Global research priorities for infections that affect the nervous system

Chandy C John, Hélène Carabin, Silvia M Montano, Paul Bangirana, Joseph R Zunt, Phillip K Peterson, Chandy C John, Hélène Carabin, Silvia M Montano, Paul Bangirana, Joseph R Zunt, Phillip K Peterson

Abstract

Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries.

References

    1. Fooks AR, et al. Current status of rabies and prospects for elimination. Lancet. 2014;384:1389–1399.
    1. Labeaud AD, Bashir F, King CH. Measuring the burden of arboviral diseases: the spectrum of morbidity and mortality from four prevalent infections. Popul. Health Metr. 2011;9:1.
    1. Whitley R. In: Infections of the Central Nervous System. Whitley RJ, et al., editors. Lippincott Williams & Wilkins; 2014. pp. 137–157.
    1. McGrath N, Anderson NE, Croxson MC, Powell KF. Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J. Neurol. Neurosurg. Psych. 1997;63:321–326.
    1. Richter RW, Shimojyo S. Neurologic sequelae of Japanese B encephalitis. Neurology. 1961;11:553–559.
    1. Dutta K BA. In: Neuroinflammation and Neurodegeneration. Toborek Peterson M, editor. Springer; 2014. pp. 309–335.
    1. Kleinschmidt-DeMasters BK, Gilden DH. Varicella-Zoster virus infections of the nervous system: clinical and pathologic correlates. Arch. Pathol. Lab. Med. 2001;125:770–780.
    1. Insinga RP, Itzler RF, Pellissier JM, Saddier P, Nikas AA. The incidence of herpes zoster in a United States administrative database. J. Gen. Internal Med. 2005;20:748–753.
    1. Swanson EC, Schleiss MR. Congenital cytomegalovirus infection: new prospects for prevention and therapy. Pediatr. Clin. North Am. 2013;60:335–349.
    1. Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK. The “silent” global burden of congenital cytomegalovirus. Clin. Microbiol. Rev. 2013;26:86–102.
    1. Bhatt S, et al. The global distribution and burden of dengue. Nature. 2013;496:504–507.
    1. Robin S, et al. Neurologic manifestations of pediatric chikungunya infection. J. Child Neurol. 2008;23:1028–1035.
    1. World Health Organization Number of people (all ages) living with HIV. 2015
    1. Ances BM, Ellis RJ. Dementia and neurocognitive disorders due to HIV-1 infection. Semin. Neurol. 2007;27:86–92.
    1. Tan IL, Smith BR, von Geldern G, Mateen FJ, McArthur JC. HIV-associated opportunistic infections of the CNS. Lancet Neurol. 2012;11:605–617.
    1. Spudich S, Meyer AC. HIV Neurology. Preface. Semin. Neurol. 2014;34:5–6.
    1. Jarvis JN, Harrison TS. HIV-associated cryptococcal meningitis. AIDS. 2007;21:2119–2129.
    1. Desalermos A, Kourkoumpetis TK, Mylonakis E. Update on the epidemiology and management of cryptococcal meningitis. Expert. Opin. Pharmacother. 2012;13:783–789.
    1. Falusi O, et al. Prevalence and predictors of Toxoplasma seropositivity in women with and at risk for human immunodeficiency virus infection. Clin. Infect. Dis. 2002;35:1414–1417.
    1. Baud O, Aujard Y. Neonatal bacterial meningitis. Handb. Clin. Neurol. 2013;112:1109–1113.
    1. Seale AC, et al. Neonatal severe bacterial infection impairment estimates in South Asia, sub-Saharan Africa, and Latin America for 2010. Pediatr. Res. 2013;74(Suppl.):73–85.
    1. Gray KJ, Bennett SL, French N, Phiri AJ, Graham SM. Invasive group B streptococcal infection in infants, Malawi. Emerg. Infect. Dis. 2007;13:223–229.
    1. Iregbu KC, Elegba OY, Babaniyi IB. Bacteriological profile of neonatal septicaemia in a tertiary hospital in Nigeria. Afr. Health Sci. 2006;6:151–154.
    1. Kayange N, Kamugisha E, Mwizamholya DL, Jeremiah S, Mshana SE. Predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, Mwanza-Tanzania. BMC Pediatr. 2010;10:39.
    1. Mehar V, et al. Neonatal sepsis in a tertiary care center in central India: microbiological profile, antimicrobial sensitivity pattern and outcome. J. Neonatal Perinatal Med. 2013;6:165–172.
    1. van de Beek D. Progress and challenges in bacterial meningitis. Lancet. 2012;380:1623–1624.
    1. Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst. Rev. 2013;6:CD004405.
    1. Thwaites GE, van Toorn R, Schoeman J. Tuberculous meningitis: more questions, still too few answers. Lancet Neurol. 2013;12:999–1010.
    1. World Health Organization . Global incidence and prevalence of selected curable sexually transmitted infections — 2008. Vol. 20. WHO; 2008.
    1. John CC, et al. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics. 2008;122:e92–e99.
    1. Bangirana P, et al. Severe malarial anemia is associated with long-term neurocognitive impairment. Clin. Infect. Dis. 2014;59:336–344.
    1. Birbeck GL, et al. Blantyre Malaria Project Epilepsy Study (BMPES) of neurological outcomes in retinopathy-positive paediatric cerebral malaria survivors: a prospective cohort study. Lancet Neurol. 2010;9:1173–1181.
    1. Nankabirwa J, et al. Asymptomatic Plasmodium infection and cognition among primary schoolchildren in a high malaria transmission setting in Uganda. Am. J. Trop. Med. Hyg. 2013;88:1102–1108.
    1. Fleury A, et al. High prevalence of calcified silent neurocysticercosis in a rural village of Mexico. Neuroepidemiology. 2003;22:139–145.
    1. Carabin H, et al. Clinical manifestations associated with neurocysticercosis: a systematic review. PLoS Negl. Trop. Dis. 2011;5:e1152.
    1. Ferrari TC, Moreira PR. Neuroschistosomiasis: clinical symptoms and pathogenesis. Lancet Neurol. 2011;10:853–864.
    1. Finkelstein JL, Schleinitz MD, Carabin H, McGarvey ST. Decision-model estimation of the age-specific disability weight for schistosomiasis japonica: a systematic review of the literature. PLoS Neglected Trop. Dis. 2008;2:e158.
    1. Coyle CM. Schistosomiasis of the nervous system. Handb. Clin. Neurol. 2013;114:271–281.
    1. Kvalsvig J, Albonico M. Effects of geohelminth infections on neurological development. Handb. Clin. Neurol. 2013;114:369–379.
    1. Deckers N, Dorny P. Immunodiagnosis of Taenia solium taeniosis/cysticercosis. Trends Parasitol. 2010;26:137–144.
    1. Bang AT, et al. Is home-based diagnosis and treatment of neonatal sepsis feasible and effective? Seven years of intervention in the Gadchiroli field trial (1996 to 2003). J. Perinatol. 2005;25(Suppl.):62–71.
    1. Murray CJ, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2197–2223.
    1. Alarcon F, Vanormelingen K, Moncayo J, Vinan I. Cerebral cysticercosis as a risk factor for stroke in young and middle-aged people. Stroke. 1992;23:1563–1565.
    1. Lengeler C. Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database Syst. Rev. 2004:Cd000363.
    1. Strode C, Donegan S, Garner P, Enayati AA, Hemingway J. The impact of pyrethroid resistance on the efficacy of insecticide-treated bed nets against African anopheline mosquitoes: systematic review and meta-analysis. PLoS Med. 2014;11:e1001619.
    1. DeBiasi RL, Kleinschmidt-DeMasters BK, Richardson-Burns S, Tyler KL. Central nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis. J. Infect. Dis. 2002;186:1547–1557.
    1. Cobbs CS, et al. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 2002;62:3347–3350.
    1. Peterson PK, Toborek M, editors. Neuroinflammation and Neurodgeneration. Springer; 2014.
    1. Thwaites GE, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N. Engl. J. Med. 2004;351:1741–1751.
    1. Hoffman SL, et al. Immunity to malaria and naturally acquired antibodies to the circumsporozoite protein of Plasmodium falciparum. N. Engl. J. Med. 1986;315:601–606.
    1. Good MF, et al. Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule. Proc. Natl Acad. Sci. USA. 1988;85:1199–1203.
    1. Stoute JA, et al. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. N. Engl. J. Med. 1997;336:86–91.
    1. Agnandji ST, et al. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N. Engl. J. Med. 2011;365:1863–1875.
    1. Boulware DR, et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N. Engl. J. Med. 2014;370:2487–2498.
    1. Boivin MJ, et al. A year-long caregiver training program improves cognition in pre-school Ugandan children with human immunodeficiency virus. J. Pediatr. 2013;163:1409–1416.
    1. Engle PL, et al. Strategies for reducing inequalities and improving developmental outcomes for young children in low-income and middle-income countries. Lancet. 2011;378:1339–1353.
    1. Bangirana P, et al. Immediate neuropsychological and behavioral benefits of computerized cognitive rehabilitation in Ugandan pediatric cerebral malaria survivors. J Dev. Behav. Pediatr. 2009;30:310–318.
    1. Boivin MJ, et al. A pilot study of the neuropsychological benefits of computerized cognitive rehabilitation in Ugandan children with HIV. Neuropsychology. 2010;24:667–673.
    1. Waiswa P, et al. The Uganda Newborn Study (UNEST): an effectiveness study on improving newborn health and survival in rural Uganda through a community-based intervention linked to health facilities — study protocol for a cluster randomized controlled trial. Trials. 2012;13:213.
    1. Bruckner TA, et al. Bull. Vol. 89. WHO; 2011. The mental health workforce gap in low-and middle-income countries: a needs-based approach. pp. 184–194.
    1. World Health Organization . Mental Health Atlas 2011. WHO; 2011.
    1. Liu L, et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012;379:2151–2161.
    1. Black RE, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375:1969–1987.
    1. Walker CLF, et al. Global burden of childhood pneumonia and diarrhoea. Lancet. 2013;381:1405–1416.
    1. Guerrant RL, DeBoer MD, Moore SR, Scharf RJ, Lima AAM. The impoverished gut—a triple burden of diarrhoea, stunting and chronic disease. Nature Rev. Gastroenterol. Hepatol. 2013;10:220–229.
    1. Walker CLF, et al. Does childhood diarrhea influence cognition beyond the diarrhea-stunting pathway? PloS ONE. 2012;7:e47908–e47908.
    1. Richard SA, et al. Catch-up growth occurs after diarrhea in early childhood. J. Nutr. 2014;144:965–971.
    1. Collins SM, Surette M, Bercik P. The interplay between the intestinal microbiota and the brain. Nature Rev. Microbiol. 2012;10:735–742.
    1. Foster JA, McVey Neufeld KA. Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013;36:305–312.
    1. Ochoa-Reparaz J, Mielcarz DW, Begum-Haque S, Kasper LH. Gut, bugs, and brain: role of commensal bacteria in the control of central nervous system disease. Ann. Neurol. 2011;69:240–247.
    1. Hsiao EY, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451–1463.
    1. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220–230.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir