Medical implications of endosymbionts of human lice

Infestations of head lice among schoolchildren are increasing dramatically as resistance to the insecticides used in shampoo-based treatments becomes more common The identification of the endosymbiotic bacterium of human head and body lice might facilitate the development of antibiotic treatments as a supplement to conventional pediculosis treatments based on the neurotoxicity of insecticides to kill lice It is likely that this new, highly modified endosymbiont of lice, Riesia pediculicola, lacks the ability to rapidly evolve resistance to antibiotic agents, and therefore represents a viable target for treatment with antibiotics that have lost their clinical value

Lice have been with humans since the earliest times Treatments for head lice are widely available; nevertheless, the prevalence of lice in developed countries seems to increase Roberts and Burgess report that in a random sample of primary schoolchildren from Wales more than 1 in 10 were infected, whereas in a UK study 58% of 7- to 8-year-old schoolchildren were found infested (Roberts and Burgess, 2005) In developing countries attack rates are even higher, with prevalences over 50% of the general population In the United States, pediculosis capitis is estimated to affect 6 to 12 million people per year Lice infestations are an underestimated worldwide problem that crosses all social and demographic boundaries Lice infestations can also lead to unexpected conditions such as cervical lymphadenopathy or corneal epithelial keratitis Body lice are important vectors for louse-borne relapsing fever, trench fever, and epidemic typhus, especially among refugees Typhus, for example, may be brought home by foreign troops returning from endemic regions such as the former Yugoslavia Typhus might also be obtained from a reservoir host like American flying squirrels In big cities of developed countries, body lice are increasingly important for the transmission of urban trench fever in homeless people

Recent experiments with artificially infected lice suggest that the disease spectrum that human body lice can vector might be much wider than is currently known (Houhamdi et al , 2006; Houhamdi and Raoult, 2006a, 2006b)

Treatment of human head lice is plagued by growing numbers of treatment failures due to the emergence of insecticide-resistant and cross-resistant lice populations, toxicity of the insecticide, and/or inherent limitations and deficiencies of the agents and procedures applied . In a suburb of Paris, France, 36 . 7% of the lice were homozygously resistant against pyrethroids (Durand et al , 2007) All insecticides currently in use are reliant on neuro-toxicity to kill the lice at the nymphal or adult stage. The organophosphate insecticide malathion has been the most prescribed pediculicide in the United Kingdom for around 10 years (Burgess et al , 2007) Alternative classes of chemicals such as essential plant oils to repel or kill lice are limited and sometimes plagued with clinical trails producing contradictory results (Audino et al , 2007; Williamson, 2007; Williamson et al , 2007; Rossini et al , 2008) It remains to be determined whether the antibiotic effect of some essential oils especially in combination with other compounds might successfully impair the endosym-bionts of lice at a very early embryonic stage (Rosato et al , 2007; Bakkali et al , 2008) The need for new pediculicides is so great that more and more oral antiparasitic agents such as ivermectin, albendazole, levamisole, and thiabendazole are considered in the fight against lice (Namazi, 2001, 2003; Akisu et al , 2006; Foucault et al , 2006) Some clearance of head lice also occurs as a side effect of mass treatment campaigns for the control of river blindness (Anosike et al , 2007) Ivermectin is now also available as a topical formulation to kill permethrin-resistant head lice (Strycharz et al , 2008)

The obligate endosymbiont embodies a new, specific target for the development of novel antilouse agents, especially for cases were classical treatment regimes fail This is underpinned by the fact that pragmatic trials with a randomly chosen antibiotic that was orally administered showed promising effects Shashindran and colleagues discovered by accident that a 12-year-old girl treated with co-trimoxazole (trimethoprim and sulfamethoxa-zole) for a bacterial upper respiratory infection also was freed of a head lice infestation without any external antipediculosis intervention (Shashindran et al , 1978) Burns proposed that the antibiotic was killing the symbiotic bacteria in the gut of the louse (Burns, 1987) The stomach disc is very closely situated to the midgut of the louse but there is in fact no connection between the mycetome and the gut lumen . The bacteria stay permanently inside the body of the louse and are transovarially transmitted This distinction is important because the chosen antibiotic has to cross the midgut to the hemolymph and then the wall of the mycetome to the bacterial chambers Other antibiotics might be much more efficient at that and should be systematically tested (Morsy et al , 1996) Hipolito and colleagues recommend the dual therapy of 1% permethrin as a cream and co-trimoxazole orally in cases of multiple treatment failures or cases of suspected louse-related resistance to therapy (Hipolito et al , 2001) It is important to note that this endosymbiotic bacterium is not infectious and does not have an extracorporeal stage This means that it should not have been subjected to any exchange of antibiotic resistance mechanisms common to free-living bacteria The only exchange with the environment might be through bac-teriophages, which so far have not been implicated in vectoring antibiotic resistance The clinical implication of this might be that the obligate louse bacteria are still susceptible to antibiotics that have completely lost their therapeutic value The accidental discovery that the major parasitic nematodes of humans carry Wolbachia as the obligate symbiont has revolutionized the antibiotic treatment of elephantiasis caused by Bancroftian and Brugian filariasis and blindness caused by onchocerciasis (Hoerauf et al , 2000; Taylor et al , 2005) Aside from the medical importance, lice endosymbionts might also support investigations into the evolution of humans; this ranges from the origin of body lice and the emergence of human clothing to the dispersal of Homo sapiens and its probable physical and possible sexual contact with H. erectus (Kittler et al ., 2003; Reed et al ., 2004; Raoult et al ., 2008) .

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