Working Internationally

In the area of vaccine-preventable diseases, our scientists are involved in a number of international initiatives to evaluate pneumococcal vaccine roll-out. Our molecular serotyping approach developed by this group is being applied to studies worldwide, including Kenya, The Gambia, South Africa, Indonesia, Fiji, Nepal, Mongolia, Laos, Papua New Guinea and Vietnam.

Since 1999, the institute has supported a clinical research team in Ecuador, investigating infection and immunity in children. Our studies show the impact of parasitic infections and urbanisation on immune responses to childhood vaccines and the development of allergic sensitisation, eczema and asthma.

The spread of antimicrobial resistance (AMR) is an urgent, global threat, raising the possibility of a world without effective antibiotics. Among the initiatives being planned to prevent (or at least control) such a crisis, special attention is required for newborn babies (neonates), since their immune system is not yet fully developed, and therefore they are particularly vulnerable to infection. At present, treatments are delivered often without knowledge of optimal dosing, exposure and efficacy of the drugs, off label use, inappropriate choices given the pathogens and resistance patterns involved, and inadequate formulations. A solution for this vulnerable group is urgently required.

Group-B streptococcal (GBS) disease is a major cause of infant mortality and morbidity globally. In low/middle income settings, the disease burden remains uncertain although in several countries of Southern Africa appears comparable to that of high-income countries (1.4/1000 live births). Colonisation rates in pregnant women range from 12-50% and around 50% of their infants will be colonised. Of these, ca. 1% are known to develop GBS disease with 10% mortality and subsequent severe disability in up to 50% in survivors of GBS meningitis. Since there are geographical differences in strain distribution, the global effectiveness of GBS vaccines currently in development is unknown, and GBS-serotype specific recent data from Africa are lacking to predict potential impact. The effect of maternal GBS carriage on serotype-specific antibody transfer to her infant and subsequent antibody function, and the natural history of decline in antibody in infant blood and breastmilk has not been evaluated but matters for future vaccination strategies. Our researchers are currently undertaking several studies to answer important questions about serocorrelates of protection in Uganda and the UK, including the standardisation of GBS antibody assays.

CryptoMAG is an international, multi-organizational coalition to address gaps in the prevention, prompt diagnosis and management of cryptococcal meningitis, a leading cause of HIV-related death in African low- and middle-income countries (LMICs).

CryptoMAG is chaired and has been led by a clinical academic from the institute since 2013 in partnership with the Centres for Disease Prevention and Control (CDC). The coalition has proven to be an important forum for implementers, policy makers, funders, civil society and academic experts and includes over 10 different organizationsincluding: the WHO, Médecins sans Frontières (MSF)-Access Campaign, Clinton Health Access Initiative (CHAI), Elizabeth Glazer Paediatric Foundation (EGPAF), Coalition PLUS, Global Action Fund for Fungal Infections (GAFFI), National Institute of Communicable Diseases (NICD) SA and renowned academic experts from the US and Europe (University of Minnesota, University of Oxford, Institut Pasteur etc).

Priority aims for the advocacy efforts of the cryptoMAG group are:

1. Obtaining sustainable access to essential medicines (flucytosine, fluconazole and amphotericin B (deoxycholate and liposomal formulations) and diagnostic tests including the cryptococcal antigen lateral flow assay (CrAg LFA).

2. The implementationof cryptococcal antigen (CrAg) screening & pre-emptive treatment programs that prevent or identify cryptococcal disease earlier.

3. Implementation of optimised, effective treatment strategies for confirmed cases of cryptococcal meningitis in resource limited settings in line with the results of the St George's-led ACTA trial and latest 2018 WHO guidance on cryptococcal disease.

4. Drive the research and development of new antifungals.  No new antifungals for cryptococcal meningitis developed in over 25 years.

Key achievements of the cryptoMAG group to date include:

• lobbying of essential antifungal medicine manufacturers in close partnership with MSF’s Access Campaign

• lobbying of Unitaid which played a role in the recently launched Unitaid/CHAI initiative on advanced HIV disease 

• amphotericin B (AmB) and flucytosine (5FC) listed on WHO’s Essential Medicines List (EML)

• cryptococcal meningitis included in the global health Policy Cures Research’s G-Finder report since 2013

• supportive application made to the Tropical Disease Priority Review Voucher program which helped lead to the successful inclusion of cryptococcal meningitis

• 3 high-impact editorials (2 Lancet Infectious diseases & 1 Plos NTD) published; 1 BBC World interview & 2 journalistic pieces on cryptococcal meningitis

• 1 key burden of cryptococcal meningitis disease Lancet ID paper publication through collaboration of cryptoMAG members

• high-impact work with community activists and patient advocates on cryptococcal meningitis and advanced HIV disease around AIDS Amsterdam 2018.