Transmission modes of severe acute respiratory syndrome coronavirus 2 and implications for infection control: a review

The complete picture regarding transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. This review summarises the available evidence on its transmission modes, our preliminary research findings and implications for infection control policy, and outlines future research directions. Environmental contamination has been reported in hospital settings occupied by infected patients, and is higher in the first week of illness. Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 ribonucleic acid in air samples, none has isolated viable virus in culture. Transmission likely lies on a spectrum between droplet and airborne transmission, depending on the patient, disease and environmental factors. Singapore's current personal protective equipment and isolation protocols are sufficient to manage this risk.

Paediatric emergency department attendances during COVID-19 and SARS in Singapore

INTRODUCTION@#We evaluated the impact of public health measures on paediatric emergency department attendances during the COVID-19 and severe acute respiratory syndrome (SARS) outbreaks in Singapore.@*METHODS@#Between 1 January 2020 and 31 July 2020, we retrospectively reviewed paediatric emergency department attendances and admissions in a tertiary paediatric hospital in Singapore before and after a national lockdown to combat the spread of COVID-19 in Singapore. Hospital attendances and admissions were compared with data from a corresponding period in 2019 (1 January 2019 to 31 July 2019), as well as during and after the SARS outbreak (1 January 2003 to 31 December 2004).@*RESULTS@#Compared with a corresponding non-outbreak period, emergency department attendances decreased in line with nationwide public health measures during the COVID-19 and SARS outbreaks (2020 and 2003 respectively), before increasing gradually following lifting of restrictions, albeit not to recorded levels before these outbreaks. During the COVID-19 outbreak, mean daily attendances decreased by 40%, from 458 per day in January-July 2019, to 274 per day in January-July 2020. The absolute number of hospital inpatient admissions decreased by 37% from January-July 2019 (19,629) to January-July 2020 (12,304). The proportion of emergency department attendances requiring admission remained similar: 20% in January-July 2019 and 21% in January-July 2020.@*CONCLUSION@#Nationwide public health measures in Singapore have had an impact on paediatric emergency department attendances and hospital inpatient admissions. Data from this study could inform planning and resource allocation for emergency departments in Singapore and internationally.

Management of HIV-positive pregnant women: a Singapore experience

INTRODUCTION@#Perinatal transmission remains one of the important causes of transmission of the human immunodeficiency virus (HIV). Over the years, with better knowledge and awareness of HIV infection, the perinatal transmission rate has been significantly reduced. We previously reported on the pregnancy outcomes of HIV-positive mothers from 1997 to 2007 in our institution. This article aimed to review the standards of care of HIV-positive pregnant women since then.@*METHODS@#A retrospective study reviewed 84 HIV-positive women who delivered in a tertiary centre from January 2008 to December 2015. Patient demographics and antenatal, intrapartum, postnatal and immediate neonatal data were analysed.@*RESULTS@#A total of 97 deliveries with 98 neonates were recorded; 12 women delivered more than once, and there was one set of twins. The mean maternal age at diagnosis of HIV infection was 27.8 years. Of the study population, 63.1% of women were non-Singaporeans. 56 women were known to have HIV infection on presentation and 90.7% were on antiretroviral therapy during pregnancy. 88.7% of the women received intrapartum intravenous zidovudine, and 93.1% of women with detectable and 58.7% with undetectable viral load underwent Caesarean sections. All neonates were HIV-negative.@*CONCLUSION@#The high standards of care for HIV-positive women have successfully reduced our perinatal transmission rate to zero.

Pregnancy Outcomes in COVID-19: A Prospective Cohort Study in Singapore

INTRODUCTION@#Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore.@*METHODS@#Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission.@*RESULTS@#Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5).@*CONCLUSION@#The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.

Gender-Specific Reference Charts of Fetal Head Circumference in a Singaporean Population

<p><b>INTRODUCTION</b>With the global outbreak of Zika virus and its association with microcephaly, an up-to-date fetal head circumference (HC) nomogram is crucial to offer a reference standard in order to make an accurate diagnosis. This study was conducted to revise the local fetal HC nomogram.</p><p><b>MATERIALS AND METHODS</b>In this retrospective study, ultrasound data was used for construction of the fetal HC nomogram from a total of 6155 pregnancies in the ethnic Chinese population with low risk profile at KK Women's and Children's Hospital over a 10-year period. Regression model was fitted to calculate the mean and standard deviation of HC at each gestational age (GA). Comparison of HC between ethnic groups (no significant differences) and genders were made. The revised chart was compared with another commonly used reference chart (Hadlock). In an independent test population, different reference charts were used to estimate number of cases with microcephaly.</p><p><b>RESULTS</b>A statistically significant difference of HC between the genders was observed across all gestational ages. Gender-specific reference charts and equation were computed. Our revised fetal HC chart showed a different distribution from the Hadlock chart. Compared with the gender-specific charts, the Hadlock HC chart would significantly under-report microcephaly cases in male fetuses, and tend to over-report in female fetuses.</p><p><b>CONCLUSION</b>This study provides a new set of gender-specific fetal HC charts in the Singaporean population for antenatal ultrasound surveillance of microcephaly.</p>

Ministry of Health Clinical Practice Guidelines: Prevention, Diagnosis and Management of Tuberculosis

The Ministry of Health (MOH) has developed the clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis to provide doctors and patients in Singapore with evidence-based treatment for tuberculosis. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis, for the information of SMJ readers. The chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Enteric Fever in a Tertiary Paediatric Hospital: A Retrospective Six-Year Review

<p><b>INTRODUCTION</b>Enteric fever is a multisystemic infection which largely affects children. This study aimed to analyse the epidemiology, clinical presentation, treatment and outcome of paediatric enteric fever in Singapore.</p><p><b>MATERIALS AND METHODS</b>A retrospective review of children diagnosed with enteric fever in a tertiary paediatric hospital in Singapore was conducted from January 2006 to January 2012. Patients with positive blood cultures for Salmonella typhi or paratyphi were identified from the microbiology laboratory information system. Data was extracted from their case records.</p><p><b>RESULTS</b>Of 50 enteric fever cases, 86% were due to Salmonella typhi, with 16.3% being multidrug resistant (MDR) strains. Sixty-two percent of S. typhi isolates were of decreased ciprofloxacin susceptibility (DCS). Five cases were both MDR and DCS. The remaining 14% were Salmonella paratyphi A. There were only 3 indigenous cases. Ninety-four percent had travelled to typhoid-endemic countries, 70.2% to the Indian subcontinent and the rest to Indonesia and Malaysia. All patients infected with MDR strains had travelled to the Indian subcontinent. Anaemia was a significant finding in children with typhoid, as compared to paratyphoid fever (P = 0.04). Although all children were previously well, 14% suffered severe complications including shock, pericardial effusion and enterocolitis. None had typhoid vaccination prior to their travel to developing countries.</p><p><b>CONCLUSION</b>Enteric fever is largely an imported disease in Singapore and has contributed to significant morbidity in children. The use of typhoid vaccine, as well as education on food and water hygiene to children travelling to developing countries, needs to be emphasised.</p>

Risk Factors for Severe Adenovirus Infection in Children during an Outbreak in Singapore

<p><b>BACKGROUND</b>Human adenoviruses (HAdVs) can cause a variety of human illnesses, with associated temporal and geographic changes in disease incidence. We report the emergence of an outbreak of HAdV infections in Singapore, presumably caused by a change of the predominating type to HAdV-7. We examined the clinical features of children admitted with HAdV infection to 1 institution and the risk factors for severe infection.</p><p><b>MATERIALS AND METHODS</b>This is a retrospective case-control study of all HAdV-infected children admitted during weeks 1 to 19 in 2013, as identified from laboratory records. A descriptive retrospective analysis of epidemiology, clinical data and the outcome of these children was also performed. Patients with severe infections were defined as cases, those with non-severe infections as controls, and the 2 groups were compared to find possible independent risk factors.</p><p><b>RESULTS</b>Eighty-five patients with HAdV infection were studied, including 11 (12.9%) cases and 74 (87.1%) controls. Binary logistic regression showed that cases were more likely to be <2 years old (adjusted OR 10.6, 95% CI, 1.8 to 63.2) and to have significant comorbidities (adjusted OR 19.9, 95% CI, 3.4 to 116.1) compared to controls. The predominant type in 2013 was HAdV-7, which differed from 2011 and 2012, when HAdV-3 was more common. There was a trend towards pneumonia being more common in patients infected with HAdV-7 than in patients infected with other types, although this did not reach statistical significance (OR 2.8, 95% CI, 0.9 to 8.7).</p><p><b>CONCLUSION</b>The emergence of HAdV-7 in a population where other HAdV types had circulated previously may have caused the outbreak in Singapore, and this was associated with more serious infections in children. Young age (<2 years) and significant comorbidities were associated with more severe HAdV infection.</p>

Granulomatous cervicofacial lymphadenitis in children: a nine-year study in Singapore

<p><b>INTRODUCTION</b>Granulomatous cervicofacial lymphadenitis (GCL) is not uncommon in children. Nontuberculous mycobacteria (NTM) seem to be the predominant cause. We sought to study the clinical and microbiological profile of patients with GCL, and identify features that may impact outcome.</p><p><b>METHODS</b>Children aged < 16 years who presented to KK Women's and Children's Hospital, Singapore, between January 1998 and December 2006, and who had GCL were identified from laboratory records. Clinical and laboratory data was collected and analysed for risk factors for patients with positive lymph node cultures, and for patients with and without recurrence after treatment.</p><p><b>RESULTS</b>In all, 60 children were identified, with a median age of 56 (interquartile range [IQR] 34-101) months. Median duration of symptoms before presentation was 5 (IQR 4-8) weeks. The majority presented with single (73.3%) or unilateral (96.7%) lymphadenopathy, located in the submandibular, preauricular/parotid or infra-/post-auricular region (76.7%). Out of 51 patients, 26 (51.0%) had a tuberculin skin test reading of ≥ 10 mm. Out of 52 patients, 10 (19.2%) had positive mycobacterial cultures, which included seven isolates of NTM. Out of 34 cases, tuberculous polymerase chain reaction was positive in 11 (32.4%). With regard to recurrence after initial treatment, age < 5 years at presentation was found to be a predictor for recurrence (p = 0.008), while initial complete excision of affected nodes predicted no recurrence (p = 0.003).</p><p><b>CONCLUSION</b>In our study, younger age was noted to be associated with a higher chance of recurrence, while complete excision of the involved node at initial presentation predicted non-recurrence.</p>

Risk Factors for Complicated Influenza A (H1N1) 2009 Disease in Children

<p><b>INTRODUCTION</b>Singapore had its first case of pandemic influenza A (H1N1) 2009 on 26 May 2009. As of 3 August 2009, 440 children with confirmed H1N1were admitted to KK Women's and Children's Hospital (KKH).</p><p><b>MATERIALS AND METHODS</b>This is a retrospective case control study of children admitted from 26 May 2009 to 19 July 2009 with H1N1infection. Cases and controls were first differentiated by whether they were complicated or non-complicated in nature, and subsequently analysed with regards to possible independent risk factors.</p><p><b>RESULTS</b>We analysed 143 admitted children; 48 cases and 95 controls (1: 2 ratio). Significant comorbidity was found in 20.3% (n = 29) of patients with the majority having asthma (n = 18, 12.6 %) followed by obesity (n = 7, 4.9%). Binary logistic regression analysis showed risk factors for complicated disease were comorbidity (adjusted OR 6.0, 95% CI, 2.5 to 14.6, P < 0.0001) and age <2 years (adjusted OR 9.8, 95% CI, 2.4 to 40, P = 0.001). Age less than 5 years was not found to be a risk factor.</p><p><b>CONCLUSION</b>In the early stages of an evolving influenza epidemic when oseltamivir stocks are low, oseltamivir treatment for influenza can be streamlined and offered to those at highest risk who are under 2 years old or have significant comorbidity to prevent complicated disease.</p>

Clinical evaluation of an in-house human immunodeficiency virus (HIV) genotyping assay for the detection of drug resistance mutations in HIV-1 infected patients in Singapore

<p><b>INTRODUCTION</b>Human immunodeficiency virus type 1 (HIV-1) genotyping resistance test (GRT) is essential for monitoring HIV-1 drug resistance mutations (DRMs). High cost and HIV-1 genetic variability are challenges to assay availability in Singapore. An in-house Sanger sequencing-based GRT method was developed at the Communicable Disease Centre (CDC), Singapore's HIV national treatment reference centre for both subtype B and non-subtype B HIV-1.</p><p><b>MATERIALS AND METHODS</b>The in-house GRT sequenced the fi rst 99 codons of protease (PR) and 244 codons of reverse transcriptase (RT) in the pol gene. The results were compared with the Food and Drug Administration (FDA)-approved ViroSeq™ HIV-1 Genotyping System.</p><p><b>RESULTS</b>Subtype assignment for the 46 samples were as follows: 31 (67.4%) CRF01_AE, 14 (30.5%) subtype B and 1 (2.1%) subtype C. All 46 samples had viral load of ≥500 copies/mL, and were successfully amplified by the in-house primer sets. Compared to the ViroSeq™ test, our in-house assay showed drug-resistance conferring codon concordance of 99.9% at PR and 98.9% at RT, and partial concordance of 0.1% at PR and 1.1% at RT. No discordant result was observed.</p><p><b>CONCLUSION</b>The assay successfully identified DRMs in both subtype AE and B, making it suitable for the efficient treatment monitoring in genetically diverse population. At less than half of the running cost compared to the ViroSeq™ assay, the broadly sensitive in-house assay could serve as a useful addition to the currently limited HIV genotyping assay options for resource-limited settings, thereby enhancing the DRM surveillance and monitoring in the region.</p>

Survey of healthcare workers' attitudes, beliefs and willingness to receive the 2009 pandemic influenza A (H1N1) vaccine and the impact of educational campaigns

<p><b>INTRODUCTION</b>Vaccination against the 2009 pandemic influenza A (H1N1) represents the best method of controlling spread, morbidity and mortality due to the pandemic. While this has been recommended for all healthcare-workers locally, it is unclear if they are willing to accept the vaccination.</p><p><b>MATERIALS AND METHODS</b>A cross-sectional survey was conducted before and after an educational talk on pandemic influenza and vaccines to ascertain responses and stated reasons, as well as identify associated factors.</p><p><b>RESULTS</b>For 235 returned forms prior to the talk, 182 (77.4%) responded positively, while 161 of 192 (83.8%) who returned forms after the talk responded positively. Importantly, 12 of 47 (25.5%) initially negative responses turned positive after education. The desire to protect family, self and patients were the 3 most important reasons for staff wanting to receive the vaccine, while the concern regarding potential side effects was the most important reason for refusal.</p><p><b>CONCLUSIONS</b>A high rate of willingness to receive pandemic influenza vaccine was found, which was in contrast to acceptance rates elsewhere and during previous influenza seasons. Education can play an important role in altering vaccine acceptance behaviour, with an emphasis on addressing concerns with regard to potential side effects.</p>