JOURNAL CLUB

Dr.Santosh Reddy
 Using Clinical Profiles and Complete Blood Counts to
Differentiate Causes of Acute Febrile Illness

• Source - Journal of Tropical Pediatrics.

• Published Volume 66, Issue 5, October 2020,
 Introduction
• Dengue viral infection (DVI) is endemic in Thailand, and with no
specific treatment, early diagnosis, quick detection of plasma leakage
and appropriate supportive care are the most important steps to
prevent potentially serious complications. Early and accurate
diagnosis is also desirable in typhoid fever, as prompt treatment can
reduce serious complications in 10–15% of cases, and mortality in 1–
4% .
• During 2009–11, there were concurrent typhoid and chikungunya
(CHIK) outbreaks in Songkhla province, Thailand. When the outbreaks
had subsided, an effort was made to determine if the clinical profiles
and complete blood counts of the outbreak patients could reliably
differentiate these diseases from DVI or other acute febrile illnesses
(AFIs) before laboratory confirmation to enable prompt treatment in
future outbreaks.
• DVI, CHIK and typhoid can present with similar symptoms in the early stages,
thus timely and accurate differentiation between these diseases in a situation
where these diseases are endemic is quite difficult.
• Patients with typhoid fever can present with high fever, hepatomegaly,
leukopenia and/or thrombocytopenia, which are also common in DVI .
However, clinical and laboratory profiles of these diseases vary at different
time points of illness; for example, with DVI, thrombocytopenia and
leukopenia will develop after day 3 of fever and hepatomegaly in typhoid
fever will be found after the first week of illness. Fever with rash, myalgia and
arthralgia is common in CHIK, but are also included in clinical criteria of DVI
according to the WHO 1997 and 2009.
•The WHO 1997 criteria for The WHO 2009 criteria for DVI are
DVI are 2/7 of the following: 2/6 of the following:
Headache, retro-orbital pain, myalgia or

Headache, arthralgia,

Retro-orbital pain, Rash,
Nausea or vomiting,

Myalgia, Positive tourniquet test (TT),

Arthralgia, Leukopenia,
One of the seven warning signs

Rash, 1.Abdominal pain or tenderness,
2.Persistent vomiting,

Bleeding disorder and 3.Clinical fluid accumulation,


4.Mucosal bleeding,
Leucopenia. 5.Lethargy or restlessness,
6.Liver enlargement >2 cm and
7.Increase in hemoconcentration with rapid decrease
in platelet count.
 Place, Duration, Type of study
• Patients aged 2–15 years having fever on first visit < 3 days
without localizing signs who visited Songkhla Hospital during
the typhoid and CHIK outbreaks in Songkhla province during
2009–11 were enrolled retrospectively.
 Objectives

• To use complete blood counts and clinical profiles to differentiate DVI,

CHIK, Typhoid Fever, Other AFI’s to facilitate earlier specific treatment.
Methods
• Typhoid fever was confirmed by hemoculture,
• Dengue viral infection (DVI), by nonstructural protein-1 or polymerase
chain reaction (PCR),
• Chikungunya (CHIK) by PCR.
• Febrile children with negative results for these infections were classified
as other acute febrile illness (AFI).
• They found as in previous studies that the WHO 1997 criteria of DVI had lower
sensitivity and higher specificity than the WHO 2009 criteria to differentiate
DVI from other AFIs. However, they found that during the Songkhla CHIK
outbreak, both the WHO 1997 and WHO 2009 criteria had low specificity and
PPV to diagnose DVI, since the majority of CHIK patients had
arthralgia/myalgia/headache or rash, which are also in the criteria for
diagnosis of DVI.
• They found that arthralgia was uncommon in children with DVI, unlike adult
studies which have reported that two-thirds of DVI cases had arthralgia.
Therefore, in children, they concluded that arthralgia is a good sign to
differentiate CHIK from DVI in children old enough to talk about pain.
• Thrombocytopenia is more commonly found in DVI than the other AFIs

• They found that during the first 3 days of fever only 23% of the DVI group
had thrombocytopenia.

• In general, the platelet count decreases 1 day prior to the toxic phase, or
around fever days 4–5.
• During the first 3 days of fever, leukopenia was more helpful than
thrombocytopenia in differentiating DVI from other AFIs.
• Patients who had leukopenia with a positive TT had increased likelihood
of DVI
An algorithm to differentiate CHIK, DVI and
typhoid from other AFIs

• They found that arthralgia had sensitivity (0.96), specificity (0.97), PPV
(0.80) and negative predictive value (0.99) (NPV) to differentiate CHIK
from the other three groups.
• Children who did not have arthralgia but had headache, myalgia or
leukopenia were more likely to have DVI with sensitivity of 0.84,
specificity of 0.76 and PPV of 0.92.
• Children who did not have arthralgia, headache, myalgia or leukopenia,
but had one of abdominal pain, diarrhea or body temperature >39.5C
were more likely to have typhoid fever than one of the other AFIs with
sensitivity, specificity and PPV of 0.95, 0.50 and 0.90, respectively
Algorithm chart to differentiate chikungunya (CHIK), dengue viral infection (DVI) and typhoid fever from
other acute febrile illnesses (AFIs).
 Results
• Of the 264 cases,
• Typhoid fever (56), DVI(164), CHIK(25), AFI (19).
• Arthralgia had sensitivity, specificity, positive predictive value (PPV) and
negative predictive value of 0.96, 0.97, 0.80 and 0.99, respectively, to
differentiate CHIK from the others.
• After excluding CHIK by arthralgia, the PPV of the WHO 1997 and 2009
criteria for DVI increased from 0.65 and 0.73 to 0.95 and 0.84, respectively.
• Children with one of myalgia, headache or leukopenia had sensitivity of 0.84,
specificity of 0.76 and PPV of 0.92 to differentiate DVI from typhoid and other
AFIs. Patients with one of abdominal pain, diarrhea or body temperature
>39.5C were more likely to have typhoid fever than another AFI with PPV of
0.90.
Limitations of the Study
• This study had the unavoidable limitations commonly found in
retrospective studies, especially missing data and notably TT data
were missing in most of the non dengue cases.
• Most importantly, the described algorithm has limited use in children
who cannot accurately describe whether or where they have pain.
• The study was also a hospital-based surveillance study which cannot
be used to represent true disease burden.
Conclusion

• Using the above flow chart can help direct physicians to perform more
specific tests to confirm the diagnosis and provide more specific
treatment. Nevertheless, clinical follow-up is the most important tool
in unknown causes of febrile illness.
Thank You