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Introduction: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity., Method: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases., Results: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P <0.05) and chemotherapy (92.8%±18.1, P <0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection., Conclusion: This study demonstrates the benefit of early administration of the third dose among cancer patients.

It has been about 100 years since the Spanish influenza pandemic of 1918-19 that killed an estimated 50 million individuals globally. While we have made remarkable progress in reducing infection-related mortality, infections still account for 13 to 15 million deaths annually. This estimate is projected to remain unchanged until 2050. We have identified 4 megatrends in infectious diseases and these are "emerging and re-emerging infections", "antimicrobial resistance", "demographic changes" and "technological advances". Understanding these trends and challenges should lead to opportunites for the medical community to reshape the future. Further inroads will also require broad approaches involving surveillance, public health and translating scientific discoveries into disease control efforts.

Introduction: Cone beam computed tomography (CBCT) is a relatively new technological innovation that utilises fl at-panel detector technology to obtain CT-like images. The key strength of a CBCT system is that cross-sectional imaging can be obtained using the angiographic fl at panel unit without having to move the patient, allowing the radiologist to obtain soft tissue imaging during the procedure. This allows treatment planning, guidance, and assessment of outcome to be performed in one interventional suite., Materials and Methods: From December 2008 to June 2009, 24 CBCT scans were performed during vascular interventional procedures on our department's newly installed multi-axis fl at panel angiographic unit., Results: Ten cases were performed for hepatic trans-arterial chemoembolisation, 9 cases for hepatic arterial Yttrium-90 infusion, while 5 cases were for other indications. CBCT was found to be useful in 20 of the 24 cases., Conclusion: Our early experience showed that CBCT was useful in impacting decisions during selected vascular interventional procedures. As CBCT technology improves, we can foresee wider applications of this technology.

Introduction: Living donor liver transplantation (LDLT) has progressed dramatically in Asia due to the scarcity of cadaver donors and is increasingly performed in Singapore. The authors present their experience with adult LDLT., Materials and Methods: Adult LDLTs performed at the Asian Centre for Liver Diseases and Transplantation, Singapore from 20 April 2002 until 20 March 2006 were reviewed. All patients received right lobe grafts and were managed by the same team throughout this period. Data were obtained by chart review. This study presents both recipient and donor outcomes in a single centre., Results: A total of 65 patients underwent LDLT. Forty-three were genetically related while 22 were from emotionally-related donors. The majority were chronic liver failure while 14% were acute. The most common indication for LDLT was end-stage liver disease due to hepatitis B virus. A total of 22 patients with hepatoma were transplanted and overall 1-year disease specific survival was 94.4%. The mean model for end-stage liver disease (MELD) score was 17.4 +/- 9.4 (range, 6 to 40). Six patients had preoperative molecular adsorbent recycling system (MARS) dialysis with 83% transplant success rate. The mean follow-up was 479.2 days with a median of 356 days. One-year overall survival was 80.5%. There was 1 donor mortality and morbidity rate was 17%. Our series is in its early stage with good perioperative survival outcome with 1-month and 3-month actuarial survival rates of 95.4% and 87.3% respectively., Conclusion: The study demonstrates that LDLT can be done safely with good results for a variety of liver diseases. However, with dynamically evolving criteria and management strategies, further studies are needed to maximise treatment outcome.

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.

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.

In areas where tuberculosis is endemic, a positive sputum acid-fast bacilli (AFB) smear is frequently regarded as almost diagnostic of pulmonary tuberculosis (PTB). The main problem arises when the AFB smear is negative. The main aim of this study was to determine the clinical utility of rapid mycobacterial tuberculosis (MTB) detection in bronchoalveolar lavage (BAL) samples by polymerase chain reaction (PCR) in 52 patients who underwent diagnostic bronchoscopy for suspected PTB. These patients had either upper lobe infiltrates (n = 31) or bronchiectasis (n = 21). Mycobacterial culture is usually used as the gold standard of diagnosis. We chose to define active PTB based on positive mycobacterial cultures and/or histological evidence of caseous necrosis and AFB, and/or when there was clinical plus radiological improvement following therapy. We compared AFB smear, respiratory mycobacterial culture, BAL PCR for MTB and clinical active PTB. Four patients who were smear and culture negative had clinical and radiological clearance following anti-tuberculous therapy showing that using mycobacterial culture as a gold standard may have its limitations. When Kappa (a chance-corrected measure of agreement) was calculated for acid-fast bacilli smear and BAL PCR against our definition of active PTB, it was 0.28 (fair agreement) and 0.73 (substantial agreement), respectively. BAL PCR gave a sensitivity, specificity, positive and negative predictive values of 66.7%, 100%, 100% and 88%, respectively, for the group with upper lobe infiltrates. We also demonstrated that BAL for PCR has a good concordance with the final diagnosis of active tuberculosis.

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.

Travel Medicine has come a long way since it was started in the 1980s. Today, with the advances in electronic communications and efficient international travel, the demand for up-to-date information on international health situation is more urgent than before. Disease outbreaks can be updated and be available immediately across to the whole world in a matter of hours via the Internet. Travel medicine specialists no longer can give the excuse that they are unaware of such a situation because it is posted all over the net. Advances in vaccine development and the work of international agencies like the World Health Organization and the Centres for Disease Control have helped further the strategies and the knowledge we have in travel health risks. For the traveller, this means that they should no longer be travelling to a destination without knowing the health hazards and without taking the appropriate prophylaxis and precautions.

Singapore's tuberculosis incidence of 49 to 57 per 100,000 population for 1987 to 1996 presents a picture that is intermediate between developed and developing countries. The proportion of drug-resistant isolates has remained stable at 4.3% to 5.5% from 1992 to 1996 despite rising HIV rates. From 1995 to 1996, of the 199 consecutive drug-resistant isolates at the Central Tuberculosis Laboratory, 66% were mono-resistant, 22% dual-resistant and 12% resistant to more than two drugs. Isoniazid resistance was most prevalent, being found in 72% of isolates, followed by streptomycin resistance in 45%. Resistance to isoniazid and streptomycin (21%) was more common than to isoniazid and rifampicin, i.e. multidrug resistance (MDR) (14%). The small numbers indicated by the low overall prevalence of resistance and the predominance of single-drug resistance support the current initial choice of the standard short course with its three-drug initial phase. Of the 170 cases with matching National Tuberculosis Registry data, 72% of drug-resistant cases represented initial and 28% acquired resistance; testifying to the effectiveness of present day treatment regimens in suppressing resistance when compliance is assured. Case-control analysis using 244 drug-sensitive controls randomly selected from notifications in 1995 to 1996 showed an odds ratio for drug-resistance between subjects with a previous history and no previous history of tuberculosis of 2.47 (95% CI 1.40 to 4.37; P = 0.0007). With each increment in the number of episodes of tuberculosis experienced, there was a trend of resistance to progressively more drugs (P = 0.000004). This association remained even when a logistic regression model including all predictor variables was fitted. No associations were found with age, history of contact with tuberculosis, cavitary disease and, most notably, with human immunodeficiency virus infection. This study reaffirms that a history of previous tuberculosis should increase clinicians' index of suspicion for drug resistance, the urgency with which culture and sensitivity results are sought and the vigour with which patients are followed-up and compliance monitored.

Although visceral and cutaneous leishmaniasis are important clinical and public health problems worldwide, these diseases are not endemic in Singapore and the medical profession here has little opportunity to diagnose and manage these conditions. We report our experience with two patients with culture-proven visceral leishmaniasis and one with histologically-proven cutaneous leishmaniasis. The patients with kala-azar were migrant workers from countries in which the disease is endemic. The patient with proven cutaneous leishmaniasis (and another who was diagnosed to have the condition clinically) had entered the jungles of an endemic area. With increasing travel on the part of Singaporeans along less well-trodden paths to exotic destinations as well as the burgeoning traffic of migrant workers from less developed countries, doctors in Singapore will continue to see diseases such as leishmaniasis.

The number of patients with human immunodeficiency virus (HIV) infection in Singapore has risen over the years. A considerable proportion of them present with acquired immunodeficiency syndrome (AIDS). In this study, we document the clinical characteristics and natural history of a consecutive series of 50 patients who were found to have HIV infection when they were seen at a tertiary care hospital. The majority were in the 30 to 49 age group and the most common mode of acquisition was heterosexual contact. The patients presented with a variety of symptoms to 11 different clinical departments. Fifty-eight per cent of the patients had AIDS-defining illnesses at presentation, with Pneumocystis carinii pneumonia being the most common. On follow-up, the most frequently occurring opportunistic infection that developed was Cytomegalovirus retinitis. Most patients had multiple subsequent admissions--for both AIDS-defining and non AIDS-defining conditions. The median CD4 count of the cohort at presentation was 72/mm3. The median survival was 399 and 822 days in those who had and those who did not have an AIDS-defining illness at presentation, respectively. Mortality was most commonly attributed to pneumonia. HIV infection has protean manifestations and patients may present to various specialty departments; hence, doctors need to be aware of the spectrum of disease in order to make a diagnosis.

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.

The objectives of this study were: (a) to assess the predictive performance of a 2-compartment Bayesian vancomycin forecasting programme in critically ill patients in the surgical intensive care unit, and (b) to show the applicability of the programme, which is based on parameters derived from Western population, in our local Asian population. Twenty critically ill patients were enrolled into the study programme. All patients received multiple-dose vancomycin for infections due to methicillin-resistant staphylococcus aureus (MRSA). The patients dosage regimen were optimised by entering a set of peak and trough vancomycin serum levels into a clinical computer program (MB; USC*PACK PC collection; University of Southern California, USA) by utilising a 2-compartment Bayesian population model. The correlation between observed and predicted serum peak and trough concentrations were evaluated for both the non-fitted and fitted models by linear regression analysis. There was a significant correlation between observed and predicted concentrations using the fitted model (r = 0.97, P < 0.05). There was no significant correlation of these concentrations in the non-fitted model (r = 0.8). This study shows that the Bayesian programme is able to accurately predict future vancomycin concentrations in our local Asian population. It is possible to optimise patients dosage regimens with the knowledge of two concentrations of vancomycin in order to achieve targeted therapeutic goals.

Chlamydia pneumoniae, previously known as Chlamydia psittaci strain TWAR, causes both upper and lower respiratory tract infection. We report the first two cases of culture-positive Chlamydia pneumoniae lower respiratory infection in Singapore. Both patients had underlying fibrosing alveolitis and presented with a history of prolonged productive cough and fever. Chlamydia pneumoniae was isolated from the bronchoalveolar lavage fluid in the absence of other pathogens. The patients responded clinically to three weeks of oral doxycycline therapy. Infection due to Chlamydia pneumoniae should be considered when a patient with community-acquired pneumonia fails to respond to the usual standard antimicrobial therapy.

Three cases of tetanus in Singapore are presented. One local resident had cephalic tetanus most likely secondary to otitis media and the other two, residents from surrounding Asean countries, had generalised tetanus. The portal of entry was a puncture wound on the foot in one patient and the ear in another. No portal of entry was identified in one patient. All three patients required tracheostomy, ventilatory support and intensive care management for periods ranging from 11 to 22 days. One patient died from complications of nosocomial septicaemia and one patient required prolonged rehabilitation. There was a questionable history of tetanus immunization in the Singapore resident whereas the other two patients who were foreigners had never received any immunization. Tetanus is an uncommon but important disease in Singapore. In spite of the availability of intensive care management, it continues to be a disease with significant morbidity and mortality. Early recognition and treatment of the disease are critical factors in determining the prognosis. This is a disease that may be largely prevented by adequate immunization.

The use of monoclonal antibody especially in immunophenotyping of lymphomas is firmly established in clinical practice. This has helped in refining the classification of non-Hodgkin's lymphomas and the updated Kiel Classification is now much favoured by the Europeans. Nonetheless, clinicians by and large preferred the National Cancer Institute Working Formulation Classification. This article explores the potential usage of monoclonal antibodies reactive to the so-called Clusters of Differentiation antigens on lymphoid cells and the role of a clinical pathologist in achieving an accurate clinical diagnosis. Such immunophenotyping is only complementary to the morphological diagnosis of lymphomas.