Safety and effectiveness of switching to Abacavir/Lamivudine plus rilpivirine for maintenance therapy in virologically suppressed HIV-1 individuals in Singapore (SEALS).

BACKGROUND: The efficacy and tolerability of an antiretroviral regimen are important considerations for selection of HIV-1 infection maintenance therapy. Abacavir/lamivudine plus rilpivirine (ABC/3TC + RPV) has been shown in international studies to be effective and well-tolerated in virologically suppressed individuals. This study evaluated the effectiveness and safety of switching to ABC/3TC + RPV as maintenance therapy in virologically suppressed HIV-1 infected individuals in Singapore. METHODS: In this retrospective, single-centre study, we included individuals who were prescribed ABC/3TC + RPV, had HIV-1 viral load (VL) < 50 copies/ml immediately pre-switch, and had no documented history of resistance mutations or virologic failure to any of the components. The follow-up period was 48 ± 12 weeks. The primary outcome was the proportion of individuals who maintained virologic suppression of HIV-1 VL < 50 copies/ml at the end of follow-up period based on on-treatment analysis. The secondary outcomes were the resistance profiles associated with virologic failure, changes in immunologic and metabolic parameters, and the safety profile of ABC/3TC + RPV. RESULTS: A total of 222 individuals were included in the study. The primary outcome was achieved in 197 individuals [88.8%, 95% confidence interval: 83.7-92.4%]. There were 21 individuals (9.5%) who discontinued treatment for non-virologic reasons. The remaining 4 individuals experienced virologic failure, of whom, 3 of these individuals had developed emergent antiretroviral resistance and had HIV-1 VL > 500 copies/ml at the end of the 48 ± 12 weeks follow-up period. The remaining individual experienced sustained low level viremia and subsequently achieved viral suppression without undergoing resistance testing. A total of 49 adverse events were observed in 31 out of 222 individuals (14.0%), which led to 13 individuals discontinuing therapy. Neuropsychiatric adverse events were most commonly observed (53.1%). A statistically significant increase in CD4 was observed (p < 0.01), with a median absolute change of 31 cells/uL (interquartile range: - 31.50 to 140.75). No significant changes in lipid profiles were detected. CONCLUSION: ABC/3TC + RPV is a safe and effective switch option for maintenance therapy in virologically suppressed HIV-1 individuals with in Singapore.

Olfactory taste disorder as a presenting symptom of COVID-19: a large single-center Singapore study.

PURPOSE: To investigate the prevalence and epidemiological risk factors of olfactory and/or taste disorder (OTD), in particular isolated OTD, in patients with laboratory-confirmed COVID-19 infection. METHODS: We conducted a retrospective and cross-sectional study. Patients with laboratory-confirmed COVID-19 infection were recruited from the National Centre for Infectious Diseases (NCID) Singapore between 24 March 2020 and 16 April 2020. The electronic health records of these patients were accessed, and demographic data and symptoms reported (respiratory, self-reported OTD and other symptoms such as headache, myalgia and lethargy) were collected. RESULTS: A total of 1065 patients with laboratory-confirmed COVID-19 were recruited. Overall, the prevalence of OTD was 12.6%. Twelve patients (1.1%) had isolated OTD. The top three symptoms associated with OTD were cough, fever and sore throat. The symptoms of runny nose and blocked nose were experienced by only 29.8 and 19.3% of patients, respectively. Multivariate analysis demonstrated that the female gender, presence of blocked nose and absence of fever were significantly associated with OTD (adjusted relative risks 1.77, 3.31, 0.42, respectively). All these factors were statistically significant. CONCLUSION: Patients with COVID-19 infection can present with OTD, either in isolation or in combination with other general symptoms. Certain demographic profile, such as being female, and symptomatology such as the presence of blocked nose and absence of fever, were more likely to have OTD when infected by COVID-19. Further studies to elucidate the pathophysiology of OTD in these patients will be beneficial.

Does incubation period of COVID-19 vary with age? A study of epidemiologically linked cases in Singapore.

This study estimates the incubation period of COVID-19 among locally transmitted cases, and its association with age to better inform public health measures in containing COVID-19. Epidemiological data of all PCR-confirmed COVID-19 cases from all restructured hospitals in Singapore were collected between 23 January 2020 and 2 April 2020. Activity mapping and detailed epidemiological investigation were conducted by trained personnel. Positive cases without clear exposure to another positive case were excluded from the analysis. One hundred and sixty-four cases (15.6% of patients) met the inclusion criteria during the defined period. The crude median incubation period was 5 days (range 1-12 days) and median age was 42 years (range 5-79 years). The median incubation period among those 70 years and older was significantly longer than those younger than 70 years (8 vis-à-vis 5 days, P = 0.040). Incubation period was negatively correlated with day of illness in both groups. These findings support current policies of 14-day quarantine periods for close contacts of confirmed cases and 28 days for monitoring infections in known clusters. An elderly person who may have a longer incubation period than a younger counterpart may benefit from earlier and proactive testing, especially after exposure to a positive case.

Methicillin-resistant Staphylococcus aureus colonisation: epidemiological and molecular characteristics in an acute-care tertiary hospital in Singapore.

Current knowledge of methicillin-resistant Staphylococcus aureus (MRSA) colonisation in relation to epidemiological characteristics is incomplete. We conducted a cross-sectional study at an acute-care tertiary infectious diseases hospital of MRSA isolates identified through routine surveillance from January 2009 to December 2011. We randomly selected 205 MRSA isolates (119 inpatients) from 798 isolates (427 inpatients) for molecular profiling using multilocus sequence typing. Multilevel multinomial logistic regression was used to estimate odds ratio (OR) assessing the predilection of MRSA strains for anatomic sites, and associations of strains with human immunodeficiency virus (HIV) infection. The most frequent sequence types (STs) were 239, 22 and 45. The proportion of ST22 increased over the sampling period, replacing ST239 as the dominant lineage. However, ST239 remained the most prevalent among HIV-seropositive individuals who were six times more likely to be colonised with this strain than non-HIV patients (adjusted OR (aOR) 6.44, 95% confidence interval (CI) 1.94-21.36). ST45 was >24 times more likely to be associated with perianal colonisation than in the nares, axillae and groin sites (aOR 24.20, 95% CI 1.45-403.26). This study underlines the clonal replacement of MRSA in Singapore as previously reported but revealed, in addition, key strain differences between HIV-infected and non-infected individuals hospitalised in the same environment.

Contacts of healthcare workers, patients and visitors in general wards in Singapore.

To characterize contacts in general wards, a prospective survey of healthcare workers (HCWs), patients and visitors was conducted using self-reported diary, direct observation and telephone interviews. Nurses, doctors and assorted HCWs reported a median of 14, 18 and 15 contact persons over one work shift, respectively. Within 1 h, we observed 3·5 episodes with 25·6 min of cumulative contact time for nurses, 2·9 episodes and 22·1 min for doctors and 5·0 episodes with 44·3 min for assorted-HCWs. In interactions with patients, nurses had multiple brief episodes of contact; doctors had fewer episodes and less cumulative contact time; assorted-HCWs had fewer contact episodes of longer durations (than for nurses and doctors). Assortative mixing occurred amongst HCWs: those of the same HCW type were the next most frequent class of contact after patients. Over 24-h, patients contacted 14 persons with 23 episodes and 314·5 min of contact time. Patient-to-patient contact episodes were rare, but a maximum of five were documented from one patient participant. 22·9% of visitors reported contact with patients other than the one they visited. Our study revealed differences in the characteristics of contacts among different HCW types and potential transmission routes from patients to others within the ward environment.

Serodiagnosis of dengue virus infection using commercially available antibody and NS1 antigen ELISAs.

Accuracy of the InBios DENV Detect IgM, IgG and NS1 antigen (Ag) ELISAs (Seattle, WA) for detection of dengue virus (DENV) infection were evaluated using 100 retrospectively selected sera from acutely febrile patients presenting to a Singapore hospital. The InBios DENV NS1, IgM and IgG ELISAs had an overall sensitivity of 83.6%, 40% and 58.2% and an overall specificity of 97.8%, 97.8% and 55.6%, respectively. Simultaneous testing for NS1 and IgM-antibodies yielded a sensitivity and specificity of 85.5% and 95.5%, respectively, which did not significantly differ from testing for NS1 Ag alone. Using sera positive for IgM- or IgG-class antibodies to six common arboviruses, the InBios IgM and IgG ELISAs showed an overall analytic specificity of 89.2% and 66.4%, respectively. This study suggests that recent DENV infection can reliably be detected by the InBios NS1 Ag ELISA alone and that InBios DENV IgG reactivity should be interpreted with caution.

Risk assessment and laboratory investigation of respiratory illness in travellers returning to Singapore 2012-2015: experience from the MERS-CoV Surveillance Programme.

Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV), Singapore has enhanced its national surveillance system to detect the potential importation of this novel pathogen. Using the guidelines from the Singapore Ministry of Health, a suspect case was defined as a person with clinical signs and symptoms suggestive of pneumonia or severe respiratory infection with breathlessness, and with an epidemiological link to countries where MERS-CoV cases had been reported within the preceding 14 days. This report describes a retrospective review of 851 suspected MERS-CoV cases assessed at the adult tertiary-care hospital in Singapore between September 2012 and December 2015. In total, 262 patients (31%) were hospitalized. All had MERS-CoV infection ruled out by RT-PCR or clinical assessment. Two hundred and thirty (88%) of the hospitalized patients were also investigated for influenza virus by RT-PCR. Of these, 62 (27%) tested positive for seasonal influenza. None of the patients with positive influenza results had been vaccinated in the year prior to hospital admission. Ninety-three (36%) out of the 262 hospitalized patients had clinical and/or radiological evidence of pneumonia. This study demonstrates the potential benefits of pre-travel vaccination against influenza and pneumococcal disease.

Performance of case definitions for influenza surveillance.

Influenza-like illness (ILI) case definitions, such as those from the European Centre for Disease Control and Prevention, World Health Organization (WHO) and United States Centers for Disease Control and Prevention, are commonly used for influenza surveillance. We assessed how various case definitions performed during the initial wave of influenza A(H1N1) pdm09 infections in Singapore on a cohort of 727 patients with two to three blood samples and whose symptoms were reviewed fortnightly from June to October 2009. Using seroconversion (≥ 4-fold rise) to A/California/7/2009 (H1N1), we identified 36 presumptive influenza A(H1N1)pdm09 episodes and 664 episodes unrelated to influenza A(H1N1)pdm09. Cough, fever and headache occurred more commonly in presumptive influenza A(H1N1)pdm09. Although the sensitivity was low (36%), the recently revised WHO ILI case definition gave a higher positive predictive value (42%) and positive likelihood ratio (13.3) than the other case definitions. Results including only episodes with primary care consultations were similar. Individuals who worked or had episodes with fever, cough or sore throat were more likely to consult a physician, while episodes with Saturday onset were less likely, with some consultations skipped or postponed. Our analysis supports the use of the revised WHO ILI case definition, which includes only cough in the presence of fever defined as body temperature ≥ 38 °C for influenza surveillance.

Current epidemiology and clinical practice in arboviral infections - implications on blood supply in South-East Asia.

Arthropod-borne viruses (arboviruses) are a growing threat to global health. Complex vector-virus-host interactions lead to unpredictable epidemiological patterns. Difficulties in accurate surveillance including imperfect diagnostic tools impair effective response to outbreaks. With arboviral infections causing a wide spectrum of disease severity, from asymptomatic infection to fatal neuroinvasive and haemorrhagic fevers, the potential impact on blood safety is significant. Asymptomatic or presymptomatic individuals may introduce virus into the blood supply by donation, while recipients can potentially suffer severe consequences. Dengue, West Nile and chikungunya outbreaks have led to responses by blood transfusion services which can inform future planning. Reports of transfusion-associated transmission demonstrate the potentially fatal consequences of lack of haemovigilance. South-East Asia remains vulnerable to arboviruses with permissive climate and high levels of endemic transmission as well as the potential for emerging and re-emerging arboviral diseases. Resource limitations constrain the use of expensive technologies for donor screening. Continued surveillance and research will be required to manage the arboviral threat to the blood supply.

Dengue myocarditis in Singapore: two case reports.

The authors report two cases of complicated dengue viral infection with acute myocarditis involving young male adults, of which one was fatal. The first case presented with typical signs of myocardial disease: chest pain and diaphoresis with myocardial depression in the electrocardiograph. The second case deteriorated rapidly and demised within the first day of admission. Histology of the heart muscles showed multiple small foci of myocyte necrosis surrounded by lymphocytes, in keeping with viral myocarditis. Both cases fulfilled the World Health Organization (WHO) diagnosis of probable dengue: the first case had positive dengue serology, both IgM and IgG at day six of illness, and the second case was polymerase chain reaction (PCR) positive for dengue and identified as serotype 2. Despite the severe outcome, both cases did not completely fulfil the criteria for dengue haemorrhagic fever (DHF). Although severe cardiac impairment is not commonly reported in dengue infection, it can be life threatening.

An unexpected cause for aplastic anaemia in an elderly woman.

Aplastic anaemia is a rare clinical syndrome associated with diminished or absent precursors in the bone marrow. Acquired aplastic anaemia secondary to human immunodeficiency virus (HIV) is very rare. We present a 71-year-old woman with severe aplastic anaemia secondary to HIV infection, which was after extensive exclusion of other causes. She achieved undetectable viral load after 5 months of combination antiretroviral therapy but remains profoundly pancytopenic, complicated by recurrent infectious and bleeding complications. HIV infection should be considered in patients with pancytopenia.

Comparison of neutralizing antibody and cell-mediated immune responses to pandemic H1N1 2009 influenza virus before and after H1N1 2009 influenza vaccination of elderly subjects and healthcare workers.

BACKGROUND: The recent H1N1 pandemic virus that emerged in 2009 resulted in high morbidity rates mainly in younger individuals, albeit with relatively low mortality. We investigated both humoral and cellular immune responses against the pandemic H1N1 2009 virus before and after immunization with inactivated H1N1 2009 vaccine. METHODS: We obtained paired blood specimens from a cohort of participants from nursing homes (n=108) and a public hospital (n=60) in Singapore. Serum samples were tested for neutralizing antibodies against H1N1 2009 using microneutralization assays, while peripheral blood mononuclear cells were subjected to interferon-γ enzyme-linked immunosorbent spot (ELISPOT) assays for whole virus-specific T-cell responses. RESULTS: We observed significant increases in geometric mean titers of neutralizing antibodies after H1N1 2009 vaccination (from 23.6 pre-vaccination to 94.7 post-vaccination). Approximately 77% and 54% of the cohort exhibited ≥2-fold and ≥4-fold increases in neutralizing antibody titers following vaccination; 89.9% of the cohort had a post-vaccination antibody titer of ≥32. Adjusted for gender, participants aged ≥60 years were less likely to have a ≥4-fold increase in antibody titers after vaccination than those aged <60 years (0.48; 95% confidence interval (95% CI) 0.32-0.71, p=0.007). There was a 1.4-fold elevation in H1N1 2009-specific T-cell responses after vaccination (p<0.05). Adjusted for gender, age ≥60 years was positively associated with a greater increase in T-cell response (ß=4.9, 95% CI 1.58-8.29, p=0.018). No significant correlation was observed between humoral and cellular immune responses. CONCLUSIONS: Influenza vaccination elicits significant neutralizing antibody and T-cell responses to pandemic H1N1 2009 influenza virus. However, in response to vaccination, increases in neutralizing antibody titers were comparatively lower but T-cell responses were higher in older participants. Therefore, our study suggests that memory T-cells may play a crucial role in protecting older individuals against pandemic H1N1 2009 infection.

Acute HIV infection in Singapore: predominance of men who have sex with men.

INTRODUCTION: The incidence of human immunodeficiency virus (HIV) infection in Singapore is on the rise. We aimed to study the clinical epidemiology of acute HIV infection in Singapore. METHODS: All patients that fulfilled the criteria for definite and probable acute HIV infection were prospectively identified from January 1, 2003 to June 30, 2006. Demographic, clinical and laboratory data were recorded. RESULTS: A total of 16 out of 34 patients had definite acute HIV infection, and 68 percent of the entire cohort comprised men who have sex with men (MSM). Ten percent of the patients were co-infected with hepatitis B and C viruses, while 27 percent were infected with syphilis. Signs and symptoms were nonspecific, with fever, rash and diarrhoea being the three most common symptoms. Only 35 percent of the patients required hospitalisation. CONCLUSION: Men who have sex with men account for the majority of patients with acute HIV infections in Singapore, many of them also being co-infected with syphilis. Safer sex campaign among MSM should be implemented or intensified.

Ministry of Health clinical practice guidelines: Chronic Hepatitis B Infection.

The Ministry of Health (MOH) publishes clinical practice guidelines on Chronic Hepatitis B Infection to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Chronic Hepatitis B Infection, for the information of readers of the Singapore Medical Journal. 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/mohcorp/publications.aspx?id=26108). 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.

Chikungunya fever in Singapore: acute clinical and laboratory features, and factors associated with persistent arthralgia.

BACKGROUND: In Singapore, the first local outbreak of chikungunya was reported in January 2008, followed by a larger outbreak occurred in August 2008. During the initial outbreak period, a strict containment strategy was adopted and all chikungunya PCR-confirmed cases were isolated and hospitalised at the designated national outbreak management centre. OBJECTIVES: To detail daily clinical and laboratory features of chikungunya cases during acute illness, and determine factors associated with persistent arthralgia at week 6. STUDY DESIGN: Prospective cohort study of patients with PCR-confirmed chikungunya infection and hospitalised within 5 days of illness onset, from 1st August to 10th November 2008. Post-hospital discharge, patients were followed up at the specialist outpatient clinic, and assessed for arthralgia at week 6 of illness. RESULTS: Of the 97 patients in the study, the most common presenting symptoms were fever (89.7%) and arthralgia (87.6%). Mean nadir leukocyte and platelet counts were 3.5(SD 1.9) × 10(9)/L and 165(SD 42) × 10(9)/L respectively. Of the 39 patients who were evaluated at week 6, 14 (35.9%) had persistent arthralgia. Those with persistent arthralgia tended to be females (p = 0.003), and had a lower peak creatinine level (p = 0.036) than those without. Peak viral load (p = 0.664), and duration of fever (p = 0.056) and viremia (p = 0.55) respectively, were not significantly different between those with persistent arthralgia and those without. CONCLUSIONS: This study details the daily clinical and laboratory features of chikungunya patients during acute illness. Those with persistent arthralgia tended to be females, who had significantly lower peak creatinine level.

The benign nature of acute dengue infection in hospitalized older adults in Singapore.

OBJECTIVES: In Singapore, dengue primarily affects adults. This study aimed to determine if older dengue patients in Singapore have greater morbidity and mortality. METHODS: All laboratory diagnosed dengue patients admitted to Tan Tock Seng Hospital in 2004 were retrospectively reviewed. Cases were re-classified into dengue fever and dengue hemorrhagic fever based on World Health Organization criteria. Demographic, clinical, laboratory, and outcome data of patients aged > or = 60 years and <60 years were collected. RESULTS: Of 1971 laboratory confirmed dengue cases, 66 were aged > or = 60 years. Older patients were significantly less likely to be male (44% vs. 64%), and more likely to have diabetes (17% vs. 2%), hypertension (48% vs. 4%), ischemic heart disease (6% vs. 0.1%), hyperlipidemia (18% vs. 1%), and secondary dengue infections (64% vs. 34%). Clinical features were similar except older patients were significantly less likely to report fever (92% vs. 99%), or have leukopenia (32% vs. 51%) or hemoconcentration (0 vs. 5%) on admission. Older patients had similar dengue hemorrhagic fever, bleeding, hypotension, severe thrombocytopenia, and elevated transaminase rates. Length of hospital stay, risk of intensive care unit admission, and outcome of death were not statistically different. CONCLUSIONS: Despite greater co-morbidity and secondary dengue infection, older dengue patients in Singapore did not have greater morbidity or mortality.

Clinical features and epidemiology of chikungunya infection in Singapore.

Chikungunya is a re-emerging mosquito-borne viral infection that has spread from East Africa to Indian Ocean islands and re-emerged in India since 2004. In Malaysia, chikungunya re-emerged after a hiatus of seven years, causing a localised outbreak in a north-western coastal town in 2006 and subsequently widespread outbreaks in 2008. Since the first local outbreak of chikungunya in Singapore in January 2008, chikungunya infections have been increasingly reported in Singapore. In this case series, five patients aged 37-62 years, with chikungunya infection confirmed in August 2008, were reported. Three of the five were male, and only one had medical comorbidities. Two had a travel history to Johor, Malaysia, where local outbreaks of chikungunya had been reported. Fever, arthralgia and rash were the most common symptoms. Fever lasted four to five days while viraemia lasted four to 11 days, persisting two to three days after defervescence in three patients. A biphasic pattern of fever was observed in two patients. Leucopenia was noted in all patients, while mild thrombocytopenia and transaminitis occurred in three of five patients. Two patients had persistent polyarthralgia at two to three weeks after the onset of symptoms. Fever, arthralgia and rash should prompt consideration of acute chikungunya in Singapore. While taking the travel history, doctors should be mindful that indigenous chikungunya cases can occur.