The potential biomarkers for tuberculosis that we identified through proteomic fingerprinting and pattern recognition have a plausible biological connection with the disease and could be used to develop new diagnostic tests.

In rural tropical areas, patients frequently present with malaria and require urgent therapy. Facilities may not exist for parenteral drug administration, and oral dosing is precluded by obtundation or vomiting. In these circumstances, the rectal route of administration may allow initiation of antimalarial therapy while patients await transfer to hospital, a process that may take many hours.Artesunate (ARS) is a water-soluble hemisuccinate dihydroartemisinin (DHA) derivative being developed for the treatment of malaria and is particularly valuable against multidrugresistant infections (2, 13). ARS is currently formulated for administration by the oral and parenteral routes (3, 11). ARS suppositories (Rectocaps; 50 mg of artesunate; Mepha Pharmaceuticals Ltd.) Aesch-Basle, Switzerland) have recently undergone preliminary assessment in Gabonese children (8). However, formal bioavailability studies with this formulation are lacking. Circulating ARS is quickly converted to DHA by blood esterases and hepatic metabolism (14). As DHA is the principal antimalarial metabolite of ARS, the bioavailability of DHA was studied by comparing intrarectally (i.r.) and intravenously (i.v.) administered ARS in Ghanaian children with moderate malaria. High-performance liquid chromatography (HPLC) with electrochemical detection, currently the most precise and sensitive assay, was used to measure ARS and DHA levels. This crossover study was also designed to test the hypothesis that within the first 24 h there is no disease effect on the pharmacokinetics of ARS. These studies are critical to the design of larger (phase III-IV) studies seeking to use rectal ARS to reduce mortality from malaria. MATERIALS AND METHODS Study design description.This was an open, randomized, crossover comparison between i.v. ARS and ARS suppositories conducted on a pediatric research ward at Komfo-Anokye Teaching Hospital, Kumasi, Ghana, from August to October 1996. This study was approved by The Committee of Research, Publication and Ethics of the School of Medical Sciences, University of Science and Technology, Kumasi, Ghana, and the Review Board of the World Health Organization. A computer-generated randomization list allocating patients to one of three treatment categories was prepared (in permuted blocks of 12 patients). The treatment category for each patient was provided in an opaque sealed envelope opened only when a patient entered the study. Treatment categories were as follows: group I, i.r. ARS at 10 mg/kg of body weight, followed 12 h later by i.v. ARS at 2.4 mg/kg; group II, i.r. ARS at 20 mg/kg, followed 12 h later by i.v. ARS at 2.4 mg/kg; and group III, i.v. ARS at 2.4 mg/kg, followed 12 h later by i.r. ARS at 20 mg/kg. The doses of i.r. ARS were based on preliminary pharmacodynamic analysis of a similar study of i.r. ARS in Thai adults with moderate malaria (S. Looareesuwan, personal communication).Inclusion criteria. Patients aged 18 months to 7 years (inclusive) with a diagnosis of moderate Plasmodium falciparum malaria were eligible, pro...

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This study is the first, to our knowledge, to show an association between MBL deficiency and acute invasive aspergillosis in humans. Further study is required to investigate the causal nature of this association and to define whether diagnosis of MBL deficiency may identify immunocompromised patients at increased risk of invasive aspergillosis.

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The United Kingdom is free from rabies, with the last human death from indigenous rabies recorded in 1902. However, between 1946 and 2000, 20 deaths were reported in the United Kingdom in people who were bitten and infected while abroad in rabies endemic areas. The rapid diagnosis of suspected human rabies cases influences the use of anti-rabies post-exposure prophylaxis for potential contacts with the victim. In addition, the occurrence of a human rabies case requires urgent investigation to support patient management policies. In May 2001, a case of human rabies imported into the United Kingdom from the Philippines was identified. A 55-year-old man was admitted to University College Hospital, London, with clinical symptoms and a history consistent with exposure to rabies. Saliva, cerebrospinal fluid), and skin biopsies (from the wound site and nape of the neck) were submitted for conventional ante-mortem diagnostic techniques. Established diagnostic techniques, including the fluorescent antibody test (FAT), mouse inoculation test, (MIT) and the rabies tissue culture inoculation test (RTCIT), failed to detect the virus. In contrast, hemi-nested reverse transcription-polymerase chain reaction (RT-PCR), followed by automated sequencing confirmed the presence of classical rabies virus (genotype 1) in both the saliva and skin specimens within 36 hr of sample submission. Subsequent phylogenetic analysis demonstrated that this isolate was closely related to that of canine variants currently circulating in the Philippines.

Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1 . Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed.AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells.Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins.HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.