Uncommon infection in elderly

Lau CC, NTWC

Common Infection

Most of the elderly admitted to medical ward with those “common” infection

Usually presented common symptoms like fever, chest symptoms, urinary symptoms, altered conscious level…

How many of those indeed resulted from “uncommon” infections?

The Patient…

Ms Hokawa

Female, 69 yro

Japanese

Borned in Singapore, finally worked and stayed in HK for more than 30 years

Lived with boyfriend and son

Retired for 10 years

ADL I

Ms Hokawa

HT

Congenital single kidney

Depression FU psychiatry

? Colonic neoplasm with operation done in Singapore

Ms Hokawa

Admitted for on and off fever for 2 weeks

Sleepy for most of the time at home

Urinary and bowel incontinence

No chest symptoms,

No witness convulsion

No recent travel history

Visited GP twice, completed medication given by GP but no improvement

Ms Hokawa

High fever ~ temp 39*c

Blood pressure was high , tachycardia

No desaturation in room air

Chest clear

Cardiovascular: no murmur HS dual

Abdomen soft nontender

Joints nad

Ms Hokawa

Confused in speech

GCS E4V3M5

No facial asymmetry

4 limbs spontaneous movement

Reflexes normal

Investigations

WCC 21.1 10^9/L (N:3.9-10.7 ) 93% neutrophlic, lymphocyte 0.9 ; CRP 235 ESR 128

Hb/ plt normal INR 1.1

Na/ K / Ca normal ; Cr 120

LFT bil ALP ALT– normal

ABG pH 7.34 , no CO2 retention

CXR

CXR~ left Lower zone hazziness

Investigations

Blood Culture saved and pending results

NPs negative, PCR negative

Urine: c/st saved

Urine toxicology screening:

atenolol

trazodone and its metabolites

zopiclone and its metabolites

chlorpheniramine and its metabolites

citalopram and its metabolites

Common infections?

Less likely suspected

CT brain

Small vessel disease of brain

Bilateral old cerebral infarcts

Lumbar Puncture

CSF slightly turbid

Open pressure ~ 16 mmH2O

CSF glucose < 0.3 (vs blood glucose 9.1, < 50%) mmol/L

CSF protein 8.75 g/L

WCC: 325 (90% polymorphs) per c m.m.

Lumbar Puncture

Gram stain: Gram-possitive cocci

Bacterial antigen: Streptococcus pneumoniae positive

HSV PCR negative

AFB smear negative

DDx: Gram +ve cocci meningitis(mostly likely causative agent: streptococcus Pneumonia)

Treatment

Based on the preliminary results:

3rd generation cephalosporins, ceftriazone 2g Q12H

the beta-lactams of choice in the empiric treatment of meningitis

consistent CSF penetration and potent activity against the major pathogens of bacterial meningitis

Pubmed; Practice guidelines for the management of bacterial meningitis.; Clin Infect Dis. 2004;39(9):1267

? Dexamethasone

Added dexamethasone as a treatment

Permanent neurologic sequelae, such as hearing loss and focal neurologic deficits, are not uncommon in survivors of bacterial meningitis, particularly patients with pneumococcal meningitis

Early administration of glucocorticoid, dexamethasone, were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51-0.88), any hearing loss (RR 0.74, 95% CI 0.63-0.87), and short-term neurologic sequelae other than hearing loss. But not recommend to use after antibiotics administration

The recommended intravenous dexamethasone regime is 0.15mg/kg every six hours for four days

Pubmed; Corticosteroids for acute bacterial meningitis; Cochrane Database Syst Rev. 2013 Jun;6:CD004405.

?vancomycin

Reviewed by MID team, suggested to add vancomycin

With the worldwide increase in the prevalence of penicillin-resistant pneumococci, vancomycin should be added untill culture and susceptibility results are available

Pubmed; Community-acquired bacterial meningitis in adults.; N Engl J Med. 2006;354(1):44.

Ms Hokawa

CSF Culture: streptococcus pneumoniae

Blood culture: streptococcus pneumoniae

All culture results sensitive to ceftriaxone

Thus, ceftriaxone continued and vancomycin taken off

Ms Hokawa

General condition improved without confusion in speech

Back to premorbid level according to family members

Started walking exercise and ADL training by physiotherapist and occupational therapist

? Is this the end of the story

Ms Hokawa

Consent for checking blood for HIV Ab

Why? In her age?

Bacterial infection and HIV infection

Even in the HAART era, risk of pneumococcal meningitis is 19 times more in HIV-1 infected patients than among uninfected one

It tends to present in severely immunosuppressed patients who didn’t receive prior vaccination and off antiretroviral therapy. With a concomitant extra-meningeal infection, bacteriaemia and focal neurological signs, and is caused by Streptococcal pneumoniae.

Bacterial meningitis in HIV-1 infected patients carried a worse prognosis than uninfected ones in terms of mortality and sequelae

J.acquired def synd 2009, Aug (15,51(5)582-7; bacterial meningitis in HIV-1 in the ear of HAART

Ms Hokawa

Blood results: HIV +ve

Blood lymphocyte count slighly low

WCC 21.1; 90% neutrophilic, lymphocyte count: 0.9 (1.2-3.4 10^9)

CD4 172.7

HIV statistics in HK, from DH

HIV statistics in HK, from DH

HIV statistics in HK, from DH

Infection in elderly

Because HIV has primarily afflicted younger adults (in their twenties and thirties), most of the HIV literature defines ‘older adults’ as those age 50 years or over.

The success of highly-active antiretroviral therapy (HAART) has resulted in the long-term survival of many patients with HIV, increasing the number of older adults with this disorder.

Infection in elderly

Additionally, newly-acquired infections are becoming more prevalent among older adults. Elderly typically acquire HIV infection via sexual activity, and subjects >50 years of age account for about 15 percent of all new diagnoses of AIDS in the US

Elderly, as concerns over pregnancy decline with age use of barrier methos of contraception wane. Thus they are the least likely to practise safe sex

Infection in elderly

A lack of HIV awareness, affecting both patients and their clinicians, confounds appropriate diagnosis.

Nonspecific symptoms such as poor appetite and weight loss and specific infections such as zoster, tuberculosis, or frequent pneumonias are often mistaken for symptoms related to aging or comorbidity and do not prompt HIV testing as they would in younger adults.

Special consideration should be given to HIV as a potentially treatable cause of dementia in those with memory loss.

However no literature has compared the relative likelihood of identifying and reversing dementia due to HIV infection, compared with other reversible causes of dementia (eg, thyroid disease, vitamin deficiency, or syphilis).

Infection in elderly

HIV infection in older adults tends to present at more advanced stages than in younger individuals, likely due both to delayed diagnosis and impaired immune response. Untreated, HIV pursues a more rapidly progressive course in older adults

Addtionally, HIV is impacted by comorbidities that are more common in elderly, eg DM, IHD. Thu measures of multi-morbidity has been shown to be more accurate predictor of prognosis in HIV-infected elderly(traditionally e.g. CD4 count, viral load…)

Infection in elderly

Addtionally, HIV is impacted by comorbidities that are more common in elderly, eg DM, IHD. Thus measures of multi-morbidity has been shown to be more accurate predictor of prognosis in HIV-infected elderly(traditionally e.g. CD4 count, viral load…)

Further, frailty, a syndrome of high vulnerability to disease and disability usually seen in much older adults, is more frequent at young ages in HIV-infected persons and predicts mortality

Ms Hokawa

Further history taking and review of past medical record,

Follow up by psychiatrist for depression also mentioning about memory impairment

During stay in hospital, MMSE 11/30

HIV-associated neurocognitive disorders

Cognitive impairment can be related to variety of disease in elderly

Epidemiologic findings suggest that increasing age is a significant risk factor for HIV-associated dementia

Pubmed; Cognitive functioning in younger and older HIV-1-infected adults. J Acquir Immune Defic Syndr. 2003;33 Suppl 2:S93.

HIV-associated neurocognitive disorders

One longitudinal study compared 106 HIV-infected patients >50 years of age to 96 patients ranging from 20 to 39 years of age. After adjusting for viral load, CD4 count. The count of having HIV-associated dementia among individuals in older age group was threefold higher than that of the younger group. (No apparent of association was noted between the duration of HIV infection)

Pubmed; Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort.; Neurology. 2004;63(5):822.

Clinical features

Mainly affect subcortical brain, ie memory and motor function

The deficits associated with HIV-associated Neurocognitive disorder may wax and wane over time, unlike the progressive neurological decline seen in other neurodegenerative diseases, such as Alzheimer disease.

Cognitive impairment

include substantial memory deficits, negative personality and mood changes, impaired executive functioning, poor attention and concentration, mental slowing, and apathy

In its advanced form, HIV associated Dementia presents with these features in associated with severe immunodeficiency

The absence of higher cortical dysfunction including aphasia, agnosia, and apraxia help distinguish HIV associated Dementia from classical "cortical" dementia, such as Alzheimer disease. However, the distinction between cortical and subcortical dementias can be blurred as a patient with late and severe form may have dysfunction in both language and praxis.

motor

Early motor symptoms include unsteady gait, leg weakness, and tremor

Most patients with HIV associated Dementia exhibit slowness of movement

in addition, patients can experience impaired saccadic eye movements, marked difficulty with smooth limb movement(esp in the lower extremities), dysdiadochokinesia, hyperreflexia and frontal release sign such as grasp, root, snout and glabellar reflexes

imaging

cerebral atrophy, most often in the basal ganglia (particularly the caudate) and frontal white matter

On magnetic resonance imaging (MRI), T2-weighted images also demonstrate bilaterally symmetrical, periventricular white matter hyperintensitieswhich may correlate neuropathologically with high levels of HIV in those regions of the brain

Imaging

magnetic resonance spectroscopy, functional MRI, single photon emission computed tomography (SPECT), and positron emission tomography (PET) also demonstrate abnormalities in the subcortical regions, in some cases even in patients with more mild neurocognitive deficits

MRI brain T2W of our patient

MRI

Small vessels disease

Likely atherosclerotic disease of circle of Willis

Linear signal void structure running at the left side of cerebellar vermis with faint brush like enhancement in the left cerebellar hemisphere, probably capillary telangiectasia

Paranasal sinusitis

Ms Hokawa

We do suspect but there is no specific method to confirm whether HIV-associated Dementia

What other ways to help our patient?

Initiation of therapy

Although morbidity and mortality rates in older HIV-infected patients appear higher than younger HIV-infected patients, the initiation of antiretroviral therapy leads to a significant reduction in risk of death. In HIV-infected patients older than 50 years of age, antiretroviral therapy should be initiated regardless of CD4 count.

Initiation of therapy

Several studies have suggested that older HIV-infected patients tend to be more adherent with medications than younger patients, with some studies reporting more than 95 percent adherence. However, the older patient may be at higher risk for drug-related toxicity

Initiation of therapy

Less robust CD4 T cell increments in response to antiretroviral therapy have been reported in older HIV-infected patients, which may be related to immunosenescence

Initiation of treatment in elderly

HIV treatment guidelines from the United States Department of Health and Human Services (DHHS) and the International Antiviral Society-USA Panel now recommend antiretroviral treatment in all patients with HIV infection, regardless of CD4 cell counts

Initiation of therapy

It is unclear if older HIV-infected patients have an increased risk for cardiovascular disease, although treatment with antiretroviral therapy may increase the risk of metabolic abnormalities, such as hypertriglyceridemia

Goals of therapy

The primary goals of combination antiretroviral therapy are to increase disease-free survival through suppression of HIV replication and improvement in immunologic function

Viral suppression also decreases the risk of HIV transmission to an uninfected sexual partner

Ms Hokawa

Would it help if our patient suffered from HIV associated Dementia?

HIV-associated neurocognitive deficits

The incidence of HIV-associated dementia has declined since the introduction of potent ART. In one cohort, patients with viral suppression on ART had a lower risk of HIV-associated dementia than patients with detectable plasma HIV RNA

Observational data also suggested that patients with HIV dementia improve clinically after the initiation of HIV therapy

Ms Hokawa

For treatment of meningitis, iv ceftriaxone completed in our convalescence bed.

Rehabilitation was started

Latest BI 64/ 100 be able to walk unaided with supervision level

MMSE 11/30

Referred to PMH MID team to started HAART

Will continue to follow up in our clinic for cognitive function

THANK YOU…