TITLE: Risk factors and neuroimaging features in stroke patients at Kamuzu Hospital,
Lilongwe, Malawi
RESEARCH PLAN
A.
Specific Aims
(1) Describe epidemiologic features of stroke patients admitted to Kamuzu Central
Hospital, a tertiary care referral hospital in the capital of Malawi in sub-saharan Africa
(2) Determine significant risk factors for ischemic and hemorrhagic stroke in this patient
population
(3) Determine imaging features based on computed tomography (CT) (i.e. small vessel
verses large vessel, hemorrhagic verses ischemic)
(4) Determine the proportion of stroke patients with intra- and extracranial vessel stenosis
based on CT angiography
(5) Describe the stroke burden in the HIV-positive population admitted to Kamuzu Central
Hospital
(6) Determine 30-day mortality and functional disability in stroke patients admitted to
Kamuzu Hospital
B.
Background and Significance
Death from stroke in low and middle-income countries accounts for 85% of stroke
deaths worldwide, and the disability adjusted life years (DALYs) lost in these countries
is almost seven times those lost in high-income countries (1). In addition, while higherincome countries experienced a combined 42% reduction in stroke incidence, in middleand lower income countries, stroke incidence has risen by more than 100% in the last
decade (2). Current projections suggest that by 2030, coronary and cerebrovascular
disease will supersede HIV and AIDS as the leading causes of morbidity and mortality
in Sub-Saharan Africa (3). In a systematic review on stroke in Sub-Saharan Africa since
1966, the proportion of hemorrhagic stroke in Africa (34%) was significantly higher than
the global average (24%) and much higher than that observed in high-income countries
(9%) (4).
Few studies have examined epidemiologic features and modifiable risk factors in stroke
patients in sub-Saharan Africa (5-9). The Tanzanian Stroke Incidence Project (TSIP),
reported the incidence of stroke from two well-defined communities in urban and rural
East Africa (10). Hypertension has been found to be the most significant risk factor for
stroke in previous studies, though other important risk factors in the region include HIV
and other communicable infections. In addition to hypertension and communicable
diseases such as HIV, a retrospective analysis in Nigeria found that diabetes mellitus,
previous TIA within the last four years, and tobacco smoking were the strongest risk
factors in the patients with stroke (11).
There have also been few studies of vascular imaging in acute and subacute stroke
cases in sub-Saharan Africa. In the TSIP study, duplex ultrasonography was used to
determine the prevalence of carotid artery stenosis where it was found that only one
stroke patient in 56 had evidence of significant carotid disease (12). In a large urban
South African teaching hospital, no evidence of large vessel atherosclerosis was found
based on CT angiography though not all patients had CTA done and there was no
comment on the prevalence of intracranial disease (13). Our study will be the first to
delineate the prevalence of intracranial and extracranial atherosclerosis in a large HIV
positive population in Malawi. Malawi, a country in which 12% of the population is HIV
positive, is known to have a high prevalence of stroke as well as poor outcome with
nearly 50% of patients dying within 30 days post-hospital discharge (14-16).
Our study aims to determine stroke risk factors and epidemiological features of those
patients admitted to Kamuzu Hospital with acute and subacute infarcts. Our focus will
be on radiographic imaging and in particular, we will examine whether significant
intracranial or extracranial stenosis exists in this patient population. In addition, we will
gather detailed clinical information as well as outcome at hospital discharge and 30-day
mortality and disability.
D.
Research Design and Methods
This will be a prospective study performed at Kamuzu Central Hospital, a large
government hospital in the capitol of Malawi, Lilongwe, between September 2013 and July
2014. Ethical clearance was obtained from the hospital research ethics committee and
informed consent will be obtained from all patients or their healthcare proxies if the
patient is unable to complete the consent. Demographic, clinical, and laboratory data
will be obtained from patients or their proxies and entered in a structured datasheet.
We will enroll all patients clinically diagnosed with stroke or transient ischemic attack who
presented to Kamuzu Central Hospital within one week of symptom onset. All cases
diagnosed clinically as stroke will undergo CT/CT angiography on admission to Kamuzu
Hospital. Patients will be excluded from the study if they are less than 18 years old, and do
not fit the WHO criteria for stroke or transient ischemic event. On admission, patients will
be consented (or guardian in the cases where they are unable to be consented). The
admitting clinical officer will document basic demographic information (including age and
gender), vital signs, random blood glucose, NIH stroke scale, time of onset of symptoms
and symptoms not delineated in the NIHSS (including constitutional symptoms) at the time
of admission. The patient will be admitted to the Kamuzu Central Hospital medical
inpatient service where he/she will continue with routine post-stroke care.
The patient will be seen daily by primary investigators, TC and TK. Within 24 hours of
hospital admission, the investigators will gather further clinical information including
demographic details (race, ethnicity, home region), pre-morbid history (i.e. stroke, transient
ischemic attack, myocardial infarction, HIV status, sickle cell), social history (i.e. education,
alcohol and smoking use, biomass fuel exposure) and family history. Vital signs and
random blood sugar will be documented daily while the patient remains on the inpatient
medical service. Laboratory testing sent on admission will include complete blood count,
complete metabolic panel, ESR, total cholesterol, HgbAIC, CD4 count, blood cultures if
febrile.
A blinded board-certified neuroradiologist at Kamuzu Central Hospital (SM) will perform
radiographic interpretation. Radiographic characteristics to be assessed include vascular
territory, whether the stroke is hemorrhagic or ischemic and the size of the infarct. Vessel
imaging will be assessed for evidence of significant intra- verses extracranial stenosis,
evidence suggestive of vasculitis or structural vascular abnormalities such as aneurysm
formation.
Outcome information will be gathered on hospital discharge. The modified rankin score
(MRS) will be used as a surrogate marker of disability at hospital discharge. Patients will
be seen by study leaders in the department of medicine at 30-days post hospital
discharge. MRS and NIHSS will be obtained during the follow-up clinic visit.
Statistical analysis will be performed with statistical package for the social sciences
(SPSS) version 14.0 software. Means of continuous variables were compared using
Student's unpaired t test, whereas categorical variables were analyzed by the Chisquare test. P values less than 0.05 were considered significant.
E.
Study Population –(Gender and Minority Inclusions):
Anticipated number of patients: 200
Inclusion criteria: acute onset of stroke symptoms as defined by WHO criteria within one
week of hospital admission
Exclusion criteria: CT evidence consistent with an alternate diagnosis, symptoms>1 week
prior to hospitalization, patients<18 years old
F.
Human Subjects (Risks & Benefits)
Sources of research material will include healthcare passports obtained from patients or
their guardian and healthcare records at Kamuzu Hospital. Use will be made of existing
blood specimens collected on the patient for other purposes (not solely research
purposes).
There are no procedures, situations, or materials that may be hazardous to personnel and
the precautions to be taken to ensure safety.
Describe plans for recruitment of subjects and the consent procedures to be followed;
Patients will be recruited upon admission to Kamuzu hospital. A consent process will be
obtained at the time of admission. If the patient is not able to give consent, the primary
guardian of the patient will be consented. We will provide all details on the nature of the
study and tests that will be performed. There will be no payment for participation for the
research project. We will complete a consent form.
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