Active and latent TB screening in recently arrived persons from Afghanistan: feasibility and lessons learned.

We describe an active and latent tuberculosis (TB) screening programme undertaken in Manchester, UK in response to the arrival of a cohort of refugees from Afghanistan. In total, 217 adults and 347 children were offered screening, which involved a symptom questionnaire, Mantoux test or interferon gamma release assay, blood-borne virus screening and a chest X-ray in participants over the age of 11. We found a latent TB infection (LTBI) rate of 15% in adults and 1.5% in children, which is lower than global LTBI estimates. One case of active TB was detected. Screening was undertaken in the hotels where participants were temporarily housed, leading to high participant engagement levels. Attendance rates were almost doubled compared with a previous hospital-based screening programme. Hotel-based screening for TB presented several challenges, including transfer of information and results to secondary care. Understanding these challenges and learning from the programme has helped us refine our screening protocol to optimise migrant TB screening in Manchester in the future.

Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients.

BACKGROUND AND PURPOSE: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. METHODS: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. RESULTS: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. CONCLUSION: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.

Does interferon-sparing tenofovir disoproxil fumarate-based therapy have a role in the management of severe acute hepatitis delta superinfection?

Infection with hepatitis delta virus (HDV) always occurs in association with hepatitis B virus (HBV) and is a cause of significant morbidity and mortality. We present a case of severe acute HDV infection superimposed on a previously unrecognized HBV infection, in which an interferon-sparing antiviral therapy consisting of tenofovir disoproxil fumarate (TDF) and lamivudine was initiated and subsequently maintained. Evidence of successful suppression of HDV ribonucleic acid (RNA) was obtained after 65 weeks of TDF-based treatment. This was mirrored by a significant reduction in the levels of HBV DNA and HBV surface antigen. HDV RNA subsequently rebounded after our patient stopped antiviral therapy of his own accord. Interferon-sparing TDF-based antiviral therapy was safe and effective in achieving HDV RNA suppression in acute HDV superinfection. Further research into the utility of interferon-sparing TDF-based regimes in the treatment of acute HDV infection is needed.

Allergic bronchopulmonary aspergillosis and related allergic syndromes.

While allergic bronchopulmonary aspergillosis (ABPA) is well recognized as a fungal complication of asthma, severe asthma with fungal sensitization (SAFS) is not. In ABPA the total immunoglobulin E (IgE) is usually >1,000 IU/mL, whereas in SAFS it is <1,000 IU/mL, and either skin prick tests or fungus-specific IgE tests are positive. ABPA may present with any severity of asthma, and occasionally with no asthma or cystic fibrosis, the other common underlying disease. SAFS is a problem in patients with poorly controlled asthma and occasionally presents in the intensive care unit (ICU). Production of mucous plugs and coughing paroxysms is more common in ABPA. Certain underlying genetic defects seem to underpin these remarkable phenotypic differences. From a management perspective both ABPA and SAFS respond to both high doses of corticosteroids and oral antifungal agents, with ∼60% response rate in both ABPA and SAFS with itraconazole. In 50% of patients itraconazole boosts inhaled corticosteroid exposure, sometimes leading to cushingoid features. Second-line therapy data are scant, but we have shown that 70 to 80% of patients who tolerate either voriconazole or posaconazole also respond. Other useful therapies include nebulized hypertonic saline to aid expectoration of thick sputum and long-term azithromycin for its anti-inflammatory effect on the airways. Omaluzimab is useful in some patients with SAFS and occasionally in ABPA. Complications of ABPA include bronchiectasis, typically central in distribution, and chronic pulmonary aspergillosis. Most patients with ABPA and SAFS can be stabilized for long periods with inhaled corticosteroids and itraconazole or another antifungal agent. Novel immunotherapies are on the horizon.

Improved pregnancy outcome in refugees and migrants despite low literacy on the Thai-Burmese border: results of three cross-sectional surveys.

BACKGROUND: Maternal and infant health has been associated with maternal education level, which is highly associated with literacy. We aimed at estimating literacy rates among reproductive age women attending antenatal clinics in camps for refugees and in migrant clinics in Tak province, north-western Thailand, to determine whether illiteracy had an impact on birth outcomes. METHODS: Three reading assessments were conducted using an identical method each time, in 1995-97, 2003 and 2008. Midwives chose at random one of four pre-set sentences. Each woman was asked to read aloud and scoring was based on a "pass/fail" system. Pregnancy outcomes were compared with maternal literacy rate. RESULTS: Overall, 47% (1149/2424) of women were able to read. A significant improvement was observed among migrant (34% in 2003 vs. 46% in 2008, p = 0.01), but not refugee (47% in 1995-97, 49% in 2003, and 51% in 2008) women. Literate women were significantly more likely to be of non-Karen ethnicity, primigravidae, non-smokers, to remain free from malaria during pregnancy and to deliver in a health clinic. Significant improvements in pregnancy outcome (reductions in premature births, low birth weight newborns and neonatal death) between 1995-97 and 2003 were unrelated to literacy. CONCLUSIONS: Significant reductions in poor pregnancy outcome over time have not been driven by changes in literacy rates, which have remained low. Access to early diagnosis and treatment of malaria in this population, and delivery with skilled birth attendants, despite ongoing low literacy, appears to have played a significant role.

Neurological complications in HIV.

HIV is neuroinvasive with early involvement of the nervous system and has the potential to cause disease at any site of the neuro-axis during the evolution from seroconversion to late stage HIV. Disease may result from direct viral infection, indirect immune-deficiency driven opportunistic infections, AIDS-defining cancers, antiretroviral (ARV) drug therapy, or less well elucidated associations, such as vascular events (Table 1). Recognition of each of these is paramount in the prevention or attenuation of long-term morbidity. Though the epidemiology of neurological disease has altered substantially since the arrival of combination antiretroviral therapy (cART), with reduced incidence and improved survival, the spectrum of central nervous system (CNS) diseases has remained relatively unchanged. Despite available treatment options, mortality remains high and the morbidity significant. CNS diseases can result in long hospital stays, reduced quality of life and marked disability. The majority of disease occurs in the advanced stages of HIV infection where immunosuppression is the predominant influence. Diagnosis can prove challenging as presentation is often atypical and there can be significant neurological involvement with limited evidence of disease. Multiple aetiologies can co-exist and investigations may yield unexpected results, rendering interpretation difficult. Paradoxically, cART may also alter the way CNS disease manifests and unmask opportunistic infections or cause clinical representation of the opportunistic infections, when it represents immune reconstitution syndrome (IRS). Clinical assessment, imaging (typically magnetic resonance imaging (MRI)) and cerebral spinal fluid (CSF) sampling remain the chief diagnostic tools. This conference summary reviews these differing aspects.