Association of bacteria with hydrocephalus in Ugandan infants

Clinical article

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Object

Infantile hydrocephalus in East Africa is predominantly postinfectious. The microbial origins remain elusive, since most patients present with postinfectious hydrocephalus after antecedent neonatal sepsis (NS) has resolved.

Methods

To characterize this syndrome in Ugandan infants, the authors used polymerase chain reaction targeting bacterial 16S ribosomal DNA from CSF to determine if bacterial residua from recent infections were detectable. Bacteria were identified based on the relationship of genetic sequences obtained with reference bacteria in public databases. The authors evaluated samples from patients presenting during dry and rainy seasons and performed environmental sampling in the villages of patients.

Results

Bacterial DNA was recovered from 94% of patients. Gram-negative bacteria in the phylum Proteobacteria were the most commonly detected. Within this phylum, Gammaproteobacteria dominated in patients presenting after infections during the rainy season, and Betaproteobacteria was most common following infections during the dry season. Acinetobacter species were identified in the majority of patients admitted after rainy season infection.

Conclusions

Postinfectious hydrocephalus in Ugandan infants appears associated with predominantly enteric gram-negative bacteria. These findings highlight the need for linking these cases with antecedent NS to develop more effective treatment and prevention strategies.

Abbreviations used in this paper: NS = neonatal sepsis; PCR = polymerase chain reaction; PIH = postinfectious hydrocephalus.

Article Information

* Drs. Li and Padhi and Ms. Ranjeva contributed equally to this work.

Address correspondence to: Steven J. Schiff, M.D., Ph.D., Center for Neural Engineering, 212 Earth-Engineering Sciences Building, University Park, Pennsylvania 16802. email: sschiff@psu.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Characteristic CT scans from 3 Ugandan infants younger than 6 months of age at the time of their treatment for PIH. In addition to severe hydrocephalus, frequent evidence of severe scarring and loculations within the ventricular system is visible (arrows).

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    Depiction of the phylogenetic relationship of all unique 16S rRNA gene sequences obtained from patient CSF samples. Organisms are classified based on relatedness to known bacterial sequences. The data indicate the diversity of bacterial phyla detected.

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    Upper: Graph showing the percentage composition of the different bacterial classes in each patient. Taxonomic placement was determined using criteria of the Ribosomal Database Project (see Lebel et al., 1988). Lower: Percentage composition of different genera of Gammaproteobacteria in different patients. Samples from patients in Cases 26–50 were evaluated by culture only.

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    Genetic clustering among the Acinetobacter species detected from Cohorts 1 and 3 and environmental samples. The size of each circle is proportional to the number of sequences. The lines connecting the circles represent the number of mutations (see key in the figure) that separate groups of related sequences. The species level Acinetobacter identification was based on the phylogenetic tree shown in Fig. 10. Also see Fig. 11 for the individual relationships among all patient and environmental samples.

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    Phylogenetic relationships among the different genera of Gammaproteobacteria sampled from patients (indicated by P) and the environment. Bootstrap supports indicate the confidence in the placement of a sequence and are noted at the base of each node. Environmental samples (indicated by E) are highlighted by blue boxes. The phylogenetic color scheme in Figs. 59 corresponds to that of Fig. 2.

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    Phylogenetic relationships among Beta-, Alpha-, and Deltaproteobacteria.

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    Phylogenetic relationships among different isolates belonging to the phylum Bacteroidetes.

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    Phylogenetic relationships among the gram-positive isolates belonging to the phyla Firmicutes and Actinobacteria and the genus Deinococcus.

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    Phylogenetic relationships among the unclassified isolates.

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    Species affiliation of the Acinetobacter isolates collected from Cohorts 1 and 3 and the environment. Reference sequences are displayed with the GenBank accession numbers. Red and blue represent Cohort 1 and the environmental samples, respectively. Green represents clustering of a few samples from Cohorts 1 and 3 with the environmental samples. The names in red (starting with P) are individual patient samples from Cohort 1 that did not cluster in the other groups.

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    Genetic relationships among the individuals within each cluster. There are 4 unique clusters. While 3 clusters are connected to each other, 1 cluster, mostly represented by the environmental samples, could not be connected to the other clusters. Each colored circle within each cluster represents a unique sequence, and the small white circles represent a hypothetical sequence not observed in the sample that is needed to connect samples with 95% confidence. The solid line between 2 consecutive circles represents 1 mutational difference. The size of the circle is proportional to the number of identical sequences from different patients. Case number is indicated in each circle. Cohort 1 and 3 sequences appear in blue and yellow, respectively. Environmental samples appear in green. Red, green, and blue lines surrounding the clusters refer to the colored wedges shown in the phylogeny in Fig. 10.

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