Is the level of varicella-zoster virus IgG associated with symptomatic status of genital herpes simplex virus infection? A case-control study.

BACKGROUND: Herpes simplex virus (HSV) is a common infection, affecting the majority of the population by age of 50. Recurrent symptomatic outbreaks, experienced by a minority, have significant psychological and psychosexual effects. The varicella zoster virus (VZV), resembling HSV, shows potential for a functional cure via vaccination. This study seeks to investigate if there is an association between low VZV antibody levels and recurrent HSV outbreaks. METHODS: A total of 110 patients with symptomatic and asymptomatic HSV were recruited during their sexual health screen. Serum samples were collected between Aug 2019 - July 2022; breaks in the study occurred due to COVID. The primary outcome measure was the serological status of HSV and VZV IgG titre level. RESULTS: The average age was 37.3 years (range 21-65 years). For people with asymptomatic genital HSV2 the average VZV IgG titre was 2373.9 IU/mL (n = 17); and 1219.0 IU/mL for the symptomatic group (n = 67); p ≤ 0.00001), with similar results for HSV1. CONCLUSION: There is a strong association between average higher varicella-zoster virus (VZV) IgG level and being an asymptomatic carrier of herpes simplex sirus (HSV)1&2. A feasibility study to assess the use of the VZV vaccine as a treatment of HSV is planned.

Fulminant diffuse cerebral toxoplasmosis as the first manifestation of HIV infection.

Individuals with HIV may present to the emergency department with HIV-related or HIV-unrelated conditions, toxicity associated with antiretroviral therapy or primary HIV infection (seroconversion). In individuals with HIV infection, central nervous system toxoplasmosis occurs from reactivation of disease, especially when the CD4+ count is <100 cells/µL, whereas in those taking immunosuppressive therapy, this can be either due to newly acquired or reactivated latent infection. It is a rare occurrence in immune-competent patients. Vertical transmission during pregnancy can manifest as congenital toxoplasmosis in the neonate and is often asymptomatic until the second or third decade of life when ocular lesions develop. Toxoplasmosis is an infection caused by the intracellular protozoan parasite Toxoplasma gondii and causes zoonotic infection. It can cause focal or disseminated brain lesions leading to neurological deficit, coma and death. Typical radiological findings are multiple ring-enhancing lesions. Histopathological examination demonstrating tachyzoites of T. gondii and the presence of nucleic material in the spinal cerebrospinal fluid (CSF) confirms the diagnosis. The authors present the case of a 52-year-old male UK resident, born in sub-Saharan Africa, with a 3-week history of visual hallucinations. He attended the emergency department on three occasions. Laboratory investigations and a CT head were unremarkable. He was referred to psychological medicine for further evaluation. On his third presentation, 2 months later, a CT head showed widespread lesions suggestive of cerebral metastasis. Dexamethasone was initiated and he developed rigours. An MRI head showed multiple ring-enhancing lesions disseminated throughout his brain parenchyma. CSF analysis and serology confirmed the diagnosis of HIV and toxoplasmosis, respectively. His CD4 count was 10 and his viral load (VL) was 1 245 003. He was then initiated on Biktarvy 50 mg/200 mg/25 mg, one tablet daily, which contains 50 mg of bictegravir, 200 mg of emtricitabine and tenofovir alafenamide fumarate equivalent to 25 mg of tenofovir alafenamide. After 3 months of antiretroviral therapy, his HIV VL reduced to 42. However, his abbreviated mental test remained at 2/10. Despite presenting with neurocognitive impairment and being born in a HIV prevalent region, an HIV test was not offered. This case highlights missed opportunities to request HIV serology and raises awareness that cerebral toxoplasmosis can occur as the first manifestation of HIV. Prompt diagnosis and early initiation of antiretroviral therapy reduces morbidity and mortality in this patient cohort.

Missed opportunity to diagnose HIV with Pneumocystis carinii pneumonia as its sequela.

Pneumocystis carinii pneumonia (PCP) is an opportunistic infection of the lung occurring primarily in patients with HIV infection with a CD4 cell count <200 mm3, solid organ transplant recipients and those taking immunosuppressive therapy. The 1980s heralded the HIV pandemic, turning PCP into a major medical and public health problem worldwide. Manifestations of unusual infections such as pneumocystis and Kaposi's sarcoma, were, after all, the first signs of the emerging pandemic to be recognised and may indeed, be the presenting feature of a previously undiagnosed HIV infection. With the advent of pneumocystis chemoprophylaxis and the initiation of highly active antiretroviral therapy, there has been a decreased incidence in developed countries, but it remains high in developing countries. Unfortunately, late presentation of HIV remains a problem resulting in significant morbidity and mortality. The authors report the case of a new diagnosis of HIV infection in a 45-year-old woman, presenting with a dry cough, dyspnoea, unintentional weight loss and PCP. Two weeks after commencing highly active antiretroviral therapy, she was diagnosed with immune reconstitution inflammatory syndrome. Research shows that stigma and discrimination in the healthcare setting contributes to keeping individuals from accessing HIV prevention, care and treatment services and adopting key preventive behaviours. The barriers to HIV testing and stigma eradication in primary care will be explored as well as missed opportunities to diagnosis HIV in primary care in individuals presenting with signs and symptoms of immunosuppression, in this case shingles.

Factors influencing coroners' verdicts: an analysis of verdicts given in 12 coroners' districts to researcher-defined suicides in England in 2005.

BACKGROUND: To investigate the variation between coroners in the verdicts given to deaths thought by researchers to be probable suicides and analyse factors associated with the coroners' verdict. METHODS: Data were collected from 12 English coroner districts on all deaths in 2005 given a suicide, open, accidental or narrative verdict where suicide was considered a possibility. The data were reviewed by three experienced suicide researchers. Regression models were used to investigate factors associated with the coroners' verdict. RESULTS: The researchers classified 593 deaths as suicide, of which 385 (65.4%) received a suicide verdict from the coroner. There was marked variation between coroner districts in the verdicts they gave. The suicide method was associated strongly with the coroners' verdict; deaths from poisoning and drowning were the least likely to be given suicide verdicts. The other factors strongly associated with a coroner's verdict of suicide were: whether a note was left, age over 60 years and being married or widowed compared with being single. CONCLUSION: Coroners vary considerably in the verdicts they give to individuals who probably died by suicide. This may compromise the usefulness of suicide statistics for assessing area differences in rates for public health surveillance.

Meta-analysis of three case controlled studies and an ecological study into the link between cryptogenic epilepsy and chronic toxoplasmosis infection.

UNLABELLED: A meta-analysis was performed on three case controlled studies which examined the relationship between latent toxoplasmosis gondii infection in the immunocompetent host and cryptogenic epilepsy. Further comparison was also made by examining the seroprevalence of toxoplasmosis rates for 17 various countries, cities or regions against the prevalence rates for epilepsy in those regions. RESULTS: The results for the meta-analysis showed a log-odds ratio of 4.8 which approximates to a similar relative risk, (CI 2.6 to 7.8), with CI for all three studies being above 1. Seroprevalence rates for toxoplasmosis and prevalence rates of epilepsy showed a strong association (p<0.001). DISCUSSION: The prevalence of toxoplasmosis is an important factor in the prevalence of epilepsy with a probable link in the cryptogenic epilepsies. An area with a reduced burden of toxoplasmosis will also have a reduced burden of epilepsy. Neuropathophysiology findings from various studies show a common physical relationship of microglial nodule formation in Toxoplasma gondii infection and epilepsy. This analysis raises the possibility that one of the many causes of epilepsy may be an infectious agent, or that cryptogenic epilepsy may be a consequence of latent toxoplasmosis infection. This raises the possibility that public health measures to reduce toxoplasmosis infection may also result in a reduction in epilepsy.