Paul R. Hunter

Epidemiology and Clinical Features of Cryptosporidium Infection in Immunocompromised Patients

SUMMARY Cryptosporidium spp. are a major cause of diarrheal disease in both immunocompetent and immunodeficient individuals. They also cause waterborne disease in both the United States and United Kingdom. Studies on the mechanisms of immunity to cryptosporidiosis indicate the importance of the T-cell response. The spectrum and severity of disease in immunocompromised individuals with cryptosporidiosis reflect this importance since the most severe disease is seen in individuals with defects in the T-cell response. The most commonly studied group is that of patients with AIDS. These patients suffer from more severe and prolonged gastrointestinal disease that can be fatal; in addition, body systems other than the gastrointestinal tract may be affected. The widespread use of antiretroviral therapy does appear to be having a beneficial effect on recovery from cryptosporidiosis and on the frequency of infection in human immunodeficiency virus-positive patients. Other diseases that are associated with increased risk of severe cryptosporidiosis, such as primary immunodeficiencies, most notably severe combined immunodeficiency syndrome, are also predominantly associated with T-cell defects. Of the remaining groups, children with acute leukemia seem to be most at risk from cryptosporidiosis. There is less evidence of severe complications in patients with other malignant diseases or in those receiving immunosuppressive chemotherapy.

Longitudinal study of infectious intestinal disease in the UK (IID2 study): incidence in the community and presenting to general practice

Objectives To estimate, overall and by organism, the incidence of infectious intestinal disease (IID) in the community, presenting to general practice (GP) and reported to national surveillance. Design Prospective, community cohort study and prospective study of GP presentation conducted between April 2008 and August 2009. Setting Eighty-eight GPs across the UK recruited from the Medical Research Council General Practice Research Framework and the Primary Care Research Networks. Participants 6836 participants registered with the 88 participating practices in the community study; 991 patients with UK-acquired IID presenting to one of 37 practices taking part in the GP presentation study. Main outcome measures IID rates in the community, presenting to GP and reported to national surveillance, overall and by organism; annual IID cases and GP consultations by organism. Results The overall rate of IID in the community was 274 cases per 1000 person-years (95% CI 254 to 296); the rate of GP consultations was 17.7 per 1000 person-years (95% CI 14.4 to 21.8). There were 147 community cases and 10 GP consultations for every case reported to national surveillance. Norovirus was the most common organism, with incidence rates of 47 community cases per 1000 person-years and 2.1 GP consultations per 1000 person-years. Campylobacter was the most common bacterial pathogen, with a rate of 9.3 cases per 1000 person-years in the community, and 1.3 GP consultations per 1000 person-years. We estimate that there are up to 17 million sporadic, community cases of IID and 1 million GP consultations annually in the UK. Of these, norovirus accounts for 3 million cases and 130 000 GP consultations, and Campylobacter is responsible for 500 000 cases and 80 000 GP consultations. Conclusions IID poses a substantial community and healthcare burden in the UK. Control efforts must focus particularly on reducing the burden due to Campylobacter and enteric viruses.

Climate change and waterborne and vector-borne disease

This paper considers the potential impact on human health from waterborne and vector-borne infections. It concentrates on the impact of two possible changes to climate; increased frequency of heavy rainfall events, with associated flooding and increased temperature. Flooding is associated with increased risk of infection in developing nations but not in the West unless water sources are compromised. There have been numerous reported of outbreaks that followed flooding that led to contamination of underground sources of drinking water. Heavy rainfall also leads to deterioration in the quality of surface waters that could adversely affect the health of those engaged in recreational water contact. It is also concluded that there may be an increase in the number of cyanobacterial blooms because of a combination of increased nutrient concentrations and water temperature. It is considered unlikely that climate change will lead to an increase in disease linked to mains drinking water, although private supplies would be at risk from increased heavy rainfall events. Although increased temperature could lead to climatic conditions favourable to increases in certain vector-borne diseases such as malaria, the infrastructure in the UK would prevent the indigenous spread of malaria.

Burden of disease from inadequate water, sanitation and hygiene in low- and middle-income settings: a retrospective analysis of data from 145 countries

To estimate the burden of diarrhoeal diseases from exposure to inadequate water, sanitation and hand hygiene in low‐ and middle‐income settings and provide an overview of the impact on other diseases.

Water supply and health.

As one article in a four-part PLoS Medicine series on water and sanitation, Paul Hunter and colleagues argue that much more effort is needed to improve access to safe and sustainable water supplies.

Sporadic Cryptosporidiosis Case- Control Study with Genotyping

Risk factors for Cryptosporidiosis in United Kingdom.

Estimating the impact on health of poor reliability of drinking water interventions in developing countries

Recent evidence suggests that many improved drinking water supplies suffer from poor reliability. This study investigates what impact poor reliability may have on achieving health improvement targets. A Quantitative Microbiological Risk Assessment was conducted of the impact of interruptions in water supplies that forced people to revert to drinking raw water. Data from the literature were used to construct models on three waterborne pathogens common in Africa: Rotavirus, Cryptosporidium and Enterotoxigenic E. coli. Risk of infection by the target pathogens is substantially greater on days that people revert to raw water consumption. Over the course of a few days raw water consumption, the annual health benefits attributed to consumption of water from an improved supply will be almost all lost. Furthermore, risk of illness on days drinking raw water will fall substantially on very young children who have the highest risk of death following infection. Agencies responsible for implementing improved drinking water provision will not make meaningful contributions to public health targets if those systems are subject to poor reliability. Funders of water quality interventions in developing countries should put more effort into auditing whether interventions are sustainable and whether the health benefits are being achieved.

Detection of Mycobacterium avium subspecies paratuberculosis from patients with Crohn's disease using nucleic acid-based techniques: a systematic review and meta-analysis.

This study is a systematic review and meta‐analysis of studies using nucleic acid‐based techniques to detect Mycobacterium avium paratuberculosis (MAP) in patients with Crohns disease (CD) compared with controls. Database searches were conducted and risk difference estimates were calculated using meta‐analysis. Fifty‐eight studies were reviewed, 47 of which were included in the analysis. The pooled estimate of risk difference from all studies was 0.23 (95% confidence interval [CI], 0.14–0.32) using a random effects model. Similarly, MAP was detected more frequently from patients with CD compared with those with ulcerative colitis (risk difference 0.19, 95% CI, 0.10–0.28). Year of study, assay type, and inclusion of children explained some but not all of the observed heterogeneity. The data confirms the observation that MAP is detected more frequently among CD patients compared with controls. However, the pathogenic role of this bacterium in the gut remains uncertain. Our analysis demonstrates that there is an association between MAP and CD, across many sites, by many investigators, and controlling for a number of factors; however, this association remains controversial and inconclusive. Future studies should determine whether there is a pathogenic role.

Cryptosporidium Pathogenicity and Virulence

SUMMARY Cryptosporidium is a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation of Cryptosporidium virulence factors have been hindered by the renowned difficulties pertaining to the in vitro culture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors for Cryptosporidium. This progress has been accelerated since the publication of the Cryptosporidium parvum and C. hominis genomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge on Cryptosporidium infectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence.

Assessing the impact of drinking water and sanitation on diarrhoeal disease in low- and middle-income settings: Systematic review and meta-regression

To assess the impact of inadequate water and sanitation on diarrhoeal disease in low‐ and middle‐income settings.