Do infants increase the risk of re-emergent infection in households after mass drug administration for trachoma?
ABSTRACT Mass treatment with azithromycin for trachoma endemic communities typically excludes infants under age 6 months, whose parents are provided with tubes of tetracycline to administer daily over 4 to 6 weeks. The authors sought to determine whether infants aged <6 months are a source of re-emergent infection in their families after mass treatment in trachoma-endemic communities.
In a longitudinal study of all children aged less than 10 years in four communities, the authors identified 91 infants aged <6 months living in 86 of 1241 households. All children aged <ten years in all households were examined for trachoma and ocular infection with C. trachomatis at baseline, and 6 months after mass drug administration.
The prevalence of infection at baseline in the infants was 5.9%. At 6 months post mass drug administration, the rate of infection among children older than 6 months and less than 10 years who resided in households with infants was 6.0% compared with 11.1% in children in households without infants (P = 0.18). After adjustment for age, sex, baseline infection status, and treatment, residing in a household with an infant was not associated with infection at 6 months (odds ratio [95% confidence interval] 0.50 [0.20-1.22]).
This prospective study did not find evidence that living in a household with an infant increased the risk of infection 6 months post mass drug administration in other children residing in the household.
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ABSTRACT: Trachoma, the leading infectious cause of blindness, is a chronic conjunctivitis caused by repeated reinfections with Chlamydia trachomatis. Trachoma is a disease of entire communities, with the reservoir of infection residing in children, especially preschool children. The World Health Assembly has targeted the year 2020 for the elimination of blinding trachoma as a public health problem, and mass treatment with antibiotics is part of the multifaceted SAFE strategy recommended for country programs. Tanzania was one of the first countries to be the recipient of azithromycin for use in mass distribution programs and has been the site of a continuous research effort on trachoma control in the Kongwa district, the Kongwa Trachoma Project, since 1986. The authors discuss some events leading up to the use of azithromycin for trachoma, our experiences and lessons learned with use of azithromycin, intervention goals, achieving high coverage and the challenges to achieving elimination by 2020.Expert Review of Ophthalmology 01/2014; 8(3).
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ABSTRACT: To review recent clinical and epidemiological studies regarding the prevention, diagnosis, and treatment of trachoma. Newer studies propose novel diagnostic tests that appear sensitive for the detection of ocular chlamydial infection. For example, recent studies with ribosomal RNA-based nucleic acid amplification tests (NAATs) have demonstrated improved sensitivities compared to DNA-based NAATs; and the progression of scarring has now been characterized with confocal microscopy. Immunologic studies have further explored the etiology of clinical sequelae, suggesting that chronic inflammation can lead to progressive scarring even in the absence of Chlamydia. Mass oral azithromycin distributions remain a mainstay of treatment; studies have assessed the appropriate frequency and duration of treatment programs. Current studies have also explored ancillary effects of azithromycin distribution on mortality and bacterial infections. Trachoma programs have had remarkable success at reducing chlamydial infection and clinical signs of trachoma. Recent work suggests improved methods to monitor infection and scarring, and better ways to distribute treatment. Whereas studies continue to demonstrate reduction in infection in hyperendemic areas, more work is necessary to achieve elimination of this blinding disease.Current opinion in ophthalmology 05/2012; 23(4):288-95. · 2.49 Impact Factor
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ABSTRACT: Trachoma, a chronic conjunctivitis caused by Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. In recognition of this public health problem, the World Health Assembly has targeted the year 2020 to eliminate blinding trachoma, and a multifaceted strategy (SAFE) is recommended, including antibiotics for treatment of infection. Trachoma is a disease of entire communities, and the pool of infection resides largely in preschool age children. Thus, for endemic communities, mass treatment with antibiotics annually for at least 3-5 years is carried out. The antibiotics used, the effectiveness of this approach, and the challenges of antibiotic treatment of communities are discussed, concluding with a view towards the elimination of trachoma in the future.Expert Review of Anticancer Therapy 01/2012; 10(1):75-83. · 3.22 Impact Factor
Do Infants Increase the Risk of Re-emergent Infection
in Households after Mass Drug Administration
Sheila K. West,1Dianne Stare,1Harran Mkocha,2Beatriz Munoz,1Charlotte Gaydos,3
and Thomas C. Quinn3,4
PURPOSE. Mass treatment with azithromycin for trachoma en-
demic communities typically excludes infants under age 6
months, whose parents are provided with tubes of tetracycline
to administer daily over 4 to 6 weeks. The authors sought to
determine whether infants aged ?6 months are a source of
re-emergent infection in their families after mass treatment in
METHODS. In a longitudinal study of all children aged less than
10 years in four communities, the authors identified 91 infants
aged ?6 months living in 86 of 1241 households. All children
aged ?ten years in all households were examined for trachoma
and ocular infection with C. trachomatis at baseline, and 6
months after mass drug administration.
RESULTS. The prevalence of infection at baseline in the infants
was 5.9%. At 6 months post mass drug administration, the rate
of infection among children older than 6 months and less than
10 years who resided in households with infants was 6.0%
compared with 11.1% in children in households without in-
fants (P ? 0.18). After adjustment for age, sex, baseline infec-
tion status, and treatment, residing in a household with an
infant was not associated with infection at 6 months (odds ratio
[95% confidence interval] 0.50 [0.20–1.22]).
CONCLUSIONS. This prospective study did not find evidence that
living in a household with an infant increased the risk of
infection 6 months post mass drug administration in other
children residing in the household. (Invest Ophthalmol Vis Sci.
tious cause of blindness worldwide.1The World Health Orga-
nization (WHO) has endorsed SAFE (Surgery for trichiasis,
Antibiotics for active trachoma, Facial hygiene and Environ-
rachoma, a chronic conjunctivitis caused by repeated re-
infection with C. trachomatis, remains the leading infec-
mental improvement to reduce transmission), a multi-faceted
strategy for trachoma control in endemic areas. Where the
prevalence of follicular trachoma (TF) is greater than 10% in
children aged 1 to 9 years, WHO recommends mass drug
administration (MDA) for everyone, preferably with azithromy-
cin, a single dose antibiotic given annually and currently do-
nated to countries in need by the manufacturer.
However, the use of azithromycin in children aged ?6
months is not approved in many trachoma-endemic countries.
Instead, parents of infants are provided with tubes of 1%
topical tetracycline to be administered one to two times a day
for 4 to 6 weeks. Research suggests that adherence to this
protracted regimen of topical tetracycline is less than with a
single dose of azithromycin.2In a study of a single village, some
of the highest loads of infection were found in a few infants
before mass treatment.3Thus, there is concern that these
infants may be a source of re-emergent infection in trachoma-
endemic communities after mass treatment.
Conversely, if infants are largely cared for by mothers they
may have less exposure to infection from other children, and
less opportunity to transmit infection, and thus they may not
represent a major source of re-emergent infection. If so, the
risk of significant re-emergent infection from the few infants
that were infected post MDA could be very low. There are few
data on infection and disease in this very young age group of
infants, and we sought to investigate the role of infants as a
source of re-emergent infection in trachoma-endemic commu-
nities after mass treatment.
In the context of a longitudinal cohort study of all children
aged under 10 years in four communities undergoing mass
treatment in Tanzania, we evaluated the impact of residing in
a household with an infant aged ?6 months on the risk of
re-emergent infection after mass treatment. We hypothesized
that children residing in households with infants aged ?6
months at baseline would have higher rates of infection with C.
trachomatis 6 months post MDA compared with children
residing in households with no infants.
All infants and children from four communities located in the Kongwa
District of central Tanzania were selected for the study. A household
census was conducted in these communities in 2009. Children aged
?10 years were identified and their parent or guardian was invited to
have their child participate in a longitudinal study of trachoma and
infection over a three-year period. When available, maternal and child
health cards allowed for the determination of exact birth date. When
unavailable, infants’ ages were determined in reference to village
events in the past year, categorized as likely aged 6 months and older,
and likely aged 6 months and younger.
Detailed study methods on the ocular examination and specimen
analysis are described elsewhere.4In summary, trained trachoma grad-
From the1Dana Center for Preventive Ophthalmology, Wilmer
Eye Institute and the3Department of Infectious Diseases, Johns Hop-
kins University, Baltimore, Maryland; the2Kongwa Trachoma Project,
Kongwa, Tanzania; and the4National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, Maryland.
Supported by the Bill and Melinda Gates Foundation. Pfizer pro-
vided azithromycin to Tanzania as part of their donation program. SKW
received a Senior Scientific Investigator award from Research to Pre-
vent Blindness. TCQ was supported by the Division of Intramural
Submitted for publication February 10, 2011; revised April 20,
2011; accepted April 21, 2011.
Disclosure: S.K. West, None; D. Stare, None; H. Mkocha, None;
B. Munoz, None; C. Gaydos, None; T.C. Quinn, None
Corresponding author: Sheila K. West, Dana Center for Preventive
Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, 600
North Wolfe Street, Wilmer Room 129, Baltimore, MD 21287-9019;
Clinical and Epidemiologic Research
Investigative Ophthalmology & Visual Science, July 2011, Vol. 52, No. 8
Copyright 2011 The Association for Research in Vision and Ophthalmology, Inc.
ers performed an ocular examination using 2.5? loupes and a torch to
determine active trachoma. The trachoma graders were standardized
during a 2 week training exercise before the start of the study. Inter-
observer agreement, and agreement with a senior grader had to be
above kappa ? 0.6 for TF and inflammatory trachoma (TI). Graders are
monitored every 6 months by comparison of grades against the senior
grader using a series of trachoma images.4Active trachoma was graded
using the World Health Organization simple grading scheme.5
An eyelid-conjunctival swab was obtained to assess infection with
C. trachomatis. These swabs were taken using strict protocols to avoid
contamination. Both the trachoma grader and eyelid flipper used
gloves and changed them between each child examined. In addition,
“air control” swabs were taken on a random sample of 5% of children.
The swabs were waved in the air above the child but do not touch
anything, marked as per any other sample, and sent for processing. If
positive, further investigations were carried out to determine the
source of contamination. The samples were kept at ?20°C until they
were sent to the International Chlamydia Laboratory at Johns Hopkins
University for processing. The samples were analyzed using polymer-
ase chain reaction (Amplicor; Roche Molecular Systems, Indianapolis,
IN) according to manufacturer’s directions. Optical density was used to
identify positive results and defined as ?0.7. Optical densities between
0.2 and 0.7 were considered equivocal and were retested. Results of
these “air control” swabs showed some evidence of laboratory con-
tamination that affected 34 samples at baseline. These contaminated
samples were excluded; all further tests for contamination were neg-
ative at baseline and follow-up.
At the time of MDA, parents of infants aged ?6 months were
provided with tubes of 1% topical tetracycline with instruction to
administer 1 to 2 times a day for 6 weeks. Children aged greater than
6 months were given a single dose of azithromycin (20 mg/kg up to
1 g). Community treatment assistants directly observed treatment with
azithromycin; however, compliance with topical tetracycline was not
monitored. Children and infants were re-evaluated at 6 months for the
presence of active trachoma and C. trachomatis.
The association between infection in children at 6 months and
presence of infants in the house was examined using a logistic model
with infection as the outcome and presence of infants in the house as
the predictor; the model accounted for the clustering of infection
within children residents of the same household. An expanded model
of infection was used to examine the independent contribution of age,
sex, baseline chlamydial infection, and treatment at baseline, as well as
presence of infants in the household. Odds ratios (ORs) and 95%
confidence intervals (CIs) are presented where the generalized esti-
mating equation (GEE) approach was used to correct the standard
errors to account for the correlation among members of the same
house, using the procedure GENMOD in SAS (Cary, NC) with binomial
distribution, logit link function, and exchangeable correlation struc-
Written informed consent was obtained at the time of examination
from all parents or guardians of children in the study. All procedures
for the study were approved by the Johns Hopkins University Institu-
tional Review Board (JHU IRB) and the National Institute of Medical
Research (NIMR) in Tanzania and conducted in accordance with the
Declaration of Helsinki.
Of the 1241 households identified in the four communities, a
total of 91 infants aged ?6 months were found to reside in 86
(7%) of households. Of the total, 81.3% of infants lived with
other children aged ?10 years. Baseline examinations were
conducted on 93% of the infants, and 94% of all children aged
?6 months and ?10 years. Precise birth date information was
available for 80/91 (88%) of the infants.
At baseline, the prevalence of chlamydia infection in infants
was 5.9% and 1.2% had follicular trachoma (Table 1). The
prevalence of infection and active trachoma was lower in
infants than in older children. The prevalence of TF in those
less than 3 months of age was 1.8% (1/55) compared with 0%
(0/31) in those 3 to 6 months (Fisher’s exact test P ? 1.0).
With increasing age, the likelihood of signs of trachoma
lingering after infection was gone also increased (Table 2). In
children aged ?1 year, clinical signs were highly associated
Of the 91 infants in the census at baseline, seven were not
seen during MDA and thus were not provided with topical
tetracycline. Of those seven, six infants were found to be not
infected at baseline and one had an unknown infection status.
TABLE 1. Prevalence of Trachoma and Infection Prior to Mass Drug Administration and Coverage with
Azithromycin, by Age in Children in Kongwa, Tanzania
% TI with or
without TF% Infection
% Coverage with
* Not applicable, as the children were offered topical tetracycline.
TABLE 2. Prevalence of Active Trachoma by Infection Status,
Stratified by Age of Children
Age GroupInfection Status
% TF and/or TI
TABLE 3. Prevalence of Infection at Six Months Post Mass Treatment
by Residence in a Household with an Infant
Lives in a Household with
an Infant Aged <6 Mo
of Infection (%)
Table data excludes the infant.
* Adjusted for household clustering.
IOVS, July 2011, Vol. 52, No. 8
Infants and Infection Post Mass Treatment6041
Mass drug administation (MDA) coverage of children older
than 6 months with azithromycin was overall very high and
Six months post mass treatment, 82 of the 91 infants were
examined and two (1.2%) were found to be infected (both
were negative for infection at baseline). None of the infants
with infection at baseline had infection at 6 months (data not
shown). The prevalence of infection among children aged ?10
years who resided in households with infants was 6.0% com-
pared with 11.1% for children who resided in households
without infants (P ? 0.18; Table 3). In fact, contrary to our
hypothesis, when controlling for age, sex, treatment status,
and baseline infection status, children residing in a household
with an infant had a reduced, but not statistically significant,
risk of infection at 6 months [odds ratio [95% confidence
interval] 0.50 [0.20–1.22]; Table 4).
This prospective study found no evidence to indicate that
children living in a household with an infant had an increased
risk of infection 6 months post MDA. None of the infants
infected at baseline were found to have infection at 6 months
post MDA, suggesting that not only had the infection cleared
(either with treatment or on its own), but that the infants had
largely not become re-infected.
It is possible that compliance with topical tetracycline in
the infants was better than expected. We did not monitor
compliance with topical treatment to confirm compliance,
which we did for azithromycin. Coverage with azithromycin
was very high, and was likely instrumental in preventing cross
infection of the infants up to 6 months. Other studies have
reported topical tetracycline to be equally effective as oral
azithromycin in decreasing infection when compliance is
We have shown that treatment with azithromycin decreases
the load of infection, but if the load of infection pretreatment
is high, eliminating infection with a single dose is less likely.7
We did not measure the load of infection in these infants, but
we would not expect the load of infection pre-MDA to be
lower than observed elsewhere. Thus, if the infants had high
organism loads, as reported in other studies,3and topical tet-
racycline was not as effective in such cases, the infants would
be a risk to other children in the households. Our finding of no
increased risk suggests that topical tetracycline may have been
adequate treatment and/or infants are not a significant source
of infection for older children in the family.
Only one infant ?6 months old presented at baseline with
follicular trachoma. The infection rate was higher, 6%, suggest-
ing most children in this age group still cannot mount a clinical
response to infection. Few children aged ?1 year had clinical
signs of trachoma that were not associated with infection, as
contrasted with older children whose follicular response tends
to linger. The fact that 6% of infants ?6 months old had
infection indicates how early in life exposure to C. trachomatis
may occur. Consequently, researchers working on a chlamydia
vaccine ought to give consideration toward the provision of
protection at an early age to those in trachoma-endemic com-
In summary, our data suggest that the topical alternative for
infants, in a setting of high compliance with azithromycin
during MDA, did not leave a reservoir of infection that resulted
in risk of infection in other children in the families. High
coverage with MDA in trachoma-endemic areas is critical in
reducing the burden of infection and trachoma, and may pro-
vide protection against new acquisition of infection in infants.
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TABLE 4. Risk Factors for Infection at 6 Months Post Mass Treatment
among Children Aged ?10 Years
Factor OR95% CI*
Lives in house with infant
Treated at baseline
* Adjusted for age, sex, and clustering at household level.
6042 West et al.
IOVS, July 2011, Vol. 52, No. 8