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Updates on chikungunya epidemiology, clinical disease, and diagnostics

Sam IC, Kümmerer BM, Chan YF, Roques P, Drosten C, AbuBakar S

Vector Borne Zoonotic Dis, 2015 Apr;15(4):223-30.
PMID: 25897809 DOI: 10.1089/vbz.2014.1680

Chikungunya virus (CHIKV) is an Aedes-borne alphavirus, historically found in Africa and Asia, where it caused sporadic outbreaks. In 2004, CHIKV reemerged in East Africa and spread globally to cause epidemics, including, for the first time, autochthonous transmission in Europe, the Middle East, and Oceania. The epidemic strains were of the East/Central/South African genotype. Strains of the Asian genotype of CHIKV continued to cause outbreaks in Asia and spread to Oceania and, in 2013, to the Americas. Acute disease, mainly comprising fever, rash, and arthralgia, was previously regarded as self-limiting; however, there is growing evidence of severe but rare manifestations, such as neurological disease. Furthermore, CHIKV appears to cause a significant burden of long-term morbidity due to persistent arthralgia. Diagnostic assays have advanced greatly in recent years, although there remains a need for simple, accurate, and affordable tests for the developing countries where CHIKV is most prevalent. This review focuses on recent important work on the epidemiology, clinical disease and diagnostics of CHIKV.

Matched MeSH terms: Chikungunya Fever/diagnosis
Haemolytic anaemia precipitated by dengue fever

Abdullah NH, Mohammad N, Ramli M, Wan Ghazali WS

BMJ Case Rep, 2019 Aug 28;12(8).
PMID: 31466966 DOI: 10.1136/bcr-2018-226760

We reported a case of a woman with no past medical illness who presented with a few days' history of fever, myalgia, arthralgia, hypochromic microcytic anaemia and thrombocytopaenia and who was nonstructural protein 1 antigen (NS1Ag)-positive. Haemolytic anaemia including full blood picture work-up revealed high reticulocyte count and haemolysis with positive direct Coombs test. She was started on prednisolone and was discharged well.

Matched MeSH terms: Fever/diagnosis
Fulltext External quality assessment of dengue and chikungunya diagnostics in the Asia Pacific region, 2015

Soh LT, Squires RC, Tan LK, Pok KY, Yang H, Liew C, et al.

Western Pac Surveill Response J, 2016 04 22;7(2):26-34.
PMID: 27508088 DOI: 10.5365/WPSAR.2016.7.1.002

OBJECTIVE: To conduct an external quality assessment (EQA) of dengue and chikungunya diagnostics among national-level public health laboratories in the Asia Pacific region following the first round of EQA for dengue diagnostics in 2013.
METHODS: Twenty-four national-level public health laboratories performed routine diagnostic assays on a proficiency testing panel consisting of two modules. Module A contained serum samples spiked with cultured dengue virus (DENV) or chikungunya virus (CHIKV) for the detection of nucleic acid and DENV non-structural protein 1 (NS1) antigen. Module B contained human serum samples for the detection of anti-DENV antibodies.
RESULTS: Among 20 laboratories testing Module A, 17 (85%) correctly detected DENV RNA by reverse transcription polymerase chain reaction (RT-PCR), 18 (90%) correctly determined serotype and 19 (95%) correctly identified CHIKV by RT-PCR. Ten of 15 (66.7%) laboratories performing NS1 antigen assays obtained the correct results. In Module B, 18/23 (78.3%) and 20/20 (100%) of laboratories correctly detected anti-DENV IgM and IgG, respectively. Detection of acute/recent DENV infection by both molecular (RT-PCR) and serological methods (IgM) was available in 19/24 (79.2%) participating laboratories.
DISCUSSION: Accurate laboratory testing is a critical component of dengue and chikungunya surveillance and control. This second round of EQA reveals good proficiency in molecular and serological diagnostics of these diseases in the Asia Pacific region. Further comprehensive diagnostic testing, including testing for Zika virus, should comprise future iterations of the EQA.

Matched MeSH terms: Chikungunya Fever/diagnosis*
Fulltext The discrimination of d-tartrate positive and d-tartrate negative S. enterica subsp. enterica serovar Paratyphi B isolated in Malaysia by phenotypic and genotypic methods

Ahmad N, Hoon ST, Ghani MK, Tee KY

Malays J Pathol, 2012 Jun;34(1):35-9.
PMID: 22870596 MyJurnal

Serotyping is not sufficient to differentiate between Salmonella species that cause paratyphoid fever from the strains that cause milder gastroenteritis as these organisms share the same serotype Salmonella Paratyphi B (S. Paratyphi B). Strains causing paratyphoid fever do not ferment d-tartrate and this key feature was used in this study to determine the prevalence of these strains among the collection of S. Paratyphi B strains isolated from patients in Malaysia. A total of 105 isolates of S. Paratyphi B were discriminated into d-tartrate positive (dT+) and d-tartrate negative (dT) variants by two lead acetate test protocols and multiplex PCR. The lead acetate test protocol 1 differed from protocol 2 by a lower inoculum size and different incubation conditions while the multiplex PCR utilized 2 sets of primers targeting the ATG start codon of the gene STM3356. Lead acetate protocol 1 discriminated 97.1% of the isolates as S. Paratyphi B dT+ and 2.9% as dT while test protocol 2 discriminated all the isolates as S. Paratyphi B dT+. The multiplex PCR test identified all 105 isolates as S. Paratyphi B dT+ strains. The concordance of the lead acetate test relative to that of multiplex PCR was 97.7% and 100% for protocol 1 and 2 respectively. This study showed that S. Paratyphi B dT+ is a common causative agent of gastroenteritis in Malaysia while paratyphoid fever appears to be relatively uncommon. Multiplex PCR was shown to be a simpler, more rapid and reliable method to discriminate S. Paratyphi B than the phenotypic lead acetate test.

Matched MeSH terms: Paratyphoid Fever/diagnosis
A comparison between infrared tympanic thermometry, oral and axilla with rectal thermometry in neutropenic adults

Dzarr AA, Kamal M, Baba AA

Eur J Oncol Nurs, 2009 Sep;13(4):250-4.
PMID: 19386547 DOI: 10.1016/j.ejon.2009.03.006

This study assessed the agreement between infrared tympanic membrane (TM), axillary, corrected axillary (+0.5 degrees C), oral, and corrected oral (+0.3 degrees C) to rectal thermometry as reference standard in neutropenic adults. The sensitivity and specificity of the mentioned thermometries in detecting rectal fever (> or =38 degrees C) were also analysed.

Matched MeSH terms: Fever/diagnosis*
Fulltext Crystal structure of an antigenic outer-membrane protein from Salmonella Typhi suggests a potential antigenic loop and an efflux mechanism

Guan HH, Yoshimura M, Chuankhayan P, Lin CC, Chen NC, Yang MC, et al.

Sci Rep, 2015 Nov 13;5:16441.
PMID: 26563565 DOI: 10.1038/srep16441

ST50, an outer-membrane component of the multi-drug efflux system from Salmonella enterica serovar Typhi, is an obligatory diagnostic antigen for typhoid fever. ST50 is an excellent and unique diagnostic antigen with 95% specificity and 90% sensitivity and is used in the commercial diagnosis test kit (TYPHIDOT(TM)). The crystal structure of ST50 at a resolution of 2.98 Å reveals a trimer that forms an α-helical tunnel and a β-barrel transmembrane channel traversing the periplasmic space and outer membrane. Structural investigations suggest significant conformational variations in the extracellular loop regions, especially extracellular loop 2. This is the location of the most plausible antibody-binding domain that could be used to target the design of new antigenic epitopes for the development of better diagnostics or drugs for the treatment of typhoid fever. A molecule of the detergent n-octyl-β-D-glucoside is observed in the D-cage, which comprises three sets of Asp361 and Asp371 residues at the periplasmic entrance. These structural insights suggest a possible substrate transport mechanism in which the substrate first binds at the periplasmic entrance of ST50 and subsequently, via iris-like structural movements to open the periplasmic end, penetrates the periplasmic domain for efflux pumping of molecules, including poisonous metabolites or xenobiotics, for excretion outside the pathogen.

Matched MeSH terms: Typhoid Fever/diagnosis
Zika Virus Infection: Current Concerns and Perspectives

Maharajan MK, Ranjan A, Chu JF, Foo WL, Chai ZX, Lau EY, et al.

Clin Rev Allergy Immunol, 2016 Dec;51(3):383-394.
PMID: 27236440

The Zika virus outbreaks highlight the growing importance need for a reliable, specific and rapid diagnostic device to detect Zika virus, as it is often recognized as a mild disease without being identified. Many Zika virus infection cases have been misdiagnosed or underreported because of the non-specific clinical presentation. The aim of this review was to provide a critical and comprehensive overview of the published peer-reviewed evidence related to clinical presentations, various diagnostic methods and modes of transmission of Zika virus infection, as well as potential therapeutic targets to combat microcephaly. Zika virus is mainly transmitted through bites from Aedes aegypti mosquito. It can also be transmitted through blood, perinatally and sexually. Pregnant women are advised to postpone or avoid travelling to areas where active Zika virus transmission is reported, as this infection is directly linked to foetal microcephaly. Due to the high prevalence of Guillain-Barre syndrome and microcephaly in the endemic area, it is vital to confirm the diagnosis of Zika virus. Zika virus infection had been declared as a public health emergency and of international concern by the World Health Organisation. Governments and agencies should play an important role in terms of investing time and resources to fundamentally understand this infection so that a vaccine can be developed besides raising awareness.

Matched MeSH terms: Chikungunya Fever/diagnosis
Complications of bacteriologically confirmed typhoid fever in children

Malik AS

J Trop Pediatr, 2002 Apr;48(2):102-8.
PMID: 12022423

To find the incidence, markers and nature of complications of typhoid fever, we studied 102 children with cultures positive for Salmonella typhi in a cross-sectional study, prospectively, over a period of almost 5 years. All isolates were sensitive to commonly used antibiotics. One third of these children developed complications which included: anicteric hepatitis, bone marrow suppression, paralytic ileus, myocarditis, psychosis, cholecystitis, osteomyelitis, peritonitis, pneumonia, haemolysis, and syndrome of inappropriate release of antidiuretic hormone (SIADH). Twelve children developed multiple complications. If hepatitis is excluded from the complications, the rate of complications in bacteriologically confirmed cases of typhoid fever drops to 11 per cent. These complications were not related to: the age or sex of patients, duration of illness before admission, use of antibiotics before admission, nutritional status, level of 'O' or 'H' titre, presence of IgM or IgG antibodies, or treatment with chloramphenicol or ampicillin. Children with splenomegaly, thrombocytopenia or leukopenia were more likely to develop complications.

Matched MeSH terms: Typhoid Fever/diagnosis
Detection of antibodies against Salmonella typhi outer membrane protein (OMP) preparation in typhoid fever patients

Verdugo-Rodriguez A, Gam LH, Devi S, Koh CL, Puthucheary SD, Calva E, et al.

Asian Pac J Allergy Immunol, 1993 Jun;11(1):45-52.
PMID: 8216558

An indirect ELISA was used to detect antibodies against outer membrane protein preparations (OMPs) from Salmonella typhi. Sera from patients with a definitive diagnosis of typhoid fever (TF) gave a mean absorbance reading, at 414 nm, of 1.52 +/- 0.23 as compared to 0.30 +/- 0.11 for sera from healthy individuals. This gave a positive to negative ratio of absorbance readings of approximately 5.1. Suspected TF patients (no isolation of S. typhi), with positive and negative Widal titers had mean absorbance readings of 1.282 +/00.46 and 0.25 +/- 0.19, respectively. Sera from patients with leptospirosis, rickettsial typhus, dengue fever, and other infections gave mean absorbances of 0.20 +/- 0.08, 0.24 +/- 0.08, 0.27 +/- 0.08, and 0.31 +/- 0.16, respectively. The sensitivity, specificity, positive and negative predictive values were 100%, 94%, 80% and 100%, respectively. The antibody response detected in the definitive TF cases was predominantly IgG in nature and no cross-reactivity was seen with OMP preparations extracted from E. coli. Variable reactivity was noted with OMP preparations obtained from other Salmonella spp. Three major OMPs are presented in the antigen preparation and strong binding of positive sera was detected to all three bands.

Matched MeSH terms: Typhoid Fever/diagnosis
Fulltext Retrospective review of dot enzyme immunoassay test for typhoid fever in an endemic area

Jackson AA, Ismail A, Ibrahim TA, Kader ZS, Nawi NM

Southeast Asian J. Trop. Med. Public Health, 1995 Dec;26(4):625-30.
PMID: 9139364

Typhoid fever remains a common problem in Malaysia, but for its diagnosis both blood culture and the Widal test have drawbacks. A dot enzyme immunoassay (EIA) has been developed which detects IgM and IgG antibodies to a specific 50 kDa outer membrane protein on Salmonella typhi. This study was performed among outpatients attending the university hospital in Kelantan, a state on the east coast of Peninsular Malaysia where typhoid is endemic. The dot EIA was done on 149 outpatients of all ages in whom typhoid was suspected. Of these, 60 were not analysable due to insufficient data. The other 89 were retrospectively classed as typhoid (total = 21), or not typhoid (total = 68). The criteria for diagnosis of typhoid was either, blood culture was positive, or with blood culture negative, temperature was at least 38 degrees C and Widal O and/or H titer greater than or equal to 1/160. We then compared the diagnosis with the EIA result. For the result where either IgM or IgG was positive, sensitivity was 90%, specificity 91% and negative predictive value 97%. For IgM positive, specificity was 100%. But the specificity of IgG positive alone was reduced by six false positives, which were probably due to persistence of IgG after acute infection. Other cases were found where IgG positive alone appeared in the first week of typhoid fever, probably due to rapid response in a second or subsequent infection. We also found that IgM-producing patients were significantly younger than those showing IgG alone positive.
Study site: Community Medicine clinic, Accident & emergency department, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia

Matched MeSH terms: Typhoid Fever/diagnosis*
A serological survey of scrub, tick, and endemic typhus in Sabah, East Malaysia

Taylor AC, Hii J, Kelly DJ, Davis DR, Lewis GE

Southeast Asian J. Trop. Med. Public Health, 1986 Dec;17(4):613-9.
PMID: 3107139

A seroepidemiological survey of 837 people and 383 febrile patients was performed in rural areas of Sabah. We determined that the rickettsial diseases scrub typhus and endemic typhus were uncommon causes of febrile illness, as was tick typhus, except in forest dwelling peoples. The rate of occurrence of SFGR specific antibody was 16.5% among 412 forest dwellers, indicating that tick typhus may be a frequent cause of illness in this population.

Matched MeSH terms: Rocky Mountain Spotted Fever/diagnosis
Further evaluation of a multiplex PCR for differentiation of Salmonella paratyphi A from other salmonellae

Teh CS, Chua KH, Puthucheary SD, Thong KL

Jpn J Infect Dis, 2008 Jul;61(4):313-4.
PMID: 18653978

Salmonella enterica serovar Paratyphi A is a causative agent of paratyphoid fever. The clinical syndrome caused by paratyphoid fever overlaps with other febrile illnesses and cannot be distinguished from typhoid fever. Conventional methods used for diagnosis are time consuming, costly, and labor-intensive. We evaluated the specificity, sensitivity, and application of a multiplex polymerase chain reaction (PCR) previously developed by the method (Ou, H.Y., Teh, C.S.J., Thong, K.L., et al., J. Mol. Diagn., 9, 624-630, 2007) using 6 S. Paratyphi A, 22 S. Typhi, and 85 other Salmonella serovars as well as 36 non-Salmonella strains. The detection limit of the multiplex PCR was 4 x 10(4) cfu ml(-1). In a blind test of the other 50 strains, this multiplex PCR correctly identified the only S. Paratyphi A in the panel of strains. The sensitivity of this PCR using spiked blood and stool samples was 1 x 10(5) cfu ml(-1) and 2 x 10(5) cfu ml(-1), respectively, but increased to 1 x 10(4) cfu ml(-1) and 2 x 10(3) cfu ml(-1) after 5-h enrichment. We believe that this multiplex PCR is a promising technique for the specific and sensitive detection of S. Paratyphi A in clinical, environmental, and food samples.

Matched MeSH terms: Paratyphoid Fever/diagnosis*
Fulltext Invasive Salmonella infections among children in Bintulu, Sarawak, Malaysian Borneo: a 6-year retrospective review

Mohan A, Munusamy C, Tan YC, Muthuvelu S, Hashim R, Chien SL, et al.

BMC Infect Dis, 2019 Apr 18;19(1):330.
PMID: 30999894 DOI: 10.1186/s12879-019-3963-x

BACKGROUND: Invasive Salmonella infections result in significant morbidity and mortality in developing countries. In Asia, typhoid and paratyphoid fever are reported to be the major invasive Salmonella infections, while invasive non-typhoidal Salmonella (iNTS) infections are believed to be uncommon. Data from Sarawak, in Malaysian Borneo, are limited.
METHODS: A retrospective study identifying all children aged fever. The average annual iNTS incidence was 32.4 per 100,000 children aged fever without a source, septic arthritis and meningitis. Salmonella Enteritidis was identified in 76% of those with pneumonia, significantly more frequently than in children with other manifestations. Over 25% of children with iNTS developed severe disease and nearly 10% suffered long term morbidity or mortality. While 78% of Salmonella Java isolates were multi-drug resistant, nearly all other isolates were susceptible to most antimicrobials, including ampicillin.
CONCLUSIONS: Bintulu Division in Sarawak observed a very high incidence of childhood iNTS infections. Enteric fever was uncommon. The epidemiology of invasive Salmonella infections in Malaysian Borneo differs considerably from that of neighbouring countries in Asia.

Matched MeSH terms: Typhoid Fever/diagnosis
Differential Diagnosis of Flavivirus Infections in Horses Using Viral Envelope Protein Domain III Antigens in Enzyme-Linked Immunosorbent Assay

Piyasena TBH, Setoh YX, Hobson-Peters J, Prow NA, Bielefeldt-Ohmann H, Khromykh AA, et al.

Vector Borne Zoonotic Dis, 2017 12;17(12):825-835.
PMID: 29083957 DOI: 10.1089/vbz.2017.2172

In Australia, infection of horses with the West Nile virus (WNV) or Murray Valley encephalitis virus (MVEV) occasionally results in severe neurological disease that cannot be clinically differentiated. Confirmatory serological tests to detect antibody specific for MVEV or WNV in horses are often hampered by cross-reactive antibodies induced to conserved epitopes on the envelope (E) protein. This study utilized bacterially expressed recombinant antigens derived from domain III of the E protein (rE-DIII) of MVEV and WNV, respectively, to determine whether these subunit antigens provided specific diagnostic markers of infection with these two viruses. When a panel of 130 serum samples, from horses with known flavivirus infection status, was tested in enzyme-linked immunosorbent assay (ELISA) using rE-DIII antigens, a differential diagnosis of MVEV or WNV was achieved for most samples. Time-point samples from horses exposed to flavivirus infection during the 2011 outbreak of equine encephalitis in south-eastern Australia also indicated that the rE-DIII antigens were capable of detecting and differentiating MVEV and WNV infection in convalescent sera with similar sensitivity and specificity to virus neutralization tests and blocking ELISAs. Overall, these results indicate that the rE-DIII is a suitable antigen for use in rapid immunoassays for confirming MVEV and WNV infections in horses in the Australian context and warrant further assessment on sensitive, high-throughput serological platforms such as multiplex immune assays.

Matched MeSH terms: West Nile Fever/diagnosis
Fulltext Rapid testing requires clinical evaluation for accurate diagnosis of dengue disease: A passive surveillance study in Southern Malaysia

Ngim CF, Husain SMT, Hassan SS, Dhanoa A, Ahmad SAA, Mariapun J, et al.

PLoS Negl Trop Dis, 2021 05;15(5):e0009445.
PMID: 34014983 DOI: 10.1371/journal.pntd.0009445

BACKGROUND: Dengue fever is the most common mosquito-borne infection worldwide where an expanding surveillance and characterization of this infection are needed to better inform the healthcare system. In this surveillance-based study, we explored the prevalence and distinguishing features of dengue fever amongst febrile patients in a large community-based health facility in southern peninsular Malaysia.
METHODS: Over six months in 2018, we recruited 368 adults who met the WHO 2009 criteria for probable dengue infection. They underwent the following blood tests: full blood count, dengue virus (DENV) rapid diagnostic test (RDT), ELISA (dengue IgM and IgG), nested RT-PCR for dengue, multiplex qRT-PCR for Zika, Chikungunya and dengue as well as PCR tests for Leptopspira spp., Japanese encephalitis and West Nile virus.
RESULTS: Laboratory-confirmed dengue infections (defined by positive tests in NS1, IgM, high-titre IgG or nested RT-PCR) were found in 167 (45.4%) patients. Of these 167 dengue patients, only 104 (62.3%) were positive on rapid diagnostic testing. Dengue infection was significantly associated with the following features: family or neighbours with dengue in the past week (AOR: 3.59, 95% CI:2.14-6.00, p<0.001), cutaneous rash (AOR: 3.58, 95% CI:1.77-7.23, p<0.001), increased temperature (AOR: 1.33, 95% CI:1.04-1.70, p = 0.021), leucopenia (white cell count < 4,000/μL) (AOR: 3.44, 95% CI:1.72-6.89, p<0.001) and thrombocytopenia (platelet count <150,000/μL)(AOR: 4.63, 95% CI:2.33-9.21, p<0.001). Dengue infection was negatively associated with runny nose (AOR: 0.47, 95% CI:0.29-0.78, p = 0.003) and arthralgia (AOR: 0.42, 95% CI:0.24-0.75, p = 0.004). Serotyping by nested RT-PCR revealed mostly mono-infections with DENV-2 (n = 64), DENV-1 (n = 32) and DENV-3 (n = 17); 14 co-infections occurred with DENV-1/DENV-2 (n = 13) and DENV-1/DENV-4 (n = 1). Besides dengue, none of the pathogens above were found in patients' serum.
CONCLUSIONS: Acute undifferentiated febrile infections are a diagnostic challenge for community-based clinicians. Rapid diagnostic tests are increasingly used to diagnose dengue infection but negative tests should be interpreted with caution as they fail to detect a considerable proportion of dengue infection. Certain clinical features and haematological parameters are important in the clinical diagnosis of dengue infection.

Matched MeSH terms: Fever/diagnosis
Ongoing outbreak of an acute muscular Sarcocystis-like illness among travellers returning from Tioman Island, Malaysia, 2011-2012

Esposito DH, Freedman DO, Neumayr A, Parola P

Euro Surveill, 2012 Nov 08;17(45).
PMID: 23153473

As of 4 November, 2012, 100 patients with an acute muscular Sarcocystis-like illness associated with travel to Tioman Island, Malaysia, have been identified. Thirty-five travelled there mostly during July and August 2011 and 65 mostly during July and August 2012, suggesting an ongoing outbreak. Epidemiological investigations are ongoing. Public health agencies and practicing clinicians should be aware of this rarely-reported disease in humans and consider it as differential diagnosis in travellers returning from Tioman Island.

Matched MeSH terms: Fever/diagnosis
Clinical prognostic factors and survival outcome in renal cell carcinoma patients--a malaysian single centre perspective

Yap NY, Ng KL, Ong TA, Pailoor J, Gobe GC, Ooi CC, et al.

Asian Pac J Cancer Prev, 2013;14(12):7497-500.
PMID: 24460324

BACKGROUND: This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms.
MATERIALS AND METHODS: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis.
RESULTS: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, 9.5±4.3cm, was larger than non palpable masses, 5.3±2.7cm (p<0.001).
CONCLUSIONS: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.

Matched MeSH terms: Fever/diagnosis*
Longevity of antibody responses to a Salmonella typhi-specific outer membrane protein: interpretation of a dot enzyme immunosorbent assay in an area of high typhoid fever endemicity

Choo KE, Davis TM, Ismail A, Ong KH

Am J Trop Med Hyg, 1997 Dec;57(6):656-9.
PMID: 9430522

The objective of this study was to investigate the longevity of positive dot enzyme immunosorbent assay (dot EIA) results for IgM and IgG to a Salmonella typhi outer membrane protein in Malaysian children with enteric fever. The patients were children one month to 12 years of age with clinical evidence of typhoid fever, positive blood or stool cultures for S. typhi, and/or a positive Widal test result who were admitted over a two-year period to General Hospital (Kota Bharu, Malaysia). These patients received standard inpatient treatment for enteric fever including chloramphenicol therapy for 14 days. Dot EIA tests were performed as part of clinical and laboratory assessments on admission, at two weeks, and then at 3, 6, 9, 12, 15, 18, and 21 months postdischarge. Assessment of the longevity of positive dot EIA IgM and IgG titers was done by Kaplan-Meier analysis. In 94 evaluable patients, 28% were dot EIA IgM positive but IgG negative on admission, 50% were both IgM and IgG positive, and 22% were IgM negative and IgG positive. Mean persistence of IgM dot EIA positivity was 2.6 months (95% confidence interval = 2.0-3.1 months) and that of IgG was 5.4 months (4.5-6.3 months). There were no significant differences between the three subgroups. Thus, positive IgM and IgG results determined by dot EIA within four and seven months, respectively, following documented or suspected enteric fever in a child from an endemic area should be interpreted with caution. In other clinical situations, the dot EIA remains a rapid and reliable aid to diagnosis.

Matched MeSH terms: Typhoid Fever/diagnosis*
Macrophage activation syndrome as an initial presentation of systemic lupus erythematosus with sensorineural hearing loss in a young male patient

Tan CL, Yahaya MH, Ahmad NS, Lim CH

BMJ Case Rep, 2020 Mar 12;13(3).
PMID: 32169986 DOI: 10.1136/bcr-2019-233330

An 18-year-old male adolescent presented with prolonged high spiking temperature, photosensitive rash, oral ulcers and reduced hearing bilaterally of recent onset. Examination revealed malar rash, vasculitis rash over bilateral palms and soles, oral and buccal ulcers, palpable posterior auricular and inguinal lymph nodes, and reduced hearing bilaterally. His further investigations noted pancytopaenia, elevated transaminases, hyperferritinaemia, low C3 and C4 levels, positive antinuclear antibody, double-stranded DNA and direct Coombs test, while bone marrow aspiration revealed active phagocytic activity suggestive of hemophagocytic syndrome. We made a diagnosis of systemic lupus erythematosus with macrophage activation syndrome. We treated him with pulse intravenous methylprednisolone and his condition improved drastically. Temperature resolved on the next day after intravenous methylprednisolone; bilateral sensorineural hearing loss improved to near-normal hearing after treatment. He remained well during follow-up with a tapering dose of prednisolone.

Matched MeSH terms: Fever/diagnosis

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