Resource impact of managing suspected Middle East respiratory syndrome patients in a UK teaching hospital.

Clinical challenges exist in the management of hospitalized patients returning to the UK with potential Middle East respiratory syndrome coronavirus (MERS-CoV) infection, particularly with its clinical overlap with influenza, as demonstrated in this case-series and cost-analysis review of returning Hajj pilgrims. These patients were hospitalized with acute febrile respiratory illness, initially managed as potential MERS-CoV infections, but were eventually diagnosed with influenza. Additional costs were small, yet enhanced infection prevention measures created significant burdens on isolation rooms and staff time. Planning for predictable events such as Hajj is important for resource management. Here, in-house MERS-CoV diagnostic testing would have facilitated earlier diagnosis and discharge.

Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/µL. We describe the demographics, HIV-specific characteristics and medical history of this cohort. METHODS: Data collected at baseline include demographics, HIV-specific laboratory values, prior medical diagnoses and concomitant medications. Baseline characteristics were compared by geographical region, gender and age. RESULTS: START enrolled 4685 HIV-positive participants from 215 sites in 35 countries. The median age is 36 years [interquartile range (IQR) 29-44 years], 27% are female, and 45% self-identify as white, 30% as black, 14% as Latino/Hispanic, 8% as Asian and 3% as other. The route of HIV acquisition is reported as men who have sex with men in 55% of participants, heterosexual sex in 38%, injecting drug use in 1% and other/unknown in 5%. Median time since HIV diagnosis is 1.0 year (IQR 0.4-3.0 years) and the median CD4 cell count and HIV RNA values at study entry are 651 cells/µL (IQR 584-765 cells/µL) and 12,754 HIV RNA copies/mL (IQR 3014-43,607 copies/mL), respectively. CONCLUSIONS: START has enrolled a diverse group of ART-naïve individuals with high CD4 cell counts who are comparable to the HIV-positive population from the regions in which they were enrolled. The information collected with this robust study design will provide a database with which to evaluate the risks and benefits of early ART use for many important outcomes.

Antenatal hepatitis B in a large teaching NHS Trust - implications for future care.

OBJECTIVES: To establish the workload expected as a result of introducing antenatal antivirals for the prevention of vertical transmission of hepatitis B virus. METHODS: Retrospective review of all HBsAg-positive women and their infants, between 2005 and 2011, in a large (population 1 million) teaching NHS Trust in Leicester, UK, a highly ethnically diverse city. RESULTS: 7% of pregnancies occurred in women who were taking, or would now be recommended to take, antenatal antivirals. 176 infants were born to 140 HBsAg-positive women through 172 pregnancies (mean 29 pregnancies/year). Two (1.1%) were vertically infected, including one born to a mother with HBeAg(-)/HBeAb(+) disease and HBV viral load 2 million IU/ml who would not currently be recommended for antenatal antivirals. 81.1% infants completed all HBV vaccinations; 79.5% completed serology testing. 96.4% women were referred to the hepatitis clinic, but 30% disengaged from clinic follow-up, with no significant difference between ethnic groups in terms of maternal disengagement, or failure to complete infant vaccinations or serology testing. CONCLUSIONS: Only a small percentage of HBsAg-positive women are likely to meet the newly published criteria for antenatal anti-viral treatment. Strengthened community engagement across multiple ethnic groups is of paramount importance to improve maternal and infant outcomes.

The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy.

Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost-effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium-term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS 'Payment by Results' database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non-SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5-year post-treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13-fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56-fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real-life data for future cost-effectiveness analyses related to the treatment for chronic HCV infection.

Thrombotic thrombocytopaenic purpura occurring in consecutive pregnancies in an HIV-infected patient.

We present an HIV-infected patient who presented with thrombotic thrombocytopaenic purpura (TTP) during two consecutive pregnancies. To our knowledge, relapse of TTP during successive pregnancies in HIV infection has never been reported. This case reiterates that TTP should be considered in HIV-infected patients presenting with pregnancy-related complications.

Progressive symptoms and signs following institution of highly active antiretroviral therapy and subsequent antituberculosis therapy: immune reconstitution syndrome or infection?

A 36 year old man presented with weight loss, cough, fever, and exertional dyspnoea shortly after a diagnosis of HIV infection. Symptoms and initial radiological abnormalities worsened after highly active antiretroviral therapy was started. An eventual diagnosis was established but multiple problems occurred throughout the treatment period. Differentiation between immune reconstitution inflammatory syndrome and an infective cause was problematic.

Disseminated Sporothix schenckii in a patient with AIDS.

Sporothrix schenckii is a widespread dimorphic fungus which can cause cutaneous infection following local implantation. Disseminated sporotrichosis may occur in immunodeficient individuals but meningitis remains a rare complication. Diagnosis is usually difficult, requiring isolation of the organism from the CSF or skin so appropriate treatment can be promptly initiated. We present the first case of S. schenckii meningitis reported in the UK in a patient with AIDS. He presented with insidious features of meningoencephalitis, hydrocephalus and multiple cutaneous lesions and failed to respond to therapy.

Invasive pulmonary aspergillosis complicating chronic obstructive pulmonary disease in an immunocompetent patient.

Immunocompromised individuals are susceptible to pulmonary aspergillus infection, but invasive aspergillus infection is extremely rare in the presence of normal immunity. We report a case of invasive aspergillosis in an immunocompetent 63-year-old male with chronic obstructive pulmonary disease (COPD). Patients with COPD may be at risk for developing pulmonary aspergillus infection, which should be considered as a diagnostic possibility in patients with unresolving pulmonary infection.

Impact of human immunodeficiency virus (HIV) infection on the progression of liver fibrosis in hepatitis C virus infected patients.

OBJECTIVES: To compare the rate of hepatic fibrosis progression in hepatitis C virus (HCV) infected and human immunodeficiency virus (HIV)-HCV coinfected patients, and to identify factors that may influence fibrosis progression. PATIENTS AND METHODS: A total of 153 HCV infected and 55 HCV-HIV coinfected patients were identified from two London hospitals. Eligible patients had known dates of HCV acquisition, were HCV-RNA positive, and had undergone a liver biopsy, which was graded using the Ishak score. Univariate and multivariate logistic regression analyses were used to identify factors associated with fibrosis progression rate and the development of advanced fibrosis (stages 3 and 4). RESULTS: The estimated median fibrosis progression rate was 0.17 units/year (interquartile range (IQR) 0.10-0.25) in HIV-HCV coinfected and 0.13 (IQR 0.07-0.17) in HCV monoinfected patients (p=0.01), equating to an estimated time from HCV infection to cirrhosis of 23 and 32 years, respectively. Older age at infection (p<0.001), HIV positivity (p=0.019), higher alanine aminotransferase (ALT) level (p=0.039), and higher inflammatory activity (p<0.001) on first biopsy were all independently associated with more rapid fibrosis progression. ALT was correlated with histological index (r=0.35, p<0.001). A CD4 cell count < or =250 x 10(6)/l was independently associated with advanced liver fibrosis (odds ratio 5.36 (95% confidence interval 1.26-22.79)) and was also correlated with a higher histological index (r=-0.42, p=0.002). CONCLUSION: HIV infection modifies the natural history of HCV by accelerating the rate of fibrosis progression by 1.4 fold, and the development of advanced fibrosis threefold. A low CD4 cell count was independently associated with advanced disease and correlated with higher histological index, which suggests that early antiretroviral therapy may be of benefit in slowing HCV progression in coinfected patients.

Polyarteritis nodosa presenting as a pyrexia of unknown origin.

A case of an 18 year old woman is reported who presented with a pyrexia of unknown origin having returned from a trip to India. She initially had constitutional symptoms only, which rapidly progressed to a multisystem disorder. The difficulty in making the diagnosis of polyarteritis nodosa, especially with the possible differential diagnosis of infection after her recent travel, is discussed. The discussion reviews the condition of polyarteritis nodosa and analyses the diagnostic difficulties in this case.

New World leishmaniasis from Spain.

A 69 year old man living in Spain contracted mucocutaneous leishmaniasis involving the nose. The infecting organism was Leishmania infantum, which only rarely causes the New World form of the disease. The source of infection was probably a neighbour's dog. The patient began treatment with liposomal amphotericin B but died of pneumonia two months later.

Resistance-associated mutations in the human immunodeficiency virus type 1 subtype c protease gene from treated and untreated patients in the United Kingdom.

This work reports the variability of human immunodeficiency virus type 1 (HIV-1) protease from treated and untreated patients infected with HIV-1 subtype C in the United Kingdom. The most common primary mutation observed in treated patients was L90M. D30N, M46I, V82A/F, and I84V were seen rarely. M36I and I93L mutations were observed in nearly all samples from both treated and untreated patients and so cannot be considered as resistance-associated mutations in this subtype.

Drug treatment of tropical parasitic infections: recent achievements and developments.

Drug development offers potential solutions to a number of tropical health diseases, although the expense of pharmaceutical research and lack of return on investment has limited the production of new agents. The greatest successes have been through the development of single dose therapy and mass treatment control programmes for a number of diseases. We review some of the current treatment regimens for malaria, intestinal helminth infection, onchocerciasis, filariasis and schistosomiasis, and their use in clinical practice. Geographical spread and emergence of drug resistant parasites have hindered the control of malaria, the most important global parasitic infection. Artemisinin compounds have proved effective antimalarial agents producing rapid reduction of parasite load and can be used in combination treatment regimens to combat multidrug resistance. Intestinal helminth infections are widespread, giving rise to nutritional deficiencies and impaired childhood cognitive development. Pregnant women in developing countries are at increased risk of morbidity. Treatment with a single dose benzimidazole such as albendazole or mebendazole has beneficial effects on morbidity and rates of transmission. Diethylcarbamazine has been used in the treatment of onchocerciasis and human filariasis. A complicated escalating dose regimen over several weeks is associated with systemic and allergic reactions and may require corticosteroid cover. Simplified regimens for mass population treatment with ivermectin have proved useful and been used in combination with single dose albendazole and diethylcarbamazine. The African Programme for Onchocerciasis Control in West and Central Africa has been one of the most successful mass control programmes virtually eliminating new infections by a combination of chemotherapy, education and vector control. Schistosomiasis is of increasing importance as a result of the creation of new snail habitats by agricultural and economic development. Praziquantel has become the most widely available and effective chemotherapy for schistosomiasis. There have been a number of reports of persistent schistosome egg shedding after treatment posing concerns about the emergence of drug resistance. Eflornithine has been successfully used in patients with human trypanosomiasis failing melarsoprol therapy however expense and availability have limited its potential. Mass control treatment programmes have targeted schoolchildren, adolescents and pregnant women. The integration of schistosomiasis, onchocerciasis, filariasis and helminth control programmes has been considered as a cost-effective method of delivering treatment. It is likely that future control will be based on this optimisation and integration of existing regimens, rather than the development of new agents.

Extensive psoriasis induced by interferon alfa treatment for chronic hepatitis C.

A 47 year old man with chronic hepatitis C was treated with interferon alfa, 3 million units three times a week, and developed widespread plaque psoriasis within weeks of starting interferon therapy. There was no previous history of psoriasis. The psoriasis was characterised by extensive nail involvement and plaques at the interferon injection sites. The patient relapsed after a total of 12 months of interferon and was subsequently treated with interferon and tribavirin (ribavirin) with recurrence of the psoriasis.