Mike Beadsworth

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.

Characterization of Genotypes of Enterocytozoon bieneusi in Immunosuppressed and Immunocompetent Patient Groups

ABSTRACT. A retrospective phylogenetic analysis was performed on isolates of Enterocytozoon bieneusi to characterize the genotypes in different patient cohorts. Fifty‐seven isolates, collected from patients living in Malawi and the Netherlands, were classified by age and immune status of the hosts. Sequence analysis of the internal transcribed spacer (ITS) region identified 16 genotypes; nine have not previously been described. Genotypes K and D were most prevalent among patient groups, whereas genotype C was restricted to transplantation patients receiving immunosupressives and genotype B showed a predisposition toward patients living with HIV/AIDS. Different genotypes showed more dispersion among isolates from Malawi compared with those from the Netherlands. A constructed map estimating the genealogy of the ITS region reveals a dynamic evolutionary process between the genotypes.

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

Clinical and diagnostic findings of an echovirus meningitis outbreak in the north west of England

Introduction: An outbreak of echovirus meningitis occurred in the north west of England in 2001. This paper reviewed the clinical features and the role of different diagnostic methods. Methods: This was a prospective study of adults admitted to a regional infectious disease unit with a probable diagnosis of meningitis, March to August 2001. Results: Half the 40 cases were male; median age was 28 (range 16–51) years. Fifteen of 38 (39.5%) were smokers, and 20 of 24 (83.3%) had close contact with children. Median (range) duration of symptoms was 1.1 (0.25–7) days. Symptoms included headache (100%), photophobia (87.5%), and nausea (67.5%), and severity ranged from minimal signs to those consistent with a meningoencephalitis. The diagnosis was confirmed virologically in 29 of 40 (72%); echovirus 30 was isolated from six. Cerebrospinal fluid (CSF) enterovirus polymerase chain reaction (PCR) was positive in 26 of 32 (81%), and CSF virus culture in 3 of 16 (19%). Thirty one per cent of CSF samples had a neutrophil predominance, and 3 of 29 (10%) virologically confirmed cases had normal CSF microscopy and biochemistry. Conclusion: CSF microscopy may be normal or suggest bacterial meningitis in a substantial minority of cases of echovirus meningitis. CSF PCR for enterovirus seems to be more sensitive than virus culture of CSF, although PCR does not yield information on circulating virus type. Early and accurate diagnosis could reduce both use of parenteral antibiotics and length of hospital stay with both morbidity and cost implications. Close contact with children may be a risk factor, particularly if good hygiene measures are not practised.

Community-acquired pneumonia: doctors do not follow national guidelines

Objectives: Appropriate assessment of community-acquired pneumonia (CAP) allows accurate severity scoring and hence optimal management, leading to reduced morbidity and mortality. British Thoracic Society (BTS) guidelines provide an appropriate score. Adherence to BTS guidelines was assessed in our medical assessment unit (MAU) in 2001/2 and again in 2005/6, 3 years after introducing an educational programme. Methods: A retrospective case-note study, comparing diagnosis, documentation of severity, management and outcome of CAP during admission to MAU during 3 months of each winter in 2001/2 and 2005/6. Results: In 2001/2, 65/165 patients were wrongly coded as CAP and 100 were included in the study. In 2005/6 43/130 were excluded and 87 enrolled. In 2005/6, 87% did not receive a severity score, a significant increase from 48% in 2001/2 (p<0.0001). Parenteral antibiotics were given to 79% of patients in 2001/2 and 77% in 2005/6, and third generation cephalosporins were given to 63% in 2001/2 and 54% in 2005/6 (p = NS). In 2001, 15 different antibiotic regimens were prescribed, increasing to 19 in 2005/6. Conclusions: Coding remains poor. Adherence to CAP management guidelines was poor and has significantly worsened. Educational programmes, alone, do not improve adherence. Restriction of antibiotic prescribing should be considered.

Calprotectin and Lactoferrin Faecal Levels in Patients with Clostridium difficile Infection (CDI): A Prospective Cohort Study

Measurement of both calprotectin and lactoferrin in faeces has successfully been used to discriminate between functional and inflammatory bowel conditions, but evidence is limited for Clostridium difficile infection (CDI). We prospectively recruited a cohort of 164 CDI cases and 52 controls with antibiotic-associated diarrhoea (AAD). Information on disease severity, duration of symptoms, 30-day mortality and 90-day recurrence as markers of complicated CDI were recorded. Specimens were subject to microbiological culture and PCR-ribotyping. Levels of faecal calprotectin (FC) and lactoferrin (FL) were measured by ELISA. Statistical analysis was conducted using percentile categorisation. ROC curve analysis was employed to determine optimal cut-off values. Both markers were highly correlated with each other (r2 = 0.74) and elevated in cases compared to controls (p<0.0001; ROC>0.85), although we observed a large amount of variability across both groups. The optimal case-control cut-off point was 148 mg/kg for FC and 8.1 ng/µl for FL. Median values for FL in CDI cases were significantly greater in patients suffering from severe disease compared to non-severe disease (104.6 vs. 40.1 ng/µl, p = 0.02), but were not significant for FC (969.3 vs. 512.7 mg/kg, p = 0.09). Neither marker was associated with 90-day recurrence, prolonged CDI symptoms, positive culture results and colonisation by ribotype 027. Both FC and FL distinguished between CDI cases and AAD controls. Although FL was associated with disease severity in CDI patients, this showed high inter-individual variability and was an isolated finding. Thus, FC and FL are unlikely to be useful as biomarkers of complicated CDI disease.

Lyme disease in a British referral clinic

BACKGROUND Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK. AIM To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed. DESIGN Descriptive study conducted by retrospective casenotes review. METHODS Retrospective casenotes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006-2010). RESULTS Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners. CONCLUSION A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non-NHS settings.

Autopsies in HIV: still identifying missed diagnoses

This study reviews the deaths and autopsies carried out over 23 years, 1983–2005, in a British Infection Unit in HIV patients. Of 115 HIV patients known to have died, we obtained data on 93%. Of this 80% were male, median age 38 (25–68) years; 83% were Caucasian; 12% Black African. Major risk factors were men who have sex with men, 52%; heterosexual in Africa, 17%; and injecting drug use, 8%. The commonest diagnosis pre- and post-autopsy diagnosis was pneumonia. Changes in diagnoses in the 38% who underwent autopsy were high (we requested autopsy in 50%). Primary diagnosis changed in 70%, and 36% of all opportunistic infections were missed. This included six of nine cytomegalovirus, all tuberculosis and 75% of Kaposis sarcoma. Lymphoma was overdiagnosed. Thus, despite excellent resources, the majority of primary diagnoses were wrong, suggesting inadequacy of current diagnostics. To improve these and improve both epidemiological data and future management autopsy should be considered for all deaths.

Reliability of rapid testing for hepatitis B in a region of high HIV endemicity

Hepatitis B (HBV) and HIV co-infection is common in resource-poor settings. A recent study from Malawi revealed poor correlation between hepatitis B surface antigen (HBsAg) point-of-care tests and reference tests in patients co-infected with HIV. We studied a cohort of 300 Malawian adults entering a treatment programme for HIV. Sera were tested for HBsAg first using the Determine rapid test and re-tested using a commercial enzyme immunoassay (EIA). All tests were done under optimal conditions in Liverpool, UK. Sera from all 25 patients positive for HBsAg using the rapid test and from 50 who were negative, were re-tested using the EIA, with complete concordance of results. The kappa correlation was 1, specificity 100% (93-100%) and sensitivity 100% (86-100%) compared to the reference test. Patients had advanced immune suppression (mean CD4=175 cells x 10(6)/l). In a non-field setting, the results of point-of-care Determine rapid hepatitis B tests appear reliable in patients with HIV-1 co-infection.

Multiorgan dysfunction caused by travel-associated African trypanosomiasis.

We describe a case of multiorgan dysfunction secondary to Trypanosoma brucei rhodesiense infection acquired on safari in Zambia. This case was one of several recently reported to ProMED-mail in persons who had traveled to this region. Trypanosomiasis remains rare in travelers but should be considered in febrile patients who have returned from trypanosomiasis-endemic areas of Africa.