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PubMed1990

Persistent lower respiratory tract inflammation associated with interstitial lung disease in patients with tropical pulmonary eosinophilia following conventional treatment with diethylcarbamazine.

Tropical pulmonary eosinophilia (TPE) presents as an acute syndrome with dyspnea, fluffy infiltrates, and rounded opacities on the chest radiograph, reduced lung function, marked eosinophilia in the blood and lower respiratory tract, and high titers of specific IgE and IgG antifilarial antibodies. The standard therapy for TPE is a 3-wk course of diethylcarbamazine (DEC) following which there is almost always a marked improvement in all parameters. However, clinical observations suggest that the disease can persist despite DEC therapy and lead to chronic dyspnea with restrictive lung impairment. To evaluate the concept that DEC therapy is not completely "curative" for TPE, but rather leaves most individuals with a mild, chronic form of TPE defined by persistent inflammation of the lower respiratory tract, we evaluated 23 individuals an average of 12 +/- 2 months following a standard 3-wk course of diethylcarbamazine for acute TPE. In the majority there were mild, persistent symptoms referrable to the lung, chest X-ray abnormalities, blood eosinophilia, and elevated serum IgE and filarial specific IgG. On the average, lung function was consistent with the presence of chronic, mild interstitial lung disease. When the inflammatory cells from the lower respiratory tract were examined, there was a persistent eosinophilic alveolitis (TPE/post-DEC 1769 +/- 376 eosinophils/microliters epithelial lining fluid; normal subjects 256 +/- 38, p less than 0.02). Evaluation of the lower respiratory tract inflammatory cells recovered from the TPE/post-DEC-treated individuals demonstrated spontaneous release of exaggerated amounts of O2-. and H2O2 compared to normal subjects (p less than 0.05, both comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1985

Diethylcarbamazine inhibits acute and chronic hypoxic pulmonary hypertension in awake rats.

Leukotriene inhibitors preferentially inhibit the acute pressor response to hypoxia in isolated rat lungs. If leukotrienes are important in hypoxic pulmonary vasoconstriction, then inhibition of their synthesis could prevent the development of chronic hypoxic pulmonary hypertension. We found that diethylcarbamazine (DEC), a leukotriene synthesis blocker, reversibly inhibited acute hypoxic pulmonary vasoconstriction in the awake rat. Rats exposed to chronic hypobaric hypoxia showed pulmonary hypertension and the production of a slow-reacting substance compared with low altitude control rats. The higher of 2 doses of DEC blocked the pulmonary hypertension and the production of slow-reacting substance in all of the hypoxic rats treated. The lower dose of DEC attenuated the pulmonary hypertension in only some of the rats. Changes in weight gain, hematocrit, or generation of prostacyclin did not explain the prevention of the pulmonary hypertension by DEC. We conclude that diethylcarbamazine inhibits acute and chronic pulmonary hypertension in the intact rat.

Acute Disease↗

PubMed2002

Pharmacokinetics of diethylcarbamazine after single oral dose at two different times of day in human subjects.

In most Wuchereria bancrofti and Brugia malayi infections, the microfilaria are found in the blood in greatest number between 10 p.m. and 2 a.m., indicating that chronotherapy may be beneficial in treating such infections. This study reports the influence of time of administration on the pharmacokinetics of diethylcarbamazine (DEC) in healthy volunteers. The study was conducted in 12 healthy volunteers by administering a 150 mg single oral dose of diethylcarbamazine citrate at 0600 or 1800 h in a balanced crossover design with the approval of an institutional ethics committee. The subjects fasted for about 10 hours before and 3 hours after drug treatment. Blood samples were collected at predetermined time intervals, and the drug content in the serum was estimated using HPLC with an electrochemical detector. Pharmacokinetic analysis was performed using noncompartmental methods employing WinNonlin (version 3.1), and the means of various pharmacokinetic parameters were compared for any dosing time-related changes using a paired t-test at a probability level of 95%. The mean +/- SD values of pharmacokinetic parameters of DEC for the treatments at 0600 versus 1800 h were as follows: Cmax, 500+/-227 versus 637+/-401 ng/ml; tmax, 2.3+/-0.7 versus 2.7+/-1 h; Ka, 2.23+/-0.72 versus 1.96+/-0.97 h(-1); t1/2, 14.6+/-6.7 versus 11.4+/-4.9 h; AUC0-t, 5,334+/-1,853 versus 6,901+/-4,203 ng x h/ml; AUC0-infinity, 5,840+/-1,922 versus 7,220+/-4,205 ng x h/ml; CL/F, 36,058+/-19,011 versus 32,189+/-25,293 ml/h/kg; Vd/F, 570+/-225 versus 533+/-447 L; and MRT 17.7+/-5.9 versus 15.3+/-5.2 h. None of the parameters was significantly changed (p > 0.05) as a function of time of administration.

Administration, Oral↗

PubMed1985

Liver changes, following diethylcarbamazine administration, in microfilaremic dogs infected with Dirofilaria immitis.

Livers of dogs which were microfilaremic due to infection with Dirofilaria immitis were studied after the administration of diethylcarbamazine. Most dogs had a severe shock-like clinical reaction. The main hepatic features were congestion and hemorrhage around the central vein and irregularly scattered foci of inflammation. The severity of the vascular reaction was associated with the number of microfilariae in the livers. Mast cells associated with the vascular reaction were not degranulated, suggesting that histamine-mediated anaphylaxis was not the cause of the reaction. The observations suggest that the mediator of the hepatic vascular reaction originates from the microfilariae and is influenced or activated by diethylcarbamazine.

Animals↗

PubMed2003

The prevalences of Wuchereria bancrofti antigenaemia in communities given six rounds of treatment with diethylcarbamazine, ivermectin or placebo tablets.

The ICT filariasis card test was used to determine the prevalences of Wuchereria bancrofti antigenaemia among villagers in India. Prior to the tests, those living in the 15 study villages had been treated six times, in six rounds of mass treatment (with 54%-75% coverage) spread over 6 years, with single doses of diethylcarbamazine (five villages), ivermectin (five villages) or placebo (five villages). The corresponding overall prevalences (and ranges) of filarial antigenaemia were 20.2% (13.7%-28.6%), 22.6% (15.3%-34.3%) and 25.9% (22.6%-29.3%), respectively. The overall prevalence of antigenaemia in the villages where diethylcarbamazine (DEC) had been distributed (but not that in the 'ivermectin' villages) was significantly lower than that recorded in the 'placebo' villages (z =2.56; P <0.05). The prevalences of antigenaemia among the villagers aged 1-5 years (18.9%, 15.6% and 22.4% in the DEC, ivermectin and placebo villages, respectively) did not differ significantly with treatment (P >0.05). The results indicate that annual mass treatments based on DEC or ivermectin, with 54%-75% treatment coverage, may have only a limited effect on the prevalence of infection with adult W. bancrofti. The possible reasons for the antigenaemias observed are discussed.

Animals↗

PubMed1976

Clinical and laboratory changes consequent to diethylcarbamazine in patients with onchocerciasis.

This controlled study assesses the effect of a single oral dose of diethylcarbamazine (DEC) in a Guatemalan population with light infections of Onchocerca volvulus. From 8 to 24 hours after DEC, microfilariae were found with increased frequency in the urine, blood, and sputum, while the number of microfilariae per mm2 of skin decreased. The onset of signs and symptoms of reaction coincided with the appearance of microfilariae in the body fluids. Motile microfilariae were noted in the anterior chamber of the eye after the administration of diethylcarbamazine. Medication with corticosteroids appeared to reduce the symptoms of reaction without changing the laboratory results.

Adolescent↗

PubMed1985

The Mazzotti reaction following treatment of onchocerciasis with diethylcarbamazine: clinical severity as a function of infection intensity.

To determine definitively whether or not the severity of the Mazzotti reaction was correlated with infection intensity, as determined by skin snip quantification, 21 infected Ghanian patients were evaluated during 7 days of treatment with 200 mg/day of diethylcarbamazine. Serial blood, urine and skin biopsy samples were collected during the progression of the Mazzotti reaction. Hypotension, fever, adenitis and pruritus were all correlated with infection intensity in these patients while arthralgia and tachycardia were not. Peripheral blood eosinopenia and neutrophilia also correlated with intensity of infection and appeared to reflect the accumulation of degranulating eosinophils around "mobilized" microfilariae that migrated from the dermis to the epidermis after diethylcarbamazine (DEC). Other mobilized microfilariae apparently were cleared by the liver and resulted in abnormal liver enzyme levels in the serum which, again, were directly correlated with the patients' microfilarial density. Though the severity of the Mazzotti reaction clearly correlated with intensity of infection, the different times of onset of symptoms, and cellular and serum chemistry changes indicate that there are probably multiple infection intensity-dependent mechanisms responsible for mediating this complex reaction.

Adolescent↗

PubMed1994

Diethylcarbamazine salt in the control of lymphatic filariasis.

Where lymphatic filariasis has diminished since about the 1950s, it has most frequently, though not always, been a direct result of chemotherapeutic intervention against the parasite. Diethylcarbamazine (DEC), a well-established drug, has been the single agent of chemotherapeutic control and has been successful in a wide variety of regimens. This paper reviews the experience with one strategy: long-term, low-dose treatment through DEC-medicated common salt. Diethylcarbamazine-medicated salt played a major role in the Chinese filariasis control program and has been successful in more limited trials in India, Brazil, and Tanzania. It is not being used today in any endemic area, but the evidence suggests that it is safe, effective, and relatively inexpensive. Enough is already known about the beneficial effects of DEC-medicated salt from community-wide studies to develop specific guidelines for its use in community programs.

Animals↗

PubMed1997

Clearance of Wuchereria bancrofti antigen after treatment with diethylcarbamazine or ivermectin.

The present study was undertaken to assess the relationship between microfilarial clearance and clearance of circulating filarial antigen from the blood of Wuchereria bancrofti-infected persons following chemotherapy with either diethylcarbamazine or ivermectin. Patients received either 12 weekly doses of 6 mg/kg of diethylcarbamazine (DEC), a single dose of 6 mg/kg of DEC, a single dose of 420 microg/kg of ivermectin, or 20 microg/kg of ivermectin, followed by 6 mg/kg of DEC five days later. Microfilarial clearance was marked in all groups, but was significantly less in the single-dose DEC. In contrast, as monitored by the Og4C3 monoclonal anitbody assay, clearance of circulating filarial antigen was highly variable, not only between groups but within each group. As a result, there were few statistically significant differences in antigen clearance between groups. In no instance did the antigen level fall to zero, even in individuals that remained microfilaria negative during two or three years of follow-up. These results suggest that living adult worms persist in almost all persons treated with DEC and/or ivermectin.

Adolescent↗

PubMed2001

A community-based trial for the control of lymphatic filariasis and iodine deficiency using salt fortified with diethylcarbamazine and iodine.

To evaluate the effectiveness of salt fortified with diethylcarbamazine (DEC) and iodine for elimination of Bancroftian filariasis and iodine deficiency, all consenting residents of Miton, Haiti (n = 1,932) were given salt fortified with 0.25% diethylcarbamazine and 25 ppm of iodine for one year. Wuchereria bancrofti microfilaria prevalence and intensity, antigenemia, and urinary iodine were measured before and one year after salt distribution began. To measure the effect of DEC-fortified salt on adult worm motility, 15 microfilaria-positive men were examined by ultrasound of the scrotal area. Entomologic surveys were conducted to determine the proportion of W. bancrofti-infected Culex quinquefasciatus. After one year of treatment, the prevalence and intensity of microfilaremia were both reduced by more than 95%, while antigenemia levels were reduced by 60%. The motility of adult worms, as detected by ultrasound, was decreased, but not significantly, by DEC-fortified salt. The proportion of vector mosquitoes carrying infective stage larvae decreased significantly from 2.3% in the nine months before the intervention to 0.2% in the last three-month follow-up period. Iodine deficiency, which had been moderate to severe, was eliminated after one year of iodized salt consumption. The DEC-fortified salt was well accepted by the community and reduced microfilaremia and transmission to low levels in the absence of reported side effects. Based on these results, salt cofortified with DEC and iodine should be considered as a concurrent intervention for lymphatic filariasis and iodine deficiency elimination programs.

Adolescent↗

PubMed2006

Implication of diethylcarbamazine induced morbidity and the role of cellular responses associated with bancroftian filariasis pathologies.

Pre and post-diethylcarbamazine treatment clinical expression, microfilaraemia prevalence and cellular responses were investigated in individuals in Tanga, Tanzania. Fifty-seven male individuals (aged = 15 years old) were identified for further studies on IL-4, IL-6, IL-8. IFN-gamma, IL-beta, TNF-alpha and nitric oxide in plasma and hydrocoele fluid. Microfilarial prevalence in the examined individuals was 12% with a geometric mean intensity (GMI) of 838 mff/ml in a community with a population of 1018 individuals. Microfilaraemic hydrocoele stage II and III were the most frequent pathologies observed with prevalence of 17.5% and 42. 1 %, respectively. All study individuals treated with diethylcarbamazine (DEC) standard dose of 6 mg/kg experienced post-treatment adverse events. There was no direct relationship between elevated IL-6 and the occurrence and severity of clinical adverse effects post-treatment. The findings from this study suggests that, blood elevated cytokine profile is not the main etiological factor in the inflammatory responses developing after treatment of bancroftian filariasis infections and pathology with DEC. Plasma levels of cellular (cytokines) responses during treatment revealed a proportion of symptomatic patients. Prior to treatment, patients with hydroecoele had high levels of IL-6 than those without the pathology. In conclusion these findings do not support the hypothesis that pro-inflammatory cytokines are directly responsible for adverse events to DEC chemotherapy in bancroftian filariasis infections and pathologies such as hydrocoele, lymphoedema and elephantiasis.

Adolescent↗

PubMed2003

Relationships between Wuchereria bancrofti microfilaria counts in human blood and parasite uptake and maturation in Culex pipiens, with observations on the effects of diethylcarbamazine treatment on these parameters.

This study examined relationships between blood microfilaria (MF) counts and parasite uptake and maturation in Culex pipiens fed on Egyptian volunteers with bancroftian filariasis. Uptake of MF and production of infective larvae (L3) were more closely correlated with MF counts in finger prick blood than in venous blood. Only a minority of ingested MF developed into L3. Few MF were ingested, and very few L3 were produced by mosquitoes that fed on infected subjects who were amicrofilaremic by 50 microL thick blood smear; the contribution of such carriers to filariasis transmission in Egypt is probably negligible. These results suggest that filariasis elimination programs should aim to achieve MF smear rates of zero. Single-dose diethylcarbamazine therapy reduced MF counts by 87.9% 6-7 months after treatment; similar reductions were observed for MF uptake, MF/mosquito, infectivity, and L3/mosquito. Thus, single-dose diethylcarbamazine had a major impact on MF ingestion and L3 production by mosquitoes.

Animals↗

PubMed1992

Effect of diethylcarbamazine on acetylcholine and gamma amino butyric acid in Setaria digitata.

In vitro studies on the effect of neurotransmitter amino acids and amines on the motility of S. digitata showed that acetylcholine (Ach) had a stimulatory and gama amino butyric acid (GABA) an inhibitory effect on the parasite. When the worms were incubated in different concentrations of diethylcarbamazine there was a significant dose related increase in the level of Ach, and the level of GABA remained unchanged. Inhibition of acetylcholine esterase activity by diethylcarbamazine caused the accumulation of Ach in the synapses resulting in receptor desensitization and after a momentary stimulation causes paralysis of the parasite.

Acetylcholine↗

PubMed1990

Diethylcarbamazine decreases ethanol-injury to the gastric mucosa of the rat.

Exposure of the rat stomach to ethanol stimulates the generation of leukotrienes. Leukotrienes are potent mediators of tissue inflammation and injury. In this work we show that pretreatment with diethylcarbamazine, a lipoxygenase enzyme inhibitor, significantly decreases ethanol injury to the rat gastric mucosa. At a dose of 250 mg/kg the compound significantly reduced the ETOH-stimulated mucosal LTC4 generation by 40% and PGE2 generation by 79%. We conclude that diethylcarbamazine is an inhibitor of the cyclooxygenase and lipoxygenase enzymes in the gastric mucosa. That inhibition of leukotriene synthesis decreases the extent of ethanol-stimulated suggests that leukotrienes play a key role in mediating ethanol-injury to that tissue.

Animals↗

PubMed1989

[Effects of diethylcarbamazine and ivermectin on the mobilization of microfilariae of Onchocerca volvulus].

Microfilaria of Onchocerca volvulus are localized in superficial dermis. However, they are sometimes noticed in the blood and urines, when there is an important infestation. Diethylcarbamazine (DEC) bring on an increase of microfilaria, successively in the blood and after, in the urines. This study of 30 patients, treated in double blind by placebo, DEC and ivermectin, a new molecule with spectacular action on this filariasis, allowed to compare effect of each one on apparition of microfilariae in the blood and urines. Ivermectin bring on very important increase of microfilaremia without microfilaruria, unlike diethylcarbamazine. This establishment bring to discuss very different physiologic mechanisms between them. It should have an incidence on diagnosis and treatment of this dangerous parasite.

Adult↗

PubMed1988

Effects of high doses of diethylcarbamazine on adult Onchocerca volvulus examined by the collagenase technique and by histology.

Thirty adult male nodule carriers from a hyperendemic onchocerciasis area in the Liberian rain forest were treated with high doses of diethylcarbamazine (30 mg/kg/d) over one week. Another ten patients received placebo tablets and served as a control. All detectable nodules were removed from half of the patients at two months and from the remaining patients at ten months after chemotherapy. The adult worms in the nodules were examined for pathological alterations by the collagenase technique including embryogram, and by histology. No macrofilaricidal effect was observed at either time, and no significant reduction of microfilariae in the uteri of the female worms or in the tissue of the nodules was seen. Two months after the therapy there was a significant increase of degenerated stretched intrauterine microfilariae but this effect was no longer observed after ten months. No pathological effect was seen on the intrauterine coiled microfilariae. On the contrary, their number had significantly increased after ten months which could mean a stimulation of the embryogenesis. No effect on spermatogenesis was observed. Both techniques, the collagenase digestion and the histological examination of the nodules, provided similar results to demonstrate that there was no marked long lasting effect on O. volvulus after a treatment with high doses of diethylcarbamazine.

Animals↗

PubMed1968

The intake and transmissibility of Onchocerca volvulus microfilariae by Simulium damnosum fed on patients treated with Diethylcarbamazine, suramin or Mel W.

The best hope for the control of transmission of Onchocerca volvulus over much of Africa lies in combining larvicidal measures directed against the Simulium vectors with chemotherapeutic measures designed to reduce the reservoir of transmissible microfilariae in man.There are few drugs effective against O. volvulus. Diethylcarbamazine kills the microfilariae but has virtually no effect on the adult worms. Suramin kills adult worms and many, but not all, of the microfilariae. Mel W kills adult worms but has little or no action on microfilariae. All these drugs suffer at present from disadvantages of toxicity, which tend to limit their use on a mass scale in the field. Nevertheless, before they, or indeed any new drugs with similar actions on the parasites, can be used intelligently for the control of onchocerciasis transmission, it is necessary to have accurate quantitative information on the effect that each of them has on the microfilarial population available for intake by Simulium, as well as on their actions on the developmental potential of those microfilariae ingested by the flies.The present paper describes the effects of treatment with various courses of diethylcarbamazine, suramin or Mel W on the numbers of microfilariae ingested by groups of S. damnosum and on the numbers of infective larvae developing therefrom.

Arsenicals↗

PubMedDate not supplied

[Onchocerciasis chemotherapy. II. Evaluation of two therapeutic schemes on microfilarial density, utilising the association diethylcarbamazine and levamisole (author's transl)].

As the study of the association diethylcarbamazine-levamisole gave encouraging results on the dermal microfilarial density of Onchocerca volvulus (Leuckart, 1893), the authors followed it up in order to determine the optimum regimen for mass treatment. Two therapeutic schemes have been tested: A--Initial treatment: 14 days with the dayly dosis of respectively 200 mg of diethylcarbamazine and 120 mg of levamisole progressively reached in four days. After one year: a single dayly dosis of respectively 200 mg and 60 mg for five days. B--Initial treatment: 7 days with the same dosis as above. After one year: dayly dosis of respectively 200 mg and 60 mg for seven days. It appears that scheme A may be considered as the best baseline to achieve the optimum regimen for the mass treatment of onchocerciasis. The aim of such a treatment is to decrease the dermal microfilarial density to a level compatible with the patient good condition.

Adolescent↗