Table 1 Neurocognitive and mental health consequences of major infectious diseases that affect the nervous system.

Dengue virus

Global, most common in South Asia, Africa and Latin America

390 million (95% CI, 284–528 million)

• Meningitis, meningoencephalitis, encephalitis, seizures, Guillain–Barré syndrome, neuralgic amyotrophy, hypokalaemic paralysis, and dengue myositis

• In one cohort, dengue had neurological manifestations in 9.3% of children and adults

• There is limited information about long-term sequelae in dengue, but there is evidence of significant long-term neurological complications

•Not studied

Case reports of mania and depression

Chikungunya virus

Global, most common in South Asia, Africa and Latin America

33,000–93,000

• Encephalitis, febrile seizures, meningismus, myelopathy or myeloneuropathy

• Not studied

Not studied

Japanese encephalitis

Southeast Asia

35,000–50,000

• CNS complications during the acute illness include delirium, seizures, axial rigidity, extrapyramidal signs, cranial nerve palsies, ataxia, paraplegia and segmental sensory disturbances

• Among survivors, 30–50% have significant neurological, cognitive or psychiatric sequelae

Among survivors, 30–50% have significant neurological, cognitive, or psychiatric sequelae

Rabies

Global, greatest in sub-Saharan Africa, Southeast Asia and Latin America

60,000 (probably an underestimate)

• Severe encephalitis, which is almost 100% fatal

• Fatal

Fatal

HSV encephalitis

Global

Present in all countries where HSV testing has been performed, but no reliable global estimates

• If untreated, as in most LMICs, there is a high fatality rate for HSV-1 (around 70%), lower (around 15%) if treated. Long-term neurological complications occur in around 70% of adult survivors, including seizure disorder and hemiparesis. In one cohort, neurological sequelae occurred in 63% of infections in children, including seizures in 44% and developmental delays in 25%

• In one study of adult survivors, long-term cognitive sequelae included memory impairment (69%)

Personality or behavioural impairment in 45% of adult survivors

VZV

Global

No reliable global estimates

• CNS: stroke, meningoencephalitis, myelitis

• PNS (more common): herpes zoster with chronic pain

• Very limited studies with conflicting results

Major depression

Congenital cytomegalovirus

Global

0.6–0.7% of live births in high-income countries and 1–5% of live births in LMICs

• Most common non-hereditary cause of hearing loss in children in the United States

• There are no reliable estimates for frequency of hearing loss due to the infection in most LMICs

• Symptomatic infection, seen in 10–15% of congenitally infected children, is associated with significant global developmental delay in around 50% of affected children

Behavioural problems

HIV

Global, greatest burden in sub-Saharan Africa and Asia

Annual incidence estimate is 2.3 million (95% CI, 1.9–2.7 million) with 34 million people living with HIV/AIDS worldwide, of whom 23 million live in sub-Saharan Africa and 3.5 million live in Southeast Asia

• HIV associated opportunistic infections, aseptic meningitis, AIDS encephalopathy, Bell's palsy, progressive multifocal leukoencephalopathy, primary CNS lymphoma, stroke, transverse myelitis, HIV-associated peripheral neuropathy, inflammatory demyelinating polyneuropathy, immune reconstitution inflammatory syndrome and vacuolar myelopathy

• Asymptomatic neurocognitive impairment, mild neurocognitive disorder and HIV-associated dementia

Delirium, major depression, bipolar disorder (including AIDS mania), schizophrenia, substance abuse or dependence and post-traumatic stress disorder

Cryptococcal meningitis

Global, greatest burden in sub-Saharan Africa and Asia

Annual incidence estimate: 957,900 in 2009, approximately 624,700 deaths annually

• Headache, meningismus, intracranial hypertension, mental status changes, focal intracerebral granulomas (cryptococcomas), hydrocephalus (communicating and non-communicating), papilledema, sensorineural deafness, cranial nerve palsies, motor and sensory deficits, cerebellar dysfunction and seizures

• Mimicking of vascular dementia, and reversible dementia

Personality change, confusional psychosis and mania

Toxoplasma encephalitis

Global, greatest burden in sub-Saharan Africa and Asia

No reliable global estimates of incidence of toxoplasma encephalitis, but toxoplasma infection is present in 14% of the population in the United States, compared with 23–47% in some European, Latin American and African countries

• Headache, focal neurological deficit, seizures and altered mental status

• Dementia

Schizophrenia and behaviour disorders

Neonatal sepsis and meningitis

Global

Annual incidence estimates for south Asia, sub-Saharan Africa and Latin America: neonatal sepsis, 1.7 million (uncertainty estimate, 1.1–2.4 million); neonatal meningitis, 200,000; 95% CI, 21,000–350,000)

• Little data for neonatal sepsis globally, especially among those more than 32 weeks gestation or more than 1,500g

• 23% (95% CI, 19–26%) of neonatal meningitis survivors (or 18,000 children; 95% CI, 2,700–35,000) estimated to sustain moderate to severe neurodevelopmental impairment

• In sepsis or meningitis, the primary neurological sequelae are cerebral palsy, impairment to vision, hearing and motor function, and seizure disorders

• Limited studies reporting cognitive impairment; developmental delay or learning difficulties are frequent in sepsis (30.0%; IQR, 26.4–44.4%) and meningitis (33.3%; IQR, 26.7–36.8%)

No data

Bacterial meningitis

Global

Annual incidence estimate: 1.2 million

• 22.8% (IQR, 12.1–29.2%) have at least 1 neurocognitive sequela at discharge, 19.9% (IQR, 12.1–35.2%) have at least 1 sequela post-discharge; 16.0% (IQR, 7.1–21.2%) have at least 1 major sequela at discharge, 12.8% (IQR, 7.1–21.1%) have at least 1 major sequela post discharge

• Neurological sequelae include motor deficits, hearing loss and visual disturbances

• Risk of major sequelae is higher in Africa (25.1%) and southeast Asia (21.6%) compared with Europe (9.4%)

• In children, cognitive impairment including low IQ, academic limitations, and impared executive function and in adults, cognitive impairment with slower cognitive speed seen

Behavioural changes and emotional disturbance including ADHD and learning difficulties

Tuberculous meningitis (also an opportunistic infection in HIV)

Global, most burden in sub-Saharan Africa and Asia

No reliable global incidence estimates; highest in countries with high prevalence of HIV infection

• Neurological sequelae in 53.9% of child survivors (95% CI, 42.6–64.9)

• Gross and fine motor impairment in children

• Motor deficits, optic atrophy, ophthalmoplegia, and hearing impairment in adults and older children

• Cognitive impairment in all areas tested, and poor scholastic progress

Emotional disturbance

Neurosyphilis

Global

No reliable global incidence estimates; most cases occur in HIV-positive individuals

• Meningitis, cerebrovascular infarction, and paresis, tabes dorsalis (ataxia, paraesthesia and bladder dysfunction)

• Impaired memory, disorientation and dementia

Dementia, depression, delirium, mania and psychosis

Neurocysticercosis

Global, greatest burden in pig-raising areas with poor sanitation

2010 prevalence estimate: 1.4 million (95% CI, 1.3–1.6 million) (epilepsy only)

• Among people with symptomatic neurocysticercosis diagnosed with brain imaging: seizures and epilepsy (78.8%; 95% CI, 65.1–89.7%), headaches (37.9%; 95% CI, 23.3–53.7%), focal deficits (16.0%; 95% CI, 9.7–23.6%) and symptoms associated with increased intracranial pressure (11.7%; 95% CI, 6.0–18.9%)

• Case reports of cognitive decline

• Cognitive symptoms of neurocysticercosis with active cysts: affects naming, verbal fluency and non-verbal memory

Neurocysticercosis with active cysts: dementia (12.5%) and cognitive impairment, but not dementia (27.5%); psychosis

Malaria

Sub-Saharan Africa, Latin America, Asia and Oceania

Annual incidence estimate: 216 million

• Cerebral malaria: 5–28% of children have neurological deficits on discharge, including epilepsy, acute hemiparesis, hypertonia, cortical blindness and ataxia

• By 6-month follow-up the percentage of children with deficits has decreased to 0–4.4%, primarily in the areas of gross motor and fine motor skills

• Uncomplicated malaria: motor skills

• Cerebral malaria affects general cognition, attention, working memory, visual spatial skills, somatosensory discrimination, speech and language, and receptive and expressive language

• Thirteen IQ point difference from non-affected children 1 year after episode, and around 26% of children have impairment 2 years after

• Severe malaria with neurological involvement affects executive function

• Severe malarial anaemia affects overall cognition estimated to lead to the equivalent of an 11 IQ point difference from non-affected community children

• Malaria with multiple seizures leads to speech and language problems

• Malaria with impaired consciousness leads to attention/language problems

• Uncomplicated malaria leads to language problems

• Asymptomatic malaria leads to problems with fine motor coordination, attention and abstract reasoning

Cerebral malaria: internalizing and externalizing problems, ADHD, disruptive behaviour, psychosis and depression

STH infection

Global, greatest burden in sub-Saharan Africa and Southeast Asia

Estimated 2010 prevalence: hookworm infected 439 million (95% CI, 406–480), Ascaris lumbricoides infected 819 million (95% CI, 772–892) and Trichuris trichiura infected 465 million (95% CI, 430–508).

• Not described

• School-aged children: T. trichiura and A. lumbricoides affected learning and verbal memory in one study

• In another, general STH infection reduced memory capacity, rate of processing and attention

Children under 5 years of age: social and emotional disturbances (combined with anaemia)

Schistosomiasis

Global, greatest in sub-Saharan Africa and Southeast Asia

Estimated 2010 prevalence: 252 million infected

• Acute schistosomal encephalopathy: headache, confusion, seizure, loss of consciousness, focal deficits, visual impairment and ataxia

• Cerebral schistosomiasis: headaches, motor deficits, visual abnormalities, seizures, altered mental status, vertigo, sensory impairment, speech disturbances and ataxia

• Spinal cord schistosomiasis: lower limb weakness, bladder dysfunction, lower limb paraesthesia, hypoaesthesia/anaesthesia, deep tendon reflex abnormalities, constipation and impotence in 80% of cases

• For Schistosoma japonicum infection in children (not neurological infection): verbal memory and verbal fluency affected

No data