MENINGITIS, POSTINFECTIOUS HYDROCEPHALUS, ACINETOBACTER - UGANDA: (MBALE)
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A ProMED-mail post
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http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
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http://www.isid.org>
Date: Mon 3 Jan 2011
Source: Eurekalert.org [edited]
<
http://www.eurekalert.org/pub_releases/ ... 122210.php>
Hydrocephalus in children [in Uganda] and other developing countries
is seasonal, linked to farm animals and in part, caused by previous
bacterial infection, according to an international team of
researchers from Uganda and the United States, who believe that the
best approach to this problem is prevention.
"Hydrocephalus in infants in developing countries is a grand medical
mystery," said Steven Schiff, the Brush Chair professor of
engineering and director, Penn State Center for Neural Engineering.
Hydrocephalus is a build up of the fluid that normally surrounds the
brain. The increased pressure causes the head to swell and damages
brain tissue. Treatment includes placing a shunt to drain the fluid,
but inevitably these shunts become plugged and require emergency
care, not always available in rural Africa and other resource-limited
regions of the developing world. Surgeons vigorously explore the use
of new brain endoscopes to divert fluid buildup internally in such
children, but this approach addresses the fluid and does not fix
previous infection damage to the brain.
"Brains of children with hydrocephalus can be completely or mostly
destroyed either by the scarring from the disease or by the pressure
of the cerebrospinal fluid that cannot escape," said Schiff. "Many of
these children with the worst aftereffects of infection will be
mentally deficient and survive only as long as their mothers can
adequately care for them. Understanding the causes could eliminate or
prevent the enormous costs to lives and families that hydrocephalus brings."
Hydrocephalus in infants in sub-Saharan Africa is thought to be
caused most often by meningitis-type infections during the 1st month
of life. The U.S. and Ugandan researchers looked at the fluid from
the brains of 3 sets of 25 consecutive infant hydrocephalus patients
during January, July and October [2010] to try to determine the cause
of the disease. By the time parents bring infants with rapidly
growing heads to the CURE Children's Hospital in Mbale, Uganda, the
underlying infection is gone. The researchers were unable to culture
any bacteria from the samples.
To identify traces of previous bacterial infection, the researchers
used DNA sequencing to look for 16S ribosomal DNA that exists in all
bacteria. They reported their findings in the current issue of the
Journal of Neurosurgery: Pediatrics [Lingling L, et al. Association
of bacteria with hydrocephalus in Ugandan infants. J Neurosurg
Pediatrics 2011; 70:73-87. Available at:
<
http://www.esm.psu.edu/wiki/_media/rese ... s_2011.pdf>],
showing that 94 percent of the samples contained bacterial remnants.
The researchers found a seasonal difference between samples
representing infection during the dry season that were predominantly
Betaproteobacteria and [infection during the rainy season that were
predominantly Gammaproteobacteria]. [Betaproteobacteria is a class of
Gram-negative bacteria in the phylum Proteobacteria, which includes
_Burkholderia_ and _Neisseria meningitidis_, and Gammaproteobacteria
is a class of Gram-negative bacteria in the phylum Proteobacteria,
which includes _Pseudomonas_, _Escherichia_, and _Acinetobacter_.]
_Acinetobacter_ appeared in the majority [95 percent according to the
Lingling et al J Neurosurg Pediatrics study] of patients following
rainy season infection. Some sequences that appeared in the DNA
analysis were from unknown bacteria, and in many cases, the bacterial
fragments were not identifiable as to the type of _Acinetobacter_
they represented.
In the United States and other industrialized countries, infant
hydrocephalus is usually due to either a congenital anomaly or, in
low birth weight premature infants, due to brain hemorrhages from
immature blood vessels. At one time, Group B _Streptococcus_ was a
common cause of postinfectious hydrocephalus in infants in
industrialized countries, but now physicians test mothers for the
infection and treat with antibiotics before they give birth, and the
infections are rare. Surprisingly, according to Schiff, in Uganda,
none of the remnant DNA in the infants was from Group B _Streptococcus_.
Looking for the source of the neonatal infections, the researchers
targeted the living environment from infants with evidence of prior
_Acinetobacter_ infection and located patients' homes. What they
found were villages of huts where cow dung was pounded into the hut
floors to keep water and ants out and used in patios around the huts
where vegetation is cleared to protect against snakes. Newborns enter
an environment where they not only live near animals but also are
surrounded by their material.
The researchers sampled both the cow dung floors and excrement from
cattle, goats and chickens. They found similar genetic sequences from
the bacteria retrieved from the infants as in the hut floors and
nearby dung. "It is really hard to keep infants to an adequate
standard of cleanliness in this environment," said Schiff. "The
bacteria we found reflects, I think, a significant environmental
influence." While the researchers have not yet proven that these
bacterial infections are the cause of the devastating hydrocephalus
occurrences, they believe that in part, bacterial infections from
animals are the cause.
Historically, certain East African peoples have applied cow dung to
stem bleeding in umbilical cord stumps, which caused newborn
infections. Although such infections are now rare, the scope of
newborn bacterial infections related to living in close proximity to
domestic animals remains poorly categorized.
"As far as we can tell, these types of environmental newborn
infections are the dominant cause of hydrocephalus on the planet,"
said Schiff. "We may be dealing with bacteria that we can't culture,
viruses or parasites, and we may be dealing with different organisms
in different locations."
The researchers are continuing their work and forming an African
Hydrocephalus Consortium with Rwanda, Kenya, Tanzania and Zambia.
They are conducting follow-up clinical trials at the Mbarara
University of Science and Technology in southwest Uganda on
mother-infant pairs with new neonatal infections, and at the CURE
Children's Hospital of Uganda on older infants with postinfectious
hydrocephalus. These trials use next-generation technologies and high
quality microbiology to sort out the causative agents affecting these
infants. They are also continuing to explore the environmental
connection so that public health strategies toward preventing the
initial infections might be found.
[Byline: A'ndrea Elyse Messer]
--
Communicated by:
Thomas James Allen
<
tjallen@pipeline.com>
[Hydrocephalus, which is an abnormal accumulation of cerebrospinal
fluid (CSF) in the brain, is a recognized post-infectious
complication in survivors of neonatal meningitis. The investigators
cited in the news release above (Lingling L, et al. Association of
bacteria with hydrocephalus in Ugandan infants. J Neurosurg
Pediatrics 2011; 70:703--00807. Available at:
<
http://www.esm.psu.edu/wiki/_media/rese ... s_2011.pdf>)
found most commonly _Acinetobacter_ and _Burkholderia_ DNA by PCR
(polymerase chain reaction) amplification in CSF samples obtained
from Ugandan infants. The children were under one year of age with no
history of hydrocephalus at birth and with either a history of
febrile illness and/or seizures preceding the onset of hydrocephalus,
or endoscopic or imaging findings indicative of prior ventriculitis.
Although post-neurosurgical nosocomial _Acinetobacter_ meningitis is
a known problem (<
http://www.jstor.org/pss/4457446>), widespread
community-acquired _Acinetobacter_ meningitis in infants is not a
common problem in developed countries. However, Lingling et al cite
WHO data on _Acinetobacter_ meningitis in community-acquired
meningitis occurring in infants in developing countries.
Nevertheless, they acknowledge that _Burkholderia_ species have been
thought to be a very rare cause of community-acquired meningitis.
Lingling et al state that their cases in Uganda originated south of
the seasonal African meningococcal meningitis belt, and they found no
bacterial DNA consistent with the prior presence of the usually more
common meningitis pathogen _Neisseria meningitidis_ in any of the
samples and rarely encountered that of streptococcal meningitis
pathogens (e.g., Group B streptococcus or _Streptococcus pneumoniae_).
These data raise the issue of possible contamination when trying to
interpret the finding of bacterial DNA in CSF in the absence of
viable organisms. PCR amplifies a single or a few copies of a piece
of DNA, generating thousands to millions of copies of a particular
DNA sequence and, therefore, is especially vulnerable to
contamination. In addition, _Acinetobacter_
(<
http://epinews.com/Newswire/2010/06/11/ ... ves-gowns/>)
and _Burkholderia_
(<
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm53d827a1.htm>) are
common contaminants frequently found in moist environments. Lingling
et al say they made efforts to avoid contamination with ubiquitous
environmental microorganisms, and genetic analyses indicated
sufficient diversity among the _Acinetobacter_ sequences_ recovered
to suggest that they did arise from a common origin. Nevertheless,
confirmatory data is needed. As Lingling et al point out in their
paper, microbiological studies that attempt to recover viable
microorganisms from CSF in neonatal sepsis and meningitis in Ugandan
infants need to be performed to further address these issues.
Mbale, a city in southeastern Uganda where the CURE Children's
Hospital is located, is approximately 245 km (152 miles) northeast of
Kampala (<
http://en.wikipedia.org/wiki/Mbale>). A map of Uganda
showing the Mbale district can be found at
<
http://www.reliefweb.int/rw/fullmaps_af ... penElement>.
A map of the African bacterial meningitis belt can be found at
<
http://wwwnc.cdc.gov/travel/images/380.ashx>. The
HealthMap/ProMED-mail interactive map of Uganda is available at
<
http://healthmap.org/r/01ex>. - Mod.ML]
