Sherine Thomas

Ribavirin for Crimean-Congo hemorrhagic fever: systematic review and meta-analysis

BackgroundCrimean-Congo hemorrhagic fever epidemics often occur in areas where health services are limited, and result in high case fatality rates. Besides intensive care, ribavirin is often recommended. A solid evidence base for the use of this drug will help justify assuring access to the drug in areas where epidemics are common.MethodsWe carried out a systematic review of observational and experimental studies of people with suspected or confirmed Crimean-Congo hemorrhagic fever that included comparisons between patients given ribavirin and those not. We extracted data on mortality, hospital stay, and adverse events. Risk of bias was assessed using a standard checklist, and data were presented in meta-analytical graphs, stratified by study design, and GRADE tables presented. The risk of bias was summarised using the GRADE method.Results21 unique studies, including one randomised controlled trial of ribavirin, were included. Quality of the evidence was very low, with a Down and Black median score of 4 (maximum possible 33). Ribavirin treatment was not shown to be superior to no ribavirin treatment for mortality rate in a single RCT (RR: 1.13, 95%CI: 0.29 to 4.32, 136 participants, GRADE=low quality evidence); but ribavirin was associated with reduced mortality by 44% when compared to no ribavirin treatment in the pooled observational studies (RR: 0.56, 95%CI: 0.35 to 0.90, 955 participants; GRADE=very low quality evidence). Adverse events were more common with the ribavirin patients, but no severe adverse events were reported. No difference in length of hospital stay was reported.ConclusionsNo clear message of benefit is available from the current data on ribavirin as observational data are heavily confounded, and the one trial carried out has limited power. However, ribavirin could potentially have benefits in this condition and these results clearly indicate a pragmatic, randomised controlled trial in the context of good quality supportive care, is urgently needed and ethically justified.

Increasing Frequency of Pneumocystis jirovecii Pneumonia in Renal Transplant Recipients in the United Kingdom: Clonal Variability, Clusters, and Geographic Location

To the Editor—Pneumocystis jirovecii is a well-described opportunistic pathogen in human immunodeficiency virus (HIV) infection, but it is less commonly associated with pneumonia in other states of immunocompromise. However, outbreaks of P. jirovecii pneumonia (PCP) have been described in renal transplant recipients in both Europe and Asia [1–3]. Explanations for this, including the possible modes of transmission, have not been established, and risk factors for the development of PCP remain poorly understood. However, policies relating to immunosuppression and HLA matching have changed in recent years [4], and PCP prophylaxis guidance in renal transplant recipients has a poor evidence base [5]. We write to draw attention to the preliminary results of investigation of 2 concurrent outbreaks of PCP in renal transplant recipients in the Northwest of England, followed by a United Kingdom–wide surveillance questionnaire of renal units with responses suggesting that there has been a national upsurge in such cases. Between November 2008 and July 2010, 21 cases of PCP were diagnosed in renal transplant recipients attending the transplant unit at the Royal Liverpool University Hospital, compared with 1 case in the

Review of Crimean Congo Hemorrhagic Fever Infection in Kosova in 2008 and 2009: Prolonged Viremias and Virus Detected in Urine by PCR

Crimean-Congo hemorrhagic fever (CCHF) is a virus transmitted predominantly by ticks. However, contact with infected body fluids or tissues can result in animal-to-human or human-to-human transmission. Numbers of CCHF cases appear to be increasing, especially in Europe. We reviewed cases admitted to a tertiary referral unit in Kosova with suspected CCHF in 2008 and 2009, and looked at a smaller number of specimens which were sent to the Health Protection Agency, Porton Down, U.K., in further detail. The clinical features of cases admitted with suspected CCHF infection were assessed in more detail, and these are the focus of this article. Between 2008 and 2009, the numbers of patients admitted for suspected CCHF infection increased. Of the samples received in Porton Down, CCHF virus was detected in urine samples, and these patients were found to have prolonged viremia. The detection of CCHF in urine, as well as the prolonged viremias seen, are important for clinicians to know, as they may have public health implications with regard to the risk of infection, as well as provide insights into the biology and pathophysiology of infection. Further studies are required regarding the pathogenesis of this virus.

‘Septrin psychosis’ among renal transplant patients with Pneumocystis jirovecii pneumonia

OBJECTIVES To report on the temporal relationship between administration of trimethoprim/sulfamethoxazole to medically immunosuppressed HIV-negative renal patients with Pneumocystis jirovecii pneumonia (PCP) and the development of an acute psychosis. METHODS We investigated a retrospective case series of renal transplant and immunosuppressed patients with PCP within an ongoing outbreak in the northwest of England since 2009. Four patients with PCP developed psychosis following treatment with trimethoprim/sulfamethoxazole. RESULTS Four of twenty patients developed acute psychoses following administration of trimethoprim/sulfamethoxazole, including one accidental re-challenge. Symptoms resolved within 24 h of changing the therapy. The striking temporal relationship between the initiation and discontinuation of the drug and the behavioural changes suggests a causal relationship. CONCLUSIONS With increasing solid organ transplantation and the use of immunosuppressants, vigilance regarding trimethoprim/sulfamethoxazole dose modification is required and the routine use of therapeutic drug monitoring should be considered.

Viral and atypical bacterial aetiologies of infection in hospitalised patients admitted with clinical suspicion of influenza in Thailand, Vietnam and Indonesia

Influenza constitutes a leading cause of morbidity and mortality worldwide. There is limited information about the aetiology of infection presenting clinically as influenza in hospitalised adults and children in South‐East Asia. Such data are important for future management of respiratory infections.

First report of human psittacosis in Vietnam.

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Acute presentations of HIV are still missed in low prevalence areas.

Objectives To evaluate missed opportunities and delays in the diagnosis of HIV in a low prevalence setting over a 24 year period. Methods Patients with acute presentations of HIV were included in a retrospective note based review. Data were compared from acute presentations in 1985–2001 (88/241 new patients) with 2005–2007 (99/136 new patients). The number of recorded clinical and laboratory clues to infection and subsequent time delays to diagnosis of HIV were evaluated. Results The findings reflect the shifting demographics of HIV in the UK over the past two decades, exemplified by an eightfold increase in tuberculosis at presentation. Despite recording clinical stigmata of HIV (clues) in the notes, the number of missed clues increased, and many clinicians failed to request HIV testing. The median delay between presentation and diagnosis reduced from 5 to 1 day (p<0.001), and mortality dropped from 14% to 4% among patients presenting with acute symptoms. However, there was still a delay of more than 30 days before diagnosis for almost one in five patients. Conclusions Despite some improvement and better awareness, there are still significant delays before hospital doctors consider the diagnosis of HIV for patients in low prevalence areas, even among some patient groups with high risk. Hospitals should consider moving to opt-out routine HIV testing of all medical admissions.