cercariae. at 1.9 million disability-adjusted life years (DALYs) [4], although reported DALY figures vary considerably with 70 million being the highest [4]. Open in a separate window Fig. 1 Life cycle of human schistosomes. Adult schistosome worms parasitise the blood vessels of Articaine HCl humans and other vertebrates which act as definitive hosts, but their life cycle necessitates a phase of asexual multiplication and development within a freshwater snail. Infective larvae (cercariae) are periodically released from the snail, and these actively seek and penetrate the skin of the human definitive host; in zoonotic schistosomiasis (caused by and and spp. for spp. for spp. for and [1C4]. Established active and late chronic schistosomiasis are found mainly in people with long-standing schistosome infection who live in poor rural areas. The clinical manifestations are inflammatory and obstructive and result from immunopathological reactions against schistosome eggs trapped in host tissues [1C4]. In and infections, we see intestinal disease by advanced hepatosplenic schistosomiasis, whereas in infection, the disease is urogenital mainly involving lesions of not only the bladder wall but also the reproductive system [1C4]. Morbidity is especially pronounced in high-intensity infections (i.e. those with a high worm burden) with large numbers of eggs released daily [1C4]. Importantly, morbidity/mortality associated with infections is exacerbated due to the substantially higher number of eggs, often released in packages, Articaine HCl by this species [6]. The three phases of the disease mentioned above are dictated by the length of infection [4]. These differ with respect to symptoms and clinical consequences as well as to the rates of schistosome egg excretion in urine or faeces [4]. Immediate manifestations The first clinical manifestation following infection is a maculopapular pruritic eruption, termed cercarial dermatitis, which may arise at the site of skin penetration by schistosome cercariae [7]. Cercarial dermatitis results from an innate immune response giving rise to hypersensitivity reactions to dead or dying parasites and can be observed with all human schistosome species. These skin reactions comprise discrete erythematous raised lesions varying in size (1C3?cm) which may develop within a few hours post-infection, although a rash may appear up to 7? days later in tourists or migrants moving into an area endemic for schistosomiasis for the first time. The resulting dermatitis is similar to, but less severe than swimmers itch, which is a response in persons when infected by schistosomes not adapted to humans (e.g. those adapted to birds) [1, 7]. Acute schistosomiasis Following cercarial penetration and schistosomula maturation, the infection may proceed to the symptomatic acute schistosomiasis stage although the first clinical manifestations in non-immune subjects may be delayed by several weeks or even months following exposure [1, 7]. The symptom complex, known as Katayama fever or Katayama syndrome, is common in areas with high rates of schistosomiasis transmission and is an early clinical indicator of a first infection or a heavy reinfection with spp. cercariae. Acute schistosomiasis is the disease manifestation most likely to be underdiagnosed or misdiagnosed by physicians in non-endemic countries and remains, compared with the other clinical stages of schistosomiasis, poorly understood [7]. The syndrome is named after the Katayama District of Hiroshima prefecture in Japan where the first human case of was described in 1904 [8]. Patients commonly recall prior Articaine HCl contact with natural freshwater bodies, such as streams or lakes between 2?weeks and 3?months earlier [7]. Common symptoms include generalised myalgia, right-upper-quadrant pain, bloody diarrhoea, headache, fever, eosinophilia, non-productive cough and patchy pulmonary infiltrates observed on chest Articaine HCl radiography [3, 7]. These vary in severity depending on the infecting species but are thought to be due to systemic hypersensitivity reactions mediated by the immune system against antigens released by migrating schistosomula or, in most cases, eggs following their deposition in host tissues [3, 7]. Sox18 Whereas the majority of patients recover spontaneously after 2C10?weeks, some develop a generalised rash and more serious and persistent disease with dyspnoea, abdominal pain, weight loss, hepatomegaly and diarrhoea [3, 7]. While Katayama fever caused by infections is commonly reported, it is rarely observed in relation to or in individuals from chronically exposed communities and may be the result of in-utero de-sensitisation and a lowering of immune responsiveness to schistosome antigens in infants born to infected mothers [4, 7]. An alternative explanation might be repeated exposure to schistosome cercarial antigens inducing.