Cytokine profile of patients with leptospirosis in Sabah, Malaysia

Background: Leptospirosis is a zoonotic disease withsymptoms ranging from a mild, febrile illness to a severeform with multiorgan failure. Severe leptospirosis mayrequire medical interventions in the form of dialysis and/ormechanical ventilation and often leads to mortality. Anexaggerated host immune response—in particular, a“cytokine storm”—that causes endothelial and organdamage is associated with the disease severity andmortality.Methods: Microscopic agglutination test (MAT)-positive andMAT-negative human serum samples (n=30) from patientswith leptospirosis were obtained from the Public HealthLaboratory, Kota Kinabalu, Sabah, Malaysia and controlserum samples (n=10) were obtained from healthy studentvolunteers. We estimated the levels of IL-1β, IL-6, IL-8, IL-10,and TNF-α in serum samples by a Luminex assay.Results: The levels of IL-6, IL-8, and IL1-β were significantlyhigher in 13% of the patients with leptospirosis compared tothe healthy controls, while the levels of IL-10 and TNF-α werenot elevated in either group.Conclusion: Our data suggest that elevated levels of IL-6, IL-8, and IL1-β may be associated with leptospirosis diseaseseverity, which requires patient follow-up for confirmation.

Recombinant LipL32 Protein Developed Using a Synthetic Gene Detects Leptospiraspecific Antibodies in Human Serum Samples

Background: Synthetic biology is emerging as a viable alternative for the production of recombinant antigens for diagnostic applications. It offers a safe alternative for the synthesis of antigenic principles derived from organisms that pose a high biological risk. Methods: Here, we describe an enzyme-linked immunosorbent assay (ELISA) using the synthetic recombinant LipL32 (rLipL32) protein expressed in Escherichia coli for the detection of Leptospira-specific antibodies in human serum samples. The rLipL32-based ELISA was compared with a microscopic agglutination test (MAT), which is currently used as the gold standard for the diagnosis of leptospirosis. Results: Our results showed that all the MAT-positive serum samples were positive for Leptospira-specific IgG in an ELISA, while 65% (n = 13) of these samples were also positive for Leptospira-specific IgM. In the MAT-negative serum samples, 80% and 55% of the samples were detected as negative by an ELISA for Leptospira-specific IgM and IgG, respectively. Conclusion: An ELISA using the synthetic rLipL32 antigen was able to distinguish Leptospira-specific IgM (sensitivity 65% and specificity 80%) and IgG (sensitivity 100% and specificity 55%) in human serum samples and has the potential to serve as a rapid diagnostic test for leptospirosis.

Diagnosis of tuberculous meningitis: challenges and promises

Tuberculosis (TB) which is caused by Mycobacterium tuberculosis infects primarily the lungs but it also affects other parts of the body. Tuberculous meningitis (TBM) is the most severe form of TB and has the highest mortality and morbidity rate compared to other forms of TB. It is common in young children and HIV-infected patients, but is also seen in adults. Despite anti-tuberculosis treatment, TBM is still a major cause of death and neurological sequelae as treatment given to the patients is often delayed. Early diagnosis is challenging due to the non-specific symptoms of TBM and the low number of tubercle bacilli in cerebrospinal fluid (CSF). Until now, there is no established diagnostic method that can rapidly detect M. tuberculosis in TBM patients with high sensitivity and specificity. The emergence of drug resistant M. tuberculosis strains further complicates the diagnosis and treatment regimen of TBM. This review summarizes challenges of the currently used diagnostic methods and the potential future use of molecular diagnostic methods for TBM.

Individualised second line anti-tuberculous therapy for anextensively resistant pulmonary tuberculosis (XDR PTB) in East Malaysia

Clinical experience with extensively Drug Resistant tuberculosis (XDR-TB) has not been reported in Malaysia before. We describe the clinical characteristics, risk factors, progress and therapeutic regimen for a healthcare worker with XDR-TB, who had failed therapy for multidrug resistant TB (MDR TB) in our institution. This case illustrates the risk of TB among healthcare workers in high TB-burden settings, the importance of obtaining upfront culture and susceptibility results in all new TB cases, the problem of acquired drug resistance developing during MDR-TB treatment, the challenges associated with XDR-TB treatment regimens, the value of surgical resection in refractory cases, and the major quality of life impact this disease can have on young, economically productive individuals.

A Review of Malaria Research in Malaysia

One hundred and thirteen articles related to Malaria were found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. Thirty eight articles were selected and reviewed on the basis of clinical relevance and future research implications. The epidemiology of malaria has undergone a significant change over the last decade with P. knowlesi, formerly a relatively unknown simian parasite rapidly becoming the most predominant malaria species to infect humans in Malaysia. The epidemiology, clinical features, diagnostic methods and treatment for P. knowlesi infection are described in these studies. In Malaysia, imported malaria from foreigners also poses a challenge. In view of these changes, new strategies on malaria control need to be devised and implemented, and treatment regimens need to be redefined to help Malaysia achieve the goal of malaria elimination by the year 2020.