Epidemiological risk factors for hypersensitivity reactions to abacavir

We investigated risk factors for hypersensitivity reactions (HSR) to abacavir in a case-control study. In a multivariate analysis, white race [odds ratio (OR), 5.16; 95% confidence interval (CI), 1.16-22.97] and a higher CD8 cell count at initiation of abacavir (>850 vs. < or =850 cells: OR, 3.74; 95% CI, 1.19-11.77) were found to be significantly associated with the development of HSR. Age, gender, stage of disease, prior antiretroviral exposure and type of concurrent antiretroviral therapy were not associated with HSR. Differences in predisposition to HSR according to ethnicity and baseline CD8 cell count may be explained by the reported MHC genetic associations with HSR.     

Herpesvirus saimiri-immortalized human lymphocytes: novel hosts for analyzing HIV type 1 in vitro neutralization

Herpesvirus saimiri-immortalized CD4(+) T lymphocytes (HVS T cells) are activated memory cells that support efficient replication of primary R5 strains of HIV-1, which predominate in virus transmission. Being continuous, they are phenotypically more stable and technically less demanding than peripheral blood mononuclear cells (PBMCs). Here we present the first report using HVS T cells to assay HIV-1 neutralization in vitro. Neutralization sensitivities of paired viruses isolated from individuals in both HVS T cells (CN-2 cells) and PBMCs were similar, with homologous and heterologous plasma/sera in both CN-2- and PBMC-based assays. Analysis of V3 loop and CD4-binding site (CD4-BS) sequences showed that changes present in CN-2 isolates were neither more numerous nor more significant than those selected in their PBMC counterparts. Neutralization profiles of CN-2/PBMC virus pairs were similar again when V3- and CD4-binding site (BS)-specific monoclonal antibodies, whose mapped epitopes were conserved or of similar sequence in the virus pairs, were tested. Unlike other T cell line isolates, CN-2 isolates were not more sensitive to neutralization than their PBMC counterparts. We also show that HVS T cells do not appear to exert significant biological selection pressures on primary isolates. Paired viruses have a similar phenotype with respect to syncytium formation, cell tropism, and coreceptor usage. Thus CN-2 cells are suitable hosts for assaying neutralization and could be useful in standardizing neutralization assays performed in different laboratories.     

The changing pattern of AIDS-defining illnesses with the introduction of highly active antiretroviral therapy (HAART)in a London clinic

OBJECTIVES: To quantify the progressive impact of combination antiretroviral therapy (ART) on the incidence of AIDS-defining illnesses (ADIs) over a 9-year period. METHODS: Retrospective cohort study. Eligible patients were 1538 AIDS-free, HIV-1-positive patients attending a large HIV clinic in west London who were at risk of developing AIDS because their CD4 count had declined to < or =350 x 10(6)/l cells during the period 1 January 1990 and 31 December 1998. Incidence rates for the 12 most frequent ADIs were compared for two time periods, 1990-1995 (pre-HAART) and 1996-1998 (post-HAART), using Poisson regression methods. Multivariate Poisson regression models were used to examine the contribution of ART and HAART to any observed temporal trends in incidence rates. RESULTS: After a median follow-up of 35 months, 450 (29%) patients had developed AIDS. Between the two time periods there was a significant decrease in the incidence of Pneumocystis carinii pneumonia (PCP) by 35% (4.11 per 100 person-years in 1990-1995 vs. 2.67 in 1996-1998;P= 0.007), Kaposi's sarcoma by 34% (3.27 vs. 2.17;P= 0.022) and cryptosporidiosis by 60% (0.76 vs. 0.31;P= 0.029). A non-significant reduction in incidence was observed for cryptococcosis by 45% (0.81 vs. 0.45;P= 0.11), oesophageal candidiasis by 29% (3.34 vs. 2.39;P= 0.053) and mycobacterium avium complex by 18% (1.58 vs. 1.29;P= 0.4), and a non-significant increase was observed for tuberculosis by 17% (0.62 vs. 0.73;P= 0.66) and non-Hodgkins lymphoma (NHL) by 51% (0.43 vs. 0.65;P= 0.31). The incidence of cerebral toxoplasmosis, cytomegalovirus, recurrent bacterial chest infections and dementia remained stable. There was a clear stepwise reduction in the incidence of PCP, Kaposi's sarcoma and cryptosporidiosis with the use of non-H AART and HAART regimens relative to no ART. In a multivariate analysis, the use of ART and HAART explained the progressive decrease in incidence of PCP and Kaposi's sarcoma. CONCLUSIONS: The incidence of most ADIs has decreased over the last 9 years. The striking reduction in the inci-dence of PCP and Kaposi's sarcoma since 1996 can be attributed to the use of combination ART and particularly HAART. The non-significant increase in the incidence of NHL and tuberculosis needs confirmation in other patient cohorts.     

Norway rat population in Baltimore, Maryland, 2004

Norway rats are reservoirs for several zoonotic agents, including hantaviruses, and are implicated in the transmission of pathogens to humans in urban environments. The rat population of Baltimore, Maryland was estimated from surveys in 1949 and again in 1952, but has not been evaluated for more than 50 years. Previously identified sociodemographic risk factors for rat infestation, including median income, human density, and percentage of rental properties, were used to categorize census block groups in Baltimore. Rat infestation risk factors, including median income and human density, have improved over the last 50 years in Baltimore. Rat infestation was determined both by observation and trapping of rats in alleys that were representative of the different strata of risk factors. Despite improvements in risk factors, the outdoor, residential rat population of Baltimore in 2004 was estimated to be approximately 48,420 +/- 14,883 rats, which is comparable to the 1949 and 1952 estimates. Approximately half of the rats trapped in Baltimore City had detectable antibody against Seoul virus. The failure to substantially impact rat population levels in the past 50 years indicate that alternative control strategies for rat infestation are needed to reduce the risk of rat-borne pathogen spillover to the human population.     

Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes

Highly active antiretroviral therapy (HAART) has been advocated for the management of primary HIV-1 infection without clear understanding of its immunological effects. Here, we demonstrate that early use of HAART during primary infection preserves HIV-specific CD8(+) T cells physically and functionally while HIV-specific T cell help is sustained. We also show that even transient administration of HAART at seroconversion can preserve HIV-specific immunity. In contrast, delayed initiation of HAART is associated with a progressive loss of HIV-specific CD8(+) T cells and absent HIV-specific T cell help. These results imply that HIV-specific T help is damaged during primary HIV-1 infection. Early drug treatment, which preserves this immunity, also preserves HIV-specific CD8(+) T cells. These results have implications for understanding the early pathogenesis of HIV-1 infection and suggest that acute HIV infection should be treated aggressively and as early as possible.     

Use of cannabis in severe childhood epilepsy and child protection considerations

The use of medical cannabis in chronic illness is increasingly investigated, yet little is known about its use in paediatric populations. As child protection clinicians are often asked to provide advice around whether parents' actions to give medical cannabis to their chronically ill child constitutes harm or risk of harm, a review of the evidence base is required. This systematic review explores the use of cannabis‐derived products in children with seizure disorders. While a reduction in seizure activity was observed in some children, included studies were poorly designed and too small to extrapolate reliable conclusions about clinical use. Due to the lack of high‐quality evidence, the use of cannabis‐derived products is currently not recommended in children with seizure disorders. However, in assessing risk and harm to subject children by child protection physicians in Australia with existing State and Territory legislation, evaluation must occur on a case‐to‐case basis with each instance considered on its individual merits. Clinical trials addressing drug efficacy and long‐term safety of cannabis‐derived products are required.     

Raised intracranial pressure complicating cryptococcal meningitis: immune reconstitution inflammatory syndrome or recurrent cryptococcal disease?

We report the case of a patient with advanced HIV disease and cryptococcal meningitis, who after an initially good clinical and mycological response to systemic anti-fungal treatment developed symptomatic raised intracranial pressure 10 days after initiation of highly active anti-retroviral therapy. We describe the subsequent clinical management and the features that suggest that this persistently raised ICP was more likely due to an immune reconstitution syndrome (IRIS) following HAART rather than relapse of cryptococcal disease or failure of anti-fungal therapy.     

Improvement in low back pain following spinal decompression: observational study of 119 patients

Study design

Prospective clinical observational study of low back pain (LBP) in patients undergoing laminectomy or laminotomy surgery for lumbar spinal stenosis (LSS).

Objectives

To quantify any change in LBP following laminectomy or laminotomy spinal decompression surgery.

Patients and methods

119 patients with LSS completed Oswestry Disability Index questionnaire (ODI) and Visual Analogue Scale for back and leg pain, preoperatively, 6 weeks and 1 year postoperatively.

Results

There was significant (p < 0.0001) reduction in mean LBP from a baseline of 5.14/10 to 3.03/10 at 6 weeks. Similar results were seen at 1 year where mean LBP score was 3.07/10. There was a significant (p < 0.0001) reduction in the mean ODI at 6 weeks and 1 year postoperatively. Mean ODI fell from 44.82 to 25.13 at 6 weeks and 28.39 at 1 year.

Conclusion

The aim of surgery in patients with LSS is to improve the resulting symptoms that include radicular leg pain and claudication. This observational study reports statistically significant improvement of LBP after LSS surgery. This provides frequency distribution data, which can be used to inform prospective patients of the expected outcomes of such surgery.     

Prevalence and burden of HBV co‐infection among people living with HIV: A global systematic review and meta‐analysis

Globally, in 2017 35 million people were living with HIV (PLHIV) and 257 million had chronic HBV infection (HBsAg positive). The extent of HIV‐HBsAg co‐infection is unknown. We undertook a systematic review to estimate the global burden of HBsAg co‐infection in PLHIV. We searched MEDLINE, Embase and other databases for published studies (2002‐2018) measuring prevalence of HBsAg among PLHIV. The review was registered with PROSPERO (#CRD42019123388). Populations were categorized by HIV‐exposure category. The global burden of co‐infection was estimated by applying regional co‐infection prevalence estimates to UNAIDS estimates of PLHIV. We conducted a meta‐analysis to estimate the odds of HBsAg among PLHIV compared to HIV‐negative individuals. We identified 506 estimates (475 studies) of HIV‐HBsAg co‐infection prevalence from 80/195 (41.0%) countries. Globally, the prevalence of HIV‐HBsAg co‐infection is 7.6% (IQR 5.6%‐12.1%) in PLHIV, or 2.7 million HIV‐HBsAg co‐infections (IQR 2.0‐4.2). The greatest burden (69% of cases; 1.9 million) is in sub‐Saharan Africa. Globally, there was little difference in prevalence of HIV‐HBsAg co‐infection by population group (approximately 6%‐7%), but it was slightly higher among people who inject drugs (11.8% IQR 6.0%‐16.9%). Odds of HBsAg infection were 1.4 times higher among PLHIV compared to HIV‐negative individuals. There is therefore, a high global burden of HIV‐HBsAg co‐infection, especially in sub‐Saharan Africa. Key prevention strategies include infant HBV vaccination, including a timely birth‐dose. Findings also highlight the importance of targeting PLHIV, especially high‐risk groups for testing, catch‐up HBV vaccination and other preventative interventions. The global scale‐up of antiretroviral therapy (ART) for PLHIV using a tenofovir‐based ART regimen provides an opportunity to simultaneously treat those with HBV co‐infection, and in pregnant women to also reduce mother‐to‐child transmission of HBV alongside HIV.     

Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice

Highly pathogenic H5N1 influenza shares the same neuraminidase (NA) subtype with the 2009 pandemic (H1N1pdm09), and cross-reactive NA immunity might protect against or mitigate lethal H5N1 infection. In this study, mice were either infected with a sublethal dose of H1N1pdm09 or were vaccinated and boosted with virus-like particles (VLP) consisting of the NA and matrix proteins, standardized by NA activity and administered intranasally, and were then challenged with a lethal dose of HPAI H5N1 virus. Mice previously infected with H1N1pdm09 survived H5N1 challenge with no detectable virus or respiratory tract pathology on day 4. Mice immunized with H5N1 or H1N1pdm09 NA VLPs were also fully protected from death, with a 100-fold and 10-fold reduction in infectious virus, respectively, and reduced pathology in the lungs. Human influenza vaccines that elicit not only HA, but also NA immunity may provide enhanced protection against the emergence of seasonal and pandemic viruses.