Clinical and laboratory features associated with serum phosphate concentrations in malaria and other febrile illnesses.

Background: Hypophosphatemia is common in severe infections including malaria. Previous studies suggested that serum phosphate concentrations correlate with temperature, but it is unclear whether the type of infection and other factors occurring during infection influence this association. Here relationships were investigated between serum phosphate levels, cause of fever, demographic, clinical and laboratory parameters.

Group 5 drugs for multidrug-resistant tuberculosis: individual patient data meta-analysis.

The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

Background: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis.

Risk factors for UK Plasmodium falciparum cases.

Background: An increasing proportion of malaria cases diagnosed in UK residents with a history of travel to malaria endemic areas are due to Plasmodium falciparum.

Methods: In order to identify travellers at most risk of acquiring malaria a proportional hazards model was used to estimate the risk of acquiring malaria stratified by purpose of travel and age whilst adjusting for entomological inoculation rate (EIR) and duration of stay in endemic countries.

Results: Travellers visiting friends and relatives and business travellers were found to have significantly higher hazard of acquiring malaria (adjusted hazard ratio (HR) relative to that of holiday makers 7.

Native valve right sided infective endocarditis.

Right-sided infective endocarditis (RSIE) accounts for 5-10% of all cases of infective endocarditis (IE), and is predominantly encountered in the injecting drug user (IDU) population, where HIV and HCV coinfections often coexist. Staphylococcus aureus is the most common pathogen. The pathogenesis of RSIE is still not well understood.

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.

Methods And Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB.

Likely health outcomes for untreated acute febrile illness in the tropics in decision and economic models; a Delphi survey.

Background: Modelling is widely used to inform decisions about management of malaria and acute febrile illnesses. Most models depend on estimates of the probability that untreated patients with malaria or bacterial illnesses will progress to severe disease or death. However, data on these key parameters are lacking and assumptions are frequently made based on expert opinion.

Brucellosis acquired by eating imported cheese.

Pyrexia of unknown origin is an important clinical presentation in both paediatric and adult medicine. We present a case of pyrexia of unknown origin in a 14 year-old boy which turned out to be due to infection with Brucella melitensis, despite the patient not having left Great Britain - an officially brucellosis-free country - in six years. Repeated history-taking provided a clue to the diagnosis.

Protective hemoglobinopathies and Plasmodium falciparum transmission.

Human hemoglobin variants are known to protect the host against severe malaria due to P. falciparum. A new study demonstrates that such genetic variation may also be associated with increased transmission of this pathogen from the human host to the Anopheles vector.

Frequencies of region of difference 1 antigen-specific but not purified protein derivative-specific gamma interferon-secreting T cells correlate with the presence of tuberculosis disease but do not distinguish recent from remote latent infections.

The majority of individuals infected with Mycobacterium tuberculosis achieve lifelong immune containment of the bacillus. What constitutes this effective host immune response is poorly understood. We compared the frequencies of gamma interferon (IFN-gamma)-secreting T cells specific for five region of difference 1 (RD1)-encoded antigens and one DosR-encoded antigen in 205 individuals either with active disease (n = 167), whose immune responses had failed to contain the bacillus, or with remotely acquired latent infection (n = 38), who had successfully achieved immune control, and a further 149 individuals with recently acquired asymptomatic infection.

New developments in the management of malaria in adults.

In dealing with malaria, the challenge that remains is prompt diagnosis and initiation of specific and supportive treatment. Physicians should be aware of the therapeutic and prognostic implications of life-threatening falciparum vs. non-falciparum malaria and be able to at least recognize the severe manifestations of malaria which may require an increased level of care or referral to a specialist unit.

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.

High levels of multidrug resistant tuberculosis in new and treatment-failure patients from the Revised National Tuberculosis Control Programme in an urban metropolis (Mumbai) in Western India.

Background: India, China and Russia account for more than 62% of multidrug resistant tuberculosis (MDRTB) globally. Within India, locations like urban metropolitan Mumbai with its burgeoning population and high incidence of TB are suspected to be a focus for MDRTB. However apart from sporadic surveys at watched sites in the country, there has been no systematic attempt by the Revised National Tuberculosis Control Programme (RNTCP) of India to determine the extent of MDRTB in Mumbai that could feed into national estimates.

Risk factors for severe disease in adults with falciparum malaria.

Background: Over a 16-year period, we conducted a clinical study of malaria acquired worldwide in adults from malaria-nonendemic countries, to determine risk factors for severe Plasmodium falciparum malaria.

Methods: All patients with confirmed malaria who were managed by our unit from 1991 to 2006 were prospectively evaluated. Factors predicting disease severity according to (1) strict World Health Organization (WHO) criteria, (2) a composite measure of unfavorable outcome, and (3) length of hospital stay were identified by logistic and linear regression analyses.

Recent advances in tropical medicine.

There have been significant advances in both the classical and neglected tropical diseases, with Guinea worm looking set to be the next disease after smallpox to be eradicated. Aided by a combination of enhanced understanding of the biology of the pathogens, intensification of immunisation activities or mass drug administration, together with the development of synergies with control programmes for co-endemic tropical diseases, polio, lymphatic filariasis, trachoma and onchocerciasis all appear to be in global decline, with good prospects for eventual successful elimination. While the global incidence of new cases of leprosy continues to decrease, the focus of leprosy control efforts has shifted following more widespread recognition that cure of infection does not necessarily prevent disability.

Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in Mycobacterium tuberculosis-infected individuals.

Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care.

Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI.

Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals.

Mutations in the Plasmodium falciparum cytochrome b gene are associated with delayed parasite recrudescence in malaria patients treated with atovaquone-proguanil.

Background: Fixed-dose combination antimalarial drugs have played an increasingly important role in the treatment and chemoprophylaxis of falciparum malaria since the worldwide failure of monotherapy with chloroquine. Atovaquone-proguanil is one such combination drug used both for prophylaxis in travellers, and for treatment of acute malaria cases in European hospitals and clinics.

Methods: A series of eight atovaquone-proguanil treatment failures and two prophylaxis breakthroughs from four UK hospitals from 2004-2008 were analysed for evidence of mutations in the pfcyt-b gene, previously found to be associated with failure of the atovaquone component.

Rapid molecular detection of rifampicin resistance facilitates early diagnosis and treatment of multi-drug resistant tuberculosis: case control study.

Background: Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months.

Cluster of falciparum malaria cases in UK airport.

A cluster of 6 cases of Plasmodium falciparum malaria occurred in a UK airport among 30 travelers returning to the United States from East Africa. Molecular genotyping analysis indicated that all had been exposed to different parasites. The travelers' use of chemoprophylaxis was poor; their perception of risk was limited.

Improved diagnostic evaluation of suspected tuberculosis.

Background: The role of new T-cell-based blood tests for tuberculosis in the diagnosis of active tuberculosis is unclear.

Objective: To compare the performance of 2 interferon-gamma assays and tuberculin skin testing in adults with suspected tuberculosis.

Design: Prospective study conducted in routine practice.