The WHO recognises neurological disorders as “one of the greatest threats to public health”, with neurological infections listed in the top ten most important disorders [1]. Acute neurological infections, such as meningitis and encephalitis, are a major cause of death and disability globally [2], and have a disproportionately large impact in many Development Assistance Committee (DAC) list countries including Malawi, India and Brazil. Unlike the majority of neurological diseases for which there is no therapy, for many acute neurological infections appropriate therapies exist, but treatment is often poor because of failure to diagnose the microbial cause [3, 4]. 

In many LMIC settings the basic but critical investigations, such as a lumbar puncture (LP) and microbiology are performed poorly, or not at all. For example, in one survey of 13 rural African hospitals, 7% of all 639 children admitted had fever and neck stiffness, but not a single one had a LP performed [5]. Even where LPs are done, an aetiological diagnosis is only made in 30-49% in many LMIC settings [6-9]; however, yields can be increased considerably by applying the latest molecular diagnostic approaches, which are becoming increasingly suitable for recourse-poor settings [10, 11]. With no aetiological diagnosis, clinicians are forced to give blind syndromic treatment; yet the drugs for common brain infections, such as pneumococcal meningitis, herpes encephalitis, or tuberculous meningitis are completely different. Doctors are therefore faced with covering all possibilities, which risks unnecessary side effect and contributes to antimicrobial resistance, or guessing at the diagnosis, which risks getting it wrong [3, 4]. In one recent systemic review, the fatality rates from brain infections in resource-poor countries was 15-58%, with 31-67% percent of survivors having neurological sequelae [3].

This GHRG programme will comprise a series of projects in interlinked themes addressing these issues.

At the end of 3 years we will have strengthened diagnostic capabilities and capacities in our partner LMICs, and improved patient outcomes. The GHRG will also have provided a platform for generating external funding to support subsequent interventional studies in a range of brain infections.

References

1. World Health Organisation. Neurological Disorders: Public Health Challenges. In: WHO, editor. Geneva, Switzerland: WHO Press; available online at http://www.who.int/mental_health/neurology/neurodiso/en/; 2007.

2. DALYs GBD, Collaborators H. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390: 1260-344.

3. Gwer S, Chacha C, Newton CR, Idro R. Childhood acute non-traumatic coma: aetiology and challenges in management in resource-poor countries of Africa and Asia. Paediatr Int Child Health 2013; 33: 129-38.

4. Scarborough M, Thwaites GE. The diagnosis and management of acute bacterial meningitis in resource-poor settings. Lancet Neurol 2008; 7: 637-48.

5. English M, Esamai F, Wasunna A, et al. Assessment of inpatient paediatric care in first referral level hospitals in 13 districts in Kenya. Lancet 2004; 363: 1948-53.

6. Griffiths MJ, Lemon JV, Rayamajhi A, et al. The functional, social and economic impact of acute encephalitis syndrome in Nepal - a longitudinal follow-up study. PLoS Negl Trop Dis 2013; 7: e2383.

7. Ho Dang Trung N, Le Thi Phuong T, Wolbers M, et al. Aetiologies of central nervous system infection in Viet Nam: a prospective provincial hospital-based descriptive surveillance study. PLoSOne 2012; 7: e37825.

8. Mallewa M, Vallely P, Faragher B, et al. Viral central nervous system infections in children from a malaria-endemic area of Malawi: a prospective cohort study Lancet Global Health 2013; 1: e153–e60.

9. Wall EC, Cartwright K, Scarborough M, et al. High mortality amongst adolescents and adults with bacterial meningitis in sub-Saharan Africa: an analysis of 715 cases from Malawi. PLoS One 2013; 8: e69783.

10. Benjamin LA, Lewthwaite P, Vasanthapuram R, et al. Human parvovirus 4 as potential caus of encephalitis in children, India. Emerg Infect Dis 2011; 17: 1484-7.

11. Dittrich S, Tadesse BT, Moussy F, et al. Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings: An Expert Consensus. PLoS One 2016; 11: e0161721.