Public Health Fellowship Program – Field Epidemiology Track

Typhoid Over diagnosis in District, June 2016

Dr. Kusiima Joy, MBChB-MHSR Fellow,2016

Typhoid Alert

May June 2016 2016 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Notification Data Audit ,12 health Reviewed HMIS data facilities Nakaseke 84 cases/ 50,000 by FFETP(wk 15-21) Typhoid Outbreak verification exercise 323 Typhoid cases reported 2

Typhoid verification in

Objectives

. Verify the existence of an outbreak . Verify reported diagnosis using standard case definition . Recommend public health action

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Typhoid verification in Nakaseke District District location

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Typhoid verification in Nakaseke District Facilities selected

. Private hospital - . Government hospital - Nakaseke . Health center IV - . Health center III -

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Typhoid verification in Nakaseke District Data collection

. Extracted records from registers (1st/12/ 2015 to 14th/06/2016) . Discussed with clinicians & lab personnel . Took clinical history &examined typhoid suspects

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Typhoid verification in Nakaseke District Standard case definition

. Suspected case: Onset of fever ≥3days,negative malaria test, resident of Nakaseke district Plus any of following: chills, malaise, headache, sore throat, cough, abdominal pain, constipation, diarrhea . Probable case: Suspected case plus positive antigen test (Widal) . Confirmed case: Suspected case plus salmonella typhi (+) blood or stool by culture

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Typhoid verification in Nakaseke District Data quality assessment

. Reviewed laboratory testing procedures . Reviewed data capture &recording procedures . Took samples for blood culture at CPHL

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Typhoid verification in Nakaseke District 80% of typhoid diagnoses were clinical

Variable Frequency (n) Percent (%) Patient category Admitted 18 1.7 Outpatient 1007 98.2 Basis of diagnosis & treatment Blood culture 0 0 Clinical diagnosis 829 81.2 Clinical+ widal test 192 18.8 Matching case definition** case definition 5 27.8 case definition did not match 13 72.2

** only admitted , N=1025 9

Typhoid verification in Nakaseke District Highest attack rates among females/per 1000

7 6.3 6

5 4.6

4 Rate/1000 3.1 persons 3

2

1

0 Males Females Total Gender 10

Typhoid verification in Nakaseke District Highest attack rate in Nakaseke subcounty

12 11.2 10 7.8 8 6.7 Rate/1000 6 persons 3.7 4 3.3 3 2 0.6 0.6 0.3 0.2 0.1 0

Subcounties

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Typhoid verification in Nakaseke District No clear pattern over time

Rainy season Rainy season Dry season

Investigation

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Typhoid verification in Nakaseke District More cases reported in 2016 vs 2015

300 281

250

200

152 Cases 150 2015 127 121 2016 97 100 73

50

0 Kiwoko Nakaseke Semuto Health facility 13

Typhoid verification in Nakaseke District No capacity to confirm typhoid at district

. Typhoid screening done using antigen/antibody reagent. . High 0 titers (1:160) supports diagnosis . Lower level facilities have no screening reagents . All 5 samples negative on blood culture . None of the reviewed records recorded a perforation

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Typhoid verification in Nakaseke District Conclusions

. Available evidence not sufficient to support presence of outbreak in the district . Over diagnosis of typhoid highly suspected . Typhoid diagnosis based on typhoid titre and clinical symptoms

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Typhoid verification in Nakaseke District Public health implications

. Wastage of resources (personnel,supplies,time) . Antibiotics over prescription posing threat to antibiotic resistance . Typhoid over diagnosis likely to lead to delay of true diagnosis

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Typhoid verification in Nakaseke District Recommendations

. Strengthen capacity district laboratories to preform culture& sensitivity. . Proactive measures to engage clinicians in typhoid surveillance . Continuous Quality Improvement project to improve typhoid diagnosis and reporting

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Typhoid verification in Nakaseke District Public Health Fellowship Program – Field Epidemiology Track

Acknowledgment

. Local Government, Nakaseke district . In charges of health facilities . PHFP secretariat . CDC . FFETP

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Typhoid verification in Nakaseke District Comparison of typhoid cases vs Nakaseke (between 2014 -2016)

14000 12000 10000 8000 6000 Nakaseke District 4000 2000 0 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 2014 2014 2014 2014 2015 2015 2015 2015 2016 2016 2016

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Typhoid verification in Nakaseke District Reporting rates in Nakaseke

Reporting rate in Nakaseke 2014-2015 100 90 83.7 86.2 80 75.3 75.6 72.4 70.5 70.5 69.9 67.6 66.7 70 61.2 60 50 40 30 20 10 0 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 2014 2014 2014 2014 2015 2015 2015 2015 2016 2016 2016 21

Typhoid verification in Nakaseke District No clear pattern in Nakaseke sub county

9 8 7 6 5 Cases 4 3 2 1

0

06-Apr-16 18-Apr-16 30-Apr-16

13-Jan-16 25-Jan-16 01-Jan-16 05-Jun-16 17-Jun-16 29-Jun-16

06-Feb-16 18-Feb-16 01-Mar-16 13-Mar-16 25-Mar-16

14-Nov-15 26-Nov-15 08-Dec-15 20-Dec-15

12-May-16 24-May-16 Reporting date 22

Typhoid verification in Nakaseke District Typhoid diagnosis

. The definitive diagnosis of typhoid fever depends on the isolation of S. typhi from blood, bone marrow or a specific anatomical lesion. . Presence of clinical symptoms characteristic of typhoid fever or the detection of a specific antibody response is suggestive of typhoid fever but not definitive. . Blood culture is the mainstay of the diagnosis of this disease.

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Typhoid verification in Nakaseke District Chronic carriers . Defn: Excretion of S. typhi in stools for >1yr after the onset of acute typhoid fever (or repeated positive bile or duodenal string cultures). . Burden of carrier state: 1-5% . Epidemiological role of chronic carriers not as important as that of chronic . Some patients excreting S. typhi have no history of typhoid fever.

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Typhoid verification in Nakaseke District Blood culture is definitive but bone marrow is standard . Reasons for failure to isolate organism from blood - Limitations of laboratory media - Presence of antibiotics : - Volume of the specimen cultured; -Time of collection, - Duration of fever fever* 7 to 10 days more likely than others to have a positive blood culture. - Without antibiotics blood cultures are positive in > 80% of the patients in 1st wk illness. - 20%-30% of untreated patients positive blood cultures late as the third week of illness . Bone marrow aspirate is gold standard 25

Typhoid verification in Nakaseke District Widal has limited sensitivity and specificity

. Dependent on O and H surface antigens . O and H antigens shared with other salmonella species increasing likelihood of false positive . False positive results may occur in other clinical conditions, e.g. malaria, typhus, bacteraemia caused by other organisms, and cirrhosis.

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Typhoid verification in Nakaseke District Interpretation of results dependent

. Two tests recommended (acute and convalescent phase) a four fold increase may be diagnostic of typhoid. . Need to establish threshold titre levels in the community.

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Typhoid verification in Nakaseke District Upcoming new diagnostics

New test Basis of test Comment IDL Tubex IgM 09 O9 only found in salmonella typhi Typhidot IgM and IgG Detects acute and ongoing infection Typhidot M IgM Detects acute infection . High sensitivity(>93%) High negative predicative value IgM dipstick test

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Typhoid verification in Nakaseke District