Case 2.

Severe infection due to bacterial water contamination

Learning objectives:
1. Establishing a case definition;
2. Identifying the study design;
3. Consideration of sampling strategy;
4. Consideration of non-participant bias;
5. Consideration of exposure routes;
6. Recommending changes to prevent recurrence of epidemic.

PART 1 - INTRODUCTION

Salmonella infections pose a particularly serious risk if they become blood-borne in the host (septicaemia), carry

The term salmonellosis refers to infection caused by bacteria of the genus Salmonella, of which there are 3 prima

Salmonella septicaemia results when pathogenic species enter and multiply in the bloodstream. This may or may

Infections result from ingestion of food or water contaminated from human or animal sources. Animal sources in

The main goal of the study is to learn more about salmonella septicaemia in Kenya, particularly to understand wh

Question 1: Re-state the main problem in the form of hypotheses that should be
investigated.
Question 2: What kind of epidemiological study would you suggest? What are some of the
potential problems that might be associated with this type of study?

PART 2 - DEFINITION OF A CASE

You decide to do a case-control study. You define a case as follows:

Study Case Definition:

Any child admitted to the paediatric wards in Kenyatta National Hospital (KNH) and the Infectious Disease Hosp

Cases will be identified and enrolled prospectively into the study over the 5-month period. You plan to obtain inf

Question 3: What are the advantages and limitations of this case definition?
Question 4: List the kinds of information you would like to obtain in your interviews with
the parent or guardian.

PART 3 - CHOICE OF CONTROLS

You have a long discussion with your colleagues about the choice of a control group. A number
of control groups are considered, including: a) community controls - children of same age in the
community who did not get sick, and b) hospital controls. You finally decide to use hospital
controls - a set of children with the same age and sex distribution as the cases and who were
admitted consecutively to the Paediatric Emergency Ward, KNH. 108 children are selected as
controls.
Question 5: Discuss some of the considerations in choosing the control group. List the
advantages and disadvantages of community and hospital controls. Would you include
children admitted with the diagnosis of diarrhea but who do not have salmonellosis as
controls?
PART 4 - CASE PROFILE: RATES OF OCCURENCE

From a total of 4095 paediatric admissions during the survey time period (five months), 60 cases
(children with salmonella septicaemia by blood culture) were identified.
Among the 60 cases, 46 (77%) were infected with Salmonella typhimurium, 7 (12%) with other
types of non-typhoidal salmonella, and 7 (12%) with Salmonella tyhpi ("typhoid fever").
Males and females are equally affected. The age distribution of the cases by type of Salmonella
infection is shown in Figure1.

Figure 1
Age Distribution of Non-Typhoidal Salmonella Cases

Age Distribution of Typhoidal Cases

Question 6: What can you say about the pattern of the age distribution for those getting
non-typhoidal septicaemia? How does this compare tothose who get typhoidal septicaemia?

PART 5 - DESCRIPTIVE EPIDEMIOLOGY

You decide to look more closely at those cases who have community-acquired infections, in
other words, who had the infection prior to coming to the hospital. The cases who meet this
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definition are 70% (32/46) for S. typhimurium and 100% (7/7) for S. typhi infection.
You then analyse the place of residence for the children with community-acquired infections.
47% (15/32) of those with community-acquired S. typhimurium infection came from Nyanza
Province, 16% (5/32) from the eastern margins of Central Province, and 13% (4/32) from
Eastern Province. Only 13% (4/32) were from Nairobi (3 from a shanty area adjacent to a
sewage plant). 86% (6/7) of S. typhi infections were acquired in Nairobi shanty towns. The map
of the distribution of community-acquired infections is shown in Figure 2.

Figure 2
Map of Kenya showing home areas of children with community
acquired Salmonella sepicaemia

Question 7: What do you think about the geographical distribution of cases of the two
types of salmonella infection? Are they different? What hypotheses do you have about the
distribution?

Question 8: Do you think that coming from Nyanza Province is a risk factor for
developing community-acquired salmonella septicaemia? What additional information
would you need to determine the magnitude of possible risk associated with geography?

PART 6 - COMPARING CASES AND CONTROLS: PLACE OF RESIDENCE

You compare the home locations of those with community-acquired S. typhimurium septicaemia.
The results are shown in Table 1. (Note these databare not derived directly from the published
case report):
Table 1.
Home locations of cases of Salmonella typhimurium and controls

Nyanza Province
Other than Nyanza Province

Cases (N=32)
15
17

Controls (N=108)
15
93

Question 9: Calculate and interpret the odds ratio and 95% confidence interval associated
with living in Nyanza province and being hospitalised with S. typhimurium septicaemia.
Question 10: What can you now say about the factor, residence in Nyanza Province, in
terms of risk for becoming a case? Is it a causal factor? What hypotheses do you have
about these findings?

PART 7 - COMPARING CASES AND CONTROLS: HYGIENE AND SANITATION

Additional results are available to compare community-acquired cases and controls in terms of
other environmental factors. The main findings are shown in Table 2.
Table2
Prevalence of select environmental factors between cases and controls
Factor

Cases
(N=32)

Pit latrine use

31(97%)

Controls Odds 95% CI

(N=108) Ratio
49 (45%)

37.3

No piped water available

25 (77%)

23 (21%)

13.2 4.7-3.88

Domestic animals kept by

family

27 (83%)

50 (46%)

6.3 2.1-20.2

Drink milk from family cow

21 (66%)

18 (17%)

9.6 3.6-25.7

Question 11: Set up the 2 x 2 tables and calculate the odds ratio for each factor. Then, to
assess statistical significance, (i.e., the probability that the observed difference is due to
chance) calculate the chi-square value and the p value.
What do you think about the role of these risk factors in causing salmonella infection? Are
they important? How do they fit in with your main hypothesis? What additional hypotheses
could explain these findings?
Question 12: What other kinds of information would you like to have available to compare
cases and controls?

PART 8 - PUBLIC HEALTH RESPONSES

The most severe disease occurred in the 53 children with non-typhoidal septicaemia, with an
18% fatality rate (no patients with typhoid died); 19% (10/53) had coexisting malaria
parasitemia (compared to none with typhoid). Antibiotic resistance was high, especially for S.
typhimurium, and had increased significantly between 1980 and 1986. Four of the cases had
sickle cell disease; 42% of children with non-typhoidal bacteria had severe protein-energy
malnutrition (PEM).
You confirm that malarial infections (81% of cases come from malaria endemic areas),
malnutrition and sickle cell disease are all associated with increased host susceptibility to
infections like salmonellosis. But the underlying problem of contamination of food and water
sources must be addressed.

Question 13: What recommendations would you make to reduce the risk of Salmonella
infections?
Question 14: What role can you as a health officer play in helping to assist in implementing
these recommendations? Which are most important? Which are most feasible?
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Based in part on a report by Nesbitt, A. & Mirza, N.B. Salmonella Septicaemias in Kenyan children. J. of Tropical
Paediatrics, 1989, 35: 35-39.