Nicholas J. Beeching

Sporadic Cryptosporidiosis Case- Control Study with Genotyping

Risk factors for Cryptosporidiosis in United Kingdom.

Traveller's diarrhoea

Travellers diarrhoea affects over 50% of travellers to some destinations and can disrupt holidays and business trips. This review examines the main causes and epidemiology of the syndrome, which is associated with poor public health infrastructure and hygiene practices, particularly in warmer climates. Although travellers may be given common sense advice on avoidance of high-risk foods and other measures to prevent travellers diarrhoea, adherence to such advice is sometimes difficult and the evidence for its effectiveness is contradictory. However, non-antimicrobial means for prevention of travellers diarrhoea are favoured in most settings. A simple stepwise approach to the management of travellers diarrhoea includes single doses or 3-day courses of antimicrobials, often self administered. The antibiotics of choice are currently fluoroquinolones or azithromycin, with an emerging role for rifaximin. In the long term, there will be greater benefit and effect on the health of local inhabitants and travellers from improving public health and hygiene standards at tourist destinations.

Viral encephalitis: a clinician’s guide

The management of patients with suspected viral encephalitis has been revolutionised in recent years with improved imaging and viral diagnostics, better antiviral and immunomodulatory therapies, and enhanced neurointensive care. Despite this, disasters in patient management are sadly not uncommon. While some patients are attacked with all known antimicrobials with little thought to investigation of the cause of their illness, for others there are prolonged and inappropriate delays before treatment is started. Although viral encephalitis is relatively rare, patients with suspected central nervous system (CNS) infections, who might have viral encephalitis, are not. In addition, the increasing number of immunocompromised patients who may have viral CNS infections, plus the spread of encephalitis caused by arthropod-borne viruses, present new challenges to clinicians. This article discusses the Liverpool approach to the investigation and treatment of adults with suspected viral encephalitis, and introduces the Liverpool algorithm for investigation and treatment of immunocompetent adults with suspected viral encephalitis (available at www.liv.ac.uk/braininfections).

Prevalence of infection with hepatitis B and C virus and coinfection with HIV in medical inpatients in Malawi

BACKGROUND Coinfection with hepatitis B (HBV) or hepatitis C (HCV) adversely affects the prognosis of HIV infection and vice versa, and results in complex interactions with antiretroviral therapy. These infections are common in sub-Saharan Africa but there are few data on prevalence of coinfection. All three components of the most common ART regimen used in Africa, stavudine, lamivudine and nevirapine, can cause hepatic problems and lamivudine resistant HBV is known to emerge after HBV monotherapy in coinfected patients. Point of care (POC) tests for HBV and HCV are widely used but have not been validated in field tests in sub-Saharan Africa. METHODS Prospective observational study of sequential adult inpatients in medical wards of a large urban teaching hospital in Malawi in 2004. Comparison of demographic risk factors with HIV antibody status determined using local double POC test protocols, and with HBsAg and HCV antibody prevalence as estimated in a reference laboratory in Liverpool, UK. Results of locally performed POC tests for HBV using Determine HBsAg (Abbott) and for HCV antibody using HCV-SPOT (Genelabs) were compared with results of reference methods in the UK. RESULTS Of 226 adults (39% male), median (range) age 35 (14-80) years, 81% had a history of traditional scarification, 12% a history of blood transfusion and 11% a history of jaundice. HIV antibodies were present in 76.1%, HBsAg in 17.5% and HCV in 4.5%, with HIV/HBV coinfection in 20.4% and HIV/HCV coinfection in 5% of those with HIV. There was no correlation between prevalence of any of the three viruses and demographic risk factors or presence of either of the other two viruses. Point of care tests gave misleading results with prevalence estimates of 38% for HBV and 4.5% for HCV. For both of these POC tests the performance indices were unacceptable for individual patient management or epidemiological survey purposes. CONCLUSIONS The high prevalence of hepatitis/HIV coinfections may impact on treatment with antiretroviral therapy, especially if there are unintended interruptions of therapy, and studies are needed to document the possible clinical impact on ART programmes. The poor performance of POC tests for HBV and HCV may be due to local operational problems or to unexpected technical issues not revealed by early validation tests. These tests are widely used in resource poor settings and should be revalidated in prospective field studies in areas of the tropics with high HIV prevalence rates.

Cryptosporidium muris infection in an HIV-infected adult, Kenya.

We describe a case of Cryptosporidium muris infection in an HIV-infected adult with diarrhea in Kenya. Sequence analysis of an 840-bp region of the 18S rRNA gene locus demonstrated the isolate had 100% nucleotide identity with C. muris recovered from a rock hyrax, 98.8% with a C. muris “calf” isolate, 95.5% with C. serpentis, but only 87.8% with C. parvum “human” type.

Gastrointestinal parasites in the immunocompromised.

Purpose of review Parasites and other infections have many effects on the gastrointestinal tract of individuals who are immunocompromised. Few reviews focus on parasitic infections, which are covered here. Recent findings The review first examines recent advances in our understanding of the taxonomy, diagnosis and treatment of pathogens such as cryptosporidia, cyclospora, isospora and microsporidia, which are recognized causes of diarrhoea in the immunocompromised, and discusses possible links between amoebiasis and HIV. The complex interactions of both intact and abnormal immune systems with helminth infections such as hookworm and strongyloidiasis, and with trematode infections such as schistosomiasis, are receiving increasing attention. These are discussed, together with the novel concept of using live helminths to treat inflammatory bowel disease. Summary Parasitic infections remain a significant problem for immunocompromised individuals in resource-poor settings, and further work is needed to develop accessible diagnostic tests and to improve our understanding and management of their pathogenic effects. New concepts about the interactions of helminths with host immunity suggest the need for collection of further epidemiological and clinical data to unravel the complexities of such immunological interactions.

Chikungunya Virus and Central Nervous System Infections in Children, India

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus best known for causing fever, rash, arthralgia, and occasional neurologic disease. By using real-time reverse transcription–PCR, we detected CHIKV in plasma samples of 8 (14%) of 58 children with suspected central nervous system infection in Bellary, India. CHIKV was also detected in the cerebrospinal fluid of 3 children.

Intracellular Accumulation of Human Immunodeficiency Virus Protease Inhibitors

ABSTRACT Intracellular accumulation of the protease inhibitors (PIs) saquinavir (SQV), ritonavir (RTV), and indinavir (IDV) was determined in 50 human immunodeficiency virus-positive patients. Following extraction, PIs were quantified by mass spectrometry. Paired plasma and intracellular samples were collected over a full dosing interval from patients (13 on SQV, 6 on RTV, 8 on IDV, 16 on SQV plus RTV, 7 on IDV plus RTV) with a plasma viral load of <400 copies/ml. Data were expressed as intracellular/plasma drug concentration ratios. A hierarchy of intracellular accumulation was demonstrated by the following medians: 9.45 for SQV > 1.00 for RTV > 0.51 for IDV. Coadministration of RTV did not boost ratios of SQV or IDV within the cell or in plasma, although absolute plasma and intracellular SQV concentrations were increased by RTV. Seven individuals receiving SQV in hard-gel capsule form (median, 32 months) had higher intracellular/plasma drug ratios than all other patients receiving SQV (median, 17.62 versus 4.83; P = 0.04), despite consistently low plasma SQV concentrations. How this occurs may provide insight into the mechanisms that limit adequate drug penetration into sanctuary sites.

Biological warfare and bioterrorism

Since the terrorist attack on the United States in September 2001 attention has been focused on the threat of biological warfare. The disruptive effects of deliberate release of anthrax in civilian settings have been well documented, and several other pathogens could also be used as biological weapons. We have described the key features of such pathogens, how they might be used in biological warfare, and the clinical syndromes they cause. We also discuss the medical and logistic response to their possible use. #### Summary points Appropriate dispersion of even a small volume of biological warfare agent may cause high morbidity and mortality, which may be exacerbated by public panic and social disruption Early symptoms of disease induced by a biological warfare agent may be non-specific or difficult to recognise Healthcare workers should be alert for unusual single cases or clusters of illness, especially in otherwise healthy adults Unusual illness should be notified immediately to public health authorities Strategic responses to the deliberate release of biological warfare agents must be rehearsed locally and nationally with multiple agencies Healthcare professionals should familiarise themselves with national and local sources of advice on deliberate release Biological warfare agents are defined as “living organisms, whatever their nature, or infected material derived from them, which are used for hostile purposes and intended to cause disease or death in man, animals and plants, and which depend for their efforts on the ability to multiply in the person, animal or plant attacked.”1 Many such agents are zoonotic and have a considerable impact on agriculture as well as on human health. Biological warfare agents are well suited for use in bioterrorism or for attack by poorer nations against the rich (so called “asymmetric methods” of attack2) as they are cheap and easy to obtain and disperse, although full scale use …

Fever in returned travellers presenting in the United Kingdom: recommendations for investigation and initial management.

International travel is increasing. Most physicians and general practitioners will encounter returned travellers with fever and the majority of travel-related infection is associated with travel to the tropics. In those returning from the tropics malaria must always be excluded, and HIV considered, from all settings. Common causes of non-malarial fever include from Africa rickettsial diseases, amoebic liver abscess and Katayama syndrome; from South and South East Asia, enteric fever and arboviral infection; from the Middle East, brucellosis and from the Horn of Africa visceral leishmaniasis. Other rare but important diseases from particular geographical areas include leptospirosis, trypanosomiasis and viral haemorrhagic fever. North and South America, Europe and Australia also have infections which are geographically concentrated. Empirical treatment may have to be started based on epidemiological probability of infection whilst waiting for results to return. The evidence base for much of the management of tropical infections is limited. These recommendations provide a pragmatic approach to the initial diagnosis and management of fever in returned travellers, based on evidence where it is available and on consensus of expert opinion where it is not. With early diagnosis and treatment the majority of patients with a potentially fatal infection related to travel will make a rapid and full recovery.