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Hemophagocytic Lymphohistiocytosis Associated With T-cell Lymphoma in Pregnancy: Diagnostic Conundrum Unveiled

Siddik NA, Abd Rahim SNH, Jamaluddin J, Yuhana MY

Cureus, 2024 Aug;16(8):e66170.
PMID: 39233937 DOI: 10.7759/cureus.66170

Hemophagocytic lymphohistiocytosis (HLH) during pregnancy is a rare and often misdiagnosed disease. The clinical manifestations are non-specific, contributing to a high maternal mortality rate. This case report details the presentation of a 31-year-old pregnant woman with high-grade fever initially treated as an infection-related condition. The diagnostic challenge arose from the rarity of HLH, its variable clinical presentation, and the lack of specificity in clinical and laboratory findings. Despite numerous tests and escalation of therapies, the patient, unfortunately, succumbed to HLH associated with T-cell lymphoma. This case report aims to raise awareness of HLH, emphasizing its challenging definition. Malignancy-associated HLH is not uncommon, and early identification and treatment are paramount to prevent progressive tissue damage, organ failure, and mortality. The atypical presentation of HLH as a clinical manifestation of T-cell lymphoma underscores the need for vigilance in diagnosing this potentially fatal syndrome.
Fulltext Combined PCR and MAT improves the early diagnosis of the biphasic illness leptospirosis

Philip N, Affendy NB, Masri SN, Yuhana MY, Than LTL, Sekawi Z, et al.

PLoS One, 2020;15(9):e0239069.
PMID: 32915919 DOI: 10.1371/journal.pone.0239069

The diagnosis of leptospirosis remains a challenge due to its non-specific symptoms and the biphasic nature of the illness. A comprehensive diagnosis that includes both molecular (polymerase chain reaction (PCR)) and serology is vital for early detection of leptospirosis and to avoid misdiagnosis. However, not all samples could be subjected to both tests (serology and molecular) due to budget limitation, infrastructure, and technical expertise at least in resource-limited countries. We evaluated the usefulness of testing the clinically suspected leptospirosis cases with both techniques on all samples collected from the patients on the day of admission. Among the 165 patient's blood/serum samples tested (from three hospitals in Central Malaysia), 43 (26%) showed positivity by microscopic agglutination test (MAT), 63 (38%) by PCR, while 14 (8%) were positive by both MAT and PCR. For PCR, we tested two molecular targets (lipL32 by qPCR and 16S rDNA or rrs by nested PCR) and detected lipL32 in 47 (29%) and rrs gene in 63 (38%) patients. The use of more than one target gene for PCR increased the detection rates. Hence, a highly sensitive multiplex PCR targeting more than one diagnostic marker is recommended for the early detection of Leptospira in suspected patients. When the frequencies for positivity detected either by MAT or PCR combined, leptospirosis was diagnosed in a total of 92 (56%) patients, a higher frequency compared to when samples were only tested by a single method (MAT or PCR). The results from this study suggest the inclusion of both serology and molecular methods for every first sample irrespective of the days post-onset of symptoms (DPO) collected from patients for early diagnosis of leptospirosis.
Fulltext Predictors of severe leptospirosis: a multicentre observational study from Central Malaysia

Philip N, Lung Than LT, Shah AM, Yuhana MY, Sekawi Z, Neela VK

BMC Infect Dis, 2021 Oct 19;21(1):1081.
PMID: 34666707 DOI: 10.1186/s12879-021-06766-5

BACKGROUND: Leptospirosis is a re-emerging disease with vast clinical presentations, that ranges from subclinical or mild to severe and fatal outcomes. Leptospirosis can be managed well if diagnosed earlier, however, similar clinical presentations by several other febrile illnesses or co-infections, and laboratory diagnostic challenges due to the biphasic nature of the illness, often result in mis- or underdiagnosis, thereby lead to severe illness. Identification of clinical predictors for the severe form of the disease plays a crucial role in reducing disease complication and mortality. Therefore, we aimed to determine the clinical predictors associated with severe illness among leptospirosis patients from Central Malaysia through a prospective multicenter observational study.
METHODS: A prospective multicenter observational study was performed on patients admitted for clinically suspected leptospirosis. Three hospitals namely Hospital Serdang, Hospital Tengku Ampuan Rahimah and Hospital Teluk Intan were included in the study. Among a total of 165 clinically suspected leptospirosis patients, 83 confirmed cases were investigated for clinical predictors for severe illness. Qualitative variables were performed using χ2 and the relationship between mild and severe cases was evaluated using logistic regression. Multivariable logistic regression was used to predict the independent variable for severity.
RESULTS: Among the 83 patients, 50 showed mild disease and 33 developed severe illness. The mean age of the patients was 41.92 ± 17.99 and most were males (n = 54, 65.06%). We identified mechanical ventilation, acute kidney injury, septic shock, creatinine level of > 1.13 mg/dL, urea > 7 mmol/L, alanine aminotransferase > 50 IU, aspartate aminotransferase > 50 IU, and platelet 50 IU and platelet
Visual loss after long-haul flight

Abdul Ghani NA, Mohd Abdullah AAB, Abdul Hamid S, Yuhana MY, Ramli N

Eur J Ophthalmol, 2020 Oct 19.
PMID: 33070639 DOI: 10.1177/1120672120965499

BACKGROUND: Deep cerebral venous sinus thrombosis is a reversible yet potentially serious thromboembolic event. A number of reports suggest a relationship between long-haul flights and thromboembolic events, mainly deep venous thrombosis (DVT) and pulmonary embolism (PE). It is rarely reported to cause deep cerebral venous sinus thrombosis. We report a case of a bilateral papilledema after long-haul flight secondary to deep cerebral venous sinus thrombosis with subsequent complete recovery post corticosteroid and anticoagulant therapy.
CASE: A case of a 21-year-old woman with no known medical illness who presented with gradual painless bilateral visual loss is described. She had a history of travelling on a long-haul flight 3 weeks prior to presentation. Examination showed presence of bilateral papilloedema, no vitritis, choroiditis and retinitis. Blood investigations showed raised international normalised ratio (INR). Otherwise, workup for infectious causes of optic disc swelling, connective tissue disease screening were normal. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the brain showed loss of flow signal in the right transverse sinus and the left sigmoid sinus. Blood workup for preexisting hypercoagulable state was normal. She was diagnosed with deep cerebral venous sinus thrombosis and showed complete recovery with oral corticosteroid and anticoagulant therapy.
CONCLUSION: Deep cerebral venous sinus thrombosis is a potentially serious consequence of long-haul flights. A high index of suspicion along with radiological techniques is needed for early detection and initiation of anticoagulation for this reversible condition.
Fulltext The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals

Rajasuriar R, Kong YY, Nadarajah R, Abdullah NK, Spelman T, Yuhana MY, et al.

J Transl Med, 2015;13:30.
PMID: 25622527 DOI: 10.1186/s12967-015-0391-6

HIV-infected individuals have an increased risk of cardiovascular disease (CVD). T-allele carriers of the CD14 C-260T single-nucleotide polymorphism (SNP) have reported increased expression of the LPS-binding receptor, CD14 and inflammation in the general population. Our aim was to explore the relationship of this SNP with monocyte/macrophage activation and inflammation and its association with sub-clinical atherosclerosis in HIV-infected individuals.
Fulltext Elevated levels of IL-8 in fatal leptospirosis

Wan Yusoff WSY, Abdullah M, Sekawi Z, Amran F, Yuhana MY, Mohd Taib N, et al.

Pathog Glob Health, 2020 03;114(2):99-103.
PMID: 32024441 DOI: 10.1080/20477724.2020.1724356

Leptospirosis causes a wide range of clinical outcomes, including organ failure and death. Early treatment significantly increases the chances of cure. Interleukin-8 (IL-8) is a chemoattractant cytokine for neutrophil and is associated with multiple organ failure. Research has indicated IL-8 to be raised in severe and fatal cases of leptospirosis, but its suitability as a prognostic biomarker has yet to be confirmed. This study aimed to evaluate the significance of IL-8 with the clinical outcomes of leptospirosis patients. Plasma IL-8 was measured in fifty-two samples from hospitalized patients and nineteen healthy controls. The comparisons were made between mild, severe-survived and fatal groups identified by clinical or laboratory findings. IL-8 was significantly higher in fatal (p = 0.01) compared to mild cases. IL-8 was also significantly higher in fatal (p = 0.02) when compared to survived cases of leptospirosis. IL-8 levels in the plasma of fatal leptospirosis cases were significantly elevated compared to survived cases and may serve as a potential prognostic biomarker in determining the possible outcome of leptospirosis patients.
Raised levels of Il-6, Il-17a, and Il-22 in fatal leptospirosis

Wan Yusoff WSY, Abdullah M, Sekawi Z, Amran F, Yuhana MY, Mohd Taib N, et al.

Eur J Clin Microbiol Infect Dis, 2019 Dec;38(12):2349-2353.
PMID: 31529307 DOI: 10.1007/s10096-019-03699-5

Clinical manifestations of leptospirosis range from mild, common cold-like illness, to a life-threatening condition. The host immune response has been hypothesized to play a major role in leptospirosis outcome. Increased levels of inflammatory mediators, such as cytokines, may promote tissue damage that lead to increased disease severity. The question is whether cytokines levels may predict the outcome of leptospirosis and guide patient management. This study aimed to assess the association between Th1-, Th2-, and Th17-related cytokines with the clinical outcome of patients with leptospirosis. Different cytokine levels were measured in fifty-two plasma samples of hospitalized patients diagnosed with leptospirosis in Malaysia (January 2016-December 2017). Patients were divided into two separate categories: survived (n = 40) and fatal outcome (n = 12). Nineteen plasma samples from healthy individuals were obtained as controls. Cytokine quantification was performed using Simple Plex™ assays from ProteinSimple (San Jose, CA, USA). Measurements were done in triplicate and statistical analysis was performed using GraphPad software and SPSS v20. IL-6 (p = 0.033), IL-17A (p = 0.022), and IL-22 (p = 0.046) were significantly elevated in fatal cases. IL-17A concentration (OR 1.115; 95% CI 1.010-1.231) appeared to be an independent predictor of fatality of leptospirosis. Significantly higher levels of TNF-α (p ≤ 0.0001), IL-6 (p ≤ 0.0001), IL-10 (p ≤ 0.0001), IL-12 (p ≤ 0.0001), IL17A (p ≤ 0.0001), and IL-18 (p ≤ 0.0001) were observed among leptospirosis patients in comparison with healthy controls. Our study shows that certain cytokine levels may serve as possible prognostic biomarkers in leptospirosis patients.
Fulltext Leptospira interrogans and Leptospira kirschneri are the dominant Leptospira species causing human leptospirosis in Central Malaysia

Philip N, Bahtiar Affendy N, Ramli SNA, Arif M, Raja P, Nagandran E, et al.

PLoS Negl Trop Dis, 2020 Mar;14(3):e0008197.
PMID: 32203511 DOI: 10.1371/journal.pntd.0008197

BACKGROUND: Leptospirosis, commonly known as rat-urine disease, is a global but endemic zoonotic disease in the tropics. Despite the historical report of leptospirosis in Malaysia, the information on human-infecting species is limited. Determining the circulating species is important to understand its epidemiology, thereby to strategize appropriate control measures through public health interventions, diagnostics, therapeutics and vaccine development.
METHODOLOGY/PRINCIPLE FINDINGS: We investigated the human-infecting Leptospira species in blood and serum samples collected from clinically suspected leptospirosis patients admitted to three tertiary care hospitals in Malaysia. From a total of 165 patients, 92 (56%) were confirmed cases of leptospirosis through Microscopic Agglutination Test (MAT) (n = 43; 47%), Polymerase Chain Reaction (PCR) (n = 63; 68%) or both MAT and PCR (n = 14; 15%). The infecting Leptospira spp., determined by partial 16S rDNA (rrs) gene sequencing revealed two pathogenic species namely Leptospira interrogans (n = 44, 70%) and Leptospira kirschneri (n = 17, 27%) and one intermediate species Leptospira wolffii (n = 2, 3%). Multilocus sequence typing (MLST) identified an isolate of L. interrogans as a novel sequence type (ST 265), suggesting that this human-infecting strain has a unique genetic profile different from similar species isolated from rodents so far.
CONCLUSIONS/SIGNIFICANCE: Leptospira interrogans and Leptospira kirschneri were identified as the dominant Leptospira species causing human leptospirosis in Central Malaysia. The existence of novel clinically important ST 265 (infecting human), that is different from rodent L. interrogans strains cautions reservoir(s) of these Leptospira lineages are yet to be identified.