Typhoid (Enteric)Fever

1. ENTERIC FEVER: PUBLIC HEALTH RESPONSE
Communicable Disease Control (CDC) Programme
Directorate: Service Priority Coordination
January 2022

2. Outline
• Introduction
• Epidemiology
• Transmission
• Clinical Presentation
• Case Definitions
• Laboratory Confirmation
• Differential Diagnosis
• Treatment
• Public Health Response
• Prevention and Control
• Enteric Fever Clusters, 2016-2017
• Challenges
• Resources
• Conclusion

3. Introduction
• Typhoid Fever is also known as enteric fever
• Systemic infection caused by Salmonella Typhi and Salmonella Paratyphi A, B
or C
• Found only in humans
• World estimates: 11 - 20 million cases with ~130 000 – 160 000 deaths each
year
• Incidence is highest in developing countries: Asia and Africa
• Enteric fever is endemic within South Africa
• Epidemic potential - Delmas (MP)
– More than 1000 cases in 1993
– More than 400 suspected cases & 3 deaths in 2005

4. Epidemiology
Closely associated with poor food
hygiene, & inadequate water &
sanitation infrastructures
Risks in developing countries
• school-aged children (5-15 years) are most
frequently affected
Risks in industrialised countries
• travellers make up a large proportion of
cases
• observed in older age groups
Mixed pattern in South Africa
• Mostly endemic disease with potential for
large scale epidemics
• Sporadic cases in more industrialised areas
of the country
• Travellers (local and international) returning
from areas with endemic transmission
Occupation
• food handlers
• those who provide care for patients, children
or the elderly
• high-risk groups due to their potential to
widely transmit infection
Socio-economic factors
• a disease of poverty

5. Transmission
Incubation period usually 9 – 21 days (range 3 – 60 days)
Hosts = humans
Faecal-oral route
• Bacteria are shed in the faeces of an infected person
• Person-to-person transmission via ingestion of contaminated food or water
Contamination of food can occur through:
• food handlers
• irrigation of gardens/crops with sewage-contaminated water or fertilizers
• sharing of food items
Contamination of water can occur through:
• Surface waters (rivers, dams etc.) contaminated with sewage
• Inadequately treated piped water which was contaminated by sewage
• Contamination of a household water source by an infected person (e.g. contamination of water
stored in a bucket/container in the household)

6. Clinical Presentation (1)
Acute enteric fever
Systemic illness characterised by:
• Fever
• Headache
• Malaise
• Gastrointestinal symptoms
• Abdominal pain/cramps
• Nausea and vomiting
• Constipation or diarrhoea
• Rash (rose spots) – uncommon in dark-skinned persons
• Dry cough

7. Clinical Presentation (2)
Case fatality rate
• Depends on presence of complications + timeliness of
antimicrobial intervention
• Untreated death rate ~ 10 - 20%
• With appropriate treatment ~2,5%
Severe illness:
• In ~ 17-27% of hospitalised patients
• GIT: perforation, bleeding
• Septic shock
Extra-intestinal complications:
• Brain – encephalopathy, meningitis
• Liver – hepatitis
• Renal system – nephritis
• Bones and joints – arthritis
• Lungs – pneumonia

8. Laboratory Investigations
Acute enteric fever
• Blood culture is the recommended test
Extra-intestinal complications and focal infections
• In patients who presents with extra-intestinal complications e.g. endocarditis, pneumonia, meningitis, arthritis or focal abscesses:
culture of appropriate specimen from the site of the focal infection, in addition to blood cultures
Urine cultures
• not routinely suggested for laboratory diagnosis
Stool cultures
• Usually positive in acute typhoid fever from the second week of illness only.
• Indicated for follow-up of cases after completion of treatment to monitor shedding and document clearance, or to screen for carriage in
contacts
Serology
• Serological tests e.g. the Widal test are not recommended for the diagnosis of typhoid fever
• High rates of false-negative and false-positive results

9. Surveillance and Public Health Response
Case definitions
Laboratory confirmation
Differential Diagnosis
Treatment

10. Case Definitions (1)
Suspected case:
A person presenting with fever for at least three out of seven consecutive
days and symptoms compatible with typhoid fever*
Confirmed case:
Isolation of Salmonella Typhi or Salmonella Paratyphi A, B or C from a
clinical specimen
Probable case (relevant only in outbreaks):
A clinically compatible case that is epidemiologically linked to a confirmed
case
*Symptoms and signs suggestive of typhoid fever include:
• Headache
• Malaise
• Gastrointestinal symptoms (abdominal pain, nausea and vomiting, diarrhoea or
constipation)
• Relative bradycardia,
• ‘Rose spots’ (erythematous maculopapular lesions)
• Splenomegaly and/or hepatomegaly
• Dry cough
• Leukopenia (low white cell count), leucocytosis (high white cell count), anaemia or
thrombocytopenia
• Hepatitis

11. Enteric Fever carriers
Case Definitions (2)
Convalescent carrier Evidence of shedding (positive stool culture) 1–12 months after finishing an appropriate
course of antimicrobial treatment and the resolution of symptoms following a laboratory-
confirmed episode of acute disease.
Definitive (chronic) Evidence of shedding (positive stool culture) at least 12 months after finishing an
appropriate course of antimicrobial treatment and the resolution of symptoms following a
laboratory-confirmed episode of acute disease
OR
Two positive stool samples 12 months apart.
Presumptive carrier Evidence of shedding (positive stool culture) of an unknown duration.

12. Differential Diagnosis
Other causes of an enteric-fever like syndrome
• Other non-typhoidal Salmonella infections
• Yersinia enterocolitica
• Campylobacter fetus
Other causes of febrile illness in returning travellers
• Malaria
• Dengue
• Hepatitis

13. Treatment
Acute uncomplicated enteric fever
>90% of enteric fever patients can be managed with oral antibiotics
• ciprofloxacin
Severe and complicated enteric fever
Patients unable to tolerate oral treatment: hospitalise + iv Rx
• ceftriaxone
Persistent infections and chronic carriers
Must be based on antimicrobial susceptibility testing;
seek expert advice

14. Public Health Response (1)
• Ongoing surveillance, thorough case management, contact tracing and environmental
investigations (food, water and sanitation)
• Training of healthcare workers and stakeholders (especially municipalities and primary health care
facility, and public health officials)
• Cooperation of the various disciplines and sectors to ensure detailed and complete investigations
for single cases, clusters, and outbreaks of enteric fever is essential to contain further spread
• All districts, sub-districts and municipalities are urged to enhance preparedness and response
activities and ensure cases are detected, notified, treated, and investigated i.e., elicit the appropriate
public health response

15. Public Health Response (2)
 If a suspected case is identified (see case definitions), contact the staff member in charge of Infection
Control at your facility
• The official will notify the Local Authority, Department of Health (District and/or Provincial CDC official) via the NMC system (paper-
based or electronic)
 The health facility must complete the patient details and exposure history, and the list of contacts; contained in
the Enteric Fever Case Investigation Form (CIF)
• Indicate critical information w.r.t. the patient’s occupation, place of work, or name of school/creche
 The laboratory (public/private) must inform the health facility (IPC practitioner/ facility manager), the Provincial CDC
Office / District Office of the identification of laboratory confirmed cases
Name Designation Tel/cell/fax Email
1. Ms Charlene A.
Lawrence
Provincial CDC Coordinator 021-483-9964 (tel)
072-356-5146 (cell)
086-6111-092 (fax)
Charlene.lawrence@westerncape.gov.za
2. Ms Babongile Ndlovu Provincial NICD
Epidemiologist
021-483-6878 (tel)
082-327-0394 (cell)
Babongile.Ndlovu@westerncape.gov.za;
babongilen@nicd.ac.za
3. Ms Washiefa Isaacs Provincial NICD NMC
Surveillance Manager
021-483-3737 (tel)
072-310-6881 (cell)
Washiefa.Isaacs@westerncape.gov.za
washiefai@nicd.ac.za
4. Ms Felencia Daniels CDC Administrative Clerk 021-483-3156 (tel) Felencia.Daniels@westerncape.gov.za

16. Public Health Response (3)
 NHLS Microbiology (referral) laboratories
• Keep line list of clearance samples from confirmed enteric fever cases, and screening samples from the contacts
• Provide results to the local authorities, district, province CDC
• Refer all S. Typhi and S. Paratyphi A, B or C isolates to the Centre for Enteric Diseases, NICD for whole-genome sequencing
 All clusters/outbreaks (two or more epidemiologically linked suspected or confirmed cases) must be immediately
notified to the health authorities for investigation and response
• Coordination of response by the local level DOH with intersectoral stakeholders/disciplines (e.g., District, Provincial and National
DOH: CDC, Environmental Health/municipalities, Infection Control, NHLS Diagnostic laboratories, private laboratories, NICD).
• Guidance on surveillance/screening and investigations will be provided.
• Thorough investigations are critical in containing the disease and preventing further cases.
• Districts/sub-districts/health facilities must utilize various mitigation measures to ensure the required public health responses are
elicited

17. Public Health Response (4)
Single Case
 Confirm diagnosis
 Notify the Department of Health
 Review case management and treatment
 Interview the case – complete the CIF
 Educate the case and caregivers (hand hygiene,
safe water and sanitation practice, food safety
practice)
 Case follow-up (3 clearance stool samples after
completion of antibiotic treatment))
 Contact management
• 1 screening stool/rectal swab sample
– Any positive culture/s: treat as case
Clusters and Outbreaks
 Confirm cluster/outbreak
 Notify the Department of Health
 Case finding, investigations and follow-up, including
CIFs, line listing
 Case management and treatment
 Conduct environmental investigations
 Control and prevention
• Health promotion, health education

18. Single Case
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19. 19
Single Case
1. Confirmed the diagnosis  Verify laboratory results and patient details
o For diagnostic support, contact the relevant microbiology laboratory
2. Notify the Department of
Health
 Notify the Local Authority, and Department of Health using the NMC (Notifiable Medical Condition)
o Complete the notification (paper-based form / electronic platform) and forward to the local authorities for
investigation, attach the laboratory report if available.
o Complete the CIF in detail, that includes the patient detail (occupation, place of work, name of school/creche) and
exposure history
3. Case management and
treatment
 Review Case Management and treatment (see NICD guidelines and quick reference)
o If enteric fever is suspected commence treatment immediately (preferably after collection of blood cultures)
o Ensure the case is receiving the appropriate treatment for enteric fever (Ciprofloxacin for uncomplicated cases and
Intravenous ceftriaxone in severe cases) and any concomitant infections
o Exclude other causes of febrile illness; particularly malaria
4. Interview the case  Interview the patient and complete a case investigation form (CIF) to ascertain risk factors for exposure
sources – send to the Provincial and District Communicable Disease Control and Surveillance focal
o Obtain information on occupation (e.g., food handler, or children/elderly) – should be excluded from activities until 3
consecutive negative cultures
o Information on possible source of infection – perform additional environmental investigations where indicated,
intervene if a source can be identified
5. Educate the case and
caregivers
 Conduct health promotion about enteric fever infection and transmission
o Emphasize the importance of good hygiene practices e.g., handwashing (especially after using the toilet and before
preparing food), safe sanitation and water use, and food safety
6. Case follow-up  Follow-up the patient after treatment with three stool specimens to confirm that s/he is not a carrier

20. Single Case
Case follow-up Follow-up the patient after treatment with three stool specimens to confirm that
s/he is not a carrier
All 3 cultures negative: release from
surveillance
Positive monthly samples after 12
months of repeat sampling: refer
chronic carrier for specialist opinion
and management
Collect 3 clearance stools or rectal swabs one week after treatment
completion (2nd
and 3rd
samples should be collected ≥48 hours
apart)
All 3 cultures negative: release from
surveillance
Any of the 3 cultures positive: consider
retreatment followed by clearance
stools as above
All 3 cultures negative: release from
surveillance
Any of the 3 cultures positive: treat as
convalescent carrier and collect
monthly clearance stools as above
All 3 cultures negative: release from
surveillance
Positive monthly samples: continue
montly stool collection and investigate
causes of prolonged carriage

21. 21
Single Case
7. Contact Management Identify all contacts at risk, and submit a stool specimen/rectal swab for culture to determine carriage
status
 Identify contacts at risk of infection e.g., household members, care givers of the case, and people who
may have eaten the implicated food/water/beverages.
 Response for all contacts at risk of infection
o Collect a stool/rectal swab sample for Salmonella Typhi culture
o Interview all contacts completing the line list at the end of the CIF
o Educate contacts on enteric fever infection, transmission, prevention and recognizing symptoms and
seeking medical care if these occur.
o If any culture is positive, refer that contact for treatment and complete the above steps 1-7 for that
person
o If any laboratory confirmed contacts are employed as food handlers, or caring for patients /
children/elderly, they should be excluded from these activities and re-deployed as far as possible.
o Salmonella Typhi in the absence of clinical illness suggests carriage

22. Cluster / Outbreak
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23. 23
Enteric Fever Cluster / Outbreak:
Two or more epidemiologically-linked suspected or confirmed case
1 Verify the diagnosis and
confirm the existence of an
outbreak
 Conduct laboratory testing on all suspected enteric fever cases
 Conduct preliminary interviews to establish any epidemiological links between cases e.g.,
common place of residence, gatherings, foods consumed, travel, place of work or education
2 Communication  Rapid communication and reporting of information, even preliminary is essential in
responding to potential outbreaks
 Communicate findings frequently to all stakeholders
3 Case finding, investigations and
follow-up including completion
of CIF
 Establish systems for detection and recording of cases e.g., line listing at each local
healthcare facility (clinics, hospital) for monitoring of the outbreak
 Investigate using standardised case definitions and case investigation form – data collected
to be rapidly analysed and shared with stakeholders
4 Review Case management and
treatment
 Ensure all cases are receiving the appropriate treatment for enteric fever and any
concomitant infections to reduce morbidity and mortality.
5 Conduct environmental
investigations
 Where indicated food, water and/or other environmental samples may be collected for
Salmonella Typhi Culture.
 Samples must be sent to the appropriate laboratories that use the correct methods to
identify Salmonella Typhi.
6 Control and prevention  If source can be identified, respond rapidly to interrupt this, and prevent additional
infections.
 Conduct health promotion campaigns on the prevention of enteric fever in the local
community.
 Further guidance on surveillance/screening activities may be recommended that may need
to be implemented locally.

24. Prevention and Control
Public Health
Ensuring access to safe water, food and proper sanitation
• Health promotion and education
• Water monitoring and treatment
• Hygiene
• Provision of proper sanitation infrastructures
Vaccine available
• Laboratory staff working with S. Typhi
• Travellers to highly endemic countries

25. Enteric Fever Clusters, 2016 - 2017
Two enteric fever clusters detected in 2016 in the Cape Town Metro District
• Cluster 1 – Southern Sub-district (August/September 2016)
• Two family members (8-yr & 14yr old cousins) presented at a district hospital, l
• Investigations identified 3 asymptomatic carriers
• All case-contacts provided with treatment
• No environmental source identified, water and sewerage and hygiene at home was
satisfactory
• Cluster 2 – Klipfontein Sub-district (September 2016)
• Two enteric fever cases reported in September 2016 in Athlone where enteric fever
cases was detected from Dec 2015 – April 2016
• Based on molecular testing on cases identified in Sept 2016 – it was related to cases
reported from Jan – March 2016 based on molecular typing
• Investigation identified a possible typhoid carrier – (one of the cases reported in
September was a previous case), The carrier was treated
• No environmental source was identified
One enteric fever cluster detected in 2017 in the Cape Winelands District
• Cluster 3 – Drakenstein Sub-district (Cape Winelands District) – Mbekweni, 2017
• 13 confirmed enteric fever cases were identified from 1 Nov 2016 - 23 June 2017, On
30 March 2017, a cluster of 5 enteric fever cases were identified. Further investigations
identified 2 additional cases. Extended families on two properties included 26 people
on one property and 19 on the other.
• Health Promotion activities on diarrhoea, enteric fever and hygiene in the community;
water samples in the affected area was collected.
• Investigations identified a further 6 culture positive cases amongst the contacts. Cases
and contacts were treated

26. Enteric Fever Clusters, 2020 - 2021
Clusters under investigation
• Breede Valley subdistrict, Cape Winelands district from October 2020
• George sub-district, Garden Route District
• Cape Town Metro (widely spread cases): 3 separate clusters

27. Challenges
Challenges Details Mitigation
1 Case and
cluster/outbreak
Investigation
• Incomplete Case Investigation Form, and data integrity
• Wrong addresses being provided
• Provision of information and progress with investigations
done by the sub-district public health officials e.g. line
listing, laboratory results of screening specimens
• Reporting of suspected clusters or outbreaks
• Training of healthcare workers and stakeholders on enteric
fever investigations and management of contacts and cases
• Clarification of roles and responsibilities of all stakeholders
i.e. facility level, EHPs at sub-district level, laboratories
(private and public)
• Follow the enteric fever guidelines
• Provincial and district level must be more responsive, and
provide guidance and coordination during clusters/outbreaks
2 Case Follow-up • Poor cooperation of either cases or contacts e.g. refusal of
case/contacts for sample collection after completion of
treatment
• Guidelines not followed by public health officials to ensure
an enteric fever case is not a carrier
• Health education and promotion w.r.t the transmission and
prevention of enteric fever
• Training of healthcare workers on guidelines
• Hospital staff to indicate to the patient / case of the
importance of clearance sample collection, or ensure samples
are collected in-hospital before patient discharge
• If clearance samples not collected at hospital, the primary
health officials needs to be informed and ensure samples are
collected or the hospital need to ensure the case returns for a
follow-up appointment.
3 Contact identification
and follow-up
• Incomplete list of contacts (mainly household members and
not others) – the case do not provide the list/gives wrong
address/case is confused and not able to provide
information
• Collection of stool samples e.g. refusal by contacts
• Health education and promotion w.r.t the transmission and
prevention of enteric fever.
• Provide stool sample collection containers in order for
contacts (child / adult) to collect it themselves.
• Rectal swabs done appropriately (with cold chain maintained)
will also be accepted if done correctly.

28. Challenges Details Mitigation
4 Laboratory
confirmation
• Guidelines not followed w.r.t collection of the appropriate specimen for
cases / contacts - e.g. urine samples being collected from
case/contacts
• Results of contact screening specimens not provided routinely
• Training of healthcare workers and stakeholders on
enteric fever investigations i.e. detection, diagnosis,
treatment & public health response
• Laboratories to share line lists of samples received
and results to provincial /district/facility when
clusters/outbreaks are identified
• Laboratories to refer S. Typhi isolates to CED, NICD
5 Social issues
.
• Violence / gangsterism, substance abuse that impedes on the
case/contact to cooperate in terms of sample collection
• Homelessness – difficult to follow-up contacts if there is no fix
address or a next of kin to contact and further investigation is
challenging.
• Involvement of law enforcement and the SAPS, and
NGO’s in the area if needed
• Sought advice on legal recourse that can be
instituted by healthcare workers to ensure
cases/contacts cooperate so that the threat of
spreading the communicable disease is minimized
(? legislation related to this specific situation
• Find a next of kin if possible, and identify the place
where the patient/case was last seen (they may
have frequented a shelter/rehab centre)

29.  Circular H18/2016: Typhoid Fever Preparedness – Recommendation for diagnosis, management and public
health response
Enteric Fever: NICD recommendations for diagnosis, management
and public health response
Typhoid Fever Preparedness Notice: An update for Physicians,
Accident & Emergency practitioners, and Laboratorians
Typhoid Frequently Asked Questions (FAQ)
Enteric Fever Case Investigation Form and Contact Line list
All you need to know about enteric fever pamphlet, Western
Cape Department of Health
Resources

30. Conclusion
The identification and investigation of clusters investigations have highlighted the need
for:
On-going surveillance and continuing thorough case management and contact tracing
Training of healthcare workers and stakeholders on complete investigations for single cases /
clusters / outbreaks of typhoid fever
So as to contain further person-to-person spread and prevent contamination of water
sources

31. Thank you
CDC and Outbreak Response Unit
021-483-9964/3156/3737/9917/6878