Population Dynamics of Nasopharyngeal Bacterial Pathogens in Febrile Tanzanian Children Open Access

Alfa, David Akoji (2014)

Permanent URL: https://etd.library.emory.edu/concern/etds/b8515n49s?locale=en%255D
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Abstract

ABSTRACT

Population Dynamics of Nasopharyngeal Bacterial Pathogens in Febrile Tanzanian Children

By David Alfa

Background: The nasopharynx of children serves as a reservoir of bacterial pathogens such as Streptococcus pneumoniae (Sp), Haemophilus influenzae (Hi), Staphylococcus aureus (Sa), Moraxella catarrhalis (Mc) and Neisseria meningitidis (Nm). These pathogens are responsible for most of the global burden of bacterial respiratory diseases, otitis media and meningitis in children. Previous studies in healthy children showed these pathogens interact with each other within the nasopharynx in a competitive or synergistic manner. However, little to nothing is known about population dynamics of these bacteria in the nasopharynx of febrile children and its biological importance for the disease process. Therefore, our studies analyzed for the first time the bacterial density, using molecular approaches, of all these pathogens in the nasopharynx of febrile African children.

Methods: This was a cross sectional study where nasopharyngeal (NP) swabs were collected from febrile Tanzanian children (N= 999) aged 2 months to 10 years old. Identification and quantification of bacterial densities was done by quantitative (q)PCR analysis utilizing template DNA purified from those NP swabs. Logistic regression models were employed (after dichotomizing bacterial densities into absence or presence of targeted gene) to determine patterns of associations between bacterial species and potential association between patterns of densities with disease processes or risk factors associated to febrile illness. Spearman correlation coefficients were used to assess correlations among bacterial densities.

Results: The overall prevalence of these bacterial species in all febrile children was: Sp (80.8%), Hi (74.2%), Sa (23.3%), Mc (90.9%) and Nm (50.1%). Most children colonized by Sp, Hi and Mc had high densities of these bacteria in their nasopharynx. Concurrent colonization in this population by more than one bacterial specie was distributed as follows: 2 species (12.5%), 3 species (32.5 %), 4 species (33.8 %) and all five species (13.5 %) respectively. Near 65% of febrile children carried both Sp and Mc in the NP. Logistic regression models showed positive associations between colonization by Sp, Hi and Mc; Sp and Hi (OR 2.21, 95% CI 1.47-3.30, p-value <0.0001), Sp and Mc (OR 5.63, 95% CI 3.27- 9.70, p-value <0.0001) and between Hi and Mc (OR 3.76 95% CI 2.17-6.51, p-value <0.0001) while adjusting for age, sex, site of enrollment and acute respiratory infection status. A negative association was seen between colonization by Sp with Sa (adjusted OR 0.56, 95% CI 0.36-0.85, p-value <0.0001). Regression analysis also showed that age of the child was associated with colonization by Nm and site of enrollment was associated with colonization by Sp, Hi and Mc.

Conclusions: Studies within this thesis revealed high prevalence rates of Sp, Hi and Mc in febrile children. Most children (~92.4 %) will carry at least 2 bacterial pathogens with near 14% carrying all five pathogens. NP carriage of Sp, Hi and Mc was common in children with acute respiratory infections, whereas the prevalence of all these pathogens in the NP of children with other febrile illnesses, including pneumonia, was relatively low. Children enrolled in rural areas were more densely colonized by Sp, Hi and Mc than those enrolled in the urban site. The strongest association was Sp and Mc.

Table of Contents

I. INTRODUCTION...7

II. LITERATURE REVIEW...10

III. METHODS...21

Study Population...21

Research Design and Study Procedures...22

Laboratory Analysis...23

Statistical Analysis...27

IV. RESULTS...28

V. DISCUSSION...32

VI. REFERENCES...36

VII. TABLES...41

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