Without realizing it perhaps, the research activities of many parasitologists are often focused upon the study of parasites most commonly found in children. Though there is little recognition of paediatric parasitology as a separate topic within medical parasitology, with the global interest in promotion of maternal and child health, alleviation of diseases associated with poverty and requirements of ‘child-sized’ medicines, a more formal consideration is now timely. Recent research, for example, has highlighted that defining precisely the ‘first-age’ at which parasites interfere with a child's health, or normal developmental processes, is being revised. Attention is now drawn towards ever younger subjects, for parasites have the capacity to also influence the health of the foetus within the in utero environment, altering immune-development. These subtle, yet evolutionary profound interactions perhaps manifest themselves as to why some children are more prone to infection(s), develop overt disease and sadly die while others do not. Here, we address the growing importance of paediatric parasitology and its applications within disease control strategies as highlighted in the 2010 Autumn Symposium of the British Society of Parasitology.

Artemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the ‘premier’ combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistance.

Intermittent preventive treatment of infants (IPTi) with sulphadoxine pyrimethamine (SP) is recommended as an additional malaria control intervention in high transmission areas of sub-Saharan Africa, provided its protective efficacy is not compromised by SP resistance. A significant obstacle in implementing SP-IPTi, is in establishing the degree of resistance in an area. Since SP monotherapy is discontinued, no contemporary measures of in vivo efficacy can be made, so the World Health Organisation has recommended a cut-off based upon molecular markers, stating that SP-IPTi should not be implemented when the prevalence of the dhps 540E mutation among infections exceeds 50%. We created a geo-referenced database of SP resistance markers in Africa from published literature. By selecting surveys of malaria infected blood samples conducted since 2004 we have mapped the contemporary prevalence of dhps 540E. Additional maps are freely available in interactive form at http://www.drugresistancemaps.org/ipti/. Eight countries in East Africa are classified as unsuitable for SP-IPTi when data are considered at a national level. Fourteen countries in Central and West Africa were classified as suitable while seven countries had no available contemporary data to guide policy. There are clear deficiencies in molecular surveillance data coverage. We discuss requirements for ongoing surveillance of SP resistance markers in support of the use of SP-IPTi.

Trypanosoma brucei gambiense sleeping sickness follows a long asymptomatic phase and persists in ancient foci from which epidemic clinical disease arises. A putative focus of T. b. gambiense infections has been identified, initially in mothers and young children, on the Lake Albert shoreline of Western Uganda leading to mass screening of 6207 individuals in September 2008. T. b. gambiense infections were identified by Card Agglutination Test for Trypanosomiasis (CATT) and sub-species-specific PCR although parasitological methods failed to confirm any patent trypanosome infections. In April 2009, CATT positives were re-visited; diagnosis of individuals by CATT and PCR was unstable over the two time points and parasites remained undetected, even using mini Anion Exchange Centrifugation Technique (mAECT). These observations suggest the possibility of a silent focus of disease, where all infected individuals are in a latent stage, and highlight our limited understanding of the local natural history and disease progression of T. b. gambiense in children and adults.

Cryptosporidiosis is a major infection of humans, leading to diarrhoea and growth failure in children, diarrhoea and malnutrition in immunocompromised adults, and is associated with increased mortality in all age groups. Using the country of Zambia as an example, I review the possible approaches to treatment and prevention in a tropical setting. The current optimal therapy for cryptosporidiosis is nitazoxanide which works well in HIV uninfected children, but treatment in patients with HIV infection remains remarkably difficult. No single drug has demonstrated efficacy in a randomised trial. No vaccine is available, so the best option for prevention for the moment is filtration and clean storage of drinking water. This would be expected to reduce cryptosporidiosis dramatically, but this needs to be demonstrated directly. Water filtration would have the added benefit of protection against many other pathogens, but the paucity of alternative approaches highlights the need for a better understanding of this important human pathogen.

In recent years, the isolation of parasitic DNA from faecal samples and PCR techniques, have been improved and simplified. Moreover, the introduction of real-time PCR has made it possible to multiplex different targets into one reaction. These new technical possibilities make it feasible to introduce PCR with its unsurpassed sensitivity and specificity in a routine laboratory setting for the diagnosis of intestinal parasites. Detection rates of the parasitic infections included in the PCR are increased significantly compared with microscopy. Molecular diagnostics, especially in children, reveal a possible cause of the gastrointestinal complaints in many more cases compared with conventional methods. Usually in GP patients no other pathogenic parasites are detected using microscopy and in the returning travellers additional parasites are found with microscopy in a minority of cases only. Multiplex real-time PCR offers a highly sensitive and specific diagnostic alternative for labour intensive microscopy in clinical laboratory practice. Additional diagnostic methods for the detection of parasitic infections that are not included as PCR target can be limited to a selected group of patients.

In 1994 and 2002, respectively, the World Health Organisation proposed that treatment for hookworm and schistosomiasis could be provided during pregnancy. It was hoped that this might have benefits for maternal anaemia, fetal growth and perinatal mortality; a beneficial effect on the infant response to immunisation was also hypothesised. Three trials have now been conducted. Two have examined the effects of benzimidazoles; one (the Entebbe Mother and Baby Study) the effects of albendazole and praziquantel. All three were conducted in settings of high prevalence but low intensity helminth infection. Results suggest that, in such settings and given adequate provision of haematinics, the benefit of routine anthelminthics during pregnancy for maternal anaemia may be small; none of the other expected benefits has yet been demonstrated. The Entebbe Mother and Baby Study found a significant adverse effect of albendazole on the incidence of infantile eczema in the whole study population, and of praziquantel on the incidence of eczema among infants of mothers with Schistosoma mansoni. Further studies are required in settings that differ in helminth species and infection intensities. Further research is required to determine whether increased rates of infantile eczema translate to long-term susceptibility to allergy, and to explore the underlying mechanisms of these effects. The risks and benefits of routine anthelminthic treatment in antenatal clinics may need to be reconsidered.

The shaping of a child's immune system starts in utero, with possible long-term consequences in later life. This review highlights the studies conducted on the development of the immune system in early childhood up to school-age, discussing the impact that environmental factors may have. Emphasis has been put on studies conducted in geographical regions where exposure to micro-organisms and parasites are particularly high, and the effect that maternal exposures to these may have on an infant's immune responses to third-party antigens. In this respect we discuss the effect on responses to vaccines, co-infections and on the development of allergic disorders. In addition, studies of the impact that such environmental factors may have on slightly older (school) children are highlighted emphasizing the need for large studies in low to middle income countries, that are sufficiently powered and have longitudinal follow-up components to understand the immunological footprint of a child and the consequences throughout life.

Despite the overlapping distribution of Schistosoma haematobium and Plasmodium falciparum infections, few studies have investigated early immune responses to both parasites in young children resident in areas co-endemic for the parasites. This study measures infection levels of both parasites and relates them to exposure and immune responses in young children. Levels of IgM, IgE, IgG4 directed against schistosome cercariae, egg and adult worm and IgM, IgG directed against P. falciparum schizonts and the merozoite surface proteins 1 and 2 together with the cytokines IFN-γ, IL-4, IL-5, IL-10 and TNF-α were measured by ELISA in 95 Zimbabwean children aged 1–5 years. Schistosome infection prevalence was 14·7% and that of Plasmodium infection was 0% in the children. 43. 4% of the children showed immunological evidence of exposure to schistosome parasites and 13% showed immunological evidence of exposure to Plasmodium parasites. Schistosome–specific responses, indicative of exposure to parasite antigens, were positively associated with cercariae-specific IgE responses, while Plasmodium-specific responses, indicative of exposure to parasite antigens, were negatively associated with responses associated with protective immunity against Plasmodium. There was no significant association between schistosome-specific and Plasmodium-specific responses. Systemic cytokine levels rose with age as well as with schistosome infection and exposure. Overall the results show that (1) significantly more children are exposed to schistosome and Plasmodium infection than those currently infected and; (2) the development of protective acquired immunity commences in early childhood, although its effects on infection levels and pathology may take many years to become apparent.

Anaemia is a severe public health issue among African preschool-aged children, yet little effective progress has been made towards its amelioration, in part due to difficulties in unravelling its complex, multifactorial aetiology. To determine the current anaemia situation and assess the relative contribution of malaria, intestinal schistosomiasis and infection with soil-transmitted helminths, two separate cross-sectional epidemiological surveys were carried out in Uganda including 573 and 455 preschool-aged children (⩽6 years) living along the shores of Lake Albert and on the islands in Lake Victoria, respectively. Anaemia was found to be a severe public health problem in Lake Albert, affecting 68·9% of children (ninety-five percent confidence intervals (95% CI) 64·9–72·7%), a statistically significant higher prevalence relative to the 27·3% detected in Lake Victoria (95% CI: 23·3–31·7%). After multivariate analysis (controlling for sex and age of the child), the only factor found to be significantly associated with increased odds of anaemia in both lake systems was malaria (Lake Albert, odds ratio (OR)=2·1, 95% CI: 1·4–3·2; Lake Victoria, OR=1·9, 95% CI: 1·2–2·9). Thus intervention strategies primarily focusing on very young children and combating malaria appear to represent the most appropriate use of human and financial resources for the prevention of anaemia in this age group and area. Looking to the future, these activities could be further emphasised within the National Child Health DaysPLUS agenda.

In sub-Saharan Africa, over 22 million people are estimated to be co-infected with both helminths and HIV-1. Several studies have suggested that de-worming individuals with HIV-1 may delay HIV-1 disease progression, and that the benefit of de-worming may vary by individual helminth species. We conducted a systematic review and meta-analysis of the published literature to determine the effect of treatment of individual helminth infections on markers of HIV-1 progression (CD4 count and HIV viral load). There was a trend towards an association between treatment for Schistosoma mansoni and a decrease in HIV viral load (Weighted mean difference (WMD)=−0·10; 95% Confidence interval (CI): −0·24, 0·03), although this association was not seen for Ascaris lumbricoides, hookworm or Trichuris trichiura. Treatment of A. lumbricoides, S. mansoni, hookworm or T. trichiura was not associated with a change in CD4 count. While pooled data from randomized trials suggested clinical benefit of de-worming for individual helminth species, these effects decreased when observational data were included in the pooled analysis. While further trials are needed to confirm the role of anthelmintic treatment in HIV-1 co-infected individuals, providing anthelmintics to individuals with HIV-1 may be a safe, inexpensive and practical intervention to slow progression of HIV-1.

Lymphatic filariasis (LF), a common parasitic infection in tropical countries, causes lymphoedema of limbs, hydrocele and acute attacks of dermato-lymphangio-adenitis. Recent advances in diagnosis have helped to recognize that LF infection is often acquired in childhood. Newly available diagnostic techniques like sensitive antigen and antibody assays, Doppler ultrasonography and lymphoscintigraphy have helped to understand the subclinical pathology caused by this infection, which was hitherto generally believed to be irreversible. Recent studies indicate that drugs used in the mass drug administration (MDA) programme under GPELF are capable of reversing the sub-clinical lymphatic damage in children and provide benefits other than interruption of transmission. Albendazole and ivermectin used in MDA are effective against soil-transmitted helminthic infections common in children in LF endemic areas. Thus MDA had other ‘beyond LF’ benefits in treated children including increased appetite, weight gain, greater learning ability and concentration, better school attendance and prevention of anaemia. MDA should no longer be viewed as a measure for interrupting transmission alone. Recent findings of reversibility of early lymphatic pathology in treated children indicate that both MDA and ‘foot-hygiene’ measures are effective strategies in preventing and managing morbidity. Programme managers should effectively utilize this information to strengthen their advocacy efforts to achieve high and sustainable coverage in MDA.

This cross-sectional study determined the prevalence and distribution of schistosome and soil-transmitted helminth (STH) infections among 1,308 children aged 10–18 years in 34 primary schools in 8 informal urban settlements in Kisumu City, western Kenya. Stool samples were collected and examined for eggs of Schistosoma mansoni and STH (Hookworms, Ascaris lumbricoides and Trichuris trichiura) using the Kato-Katz technique. Haematuria was used as a proxy indicator of urinary schistosomiasis. Schools and water bodies were mapped using a geographical information system. Overall, 34% of children were infected with one or more helminth species whereas 16·2% of children were infected with one or more STH species. Schools in closest proximity to Lake Victoria and River Nyamasaria had the highest S. mansoni prevalence while schools with STH were more homogenously distributed. Mean school prevalence of S. mansoni infection was 21% (range=0–69·7%), S. haematobium 3·6% (range=0–12%), hookworms 6·1% (range=0–20%), A. lumbricoides 4·9% (range=0–18·4%), and T. trichiura 7·7% (range=0–18·6%). Helminth-related morbidities were not associated with infection. Our study demonstrates that schistosomiasis and STH are important health priorities among schools in informal settlements of Kisumu City, and highlights the need for routine deworming in similar settings.

This study assessed the impact of adding community-directed treatment (ComDT) to the routine health facility (HF)-based treatment on prevalence and intensity of soil transmitted helminth (STH) infections among children aged 12 to 59 months. Repeated cross-sectional surveys were conducted among randomly selected children of this age group from the intervention area (HF+ComDT area) and the comparison area (HF area) at baseline (n=986), 12 months (n=796) and 18 months (n=788) follow-up. The prevalence of Ascaris lumbricoides was significantly higher in the HF+ComDT as compared to the HF area at baseline (P=0·048), but not at 12 and 18 months follow-up. At baseline the HF+ComDT area had significantly higher intensities of A. lumbricoides compared to the HF area (P<0·001), but not at 12 and 18 months follow-ups. Prevalence and intensity of hookworm did not differ significantly between treatment arms at any time. Analysis of trends showed a significant decrease in prevalence of A. lumbricoides and hookworm in the HF+ComDT area (P<0·001), of hookworm in the HF area (P<0·05), but not of A. lumbricoides in the HF area. It is concluded that the ComDT approach generally enhanced the treatment effect among under-five year children and that this alternative approach may also have advantages in other geographical settings.

Objective. There is limited information on the acceptability and safety of praziquantel for treatment of schistosomiasis in children below the age of four years. In addition, although mebendazole has been extensively used together with praziquantel against infections with schistosomiasis and soil-transmitted helminthiasis (STH) in school-aged children, no specific acceptability or safety studies have been published on this drug combination in younger children. Methods. A randomized clinical trial was conducted to determine the safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and STH in children aged 1 to 4 years. Results. A total of 596 children from Bwondha fishing community in Mayuge district and Wang-Kado fishing community in Nebbi district were investigated using duplicate Kato-Katz thick smears of two stool samples and 130 (21·8%) were found infected with S. mansoni. Of these, 19·2% (25) had heavy intensity of infections. Of the infected children, 82 were included and randomised into praziquantel (40 mg/kg) + mebendazole (500 mg) or praziquantel (40 mg/kg) alone. Conclusion. Many symptoms were reported before treatment while very few were reported after treatment and all on treatment day. No serious adverse events were reported or observed after treatment. Praziquantel with or without mebendazole was well tolerated in small children in the study area.

Where very young children come into contact with water containing schistosome cercariae, infections occur and schistosomiasis can be found. In high transmission environments, where mothers daily bathe their children with environmentally drawn water, many infants and preschool-aged children have schistosomiasis. This ‘new’ burden, inclusive of co-infections with Schistosoma haematobium and Schistosoma mansoni, is being formally explored as infected children are not presently targeted to receive praziquantel (PZQ) within current preventive chemotherapy campaigns. Thus an important PZQ treatment gap exists whereby infected children might wait up to 4–5 years before receiving first treatment in school. International treatment guidelines, set within national treatment platforms, are presently being modified to provide earlier access to medication(s). Although detailed pharmacokinetic studies are needed, to facilitate pragmatic dosing in the field, an extended ‘dose pole’ has been devised and epidemiological monitoring has shown that administration of PZQ (40 mg/kg), in either crushed tablet or liquid suspension, is both safe and effective in this younger age-class; drug efficacy, however, against S. mansoni appears to diminish after repeated rounds of treatment. Thus use of PZQ should be combined with appropriate health education/water hygiene improvements for both child and mother to bring forth a more enduring solution.

With the current paucity of vaccine targets for parasitic diseases, particularly those in childhood, the aim of this study was to compare protein expression and immune cross-reactivity between the trematodes Schistosoma haematobium, S. bovis and Echinostoma caproni in the hope of identifying novel intervention targets. Native adult parasite proteins were separated by 2-dimensional gel electrophoresis and identified through electrospray ionisation tandem mass spectrometry to produce a reference gel. Proteins from differential gel electrophoresis analyses of the three parasite proteomes were compared and screened against sera from hamsters infected with S. haematobium and E. caproni following 2-dimensional Western blotting. Differential protein expression between the three species was observed with circa 5% of proteins from S. haematobium showing expression up-regulation compared to the other two species. There was 91% similarity between the proteomes of the two Schistosoma species and 81% and 78·6% similarity between S. haematobium and S. bovis versus E. caproni, respectively. Although there were some common cross-species antigens, species-species targets were revealed which, despite evolutionary homology, could be due to phenotypic plasticity arising from different host-parasite relationships. Nevertheless, this approach helps to identify novel intervention targets which could be used as broad-spectrum candidates for future use in human and veterinary vaccines.

Drug development for paediatric applications entails a number of challenges, such as the wide age spectrum covered – from birth to adolescence – and developmental changes in physiology during biological maturation that influence the efficacy and toxicity of drugs. Safe and efficacious antiparasitic drugs for children are of pivotal importance given the large proportion of burden attributable to parasitic diseases in this age group, and growing efforts to administer, as widely as possible, antiparasitic drugs to at-risk populations, such as infants and school-aged children, often without prior diagnosis. The purpose of this review is to investigate whether antiparasitic drugs have been adequately studied for use in paediatrics. We approached this issue through a systematic review using PubMed and the Cochrane Central Register of Trials covering a period of 10 years and 8 months until the end of August 2010 to identify trials that investigated efficacy, safety and pharmacokinetic (PK) parameters of antiparasitic drugs for paediatrics. Overall, 269 clinical drug trials and 17 PK studies met our inclusion criteria. Antimalarial drugs were the most commonly studied medicines (82·6%). Most trials were carried out in Africa and children aged 2–11 years were the age group most often investigated. Additionally, we critically examined available drug formulations for anthelminthics and identified a number of shortcomings that are discussed. Finally, we shed new light on current proposals to expand ‘preventive chemotherapy’ to preschool-aged children and emphasise that new research, including risk-benefit analyses, are needed before such a strategy can be adopted more widely.