Doxycycline and Eradication of Microfilaremia in Patients with Loiasis

Brouqui, Philippe; Fournier, Pierre; Raoult, Didier

doi:10.3201/eid0707.017747

Cited by 21 publications

(8 citation statements)

References 5 publications

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“…Our results agree with the previous reports on the absence of Wolbachia in L. loa worms [1,16-20]. Other filaria species for which the absence of endobacteria has been shown by at least two independent methods are O. flexuosa [13,14], A. viteae [1,11,12], and S. equina [15].…”

Section: Discussionsupporting

confidence: 92%

“…It cannot be excluded however, that the primer sets used did not hybridise to the target sequences, though our previous results have shown that these primers amplified Wolbachia DNA of all species that have been examined so far including the sand flea T. penetrans [26]. Furthermore, our results are in line with those reported from PCR analysis of microfilariae from two patients infected with L. loa [20]. …”

Section: Discussionsupporting

confidence: 88%

“…For the three animal parasites these findings have been accepted. The absence of endobacteria from the human parasite L. loa has been reported by several authors based on electron microscopy [1,16-18], on immunohistology [19] and PCR [20]. However, because of its medical importance and the small number of samples used in most studies, the statements regarding L. loa haven been repeatedly doubted.…”

Section: Introductionmentioning

confidence: 99%

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Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa

et al. 2003

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Background: Many filarial nematodes harbour Wolbachia endobacteria. These endobacteria are transmitted vertically from one generation to the next. In several filarial species that have been studied to date they are obligatory symbionts of their hosts. Elimination of the endobacteria by antibiotics interrupts the embryogenesis and hence the production of microfilariae. The medical implication of this being that the use of doxycycline for the treatment of human onchocerciasis and bancroftian filariasis leads to elimination of the Wolbachia and hence sterilisation of the female worms. Wolbachia play a role in the immunopathology of patients and may contribute to side effects seen after antifilarial chemotherapy. In several studies Wolbachia were not observed in Loa loa. Since these results have been doubted, and because of the medical significance, several independent methods were applied to search for Wolbachia in L. loa.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa

et al. 2003

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“…Previous electron microscopy studies have failed to find intracellular bacteria in L. loa microfilariae [6,19] and adults [20,21] and PCR analysis of microfilariae from two patients also failed to detect Wolbachia [22]. Here we have used molecular and immunohistochemical analysis to confirm this finding in a larger number of samples derived from different endemic areas.…”

Section: Introductionsupporting

confidence: 59%

Evidence against Wolbachia symbiosis in Loa loa

et al. 2003

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Background: The majority of filarial nematode species are host to Wolbachia bacterial endosymbionts, although a few including Acanthocheilonema viteae, Onchocerca flexuosa and Setaria equina have been shown to be free of infection. Comparisons of species with and without symbionts can provide important information on the role of Wolbachia symbiosis in the biology of the nematode hosts and the contribution of the bacteria to the development of disease. Previous studies by electron microscopy and PCR have failed to detect intracellular bacterial infection in Loa loa. Here we use molecular and immunohistological techniques to confirm this finding.

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“…This changed with the identification of Wolbachia endobacteria (order Rickettsiales) in filariae of medical importance in the late 1990s (14,15), which prompted a series of experiments in animal models demonstrating that antibiotics (especially the tetracyclines) not only impede the growth and embryogenesis of filarial worms (16,17) but also can kill the adult parasites (18). Such effects were not observed at clinically relevant doses in filarial species that naturally lack Wolbachia symbionts (16,19). Clinical trials of doxycycline (DOX) for human onchocerciasis were implemented rapidly, which achieved sterilization of female worms using a regimen of 200 mg/day for 4 weeks (20) or 100 mg/day for 5 weeks (21).…”

mentioning

confidence: 99%

Efficacy of Three-Week Oxytetracycline or Rifampin Monotherapy Compared with a Combination Regimen against the Filarial Nematode Onchocerca ochengi

Bah

Ward

Srivastava

et al. 2014

Antimicrob Agents Chemother

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Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, is a major cause of visual impairment and dermatitis in sub-Saharan Africa. As O. volvulus contains an obligatory bacterial symbiont (Wolbachia), it is susceptible to antibiotic chemotherapy, although current regimens are considered too prolonged for community-level control programs. The aim of this study was to compare the efficacies of oxytetracycline and rifampin, administered separately or in combination, against a close relative of O. volvulus (Onchocerca ochengi) in cattle. Six animals per group were treated with continuous or intermittent oxytetracycline regimens, and effects on adult worm viability, dermal microfilarial loads, and Wolbachia density in worm tissues were assessed. Subsequently, the efficacies of 3-week regimens of oxytetracycline and rifampin alone and a combination regimen were compared, and rifampin levels in plasma and skin were quantified. A 6-month regimen of oxytetracycline with monthly dosing was strongly adulticidal, while 3-week and 6-week regimens exhibited weaker adulticidal effects. However, all three regimens achieved >2-log reductions in microfilarial load. In contrast, rifampin monotherapy and oxytetracycline-rifampin duotherapy failed to induce substantive reductions in either adult worm burden or microfilarial load, although a borderline effect on Wolbachia density was observed following duotherapy. Dermal rifampin levels were maintained above the MIC for >24 h after a single intravenous dose. We conclude that oxytetracycline-rifampin duotherapy is less efficacious against O. ochengi than oxytetracycline alone. Further studies will be required to determine whether rifampin reduces oxytetracycline bioavailability in this system, as suggested by human studies using other tetracycline-rifampin combinations.

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Doxycycline and Eradication of Microfilaremia in Patients with Loiasis

Cited by 21 publications

References 5 publications

Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa

Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa

Evidence against Wolbachia symbiosis in Loa loa

Efficacy of Three-Week Oxytetracycline or Rifampin Monotherapy Compared with a Combination Regimen against the Filarial Nematode Onchocerca ochengi

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