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L. Wijedoru1, V. Kumar2, N. Chanpheaktra2, K. Chheng2, H. Smits3, R. Pastoor3,
S. Baker4, S. Peacock5, V. Wuthiekanun5, H. Putchhat6, C. Parry7
1Child
and Reproductive Health Group, Liverpool School of Tropical Medicine (LSTM), UK, 2Paediatrics, Angkor Hospital for Children (AHC), Siem Reap, Cambodia, 3Rapid Diagnostics, Royal Tropical Institute (KIT),
Amsterdam, The Netherlands, 4Microbiology, Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam, 5Microbiology, Mahidol Oxford Tropical Medicine Unit (MORU), Bangkok, Thailand 6Laboratory
Services, Angkor Hospital for Children, Siem Reap, Cambodia, 7School of Infection and Host Defence, University of Liverpool, UK
•Differentiating bacterial infections that require antibiotics, from
common viral and parasitic causes in febrile children is often difficult
in low-resource settings (LRS) (Maitland, 2010).
To estimate the proportion of febrile children admitted to AHC that have TF.
•Angkor Hospital for Children (AHC) serves a rural population of
northern Cambodia at risk of febrile illnesses including malaria,
dengue, rickettsiosis, leptospirosis, and melioidosis.
•Cross-sectional descriptive study between April and June 2009.
•Typhoid (enteric) fever (TF) is a disease caused by Salmonella
Typhi (ST) affecting an estimated 13 million people annually in Asia,
of which a large proportion are children (Bhutta, 2008).
•Blood culture sensitivity in diagnosing TF is only 40-60%, despite
being the current gold standard. TF is often diagnosed clinically.
•Rapid diagnostic tests (RDTs) can lead to timely and appropriate
treatment, and rational prescription of drugs such as antibiotics.
•An IgMFA developed by the Royal Tropical Institute (Netherlands)
has shown to correspond with clinical pictures of TF in Indonesia
despite negative blood cultures (Pastoor et al., 2008).
•All children (< 16 years) admitted to either the in-patient department (IPD) or intensive
care unit (ICU) with a history of fever, and a documented temperature of ≥38⁰C within
the first 48 hours of admission, were eligible.
•Clinical data (history and examination) was collected.
•ST-specific NAATs (PCR and 16S-RA) + blood culture were performed on admission.
•5 microlitres of patient serum (from venous blood) was mixed with 130 microlitres of
manufacturer buffer solution on admission (Sample A).
• A second serum sample was obtained on discharge or on Day 10 of fever (Sample B).
•IgMFA results were classed as: negative, +1, +2, or +3 (as per manufacturer).
Investigations on Admission
The IgMFA RDT appears more sensitive than blood culture and
nucleic acid amplification tests (NAATs). ST-specific IgM
responses appear less affected by the factors contributing to
low blood culture sensitivity in children, such as culture
volume, pre-treatment with antibiotics, and laboratory quality.
Routine investigations
Blood Count + Film
Liver and Renal Function
C-Reactive Protein
Microbiology
Nucleic Acid Amplification
Tests (NAATs)
Polymerase Chain Reaction
16-S Ribosomal Amplification
Blood Culture
(minimum 2ml)
Serology
Sample A
ST-specific IgM lateral
flow assay (IgMFA)
On Discharge or on Day 10 of fever
(whichever was the earlier)
Laboratory Evidence
of TF (I34 Patients)
Serology
Sample B
ST-specific IgM lateral flow assay (IgMFA)
18 Suspected TF
patients
NAAT
positive only
•Five (3.7%) were confirmed typhoid cases (ST isolated from blood),
•Eighteen (13.4%) were suspected cases (positive admission and/or discharge IgM
serology and/or positive NAATs)
•Eight (6.6%) were possible cases (appropriate clinical picture but all negative tests).
Positive on
both NAAT
and IgMFA
•Twelve out of the twenty-one IgMFA positive patients (57.1%) had a rise in IgM titre,
strongly suggestive of acute TF seroconversion.
•Only four patients in total were positive by NAAT. Two of these were IgMFA positive.
IgMFA
positive only
Confirmed
Suspected
Possible
Non-TF
IgMFA Sample A
Day of Fever
(Sample A)
IgMFA Sample B
Day of Fever
(Sample B)
1+
1+
1+
4+
1+
3+
1+
3+
3+
1+
1+
1+
7
1
7
2
3
5
12
4
10
2
6
3
6
3
7
4
5
4
1+
1+
1+
2+
2+
2+
4+
1+
3+
1+
3+
1+
3+
1+
2+
2+
10
6
10
5
6
10
14
7
12
5
10
5
8
6
10
7
7
8
NAAT
Polymerase
Chain Reaction
(PCR)
+
+
-
NAAT
16S Ribosomal
Amplification
(16SRA)
+
-
Confirmed Case
Serovar
NAAT
(16SRA or
PCR)
IgMFA
(Sample A)
Day of Fever
(A)
IgMFA
(Sample B)
Day of
Fever (B)
1
Typhi
-
2+
6
3+
10
2
Typhi
-
3+
6
4+
10
3
Typhi
-
2+
3
3+
10
4
Typhi
+
(PCR)
3+
7
3+
10
5
Typhi
-
4+
8
4+
10
One in six (17.1%) of febrile children admitted to AHC had confirmed or suspected TF.
All confirmed cases were positive on IgMFA. IgMFA positivity exceeded that of both blood culture and NAATs.
The value of NAATs for the detection of ST in blood appears limited.
Further evaluation of the assay's specificity is needed among unselected febrile patients in TF endemic areas.
Bhutta, Z A . 2008. Typhoid fever in the developing world: a neglected disease? Acta Tropica. 90(2):211-214
Maitland, K. 2010. Antimicrobials in children admitted to hospital in malaria-endemic areas. British Medical Journal. 340:c1818
Pastoor, R et al 2008. Simple, rapid, and affordable point-of-care test for the serodiagnosis of typhoid fever. Diagnostic Microbiology and Infectious Disease. 61(2): 129-134