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Fulltext A case series of secondary Hemophagocytic Lymphohistiocytosis (HLH) secondary to dengue infection receiving dexamethasone in a tertiary centre

Liew Kean Yew, Suraya Hanim Abdullah, Beh Ting Yuen

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):41-41.
MyJurnal

Introduction: Secondary Hemophagocytic Lymphohistiocytosis (HLH) is a condition seen in severe dengue that can be potentially fatal. Timely management using HLH-directed treatment such as steroids or etoposide have been seen to improve the outcome of patients however there is no protocol on how to manage the disease. Two criteria commonly used to guide the direction of treatment are namely the HLH-2004 criteria and the Hscore; with the latter being used more often. The best cut-off H score is 169 corresponding to a sensitivity of 93%, specificity of 86% and accurate classification of 90% of the patients. We described of five patients diagnosed with severe dengue compli-cated with HLH. Methods: 5 cases that were diagnosed with severe dengue with secondary HLH and received dexa-methasone were reviewed retrospectively and clinical data extracted. Results: All patients had fever beyond critical or leaking phase. Four out of five cases had Hscore higher than 169 and had a mean score of 181 with only one bone marrow performed. Three patients had concurrent leaking and bleeding and three patients had fast progression of se-vere transaminitis during the critical phase. The mean peak ferritin level was 21077 micro/L. The only bone marrow aspiration done revealed increased macrophages and hemophagocytic activity. All patients received a short course of dexamethasone and discharged well. Conclusion: Short course dexamethasone is effective in treatment of HLH in dengue despite the concerns of administration of steroids in bleeding dengue patient. Secondary HLH in dengue remains a clinical diagnosis with no conclusive diagnostic criteria. It should be suspected in a severe dengue patient with hyperferritinemia and persistent fever. Technical difficulty of performing bone marrow during severe dengue makes conclusive diagnosis remains elusive.

Matched MeSH terms: Fever
Genetic variability of classical swine fever virus

Vilcek S, Stadejek T, Ballagi-Pordány A, Lowings JP, Paton DJ, Belák S

Virus Res, 1996 Aug;43(2):137-47.
PMID: 8864203

The genetic variability of classical swine fever virus was studied by comparative nucleotide sequence analysis of 76 virus isolates, collected during a half century from three continents. Parts of the E2 (gp55) and the polymerase gene coding regions of the viral genome were amplified by RT-PCR and DNA fragments of 254 and 207 bp, respectively, were sequenced. The comparative sequence analysis of the E2 region revealed two main phylogenetic groups of CSFV, indicating that the virus apparently evolved from two ancestor nodes. Group I (represented by Brescia strain) consisted of old and recent American and Asian viruses, as well as old English isolates from the 1950s. This group was subdivided into three subgroups, termed I.A-I.C. Group II (represented by Alfort strain) consisted of relatively recent isolates from Europe, together with strain Osaka, which was isolated in Japan from a pig of European origin. Based on genetic distances the group was divided into subgroups II.A and II.B. Malaysian isolates were branched into both groups, indicating multiple origins for contemporaneous outbreaks in that country. All ten vaccine strains tested were branched in group I, implying a common ancestor. The Japanese Kanagawa strain, isolated in 1974, and the British Congenital Tremor strain from 1964 were the most distinct variants of CSFV in our collection. The comparison of the nucleotide sequences of the polymerase coding region of 32 European strains distinguished subgroups II.A and II.B which were similar to the corresponding subgroups of the E2 phylogenetic tree. Thus, the results revealed that the E2 region and the polymerase coding regions seem to be appropriate for the grouping of CSFV isolates from all over the world, distinguishing two major groups of the virus. The reliability of these regions for phylogenetic analysis is indicated by the similarity of the results obtained from the two separate parts of the CSFV genome.

Matched MeSH terms: Classical swine fever virus/classification; Classical swine fever virus/genetics*; Classical swine fever virus/isolation & purification
Fulltext Rare Clinical Presentation of Tuberculous Meningitis: A Case Report

Tan JL, Nordin S, Besari AM

Malays J Med Sci, 2017 Oct;24(5):119-123.
PMID: 29386980 MyJurnal DOI: 10.21315/mjms2017.24.5.14

Introduction: Tuberculosis is the second leading cause of death under the category of infectious diseases, after the human immunodeficiency virus (HIV). Tuberculous meningitis (TBM) constitutes about 5% of all extrapulmonary disease worldwide. This report describes a case of Tuberculous meningitis with rare presentation in a 28-year-old woman, who was treated based on a collection of her social background, clinical findings and Multiplex PCR of tuberculosis.
Case presentation: A 28-year-old Malay woman with no significant medical history presented to HUSM with one month history of on and off fever, two weeks history of generalised limbs weakness and one week history of dysphagia. She was reported to have experienced visual hallucination and significant weight loss. Her laboratory result is significant for leukocytosis, elevated ESR and hypernatremia. Non-enhanced and contrast CT scan of the brain showed severe bilateral frontal cerebral atrophy. Cerebral spinal fluid (CSF) for multiplex PCR for Mycobacterium tuberculosis complex was positive. She was promptly started on anti-TB regime combined with dexamethasone. Subsequent follow-up showed significant improvement.
Conclusion: This is a rare clinical manifestation of Tuberculous meningitis that demonstrates the importance of recognising and initiating the treatment early to reduce disabilities and improve clinical outcome.

Matched MeSH terms: Fever
Fulltext Urogenital melioidosis: a review of clinical presentations, characteristic and outcomes

Chong Vh VH, Sharif F, Bickle I

Med J Malaysia, 2014 Dec;69(6):257-60.
PMID: 25934955 MyJurnal

INTRODUCTION: Melioidosis is endemic to the tropical regions, in particular Thailand and Northern Australia. Any organ can be affected by melioidosis. Involvement of the urogenital system is common in Northern Australia, but is less common in other regions. This study assesses the characteristics of melioidosis affecting the urogenital system treated in a tertiary referral centre in Brunei Darussalam.

MATERIAL AND METHODS: All patients treated for melioidosis of the urogenital system were identified and retrospectively reviewed.

RESULTS: There were 9 patients with 11 episodes of urogenital infections treated over 13 years. The median age at diagnosis was 38 years old (range 29 - 63) with men predominantly affected. The major risk factor was underlying diabetes mellitus (n=9), including three patients diagnosed at the time of diagnosis of melioidosis. The median glycosylated haemoglobin (HbA1c) was 12.8% (range 6.4 to 16.6%). One patient's risk factor was only moderate alcohol consumption. Common symptoms included; fever, lethargy, rigor and anorexia. Dysuria was reported by two patients. The median duration of symptoms before presentation was 7 days (range 2 to 21 days) and the median number of sites involved were 3 (range of 2 to 6). Urogenital involvement included prostate (n=6), kidney (n=8), seminal vesicles (n=1) and testis (n=1). Radiological imaging showed that large prostate abscesses (>4.5cm) were common, and in some patients, the kidney abscess had the 'honeycomb' previously described as typical for melioidosis liver abscess. All patients were successfully treated for melioidosis and at a median follow up of 34 months (range 1 - 97), there was one death from complications of diabetes mellitus.

CONCLUSION: Urogenital melioidosis only accounted for a small proportion of all melioidosis involvement, with prostate and kidney most commonly affected. Concomitant involvement of other sites were common. The major risk factor was poorly controlled diabetes mellitus.

Matched MeSH terms: Fever
Fulltext Mechanical and Microstructural Evaluations of Lightweight Aggregate Geopolymer Concrete before and after Exposed to Elevated Temperatures

Abdulkareem OA, Abdullah MMAB, Hussin K, Ismail KN, Binhussain M

Materials (Basel), 2013 Oct 09;6(10):4450-4461.
PMID: 28788339 DOI: 10.3390/ma6104450

This paper presents the mechanical and microstructural characteristics of a lightweight aggregate geopolymer concrete (LWAGC) synthesized by the alkali-activation of a fly ash source (FA) before and after being exposed to elevated temperatures, ranging from 100 to 800 °C. The results show that the LWAGC unexposed to the elevated temperatures possesses a good strength-to-weight ratio compared with other LWAGCs available in the published literature. The unexposed LWAGC also shows an excellent strength development versus aging times, up to 365 days. For the exposed LWAGC to the elevated temperatures of 100 to 800 °C, the results illustrate that the concretes gain compressive strength after being exposed to elevated temperatures of 100, 200 and 300 °C. Afterward, the strength of the LWAGC started to deteriorate and decrease after being exposed to elevated temperatures of 400 °C, and up to 800 °C. Based on the mechanical strength results of the exposed LWAGCs to elevated temperatures of 100 °C to 800 °C, the relationship between the exposure temperature and the obtained residual compressive strength is statistically analyzed and achieved. In addition, the microstructure investigation of the unexposed LWAGC shows a good bonding between aggregate and mortar at the interface transition zone (ITZ). However, this bonding is subjected to deterioration as the LWAGC is exposed to elevated temperatures of 400, 600 and 800 °C by increasing the microcrack content and swelling of the unreacted silicates.

Matched MeSH terms: Fever
Countries at risk of importation of chikungunya virus cases from Southern Thailand: A modeling study

Tuite AR, Watts AG, Khan K, Bogoch II

Infect Dis Model, 2019;4:251-256.
PMID: 31667444 DOI: 10.1016/j.idm.2019.09.001

Southern Thailand has been experiencing a large chikungunya virus (CHIKV) outbreak since October 2018. Given the magnitude and duration of the outbreak and its location in a popular tourist destination, we sought to determine international case exportation risk and identify countries at greatest risk of receiving travel-associated imported CHIKV cases. We used a probabilistic model to estimate the expected number of exported cases from Southern Thailand between October 2018 and April 2019. The model incorporated data on CHIKV natural history, infection rates in Southern Thailand, average length of stay for tourists, and international outbound air passenger numbers from the outbreak area. For countries highly connected to Southern Thailand by air travel, we ran 1000 simulations to estimate the expected number of imported cases. We also identified destination countries with conditions suitable for autochthonous CHIKV transmission. Over the outbreak period, we estimated that an average of 125 (95% credible interval (CrI): 102-149) cases would be exported from Southern Thailand to international destinations via air travel. China was projected to receive the most cases (43, 95% CrI: 30-56), followed by Singapore (7, 95% CrI: 2-12) and Malaysia (5, 95% CrI: 1-10). Twenty-three countries were projected to receive at least one imported case, and 64% of these countries had one or more regions that could potentially support autochthonous CHIKV transmission. The overall risk of international exportation of CHIKV cases associated with the outbreak is Southern Thailand is high. Our model projections are consistent with recent reports of CHIKV in travelers returning from the region. Countries should be alert to the possibility of CHIKV infection in returning travelers, particularly in regions where autochthonous transmission is possible.

Matched MeSH terms: Chikungunya Fever
Fulltext Paediatric oropharyngeal tularaemia requiring surgical intervention

Nemmour A, Bakri A, Fischer CA, Brand Y

BMJ Case Rep, 2019 Sep 06;12(9).
PMID: 31494583 DOI: 10.1136/bcr-2019-229754

Tularaemia is a rare infectious disease endemic in most European countries caused by the bacterium Francisella tularensis 1 Patients often show acute non-specific symptoms, which causes a delay in diagnosis and proper treatment, potentially resulting in significant morbidities such as deep neck abscess, meningitis, endocarditis and septic shock. The authors present a case of a 5-year old boy with a 4-day history of fever, sore throat and painful cervical lymphadenopathy, whose clinical progression worsened despite being treated with recommended antibiotics as per WHO guidelines once the diagnosis of Tularaemia was confirmed by serologic tests. He developed a parapharyngeal abscess and a persistent left necrotic cervical lymph node, which both were surgically drained and excised, respectively, and an extended course of antibiotic was given. Subsequently, the patient fully recovered from the illness and the follow-up was negative for relapse.

Matched MeSH terms: Fever/microbiology
Fulltext Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment

Monath TP, Seligman SJ, Robertson JS, Guy B, Hayes EB, Condit RC, et al.

Vaccine, 2015 Jan 01;33(1):62-72.
PMID: 25446819 DOI: 10.1016/j.vaccine.2014.10.004

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines.

Matched MeSH terms: Yellow fever virus/genetics*
Elizabeth Fee (1946-2018)

Birn AE, Brown TM

Am J Public Health, 2019 Apr 18.
PMID: 30998404 DOI: 10.2105/AJPH.2019.305065

Elizabeth Fee was a remarkable and influential public health historian, whose personal and professional trajectories led her to speak truth to and about power in public health, past and present. Born in Northern Ireland in 1946 to Irish-Methodist missionary parents, Liz's childhood brought her into contact with peoples and struggles across the globe. At just five weeks of age, she was whisked away by her parents to civil war-era China, where she lost hearing in one ear from an untreated bout with scarlet fever. In midchildhood, she attended school in Malaysia, after which her family returned to Belfast. There, she came of age amid festering political and religious violence, learning firsthand that history is told and retold by protagonists and witnesses, oppressors and oppressed. (Am J Public Health. Published online ahead of print April 18, 2019: e1-e4. doi:10.2105/AJPH.2019.305065).

Matched MeSH terms: Scarlet Fever
Fulltext Current concerns and perspectives on Zika virus co-infection with arboviruses and HIV

Rothan HA, Bidokhti MRM, Byrareddy SN

J Autoimmun, 2018 05;89:11-20.
PMID: 29352633 DOI: 10.1016/j.jaut.2018.01.002

Dissemination of vector-borne viruses, such as Zika virus (ZIKV), in tropical and sub-tropical regions has a complicated impact on the immunopathogenesis of other endemic viruses such as dengue virus (DENV), chikungunya virus (CHIKV) and human immunodeficiency virus (HIV). The consequences of the possible co-infections with these viruses have specifically shown significant impact on the treatment and vaccination strategies. ZIKV is a mosquito-borne flavivirus from African and Asian lineages that causes neurological complications in infected humans. Many of DENV and CHIKV endemic regions have been experiencing outbreaks of ZIKV infection. Intriguingly, the mosquitoes, Aedes Aegypti and Aedes Albopictus, can simultaneously transmit all the combinations of ZIKV, DENV, and CHIKV to the humans. The co-circulation of these viruses leads to a complicated immune response due to the pre-existence or co-existence of ZIKV infection with DENV and CHIKV infections. The non-vector transmission of ZIKV, especially, via sexual intercourse and placenta represents an additional burden that may hander the treatment strategies of other sexually transmitted diseases such as HIV. Collectively, ZIKV co-circulation and co-infection with other viruses have inevitable impact on the host immune response, diagnosis techniques, and vaccine development strategies for the control of these co-infections.

Matched MeSH terms: Chikungunya Fever/immunology; Chikungunya Fever/epidemiology*
The extended Widal test in the diagnosis of fevers due to Salmonella infection

CHAN KE

Med J Malaya, 1962 Sep;17:18-24.
PMID: 14019986
Matched MeSH terms: Fever*
Fulltext Symptomatic dengue in children in 10 Asian and Latin American countries

L'Azou M, Moureau A, Sarti E, Nealon J, Zambrano B, Wartel TA, et al.

N Engl J Med, 2016 Mar 24;374(12):1155-66.
PMID: 27007959 DOI: 10.1056/NEJMoa1503877

BACKGROUND: The control groups in two phase 3 trials of dengue vaccine efficacy included two large regional cohorts that were followed up for dengue infection. These cohorts provided a sample for epidemiologic analyses of symptomatic dengue in children across 10 countries in Southeast Asia and Latin America in which dengue is endemic.
METHODS: We monitored acute febrile illness and virologically confirmed dengue (VCD) in 3424 healthy children, 2 to 16 years of age, in Asia (Indonesia, Malaysia, the Philippines, Thailand, and Vietnam) from June 2011 through December 2013 and in 6939 children, 9 to 18 years of age, in Latin America (Brazil, Colombia, Honduras, Mexico, and Puerto Rico) from June 2011 through April 2014. Acute febrile episodes were determined to be VCD by means of a nonstructural protein 1 antigen immunoassay and reverse-transcriptase-polymerase-chain-reaction assays. Dengue hemorrhagic fever was defined according to 1997 World Health Organization criteria.
RESULTS: Approximately 10% of the febrile episodes in each cohort were confirmed to be VCD, with 319 VCD episodes (4.6 episodes per 100 person-years) occurring in the Asian cohort and 389 VCD episodes (2.9 episodes per 100 person-years) occurring in the Latin American cohort; no trend according to age group was observed. The incidence of dengue hemorrhagic fever was less than 0.3 episodes per 100 person-years in each cohort. The percentage of VCD episodes requiring hospitalization was 19.1% in the Asian cohort and 11.1% in the Latin American cohort. In comparable age groups (9 to 12 years and 13 to 16 years), the burden of dengue was higher in Asia than in Latin America.
CONCLUSIONS: The burdens of dengue were substantial in the two regions and in all age groups. Burdens varied widely according to country, but the rates were generally higher and the disease more frequently severe in Asian countries than in Latin American countries. (Funded by Sanofi Pasteur; CYD14 and CYD15 ClinicalTrials.gov numbers, NCT01373281 and NCT01374516.).
Note: Malaysia is a study site (CYD14 Primary Study Group authors: HIHJMI, Pediatric Institute, Kuala Lumpur Hospital, Kuala Lumpur; RN, Department of Paediatrics, Hospital Pulau Pinang, Pulau Pinang, Malaysia)

Matched MeSH terms: Fever/etiology
Fulltext Self-reported side effects of COVID-19 vaccines among health professions students in India

Majumder MAA, Bharatha A, Kumar S, Chatterjee M, Gupta S, Harewood H, et al.

PeerJ, 2024;12:e17083.
PMID: 38590705 DOI: 10.7717/peerj.17083

Studies focusing on the safety and common side effects of vaccines play a crucial role in enhancing public acceptance of vaccination. Research is scarce regarding the usage of COVID-19 vaccines and the side effects experienced by health professions students in India and other countries. This study aimed to document self-reported side effects associated with COVID-19 vaccination among medical and dental students of six medical and dental colleges and teaching hospitals in four states (Tamil Nadu, Madhya Pradesh, Gujarat, and West Bengal) of India. A cross-sectional survey using purposive sampling of medical and dental students was conducted from 26 April to 26 May 2021. Data was collected using a Google Forms questionnaire capturing information regarding receiving COVID-19 vaccines, side effects and symptoms, onset and duration of symptoms, use of treatment to alleviate symptoms, awareness of haematologic risks associated with vaccination, and side effects from previous (non-COVID-19) vaccinations. The majority (94.5%) of participants received both doses of the Covishield/AstraZeneca COVID-19 vaccine. Among participants (n = 492), 45.3% (n = 223) reported one or more side effects. The most frequently reported side effects were soreness of the injected arm (80.3%), tiredness (78.5%), fever (71.3%), headache (64.1%), and hypersomnia (58.7%). The two most common severe symptoms were fever (14.8%) and headache (13%). Most side effects appeared on the day of vaccination: soreness of the injection site (57%), fever (43.1%), and tiredness (42.6%). Most reported symptoms persisted for one to three days-soreness of the injection site (53%), fever (47.1%), and headache (42.6%). Logistic regression showed that women were almost 85% less likely to report side effects. The study's findings corroborate the safety of the Covishield/AstraZeneca vaccine's first dose, evidenced by the relatively minor and transient nature of the side effects. However, the study underscores the necessity for ongoing research to assess the long-term impacts of COVID-19 vaccines, especially in the context of booster doses, thereby contributing to the global understanding of vaccine safety and efficacy.

Matched MeSH terms: Fever
Notes from the field: acute muscular sarcocystosis among returning travelers - Tioman Island, Malaysia, 2011

Centers for Disease Control and Prevention (CDC)

MMWR Morb Mortal Wkly Rep, 2012 Jan 20;61(2):37-8.
PMID: 22258418

GeoSentinel (the surveillance program of the International Society of Travel Medicine and CDC) has identified 32 cases of suspected acute muscular sarcocystosis in travelers returning from Tioman Island off the east coast of peninsular Malaysia. All the patients traveled to Tioman Island during the summer of 2011. Within days or weeks of returning home, all experienced fever and muscle pain, often severe and prolonged. All had peripheral eosinophilia, and most had elevated serum creatinine phosphokinase levels. Most were tested for acute trichinosis and toxoplasmosis by serology, and all of these tests were negative. Approximately half of the patients were identified in Germany; others were reported elsewhere in Europe, and in North America and Asia. Muscle biopsy from two patients demonstrated organisms consistent with sarcocystosis, one from a group of five ill travelers and one from a group of three.

Matched MeSH terms: Fever/etiology
Update: outbreak of Nipah virus--Malaysia and Singapore, 1999

Centers for Disease Control and Prevention (CDC)

MMWR Morb Mortal Wkly Rep, 1999 Apr 30;48(16):335-7.
PMID: 10366143

During March 1999, health officials in Malaysia and Singapore, in collaboration with Australian researchers and CDC, investigated reports of febrile encephalitic and respiratory illnesses among workers who had exposure to pigs. A previously unrecognized paramyxovirus (formerly known as Hendra-like virus), now called Nipah virus, was implicated by laboratory testing in many of these cases. Febrile encephalitis continues to be reported in Malaysia but has decreased coincident with mass culling of pigs in outbreak areas. No new cases of febrile illness associated with Nipah virus infection have been identified in Singapore since March 19, 1999, when abattoirs were closed. This report summarizes interim findings from ongoing epidemiologic and laboratory investigations in Malaysia and Singapore.

Matched MeSH terms: Fever
Fulltext A Double Whammy of Mycotic Aneurysms and Acquired Dysfibrinogenemia in a Patient with Septicemia

Sim CY, Khoo CS, Mustafar R, Chai JN

Balkan Med J, 2021 01;38(1):55-56.
PMID: 32720494 DOI: 10.4274/balkanmedj.galenos.2020.2020.5.208
Matched MeSH terms: Fever/etiology
Fulltext Presenting features and treatment outcome of 78 Malaysian children with neuroblastoma

Ng SM, Abdullah WA, Lin HP, Chan LL

Southeast Asian J. Trop. Med. Public Health, 1999 Mar;30(1):149-53.
PMID: 10695803

To study the distribution of presenting features and their prognostic significance in neuroblastoma treated in a single institution in Malaysia. A retrospective study was made of 78 neuroblastoma cases diagnosed and treated in the University Hospital, Kuala Lumpur, Malaysia between June 1982 and February 1997. Diagnosis was established by standard histological criteria. The presenting features were evaluated for their distribution and prognostic influence. Disease-free survival from diagnosis was the outcome variable of interest. The ages ranged from 0.1 to 11 years old (median: 3 years old). The tumor originated from the adrenal glands in 83% and the majority of cases presented in advanced stage (stage III 22%, stage IV 66%). Bone marrow was the commonest site of distant metastasis occurring in 45% of patients. The main presenting signs and symptoms in decreasing order were pallor, fever, abdominal mass, weight loss, and bone/joint pain. Univariate analysis conferred age, initial stage and Hb level as significant prognostic factors. No influence in disease-free survival was found for sex, race, primary site, urinary vanillylmandelic acid level, white cell count and platelet count. Overall 2-year disease-free survival was achieved in 27 (39%) patients. Four patients underwent bone marrow transplant, three of whom achieved 2-year disease-free survival. The results suggest that age, initial stage and hemoglobin level are significant prognostic factors based on univariate analysis. In addition, more Malaysian children presented with adrenal primary site and advanced disease compared to previous reported studies.

Matched MeSH terms: Fever/etiology
Serum C-reactive protein concentrations in Malaysian children with enteric fever

Choo KE, Davis TM, Henry RL, Chan LP

J Trop Pediatr, 2001 Aug;47(4):211-4.
PMID: 11523761

To investigate the role of serum C-reactive protein (CRP) in the diagnosis of typhoid fever, we studied 227 febrile Malaysian children hospitalized during a 12-month period. The children were: culture-positive for Salmonella typhi (Group 1; n = 108); culture-negative but with typical clinical features of typhoid fever (Group 2; n = 60); or had non-typhoidal illness (Group 3; n = 59). Group 1 children had the highest serum CRP concentrations (geometric mean [SD range]; 43 [12-150] mg/l vs. 26 [8-85] mg/l in Group 2 and 21 [4-110] mg/l in Group 3; p < 0.001). In regression analysis, age, patient group and fever duration were independently associated with serum CRP (p < 0.05) but gender was not. In Group 1 patients, there was a significant positive association between serum CRP and Widal O and H agglutinin titres. In receiver-operator characteristic (ROC) analysis of serum CRP for Groups 1 and 2 combined, compared with Group 3, the area under the curve (AUC) was 0.65. These data show that the serum CRP is highest in culture-positive children with enteric fever and reflects the immune response to the infection in this group. Nevertheless, serum CRP had relatively low sensitivity and specificity for confirmed or clinically diagnosed typhoid fever (68 and 58 per cent, respectively at 'cut-off' concentration 30.0 mg/l), and an AUC value only moderately above that associated with no predictive power (0.5). Although of limited use as a primary diagnostic test, a raised serum CRP may still have a place as one of a range of features that facilitate assessment of a febrile child in a typhoid-endemic area.

Matched MeSH terms: Typhoid Fever/blood*; Typhoid Fever/diagnosis
Fulltext Antigenic Variation of East/Central/South African and Asian Chikungunya Virus Genotypes in Neutralization by Immune Sera

Chua CL, Sam IC, Merits A, Chan YF

PLoS Negl Trop Dis, 2016 08;10(8):e0004960.
PMID: 27571254 DOI: 10.1371/journal.pntd.0004960

BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus which causes epidemics of fever, severe joint pain and rash. Between 2005 and 2010, the East/Central/South African (ECSA) genotype was responsible for global explosive outbreaks across India, the Indian Ocean and Southeast Asia. From late 2013, Asian genotype CHIKV has caused outbreaks in the Americas. The characteristics of cross-antibody efficacy and epitopes are poorly understood.
METHODOLOGY/PRINCIPAL FINDINGS: We characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008-2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes.
CONCLUSION/SIGNIFICANCE: Immune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued outbreaks of co-circulating CHIKV genotypes and effective design of vaccines and diagnostic serological assays.

Matched MeSH terms: Chikungunya Fever/immunology; Chikungunya Fever/epidemiology
Fulltext The neutralizing role of IgM during early Chikungunya virus infection

Chua CL, Sam IC, Chiam CW, Chan YF

PLoS One, 2017;12(2):e0171989.
PMID: 28182795 DOI: 10.1371/journal.pone.0171989

The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays.

Matched MeSH terms: Chikungunya Fever/blood; Chikungunya Fever/immunology*

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