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Fulltext Mortality in Malaysians with systemic lupus erythematosus

Paton NI, Cheong I, Kong NC, Segasothy M

Med J Malaysia, 1996 Dec;51(4):437-41.
PMID: 10968030

One hundred and two patients attending the systemic lupus erythematosus (SLE) clinic of the Department of Medicine, Universiti Kebangsaan Malaysia, were studied retrospectively to determine their survival rates and causes of death. There were 21 deaths. The 1, 5, and 10 year survival rates were 93%, 86% and 70% respectively. There was a bimodal pattern of mortality with more patients dying in the first 2 years or after 5 years of disease. Infection was the direct cause of death in 52% and contributed to a further 19% of deaths. Patients with lupus nephritis had a higher relative risk (RR) of death (RR = 4.34, p < 0.02) although there was no significant increase in risk with any particular histological type on biopsy. Cerebral lupus (RR = 3.08, p < 0.001) and methylprednisolone treatment (RR = 6.24, p < 0.001) were also associated with increased risk of death. Increased awareness of infection and earlier use of antibiotic therapy may improve survival of patients suffering from SLE.
Study site: SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Risk factors for infection in Malaysian patients with systemic lupus erythematosus

Paton NI, Cheong IK, Kong NC, Segasothy M

QJM, 1996 Jul;89(7):531-8.
PMID: 8759494 DOI: 10.1093/qjmed/89.7.531

To determine the incidence, types and risk factors for infection in systemic lupus erythematosus (SLE) patients in Kuala Lumpur, Malaysia, we retrospectively reviewed the medical records of 102 patients with definite SLE attending a specialist clinic. Details of major infections (pneumonia or severe infection requiring intravenous therapy) and minor infections, and their time of onset in relation to immunosuppressive therapy and disease flares were recorded. There were 77 major and 163 minor infections during 564 patient-years of follow-up. In the month following a course of pulse methylprednisolone, the incidence of major infection was 20 times higher and the incidence of minor infection was 10 times higher than at other periods (p < 0.0001). In the month after disease flare, the incidence of major infection was 10 times higher and the incidence of minor infection six times higher than at other times (p < 0.0001). After allowing for methylprednisolone therapy and disease flares, there was no increase in the rate of infections during treatment with azathioprine, oral or intravenous cyclophosphamide. There was no effect of renal involvement on infection rate.
Late clinical and magnetic resonance imaging follow up of Nipah virus infection

Lim CC, Lee WL, Leo YS, Lee KE, Chan KP, Ling AE, et al.

J Neurol Neurosurg Psychiatry, 2003 Jan;74(1):131-3.
PMID: 12486285

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.
Fulltext Diagnosis and management of latent tuberculosis infection in Asia: Review of current status and challenges

Paton NI, Borand L, Benedicto J, Kyi MM, Mahmud AM, Norazmi MN, et al.

Int J Infect Dis, 2019 Oct;87:21-29.
PMID: 31301458 DOI: 10.1016/j.ijid.2019.07.004

Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO 'End TB' targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI.
Adjunctive pascolizumab in rifampicin-susceptible pulmonary tuberculosis: proof-of-concept, partially-randomised, double-blind, placebo-controlled, dose-escalation trial

Paton NI, Gurumurthy M, Lu Q, Leek F, Kwan P, Koh HWL, et al.

J Infect Dis, 2024 Mar 25.
PMID: 38527849 DOI: 10.1093/infdis/jiae104

BACKGROUND: Interleukin-4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit in animal models. We evaluated safety and efficacy of pascolizumab (humanised anti-IL-4 monoclonal antibody) as adjunctive tuberculosis treatment.
METHODS: Participants with rifampicin-susceptible pulmonary tuberculosis received a single intravenous infusion of pascolizumab or placebo; and standard 6-month tuberculosis treatment. Pascolizumab dose increased in successive cohorts: [1] non-randomised 0.05 mg/kg (n = 4); [2] non-randomised 0.5 mg/kg (n = 4); [3] randomised 2.5 mg/kg (n = 9) or placebo (n = 3); [4] randomised 10 mg/kg (n = 9) or placebo (n = 3). Co-primary safety outcome was study-drug-related grade 4 or serious adverse event (G4/SAE); in all cohorts (1-4). Co-primary efficacy outcome was week-8 sputum culture time-to-positivity (TTP); in randomised cohorts (3-4) combined.
RESULTS: Pascolizumab levels exceeded IL-4 50% neutralising dose for 8 weeks in 78-100% of participants in cohorts 3-4. There were no study-drug-related G4/SAEs. Median week-8 TTP was 42 days in pascolizumab and placebo groups (p = 0.185). Rate of TTP increase was greater with pascolizumab (difference from placebo 0.011 [95% Bayesian credible interval 0.006 to 0.015] log10TTP/day.
CONCLUSIONS: There was no evidence to suggest blocking IL-4 was unsafe. Preliminary efficacy findings are consistent with animal models. This supports further investigation of adjunctive anti-IL-4 interventions for tuberculosis in larger phase 2 trials.