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Between 1 and 22 March 2003, a nosocomial outbreak of Severe Acute Respiratory Syndrome (SARS) occurred at the Communicable Disease Centre in Tan Tock Seng Hospital, Singapore, the national treatment and isolation facility for patients with SARS. A case-control study with 36 cases and 50 controls was conducted of factors associated with the transmission of SARS within the hospital. In univariate analysis, contact with respiratory secretions elevated the odds ratio to 6.9 (95 % CI 1.4-34.6, P= 0.02). Protection was conferred by hand washing (OR 0.06, 95% CI 0.007-0.5, P=0.03) and wearing of N95 masks (OR 0.1, 95% CI 0.03-0.4, P=0.001). Use of gloves and gowns had no effect. Multivariate analysis confirmed the strong role of contact with respiratory secretions (adjusted OR 21.8, 95 % CI 1.7 274.8, P=0.017). Both hand washing (adjusted OR 0.07, 95 % CI 0.008-0.66, P=0.02) and wearing of N95 masks (adjusted OR 0.1, 95% CI 0.02-0.86, P=0.04) remained strongly protective but gowns and gloves had no effect.

Background: Severe acute respiratory syndrome (SARS) is a new infectious disease that caused a global outbreak in 2003. Research has shown that it is caused by a novel coronavirus. A series of cases is reported where polymerase chain reaction (PCR) testing on tears had demonstrated the presence of the virus. Detection of ocular infection from tears using the PCR technique has been widely used by ophthalmologists to diagnose infections for other viruses., Methods: This is a case series report from cases classified as probable or suspect SARS cases. Tear samples were collected from 36 consecutive patients who were suspected of having SARS in Singapore over a period of 12 days (7-18 April 2003), and analysed by PCR using protocols developed by the WHO network of laboratories., Results: Three patients with probable SARS (one female and two male patients) had positive results from their tear samples. Tear samples were used to confirm SARS in the female patient, who was positive only from her tears. The positive specimens were found in cases sampled early in their course of infection., Conclusions: This is the first case series reported with the detection of the SARS coronavirus from tears, and has important implications for the practice of ophthalmology and medicine. The ability to detect and isolate the virus in the early phase of the disease may be an important diagnostic tool for future patients and tear sampling is both simple and easily repeatable. Many healthcare workers are in close proximity to the eyes of patients and this may be a source of spread among healthcare workers and inoculating patients. Ophthalmic practices may need to change as more stringent barrier methods, appropriate quarantine, and isolation measures are vital when managing patients with SARS.

In Singapore, of 236 patients with probable severe acute respiratory syndrome (SARS), 2 were coinfected with tuberculosis, a phenomenon not previously reported. The patients' tuberculosis episodes only came to light after full recovery from SARS, when they presented with persistent respiratory symptoms and/or worsening chest radiography findings.

Aim: The study analyzes the extension of anesthesia induced by Alemanno's brachial plexus block technique on the various areas of competence of the different nerves., Methods: The study was conducted on 58 patients in ASA classes 1 and 2 scheduled to receive shoulder arthroscopy. At the end of the operation, about 2 hours after induction of anesthesia, extension of anesthesia was evaluated by the pin-prick test., Results: Anesthesia was achieved in 100% of cases for the circumflexus, musculocutaneous and radial nerves; the median nerve escaped in 7% of cases, the medial cutaneous nerve of forearm in 20%, the ulnar nerve in 27.5%, the medial cutaneous nerve of arm and intercostobrachial nerves in 46%; no major complications were associated with the technique., Conclusion: Alemanno's technique is recommended for operations on the shoulder and humerus, whereas more peripheral techniques may be preferable for interventions on the forearm and hand.

A new form of atypical pneumonia was reported in the East Asian region beginning from early 2003. This was later termed by the World Health Organisation as Severe Acute Respiratory Syndrome (SARS). The diagnosis of SARS relies on a combination of clinical features and chest radiographic findings. A preliminary review of SARS in Singapore shows chest radiographic findings of patchy airspace shadowing with severe cases progressing to diffuse air-space shadowing. We illustrate these findings with temporal correlation in our case report. As SARS is a contagious, rapidly progressive and potentially fatal condition, early diagnosis is crucial for prompt management and isolation of patients. Recognition of chest radiographic findings aids in the early diagnosis and containment of SARS.

The Nipah virus is a newly identified paramyxovirus responsible for an outbreak of fatal encephalitis in Malaysia and Singapore. This paper reports the follow up clinical and magnetic resonance imaging findings in 22 affected subjects. Of 13 patients with encephalitis, one died, one was lost to follow up, and seven recovered. Among the four remaining patients, one had residual sixth nerve palsy, another suffered from severe clinical depression, and a third patient had evidence of retinal artery occlusion. One patient with delayed onset Horner syndrome had a single lesion in the cervical spinal cord. The brain magnetic resonance findings were stable or improved in nine patients over 18 months of follow up. Among a second group of nine asymptomatic seropositive abattoir workers, magnetic resonance examination in seven subjects revealed discrete small lesions in the brain; similar to those detected in encephalitis patients. These findings suggest that in addition to encephalitis, the newly discovered Nipah virus affects the spinal cord and the retina. Late clinical and radiological findings can occur in Nipah virus infections as with other paramyxoviruses.

Designed in 1974 to study the phenomenology and consequences of a critical accident, the SILENE experimental reactor, an intense source of mixed neutron and gamma radiation, is also suited to radiobiological studies.

Following the Nipah virus (NV) outbreak in March 1999 in Singapore, a serological survey was undertaken to screen individuals potentially exposed to NV. Blood samples were tested for NV IgM, IgG and neutralizing antibodies. Twenty-two (1.5%) of 1469 people tested had antibodies suggesting NV infection. Although 12 of the 22 infected people (54.6%) were symptomatic, the remaining 10 (45.4%) were clinically well and had no past history of compatible pulmonary or neurological disease. Clinical and serological findings suggested three people had been infected with NV before the outbreak was recognized. All those who were infected were male abattoir workers. None of the people who had contact with horses, and no healthcare workers exposed to infected patients and their specimens had detectable antibodies. This study provides evidence that NV causes asymptomatic infection. All of the antibody positive individuals had direct contact with pigs and there was no evidence of human to human transmission.

Aim: To identify epidemiological, clinical and laboratory features of serologically-proven typhus in the local setting., Method & Results: Retrospective study looking at rickettsial serologies done over a six-month period and collection of the epidemological, clinical, laboratory and treatment response data from the case notes of the patients with an ordered rickettsial serology. Twenty of the 35 cases had a positive serology. Of these 20 patients, 18 were already clinically diagnosed as having murine typhus. All except one were males and all were migrant workers. Majority of the patients were construction workers staying in containers where rats abound. The most consistent clinical features were high fever (100%) for a median period of seven days, headache (94%) and cough (47%). The white cell count was usually normal (74%) but thrombocytopenia was common (68%). Transaminitis was also common (90%) with the AST component higher than the ALT in half of the cases. Response to doxycycline therapy was rapid and most (88%) were afebrile by 72 hours., Conclusion: Typhus (notably murine type) can be confidently diagnosed from consistent clinical features supported by epidemiological and laboratory clues. Early recognition with the prompt treatment response will result in shorter hospital stay with decreased cost. Serological testing may only prove useful in difficult situations when the clinical diagnosis is less clear.

Introduction: Oral lesions have been recognised as prominent features of acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection since the beginning of the epidemic., Objective: This descriptive study was conducted to study the types of oral lesions among HIV-infected patients in Singapore., Materials and Methods: Oral examination was done on 81 randomly selected HIV-infected patients attending the specialist outpatient clinic at the Communicable Disease Centre., Results: A total of 9 different lesions were observed in 45 (56%) patients. The lesions observed were oral candidosis (35%), periodontal disease (16%), aphthous-like ulcers (5%), oral hairy leukoplakia (5%) and lymphoma (1%)., Conclusion: The oral manifestations of HIV-infected patients in Singapore appear to be less frequent in comparison with those patients from Africa and Europe. Similarities in oral findings among the HIV-infected patients in Asia are evident with a notable lack of oral Kaposi's sarcoma (KS) and a low prevalence of non-Hodgkin's lymphoma and oral hairy leukoplakia.

Introduction: The landmark Paediatric AIDS Clinical Trials Group (PACTG) trial 076 showed in 1994 that antiretroviral therapy (ART) was effective in reducing maternal-child transmission of human immunodeficiency virus (HIV). This trial included antenatal oral zidovudine (ZDV), intrapartum intravenous ZDV, 6 weeks of oral ZDV to the babies and no breastfeeding., Materials and Methods: This study is an on-going, prospective, open-label trial conducted from 1995 in which we enrolled HIV-infected pregnant women using the above strategy. Since 1997, the antenatal component of the regimen was modified to include lamivudine with ZDV. All babies had serial HIV polymerase chain reaction (PCR) and antibody tests including enzyme-linked immunosorbent assay (EIA), particle agglutination (PA) and Western blot (WB) at day 1, 1 week, 1, 2, 3, 6, 12 and 18 months., Results: A total of 16 out of 19 eligible women were recruited from 1995 to 1999. The median age was 26 years (range 22 to 38 years), 38% were Singaporeans, median CD4 was 421 cells/mL (range 18 to 713 cells/mL) and median baseline gestational age was 23.5 weeks (range 8 to 32 weeks). None of the 16 children was infected as evidenced by 2 negative HIV PCRs including 1 done > 4 months old with a follow-up of 6 months to 2 years. There was a statistically significant difference between the 3 HIV antibody tests at 12 months of age (P = 0.003), there being more negative results with WB as compared to PA (P = 0.02). However, the difference between the 3 tests at 18 months was not statistically significant. No long-term side effects in these children were seen., Conclusion: Although the number of patients in this study is small, the absolute prevention of transmission (95% confidence intervals 0%-17%) in this cohort supports the recommendation of antenatal HIV screening and treatment of those infected.

The introduction of antiretroviral therapy has led to a significant decrease in the mortality and morbidity associated with human immunodeficiency virus (HIV) infection. Nucleoside reverse transcriptase inhibitors (NRTI) have been widely used as part of the antiretroviral therapy against HIV. However, one recently recognised serious complication of NRTI is the development of lactic acidosis. We report two cases of fatal NRTI-induced lactic acidosis, which occurred within five months of each other. Both were being treated with didanosine (ddI) and stavudine (d4T). Physicians involved in the care of HIV patients should recognise and be alert to the possibility of this highly fatal complication.

Introduction: Quantitative measurement of plasma HIV-1 RNA viral load has been available in Singapore since 30 November 1996. This study investigates the relationship, in antiretroviral-naïve, HIV-positive Singapore residents, between the baseline HIV-1 RNA viral load and clinical status at the time of quantification. The association of HIV-1 RNA viral load with CD4+ T-cell counts was also studied., Materials and Methods: HIV-1 RNA viral load was determined using Amplicor HIV-1 Monitor Test. One hundred and eighty subjects had baseline plasma HIV-1 RNA levels quantified during the period 30 November 1996 to 27 July 1998. They were classified into three clinical groups: A for asymptomatic infection (n = 110), B for symptomatic infection (n = 29) and C for AIDS (n = 41)., Results: The differences between mean HIV-1 RNA levels were statistically significant (P < 0.001) for groups A and B (mean difference = -0.61 log10), and for groups A and C (mean difference = -0.75 log10). However, there was no statistically significant difference (P = 0.68) between groups B and C (mean difference = -0.13 log10). Of those subjects with CD4+ T-cell counts measured within 30 days of viral load quantification, there were statistically significant negative correlations between HIV-1 viral load and CD4+ T-cell counts for groups A (n = 91, r = -0.536, P < 0.01) and C (n = 34, r = -0.446, P < 0.01) but not group B (n = 26, r = -0.297, P > 0.05)., Conclusion: This suggest that the more advanced the phase of HIV infection, the higher the baseline plasma viral load and the lower the CD4+ T-lymphocyte counts.

Introduction: Coagulase-negative staphylococci, commonly Staphylococcus epidermidis, cause 5% of native valve endocarditis. We describe a case due to Staphylococcus lugdunensis, a coagulase-negative staphylococcus identified in 1988, as a first report in Southeast Asia. It was previously misidentified as S. aureus because it is sometimes slide coagulase positive, but always tube coagulase negative, resulting in its delayed recognition as a pathogen. We also reviewed 36 other cases reported in the English literature from 1988 to 1999., Clinical Picture: Our patient was admitted 3 times over 4 months for unresolved weight loss and fever before the coagulase-negative staphylococcus bacteraemia was eventually considered significant., Treatment and Outcome: He was treated with 4 weeks of high-dose intravenous penicillin and 2 weeks of gentamicin and did not require urgent valve replacement., Conclusion: A positive blood culture of coagulase-negative staphylococcus is not always a contaminant. S. lugdunensis can cause aggressive native valve endocarditis resulting in high mortality, especially without surgical intervention.

Context: Current screening practices for blood donations have been successful in reducing human immunodeficiency virus (HIV) transmission through receipt of contaminated blood products. However, HIV-infected blood donations made prior to seroconversion and before high levels of viral replication occur could test negative using both serologic antigen and antibody tests. Testing based on nucleic acid amplification (NAT) is being implemented to screen for HIV-infected blood donated during this period, yet the issue of single vs minipool donation screening remains unresolved., Objectives: To determine HIV-1 genetic linkage between virus in 2 HIV-1-infected recipients of blood components and virus in the donor, who was HIV antigen and antibody negative at the time of donation; to screen the blood donor's plasma with HIV NAT assays, including those currently proposed for use in US blood donation screening., Design and Setting: Case study conducted in October 1997 involving the Communicable Disease Centre, Singapore General Hospital, and the Singapore Blood Transfusion Service, Singapore., Subjects: The blood donor and the 2 recipients of donor platelets and red blood cells., Main Outcome Measures: Genetic analysis of the HIV-1 p17 coding region of gag and the C2V5 region of env to determine the genetic relatedness of virus from the donor and recipients; reactivity in quantitative and qualitative assays, and reactivity in donor screening HIV NAT assays in single donation and minipool screening contexts., Results: Direct DNA sequencing demonstrated identical HIV-1 subtype E viral sequences in the donor and recipients. Based on comparisons of a qualitative and quantitative assay for HIV-1 RNA levels, a low level of viremia (range, 5-39 copies/mL in plasma) was estimated to be in the donor's undiluted blood at the time of donation. Additional testing using donor-screening NAT assays showed consistent detection of HIV RNA in the undiluted donor plasma whereas detection was inconsistent at the 1:16 and 1:24 dilution levels currently used in minipool screening of blood donations in the United States., Conclusions: Transmission of HIV from a blood donor to a platelet recipient and a red blood cell recipient occurred in the preseroconversion infectious window period. The viral load in the implicated donation was estimated to be less than 40 copies/mL of plasma. Current US minipool HIV NAT screening protocols may not be sufficiently sensitive to detect all infectious window-period donations. JAMA. 2000;284:210-214

Background: In March 1999, an outbreak of encephalitis and pneumonia occurred in workers at an abattoir in Singapore. We describe the clinical presentation and the results of investigations in these patients., Methods: Clinical and laboratory data were collected by systemic review of the case records. Serum and cerebrospinal fluid (CSF) samples were tested for IgM antibodies to Nipah virus with an IgM capture ELISA. Reverse-transcriptase PCR was done on the CSF and tissue samples from one patient who died., Findings: Eleven patients were confirmed to have acute Nipah-virus infection based on raised IgM in serum. Nipah virus was identified by reverse transcriptase PCR in the CSF and tissue of the patient who died. The patients were all men, with a median age of 44 years. The commonest presenting symptoms were fever, headache, and drowsiness. Eight patients presented with signs of encephalitis (decreased level of consciousness or focal neurological signs). Three patients presented with atypical pneumonia, but one later developed hallucinations and had evidence of encephalitis on CSF examination. Abnormal laboratory findings included a low lymphocyte count (nine patients), low platelet count, low serum sodium, and high aspartate aminostransferase concentration (each observed in five patients). The CSF protein was high in eight patients and white-blood-cell count was high in seven. Chest radiography showed mild interstitial shadowing in eight patients. Magnetic resonance imaging (MRI) showed focal areas of increased signal intensity in the cortical white marker in all eight patients who were scanned. The nine patients with encephalitis received empirical treatment with intravenous aciclovir and eight survived., Interpretation: Infection with Nipah virus caused an encephalitis illness with characteristic focal areas of increased intensity seen on MRI. Lung involvement was also common, and the disease may present as an atypical pneumonia.

Penicillium marneffei has emerged as an important opportunistic pathogen in HIV-infected patients in Southeast Asia. We report the first 5 cases of P. marneffei diagnosed in Singapore. All the patients were HIV-infected and were either Thai nationals or had frequently travelled to Thailand. Fever, weight loss, anaemia and papular skin lesions were common clinical manifestations in our patients, all of whom had the organism isolated from blood. Skin biopsy specimens showed histological evidence of P. marneffei in 2 patients. In 1 patient each, the organism grew in cultures of specimens from bone marrow and respiratory secretions. Amphotericin B therapy followed by itraconazole were used in 3 of our 5 patients and was associated with good clinical response and outcome.

The prevalence of human immunodeficiency virus (HIV) infection is increasing in Singapore. The surgical experience, however, remains limited. A retrospective review of 13 HIV-positive patients requiring abdominal surgery within Singapore was done. There were 4 females and 9 males with age ranging from 21 to 44 years. Operations included appendicectomy, colectomy, splenectomy, intestinal bypass, gastrostomy and exploratory laparotomy. Pathologic findings directly related to HIV infection were found in two-fifths (5 out of 13) of these patients. A low CD4+ count or signs of full-blown acquired immunodeficiency syndrome (AIDS) were not associated with a higher likelihood of HIV-related pathology; neither did it preclude a successful outcome. There were 2 early postoperative deaths, both with HIV-related pathology. Five of our patients who survived their abdominal surgery died on follow-up with a median survival of 17 months. In patients with typical surgical problems, e.g. appendicitis and torsion of the ovary, early surgery allows for rapid recovery similar to normal surgical patients. Care of these patients is best provided by surgeons with experience and interest in this condition together with infectious diseases physicians. Even palliative surgery offers a respite from acute and often severe problems and improves the quality of life significantly. Two patients with AIDS presented with sepsis and diffuse abdominal tenderness. Subsequent laparotomy revealed only primary bacterial peritonitis. For patients with AIDS and non-localizing abdominal signs, alternative non-invasive diagnostic modalities such as computed tomographic (CT) scan should be considered.

In this retrospective study, we report 43 cases (41 males and 2 females) of human immunodeficiency virus (HIV) infection in the Singapore population aged 50 years and above at first presentation. We found an increasing proportion of these older individuals among our HIV-seropositive patients; from 4.8% in 1991 to 16.7% by mid-1996. The mean age at presentation was 59.2 years (range 50 to 75 years). They were mainly heterosexuals (93%) and the majority (79.1%) were previously or currently married. Thirty-six (83.7%) patients had multiple sexual exposures to commercial sex workers. Nearly all had acquired the infection through the sexual route. The majority (76.7%) were symptomatic at presentation. Common clinical presentations were weight loss (72%), respiratory symptoms (60%) and oral candidiasis (56%). More than half (58.1%) of the patients had acquired immunodeficiency virus (AIDS) at the time of first presentation with a low median CD4 count of 17 cells/mm3. Pneumocystis carinii pneumonia and tuberculosis were the common AIDS-defining diseases. Survival in patients presenting with AIDS (median survival 3 months) is poorer compared to younger HIV-seropositive patients (< 50 years; median survival 1 year). No increase in age-related infection or malignancy was seen. Common causes of death were pneumonia and septicaemia. Physicians should consider HIV infection in older patients particularly when he/she presents with unexplained weight loss, respiratory symptoms and oral candidiasis. A history of high-risk sexual behaviour must be sought in all patients, including the elderly.

Visceral leishmaniasis (Indian kala-azar) caused by infection due to the protozoan Leishmania donovani is endemic in the Indian subcontinent and adjoining regions. Prolonged fever, hepatosplenomegaly, anaemia and pancytopenia, in the appropriate setting, are important clinical markers towards the diagnosis. Diagnosis is established by blood film or bone marrow examination for Leishman Donovan (LD) bodies and/or culture. Treatment with sodium stibogluconate, pentamidine isethionate or even amphotericin B is usually successful. We report the first case of culture-proven visceral leishmaniasis in Singapore, in a 30-year-old Bangladeshi worker who presented with pyrexia of unknown origin (PUO). He had the classical constellation of symptoms and signs as mentioned above. Diagnosis was confirmed by culture on the Novy, NcNeal and Nicolle (NNN) medium. He was successfully treated with 20 days of pentamidine isethionate daily infusions at a dose of 2 mg/kg/day.

The paper retrospectively reviews the spectrum of ophthalmic manifestations in human immunodeficiency virus (HIV) infection in Singapore between May 1995 and October 1996. One hundred and eighteen patients were examined for ocular abnormalities. Criteria for examination were 1) visual complaints, 2) absolute CD4 count of less than 50 cells/ul, 3) patients with acquired immunodeficiency syndrome-defining illness or 4) any relevant systemic illnesses which may have ocular involvement. Only 25 patients (21.2%) had visual symptoms. Eighteen patients (15.3%) had abnormalities associated with microvasculature. Forty-four patients (37.3%) had opportunistic infection involving the eye of which 37 were that of cytomegalovirus retinitis (CMVR). Seven patients (5.9%) had neuro-ophthalmic disorders. One patient presented with proptosis due to orbital lymphoma. Four patients (3.4%) had episcleritis and 3 patients (2.5%) had symptomatic dry eyes. It is still not known if episcleritis and dry eyes are associated with HIV infection or are coincidental. Fifty-one patients (43.2%) had no ocular pathology and remained so throughout the period of study. Nine patients (7.6%) had more than one pathology. The major cause of visual loss was due to ocular infections, with CMVR being most prevalent. Recognising the ophthalmic signs in HIV patients will facilitate early diagnosis. Prompt treatment of eye involvement can prevent or delay blindness, which is psychologically and functionally important to these patients.

We report 6 cases of marine typhus presented to us within a period of 3 months. The diagnoses were made based on the Weil-Felix reaction in the context of supportive clinical and epidemiological features, and response to appropriate antimicrobial therapy. This review serves to remind us that murine typhus is still an important cause of acute febrile illness in Singapore, especially among the migrant Indian workers.

The world is now facing the second decade of global epidemic of HIV infection. Most of the Asian countries including Singapore are seeing a trend of rapid increase of HIV infected cases each year. It is now known that the HIV disease has a prolonged asymptomatic period of several years before the onset of AIDS defining illness. A HIV-infected person may present to a physician at any point of the entire course of HIV infection. Hence, this article aims to give an overview of HIV disease and to provide information for doctors today to equip themselves with adequate knowledge to deal with this deadly infection.

Malaria remains a significant cause of morbidity and mortality in many regions of the world. In Singapore, an average of 200 cases of malaria have been reported annually, the majority of which are imported cases. Malaria eradication is a goal that may not be achieved. A more realistic aim is to educate and protect individual travellers. This paper attempts to summarise various therapeutic options including the use of monotherapy and combination therapy. The decision on therapy depends on several factors, such as the Plasmodium species, risk of transmission of the resistant parasite and the severity of infection. So far, none of the chemoprophylactic regimens available can provide an absolute protection from malaria transmission. Therefore, one needs to assess the risk of transmission against the potential risk of adverse drug reaction. Complications of anti-malaria drugs may range from minor cutaneous manifestations to death. General measures to prevent vector transmission of the disease should be emphasised while awaiting the development of an effective malaria vaccine.

A 35-year-old homosexual man who had a remote history of cocaine abuse presented to the hospital with fever, chills, drenching night sweats, and progressive dyspnea of 3 months' duration. His condition had been diagnosed as AIDS 1 1/2 years before presentation. Multiple blood cultures and serological tests failed to yield an infective etiology. Bronchoscopy with transbronchial biopsy, both performed twice, also failed to reveal an etiology. Empirical treatment for infection with the Mycobacterium avium complex yielded no response; empirical treatment, based on abnormalities revealed by gallium scanning, for Pneumocystis carinii pneumonia led to some clinical improvement. Because of rapid respiratory deterioration at the end of this treatment course, a thoracoscopic lung biopsy was performed; this procedure demonstrated classic bronchiolitis obliterans organizing pneumonia. Corticosteroid therapy resulted in a rapid salutary response. It is important to aggressively pursue a definitive diagnosis for selected patients with a nonidentifiable infectious cause so that patients receive the correct treatment.