Haemophilus influenzae type b (Hib) Invasive Disease in
Amish Children, Missouri 2014
Myers AL, Jackson MA, Zhang L, Swanson D, Gilsdorf J.
Children’s Mercy Kansas City, Kansas City, MO; Michigan State University, East Lansing, MI
University of Michigan Medical Center, Ann Arbor, MI
1760
Abstract
Background: Hib invasive infection is rarely identified in the US since the advent of conjugate vaccine in
the early 1990s. We identified 3 cases of invasive Hib disease during the first 5 months of 2014, all in
unimmunized Amish children from 2 different communities.
Objective: To describe the molecular/genetic characteristics of Hib strains isolated in a Missouri cluster
of Hib cases and to compare them to those identified in the multilocus sequence typing (MLST) data
bank which consists of 598 Hib strains from 6 countries.
Methods: The H. influenzae strains were tested by PCR for presence of capsule genes bexA and bexB,
located in the ATP transport Region I of the cap locus, and for specific capsule types a through f as
previously described and for sodC to distinguish Division I (sodC -) from Division II (sodC +) H.
influenzae. MLST was performed using the 7 standard MLST1 strain by PacBio alleles and whole
genomes of all 3 H. influenzae strains were sequenced by Illumina and.
Results: Three children presented with invasive Hib diseases characteristic of the pre-vaccine era
between Jan-May, 2014. Children in community A resided in small towns less than 10 miles apart, and
were infected with highly similar strains identified as ST45. The third child resided 250 miles south of
community A and was infected with a genetically different strain, ST6. ST45 strains are rarely reported
and represents only 3/598 (0.5%) of strains in the MLST data bank. The 3 previously identified ST45
strains were confirmed 15 years ago in a Pennsylvania outbreak in 3 Amish communities.
Conclusions: Two of three unimmunized Amish children who developed invasive Hib disease within 5
months were infected with rare ST45 strains only reported from Pennsylvania 15 years ago. While no
epidemiologic link was found, patient 2 traveled to Indiana and Wisconsin prior to development of
infection, raising the possibility of maintenance of this rare strain among Amish communities.
Background
• Haemophilus influenzae type b (Hib) was the most common cause of bacterial meningitis
and a common cause of invasive infection prior to 1985
• Invasive disease has decreased by 99% since vaccine became widely available in 1990
• The Hib vaccine eliminates the carrier state, thus producing herd immunity, but small
pockets of under- and unimmunized children remain in the US
• Hib cases occurred in a Pennsylvania community in 1999-00; 6 of the 8 cases were
Amish children and 3 of these had the ST45 strain that had not been reported previously or
subsequently in the US
• We report 3 Amish children with invasive Hib disease in Missouri from 2 communities that
are 250 miles apart (Figure 1; Table 1) 2 patients had an ST45 strain (community A; Table 2),
similar to the strains in PA (Figure 2)
Genotyping
Table 1. Characteristics and clinical outcomes of patients with invasive Hib infection
Patient Characteristics
Organism Characteristics/
Treatment
Outcome
Patient 1 (community B):
• Blood & synovial fluid cultures grew Hib
• 13 month old with fever and refusal
to bear weight on the left leg
• Ampicillin (MIC ≤1) and beta-lactamase
negative
• Pyogenic arthritis of the left hip was
found in the OR, without adjacent
osteomyelitis on imaging
• Ten days of parenteral ceftriaxone
followed by high dose amoxicillin for a 21
day course
Patient 2 (community A):
• Blood culture revealed Hib and tracheal
culture revealed Hib and MSSA
• CT revealed diffuse cerebral edema due
to infarction
• Susceptibility testing was not performed
• Life sustaining care was withdrawn at
family’s request
• 2 year old developed fever, refusal
to drink and rapid progression to
raspy breathing with panicking
• Epiglottic Inflammation noted at
intubation; dexamethasone was given
• Apnea and cyanosis followed and
CPR was initiated.
• Surgical cultures revealed Hib
• 13 month old with history of a fall from a
wagon prompting evaluation by a
chiropractor
• Beta-lactamase negative; no further
susceptibility testing performed
• Right hip pain continued with edema,
fever, erythema, and induration over the
lateral right thigh 2 weeks prior to
presentation
• MRI revealed osteomyelitis of right
acetabulum with femoral head dislocation
and necrosis, and pyomyositis
• The family, except the mother who was
pregnant, received rifampin prophylaxis
Figures 1. Map of Missouri showing the two communities with Hib infection
• Patient recovered well with only a slight
residual limp
• Rifampin prophylaxis was provided to the
family
• Initial treatment included clindamycin,
cefepime, and gentamicin
• Patient had 3 washout procedures and
spica cast
Table 2. Infection type, location, & genetic characteristics of isolated Hib Strains
Capsule genes
Date
Infection
Community
1(13mo)
2 (2 yr)
3(13mo)
Jan ’14
Feb ‘14
May ’14
Septic arthritis
Epiglottitis
Osteomyelitis
with septic
arthritis
B
A
A
ST45
Community A
Community B
Figure 2. eBURST diagram of Hib strains
Discussion
• Therapy was narrowed to amoxicillin at
discharge to complete a 6 week course
Patient #
(age)
ST6
• Rifampin was not provided as there
were no other young children in the home
• Empiric therapy was vancomycin and
ceftriaxone; transitioned to ampicillinsulbactam for 1 day
Patient 3 (community A):
• Physical exam and inflammatory markers
were normal at hospital follow up
• Serotyping performed by MO State HD and confirmed at the University of Michigan by cap
region PCR
• All strains were sequenced by Illumina; strain 1 also sequenced by PacBio and the seven
standard MLST alleles were used to establish the sequence type
• Strains 2 and 3 from community A were MLST sequence type 45 and were highly similar;
while strain 1 (ST6) from community B was genetically diverse
bexA
bexB
positive
positive
positive
positive
positive
positive
sodC
negative
negative
negative
MLST
sequence
type
ST6
ST45
ST45
• Children from underimmunized communities remain at risk for invasive Hib disease
• 2 children were rural neighbors and infected with a highly similar strain rarely reported
(3/598, 0.5%) in the MLST databank
• 3 ST45 strains were previously isolated from 3 Amish communities in PA15 years ago
• No epidemiologic link was found between our patients and the PA communities; patient 2
had traveled to Indiana and Wisconsin prior to infection onset, raising the
possibility of maintenance of this rare strain among Amish communities
• Strain MLST typing or whole genome sequencing should be considered in closed communities
• Immunization rates are generally low in Amish communities, raising the risk of vaccine
preventable diseases
• A vaccination campaign was undertaken in community A; all 40 children <5
years of age initiated the vaccine series
• The siblings of the patient in community B also received Hib vaccine