Community-directed delivery of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis in Cameroon

Wanji, Samuel; Tendongfor, Nicholas; Nji, Theolbald; Esum, Mathias Eyong; Julious, N; Nkwescheu, Armand Séraphin; Alassa, Fifen; Kamnang, Geremy; Enyong, Peter; Taylor, Mark J.; Hoerauf, Achim; Taylor, David W.

doi:10.1186/1756-3305-2-39

Cited by 100 publications

(82 citation statements)

References 34 publications

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“…However, significant adulticidal activity (killing of 60 to 70% of female worms) required a regimen of 200 mg/day for 6 weeks (20). This relatively protracted course of treatment, coupled with contraindications in children below 8 years of age and in pregnant or lactating women, have prevented approval of DOX for MDA to date; this is despite the very high rates of compliance evident in a clinical trial that was conducted in a region of Cameroon where loiasis is endemic (22). Nevertheless, DOX has been applied in a small onchocerciasis focus in Venezuela to expedite elimination efforts (23).…”

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confidence: 66%

“…Although DOX is clearly more efficacious than ivermectin, the latter can suppress Mf densities (and thus, disease manifestations) for up to 1 year following a single dose of 150 g/kg, which makes it highly amenable to MDA programs (4). In a clinical trial in a area of Cameroon where loiasis is endemic, community-wide distribution of daily DOX therapy for 6 weeks was accompanied by very high rates of compliance (22), but to date, this has not resulted in wider application of DOX by APOC.…”

Section: Discussionmentioning

confidence: 99%

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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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confidence: 66%

Section: Discussionmentioning

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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“…Diethylcarbamazine is also contra-indicated because of the risk of a strong Mazzotti reaction and exacerbation of ocular pathology, but a combination of doxycycline and albendazole [83] or doxycycline alone [84] can be used under these circumstances. Apart from ivermectin, other microfilaricides include moxidectin, which has a longer-lasting effect than ivermectin and with little re-population [85] but it has yet to be licensed.…”

Section: Microfilaricidesmentioning

confidence: 99%

Factors affecting onchocerciasis transmission: lessons for infection control

Cheke

2017

Expert Review of Anti-infective Therapy

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Introduction: Onchocerca volvulus infects in excess of 15 million people. The vectors are Simulium blackflies, varieties of which differ in their ecologies, behaviour and vectorial abilities. Control of the vectors and mass administrations of ivermectin have succeeded in reducing prevalences with elimination achieved in some foci, particularly in Central and southern America. In Africa, progress towards elimination has been less successful.Areas covered: Even with community directed treatment with ivermectin (CDTI), control has been difficult in African areas with initial prevalences in excess of 55%, especially if only annual treatments are dispensed. This is partly attributable to insufficient coverage, but the appearance of incipiently resistant non-responding parasites and lack of attention to vector biology in modelling and planning outcomes of intervention programmes have also played their parts, with recrudescence now appearing in some treated areas. Expert commentary:The biology of onchocerciasis is complex involving different vectors with differing abilities to transmit parasites, diverse pathologies related to geographical and parasite variations and endosymbionts in both parasite and vector. Modelling to predict epidemiological and control outcomes is addressing this complexity but more attention needs to be given to the vectors' roles to further understanding of where and when control measures will succeed.

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“…Wanji and colleagues, however, proved the skeptics wrong when they showed that more than 97% of ϳ13,000 people from villages where the infection is endemic who started doxycycline completed a 6-week regimen after community-directed explanation and organization of the delivery (community-directed treatment) (84). Current follow-up studies are aimed at assessing the impact of community-directed doxycycline administration (which comprised, on average, about 74% of the eligible population having started the treatment) on community microfilarial load and thus its impact on transmission.…”

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confidence: 99%

Onchocerciasis: the Role of Wolbachia Bacterial Endosymbionts in Parasite Biology, Disease Pathogenesis, and Treatment

et al. 2011

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SUMMARY The discovery of Wolbachia intracellular bacteria within filarial nematodes, including Onchocerca volvulus , the causative agent of onchocerciasis or “river blindness,” has delivered a paradigm shift in our understanding of the parasite's biology, to where we now know that the bacterial endosymbionts are essential for normal development of larvae and embryos and may support the long-term survival of adult worms. The apparent mutualistic dependency has also offered a novel approach to the treatment of onchocerciasis through the use of antibiotics to eliminate Wolbachia , delivering for the first time a treatment which has significant macrofilaricidal efficacy. Studies with other filarial nematode species have also highlighted a role for Wolbachia in transmission and infection of the mammalian host through a fascinating manipulation of mast cell-mediated vasodilation to enhance infectivity of vector-borne larvae. Wolbachia has also been identified as the principal driver of innate and adaptive Th1 inflammatory immunity, which can either contribute to disease pathogenesis or, with the Wolbachia -mediated recruitment of mast cells, enhance infectivity. The Wolbachia activation of innate inflammation also drives inflammatory adverse events in response to chemotherapy with either diethylcarbamazine (DEC) or ivermectin. In this review we summarize the experimental and field trial data which have uncovered the importance of Wolbachia symbiosis in onchocerciasis.

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Community-directed delivery of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis in Cameroon

Cited by 100 publications

References 34 publications

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

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

Factors affecting onchocerciasis transmission: lessons for infection control

Onchocerciasis: the Role of Wolbachia Bacterial Endosymbionts in Parasite Biology, Disease Pathogenesis, and Treatment

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