendazole for the treatment of human taeniasis

In order to evaluate the efficacy of albendazole for the treatment of taeniasis, regimens of 400 mg x 1 day, 800 mg x 2 days, 800 mg x 3 days, 1200 mg x 2 days, and 1200 mg x 3 days were compared. Of 66 cases treated and investigated 7-14 days after treatment, 52 were still expelling proglottids. Three months posttreatment, these cases were re-treated with atabrine at 1.2 g per case for males and 1.0 g per case for females. Fifty-seven patients expelled worms or parts of tapeworms. The nine negatives may represent the number cured by the treatment with albendazole. The cure rates with albendazole for various regimens were up to 50% for 800 mg x 3 days, 1200 mg x 2 days or 1200 mg x 3 days, 14.3% for 800 mg x 2 days, and 0% for 400 mg x 1 day or 800 mg x 1 day. This study shows that albendazole is not very effective in the treatment for taeniasis.     

Cattle protected from onchocerciasis by ivermectin are highly susceptible to infection after drug withdrawal

Ivermectin administration is now the major tool in the control of human onchocerciasis (caused by Onchocerca volvulus) based on its suppression of microfilariae and hence the prevention of disease. However, in Africa, transmission is not eliminated and treated populations continue to be exposed to infective larval (L(3)) challenge, albeit at reduced levels. We have investigated whether protective immunity might develop under such conditions using the analogous host-parasite system Onchocerca ochengi in cattle, based on our previous findings in cattle exposed to challenge, that in vivo ivermectin attenuates the development of adult infections and that irradiation-attenuated L(3) induce significant protection. In a two-phase prospective study over 4 years, groups of cattle were exposed to severe natural challenge. In the first phase, 38/40 animals treated either with ivermectin or with moxidectin at either monthly or 3-monthly intervals had not developed detectable infections after 22 months of exposure whereas, in a non-treated control group (n = 14) nodule prevalence was 78.6% and the geometric mean (range) nodule load was 4.8 (0-33). In the second phase, all drug treatments were withdrawn, a new control group (n = 8) introduced, and exposure continued at the same site. After 24 months, all groups had developed patent infections, with geometric mean (range) nodule loads of 17.4 (4-99), 38.4 (10-111), 50.7 (26-86), 14.3 (0-69) and 14.7 (0-55) for the control, monthly-ivermectin, 3-monthly ivermectin, monthly moxidectin and 3-monthly moxidectin groups, respectively. There was no evidence of protection-indeed the 3-monthly ivermectin group was significantly (P < 0.05) hyper-susceptible. In addition, microfilarial densities and the rate of increase in microfilarial load were significantly higher (P < 0.05) in the ivermectin-treated groups than in control animals. These results have important implications for ivermectin-based control of human onchocerciasis and suggest that humans exposed to ongoing transmission in endemic areas whilst receiving ivermectin are unlikely to develop immunity and will be highly susceptible should drug distribution cease.     

Rates of microfilarial production by Onchocerca volvulus are not cumulatively reduced by multiple ivermectin treatments

Regular distribution of ivermectin reduces onchocerciasis transmission and morbidity by killing, within humans, the microfilarial stage of the parasite (microfilaricidal effect). In addition, ivermectin exerts a so-called embryostatic effect by which microfilarial production by the adult female worm becomes suppressed during a number of weeks after treatment. To assess the overall effect of ivermectin on onchocerciasis transmission and evaluate the likelihood of local elimination of the infection it is important to estimate the magnitude of the anti-fertility effect over the course of a treatment programme. Estimates of the effect of repeated drug treatments on the production of microfilariae by adult Onchocerca volvulus were obtained by developing a model that was fitted to data collected from three hyperendemic communities in Guatemala, where eligible residents received ivermectin twice per year for two and a half years. The data consist of microfilarial load measurements in the skin, collected just before each six-monthly treatment during the programme. The model that is developed describes the dynamics of an individual host's expected microfilarial load over the 30-month study period. We adopt a Bayesian approach and use Markov chain Monte Carlo (McMC) techniques to fit the model to the data. Combining estimates from the three villages, average microfilarial production in the first six months post-treatment was reduced by ~64% of its pre-treatment level, regardless of values chosen for the pre-ivermectin fertility rate within plausible ranges. Increased adult worm death rate after treatment (to mimic removal of macrofilariae via nodulectomy during the programme) resulted in a smaller estimated magnitude of the embryostatic effect (rate of microfilarial production was reduced by ~58% of pre-ivermectin value). After subsequent treatments, the rate of microfilarial production appeared to be similarly decreased. The data and analyses therefore do not support the hypothesis of a cumulative effect of multiple ivermectin treatments on microfilarial production by female worms.     

Diagnostic performance of capillary and venous blood samples in the detection of Loa loa and Mansonella perstans microfilaraemia using light microscopy

BackgroundLoa loa and Mansonella perstans–the causative agents of loiasis and mansonellosis—are vector-borne filarial parasites co-endemic in sub-Saharan Africa. Diagnosis of both infections is usually established by microscopic analysis of blood samples. It was recently established that the odds for detecting Plasmodium spp. is higher in capillary (CAP) blood than in venous (VEN) blood. In analogy to this finding this analysis evaluates potential differences in microfilaraemia of L. loa and M. perstans in samples of CAP and VEN blood.MethodsRecruitment took place between 2015 and 2019 at the CERMEL in Lambaréné, Gabon and its surrounding villages. Persons of all ages presenting to diagnostic services of the research center around noon were invited to participate in the study. A thick smear of each 10 microliters of CAP and VEN blood was prepared and analysed by a minimum of two independent microscopists. Differences of log2-transformed CAP and VEN microfilaraemia were computed and expressed as percentages. Furthermore, odds ratios for paired data were computed to quantify the odds to detect microfilariae in CAP blood versus in VEN blood.ResultsA total of 713 participants were recruited among whom 52% were below 30 years of age, 27% between 30–59 years of age and 21% above 60 years of age. Male-female ratio was 0.84. Among 152 participants with microscopically-confirmed L. loa infection median (IQR) microfilaraemia was 3,650 (275–11,100) per milliliter blood in CAP blood and 2,775 (200–8,875) in VEN blood (p<0.0001), while among 102 participants with M. perstans this was 100 (0–200) and 100 (0–200), respectively (p = 0.44). Differences in linear models amount up to an average of +34.5% (95% CI: +11.0 to +63.0) higher L. loa microfilaria quantity in CAP blood versus VEN blood and for M. perstans it was on average higher by +24.8% (95% CI: +0.0 to +60.5). Concordantly, the odds for detection of microfilaraemia in CAP samples versus VEN samples was 1.24 (95% CI: 0.65–2.34) and 1.65 (95% CI: 1.0–2.68) for infections with L. loa and M. perstans, respectively.ConclusionThis analysis indicates that average levels of microfilaraemia of L. loa are higher in CAP blood samples than in VEN blood samples. This might have implications for treatment algorithms of onchocerciasis and loiasis, in which exact quantification of L. loa microfilaraemia is of importance. Furthermore, the odds for detection of M. perstans microfilariae was higher in CAP than in VEN blood which may pre-dispose CAP blood for detection of M. perstans infection in large epidemiological studies when sampling of large blood quantities is not feasible. No solid evidence for a higher odds of L. loa microfilariae detection in CAP blood was revealed, which might be explained by generally high levels of L. loa microfilaraemia in CAP and VEN blood above the limit of detection of 100 microfilariae/ml. Yet, it cannot be excluded that the study was underpowered to detect a moderate difference.     

Efficacy of mebendazole and albendazole against Trichinella spiralis in mice

Changes in the sensitivity of Trichinella spiralis to anthelmintic treatment during the first 3 days of infection in mice were studied. Oral administration of either mebendazole or albendazole at 6.25 mh/kg 2 hr after exposure to infection eliminated 95-100% of the worms as determined at necropsy on day 7 postinoculation. Beyond the first day of infection the sensitivity of the parasite to benzimidazole therapy was much reduced and an oral dose of 50 mg/kg was only partially but significantly active against the adult worms. Despite decline in drug sensitivity during the enteral phase, gavage administration of either mebendazole or albendazole at 50 mg/kg for 5 consecutive days during the invasive phase of infection significantly reduced (96 and 67%, respectively) the number of larvae subsequently recovered from host musculature on day 45 postinoculation.     

Suppression of the parasitemia in rodent filariasis (Litomosoides carinii) by immunization with BCG and microfilaria. II. Intravenous BCG application

By intravenous (i.v.) inoculation of living tuberculosis bacteria (BCG) non-specific resistance to microfilariae of Litomosoides carinii (Filarioidea) is induced in cotton rats. This is only possible using the preparation "Immune-BCG Pasteur F" (suspended germs), but not with "Vaccin-BCG pour scarifications" (lyophilized tuberculosis bacteria). After inoculation of Immune-BCG, followed by a challenge infection by 60 infective larvae 6 weeks later, a patent infection develops. However, the level of microfilaraemia is constantly lower than in the control. After challenge infection 12 weeks later, this effect has disappeared. Immune-BCG has no influence on the worm load or the output of microfilariae by the adult worms. If i.v. inoculation of Immune-BCG is combined with a subcutaneous injection of specific antigen--living embryos from the uteri of adult worms--the BCG-activated immune system undergoes specific sensitization. Upon challenge infection 6 weeks later, the microfilaraemia is completely suppressed, but the worm load and production of microfilariae by the adult female worms are normal. If Immune-BCG is injected i.v. 3 days before intraperitoneal injection of freeze-killed microfilariae, there is still constantly reduced microfilaraemia when challenge infection follows 12 weeks later. Obviously, the effect of this relatively weak antigen may be increased by BCG stimulation.     

Treatment of co-infection with bancroftian filariasis and onchocerciasis: a safety and efficacy study of albendazole with ivermectin compared to treatment of single infection with bancroftian filariasis

BACKGROUND: In order to use a combination of ivermectin and albendazole for the elimination of lymphatic filariasis, it is important to assess the potential risk of increased adverse events in individuals infected with both lymphatic filariasis and onchocerciasis. We compared the safety and efficacy of albendazole (400 mg) in combination with ivermectin (150 micrograms/kg), for the treatment of co-infections of Wuchereria bancrofti and Onchocerca volvulus with single infection of W. bancrofti. METHODS: The safety study on co-infections was a crossover, double blind design, while for the single infection of bancroftian filariasis an open design comparing two treatments was used. For co-infection, one group was allocated a single dose of ivermectin (150 micrograms/kg) plus albendazole (400 mg) (Group A). The other group received placebo (Group B). Five days later the treatment regime was reversed, with the Group A receiving placebo and Group B receiving treatment. For the single bancroftian filariasis infection, one group received a single dose of albendazole (400 mg) plus ivermectin (150 microg/kg) (Group C) while the other group received a single dose of albendazole (400 mg) alone (Group D). Blood and skin specimens were collected on admission day, day 0, and on days 2, 3, and 7 to assess drug safety and efficacy. Thereafter, blood and skin specimens were collected during the 12 months follow up for the assessment of drug efficacy. Study individuals were clinically monitored every six hours during the first 48 hours following treatment, and routine clinical examinations were performed during the hospitalisation period and follow-up. RESULTS: In individuals co-infected with bancroftian filariasis and onchocerciasis, treatment with ivermectin and albendazole was safe and tolerable. Physiological indices showed no differences between groups with co-infection (W. bancrofti and O. volvulus) or single infection (W. bancrofti). The frequency of adverse events in co-infected individuals was 63% (5/8, Group A, albendazole + ivermectin) and 57% (4/7, Group B, placebo) and of mild or moderate intensity. In single W. bancrofti infection the frequency of adverse events was 50% (6/12, Group C, albendazole + ivermectin) and 38% (5/13, Group D, albendazole) and of a similar intensity to those experienced with co-infection. There were no differences in adverse events between treatment groups. There was no significant difference in the reduction of microfilaraemia following treatment with albendazole and ivermectin in groups with single or co-infection. CONCLUSION: Our findings suggest that ivermectin plus albendazole is a safe and tolerable treatment for co-infection of bancroftian filariasis and onchocerciasis.     

Brugia malayi microfilaraemia in mice: a model for the study of the host response to microfilariae

Microfilariae of Brugia malayi were obtained from the peritoneal cavities of infected gerbils and were then injected intravenously into mice. A sub-periodic, nocturnal microfilaraemia was produced. The level of microfilaraemia was proportional to the number of parasites injected, with approximately 1-3% of microfilariae being found in the peripheral circulation. The duration of microfilaraemia was proportional to the number of parasites injected; it subsided by 30 days after injection of 104 microfilariae but was still present at a low level 120 days after injection of 2 x 105 microfilariae. A transient splenomegaly developed after injection of microfilariae. Histopathological examination revealed large numbers of microfilariae free in the lumens of pulmonary small blood vessels and without any accompanying inflammatory reaction. Lesser numbers of microfilariae were seen in the cardiac blood and hepatic and renal blood vessels for the first few days after injection. There was cellular proliferation in the splenic white pulp and vascular congestion of the red pulp. Microfilariae labelled with 51Cr were injected intravenously; 57% of radioactivity was found in the lungs, 8.5% in the liver and 2.9% in the spleen. Mice developed immediate hypersensitivity reactions to B. malayi antigen by 4 weeks after injection, but Arthus and delayed hypersensitivity reactions were not seen at any time. when mice which had been injected 5 months previously were challenged with a 2nd injection of microfilariae, there was an accelerated clearance of parasites over 2 weeks and a marked peripheral blood eosinophilia developed. In contrast with natural infections, in which the continuous production of microfilariae complicates assessment, this model provides a system in which factors controlling the circulation of microfilariae in the bloodstream can be studied independently.