Editorial: Pyoderma, group A streptococci and parasitic skin diseases – a dangerous relationship

In the tropics infectious skin diseases are extremely common. Depending on the healthcare setting between 7% and 71% of the patients present skin lesions of infectious origin (Cestari et al. 1992; Mahe 2001; Mahéet al. 2003; Ogunbiyi et al. 2004; Rodriguez 2004). The proportion of skin infections because of fungal, parasitological and bacterial aetiology varies from place to place, but bacterial skin infections always have an important share (Cestari et al. 1992; Mahe 2001; Ogunbiyi et al. 2004; Rodriguez 2004). Within the spectrum of bacterial skin diseases pyoderma is the most common condition. Pyoderma is defined as a skin infection with pyogenic bacteria, generally Staphyloccus aureus, Streptococcus pyogenes or both. Pyoderma is primary when it arises on normal skin and secondary when it complicates other skin diseases. Although pyoderma may occur in all age groups, it is particularly frequent in children. In Aboriginal communities in Northern Australia e.g. 10–90% of children had purulent skin sores (Currie & Carapetis 2000; Shelby-James et al. 2002). Group A Streptococcus (GAS) was the primary pathogen with up to 80% of pyoderma lesions being GAS culture positive (Currie & Carapetis 2000; Shelby-James et al. 2002). Staphylococcus aureus is also commonly found in pyoderma lesions but, in contrast to GAS, is usually a secondary wound colonizer (Kakar et al. 1999; Currie & Carapetis 2000; Fatani et al. 2002). If several pyoderma lesions are present in an individual they are usually colonized by different strains of GAS (Carapetis et al. 1995). Group A Streptococcus have been extensively studied with many structural components identified, and their biological functions have been elucidated. These components can roughly be divided into three categories: (a) capsule, group specific carbohydrates, peptidoglycan and lipoteichoic acid; (b) proteins anchored on the cell surface and (c) secreted factors. Capsule components and surface proteins are considered as important pathogenicity factors (Chhatwal & Preissner 1999; Preissner & Chhatwal 1999). The latter include M, T and R proteins, fibronectin binding proteins, other matrix binding proteins, and a variety of other factors. These proteins are anchored on the surface by their C-terminal end. M protein is a major surface protein of streptococci, enabling the organism to resist phagocytosis. It is capable of binding to fibrinogen and complement factor H leading to the activation of alternate complement pathway. Because of antigen variation, M protein exists in approximately 100 different serotypes. With a few exceptions, one strain expresses only one type of M-protein. The complete amino acid sequence of various M serotypes is known, and B- and T-cell epitopes have been identified (Hayman et al. 1997). There is little information on factors predisposing the development of pyodermas. Personal experience from field work in sub-Saharan Africa and South America suggests that pyoderma is rampant in children from resource-poor communities. During childhood repeated infection is common and children may experience several episodes of pyoderma in the course of 1 year (Rodriguez 2004). Kakar et al. (1999) found pyodermas more often in children from families with low socio-economic status who lived in overcrowded conditions and were undernourished. In endemic areas the incidence of pyoderma seems to vary during the year with the peak occurring in the hot and humid season (Kristensen 1991; Kakar et al. 1999). Streptococcal skin infection caused by GAS is always a matter of concern as important sequels may result if the lesion is left untreated. Erysipela, cellulitis, streptococcal gangrene and streptococcal ulcer all have the tendency to spread into deeper skin layers and subcutaneous tissue or to extend to adjacent body areas, eventually causing systemic disease (Bisno & Stevens 1996). Two long-term sequels of GAS infection, acute rheumatic fever (ARF) and post-streptococcal glomerulonephritis (PSGN) were first described in industrialized countries but have become rather rare within the last decades. But in the tropics ARF and PSGN induced by GAS still present a major disease burden (Carapetis & Currie 1996; Carapetis et al. 1999; Berrios et al. 2004). The pathophysiology of these sequels is still incompletely understood. Recent studies indicate that human collagen acts as an auto antigen in rheumatic fever (Dinkla et al. 2003). As to glomerulonephritis, one hypothesis is that nephritogenic GAS express pathogenicity factors that have high affinity for kidney cells and are able to induce inflammation by forming immune complexes (Michael et al. 1996). It has been known for many years that skin infections preferably lead to glomerulonephritis, whereas throat infections tend to cause rheumatic fever. An explanation for this could be that different M-serotypes are involved in skin and throat infections and that isolates from skin infections are not able to aggregate human collagen, which is required for induction of rheumatic fever. It is supposed that GAS tissue preferences are genetically determined and that hitherto unknown host risk factors strongly influence the differential reproduction of individual clones (Bessen et al. 2000). The factors driving the colonization of the skin and the throat by GAS in children living in a tropical environment are not known. It remains also enigmatic whether there is a mutual relationship between both infection sites. The large reservoir of GAS strains usually present on the skin may allow constant genetic reassortment, with development of new epitopes allowing to evade host defences and the sharing of virulence factors (Carapetis & Currie 1996). Parasitic skin diseases (PSD) – pediculosis, scabies, tungiasis, cutaneous larva migrans, myiasis, to name the most important ones – occur in all climates, but are especially common in the tropics. In resource-poor settings they frequently affect extended areas of the skin or cause simultaneous lesions at different topographic sites (Heuckelbach et al. 2002, 2004, 2005;Feldmeier et al. 2003). The prevalence of ectoparasitoses in the general population is rather low, but may be extremely high in vulnerable groups (Heuckelbach & Feldmeier 2004). For example, tungiasis usually affects <1% of the population, but in economically disadvantaged communities prevalence in children can reach 76% (Muehlen et al. 2003). Scabies was observed in 40–80% of certain risk groups such as patients of a dermatology clinic in sub-Saharan Africa, indigenous communities in Australia and homeless children (Kristensen 1991; Estrada 2003). In resource-poor populations it is rare to find a household that is completely free of PSD. Similar to pyoderma children bear the greatest disease burden. All PSD are extremely itchy. Breaks in the epidermis due to the burrowing of the ectoparasite, scratching by the patient and subsequent excoriations serve as an entry point for pathogenic bacteria. Therefore, in the tropics, PSD are frequently associated with superinfection of the lesions. Staphylococci and streptococci are the microorganisms most commonly isolated (Brook 1995; Currie & Carapetis 2000; Wong et al. 2001; Feldmeier et al. 2002). Of the different streptococcal serogroups GAS is the most common one. In Trinidad e.g. 50% of schoolchildren and 93% of adults with scabies had their skin lesions colonized by GAS (Svartman et al. 1973). In Aboriginal communities in Northern Australia scabies underlayed 50–70% of streptococcal pyoderma and over 80% of superinfected lesions contained GAS (Currie & Carapetis 2000). Moreover, in areas where PSD are endemic fingertips are frequently colonized with streptococci. In the Solomon islands for example, where the prevalence of scabies was of 25% in children 86% of fingertips were colonized by streptococci, of which 71% were GAS (Lawrence et al. 2005). Secondary pyoderma because of GAS may be facilitated by the particular micro-environment of the ectoparasitic lesion. In scabies e.g. it has been suggested that hitherto unknown factors within the burrows of the mites favour the propagation of GAS (Currie & Carapetis 2000). The excess of pyoderma caused by PSD is not precisely known. However, studies in which the prevalence of pyoderma was assessed before and after control of a PSD give some clues. In a control programme in the Solomon Islands the prevalence of scabies in children decreased from 25% to 1% and that of the pyoderma from 40% to 22% (Lawrence et al. 2005). In Australia the prevalence of scabies decreased between 23% and 33% and that of pyoderma between 17% and 50% after an intervention against S. scabiei carriers (Carapetis et al. 1997; Wong et al. 2001). This would indicate that in these populations up to 50% of pyodermas were because of superinfected scabies. Also important: not only did the prevalence of pyoderma fall after the reduction of scabies in a community, but also the number of pyoderma lesions per individual and the severity of the skin sores (Carapetis et al. 1997; Wong et al. 2001). So far, scabies is the only PSD for which an long-term sequel of the colonization of the skin lesions by GAS is documented. An increased risk for the development of PSGN in individuals with scabies is supported by different lines of evidence. In Chile e.g. the spatial distribution of areas with a high prevalence of scabies and high incidence of PSGN overlapped (Ximena Berríos 1990). In Trinidad a rising prevalence of scabies over time was paralleled by an increasing incidence of PSGN (Svartman et al. 1973; Reid & Poon-King 1988). Seasonal variation in the occurrence of scabies was followed by similar patterns in patients newly diagnosed with PSGN (Whittle et al. 1973; Verma et al. 1983). Epidemics of scabies coincided with epidemics of PSGN in the same population (Svartman et al. 1972; Reid et al. 1990; Ximena Berríos 1990). Finally 20 years of registration of all cases of PSGN in Chile including areas with a high prevalence of scabies indicated that the incidence of PSGN varied considerably over time and was correlated to the presence of certain M-serotypes isolated from the skin of newly diagnosed patients (Berrios et al. 2004). A similar observation has been made in Trinidad where the isolation of nephritogenic strains of streptococci from patients with PSGN increased along augmenting occurrence of scabies and PSGN in the general population (Svartman et al. 1973; Reid et al. 1990). The most convincing evidence for a causal relationship between scabies and PSGN comes from an intervention trial in the Solomon Islands. Parallel to a 96% decrease in scabies prevalence after mass chemotherapy indicators of renal damage approached almost zero (Lawrence et al. 2005). Renal complications may become obvious only with a delay of several years. White et al. (2001) examined a cohort of individuals who had been affected by a previous epidemic of scabies-related streptococcal pyoderma. The authors found that 10 years after the event there was a significant difference in the distribution of patients found to have proteinuria and haematuria between those who had been infected previously and those who had not. Although it is assumed that certain GAS M-genotypes are responsible for the development of PSGN at present it cannot be excluded that scabies itself is involved in the pathogenesis of renal disease (Hay 2003). As at community level risk factors for the presence of PSD and of pyoderma seem very similar, it does not come as a surprise that both types of skin diseases overlap spatially. In fact, PSD as well as pyoderma can be considered as typical infections of people living in poverty, characterized by low income, overcrowding, lack of sanitation, insufficient personal hygiene and – in the case of children – malnutrition (Ximena Berríos 1990; Kakar et al. 1999). It seems therefore reasonable to assume that both, pyoderma and PSDs, are intertwined in the same web of causation. Clearly, both pyoderma and PSD have a low priority on the health agenda of developing countries (Carapetis et al. 1999; Heukelbach et al. 2001; Mahéet al. 2003; Heuckelbach & Feldmeier 2004) and PSD are ignored by healthcare providers (Heuckelbach et al. 2003). This is a matter of concern as both conditions, alone or combination, are responsible for important sequels. We suggest that pyoderma and PSD demand considerably more commitment from the research community and healthcare providers than they currently receive. There is an urgent need to know the burden of disease in vulnerable populations, to identify individuals at risk for developing severe complications and to develop methods to reduce PSD and pyoderma in impoverished populations. This work was supported in part by a grant from the Bundesministerium für Bildung und Forschung, Berlin, Germany.