Seminar
Trachoma
Lancet 2014; 384: 2142–52
Published Online
July 17, 2014
http://dx.doi.org/10.1016/
S0140-6736(13)62182-0
Melbourne School of
Population and Global Health,
University of Melbourne,
Carlton, VIC, Australia
(Prof H R Taylor AC);
International Centre for
Eye Health, Department of
Clinical Research, London
School of Hygiene & Tropical
Medicine, London, UK
(M J Burton FRCOphth);
Global Vision Initiative,
Emory Eye Center, Emory
University School of Medicine,
Atlanta, GA, USA
(D Haddad MD); Wilmer Eye
Institute, Johns Hopkins
Hospital, Baltimore, MD, USA
(Prof S West PhD); and Centre
for Eye Research Australia,
University of Melbourne, East
Melbourne, VIC, Australia
(H Wright FRANZCO)
Correspondence to:
Prof Hugh R Taylor,
Harold Mitchell Chair of
Indigenous Eye Health,
Melbourne School of Population
and Global Health, University of
Melbourne, Carlton, VIC 3053,
Australia
h.taylor@unimelb.edu.au
2142
Hugh R Taylor, Matthew J Burton, Danny Haddad, Sheila West, Heathcote Wright
Trachoma is the most common infectious cause of blindness. Repeated episodes of infection with Chlamydia trachomatis
in childhood lead to severe conjunctival inflammation, scarring, and potentially blinding inturned eyelashes (trichiasis
or entropion) in later life. Trachoma occurs in resource-poor areas with inadequate hygiene, where children with
unclean faces share infected ocular secretions. Much has been learnt about the epidemiology and pathophysiology of
trachoma. Integrated control programmes are implementing the SAFE Strategy: surgery for trichiasis, mass
distribution of antibiotics, promotion of facial cleanliness, and environmental improvement. This strategy has
successfully eliminated trachoma in several countries and global efforts are underway to eliminate blinding trachoma
worldwide by 2020.
Introduction Epidemiology
Trachoma is a blinding infection caused by an ancient Trachoma is still endemic in many of the poorest and more
organism. Chlamydia trachomatis evolved with the remote areas of Africa, Asia, Australia, and the Middle East
dinosaurs, and all vertebrates have evolved with their (figure 2). Active trachoma affects an estimated 21 million
own chlamydial strains.1,2 Trachoma remains the most people with about 2·2 million blind or severely visually
common infectious cause of blindness.3 The intense impaired. A further 7·3 million have trichiasis3 (table 1).
conjunctival inflammation with follicles recognised as An intensive global trachoma mapping effort is underway
active trachoma (TF) is sustained by repeated episodes at present. WHO classes 53 countries as endemic for
of reinfection and reflects a sustained immune- trachoma10,11 and estimates that 229 million people live in
mediated response to chlamydial antigens.4 This endemic areas, with most blinding trachoma in Africa.12,13
inflammation causes scarring, distortion of the lid, and Although few up to date prevalence data are available from
inturning of the lid (entropion), with the eyelashes China and India, with their large populations even a low
touching the cornea (trichiasis) that leads to blindness prevalence could substantially alter global estimates.
(figure 1). The key to trachoma is that repeated episodes Active trachoma (follicular or severe inflammatory
of reinfection and inflammation lead to the blinding trachoma) is most common in children younger than
complications.4 5 years and the prevalence can reach 60% or more.14–16
As human beings evolved, occasional chlamydial The greatest load of infection is also in young children.17
conjunctivitis did not apparently lead to blindness. The prevalence of active trachoma decreases with age,
However, after the last Ice Age (about 8000 years BCE), few adults have signs of active trachoma, and even fewer
when people were crowded in growing communities have evidence of infection.14,17–19 As active inflammation
and hygiene was poor, the frequency of reinfection wanes, conjunctival scarring becomes more apparent;
increased and blinding trachoma resulted.6 Crowding rates increase with age so that at over 25 years, up to 90%
and poor hygiene lead to outbreaks of chlamydial of people could have scarring.20 Rates of active trachoma
infections in a range of birds, mammals, and are generally similar by sex at young ages, but scarring
marsupials.7 Trachoma rates increased greatly as trichiasis and loss of vision are generally more common
crowding and poor living standards increased at the end in women than in men.14,20 This difference is attributed to
of the Agricultural Revolution and the start of the longer exposure of women to infection because they are
Industrial Revolution, but waned in the 20th century as more likely than men are to care for young children.
living standards improved.6 The disappearance of The prevalence of scarring, trichiasis, and corneal
trachoma from more developed countries was hastened opacities in older people relates to their exposure to
with the introduction of sulpha drugs in the 1930s and trachoma when they were young. This concept is important
antibiotics in the 1940s. because even when active trachoma has disappeared, the
However, trachoma still affects millions of people late sequelae, including trichiasis, can still occur for
in the least developed countries. In recognition of the decades.21,22 Persisting episodes of infection with
likelihood that spontaneous improvement in living C trachomatis or other ocular infections can contribute to
conditions and disappearance of trachoma could take progressive scarring, so reduction of these exposures
many decades, a specific global commitment has benefit adults.
been made to eliminate trachoma. A resolution of the Many cross-sectional and longitudinal studies have
World Health Assembly in 1997 established the linked clean faces to lower risk of trachoma.6,23
Global Alliance for the Elimination of Blinding Improvement in facial cleanliness also decreases the
Trachoma by the year 2020 (GET 2020) and much severity of active disease, probably by lowering the
progress is being made to eliminate the disease. likelihood of transmission.24
Some successes have led to increased resources and Water is necessary for face washing, and trachoma often
effort as set out here. occurs in communities or households without an adequate
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water supply. Several studies have identified a positive

A B
association between the distance to the water source and
the prevalence of active trachoma.23 However, the provision
of water to communities does not necessarily ensure that
infection or active trachoma rates will decline.25 The
decision to use water for hygiene is complex and is a very
important factor.26
Within communities, trachoma clusters both by
neighbourhood and by household.14,27,28 Studies of the re-
emergence of infection after mass azithromycin
treatment show that it reappears in households within C D
6 months, but takes up to a year to be evident in
neighbouring households.29
Overcrowding is a risk factor for trachoma; the risk of
children having active disease increases with the number
of people per sleeping room.28 Crowded conditions and
close contact enable exchange of infected secretions
among children especially if they have unclean faces and
share a bed. Although a large family in itself is not a risk
factor, the increased risk of contact with potentially
infected children is. In Nathan Congdon and colleagues’ E
study,30 mothers of children with trachoma were more
likely to have active disease than women who did not take
care of children or whose children did not have trachoma.
Eye-seeking flies have been presumed to be physical
vectors for C trachomatis. Although C trachomatis has
been identified in trapped flies,31,32 whether they can
transmit infection is not known. The presence of a
functional latrine near the house has been associated
with lower trachoma prevalence.14 How the presence of a Figure 1: Clinical features of trachoma and the WHO simplified grading5
(A) Trachomatous inflammation–follicular (TF); the presence of five or more follicles in the upper tarsal conjunctiva. (B)
latrine would decrease trachoma is not clear, although Trachomatous inflammation–intense (TI); pronounced inflammatory thickening of the tarsal conjunctiva that obscures
latrines might reduce breeding sites for the eye-seeking more than half of the normal deep tarsal vessels. (C) Trachomatous scarring (TS); scars are easily visible as white lines,
fly Musca sorbens,33 or could be simply a marker for bands, or sheets in the tarsal conjunctiva. (D) Trachomatous trichiasis (TT); at least one eyelash rubs on the eyeball;
families with better overall hygiene.34 evidence of recent removal of inturned eyelashes should also be graded as trichiasis. (E) Corneal opacity (CO); easily
visible corneal opacity over the pupil.

Pathogenesis
The causative organism Active trachoma Blindness Trichiasis
Trachoma is caused by the obligate intracellular Gram- 1956 400 NA NA
negative bacterium C trachomatis, which has a single 1971 400–500 1–2 NA
chromosome of about 1 Mbp and a multicopy plasmid 1981 500 6–7 NA
that functions as a virulence factor.2 This unusual
1985 360 6–9 NA
organism has a biphasic developmental cycle. Initially the
1994 146 5·9 NA
small, hardy, metabolically inactive elementary bodies
1996 NA NA 10·6
attach to and enter epithelial cells. Once inside, elementary
2003 84·0 1·6 7·6
bodies transform into the larger, metabolically active
2007 40·6 NA 8·2
reticulate bodies within an intracytoplasmic vacuole, the
2011 21·4 2·2 7·3
inclusion body, and replicate by binary fission. The
reticulate bodies transform into elementary bodies before Data are millions of individuals. NA=not available.
host-cell lysis and their release—the elementary body is
Table 1: WHO estimates of the global burden of trachoma, by year3,6,9
the transmissible form. No non-human reservoir for the
human strains of chlamydia is known.
Endemic trachoma is caused by C trachomatis serotypes However, the ocular serotypes have lost the capacity to
A, B, Ba, and C. C trachomatis infection of the genital tract synthesise tryptophan; and there is polymorphism in the
is generally caused by serotypes D to K, which can also tarp and pmp genes.35 Whole-genome analysis of
infect the eye, causing ophthalmia neonatorium in infants C trachomatis suggests that extensive recombination
or inclusion conjunctivitis in adults. The basis for the tissue between different strains is possible and that typing based
tropism of the serotypes has not been fully elucidated. on ompA might not be as reliable as previously thought.36

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 Seminar

infection could contribute to continued development of

Algeria
Nauru scarring.44,45 The risk of scarring has also been associated
Mauritania with the presence of other ocular pathogens, which
Kiribati suggests a role for chronic non-chlamydial conjunctivitis.46
The Gambia
Australia
However, not every person within an endemic community
Burma develops scarring, and 39% of the variability is attributable
Benin to human genetic factors.47 Moreover, scarring and trichiasis
Botswana
can continue to develop in people living in regions that are
Central African Republic
Vanuatu no longer endemic,48 which suggests that tissue damaged
Solomon Islands by previous chlamydial infection can undergo progressive
Afghanistan cicatrisation, or that after damage other drivers, such as
Fiji
Burundi
other bacterial pathogens, can contribute.46
Cambodia Conjunctival scarring precedes the development of
Mali trichiasis. The 7-year incidence of trichiasis in Tanzanian
Eritrea
women was 9·2% in those with tarsal scarring, and only
Guinea-Bissau
Malawi 0·6%, in those without scarring.49 Incident trichiasis was
Guinea also associated with the presence of active trachoma at
Cameroon baseline. The presence of infection at follow-up increased
Chad
Kenya
the risk of trichiasis by two and a half times, which
South Sudan suggests that persistent episodes of infection play a part.
Zambia In The Gambia, where trachoma rates are substantially
Burkina Faso
lower than in Tanzania, the 12-year progression from
Yemen
Nepal scarring to trichiasis in a cohort of 326 people, including
Niger men, was 6·4%—about half that of Tanzania.50
Tanzania
Senegal
Uganda
Histopathology
Sudan Active follicular trachoma is characterised by a diffuse
Mozambique inflammatory-cell infiltrate of the conjunctiva
Egypt
(lymphocytes, macrophages, neutrophils, and plasma
Pakistan
Nigeria cells) punctuated by lymphoid follicles (B cells
Ethiopia surrounded by a T-cell mantle).51 Trachomatous
0 10 20 30 40 50 60 70 80 conjunctival scarring shows disruption of loose, regular
Number of people at risk (millions) type 1 stromal collagen and dense sheets and bundles of
Figure 2: Estimates of the population of at risk trachoma by countries compact type V collagen.52 The epithelial cells are thinned
Brazil (1·3 million), China (455 million), and India (425 million) have been excluded from the figure.8 and goblet cells reduced. In-vivo confocal microscopy
shows changes in apparently unscarred eyelids, which
Pathophysiology suggests a continuum from subclinical to clinically
Blinding trachoma is the result of a complex interaction apparent scarring.53 Conjunctival scarring is commonly
between chlamydial infection and the immune response associated with clinical inflammation and inflammatory-
occurring over many years.37 Scarring develops more cell infiltrates.53,54
commonly and at a younger age in populations with higher
burdens of active trachoma and chlamydial infection, Immune response
suggesting that chlamydial infection has a central role in The mucosal response to C trachomatis infection involves
the disease process.38 Longitudinal studies link scarring to several components of the immune system, although the
chronic conjunctival inflammation, which can persist long features of protective and pathological responses are still
after infection has resolved.37 unclear.37
Most children with active trachoma do not develop The infection triggers an innate immune response,
trichiasis and blindness. In hyperendemic areas, a possibly driven from the epithelium through pattern-
subgroup of children, about 8–10%, seem to have constant recognition receptors. Infection of human epithelial cells
infection39,40 and persistent severe inflammation.41 The in vitro provokes a pronounced proinflammatory response,
incidence of scarring is almost five-times higher in these with the production of chemokines and cytokines.55
children than in children with active trachoma but without Conjunctival transcriptome studies in children with active
severe inflammation.42 Variation in the response to trachoma show prominent innate responses, with
chlamydial infection might explain this difference, as could increased proinflammatory mediators and recruitment
frequency of exposure and reinfection. Infection without and activation of natural killer cells and neutrophils.56,57
an obvious inflammatory response can occur in adults, Immunohistochemistry shows that some of these factors
with scarring in hyperendemic communities.23,43 This arise from epithelial cells.58

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The resolution of chlamydial infection is thought to be
dependent on interferon γ, mediated through nitric oxide
free radicals and the depletion of intracellular tryptophan
and iron. Infected children have increased expression of
the genes IFNγ and IL12p40, which suggests a type-1
CD4-expressing T-helper lymphocyte (Th1) cell-mediated
immune response.56 Other sources of interferon γ could
include natural killer cells and CD8-expressing T cells.56,59
Human challenge experiments and trachoma vaccine
trials in the 1960s suggested that acquired immunity to
reinfection is serovar specific, weak, and short-lived.37 A
longitudinal population-based study identified shorter
infection episodes with increasing age, again suggestive
of limited acquired immunity,18 although another possible
explanation is less frequent episodes of reinfection. The
contribution of humoral immunity to infection remains
unclear, but it is probably limited.37 The degree of
protection identified in non-human primate vaccine
studies was only partial and serovar specific, although
this protection was no more than that conferred by
recovery from a primary ocular infection.60
Scarring
Trachomatous scarring can result from a T-cell-mediated
immune response to repeated chlamydial antigen
exposure54 or an innate proinflammatory response
arising from the infected epithelium. 61
Evidence for specific T-cell responses is limited.37
Findings of studies in non-human primates suggested
that the inflammatory disease resulted from a specific cell-
mediated response to a chlamydial heat shock protein,
cHsp60.4 Results from human studies are more mixed:
antibodies to cHsp60 are more common (possibly related
to increased exposure), and responses of peripheral-blood
mononuclear cells to cHsp60 are weaker in people with
conjunctival scarring than in those without scarring.62,63
However, there is little evidence from human beings to
suggest that the conjunctival scarring results from a Th2
cell-mediated immune response, by contrast with
schistosomiasis, which has been associated with a Th2
response.56,64,65
Evidence suggesting that an innate proinflammatory
epithelial response contributes to tissue damage includes
a murine TLR2 (an innate system of pattern-recognition
receptors) knockout model for genital chlamydial
infection; affected animals had lower production of
inflammatory cytokines, fewer inflammatory cells, and
less scarring than normal mice.66 The conjunctival
transcriptome analyses of both children with active
inflammatory disease and adults with scarring show
enrichment of innate pathways.56,65 Trachoma scarring has
been associated with polymorphisms of the interleukin 8
and colony-stimulating factor 2 (CSF2) loci.67
The matrix metalloproteinases are integral to tissue
homoeostasis and are also involved in tissue destruction
and fibrosis. These proteolytic enzymes are produced by
inflammatory cells, fibroblasts, and epithelium. Both
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active and scarring trachoma show increased amounts of
matrix metalloproteinases 7, 9, and 12,56,64,65 and a single
nucleotide polymorphism of the catalytic region of matrix
metalloproteinase 9 affects the risk of scarring.68 These
findings suggest a role for matrix metalloproteinases in
scar formation.
Corneal opacity and loss of vision can occur within a
year in up to a third of individuals with untreated
trichiasis.69 Even without vision loss trichiasis leads to
substantial disability and reduced quality of life.70,71
Assessment of burden of disease
Overview
Trachoma interventions are planned at the district level,
though implemented at the community or household
level. They aim to eliminate blinding trachoma, partly by
disrupting transmission of infection, and are implemented
at the district level to minimise the reintroduction of
infection into treated communities. Therefore, the district-
level trachoma prevalence is used to identify where
programmes are needed (appendix).11 See Online for appendix
At the start of 2012, trachoma control activities covered
about half of the areas deemed to be at risk of trachoma.
In June, 2012, the UK Department for International
Development gave £10 million for a Global Trachoma
Mapping Programme.8 This project aims to complete the
mapping of trachoma in unmapped districts by March,
2015. Through this consortium new methods, training
materials, and data management systems have been
developed to save time and ensure harmonisation.
Clinical grading
The WHO simplified grading system was designed for
non-specialists (eg, eye nurses) to rapidly assess the
prevalence and severity of disease within a population.5
By contrast, the earlier, more detailed systems for grading
trachoma were used by experienced eye specialists. The
simplified grading focuses on the presence or absence of
five key clinical signs of the disease. Each of the signs
should be scored independently.
Population-based assessment of the prevalence of the
clinical signs of trachoma is the starting point for a
trachoma control programme. Active trachoma is most
prevalent in young children, so screening for active
trachoma (TF and TI) is mostly restricted to children
aged 1–9 years. Adults (older than 15 years) are generally
screened for trachomatous trichiasis (TT).
Laboratory diagnosis
Trachoma is a clinical diagnosis. The laboratory detection
of C trachomatis is not used for programmatic purposes
or to diagnose individual cases, but it is often used in
research. Laboratory tests developed for urogenital
infection are often used for ocular infection. Although
laboratory diagnosis of ocular C trachomatis has
improved, there is still no single accepted gold standard.
C trachomatis has been cultured since 1957, but culture is
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expensive and time-consuming; although very specific,
it is not very sensitive.
Nucleic acid amplification techniques are highly
sensitive and specific.72,73 C trachomatis DNA or RNA is
selectively amplified and detected in ocular swabs or
nasal secretions. Although the price per test is high
(US$10–40 per test), these techniques can be cost effective
for programme assessment and decision making,
especially on whether to stop antibiotic treatment
implementation.74,75 A better understanding of the risk of
re-emergence of infection or emergence where infection
was previously absent is needed before criteria based on
testing for infection can be used.76 For programme
purposes, the whole population does not need to be
tested. Selective testing of a representative sample of
people, shared use of laboratory capacity established for
HIV and tuberculosis programmes, and pooled testing of
samples can reduce costs, although careful understanding
of the limitation of pooling is needed.
Relation between clinical disease and C trachomatis
infection
Clinical disease commonly occurs in the absence of
demonstrable infection (table 2). At any given time, only
18–40% of individuals with less severe active disease (TF)
will be PCR positive; 50–70% of those with severe
inflammation (TI) will be PCR positive.43 Clinical signs of
active trachoma can persist long after infection has been
cleared and DNA is undetectable.77 The poor association
between clinical disease and infection, and the existence
of clinical disease without detectable infection has led
some to question whether clinical signs should be the
only means to determine when to stop treatment.78
Survey methods
The gold standard is a full-scale population-based
prevalence survey with a cluster-randomised sampling
technique at the district level. Several sampling techniques
have been developed.79 If trachoma is expected to be highly
endemic and widespread, a larger geographical area could
Total Number
PCR-positive (%)
Whole population 1282 46 (4%)
WHO simplified grading
TF absent 1174 27 (2%)
TF present 108 19 (18%)
Fine grading of follicles
Normal 793 6 (1%)
Some follicles, but less than TF 383 21 (5%)
TF WHO grade 98 16 (16%)
Follicles far exceeds TF 10 3 (30%)
Modified from reference 43. TF=active trachoma.
Table 2: An example of the relation between active trachoma and
presence of infection detected by PCR in endemic communities
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be used as basis for the survey as well, to reduce costs.11
The Global Mapping for Trachoma Program uses
population-based surveys.80
Other methods have been developed. Trachoma rapid
assessment81 has convenience sampling that is biased to
find trachoma; because it targets the worst areas it can
help prioritise areas and show whether a district is free of
trachoma, but it does not provide prevalence information.
Acceptance sampling trachoma rapid assessment82 is
based on lot quality assurance sampling but has been
little used.
Management and prevention: the SAFE strategy
Overview
The GET2020 campaign uses the SAFE strategy, a four-
pronged approach to stop the cycle of reinfection within
the community and to correct trichiasis.11 WHO and
partners aim to scale up SAFE strategy programmes in
affected countries in a timely and cost-effective way to
eliminate trachoma by 2020.
Surgery
Individuals with trachomatous trichiasis and entropion
are at risk of corneal opacification and vision loss. To
prevent these features developing, the abrasive action of
lashes on the cornea must be stopped by surgical
correction of the eyelid margin, with epilation perhaps as
an acceptable short-term option.83 Both bilamellar tarsal
rotation and posterior lamellar tarsal rotation (or Trabut)
procedures are recommended by WHO.83–85
Trichiasis surgery programmes are cost effective at
13–78 international dollars per DALY.86 They have been
widely implemented; an estimated 160 000 individuals
received surgical procedures in 2012.8 Trichiasis surgery
improves vision slightly, reduces pain, and in some
cases reduces the severity of corneal opacity.85,87–89 The
success of many surgical programmes is undermined by
recurrence rates that can be as high as 60% at 3 years.87,90–95
However, in many cases the recurrent trichiasis is less
severe.85,87–89,96 Major risk factors for recurrence include
the preoperative severity of trichiasis, variability among
surgeons, and surgical technique.87,89,90 Other risk factors
include conjunctival inflammation95,97 and concurrent
chlamydial infection.98 The use of azithromycin after
surgery with the aim of reducing recurrence has been
assessed in three randomised controlled studies.87,90,99
Two showed little effect but might have been
underpowered; the largest study suggested a benefit.
Uptake of surgery is low in some areas, varying
between 10% and 60%.100,101 Higher uptake was achieved
with local village-based surgery.102 Barriers to surgery
include lack of awareness,103 fear,98,104,105 the perceived
costs, transport difficulties,91,92,94,98,104,105 other responsi-
bilities,83 and lack of an escort.83 Surgical services can be
delivered in health centres or through outreach
campaigns.83 Each has advantages, although most
surgery is delivered by outreach. Local resources and
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preferences should be taken into account. Appropriately
trained nurses can produce surgical outcomes equal to
those of ophthalmologists,106 but efficient, high-volume,
high-quality meticulous surgery with regular audit is
needed if the backlog of 7·3 million cases of trachoma-
tous trichiasis is to be cleared.
Epilation is an age-old treatment for trichiasis and is a
possible alternative if surgery is delayed, refused, or not
available. Several cross-sectional studies have found that
in people who have not had surgery the risk of corneal
opacification is lower in those who have epilation than in
those who do not.107,108 A controlled comparison of
repeated epilation with immediate surgery for minor
trachomatous trichiasis (fewer than six lashes touching
the eye) found no difference in corneal opacity or visual
acuity; however, significantly more lashes touched the
eye in the epilation group.109
Antibiotic treatment
Antibiotics, oral azithromycin or topical tetracycline, are
used to lower C trachomatis numbers within endemic
communities and thus disrupt the transmission of
infection. Azithromycin (20 mg/kg up to 1 g) is the
preferred treatment where available. It is given as a
single oral dose and is well tolerated. Topical tetracycline
must be given for 6 weeks.
Four randomised controlled trials have assessed mass
distribution of azithromycin compared with no
treatment.110–114 In all four, the rate of C trachomatis
infection was lowered by the intervention but only one
trial showed a clear reduction in clinical signs of active
disease at 12 months.114 A three-country randomised
controlled trial showed oral azithromycin to be non-
superior to topical tetracycline; infection and clinical
disease declined significantly after treatment in both
trials.115 Furthermore, a randomised controlled trial in
Ethiopia of mass distribution of azithromycin once or
twice a year showed a decline of infection from a baseline
mean of 41·9% to 1·9% at 42 months with yearly and
from 38·3% to 3·2% with twice-yearly distribution.116
Despite the limited evidence from randomised controlled
trials, the overwhelming evidence from cohort studies is
that the rate of clinical disease and the rate of infection
both drop after mass distribution of antibiotics with high
coverage.112,115,117–119 District-wide mass distribution is
indicated when the proportion of children aged 1–9 years
with trachomatous inflammation, follicular (TF) is
greater than 10%.11 For starting prevalence rates of 5–9%,
targeted treatment is recommended (figure 3).11
WHO recommends that for a starting prevalence of
10–30% mass distribution of antibiotics should continue
for 3 years before prevalence is reassessed (appendix).11
The decision to treat for 3 years is supported by a recent
randomised controlled trial in which mass distribution
would be stopped in low-prevalence Tanzanian
communities (10–20%) if C trachomatis detection (not
the rate of clinical TF) dropped below 5% before the
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District survey
TF is >10%: TF is <10%:
MDA, facial cleanliness, subdistrict level
and environmental surveys
improvements for
at least 3 years
TF is >10%: TF is >9–5%: TF is <5%:
MDA, facial cleanliness, facial cleanliness facial cleanliness,
and environmental and environmental and environmental
improvements for improvements, and improvements,
at least 3 years MDA can be targeted* but no further MDA†
Figure 3: WHO recommended interventions according to prevalence of TF11
TF=active trachoma. MDA=mass distribution of antibiotics. *Targeted means
that no further survey is needed, but by use of the best available information,
villages, or aggregates of villages, are treated where trachoma rates are
suspected to be high. †Precision for <5% is 4±2%.
third round of treatment; however, the third round could
not be stopped in any of the communities.120 Reports of
elimination after a single round of distribution might be
unrepresentative, because the coverage rate was
exceptionally high and affected individuals were given
topical tetracycline at follow-up visits.119,121 Other studies
report a striking initial drop in the prevalence of
infection after mass distribution followed up at
6 months.117,122 For starting prevalences above 30%, WHO
now advises that reassessment can be delayed for
5 years,11 although some high prevalence (>50%)
communities might need 7 or more years of treatment.123
Mass distribution of antibiotics should continue until
the prevalence of TF in children falls below 5% in
subdistricts or community clusters (appendix).11
Debate about the duration of treatment for a community
has centred on the mismatch between clinical signs and
infection. Clinical signs can persist long after infection
has been cleared;77 this persistence could lead to
unnecessary treatment of communities with low rates of
infection and more than 5% with clinical signs. Detection
of infection is not practicable without a cheap point-of-
care assay and, even if a cost-effective one became
available, the level of infection that would warrant
treatment is not clear. WHO recommendations remain
the best guide for the continuation of mass distribution of
antibiotics.
Mathematical modelling suggests that twice-yearly
treatment is more effective than annual treatment in high-
prevalence communities,124 although a 2009 randomised
controlled trial did not confirm this finding.125
In 2011, more than 45 million doses of azithromycin
were distributed.8 The total needs to be scaled up by 50%
for the GET 2020 targets to be achieved (figure 4).
Azithromycin is expensive and mass distribution is only
cost effective because of Pfizer’s continuing large-scale
donation programme.86 Because of overlapping geo-
graphical distribution, integration of mass distribution of
antibiotics for trachoma and that for other neglected
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A Model for surgery scale-up B Model for antibiotics scale-up

4500 Patients 750 120 People 80

People remaining in endemic areas (millions)

Operations Doses
Patients awaiting surgery (thousands)

4000

Doses distributed per year (millions)

Operations per year (thousands)
100
3500 60
3000 500 80
2500
60 40
2000
1500 250 40
1000 20
20
500
0 0 0 0
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
Year Year

Figure 4: Projected needs for trichiasis surgery and antibiotic distribution to eliminate trachoma in know endemic districts8

tropical diseases has been suggested.126 Little evidence is by 6 months and resistance could soon disappear in the
available on the coadministration of azithromycin with absence of further antibiotic distribution.
other drugs, and trials are underway. Mass distribution
programmes can be integrated by staggering the delivery Facial cleanliness and environmental improvements
of drugs over time. Since 2009, more than 30 million Although much attention is given to mass distribution
people have been treated in Mali without severe adverse of antibiotics and surgery, any surgical and antibiotic
reactions.127 Modelling showed that neither targeted programme should address the root cause of trachoma
treatment of households nor targeted treatment of and be accompanied by facial cleanliness campaigns
screened individuals was more cost effective than mass and efforts to improve health hardware that will enable
distribution if donated azithromycin continued.86,128 The facial cleanliness. If the basic hygiene factors that
success of mass distribution of antibiotics is related to allowed trachoma to thrive in the first place are not
coverage; WHO recommends coverage of 100%,11 with a addressed, it will return once mass distribution of
minimum coverage of 90% of total population.129 antibiotics ceases.
For large-scale mass distribution of antibiotics a very Poor facial cleanliness has been consistently associated
safe drug is needed. Azithromycin has an excellent safety with trachoma6,23,135 and is an important modifiable risk
profile. Mass distribution of azithromycin is reported to factor. Observational studies suggest the importance of
halve childhood mortality130 and to reduce rates of facial cleanliness campaigns.136 A randomised controlled
diarrhoea and respiratory-tract infections.131,132 Antibiotic trial of facial cleanliness showed a significant reduction
resistance is always a concern but macrolide resistance in severe inflammatory trachoma.24 The greatest decrease
was not identified in C trachomatis after four 6-monthly in trachoma in the Sudan was in areas with good uptake
mass treatments.133 Streptococcus pneumoniae develops of both antibiotics and children’s facial cleanliness.137
azithromycin resistance after mass azithromycin Environmental risk factors include water supply, faecal
distribution,134 but because of the fitness cost of main- and refuse disposal, animal pens within households,
taining resistance, rates of resistant bacteria tend to wane and fly density.32,33,41,138 Environmental improvements can
address such risk factors on a community-by-community
basis, although evidence to support this approach is
Search strategy and selection criteria limited. The evidence base for the environmental
We searched the University of Melbourne Discovery Library component of the SAFE strategy is poor.
with the subjects Medicine, Dentistry, and Health Science. In view of the importance of the facial cleanliness and
Databases searched included The University of Melbourne environmental components of the SAFE strategy, the
Library Catalogue, Web of Science (ISI), Scopus version 4 proportion of countries with trachoma that had
(Elsevier), Medline (ISI), CINAHL (EBSCO), and PubMed from implemented these components is disheartening;
Jan 1, 2008, to Dec 31, 2012. We used the search terms although 61% had initiated surgery and antibiotic
“trachoma”, “epidemiology”, or “SAFE strategy” in programmes, only 34% had also implemented facial
combination with “trachomatis”. We have included older key cleanliness and environmental components.139 To increase
and commonly cited publications. Several later review articles the latter activities, trachoma policies should be integrated
and books have been cited as they provide a more expansive into national water, sanitation, hygiene, and child survival
review and references on particular topics. We have also strategies; surgery and antibiotic distribution should be
included web-based reference material for some key areas linked with hygiene and sanitation programmes; and
that are not in the peer-reviewed scientific literature. implementation of hygiene and sanitation programmes
should be included in the monitoring and certification of

2148 www.thelancet.com Vol 384 December 13, 2014


elimination.140 However, more evidence is needed on the
specific contributions of the various environmental
interventions, their effect on trachoma, and their cost-
effectiveness.
Trachoma control cannot be maintained without
appropriate improvements in hygiene and sanitation.
Trachoma was eliminated from most developed countries
after access to water, waste disposal, and housing
improved. Such measures provide a useful link between
GET 2020 and general development programmes such
as the Millennium Development Goals.
Conclusion
The SAFE strategy provides a targeted way to speed up
the process of a general improvement in living conditions
and hygiene that is needed to eliminate trachoma in the
most disadvantaged areas in the developing world.
Countries such as Morocco, Ghana, and Oman have
eliminated blinding trachoma by use of the strategy.11
Activities at present cover at least half of the world’s
endemic districts, and the mapping of the remainder
should be completed soon (figures 2, 4).8 As increasing
resources are brought to bear, the likelihood of eliminating
blinding trachoma by 2020 becomes stronger. Much work
is still needed and more information is needed about the
use of azithromycin, when to stop mass distribution of
antibiotics, and a better understanding of the progression
of scarring and the treatment of trichiasis. However, we
are on the way.
Contributors
HW searched the scientific literature; all authors developed, wrote, and
revised the Seminar.
Declaration of interests
We declare no competing interests.
Acknowledgments
MB is supported by the Wellcome Trust (grant number 098481/Z12/Z).
References
1 Stephens RS. Chlamydial evolution: a billion years and counting.
In: Schachter J, Christiansen G, Clarke IN, et al, eds. Chlamydial
infections—proceedings of the Tenth International Symposium on
Human Chlamydial Infections, June 16–21, 2002, Antalya, Turkey.
San Francisco: International Chlamydia Symposium, 2002: 3–12.
2 Clarke IN. Evolution of Chlamydia trachomatis. Ann N Y Acad Sci
2011; 1230: E11–18.
3 Mariotti SP, Pascolini D, Rose-Nussbaumer J. Trachoma: global
magnitude of a preventable cause of blindness. Br J Ophthalmol
2009; 93: 563–68.
4 Taylor HR, Johnson SL, Schachter J, Caldwell HD, Prendergast RA.
Pathogenesis of trachoma: the stimulus for inflammation.
J Immunol 1987; 138: 3023–27.
5 Thylefors B, Dawson CR, Jones BR, West SK, Taylor HR. A simple
system for the assessment of trachoma and its complications.
Bull World Health Organ 1987; 65: 477–83.
6 Taylor HR. Trachoma: A blinding scourge from the Bronze Age
to the twenty-first century. Melbourne: Centre for Eye Research
Australia, 2008.
7 Kaltenboeck B. Recent advances in the knowledge of animal
chlamydial infections. In: Chernesky M, Caldwell H,
Christiansen G, et al, eds. Chlamydial infections—proceedings of
the Eleventh International Symposium on Human Chlamydial
Infections, Niagara-on-the-Lake, Ontario, Canada, June 18–23,
2006. San Francisco: International Chlamydia Symposium,
2006: 399–408.
www.thelancet.com Vol 384 December 13, 2014
Seminar
8 International Coalition for Trachoma Control. The end in sight—2020
INSight. International Coalition for Trachoma Control, 2011. http://
www.trachomacoalition.org/node/713 (accessed Feb 26, 2014).
9 WHO. Global WHO Alliance for the Elimination of Blinding
Trachoma by 2020. Wkly Epidemiol Rec 2012; 87: 161–68.
10 WHO. Trachoma: status of endemicity for blinding trachoma by
country 2013. http://apps.who.int/gho/data/node.main.A1645
(accessed Feb 26, 2014).
11 WHO. Report of the 3rd global scientific meeting on trachoma
elimination (Johns Hopkins University, Baltimore, Maryland; 19–20
July, 2010). http://www.who.int/blindness/publications/3RDGLOBAL
SCIENTIFICMEETINGONTRACHOMA.pdf (accessed Feb 26, 2014).
12 Global atlas of trachoma. http://www.trachomaatlas.org (accessed
Feb 26, 2014).
13 WHO. Global Alliance for the Elimination of Blinding Trachoma
by 2020—progress report on elimination of trachoma, 2012.
Wkly Epidemiol Rec 2013; 88: 242–51.
14 West SK, Muñoz B, Turner VM, Mmbaga BBO, Taylor HR.
The epidemiology of trachoma in central Tanzania. Int J Epidemiol
1991; 20: 1088–92.
15 Ngondi J, Onsarigo A, Adamu L, et al. The epidemiology of
trachoma in Eastern Equatoria and Upper Nile States, southern
Sudan. Bull World Health Organ 2005; 83: 904–12.
16 Ngondi J, Gebre T, Shargie EB, et al. Evaluation of three years of
the SAFE strategy (Surgery, Antibiotics, Facial cleanliness and
Environmental improvement) for trachoma control in five districts
of Ethiopia hyperendemic for trachoma. Trans R Soc Trop Med Hyg
2009; 103: 1001–10.
17 Solomon AW, Holland MJ, Burton MJ, et al. Strategies for control of
trachoma: observational study with quantitative PCR. Lancet 2003;
362: 198–204.
18 Grassly NC, Ward ME, Ferris S, Mabey DC, Bailey RL. The natural
history of trachoma infection and disease in a Gambian cohort with
frequent follow-up. PLoS Negl Trop Dis 2008; 2: e341.
19 Taylor HR, Siler JA, Mkocha HA, et al. Longitudinal study of the
microbiology of endemic trachoma. J Clin Microbiol 1991; 29: 1593–95.
20 Courtright P, Sheppard J, Schachter J, Said ME, Dawson CR.
Trachoma and blindness in the Nile Delta: current patterns and
projections for the future in the rural Egyptian population.
Br J Ophthalmol 1989; 73: 536–40.
21 Tabbara KF, al-Omar OM. Trachoma in Saudi Arabia.
Ophthalmic Epidemiol 1997; 4: 127–40.
22 Khandekar R, Mohammed AJ. The prevalence of trachomatous
trichiasis in Oman (Oman eye study 2005). Ophthalmic Epidemiol
2007; 14: 267–72.
23 Taylor HR, Rapoza PA, West S, et al. The epidemiology of infection
in trachoma. Invest Ophthalmol Vis Sci 1989; 30: 1823–33.
24 West S, Muñoz B, Lynch M, et al. Impact of face-washing on
trachoma in Kongwa, Tanzania. Lancet 1995; 345: 155–58.
25 Abdou A, Munoz BE, Nassirou B, et al. How much is not enough?
A community randomized trial of a Water and Health Education
programme for Trachoma and Ocular C trachomatis infection in
Niger. Trop Med Int Health 2010; 15: 98–104.
26 McCauley AP, Lynch M, Pounds MB, West S. Changing water-use
patterns in a water-poor area: lessons for a trachoma intervention
project. Soc Sci Med 1990; 31: 1233–38.
27 Blake IM, Burton MJ, Bailey RL, et al. Estimating household and
community transmission of ocular Chlamydia trachomatis.
PLoS Negl Trop Dis 2009; 3: e401.
28 Bailey R, Osmond C, Mabey DCW, Whittle HC, Ward ME. Analysis
of the household distribution of trachoma in a Gambian village
using a Monte Carlo simulation procedure. Int J Epidemiol 1989;
18: 944–51.
29 Broman AT, Shum K, Munoz B, Duncan DD, West SK.
Spatial clustering of ocular chlamydial infection over time
following treatment, among households in a village in Tanzania.
Invest Ophthalmol Vis Sci 2006; 47: 99–104.
30 Congdon N, West S, Vitale S, Katala S, Mmbaga BB. Exposure
to children and risk of active trachoma in Tanzanian women.
Am J Epidemiol 1993; 137: 366–72.
31 Emerson PM, Bailey RL, Mahdi OS, Walraven GE, Lindsay SW.
Transmission ecology of the fly Musca sorbens, a putative vector
of trachoma. Trans R Soc Trop Med Hyg 2000; 94: 28–32.
2149
 Seminar
32 Miller K, Pakpour N, Yi E, et al. Pesky trachoma suspect finally
caught. Br J Ophthalmol 2004; 88: 750–51.
33 Emerson PM, Lindsay SW, Alexander N, et al. Role of flies and
provision of latrines in trachoma control: cluster-randomised
controlled trial. Lancet 2004; 363: 1093–98.
34 Courtright P, Sheppard J, Lane S, Sadek A, Schachter J,
Dawson CR. Latrine ownership as a protective factor in
inflammatory trachoma in Egypt. Br J Ophthalmol 1991; 75: 322–25.
35 Carlson JH, Porcella SF, McClarty G, Caldwell HD. Comparative
genomic analysis of Chlamydia trachomatis oculotropic and
genitotropic strains. Infect Immun 2005; 73: 6407–18.
36 Harris SR, Clarke IN, Seth-Smith HM, et al. Whole-genome
analysis of diverse Chlamydia trachomatis strains identifies
phylogenetic relationships masked by current clinical typing.
Nat Genet 2012; 44: 413–19, S1.
37 Hu VH, Holland MJ, Burton MJ. Trachoma: protective and
pathogenic ocular immune responses to Chlamydia trachomatis.
PLoS Negl Trop Dis 2013; 7: e2020.
38 Ngondi J, Ole-Sempele F, Onsarigo A, et al. Blinding trachoma
in postconflict southern Sudan. PLoS Med 2006; 3: e478.
39 Wolle MA, Muñoz BE, Mkocha H, West SK. Constant ocular
infection with Chlamydia trachomatis predicts risk of scarring
in children in Tanzania. Ophthalmology 2009; 116: 243–47.
40 Bobo LD, Novak N, Muñoz B, Hsieh YH, Quinn TC, West S.
Severe disease in children with trachoma is associated with
persistent Chlamydia trachomatis infection. J Infect Dis 1997;
176: 1524–30.
41 West SK, Muñoz B, Lynch M, Kayongoya A, Mmbaga BBO,
Taylor HR. Risk factors for constant, severe trachoma among
preschool children in Kongwa, Tanzania. Am J Epidemiol 1996;
143: 73–78.
42 West SK, Muñoz B, Mkocha H, Hsieh YH, Lynch MC. Progression
of active trachoma to scarring in a cohort of Tanzanian children.
Ophthalmic Epidemiol 2001; 8: 137–44.
43 Michel CEC, Roper KG, Divena MA, Lee HH, Taylor HR.
Correlation of clinical trachoma and infection in Aboriginal
communities. PLoS Negl Trop Dis 2011; 5: e986.
44 Ward M, Bailey R, Lesley A, Kajbaf M, Robertson J, Mabey D.
Persisting inapparent chlamydial infection in a trachoma endemic
community in The Gambia. Scand J Infect Dis Suppl 1990;
69: 137–48.
45 Smith A, Muñoz B, Hsieh YH, Bobo L, Mkocha H, West S.
OmpA genotypic evidence for persistent ocular Chlamydia trachomatis
infection in Tanzanian village women. Ophthalmic Epidemiol 2001;
8: 127–35.
46 Hu VH, Massae P, Weiss HA, et al. Bacterial infection in
scarring trachoma. Invest Ophthalmol Vis Sci 2011; 52: 2181–86.
47 Bailey RL, Natividad-Sancho A, Fowler A, et al. Host genetic
contribution to the cellular immune response to
Chlamydia trachomatis: heritability estimate from a Gambian twin
study. Drugs Today (Barc) 2009; 45 (suppl B): 45–50.
48 Burton MJ, Holland MJ, Makalo P, et al. Profound and sustained
reduction in Chlamydia trachomatis in The Gambia: a five-year
longitudinal study of trachoma endemic communities.
PLoS Negl Trop Dis 2010; 4: 1–10.
49 Muñoz B, Bobo L, Mkocha H, Lynch M, Hsieh YH, West S.
Incidence of trichiasis in a cohort of women with and without
scarring. Int J Epidemiol 1999; 28: 1167–71.
50 Bowman RJC, Jatta B, Cham B, et al. Natural history of
trachomatous scarring in The Gambia: results of a 12-year
longitudinal follow-up. Ophthalmology 2001; 108: 2219–24.
51 el-Asrar AM, Van den Oord JJ, Geboes K, Missotten L, Emarah MH,
Desmet V. Immunopathology of trachomatous conjunctivitis.
Br J Ophthalmol 1989; 73: 276–82.
52 Abu el-Asrar AM, Geboes K, al-Kharashi SA, Tabbara KF,
Missotten L. Collagen content and types in trachomatous
conjunctivitis. Eye (Lond) 1998; 12: 735–39.
53 Hu VH, Weiss HA, Massae P, et al. In vivo confocal microscopy
in scarring trachoma. Ophthalmology 2011; 118: 2138–46.
54 Reacher MH, Pe’er J, Rapoza PA, Whittum-Hudson JA,
Taylor HR. T cells and trachoma: their role in cicatricial disease.
Ophthalmology 1991; 98: 334–41.
2150
55 Rasmussen SJ, Eckmann L, Quayle AJ, et al. Secretion of
proinflammatory cytokines by epithelial cells in response to
Chlamydia infection suggests a central role for epithelial cells
in chlamydial pathogenesis. J Clin Invest 1997; 99: 77–87.
56 Natividad A, Freeman TC, Jeffries D, et al. Human conjunctival
transcriptome analysis reveals the prominence of innate
defense in Chlamydia trachomatis infection. Infect Immun 2010;
78: 4895–911.
57 Burton MJ, Ramadhani A, Weiss HA, et al. Active trachoma is
associated with increased conjunctival expression of IL17A and
profibrotic cytokines. Infect Immun 2011; 79: 4977–83.
58 Abu el-Asrar AM, Geboes K, Tabbara KF, al-Kharashi SA,
Missotten L, Desmet V. Immunopathogenesis of conjunctival
scarring in trachoma. Eye (Lond) 1998; 12: 453–60.
59 Gall A, Horowitz A, Joof H, et al. Systemic effector and regulatory
immune responses to chlamydial antigens in trachomatous
trichiasis. Front Microbiol 2011; 2: 10.
60 Taylor HR. Development of immunity to ocular chlamydial
infection. Am J Trop Med Hyg 1990; 42: 358–64.
61 Stephens RS. The cellular paradigm of chlamydial pathogenesis.
Trends Microbiol 2003; 11: 44–51.
62 Peeling RW, Bailey RL, Conway DJ, et al. Antibody response to the
60-kDa chlamydial heat-shock protein is associated with scarring
trachoma. J Infect Dis 1998; 177: 256–59.
63 Holland MJ, Bailey RL, Hayes LJ, Whittle HC, Mabey DCW.
Conjunctival scarring in trachoma is associated with depressed
cell-mediated immune responses to chlamydial antigens.
J Infect Dis 1993; 168: 1528–31.
64 Burton MJ, Bailey RL, Jeffries D, Mabey DCW, Holland MJ.
Cytokine and fibrogenic gene expression in the conjunctivas of
subjects from a Gambian community where trachoma is endemic.
Infect Immun 2004; 72: 7352–56.
65 Burton MJ, Rajak SN, Bauer J, et al. Conjunctival transcriptome
in scarring trachoma. Infect Immun 2011; 79: 499–511.
66 Darville T, O’Neill JM, Andrews CW Jr, Nagarajan UM, Stahl L,
Ojcius DM. Toll-like receptor-2, but not Toll-like receptor-4, is
essential for development of oviduct pathology in chlamydial
genital tract infection. J Immunol 2003; 171: 6187–97.
67 Natividad A, Hull J, Luoni G, et al. Innate immunity in ocular
Chlamydia trachomatis infection: contribution of IL8 and CSF2
gene variants to risk of trachomatous scarring in Gambians.
BMC Med Genet 2009; 10: 138.
68 Natividad A, Cooke G, Holland MJ, et al. A coding
polymorphism in matrix metalloproteinase 9 reduces risk of
scarring sequelae of ocular Chlamydia trachomatis infection.
BMC Med Genet 2006; 7: 40.
69 Bowman RJC, Faal H, Myatt M, et al. Longitudinal study of
trachomatous trichiasis in the Gambia. Br J Ophthalmol 2002;
86: 339–43.
70 Frick KD, Melia BM, Buhrmann RR, West SK. Trichiasis and
disability in a trachoma-endemic area of Tanzania. Arch Ophthalmol
2001; 119: 1839–44.
71 Dhaliwal U, Nagpal G, Bhatia MS. Health-related quality of life in
patients with trachomatous trichiasis or entropion.
Ophthalmic Epidemiol 2006; 13: 59–66.
72 Yang JL, Schachter J, Moncada J, et al. Comparison of an rRNA-based
and DNA-based nucleic acid amplification test for the detection of
Chlamydia trachomatis in trachoma. Br J Ophthalmol 2007;
91: 293–95.
73 Keenan JD, See CW, Moncada J, et al. Diagnostic characteristics of
tests for ocular Chlamydia after mass azithromycin distributions.
Invest Ophthalmol Vis Sci 2012; 53: 235–40.
74 Keenan JD, Ayele B, Gebre T, et al. Ribosomal RNA evidence of
ocular Chlamydia trachomatis infection following 3 annual mass
azithromycin distributions in communities with highly prevalent
trachoma. Clin Infect Dis 2012; 54: 253–56.
75 See CW, Alemayehu W, Melese M, et al. How reliable are tests for
trachoma?—a latent class approach. Invest Ophthalmol Vis Sci 2011;
52: 6133–37.
76 Lakew T, House J, Hong KC, et al. Reduction and return of
infectious trachoma in severely affected communities in Ethiopia.
PLoS Negl Trop Dis 2009; 3: e376.
www.thelancet.com Vol 384 December 13, 2014

77 Keenan JD, Lakew T, Alemayehu W, et al. Slow resolution of
clinically active trachoma following successful mass antibiotic
treatments. Arch Ophthalmol 2011; 129: 512–13.
78 Munoz B, Stare D, Mkocha H, Gaydos C, Quinn T, West SK.
Can clinical signs of trachoma be used after multiple rounds
of mass antibiotic treatment to indicate infection?
Invest Ophthalmol Vis Sci 2011; 52: 8806–10.
79 Ngondi J, Reacher M, Matthews F, Brayne C, Emerson P. Trachoma
survey methods: a literature review. Bull World Health Organ 2009;
87: 143–51.
80 International Coalition for Trachoma Control. Global
Trachoma Mapping Project—training for mapping of trachoma,
version 2. International Coalition for Trachoma Control, 2013.
http://www.trachomacoalition.org/sites/default/files/uploads/
resources/GTMP_2ndEdition_Web (1).pdf (accessed Feb 26, 2014).
81 Negrel AD, Taylor HR, West S. Guidelines for the rapid assessment
for blinding trachoma. Geneva: World Health Organization, 2001.
82 Myatt M, Limburg H, Minassian D, Katyola D. Field trial of
applicability of lot quality assurance sampling survey method
for rapid assessment of prevalence of active trachoma.
Bull World Health Organ 2003; 81: 877–85.
83 Rajak SN, Collin JRO, Burton MJ. Trachomatous trichiasis and
its management in endemic countries. Surv Ophthalmol 2012;
57: 105–35.
84 Reacher M, Foster A, Huber J. Trichiasis surgery for trachoma—
the bilamellar tarsal rotation procedure. Geneva: World Health
Organization, 1993.
85 Reacher MH, Muñoz B, Alghassany A, Daar AS, Elbualy M,
Taylor HR. A controlled trial of surgery for trachomatous trichiasis
of the upper lid. Arch Ophthalmol 1992; 110: 667–74.
86 Baltussen RM, Sylla M, Frick KD, Mariotti SP. Cost-effectiveness
of trachoma control in seven world regions. Ophthalmic Epidemiol
2005; 12: 91–101.
87 Burton MJ, Kinteh F, Jallow O, et al. A randomised controlled trial
of azithromycin following surgery for trachomatous trichiasis in
the Gambia. Br J Ophthalmol 2005; 89: 1282–88.
88 Woreta TA, Munoz BE, Gower EW, Alemayehu W, West SK.
Effect of trichiasis surgery on visual acuity outcomes in Ethiopia.
Arch Ophthalmol 2009; 127: 1505–10.
89 Rajak SN, Habtamu E, Weiss HA, et al. Absorbable versus silk
sutures for surgical treatment of trachomatous trichiasis in
Ethiopia: a randomised controlled trial. PLoS Med 2011; 8: e1001137.
90 West SK, West ES, Alemayehu W, et al. Single-dose azithromycin
prevents trichiasis recurrence following surgery: randomized trial
in Ethiopia. Arch Ophthalmol 2006; 124: 309–14.
91 Khandekar R, Mohammed AJ, Courtright P. Recurrence of
trichiasis: a long-term follow-up study in the Sultanate of Oman.
Ophthalmic Epidemiol 2001; 8: 155–61.
92 Thanh TTK, Khandekar R, Luong VQ, Courtright P. One year
recurrence of trachomatous trichiasis in routinely operated
Cuenod Nataf procedure cases in Vietnam. Br J Ophthalmol 2004;
88: 1114–18.
93 Burton MJ, Bowman RJC, Faal H, et al. Long term outcome of
trichiasis surgery in the Gambia. Br J Ophthalmol 2005;
89: 575–79.
94 Ezz al Arab G, Tawfik N, El Gendy R, Anwar W, Courtright P.
The burden of trachoma in the rural Nile Delta of Egypt: a survey
of Menofiya governorate. Br J Ophthalmol 2001; 85: 1406–10.
95 Rajak SN, Makalo P, Sillah A, et al. Trichiasis surgery in The
Gambia: a 4-year prospective study. Invest Ophthalmol Vis Sci 2010;
51: 4996–5001.
96 Merbs SL, West SK, West ES. Pattern of recurrence of trachomatous
trichiasis after surgery surgical technique as an explanation.
Ophthalmology 2005; 112: 705–09.
97 West ES, Mkocha H, Munoz B, et al. Risk factors for postsurgical
trichiasis recurrence in a trachoma-endemic area.
Invest Ophthalmol Vis Sci 2005; 46: 447–53.
98 Zhang H, Kandel RP, Sharma B, Dean D. Risk factors for
recurrence of postoperative trichiasis: implications for trachoma
blindness prevention. Arch Ophthalmol 2004; 122: 511–16.
99 Zhang H, Kandel RP, Atakari HK, Dean D. Impact of oral
azithromycin on recurrence of trachomatous trichiasis in Nepal
over 1 year. Br J Ophthalmol 2006; 90: 943–48.
www.thelancet.com Vol 384 December 13, 2014
Seminar
100 Rabiu MM, Abiose A. Magnitude of trachoma and barriers to
uptake of lid surgery in a rural community of northern Nigeria.
Ophthalmic Epidemiol 2001; 8: 181–90.
101 West S, Lynch M, Muñoz B, Katala S, Tobin S, Mmbaga BBO.
Predicting surgical compliance in a cohort of women with
trichiasis. Int Ophthalmol 1994; 18: 105–09.
102 Bowman RJ, Soma OS, Alexander N, et al. Should trichiasis surgery
be offered in the village? A community randomised trial of village
vs health centre-based surgery.Trop Med Int Health 2000; 5: 528–33.
103 Rajak SN, Habtamu E, Weiss HA, et al. Why do people not attend
for treatment for trachomatous trichiasis in Ethiopia? A study of
barriers to surgery. PLoS Negl Trop Dis 2012; 6: e1766.
104 Khandekar R, Al-Hadrami K, Sarvanan N, Al Harby S,
Mohammed AJ. Recurrence of trachomatous trichiasis 17 years
after bilamellar tarsal rotation procedure. Am J Ophthalmol 2006;
141: 1087–91.
105 Habte D, Gebre T, Zerihun M, Assefa Y. Determinants of uptake
of surgical treatment for trachomatous trichiasis in North Ethiopia.
Ophthalmic Epidemiol 2008; 15: 328–33.
106 Alemayehu W, Melese M, Bejiga A, Worku A, Kebede W,
Fantaye D. Surgery for trichiasis by ophthalmologists versus
integrated eye care workers: a randomized trial. Ophthalmology
2004; 111: 578–84.
107 Rajak SN, Habtamu E, Weiss HA, et al. Epilation for trachomatous
trichiasis and the risk of corneal opacification. Ophthalmology 2012;
119: 84–89.
108 West ES, Munoz B, Imeru A, Alemayehu W, Melese M, West SK.
The association between epilation and corneal opacity among eyes
with trachomatous trichiasis. Br J Ophthalmol 2006; 90: 171–74.
109 Rajak SN, Habtamu E, Weiss HA, et al. Surgery versus epilation
for the treatment of minor trichiasis in Ethiopia: a randomised
controlled noninferiority trial. PLoS Med 2011; 8: e1001136.
110 Evans JR, Solomon AW. Antibiotics for trachoma.
Cochrane Database Syst Rev 2011; 3: CD001860.
111 Atik B, Thanh TTK, Luong VQ, Lagree S, Dean D. Impact of
annual targeted treatment on infectious trachoma and susceptibility
to reinfection. JAMA 2006; 296: 1488–97.
112 Chidambaram JD, Alemayehu W, Melese M, et al. Effect of a
single mass antibiotic distribution on the prevalence of infectious
trachoma. JAMA 2006; 295: 1142–46.
113 Lee S, Alemayehu W, Melese M, et al. Chlamydia on children
and flies after mass antibiotic treatment for trachoma.
Am J Trop Med Hyg 2007; 76: 129–31.
114 House JI, Ayele B, Porco TC, et al. Assessment of herd protection
against trachoma due to repeated mass antibiotic distributions:
a cluster-randomised trial. Lancet 2009; 373: 1111–18.
115 Schachter J, West SK, Mabey D, et al. Azithromycin in control of
trachoma. Lancet 1999; 354: 630–35.
116 Gebre T, Ayele B, Zerihun M, et al. Comparison of annual versus
twice-yearly mass azithromycin treatment for hyperendemic
trachoma in Ethiopia: a cluster-randomised trial. Lancet 2012;
379: 143–51.
117 West SK, Munoz B, Mkocha H, et al. Infection with
Chlamydia trachomatis after mass treatment of a trachoma
hyperendemic community in Tanzania: a longitudinal study.
Lancet 2005; 366: 1296–300.
118 Burton MJ, Holland MJ, Makalo P, et al. Re-emergence of
Chlamydia trachomatis infection after mass antibiotic treatment
of a trachoma-endemic Gambian community: a longitudinal study.
Lancet 2005; 365: 1321–28.
119 Solomon AW, Holland MJ, Alexander NDE, et al. Mass treatment
with single-dose azithromycin for trachoma. N Engl J Med 2004;
351: 1962–71.
120 Yohannan J, Munoz B, Mkocha H, et al. Can we stop mass
drug administration prior to 3 annual rounds in communities
with low prevalence of trachoma? PRET Ziada trial results.
JAMA Ophthalmol 2013; 131: 431–36.
121 Solomon AW, Harding-Esch E, Alexander NDE, et al. Two doses
of azithromycin to eliminate trachoma in a Tanzanian community.
N Engl J Med 2008; 358: 1870–71.
122 Melese M, Chidambaram JD, Alemayehu W, et al. Feasibility
of eliminating ocular Chlamydia trachomatis with repeat mass
antibiotic treatments. JAMA 2004; 292: 721–25.
2151
 Seminar
123 West SK, Munoz B, Mkocha H, Gaydos CA, Quinn TC. Number
of years of annual mass treatment with azithromycin needed to
control trachoma in hyper-endemic communities in Tanzania.
J Infect Dis 2011; 204: 268–73.
124 Lietman T, Porco T, Dawson C, Blower S. Global elimination
of trachoma: how frequently should we administer mass
chemotherapy? Nat Med 1999; 5: 572–76.
125 Biebesheimer JB, House J, Hong KC, et al. Complete local
elimination of infectious trachoma from severely affected
communities after six biannual mass azithromycin distributions.
Ophthalmology 2009; 116: 2047–50.
126 Hotez PJ. Mass drug administration and integrated control for
the world’s high-prevalence neglected tropical diseases.
Clin Pharmacol Ther 2009; 85: 659–64.
127 Dembélé M, Bamani S, Dembélé R, et al. Implementing preventive
chemotherapy through an integrated National Neglected Tropical
Disease Control Program in Mali. PLoS Negl Trop Dis 2012; 6: e1574.
128 Blake IM, Burton MJ, Solomon AW, et al. Targeting antibiotics to
households for trachoma control. PLoS Negl Trop Dis 2010; 4: e862.
129 West SK, Bailey R, Munoz B, et al. A randomized trial of two
coverage targets for mass treatment with azithromycin for
trachoma. PLoS Negl Trop Dis 2013; 7: e2415.
130 Keenan JD, Ayele B, Gebre T, et al. Childhood mortality in a cohort
treated with mass azithromycin for trachoma. Clin Infect Dis 2011;
52: 883–88.
131 Fry AM, Jha HC, Lietman TM, et al. Adverse and beneficial
secondary effects of mass treatment with azithromycin to eliminate
blindness due to trachoma in Nepal. Clin Infect Dis 2002;
35: 395–402.
132 Coles CL, Seidman JC, Levens J, Mkocha H, Munoz B,
West S. Association of mass treatment with azithromycin in
trachoma-endemic communities with short-term reduced risk of
diarrhea in young children. Am J Trop Med Hyg 2011; 85: 691–96.
2152
133 Hong KC, Schachter J, Moncada J, Zhou Z, House J, Lietman TM.
Lack of macrolide resistance in Chlamydia trachomatis after mass
azithromycin distributions for trachoma. Emerg Infect Dis 2009;
15: 1088–90.
134 Haug S, Lakew T, Habtemariam G, et al. The decline of
pneumococcal resistance after cessation of mass antibiotic
distributions for trachoma. Clin Infect Dis 2010; 51: 571–74.
135 Schémann J-F, Sacko D, Malvy D, et al. Risk factors for trachoma
in Mali. Int J Epidemiol 2002; 31: 194–201.
136 Hsieh YH, Bobo LD, Quinn TC, West SK. Risk factors for
trachoma: 6-year follow-up of children aged 1 and 2 years.
Am J Epidemiol 2000; 152: 204–11.
137 Ngondi J, Onsarigo A, Matthews F, et al. Effect of 3 years of SAFE
(surgery, antibiotics, facial cleanliness, and environmental change)
strategy for trachoma control in southern Sudan: a cross-sectional
study. Lancet 2006; 368: 589–95.
138 West S, Lynch M, Turner V, et al. Water availability and trachoma.
Bull World Health Organ 1989; 67: 71–75.
139 WHO. Report of the Twelfth Meeting of the WHO Alliance for the
Global Elimination of Blinding Trachoma (Geneva, Switzerland).
Geneva: World Health Organization, 2008. http://www.who.int/
entity/blindness/publications/GET12-REPORT-ENG_final.pdf
(accessed Feb 26, 2014).
140 Montgomery MA, Bartram J. Short-sightedness in sight-saving:
half a strategy will not eliminate blinding trachoma.
Bull World Health Organ 2010; 88: 82.
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