Clinical spectrum of children receiving palliative care in Malaysian Hospitals.

INTRODUCTION: Awareness for paediatric palliative care has resulted in the impetus for paediatrician-led palliative care services across Malaysia. However, there is paucity of local data on patients receiving hospital-based paediatric palliative care. We aim to review the clinical spectrum of patients referred to these services. METHODS: An observational study of children aged between 0-18 years receiving palliative care at 13 hospitals between 1st January and 31st December 2014 was carried out. RESULTS: There were 315 patients analysed, 90 (28.6%) and 46 (14.6%) were neonates and adolescents respectively. The main ICD-10 diagnostic categories for all patients were identified to be 'Congenital malformations, deformations and chromosomal abnormalities' 117 (37.1%), 'Diseases of nervous system' 76 (24.1%) and 'Neoplasms' 60 (19.0%). At referral 156 (50%) patients had holistic needs assessments. Patients with 'Diseases of nervous system' were assessed to have significantly more physical needs than the other two diagnostic categories. Majority of patients who knew of their diagnosis and prognosis were those with malignancy. Over a fifth of referrals were at their terminal admission. Of 144 who died, 111 (77.1%) had advanced care plans. There was bereavement follow-up in 98 (68.1%) patients. CONCLUSION: Patients referred for palliative care have varied diagnoses and needs. To ensure all paediatricians are competent to deliver quality care to all children, further education and training initiatives is imperative.

Sequence analysis of E/NS1 gene junction of Dengue Type-1 viruses isolated in Klang Valley 2010 to 2012.

Dengue is a mosquito-borne viral disease caused by four serotypes of dengue virus, affecting the human population for decades in many tropical and subtropical regions of the world. In Malaysia, all four dengue serotypes co-circulates in a dengue season even though any one of the serotypes can predominate. In this study, serum samples were collected from dengue fever and severe dengue fever patients within Klang Valley from 2010-2012 to determine the prevailing dengue serotypes. In addition, sequencing of the envelope/nonstructural 1 (E/NS1) gene junction of the virus isolated was performed to identify the presence of any mutations that are suggestive of increased virulence in the virus. The results showed that Dengue-1 (DEN-1) was the predominant circulating serotype. The E/NS1 gene sequences of the isolates were analysed to trace the evolutionary knowledge of the strains. All sequences of the isolates were compared with DEN-1 prototype Hawaii strain as the reference sequence. The E/NS1 sequences of other dengue strains from neighbouring regions as well as other parts of the world obtained from the GenBank database were also included in the phylogenetic tree analysis. Analyses showed that there was 97% to 100% similarity among the ten isolates at the nucleotide level. Similarly, the amino acid analogue also showed 98% to 100% homology. However, all five non-severe dengue isolates showed variation at position 780, resulting in an amino acid change from valine to alanine as compared to severe dengue isolates. A rooted phylogenetic tree was performed using neighbour-joining method with DEN-2 and DEN-3 as the outgroups. Results showed that all ten isolates were classified as genotype I. In addition, the five isolates from severe dengue patients were found to be clustered together with JN697057 and JN697058, Malaysian DEN-1 strains from the 2005 outbreak.

Sequence analysis of E/NS1 gene junction of Dengue Type-1 viruses isolated in Klang Valley 2010 to 2012

Dengue is a mosquito-borne viral disease caused by four serotypes of dengue virus, affecting the human population for decades in many tropical and subtropical regions of the world. In Malaysia, all four dengue serotypes co-circulates in a dengue season even though any one of the serotypes can predominate. In this study, serum samples were collected from dengue fever and severe dengue fever patients within Klang Valley from 2010-2012 to determine the prevailing dengue serotypes. In addition, sequencing of the envelope/nonstructural 1 (E/NS1) gene junction of the virus isolated was performed to identify the presence of any mutations that are suggestive of increased virulence in the virus. The results showed that Dengue-1 (DEN-1) was the predominant circulating serotype. The E/NS1 gene sequences of the isolates were analysed to trace the evolutionary knowledge of the strains. All sequences of the isolates were compared with DEN-1 prototype Hawaii strain as the reference sequence. The E/NS1 sequences of other dengue strains from neighbouring regions as well as other parts of the world obtained from the GenBank database were also included in the phylogenetic tree analysis. Analyses showed that there was 97% to 100% similarity among the ten isolates at the nucleotide level. Similarly, the amino acid analogue also showed 98% to 100% homology. However, all five non-severe dengue isolates showed variation at position 780, resulting in an amino acid change from valine to alanine as compared to severe dengue isolates. A rooted phylogenetic tree was performed using neighbour-joining method with DEN-2 and DEN-3 as the outgroups. Results showed that all ten isolates were classified as genotype I. In addition, the five isolates from severe dengue patients were found to be clustered together with JN697057 and JN697058, Malaysian DEN-1 strains from the 2005 outbreak.

Laboratory-confirmed case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Malaysia: preparedness and response, April 2014.

On 14 April 2014, the first laboratory-confirmed case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported in Malaysia in a man in his mid-fifties, who developed pneumonia with respiratory distress, after returning from a pilgrimage to Saudi Arabia. The case succumbed to his illness three days after admission at a local hospital. The follow-up of 199 close contacts identified through contact tracing and vigilant surveillance did not result in detecting any other confirmed cases of MERS-CoV infection.

Congenital rubella syndrome: a review of laboratory data from 2002 to 2011.

Rubella infection in pregnant women during the first trimester of pregnancy can lead to fetal anomalies, commonly known as congenital rubella syndrome (CRS). The objective of our study was to analyze the serological test results among infants suspected of having CRS aged < or = 12 months compared with their clinical status. Between January 2002 and December 2011, 3,279 serum samples from infants aged < or = 12 months from government hospitals in Malaysia were examined for rubella specific IgM and IgG antibodies using a Axsym, automated analyzer (Abbott Laboratories). Forty-eight samples were positive for rubella specific IgM antibodies and 494 samples were positive for rubella specific IgG antibodies. These were then age stratified and their clinical history reviewed for any CRS symptoms. Fifteen of 38 rubella IgM positive infants (39.5%) aged < 3 months, had a clinical appearance compatible with CRS. However, only 1 IgM positive infant aged 3 to 6 months and one infant aged 7 to 11 months had clinical appearance compatible with CRS. The most common abnormal findings in these cases were congenital heart defects and cataracts. Forty-eight point eight percent of IgM positive cases and 53.1% of IgG positive cases, had inadequate information in the chart to determine the presence of CRS. Clinical findings and timely laboratory diagnosis to determine the presence of CRS are important in infants born with congenital defects. Physicians should also be aware of the appropriate interpretation of these findings.

Seroprevalence of cytomegalovirus infection in pregnant women and associated role in obstetric complications: a preliminary study.

The objective of this study was to determine the seroprevalence of cytomegalovirus (CMV) infections through antenatal screening data and the association of this virus with obstetric complications. Serum samples from 125 apparently healthy pregnant women sent for antenatal screening from various hospitals in Malaysia between January 2007 and December 2008, were examined for CMV specific IgM and IgG antibodies using an enzyme-linked immunosorbent assay method. Of the 125 pregnant women tested, anti-CMV IgG antibody was found in 105 (84%) of the cases and anti-CMV IgM in 9 cases (7.2%). Both CMV IgM and IgG were also found in another 37 women whose serum samples were sent for investigation of various obstetric complications: 17 cases of spontaneous abortions, 15 cases of fetal anomalies detected during ultrasound examination, 1 case of incomplete abortion, 3 cases with premature delivery of infant with congenital anomalies and 1 case of infertility. Our preliminary data which only represented a small study group has shown the prevalence of CMV infection among the local population and the association of CMV in obstetric complications.

Identification of Chikungunya virus strains circulating in Kelantan, Malaysia in 2009.

Malaysia experienced its first outbreak of chikungunya virus (CHIKV) infection in late 1998 in Klang District in Selangor; six years later the virus re-emerged in the state of Perak. All the CHIKV isolates in 1988 and 2006 shared high sequence similarities and belonged to the Asian genotype. In 2007 and 2008 CHIKV infection again reemerged but the genotype was the Central/East African genotype. This strain was found to be similar to the strains causing outbreaks in the India Ocean. In 2009, the strains circulating in Malaysia, including the state of Kelantan, based on the partial E1 gene, also belong to the Central/East African genotype.

Molecular epidemiology of chikungunya virus in Malaysia since its first emergence in 1998.

Malaysia experienced the first outbreak of chikungunya (CHIK) in Klang in late 1998 due to CHIK virus of Asian genotype. The CHIK virus of Asian genotype reemerged causing outbreak in Bangan Panchor, Perak in March 2006. CHIK virus of Central/East African genotype was first detected from a patient who returned from India in August 2006. In December 2006, CHIK virus of Central/East African genotype was re-introduced into Malaysia from India and caused an outbreak in Kinta district, Perak but was successfully controlled following an early detection and institution of intensive vector control measures. In late April 2008, CHIK virus of Central/East African genotype was laboratory confirmed as the cause of CHIK outbreak in Johore which spread to other parts of Malaysia by August 2008. Phylogenetic analysis based on the 254-bp fragment of the virus envelope protein gene as the genetic marker showed that three different strains of CHIK virus of Central/East African genotype were introduced into Malaysia on three separate occasions from 2006 to 2008. The strain that was introduced into Johor state was responsible for its subsequent spread to other parts of Malaysia, inclusive of Sarawak.

Impact of a measles elimination strategy on measles incidence in Malaysia.

In Malaysia, the two dose measles - mumps - rubella (MMR) vaccine was introduced in the Expanded Program on Immunization in 2002. The Ministry of Health then initiated a measles elimination strategy which included enhanced case-based surveillance with laboratory testing of all suspected cases. The objective of our study was to analyse national measles laboratory data from 2004 to 2008 to study the impact of the nationwide strategy on measles case incidence. Blood samples collected from suspected measles cases during the acute stage of the illness were investigated for measles specific IgM. The estimated incidence of measles ranged from 22.3 cases (in 2004) to 2.27 cases (in 2006) per 100,000 population. During this time, the measles vaccination coverage was above 85%. Laboratory confirmed measles cases dropped from 42.2% in 2004, when sporadic outbreaks were reported, to 3.9% in 2007. Screening for measles IgG levels in 2008 showed that 82.8% of those > 7 years old had adequate immunity. The measles control strategy appears to have been successful in reducing the incidence of measles. Continuing high vaccination coverage rates and ongoing measles surveillance are necessary to achieve our goal of measles elimination.

Performance of a commercial rapid dengue NS1 antigen immunochromatography test with reference to dengue NS1 antigen-capture ELISA.

The performance of a commercial immunochromatography test for rapid detection of dengue NS1 antigen present in serum or plasma of patients was evaluated against a commercial dengue NS1 antigen-capture ELISA. The rapid immunochromatography test gave an overall sensitivity of 90.4% with a specificity of 99.5%. The sensitivity was highest for serum samples from which virus was isolated (96.3%) and lowest for those from which virus was not isolated and RT-PCR was negative (76.4%). The sensitivity was significantly higher for serum samples from patients with acute primary dengue (92.3%) than those from patients with acute secondary dengue (79.1%). The positive predictive value and negative predictive value of this commercial immunochromatography test were 99.6% and 87.9% respectively.

Acute flaccid paralysis surveillance: looking beyond the global poliomyelitis eradication initiative.

In 1992 surveillance of acute flaccid paralysis (AFP) cases was introduced in Malaysia along with the establishment of a national referral laboratory at the Institute for Medical Research. The objective of this study was to determine the incidence, viral etiology and clinical picture of AFP cases below 15 years of age, reported from 2002 to 2007. Six hundred seventy-eight of 688 reported cases were confirmed as AFP by expert review. The clinical presentation of acute flaccid paralysis in these cases was diverse, the most commonly reported being Guillian-Barre syndrome (32.3%). Sixty-nine viruses were isolated in this study. They were Sabin poliovirus (25), Echovirus (22), Cocksackie B (11), EV71 (5), Cocksackie A (1), and untypable (5). Malaysia has been confirmed as free from wild polio since the surveillance was established.

Determinants of linear growth in Malaysian children with cerebral palsy.

OBJECTIVE: To compare the linear growth and nutritional parameters of a group of Malaysian children with cerebral palsy (CP) against a group of controls, and to determine the nutritional, medical and sociodemographic factors associated with poor growth in children with CP. METHODOLOGY: The linear growth of 101 children with CP and of their healthy controls matched for age, sex and ethnicity was measured using upper-arm length (UAL). Nutritional parameters of weight, triceps skin-fold thickness and mid-arm circumference were also measured. Total caloric intake was assessed using a 24-h recall of a 3-day food intake and calculated as a percentage of the Recommended Daily Allowance. Multiple regression analysis was used to determine nutritional, medical and sociodemographic factors associated with poor growth (using z-scores of UAL) in children with CP. RESULTS: Compared with the controls, children with CP had significantly lower mean UAL measurements (difference between means -1.1, 95% confidence interval -1.65 to - 0.59), weight (difference between means -6.0, 95% CI -7.66 to -4.34), mid-arm circumference (difference between means -1.3, 95% CI -2.06 to -0.56) and triceps skin-fold thickness (difference between means -2.5, 95% CI -3.5 to -1.43). Factors associated with low z-scores of UAL were a lower percentage of median weight (P < 0.001), tube feeding (P < 0.001) and increasing age (P < 0.001). CONCLUSION: A large proportion of Malaysian children with CP have poor nutritional status and linear growth. Nutritional assessment and management at an early age might help this group of children achieve adequate growth.

Comparison of sequences of E/NS1 gene junction of dengue type 3 virus following culture subpassage in C6/36 cells to study the possible occurrence of mutations.

The aim of this study was to determine whether mutations could occur in the dengue virus genome following three subpassages of the virus in a mosquito cell line. This was done because sources of virus isolates used for sequencing studies are usually maintained in cell lines rather than in patients' sera. Therefore it must be assured that no mutation occurred during the passaging. For this purpose, sequencing was carried out using the polymerase chain reaction (PCR) products of the envelope/non-structural protein 1 junction region (280 nucleotides) of dengue type 3 virus. Sequence data were compared between the virus from a patient's serum against the virus subpassaged three times in the C6/36 cell line. We found that the sequence data of the virus from serum was identical to the virus that was subpassaged three times in C6/36 cell line.

The use of polymerase chain reaction (PCR) as a diagnostic tool for dengue virus.

This study describes the use of polymerase chain reaction as a diagnostic tool for detecting and typing of dengue virus. PCR was compared against virus isolation. First RT-PCR was done using dengue consensus primers after which positive samples were subjected to RT-PCR using type-specific primers. This study shows that the local strains of the dengue virus could be detected using the chosen primers. Furthermore, RT-PCR was found to be more sensitive than virus isolation in identifying the dengue positive samples.

A microbiological study of genital ulcers in Kuala Lumpur.

The microbial aetiology of genital ulcers was studied in 249 patients (241 men and 8 women) attending a Sexually Transmitted Disease Clinic in Kuala Lumpur, Malaysia. Herpes simplex virus type 2 was isolated in 48 (19.2%) patients, Haemophilus ducreyi from 22 (8.8%), Neisseria gonorrhoeae from seven (2.8%) and Chlamydia trachomatis from four (1.6%). Syphilis was diagnosed in 18 (7.2%) patients on the basis of dark field microscopy. Two (0.8%) patients were found to have both chancroid and syphilis and one (0.5%) had both gonorrhoea and syphilis. No organism was isolated in the remaining 151 (61.5%) patients. Overall, the accuracy of clinical diagnosis was 58% for single infection, 67% for herpes, 63% for syphilis, 47% for chancroid and 0% for lymphogranuloma venereum. Therefore, our study confirms the need for laboratory tests to diagnose accurately the aetiology of genital ulcer disease.