Adult studies

TIMING (opTImisation of Methods for a human INfection model for Group B streptococcus)

Group B Streptococcus (GBS) is a bacteria that can live in the genital tract of women. It is usually harmless and does not affect you unless you are pregnant. At any one time it usually can be found in the vagina or rectum of around 30% of all women, this is called colonisation. GBS comes and goes from the vagina and rectum over the course of your life and the reasons why it does this are unclear. If you are found to be colonised with GBS and you are not pregnant then you do not need to have any treatment and you are not at any risk of illness. When a woman has GBS in the vagina or rectum during pregnancy, there is a risk that it can cause an infection in the baby around the time of birth and in babies, Group B streptococcus can cause meningitis and blood stream infections. It is the number one cause of meningitis in new-born babies. The purpose of this study is to collect samples from the vagina and rectum of healthy non-pregnant women every two weeks for a period of three months. This is to find out how colonisation with GBS changes over the course of three months. We also know that when a woman is colonised with GBS, she produces antibodies (a part of the natural immune system defence which can be found in the blood and body fluids). The second purpose of the study is to see if there is a link between colonisation of the rectum and vagina with GBS and the amount of antibody that can be detected in the blood and in the nose. For this we would like to take a total of three blood samples at the beginning, middle and end of the study and we will test vaginal fluid samples for antibody every two weeks.

GenAfrica

Black ethnicity is a major risk factor for chronic kidney disease [CKD] in people with HIV infection, suggesting that genetic factors are an important determinant of kidney disease progression in this population. Genetic variants in the apolipoprotein L1 (APOL1) gene, which are largely restricted to individuals with African ancestry, are recessively associated with focal and segmental glomerulosclerosis [FSGS] and hypertensive end-stage kidney disease (ESKD) in African Americans. In HIV positive individuals, the presence of 2 APOL1 risk alleles (G1/G1, G1/G2 or G2/G2) is associated with 29-89 fold increased odds of HIVAN, the commonest and most severe form of CKD in this population, and more rapid decline in estimated glomerular filtration rate [eGFR] and progression to ESKD in individuals with uncontrolled HIV replication. Recent studies have also reported sickle cell trait (SCT), a common genetic variant in black populations, to be associated with end-stage renal disease in African Americans.

The pathogenesis of APOL1- and SCT-associated CKD is incompletely understood, and the contribution of APOL1 risk alleles and SCT to adverse kidney outcomes in black people in the UK is unknown. As people with HIV appear to be at particularly increased risk of APOL1-associated CKD and the prevalence of HIV approaches 50% in some regions of Africa, it is particularly relevant to investigate the potential contribution of these genetic polymorphisms to kidney disease in this population. We propose to study kidney disease (progression) in a large sample of black African, black Caribbean and black British individuals who participate in the UK CHIC study, the majority of whom are under regular follow up and in receipt of antiretroviral therapy (ART) with regular monitoring of kidney function.

Objectives

  • To establish a DNA Bioresource of black people living with HIV in the UK
  • To determine the prevalence of APOL1 risk alleles and SCT in people from different parts of sub-Saharan Africa and the Caribbean
  • To describe rates of CKD (progression) in participants with 0, 1 or 2 APOL1 risk alleles
  • To describe rates of CKD (progression) in participants with/without SCT
  • To identify novel genetic risk factors for HIVAN/FSGS, CKD and kidney disease progression
Pro-Positive
Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis when it enters the blood stream (sepsis) and/or crosses the blood-brain barrier (meningitis). It can be a devastating disease with serious permanent sequelae and fatalities. Certain populations, such as babies and teenagers and those with asplenia and complement deficiency are at a higher risk of developing serious disease. Recently published UK data has shown that people living with HIV are also at increased risk of IMD.
Of the thirteen serogroups that have been described, five are responsible for most cases of IMD worldwide (serogroups A, B, C, W and Y). Since routine vaccination against serogroup C (MenC) was introduced in 1999, serogroup B (MenB) has become the main cause of IMD in the UK. Disease caused by other serogroups is less common and mainly occurs in adults; however, a national outbreak of serogroup W disease is currently ongoing in the UK.
The meningococcal quadrivalent conjugate vaccine (MenACWY, Menveo®) and the recently licenced multicomponent MenB vaccine (4CMenB, Bexsero®) have already been included in the UK childhood immunisation programme. Current recommendations also include these vaccines for those with asplenia and complement deficiency. HIV infection has not been classified as risk factor for IMD and until recently, it is not been given as an indication for meningococcal vaccination. The British HIV Association (BHIVA) has recently published new guidelines concerning meningococcal vaccination in this population. HIV positive patients are recommended to have two doses of meningococcal vaccines given two months apart with the following guidance: a) MenC, MenACWY and 4CMenB for those who are <25 years of age, b) MenC, 4CMenB and MenACWY for patient with a diagnosis of asplenia or complement deficiency, c) MenACWY for travellers to endemic areas, d) any of the licenced vaccines for those who are at risk of exposure through outbreaks.
Recent surveillance undertaken by PHE between 2011 and 2013 has revealed that HIV infection is a risk factor for IMD in the UK. Compared with the HIV uninfected population the relative risk for IMD in persons living with HIV was estimated to be 4.5 (mean annual IMD incidence 6.6 per 100.000 persons with HIV-infection versus 1.5 per 100.000 persons without HIV-infection). Among HIV-infected individuals the risk of IMD by capsular group varied with age. Young adults (16-24 year-olds) appeared to be at increased risk of MenB disease while in adults aged 16-64 the risk of IMD caused by the other four common capsular groups (A/C/W/Y) was 23-fold higher compared to the general population. Those who were known to be HIV positive were receiving antiretroviral therapy (ART) at the time of infection and had not received any meningococcal vaccination prior to developing IMD. Most patients were born outside of the UK, typically in Africa. Studies in the US and South Africa have also found that HIV positive adults appear to be at significantly higher risk of IMD with 10 and 11.3-fold increased risk of mortality respectively.
Taken together, these findings strongly suggest that adults living with HIV may benefit from both the MenACWY (Menveo®) conjugate vaccine and the multicomponent 4CMenB (Bexsero®) vaccine. Studies from the US and Brazil have demonstrated the safety and immunogenicity of the quadrivalent vaccine although no studies have not been conducted in the UK. Safety and immunogenicity of the recently licenced 4CMenB (Bexsero®) vaccine has not been assessed in this population to date.
In a recently conducted UK study, 3 doses of 4CMenB (Bexsero®) and MenACWY (Menveo®) proved to be safe and immunogenic when administered concomitantly in a healthy at risk adult population. The proportion of subjects with protective SBA titres for MenB were not significantly different after the 2nd and 3rd dose of 4CMenB (Bexsero®) vaccine suggesting that 2 doses may be sufficient in adults.
We have a large diverse population of over 1700 patients with HIV infection in South London who have acquired their infection from different routes. There is a wide spectrum of ethnicity and country of origin. We recently conducted an audit of vaccination uptake in this population. Of the 100 adult patient records randomly reviewed only 4 had had any meningococcal vaccination as documented by their GP.
In the proposed study, we plan to administer two doses of MenACWY (Menveo®) and 4CMenB (Bexsero®) vaccines, one month apart, to patients aged 10-45 years living with HIV.