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Fulltext A comparison of valsartan and perindopril in the treatment of essential hypertension in the Malaysian population

Bavanandan S, Morad Z, Ismail O, Chandran A, Thayaparan T, Singaraveloo M

Med J Malaysia, 2005 Jun;60(2):158-62.
PMID: 16114156 MyJurnal

This study was conducted to determine the tolerability and efficacy of valsartan (DIOVAN) compared to perindopril (COVERSYL) in Malaysian patients with mild to moderate hypertension. Two hundred and fifty adult Malaysian patients with a mean sitting diastolic blood pressure of more than 95 mmHg and less than 115 mmHg after a 14 day washout period were randomized to receive either valsartan 80 mg once daily (n=125) or perindopril 4 mg daily (n=125) for eight weeks. The primary end point for efficacy was the change in mean sitting systolic and diastolic blood pressure (SiSBP and SiDBP). The primary criteria for evaluation of tolerability was the incidence of adverse events. There were no significant differences between the two groups with respect to sex, age, weight, baseline sitting and standing systolic and diastolic blood pressure. At 0, 4 and 8 weeks the mean SiDBP in the valsartan group were 101.4, 92.8 and 91.0 mmHg respectively. The corresponding BP for the perindopril treated group was 102.6, 93.8 and 93.2 mmHg. (95% CI -1.39 to +3.27). There were no significant differences in the mean BP measurements between the valsartan and perindopril group at 0, 4 and 8 weeks. In each group there were significant differences between the BP at 4 and 8 weeks compared to baseline. A similar pattern was seen with SiSBP. At 4 weeks 28.7% of the valsartan and 25% of the perindopril group had their BP normalized (SiDBP <90 mmHg) The percentages of patients who responded (SiDBP reduction >10 mmHg but SiDBP >90 mmHg) were 21.3 in the valsartan group and 20.8 in the perindopril group. At 8 weeks, 31.1% of the valsartan group and 30.8% of the perindopril group had their BP normalized. The response rate was 27% and 22.5% for valsartan and perindopril respectively. The major adverse event was cough which occurred in 18 patients (14.4%) in the perindopril and 1 (0.8%) in the valsartan group at 4 weeks. At 8 weeks the figures were 24 (19.2%) and 2 (1.6%) respectively. The results indicate that Valsartan is safe and efficacious in the treatment of mild to moderate hypertension. It is equally efficacious to Perindopril and not associated with any major adverse event. It has a better tolerability profile with respect to dry cough.
Ethnicity as a determinant of asthma-related quality of life in a multiracial country

Loh LC, Teh PN, Seth KD, Raman S, Vijayasingham P, Thayaparan T

Asia Pac J Public Health, 2006;18(1):49-55.
PMID: 16629438 DOI: 10.1177/10105395060180010801

In a multiracial country like Malaysia, ethnicity may influence the measurement of health-related quality of life (HRQL) in asthmatic patients. We invited 131 adult patients [44 Malays, 42 Chinese and 45 Indians; mean (95% CI) age: 43 (40.2-45.7) yrs; 28.2% male] with moderate-to-severe persistent asthma followed up in an urban-based hospital outpatient clinic to complete a disease-specific HRQL questionnaire [St Georges' Respiratory Questionnaire (SGRQ)] and to provide socio-demographic and asthma-related data. Indians reported significantly worse SGRQ total score, compared to Malays [mean (95% CI) difference: 10.15 (0.51-19.78); p = 0.037] and SGRQ activity score, compared to Malays [13.50 (1.95-25.05); p = 0.019] and Chinese [11.88 (0.19-25.05); p = 0.046]. Further analysis using multivariate linear regression showed that Indian ethnicity remained independently associated with SGRQ scores. Our finding highlights the relevance of ethnicity in assessing HRQL of asthmatic patients in a multiracial country such as Malaysia.

Study site: chest clinic of an urban-based
university teaching hospital
Fulltext Incentive spirometry as a means to score breathlessness

Loh LC, Teh PN, Raman S, Vijayasingham P, Thayaparan T

Malays J Med Sci, 2005 Jan;12(1):39-50.
PMID: 22605946 MyJurnal

Perceived breathlessness played an important role in guiding treatment in asthma. We developed a simple, user-friendly method of scoring perception of dyspnoea (POD) using an incentive spirometer, Triflo II (Tyco Healthcare, Mansfield, USA) by means of repetitive inspiratory efforts achieved within three minutes in 175 normal healthy subjects and 158 asthmatic patients of mild (n=26), moderate (n=78) and severe (n=54). Severity was stratified according to GINA guideline. The mean POD index in normal subjects, and asthmatic patients of mild, moderate and severe severity were: 6 (4-7) 16 (9-23), 25 (14-37), and 57 (14-100) respectively (p<0.001 One-Way ANOVA). Based on 17 asthmatic and 20 normal healthy subjects, intraclass correlation coefficients for POD index within subjects were high. In 14 asthmatic patients randomized to receiving nebulised b(2)-agonist or saline in a crossover, double-blind study, % FEV(1) change correlated with % changes in POD index [r(s) -0.46, p=0.012]. Finally, when compared with 6-minutes walking test (6MWT) in an open label study, respiratory POD index correlated with walking POD index in 21 asthmatic patients [r(s)= 0.58 (0.17 to 0.81) (p=0.007] and 26 normal subjects [0.50 (0.13 to 0.75) (p=0.008)]. We concluded that this test is discriminative between asthmatic patients of varying severity and from normal subjects, is reproducible, responsive to bronchodilator effect, and comparable with 6MWT. Taken together, it has the potential to score disability and POD in asthma effectively and simply.
Adverse hospital outcomes associated with the choice of empiric antibiotics in Klebsiella pneumoniae pneumonia: a retrospective observational study

Loh LC, Rosdara Masayuni MS, Nor Izran Hanim AS, Raman S, Thayaparan T, Kumar S

Ann Acad Med Singap, 2007 Aug;36(8):642-6.
PMID: 17767334

INTRODUCTION: In Malaysia, Klebsiella pneumoniae ranks high as a cause of adult pneumonia requiring hospitalisation.
PATIENTS AND METHODS: With concern over its rising microbial resistance, we explored the association of empiric antibiotics choices with the hospital outcomes of patients treated for microbial proven K. pneumoniae pneumonia in an urban-based teaching hospital.
RESULTS: In 313 eligible cases reviewed retrospectively, hospital mortality and requirement for ventilation were 14.3% and 10.8% respectively. Empiric regimes that had in vitro resistance to at least one empiric antibiotic (n = 90) were associated with higher hospital mortality (23.3% vs. 10.8%, P = 0.004) with risk increased by about two-fold [Odds ratio (OR), 2.5; 95% confidence interval (CI), 1.3 to 4.8]. Regimes (n = 84) other than the commonly recommended "standard" regimes (a beta-lactam stable antibiotic with or without a acrolide) were associated with higher ventilation rates (16.7% vs. 8.8%, P = 0.047) with similar increased risk [OR, 2.0; 95% CI, 1.0 to 4.3].
CONCLUSIONS: Our findings reiterate the clinical relevance of in vitro microbial resistance in adult K. pneumoniae pneumonia and support empiric regimes that contain beta-lactam stable antibiotics.
Effect of time delay on survival in patients with non-small cell lung cancer--a Malaysian study

Loh LC, Chan LY, Tan RY, Govindaraju S, Ratnavelu K, Kumar S, et al.

Asia Pac J Public Health, 2006;18(1):69-71.
PMID: 16629441

The prognosis of lung cancer remains poor with overall five year survival figures varying between five and 10% worldwide, However, it has been shown that surgery in patients with early stage disease in non-small cell lung cancer can achieve five year survival rates up to 80%, suggesting that early or delay diagnosis can influence prognosis. Nevertheless, studies addressing this have been inconclusive and mostly derived from Western countries.
Fulltext Influence of co-morbidity in the interpretation of tuberculin skin reactivity in multi-ethnic adult patients with tuberculosis

Loh LC, Chan SK, Ch'ng KI, Tan LZ, Vijayasingham P, Thayaparan T

Med J Malaysia, 2005 Oct;60(4):426-31.
PMID: 16570703

In the Malaysian setting of multi-ethnicity and high BCG coverage, interpretation of Tuberculin Skin Testing (TST) may be difficult. Between January 2001 and December 2003, a retrospective study on all adult patients with documented TST results treated for tuberculosis (TB) in chest clinics of two government hospitals was conducted to determine the reliability of TST and factors affecting its interpretation. One hundred and three patients [mean age (SD): 43 (17); male: 67%] were eligible for data collection: 72% and 57% of patients had positive TST results based on cut-off points of 10mm and 15mm respectively. The only significant univariate association with TST results was the severity of co-morbidity. A patient with co-morbidity score of 3 defined as those with any cancer, end-stage renal or liver disease, or HIV disease, was more likely to have a negative TST results [10mm cut-off point: Odd Ratio (95% CI) 6.6 (1.82 to 24.35), p = 0.003; 15mm cut-off point: 4.8 (1.21 to 18.95), p = 0.012]. A TST reading of 10mm had a higher sensitivity than 15mm as the cut-off point in diagnosing TB infection. Considering all possible confounding factors like ethnicity, prior BCG vaccination and TB burden in the population, severity of co-morbidity remains strongly predictive of a negative TST. Caution should be exercised in interpreting TST in these patients.
Study site: Chest clinic, Hospital Seremban, Hospital Kuala Pilah, Negeri Sembilan, Malaysia
Fulltext Metered-dose inhaler technique in asthmatic patients--a revisit of the Malaysian scene

Loh LC, Teng CL, Teh PN, Koh CN, Vijayasingham P, Thayaparan T

Med J Malaysia, 2004 Aug;59(3):335-41.
PMID: 15727379

Inefficient metered-dose inhaler (MDI) technique results in poor drug delivery, suboptimal disease control a possibility of inhaled medication overuse. The MDI technique of 134 government hospital and clinic followed-up adult asthmatic patients followed-up in a government hospital and a heath clinic was pragmatically assessed based on the 3 obligatory steps of adequate lip seal, appropriate hand-breath coordination and sufficient breath holding after inhalation. The relationship between technique efficiency and frequency of daily short-acting beta2-agonist (SABA) use via the MDI and asthma exacerbations over a 12-month period was also assessed. Fifty-six patients (42%) had inefficient MDI technique. All demographic and asthma-related variables between the 'efficient' and 'inefficient' technique groups of patients were comparable except for significantly longer mean years of MDI use in the 'efficient' technique group [mean (SD): 10 (7) vs. 7 (5); p=0.003]. There were no significant differences between the two groups in relation to frequency of daily SABA use or asthma exacerbations over the past 12 months. Despite having been available in Malaysia for a considerable period of time, the MDI device is still poorly handled by a large proportion of adult asthmatic patients. Changing to other more user-friendly devices or use of spacer devices to facilitate delivery should be considered for these patients.
Study site: Hospital Tuanku Jaafar, Seremban, Negeri Sembilan; Klinik Kesihatan Seremban, Malaysia
Adult community-acquired pneumonia in Malaysia: prediction of mortality from severity assessment on admission

Loh LC, Khoo SK, Quah SY, Visvalingam V, Radhakrishnan A, Vijayasingham P, et al.

Respirology, 2004 Aug;9(3):379-86.
PMID: 15363012

Prediction of mortality in patients with community-acquired pneumonia (CAP) can be assessed using clinical severity scores on admission to hospital. The clinical benefit of such tools is untested in Asian countries. The aim of this study was to determine the early adverse prognostic factors in patients hospitalized with CAP in Malaysia and to assess the usefulness of the British Thoracic Society (BTS) severity criteria.
A comparison of sputum induction methods: ultrasonic vs compressed-air nebulizer and hypertonic vs isotonic saline inhalation

Loh LC, Eg KP, Puspanathan P, Tang SP, Yip KS, Vijayasingham P, et al.

Asian Pac J Allergy Immunol, 2004 Mar;22(1):11-7.
PMID: 15366653

Airway inflammation can be demonstrated by the modem method of sputum induction using ultrasonic nebulizer and hypertonic saline. We studied whether compressed-air nebulizer and isotonic saline which are commonly available and cost less, are as effective in inducing sputum in normal adult subjects as the above mentioned tools. Sixteen subjects underwent weekly sputum induction in the following manner: ultrasonic nebulizer (Medix Sonix 2000, Clement Clarke, UK) using hypertonic saline, ultrasonic nebulizer using isotonic saline, compressed-air nebulizer (BestNeb, Taiwan) using hypertonic saline, and compressed-air nebulizer using isotonic saline. Overall, the use of an ultrasonic nebulizer and hypertonic saline yielded significantly higher total sputum cell counts and a higher percentage of cell viability than compressed-air nebulizers and isotonic saline. With the latter, there was a trend towards squamous cell contaminations. The proportion of various sputum cell types was not significantly different between the groups, and the reproducibility in sputum macrophages and neutrophils was high (Intraclass correlation coefficient, r [95%CI]: 0.65 [0.30-0.91] and 0.58 [0.22-0.89], p < 0.001). Overall changes in median FEV, were small and comparable between all groups. Induction using ultrasonic nebulizers together with hypertonic saline was generally less well tolerated than compressed-air nebulizers and isotonic saline. We conclude that in normal subjects, although both nebulizers and saline types can induce sputum with reproducible cellular profile, ultrasonic nebulizers and hypertonic saline are more effective but less well tolerated.
Addition of macrolide in treating adult hospitalized community-acquired pneumonia

Loh LC, Quah SY, Khoo SK, Vijayasingham P, Thayaparan T

Respirology, 2005 Jun;10(3):371-7.
PMID: 15955152

Current clinical practice guidelines, including those in south Asia, recommend the addition of a macrolide to a broad-spectrum antibiotic for the treatment of severe hospitalized community-acquired pneumonia (CAP). The aim of this study was to observe the influence of macrolide addition on clinical outcomes of hospitalized adult patients with CAP.
Nipah encephalitis outbreak in Malaysia, clinical features in patients from Seremban

Chong HT, Kunjapan SR, Thayaparan T, Tong J, Petharunam V, Jusoh MR, et al.

Can J Neurol Sci, 2002 Feb;29(1):83-7.
PMID: 11858542

BACKGROUND: An outbreak of viral encephalitis occurred among pig industry workers in Malaysia in September 1998 to April 1999. The encephalitis was attributed to a new paramyxovirus, Nipah virus. This is a description of the clinical features of 103 patients treated in the Seremban Hospital with characterization of the prognostic factors.
METHODS: Clinical case records and laboratory investigations were reviewed. The case definition was: patients from the outbreak area, direct contact or in close proximity with pigs, clinical or CSF features of encephalitis.
RESULTS: The mean age was 38 years, 89% were male, 58% were ethnic Chinese, 78% were pig farm owners or hired workers. The mean incubation period was 10 days. The patients typically presented with nonspecific systemic symptoms of fever, headache, myalgia and sore throat. Seizures and focal neurological signs were seen in 16% and 5% respectively. In the more severe cases, this was followed by drowsiness and deteriorating consciousness requiring ventilation in 61%. Autonomic disturbances and myoclonic jerks were common features. The mortality was high at 41%. Systolic hypertension, tachycardia and high fever were associated with poor outcome. On the other hand, 40% recovered fully. As for the other 19%, the residual neurological signs were mostly mild.
CONCLUSION: Nipah virus caused an encephalitis illness with short incubation period and high mortality. The prognosis for the survivors was good.
Fulltext Disease impact and patient insight--a study on a local population of asthmatics

Ahmad NS, Chan MY, Hiew FL, Sharif SA, Vijayasingham P, Thayaparan T, et al.

Med J Malaysia, 2003 Oct;58(4):526-32.
PMID: 15190628

The cornerstone of asthma management is achieving adequate symptom control and patient education. We studied in our local population of asthmatic patients how well their symptoms were controlled with currently prescribed treatment and their insight into the disease and its management. Over a 6-month period, 93 asthmatics recruited from two local government health clinics and a state hospital were interviewed using a standard questionnaire. Patients were classified into 4 groups based on the treatment they were on according to Global Initiative for Asthma (GINA) treatment guidelines. The number of patients in Step 1 (rescue medication alone), Step 2 (1 controller medication), Step 3 (2 controller medications) and Step 4 (at least 3 controller medications) were 8, 39, 34 and 12, respectively. Except for day symptoms in Step 1 group, fewer than 50% achieved minimum day or night symptoms and no restriction of daily activities. Questions on patient insight were only available for 50 patients. Weather change (74%), air pollution (66%) and physical stress (46%) were the three highest ranked common asthma triggers. More than half correctly recognized the important symptoms of a serious asthma attack but fewer than 15% were familiar with the peak flow meter and its use or with the asthma self-management plan. Most patients perceived that their treatment had helped reduce disease severity and exacerbations. We conclude that symptom control and some aspect of patient education are still lacking in our local asthmatics.
Study site: Hospital Tuanku Jaafar, Seremban, Negeri Sembilan; Klinik Kesihatan Seremban; Klinik Kesihatan Ampangan, Malaysia
Fulltext A study of admission criteria and early management of adult patients with acute asthma

Kanesalingam R, Lu YS, Ong JJ, Wong SS, Vijayasingham P, Thayaparan T, et al.

Med J Malaysia, 2003 Oct;58(4):587-93.
PMID: 15190635

We studied the admission criteria and first 24-hour management of 62 asthmatic patients admitted from Accident and Emergency (A&E) department of a state hospital. Data was collected prospectively over a 6-month period from the doctors' medical records with reference to recommendations of the Malaysian Thoracic Society (MTS) on management of acute asthma. Peak Expiratory Flow Rate (PEFR) records were present in only 14.5% of the A&E notes and 54.8% of the ward notes. Most of these readings were below 75% of predicted normal values. Over half of the patients had records on ability to speak full sentences, and respiratory and pulse rates. Based on other records on criteria for life-threatening features (including arterial blood gases), 42% of patients studied had life threatening asthma exacerbations. Most received appropriate treatment as recommended by the MTS. We conclude that while most patients were admitted and treated appropriately, medical documentation regarding acute asthma assessment were inadequate in some.
Study site: Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, Malaysia
Fulltext Klebsiella pneumoniae respiratory isolates from 2000 to 2004 in a Malaysian hospital: characteristics and relation to hospital antibiotics consumption

Loh LC, Chin HK, Chong YY, Jeyaratnam A, Raman S, Vijayasingham P, et al.

Singapore Med J, 2007 Sep;48(9):813-8.
PMID: 17728961

Klebsiella pneumoniae ranks high as a cause of community-acquired pneumonia in hospitalised patients in Malaysia.
Fulltext Hospital outcomes of adult respiratory tract infections with extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae

Loh LC, Abdul Samad NIH, Mohd Sani RM, Raman S, Thayaparan T, Kumar S

Malays J Med Sci, 2007 Jul;14(2):36-40.
PMID: 22993489 MyJurnal

Klebsiella pneumoniae ranks high as a cause of adult pneumonia requiring hospitalization in Malaysia. To study whether extended-spectrum b-lactamase (ESBL) producing K. pneumoniae was linked to hospital outcomes, we retrospectively studied 441 cases of adult respiratory tract infections with microbial proven K. pneumoniae from an urban-based university teaching hospital between 2003 and 2004. 47 (10.6%) cases had ESBL. Requirement for ventilation and median length of hospital stay, were greater in 'ESBL' than in 'non-ESBL' group [34% vs. 7.4%, p<0.001; 14 days vs. 5 days, p<0.001 respectively] but not crude hospital mortality rate [21.3% vs. 12.4%, p=0.092]. There was a four-fold increased risk of requiring ventilation [4.61 (2.72-7.85)] when ESBL was present. Our findings support the association of ESBL producing K. pneumoniae with adversed hospital outcomes and reiterate the need for vigilance on the part of treating clinicians.
Treatment of acute Nipah encephalitis with ribavirin

Chong HT, Kamarulzaman A, Tan CT, Goh KJ, Thayaparan T, Kunjapan SR, et al.

Ann Neurol, 2001 Jun;49(6):810-3.
PMID: 11409437

Nipah virus, a newly identified paramyxovirus caused a severe outbreak of encephalitis in Malaysia with high fatalities. We report an open-label trial of ribavirin in 140 patients, with 54 patients who were managed prior to the availability of ribavirin or refused treatment as control. There were 45 deaths (32%) in the ribavirin arm; 29 deaths (54%) occurred in the control arm. This represents a 36% reduction in mortality (p = 0.011). There was no associated serious side effect. This study suggests that ribavirin is able to reduce the mortality of acute Nipah encephalitis.
Fulltext Time delay and its effect on survival in malaysian patients with non-small cell lung carcinoma

Loh LC, Chan LY, Tan RY, Govindaraju S, Ratnavelu K, Kumar S, et al.

Malays J Med Sci, 2006 Jan;13(1):37-42.
PMID: 22589589 MyJurnal

While evidence indicates that early stage disease has better prognosis, the effect of delay in presentation and treatment of patients with non-small cell lung cancer (NSCLC) on survival is debatable. A retrospective study of 122 Malaysian patients with NSCLC was performed to examine the presentation and treatment delay, and its relation with patient survival. Median (25-75% IQR) interval between onset of symptoms and first hospital consultation (patient delay) and between first hospital consultation and treatment or decision to treat (doctor delay) were 2 (1.0- 5.0) and 1.1 (0.6-2.4) months respectively. The median survival rates in patient delay of <1, 1 to 3, and >3 months were 4.1 (9.9-1.7), 5.1 (10.9-3.2) and 5.7 (12.3-2.1) months respectively (log rank p=0.648), while in doctor delay, <30, 30-60, >60 days, the rates were 4.1 (10.8-1.8), 7.6 (13.7-3.2) and 5.3 (16.0-3.0) months respectively (p=0.557). Most patients presented and were treated in a relatively short time, and delays did not appear to influence survival. This Asian data is consistent with those from Western population, reiterating the need for public health measures that can identify disease early..
Survival in Patients with Non-Small Cell Lung Cancer Who Opted out of Cancer-Specific Therapy

Loh LC, Tan RY, Chan LY, Govindaraju S, Ratnavelu K, Kumar S, et al.

Malays J Med Sci, 2006 Jul;13(2):24-9.
PMID: 22589601 MyJurnal

In Malaysia, many patients opted out of cancer-specific treatment for various reasons. This study was undertaken to investigate the survival rate of patients with stages I to III non-small cell lung cancer (NSCLC) who opted out of treatment, compared with those who accepted treatment. Case records of 119 patients diagnosed with NSCLC between 1996 and 2003 in two urban-based hospitals were retrospectively examined. Survival status was ascertained from follow-up medical clinic records or telephone contact with patients or their next-of-kin. Median (25-75% IQR) survival rate for 79 patients who accepted and 22 patients who opted out of treatment, were 8.6 (16.0-3.7) and 2.2 (3.5-0.8) months respectively [log rank p< 0.001, Kaplan-Meier survival analysis]. Except for proportionately more patients with large cell carcinoma who declined treatment, there was no significant difference between the two groups in relation with age, gender, ethnicity, tumour stage, and time delays between symptom onset and treatment or decision-to-treat. We concluded that there was a small but significant survival benefit in accepting cancer-specific treatment. The findings imply that there is no effective alternative therapy to cancer-specific treatment in improving survival. However, overall prognosis for patients with NSCLC remains dismal.
Relapsed and late-onset Nipah encephalitis

Tan CT, Goh KJ, Wong KT, Sarji SA, Chua KB, Chew NK, et al.

Ann Neurol, 2002 Jun;51(6):703-8.
PMID: 12112075

An outbreak of infection with the Nipah virus, a novel paramyxovirus, occurred among pig farmers between September 1998 and June 1999 in Malaysia, involving 265 patients with 105 fatalities. This is a follow-up study 24 months after the outbreak. Twelve survivors (7.5%) of acute encephalitis had recurrent neurological disease (relapsed encephalitis). Of those who initially had acute nonencephalitic or asymptomatic infection, 10 patients (3.4%) had late-onset encephalitis. The mean interval between the first neurological episode and the time of initial infection was 8.4 months. Three patients had a second neurological episode. The onset of the relapsed or late-onset encephalitis was usually acute. Common clinical features were fever, headache, seizures, and focal neurological signs. Four of the 22 relapsed and late-onset encephalitis patients (18%) died. Magnetic resonance imaging typically showed patchy areas of confluent cortical lesions. Serial single-photon emission computed tomography showed the evolution of focal hyperperfusion to hypoperfusion in the corresponding areas. Necropsy of 2 patients showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigens but no evidence of perivenous demyelination. We concluded that a unique relapsing and remitting encephalitis or late-onset encephalitis may result as a complication of persistent Nipah virus infection in the central nervous system.

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