ORIGINAL

Niger J Paed 2013; 40 (1):45 – 49

Ikpeme EE

Etukudo OM

Ekanem EE

Clinical correlates of helicobacter

pylori infection in children seen at a

Tertiary Hospital in Uyo, Southern

Nigeria

DOI:http://dx.doi.org/10.4314/njp.v40i1,8

Accepted: 30th April 2012

Abstract Background: Helicobacter

pylori (H pylori) infection is the

commonest global chronic human

bacterial infection. Data from devel-

oped countries show that acquisition

occurs in childhood but manifesta-

tion of chronic gastroduodenal dis-

eases occur more commonly in

adulthood. H. pylori infection has

however been associated with paedi-

atric primary peptic ulcer disease,

though data is rather scanty. There

is virtually no data on the clinical

correlates of the seropositive Nige-

rian paediatric subjects though the

little data available shows higher

prevalence rates compared to that of

children from developed countries.

Objectives: A prospective observa-

tional survey was carried out to de-

termine the clinical correlates of H.

pylori infection in ill children admit-

ted in the emergency unit of our

department.

a commercial enzyme-linked immu-

nosorbent assay kit, VicTorch. Data

was analysed with using SPSS and

correlates determined as appropri-

ate.

Ikpeme EE (

Etukudo OM

)

Department of Paediatrics,

University of Uyo Teaching Hospital,

PMB1136

Uyo, Nigeria.

Tel: +2348033123336

Email: enpeks@yahoo.com

Results: The subjects were 132

(57.4%) males and 98(42.6%) fe-

males (male: female ratio= 1.3:1.0)

with an age range of 0.5-15 years

and a mean age of 5.0 (SD±4.0)

years. The overall seroprevalence

rate was 30.9%. Clinical features

including abdominal pains,

(p=0.001), fetor oris, (p=0.0001),

diarrhoea (0.041) and family history

of dyspepsia (p=0.002), showed

significant association with sero-

positivity.

Ekanem EE

Department of Paediatrics,

University of Calabar Teaching

Hospital, Calabar, Nigeria.

Conclusion: Seroprevalence of H.

pylori infection in Nigerian chil-

dren is high and is associated with

common gastroduodenal symptoms.

Keywords: Helicobacter pylori,

children, Nigeria, clinical corre-

lates.

Methods: H. pylori Immunoglobulin

G antibody was determined from

0

serum samples stored at -20 C using

Introduction

The clinical course of H. pylori infection is highly vari-

able. This is influenced by the microbial, host and envi-

ronmental factors. The dynamics of this global infection

are different for different regions but in virtually all in-

fected individuals, H. pylori infection causes a chronic

inflammation of the gastric mucosa. Gastritis develops

rapidly after acquisition of H. pylori infection and re-

mains with the persistence of the infection. This gastri-

tis is suggested to be a precu₁r₁sor of gastric cancer with

obvious grave consequencies.

Helicobacter pylori (H pylori) infection is the common-

est chronic human bacterial infection and about 50% of

adults the world over are said to be colonised with the

1

pathogen. The aetiologic agent is a flagellated spiral-

shaped Gram negative bacterium with its natural eco-

logical ni_,c₃ he being the antral portion of the human

10

2

stomach. Its colonisation of the human gastric antrum

has been associated with chronic gastroduodenal dis-

eases worldwide. Manifestations of H. pylori associated

gastroduodenal diseases have been reported principally

in adulthood although the acquisition occurs in child-

In the adult population, acute H. pylori infection is ac-

companied by mild to moderate dyspeptic symptoms

and occasional vomiting occurring within a few days of

the challenge. These symptoms peak during the second

1

hood. Primary peptic ulcer disease has been shown to

4

be associated with H. pylori infection in children.

1

2

There is a dearth of information on H. pylori associated

clinical manifestations in children even though higher

incidence rates are recorded in the socioeconomically-

challenged developing countries where₅_-₉over 50% of

children are infected by five years of age.

week of illness and then resolve. In children, the symp-

tomatology of acute H. pylori infection is not well char-

acterised. Occasionally, acute₁₃infection may cause gas-

tric ulcers and haematemesis. There is virtually no data

on clinical manifestations of H. pylori infection in

4

6

Nigerian children though the scanty available data_,₆ show

was used for the analysis as described by the manufac-

16 0

5

that the prevalence of this infection is very high. In

turer. The reagents were stored unopened at 4 C. Re-

peated freezing and thawing of the samples or microbial

contamination were avoided and icteric or turbid sam-

ples were not used (manufacturer’s precautionary ad-

vice). The cut off value for positive antibody activity

Maiduguri, Holcombe et al reported age specific preva-

lence rates of 82% and 92% in₅ children aged 5-10years

and 11-19 years respectively.

16

This study was therefore undertaken to see whether or

not the high seropositivity of H. pylori infection as

reported in Nigerian children has any clinical correlates

in children admitted for treatment of various ailments at

a tertiary health centre in southern Nigeria.

(AA) was taken at greater than 20IU. A definite infec-

tion, as determined by the antibody activity of this test

kit, was not less than ₆10% of the cut off value with accu-

1

racy level of 85.2%. The test principle is based on ap-

preciation of antibody titre with time and the 20IU is the

level at which antibody build up determined a definite

infection in comparison with urea breath test of gastric

biopsy specimens.

Subjects and methods

Ethical approval was given by the Ethical Committee of

the University Of Uyo Teaching Hospital, Uyo.

The study was conducted at the University of Uyo

Teaching Hospital, Uyo, in Akwa Ibom State. Akwa

Ibom State has a population of 3.9 million people. Uyo

is the capital city of Akwa Ibom State. It is predomi-

nantly a civil service town. The Teaching Hospital is a

Statistical analyses

14

Statistical analyses were performed using the SPSS soft-

ware package (Statistical Package for Social Sciences)

15.0 Software. Data were summarised into tables.

3

00 bed capacity hospital and the only tertiary health

institution in the state.

The seropositivity for H. pylori was computed according

to age. Correlates of H. pylori were evaluated by a com-

parison of proportions of children with and without in-

fection using Chi-square(x ) test and Fisher’s exact test

as appropriate.

The study population consisted of 230 children, admit-

ted in the children emergency unit of our hospital, aged

between six months and 15 years who required

2

venepuncture, and for whom an informed written con-

sent was obtained. The sample size was calculated using

Controlling variables for evaluation with multiple logis-

tic models were age, gender and symptoms.

The statistical significance of the adjusted seropositive

rates among comparison groups was also tested. p-value

of ≤0.05 was the significant level.

the formula

2

n

=

Z P(₂1-P)

d

Where n = Minimum sample size

Z = Standardized normal deviation (1.96)

P = Best estim₅ate of population prevalence

rate (82%)

d = Tolerable error margin (5%)

The best estimate of population p₅revalence rate for H.

Results

pylori in Nigerian children = 82%.

Two hundred and thirty children aged 6 months to 15

years with mean age of 5.0 (±4.0) years, median age of

4.0 years, comprising 132 (57.4%) males and 98

(42.6%) females had their serum samples tested for IgG

antibody reaction to H. pylori.

Therefore, minimum sample size was

2

n

=

(1.96) × 0.82₂x 0.18

= 227

(

0.05)

A clinical history was obtained from each subject, in-

cluding the family and social history and the child’s

socioeconomic status was determined using the parents/

guardians social class according to the social classifica-

Using the cut-off value for antibody activity (AA) of

20IU, 71 (30.9%) were serologically positive for H. py-

lori IgG antibodies while 159 (69.1%) were negative.

The antibody activity (AA) level of seropositive chil-

dren was >20.0IU with a mean (±SD) value of 42.0IU

(±16.1) as given by the manufacturers.

1

5

tion scheme proposed by Oyedeji. A quick clinical

examination, including oral and dental assessments, was

also done. Standard anthropometric measurements were

taken. These were recorded on the study proforma.

About 2.0mls of blood was collected from each subject

into a plain specimen bottle and taken to the laboratory

within 30 minutes and centrifuged to separate the serum,

which was stored frozen at -20 C till sufficient samples

were pooled for analysis.

The age distributions of the study subjects were as

shown in Table 1. Children less than five years of age

constituted 60.0% of the subjects. H. pylori seropositiv-

ity was highest in the one to five years age group

(36.6%) and the cumulative seropositivity was 56.3% in

the under five years age group. The least represented age

group was 11- 15 years which constituted 12.2% of the

study population with 9.9% seropositivity.

0

The VicTorch H pylori IgG test kit, with high sensitiv-

ity and specificity of 90-93% and 95-96% respectively,

4

7

The general characteristics of the subjects namely;

similar for both male and female subjects and had no

the mean age, weight, height and body mass index were

association with H. pylori Ig G antibody activity.

Table 1: Distribution of subjects by age

Age (years)

subjects

%

Cumulative

HPAP

%

Cumulative

HPAN

%

Cumulative

<

1

30

108

13.0 13.0

47.0 60.0

14

26

19.7 19.7

36.6 56.3

16

82

10.1 10.1

51.6 61.7

1

-5

6

-10

64

27.8 87.7

24

33.8 90.1

40

25.1 86.8

1

1-15

28

12.2 100

7

9.9

100

21

13.2 100

HPAP =H. pylori Antibody Positive

HPAN =H. pylori Antibody Negative

and diarrhoea (P=0.041, 95% CI=0.14,1.06) but there

was no association with irritability, heart burns, blood in

stool and frequent vomiting.

Table 2 shows that H. pylori seropositivity was signifi-

cantly associated with abdominal pain (p=0.001, 95%

CI=1.42,4.59), fetor oris (p=0.001, 95% C=2.08,9.74),

Table 3 shows that H. pylori seropositivity was associ-

ated with a positive family history of dyspepsia

(

p=0.002 95% CI=1.46,5.83).

Table 2: Relationship between clinical history, symptoms and H. pylori seropositivity

All subjects

n (%)

H.pylori IgG Reaction

p

RR

95% CI

Symptom

Positive

n (%)

Negative

n (%)

Irritability

Yes

34

12 (35.3)

59 (30.1)

22(64.7)

0.545

0.768

0.001

0.545

0.041

0.002

1.26

1.09

5.71

1.26

0.39

2.92

0.59,2.73

0.62,1.91

2.08,9.74

0.59,2.73

0.14,1.06

1.46,5.83

No

196

137 (69.9)

Frequent vomiting

Yes

123

107

39 (31.7)

84(29.9.)

84 (68.3)

75 (70.1)

No

Bad breath

Yes

19

13 (68.4)

58 (27.5)

6 (31.6)

No

211

153 (72.5)

Blood in stool

Yes

19

12 (35.3)

59 (30.1)

22 (64.7)

137(69.9)

No

196

Diarrhoea

Yes

31

5 (16.1)

26 (83.9)

No

199

66 (33.2)

133 (66.8)

Family history of dyspepsia

Yes

No

41

21 (51.2)

50 (26.5)

20(48.8)

189

139 (73.5)

Table 3: Relationship between some symptoms and H. pylori seropositivity according to age group of subjects

Symptom

yes

No

NK

AA+

AA-

AA+

AA-

AA+

AA-

p

95% CI

Abdominal pain

0.001

1.42.4.59

≤

5years

0

17

2

0

18

9

0

5

4

1

14

5

39

2

1

98

8

7

6

1

-10 years

1-15years

Heart burns

0.24

1.079,1.691

1.432,1.657

≤5 years

0

10

2

0

21

8

0

9

1

0

7

5

40

5

1

98

12

15

6

1

-10years

1-15years

Infantile colic

1 years

0.058

<

8

7

5

20

7

2

8

7

5

39

13

4

11

22

15

23

20

1

6

-5years

-10years

1

1-15years

1

4

1

5

8

9

AA+

AA-

NK

= Antibody activity positive

= Antibody activity negative

= Not known

4

8

Discussion

The production of ammonia from urea by H. pylori

which is a urease splitting organism has been docu-

mented to be the like₂ly₄ physiological basis of fetor oris

in H. pylori infection.

The seroprevalence rate of 30.9% obtained in this study

is high and suggests that H. pylori infection is signifi-

cant in the paediatric age group of the study locality.

This is consistent with high prevalence rates_-₉_,r₁e₅p_,₁o₇rted

There was no association between H. pylori seropositiv-

ity and the weight, height and body mass index of these

subjects. The relationship of growth parameters and H.

pylori infection in children as reported in previous stud-

ies has not showed a consistent pattern. The lack of as-

sociation as seen in this study was also reported by

5

among children in other developing countries.

Symptoms which were associated with H. pylori sero-

positivity included abdominal pains, fetor oris and diar-

rhoea.

2

5

The association of abdominal pains with H. pylori sero-

positivity has also been reported by other authors.

This could be as a result of gastritis which has been re-

ported to develop rapidly after acquisition of the infec-

Oderdaet al. Their study did not show any risk for

short stature in H. pylori infected children after control-

ling for the socioecono₆mic status of their families. In

1

9,20

2

contrast, Chloe et al. reported a significantly lower

1

0

tion and rema₁₉ins with the persistence of the infection.

mean height in H. pylori infected school children in

comparison to their uninfected counterparts.

Malatyet al reported that the younger children who

had recurrent abdominal pains were more likely than

older children, to be infected with H. pylori. A₀lso, in a

2

forty year review article by Bittencourtet al, it was

stated that in the under-seven years old school children,

abdominal pain was described in virtually all cases of H.

pylori infection. These reports are comparable with our

findings of higher occurrence of abdominal pain in the

five -10 year olds.

Conclusion

The IgG seropositvity rate in our study population is

high and shows positive association with clinical fea-

tures such as fetor oris, abdominal pain and diarrhoea,

as well as with a positive family history of dyspepsia.

We recommend that children presenting with any com-

bination of these features should be screened for H. py-

lori infection as early confirmation of infection in child-

hood with appropriate eradication therapy will impact

positively on the reduction or prevention of long term

sequelae of this treatable bacterial infection.

Data from this study showed a significant association

between diarrhoea and H. pylori seropositivity. Some

other studies had also suggested that infection with H.

pylori may predispose pa₂₁tients to other gastrointestinal

infections. Passaroet al reported that newly acquired

H. pylori infection was followed with increased occur-

rence of dia₂r₂rhoea. In contrast, the study by Rothen-

bacheret al reported a significantly less occurrence of

acute diarrhoeal illness in H. pylori infected children and

adults, compared to uninfected subjects. It is difficult to

exclude other confounding factors which may explain

the conflicting reports of these observational studies.

Conflict of interest: None

Funding: None

Acknowledgement

The significance of fetor oris as seen in this study was

also reported in the voluntary experimental ingestion of

Our appreciation is expressed to the parents of the chil-

dren that participated in this study for giving us the con-

sent to carry out the study, the statistician, Dr B. E. Ori-

madegun, the laboratory scientists, Dr Item Ekaidem,

Anthony Usoro, Vincent Udoh, also, Edu Isaac and Dr

Obasi Okorie for assistance with computer techniques.

23

a pure culture of H. pylori by Marshall. This symptom

among others, was noted to have resolved completely

within twenty four hours of the start of therapy with

Tinidaz₂₀ole (500mg twice a day), for eradication of H.

pylori.

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