The 2016 World Health Organization (WHO) World Malaria Report documents substantial progress towards control and elimination of malaria. However, major challenges remain. In some regions of Southeast Asia, the simian parasite Plasmodium knowlesi has emerged as an important cause of human malaria, and the authors believe this species warrants regular inclusion in the World Malaria Report. Plasmodium knowlesi is the most common cause of malaria in Malaysia, and cases have also been reported in nearly all countries of Southeast Asia. Outside of Malaysia, P. knowlesi is frequently misdiagnosed by microscopy as Plasmodium falciparum or Plasmodium vivax. Thus, P. knowlesi may be underdiagnosed in affected regions and its true incidence underestimated. Acknowledgement in the World Malaria Report of the regional importance of P. knowlesi will facilitate efforts to improve surveillance of this emerging parasite. Furthermore, increased recognition will likely lead to improved delivery of effective treatment for this potentially fatal infection, as has occurred in Malaysia where P. knowlesi case-fatality rates have fallen despite rising incidence. In a number of knowlesi-endemic countries, substantial progress has been made towards the elimination of P. vivax and P. falciparum. However, efforts to eliminate these human-only species should not preclude efforts to reduce human malaria from P. knowlesi. The regional importance of knowlesi malaria was recognized by the WHO with its recent Evidence Review Group meeting on knowlesi malaria to address strategies for prevention and mitigation. The WHO World Malaria Report has an appropriate focus on falciparum and vivax malaria, the major causes of global mortality and morbidity. However, the authors hope that in future years this important publication will also incorporate data on the progress and challenges in reducing knowlesi malaria in regions where transmission occurs.

Background: Despite significant prevention efforts, the incidence of central line-associated bloodstream infection (CLABSI) in intensive care units (ICUs) is rising at an alarming rate. CLABSI contributes to increased morbidity, mortality, prolonged hospital stays and elevated healthcare costs. This study aimed to determine the incidence rate of CLABSI, compliance with the central venous catheter (CVC) care bundle and risk factors associated with CLABSI among ICU patients. Method: This prospective observational study was conducted in one university hospital and two public hospitals in Malaysia between October 2022 to January 2023. Adult ICU patients (aged > 18 years) with CVC and admitted to the ICU for more than 48 h were included in this study. Data collected included patient demographics, clinical diagnosis, CVC details, compliance with CVC care bundle and microbiological results. All data analyses were performed using SPSS version 23. Results: A total of 862 patients with 997 CVCs met the inclusion criteria, contributing to 4330 central line (CL) days and 18 CLABSI cases. The overall incidence rate of CLABSI was 4.16 per 1000 CL days. The average of overall compliance with CVC care bundle components was 65%. The predominant causative microorganisms isolated from CLABSI episodes were Gram-negative bacteria (78.3%), followed by Gram-positive bacteria (17.4%) and Candida spp. (2.0%). Multivariate analysis identified prolonged ICU stay (adjusted odds ratio (AOR): 1.994; 95% confidence interval (CI): 1.092–3.009), undergoing surgery (AOR: 2.02, 95% CI: 1.468–5.830) and having had multiple catheters (AOR: 3.167, 95% CI: 1.519–9.313) as significant risk factors for CLABSI. Conclusions: The findings underscore the importance of robust surveillance, embedded infection-control and -prevention initiatives, and strict adherence to the CVC care bundle to prevent CLABSI in ICUs. Targeted interventions addressing identified risk factors are crucial to improve patient outcomes and reduce healthcare costs.

Streptococcus Suis (S.suis) is increasingly being recognised as a potentially preventable emerging zoonotic infection in humans with a global distribution. It is a major cause of meningitis especially among those in contact with pigs and has also been associated with a toxic shock syndrome. We report the first two human cases from Sabah, Borneo, Malaysia which expands the global reach of this important pathogen. Here, we illustrate their epidemiological risk factors, clinical presentation and resulting sequelae of both patients. The continued public health threat of zoonotic infections such as S.suis, highlights the need for accurate epidemiological surveillance, regulation of pig farming, slaughtering and continued advocacy of best practices for pork preparation and consumption.

Plasmodium knowlesi is the most common cause of human malaria in Malaysia. Acute kidney injury (AKI) is a frequent complication. AKI of any cause can have long-term consequences, including increased risk of chronic kidney disease, adverse cardiovascular events and increased mortality. Additional management strategies are therefore needed to reduce the frequency and severity of AKI in malaria. In falciparum malaria, cell-free haemoglobin (CFHb)-mediated oxidative damage contributes to AKI. The inexpensive and widely available drug paracetamol inhibits CFHb-induced lipid peroxidation via reduction of ferryl haem to the less toxic Fe3+ state, and has been shown to reduce oxidative damage and improve renal function in patients with sepsis complicated by haemolysis as well as in falciparum malaria. This study aims to assess the ability of regularly dosed paracetamol to reduce the incidence and severity of AKI in knowlesi malaria by attenuating haemolysis-induced oxidative damage. PACKNOW is a two-arm, open-label randomised controlled trial of adjunctive paracetamol versus no paracetamol in patients aged ≥ 5 years with knowlesi malaria, conducted over a 2-year period at four hospital sites in Sabah, Malaysia. The primary endpoint of change in creatinine from enrolment to 72 h will be evaluated by analysis of covariance (ANCOVA) using enrolment creatinine as a covariate. Secondary endpoints include longitudinal changes in markers of oxidative stress (plasma F2-isoprostanes and isofurans) and markers of endothelial activation/Weibel–Palade body release (angiopoietin-2, von Willebrand Factor, P-selectin, osteoprotegerin) over 72 h, as well as blood and urine biomarkers of AKI. This study will be powered to detect a difference between the two treatment arms in a clinically relevant population including adults and children with knowlesi malaria of any severity. Paracetamol is widely available and has an excellent safety profile; if a renoprotective effect is demonstrated, this trial will support the administration of regularly dosed paracetamol to all patients with knowlesi malaria. The secondary outcomes in this study will provide further insights into the pathophysiology of haemolysis-induced oxidative damage and acute kidney injury in knowlesi malaria and other haemolytic diseases. Clinicaltrials.gov, NCT03056391 . Registered on 12 October 2016.

The World Health Organization (WHO)’s list of neglected tropical diseases (NTDs) highlights conditions that are responsible for devastating health, social and economic consequences, and yet, they are overlooked and poorly resourced. The NTD list does not include conditions caused by Gram-negative bacilli (GNB). Infections due to GNB cause significant morbidity and mortality and are prevalent worldwide. Southeast Asia is a WHO region of low- and middle-income countries carrying the largest burden of NTDs. Two significant health threats in Southeast Asia are Burkholderia pseudomallei (causing melioidosis) and hypervirulent Klebsiella pneumoniae (HvKp). Both diseases have high mortality and increasing prevalence, yet both suffer from a lack of awareness, significant under-resourcing, incomplete epidemiological data, limited diagnostics, and a lack of evidence-based treatment. Emerging evidence shows that both melioidosis and HvKp are spreading globally, including in high-income countries, highlighting the potential future global threat they pose. In this article, we review both conditions, identifying current trends and challenges in Southeast Asia and areas for future research. We also argue that melioidosis and HvKp merit inclusion as NTDs, and that mandatory global surveillance and reporting systems should be established, and we make an urgent call for research to better understand, detect, and treat these neglected diseases.

Tuberculosis is a leading public health priority in eastern Malaysia. Knowledge of the genomic epidemiology of tuberculosis can help tailor public health interventions. Our aims were to determine tuberculosis genomic epidemiology and characterize resistance mutations in the ethnically diverse city of Kota Kinabalu, Sabah, located at the nexus of Malaysia, Indonesia, Philippines and Brunei. We used an archive of prospectively collected Mycobacterium tuberculosis samples paired with epidemiological data. We collected sputum and demographic data from consecutive consenting outpatients with pulmonary tuberculosis at the largest tuberculosis clinic from 2012 to 2014, and selected samples from tuberculosis inpatients from the tertiary referral centre during 2012–2014 and 2016–2017. Two hundred and eight M . tuberculosis sequences were available for analysis, representing 8 % of cases notified during the study periods. Whole-genome phylogenetic analysis demonstrated that most strains were lineage 1 (195/208, 93.8 %), with the remainder being lineages 2 (8/208, 3.8 %) or 4 (5/208, 2.4 %). Lineages or sub-lineages were not associated with patient ethnicity. The lineage 1 strains were diverse, with sub-lineage 1.2.1 being dominant (192, 98 %). Lineage 1.2.1.3 isolates were geographically most widely distributed. The greatest diversity occurred in a border town sub-district. The time to the most recent common ancestor for the three major lineage 1.2.1 clades was estimated to be the year 1966 (95 % HPD 1948–1976). An association was found between failure of culture conversion by week 8 of treatment and infection with lineage 2 (4/6, 67 %) compared with lineage 1 strains (4/83, 5 %) (P<0.001), supporting evidence of greater virulence of lineage 2 strains. Eleven potential transmission clusters (SNP difference ≤12) were identified; at least five included people living in different sub-districts. Some linked cases spanned the whole 4-year study period. One cluster involved a multidrug-resistant tuberculosis strain matching a drug-susceptible strain from 3 years earlier. Drug resistance mutations were uncommon, but revealed one phenotype–genotype mismatch in a genotypically multidrug-resistant isolate, and rare nonsense mutations within the katG gene in two isolates. Consistent with the regionally mobile population, M. tuberculosis strains in Kota Kinabalu were diverse, although several lineage 1 strains dominated and were locally well established. Transmission clusters – uncommonly identified, likely attributable to incomplete sampling – showed clustering occurring across the community, not confined to households or sub-districts. The findings indicate that public health priorities should include active case finding and early institution of tuberculosis management in mobile populations, while there is a need to upscale effective contact investigation beyond households to include other contacts within social networks.