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Epidemiologic Reviews
Copyright © 1997 by The Johns Hopkins University School of Hygiene and Public Health
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Vol. 19, No. 2
Printed in U.S.A.
Trachoma: The Forgotten Cause of Blindness
Beatriz Mufioz and Sheila West
INTRODUCTION
species, C. trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae, can be further separated into several serovars. Within C. trachomatis, the primary serovars responsible for trachoma are A, B, Ba, and C.
The serovars D-K are associated with genital infections, and L1-L3 are the lymphogranuloma venereum
serovars (2).
Trachoma, the second leading cause of blindness
world wide, continues to be hyperendemic in many
areas of Africa, Asia, and the Middle East. Caused by
an ocular infection with Chlamydia trachomatis, this
chronic conjunctivitis results in more blindness than
any other infectious eye disease. Once endemic in
most countries, trachoma has largely disappeared from
Europe and the Americas. Because of its disappearance from developed countries and its endemicity in
the poorest of communities, trachoma has been largely
forgotten as a public health issue. Communities with
trachoma are often those with the fewest resources to
take on health issues, and trachoma strikes the most
vulnerable members of those communities—women
and children. Second only to cataract as the leading
cause of blindness, trachoma affects an estimated
300-500 million people of whom 5-7 million are
blind (1).
In the last 10 years, there have been considerable advances in our understanding of the epidemiology
and approaches to trachoma control that have major
ramifications for public health measures against this disease. In this review, we summarize the characteristics
of trachoma, the epidemiology and risk factors for the
disease, and promising approaches to control strategies.
The strides made in research on trachoma clearly warrant a reprioritization of this forgotten disease.
Outer membrane proteins
From an immunologic perspective, the outer membrane proteins on C. trachomatis are the principal
antigens that distinguish the serovars. The major outer
membrane protein is the immunodominant protein,
accounting for 60 percent of the outer membrane proteins. In trachoma-endemic areas, Dean et al. (3) and
Hayes et al. (4), in Tanzania and Gambia, respectively,
have documented sequence polymorphism in the major outer membrane protein by demonstrating multiple
genovars. These gene-typing studies indicate many
more variants than previous studies of serovars have
indicated; this antigenic variation may be the mechanism by which chlamydia escape immune surveillance
and allow for multiple bouts of reinfection with the
same serovar.
Development cycle
Chlamydia have a unique developmental cycle distinguished by two forms, the elementary body and the
reticulate body. The elementary body is the metabolically inert, infectious particle that, through endocytosis, infects susceptible host cells. Endocytosis is followed by transformation of the elementary body into a
reticulate body that is metabolically active and multiplies rapidly over the next 15 hours. Chlamydia lack a
cytochrome system and cannot produce adenosine 5'triphosphate (ATP); the host cell ATP is used to transport essential nutrients across the chlamydia cell wall.
The reticulate bodies are noninfectious, but approximately 20 hours after infection, the reticulate bodies
transform into elementary bodies. The reticulate bodies and elementary bodies are enclosed in an intracellular inclusion body, which can occupy up to 90 percent of the.cell cytoplasm. With rupture of the cell,
THE ORGANISM: C. TRACHOMATIS
C. trachomatis, the causative agent of trachoma, is
an obligate intracellular organism that has no free
living state. There is no known animal reservoir for
human chlamydia infection. The chlamydia are given
a place in their own order, chlamydials. The three
Received for publication January 2,1996, and accepted for publication June 12, 1997.
Abbreviations: ATP, adenosine 5'-triphosphate; ELISA, enzymelinked immunosorbent assay; PCR, polymerase chain reaction.
From the Dana Center for Ophthalmology, Wilmer Eye Institute,
Johns Hopkins University School of Medicine, Baltimore, MD.
Reprint requests to Dr. Sheila West, Dana Center for Ophthalmology, Wilmer Eye Institute 129, Johns Hopkins University School
of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287-9019.
205
206
Munoz and West
infection of other cells by the newly transformed elementary bodies ensues. C. trachomatis targets columnar and squamocolumnar epithelial cells and is thus an
infection of the conjunctiva, genital, respiratory, and
intestinal tissues. Characteristics of the developmental
cycle of chlamydia may well explain some features of
infection, such as possible persistence.
Infection
A single episode of acute chlamydial infection, as
seen in newborns in the United States, is not considered trachoma because there is virtually no risk of
prolonged inflammation or the blinding complications
that characterize eyes exposed to multiple bouts of
infection in trachoma-endemic areas. Repeated episodes of infection throughout childhood and young
adulthood appear to be necessary to produce the complications seen in later life (5, 6). Repeated infection
induces the immunopathology that characterizes the
clinical signs of scarring, trichiasis, and entropion seen
later in life.
CLINICAL SIGNS OF TRACHOMA
Active trachoma is a chronic, follicular conjunctivitis, characterized by an inflammatory response to a
series of infections throughout childhood. Children
with active trachoma present with follicles and papillae, the latter a marker for the intensity of the inflammation. Follicles are yellow or white "spots" in the
tarsal conjunctiva and consist of lymphoid tissue containing B lymphocytes. Severe, inflammatory trachoma presents as thickening of the conjunctiva with
inflammation obscuring the deep tarsal vessels. The
presence of pus with severe inflammation usually indicates a bacterial infection. Limbal follicles may appear, and new vessels develop, producing corneal pannus. Once the limbal follicles resolve, depressions
remain on the cornea, resulting in the pathognomonic
sign of trachoma, "Herbert's pits."
The community pool of active trachoma resides in
the children, who may have ongoing signs of active
trachoma as a result of repeated infections. The signs
may never clear in children repeatedly exposed to C.
trachomatis. In a cynomologus monkey model of trachoma, animals receiving weekly inoculations of C.
trachomatis showed a waning of the severe inflammatory response after 2 months but maintained a follicular response as long as the reinoculation of the ocular
challenge was maintained (6).
Multiple infections or prolonged, severe infection is
often followed by evidence of scarring of the conjunctiva. Even in late childhood and early adulthood, the
scarring may be prominent and obscure evidence of
active disease, although in some cases of scarring
without evidence of active disease, there is laboratory
evidence of C. trachomatis infection (7, 8). By middle
age, for some cases, the scarring is significant enough
to cause trichiasis, or inturned eyelashes. Trichiasis,
and entropion, eventually require lid surgery to correct
the eyelashes rubbing on the globe and to prevent
visual loss from corneal opacification.
The visual loss from trachoma is due to irreversible
corneal damage. The damage is believed to be the
result of multiple processes. Scarring may affect the
meibomian orifices and result in atrophy of the gland
and development of features of dry eye; similarly, the
lacrimal ducts may be affected, resulting in aqueous
deficiency. Inturned eyelashes abrade the corneal surface, which may be drier than normal, and allow
secondary infections. Ultimately, the cornea develops
opacities and the destruction is irreversible.
The World Health Organization has published a
simple classification scheme for assessing trachoma in
community-based surveys (table 1) (9). Each of the
signs has relevance for understanding the epidemiology of trachoma in a population. The prevalence of
active disease is represented by the proportion of the
population with TF and/or TI. Those with TI have
severe inflammation, are more likely to have a laboratory test positive for C. trachomatis, and thus need
prompt treatment; the prevalence of TT indicates the
backlog for surgical services; and the prevalence of
CO is an indication of the potential impact of trachoma
on visual impairment in the community. The World
Health Organization trachoma grading scheme is reliable, is easy to teach to eye health workers, and has
been used in a number of surveys (10). For rapid
assessment of the magnitude of the problem of active
trachoma and for planning eye care services for the
TABLE 1. World Health Organization simplified trachoma
grading classification system
Sign
TF
TI
TS
TT
CO
Description
Follicular trachoma: the presence of five or more
follicles in the upper tarsal conjunctiva of at
least 0.5 mm
Inflammatory trachoma: pronounced inflammatory
thickening of the upper tarsal conjunctiva that
obscures more than half of the normal deep tarsal
vessels
Trachomatous scarring: the presence of easily visible
scarring in the tarsal conjunctiva
Trichiasis: evidence of at least one eyelash touching
the globe; evidence of recent removal of intumed
eyelashes is also graded as TT
Corneal opacity: the presence of easily visible corneal
opacity that obscures at least part of the pupillary
margin
Epidemiol Rev Vol. 19, No. 2, 1997
Trachoma
future, the simplified grading scheme is a valuable
tool.
DIAGNOSTIC TESTS FOR C. TRACHOMATIS
The diagnosis of infection with C. trachomatis in
the laboratory can be done by examining stained slides
of conjunctival swabs, growing the organism in tissuecultured cells, or detection of antigen or nucleic acids.
Serologic tests or tear tests for antibody are not helpful
for determining current infections.
With the advent of extremely sensitive tests for
detection of chlamydial DNA, the establishment of a
"gold standard" for determining the sensitivity and
specificity of laboratory tests for C. trachomatis has
become more complicated. Comparison against the
clinical signs of disease is not optimal because many
cases of follicular trachoma no longer have an agent;
the follicular reaction takes time to resolve once the
agent is gone. Moreover, subclinical or preclinical
infections are a well-recognized entity, and a laboratory test may well be positive in the absence of clinical
signs. The sensitivity and specificity of the tests are
affected greatly by the collection, handling, and storage of the samples in the field and in the laboratory and can change the sensitivity of, for example,
tissue culture by as much as 50 percent. Many of the
studies have used Chlamydia culture as the "gold
standard," although the newer techniques are clearly
more sensitive.
Early laboratory tests for C. trachomatis included
direct smears of conjunctival swabs stained with iodine or Giemsa. Giemsa staining is fast, economical,
and more sensitive than iodine; however, it has a low
overall sensitivity, around 30 percent, even in the
presence of severe disease (11, 12).
Tissue culture is considered the most specific test.
Ideally, the sensitivity of tissue culture should be 90
percent or better, but sensitivity is highly dependent on
the degree to which strict requirements for transport
and storage are maintained (7, 11, 13). Moreover,
negative cultures in clearly symptomatic individuals
positive for Chlamydia using other techniques have
been reported (7, 11).
Direct antigen detection tests for diagnosing chlamydial infections have been used widely in the diagnosis and screening of sexually transmitted diseases.
They are expensive and can be labor intensive when
used for trachoma surveys. Identification of elementary bodies in conjunctival smears may be made by
staining with species-specific and antimajor outer
membrane protein fluorescent-tagged antibody. Between 100 and 200 epithelial cells are needed from the
Epidemiol Rev Vol. 19, No. 2, 1997
207
ocular sample before the sample is deemed adequate
for antigen testing. In a large prevalence study of
trachoma in Tanzania, Taylor and colleagues (7) found
11.3 percent of specimens to be inadequate. In this
same study, the sensitivity of direct fluorescent antibody testing against culture was 88 percent and specificity was 87.5 percent. Direct fluorescent antibody
requires a highly trained observer and can be subjective; however, it has the advantage over nonmicroscopic antigen detection tests that the adequacy of the
sample can be determined. The enzyme-linked immunosorbent assay (ELISA) has a sensitivity compared
with culture of anywhere from 66 to 100 percent, with
a specificity of 90-99 percent (8, 11, 14, 15). Some
lipopolysaccharide-specific ELISA testing does crossreact with other microorganisms, and false-positive
tests can result unless confirmatory tests are also done.
The new tests for C. trachomatis, DNA amplification or the polymerase chain reaction (PCR) and ligase
chain reaction tests, are highly promising and gaining
wide acceptance. A number of in-house polymerase
chain reaction tests have been used for detecting C.
trachomatis using labeled DNA probes that detect
specific nucleotide sequences to ribosomal RNA, and
commercial kits are available. The tests are highly
sensitive and specific for C. trachomatis, ranging in
sensitivity from 98 to 100 percent with 99-100 percent specificity (13, 14, 16). Chlamydial PCR tests
were evaluated in trachoma endemic regions of Tanzania and The Gambia (14, 16). In both studies, the
PCR test was more sensitive than other laboratory
techniques. In Tanzania, positive results were obtained
in 95 percent of those with severe trachoma and 54
percent of those with follicular trachoma. In The Gambia, 85 percent of those with severe disease were PCR
positive, and 69 percent of those with mild disease
were positive. In both studies, between 8 percent (The
Gambia) and 24 percent (Tanzania) of those without
trachoma were also positive; in Tanzania, 70 percent
of those cases were mild, having one to four follicles.
In The Gambia, the clinically negative subjects who
were PCR positive were more likely to develop signs
of trachoma from 1 to 6 months later. These findings
suggest that some of the cases who were PCR positive
but clinically negative were either incubating the disease or were such mild cases that they did not meet the
World Health Organization definitions of trachoma.
Use of these newer diagnostic agents has energized
the epidemiologic studies of trachoma because it has
enabled more detailed studies of the relationship between infection and clinical disease and investigations
into the role of persistent or latent infection and the
risk of scarring.
208
Mufioz and West
IMMUNITY
The acquisition of repeated infections with C. trachomatis in trachoma endemic areas suggests the absence of any long-lasting protective immunity. Neutralizing antibodies against the major outer membrane
protein have been shown to protect against infection in
the laboratory, but the extent of natural immune response in producing some protection is not well clarified (17). The understanding of host defense mechanisms that promote the persistence or eliminate the
growth of C. trachomatis is essential for the design of
an effective vaccine. Specifically, research should focus on clarifying the role of Thl-like responses in
clearance of infection as well as the role of Th-2
responses in producing more severe disease.
In animal models, immunity was shown to be short
lived and serotype specific (18, 19). Reinfection with
a different serovar tends to raise antibody responses to
the previous serovar (20). There is no evidence that
tear antibodies confer protection against chlamydial
infection (21, 22). Byrne and Krueger have shown that
gamma interferon inhibits chlamydial growth and viability in cell cultures and probably serves as one host
defense mechanism (23).
In fact, the immune response may well be responsible for the serious clinical manifestations of trachoma.
Severe inflammation may be the result of a delayed
hypersensitivity response in ocular tissues elicited by
the 57-kD chlamydial heat shock protein (24-26). Some
data from cell cultures suggest a role of cytokines in
inducing the fibrogenesis characteristic of the submucosal fibrosis in chronic sequelae of trachoma (27). Data
from a trachoma region in The Gambia suggest that
the peripheral blood lymphocyte proliferative responses
in subjects with scarring showed a predominantly Th2type response to a range of chlamydial antigens. This
response suggests that chronic sequelae of infection
can occur in individuals who have an immune response that prevents clearance (28).
Genetic polymorphism
Currently there is considerable interest in characterizing the genetic variation in the ompl gene (which
encodes the major outer membrane protein) in Chlamydia. It is possible that variants are selected by
immune pressure and escape from immune surveillance, which would help explain recurrent infections.
Such findings have major implications for vaccine
development using the major outer membrane protein
as a candidate. In a study in The Gambia, Hayes and
coworkers (29) found variants of C. trachomatis in
two villages where surveys were conducted on selected individuals over a year. During that period of
time, four genovar variants accounted for 89 percent
of infections, although the introduction of novel variants was observed. The data do suggest that there was
insufficient immune response to clear the infecting
variant for the majority of those with recurrent infection at follow-up. Similar studies on samples from
Tunisia and from Tanzania have shown genovar variants in those populations (3, 30).
Persistence
There is controversy over the role, if any, of persistent infection as a factor in the pathogenesis of trachoma. Electron micrographic studies have shown that
in cell culture systems, some epithelial cells contain
aberrant, nonculturable, reticulate body-like structures
that may represent persistent or latent infection (31).
Such forms may play a role in heightened hypersensitivity to infection or may explain why conjunctival
scarring should proceed in the absence of demonstrable infection. The findings of Mabey et al. (32) and
Taylor et al. (7)—that in those with no inflammatory
disease, scarring was associated with antigen positivity—
tend to support this conjecture. However, studies of
migrant Sikh Indians showed that those with previous
trachoma who moved to Canada (an area with no
trachoma) had no additional cases of disease, suggesting that relapse or persistence is not a major factor in
recurrent disease (33). Further work, especially in the
demonstration of persistent or latent forms in vivo, is
needed.
EPIDEMIOLOGY OF TRACHOMA
History
Civilizations have been afflicted with trachoma
since ancient time (34). In Egypt, the features of
trachoma were described in the Ebers Papyrus, a collection of writings by ancient Egyptian physicians
(35); epilation devices used for removing inturned
eyelashes were present in Egyptian tombs as early as
the nineteenth century B.C. (36). Trachoma is a derivation of the Greek word for "rough," or "swelling"
(35), and ancient Greek physicians, including
Hippocrates, wrote descriptions of treating trachoma
and the chronic sequelae of infection (36-38).
In the early 1800s, Egypt became a military battle
ground for England, France, and Turkey; and trachoma quickly spread to Europe. Much of the blindness attributed to trachoma was probably gonococcal
conjunctivitis, but simultaneous infection with trachoma was likely (36). Public health strategies to
control the spread of infection were described in the
early 1900s (36, 38-40). In 1920, Elliot recommended
Epidemiol Rev Vol. 19, No. 2, 1997
Trachoma
trying to control the fly population and avoiding hand/
eye contact as mechanisms to decrease transmission (40).
Prevalence
Although trachoma has largely disappeared from
most of the Western world, it continues to be a major
cause of blindness in the developing countries. Trachoma is still prevalent in large regions of Africa, the
Middle East, Southwestern Asia, the Indian Subcontinent, and Aboriginal communities in Australia. In
addition, there are small foci of blinding disease in
Central and South America (41). Within these countries, trachoma is more common in the particularly
underdeveloped areas, where good water supplies and
basic sanitation services are lacking. Even within hyperendemic areas, trachoma clusters both at the neighborhood and at the household level (42-44). Trachoma is an infectious disease, and transmission can
occur by sharing clothes, towels, or sleeping quarters.
Therefore, trachoma is passed among family members
and, in some settings, between families in households
that are in close proximity (45). The variationin trachoma prevalence between neighborhoods in the same
village can be several-fold (42).
Crowded living conditions in the family unit appear
to increase the risk of trachoma. With increasing numbers of persons per sleeping area, the prevalence of
active trachoma has been shown to increase (43, 46,
47). The association is logical, as there is more exposure to infection or disease via close contact (32, 48).
A large family per se is not necessarily a risk factor for
active trachoma in children (49, 50). Rather, the risk
appears to be related to the likelihood of contact with
an infected individual, and larger families are more
likely to have preschool children who have the highest
prevalence of infection. Thus, several studies have
found that mothers of children with trachoma are more
likely themselves to have active disease, compared
with women who either did not take care of children or
whose children did not have trachoma (51-53). In
studies of maternal genital infection as a source of
trachoma, Brunham et al. (54) found no evidence that
maternal or perinatal transmission of C. trachomatis
was an important determinant of infection or disease in
children.
The stability and endemicity of the disease in the
community largely determines the age distribution of
the individual signs of trachoma. In hyperendemic
areas, active disease is most common in preschool
children, with prevalences as high as 60-90 percent
(42, 55). The prevalence of active trachoma decreases
with increasing age, with less than 5 percent of the
adults showing signs of active disease (42). In areas
where trachoma has been endemic for a long period of
Epidemiol Rev Vol. 19, No. 2, 1997
209
time, conjunctival scarring increases with age and is as
high as 90 percent in some areas (55). Although rates
of active disease are roughly similar in male and
female children, the later sequelae of trichiasis and
entropion and corneal opacities due to trachoma are
more common in women than in men (42, 55, 56). In
one location in Egypt, 75 percent of the women and 50
percent of the men older than 45 years had trichiasis or
entropion (55). A typical pattern of the age and sex
distribution of active and chronic trachoma for a hyperendemic area can be illustrated by figure 1.
In areas where active trachoma has largely disappeared, a different pattern of the presentation of trachoma is observed. The prevalences of lid scarring and
chronic sequela are more common than active disease,
and trachoma is present only in adults (57, 58). The
prevalence of trichiasis and corneal opacities due to
trachoma in adults reflects past episodes of disease
when this cohort were children. While the blinding
complications may continue to be a problem for generations previously exposed, the low or absent incidence of active disease in children is a good indicator
of the future absence of blinding disease.
In areas in which trachoma is not a blinding condition, the prevalence of active disease in preschool
children is less than 30 percent, and the average age of
peak prevalence is greater than in hyperendemic areas.
Although the prevalence of scars still increases with
age, the presence of trichiasis and corneal opacities is
rare (32, 43) (table 2).
Risk factors
In hyperendemic areas, preschool children have the
highest rate of trachoma, and a significant decline in
the prevalence is observed after the age of 10 years for
both males and females. The prevalence of chronic
trachoma (scars, trichiasis, and corneal opacities) increases with age and reflects the accumulated experiences with reinfection. As a general pattern, females
60
50
S 40
I 30
| 20
10
0
8-14
15-34
35-54
55+
Age Groups (Years)
FIGURE 1. Prevalence of signs of trachoma by age group. TF,
follicular trachoma; Tl, inflammatory trachoma; TS, trachomatous
scarring; TT, trichiasis; CO, corneal scarring.
210
Munoz and West
TABLE 2.
Trachoma prevalence surveys by country: 1980 to present
Active disease
Date
of
survey
No.
examined
1991
1,841
2-5 years
1987
1984
1,138
777
Ethiopia
Sidamo (46)
1988
Gambia
Jali (32, 43)
1984
Location
(reference no.)
Africa
Burkina
Faso
Sabou region (103)
Egypt
Nile Delta (55)
Qalyub (104)
Trichiasis
Scars
Type
of
survey
Age
group
(years)
%
prevalenc
e
13
£15
0.6
3 years
Primary school
59
26
225
90
1,222
5-9 years
29
£45
11
Population based
950
4-7 years
29
£20
25
Population based
13,803
0-4 years
59
Age
group*
%
prevalenc
e
Age
group
%
prevalenc
e
Overall
0
Population based
"Adult"
66
Population sample
Not stated
Population sample
Kenya
Endemic areas (57)
1977-1981
Malawi
Lower Shire Valley
(59)
1983
7,079
1-2 years
49
£15
29
Morocco
1991
1,185
0-9 years
31
£10
15
£10 years
4
Population-based sample
Tanzania
Dodoma region (42)
1986
5,574
3 years
68
£15
8
£15 years
3.5
Population based
Sudan
Omdurman County
(106)
1992
616
0-15 years
65
Zambia
Luapula Valley
(107)
1985
6,777
0-5 years
18
1982-1983
9,058
All ages
15
1980s
18,679
Overall
5
Population based
UUdiZdZale
Province (105)
Middle East Israel
West Bank, Gaza
(108)
Saudia Arabia
AI-Ahsa(109)
Australia
Northern Territory
(110)
Aboriginal
Communities
Western Australia
Golfield and
Kimberly
Regions (111)
Central and South
America
Mexico
Chiapas (54)
Brazil
Bebedouro (48)
Rural area
Northern Sao
Paulo (112)
Primary school
children
Sample of "displaced
persons"
£6
7
£6 years
0.6
Population based
All areas
0.7
Population-based survey
Random selection,
elementary schools
9.5
1985 and
later
NSt
Children
5-69
Community-wide surveys
1984-1985
547
0-9 years
12
Not stated; school and
preschool children
1983
1,097
0-10 years
25
£40
1986
2,908
3-4 years
7
£10
1989
950
4-11 years
6
Population based
100
Population-based sample
0.5
Random sample of
school children
* Age at peak prevalence, or if not, specific age group,
t NS, not specified.
Epidemiol Rev
Vol. 19, No. 2, 1997
Trachoma
appear to be at a higher risk of having every sign of
trachoma compared with males, especially the blinding stages of trichiasis and corneal opacities (32, 42,
43, 59). This excess risk among women is believed to
be related to their relatively continuous close contact
with young children, who are the main reservoir of
infection (52).
Trachoma remains a blinding disease in communities where the living conditions facilitate continuous
transmission of C. trachomatis among family members. Determination of the specific factors that increase the risk of trachoma may lead to intervention
strategies to control the disease. Below we review
some of the environmental and personal factors that
appear to affect the risk of active trachoma.
211
can carry C. trachomatis on their legs and in the
contents of their proboscis. Their ability to act as
physical vectors for the transmission of infection has
been demonstrated in laboratory settings by Forsey
and Darougar (70). In Tunisia and India, epidemics of
bacterial conjunctivitis and increases in the prevalence
of active trachoma have been observed after peaks in
the fly population (71, 72). Furthermore, studies in
Tanzania have found an association between fly density in the household or the presence of flies on children's faces and the presence and severity of trachoma
(61, 73, 74) as well as infection with C. trachomatis
(75). However, flies are probably not the most important source of transmission, as others have found trachoma where the fly populations are absent (51) or
less intense (76).
Water availability and use
Poor hygienic conditions due to lack of available
water have long been associated with the risk of trachoma. Several studies have found a positive association between the distance from the household to the
water source and the prevalence of active trachoma
(48, 59-61). Clearly the distance to water can place
constraints on the amount of water brought to the
house, and water becomes a scarce resource whose use
for hygiene purposes may be limited.
However, other research suggests that the availability of water may be less of a factor than household
decisions on how water is to be utilized. In a large
prevalence study, West et al. (42, 62) found that although distance to water was related to trachoma,
there was no relationship to the observed amount of
water available for use in the household, nor was there
a relationship between a functional water supply in the
village and the prevalence of trachoma. In addition,
Bailey et al. (63) found in a village in The Gambia that
after controlling for family size, distance to water, and
other socioeconomic factors, families with trachoma
used less water for washing children than did the
control families without trachoma, regardless of the
amount of water available for consumption. In general,
in areas where trachoma is endemic, communities with
a poor water supply are more likely to have higher
trachoma prevalence (58, 64, 65), but the provision of
adequate water does not necessarily ensure that trachoma rates will decline. The decision to use water
to improve hygienic conditions is very complex in
these communities and is clearly an important factor
as well (66).
Flies
One of the earliest risk factors noted for trachoma
was the presence of flies (67-69). Eye-seeking flies
Epidemiol Rev Vol. 19, No. 2, 1997
Cattle
Although cattle are not a reservoir or a physical
vector for Chlamydia infection, the presence of cattle
and cattle ownership has been associated with trachoma in some African countries (61, 77). In arid
environments, cattle droppings create an optimal environment for breeding flies, and this has been the
explanation for the association of cattle with trachoma.
However, flies and cattle were independent predictors
of severe trachoma in Tanzania, which suggests that
cattle ownership is a marker for other important factors (61). In some societies, cattle not only are a sign
of traditional wealth but also mark families with traditional lifestyles who tend to have the poorest living
conditions.
Hygiene
In general, poor hygienic conditions favor the transmission of C. trachomatis through contact with ocular
and other secretions that carry the infection (69). Several studies have been carried out to identify the specific hygiene practices associated with a lower risk of
active trachoma. These studies have evaluated the use
of latrines, handkerchiefs, and towels as well as face
washing in children.
The presence of a functional latrine near the house
has been associated with lower trachoma prevalence in
several different countries (59, 61, 78). The mechanism by which the presence of a latrine would decrease trachoma is not entirely clear. In Egypt,
Courtright et al. (78) found that the presence of a
latrine was related to other measures of higher socioeconomic status, such as higher occupational level and
more education of the head of the household, more
large farm animals, and larger farming plots.
212
Mufioz and West
In Tanzania, a large cross-sectional study found a
protective effect against both trachoma and severe
trachoma with the use of a handkerchief for nose
blowing and a towel for drying one's face (61). This
finding is somewhat paradoxical, since handkerchiefs
and towels would seem to enhance transmission of
secretions, especially if used among many family
members (79, 80). It may be likely that these items,
which were rarely used in general, were a marker for
a few families with better hygiene practices overall.
One potential source of infection is obviously the
ocular and nasal secretions of preschool children (16,
81, 82). Decreasing the presence of these secretions by
improving facial cleanliness may lessen the likelihood
of transmission. However, determining the frequency
of face washing among children is difficult and prone
to reporting bias since in most cultures, mothers are
aware that face washing is a desirable activity, regardless of their actual practices. In three studies, the
self-reported frequency of washing children's faces
was believed to be unreasonably high, and was not
related to the prevalence of trachoma (48, 59, 61). In
one study, there was a modest association (51). In the
Tanzanian study, investigators asked questions about
face washing and also observed children's faces in the
home. Children who had clean faces were less likely to
have trachoma or severe trachoma compared with
children who had unclean faces (61). Further research
determined the specific elements of an unclean face
that were related to the risk of trachoma in children. Of
the four elements studied (flies, nasal discharge, food
on the face, and dust), children having flies on the face
and nasal discharge had a twofold increased risk of
active trachoma compared with children who did not
have these signs (73).
The data from Tanzania suggest that children with
clean faces were less likely to have trachoma; however, cross-sectional data are not sufficient evidence
that improving face washing is protective. Face washing obviously has no effect on the course of disease
but may reduce the likelihood of autoreinfection or
transmission of infection to others. To test the effectiveness of face washing, a randomized, communitybased intervention trial was conducted in Tanzania by
West and colleagues (83). Mass antibiotic treatment at
one time point was offered to the entire study population in an effort to reduce the load of infection in
each community. Six villages were randomly assigned
to either mass treatment alone or mass treatment plus
an intensive participatory face-washing campaign that
involved the entire community. One year after mass
treatment, children who kept their faces clean were
about one half as likely to have trachoma, and one
third as likely to have severe trachoma, as children
who did not have clean faces (84, 85). The difficulties
of carrying out a behavioral intervention were evident,
but such an approach is likely to be more sustainable
for communities with trachoma than the constant provision of antibiotic treatment.
Extraocular infections
In trachoma-endemic areas, children with active ocular Chlamydia infection are also likely to have extraocular chlamydial infections (81, 82). Autoreinfection from extraocular sources of Chlamydia infection
may be one source of transmission and may explain
why treatment with topical antibiotic ointment is effective for only a short time. However, in a study of
the effect of mass topical treatment in a village in
Tanzania, West et al. (81) found that the incidence rate
of new infections was similar in those who had a
positive nasal specimen at baseline compared with
those who had a negative nasal specimen. Moreover, a
positive ocular specimen at baseline was not predictive
of the risk of a new infection after treatment, suggesting that these new infections were not the result of a
latent or persistent infection. The use of a systemic
antibiotic compared with a topical treatment for trachoma in children in a study in The Gambia did not
lower the reemergent rates of infection at follow-up
(86). These two studies suggest that the source of
Chlamydia reinfection after treatment is not likely to
be extraocular sources. The epidemiology of reinfection of trachoma will be enhanced considerably with
the use of the newer technology for genovar determination since more precise studies of the source of
reinfection will be possible.
Risk factors for sequelae
Trichiasis, entropion, and corneal opacities can be
the sequelae of active trachoma in childhood. These
complications appear in young adulthood and in middle age. In some areas, severe scarring can appear in
children, but the prevalence of severe scarring is usually low in children and increases with age. Because of
the long time course from repeated active infections in
childhood to the development of blinding sequelae in
middle-aged adults, there are few longitudinal studies
of risk factors for scarring and none for trichiasis/
entropion. In fact, the pathophysiologic change from
scarring to trichiasis and visual loss have not been
clearly defined. This area is of considerable interest
because, although the majority of children in trachoma
endemic areas have active disease, only a small percentage go on to develop the blinding complications.
The detection of chlamydial antigen or DNA suggests that cryptic infection may continue to drive the
Epidemiol Rev Vol. 19, No. 2, 1997
Trachoma
progression to severe scarring and trichiasis (87).
Clearly, prospective studies are needed to determine
the importance of cryptic or persistent infection in the
development of blinding complications of trachoma.
It is clear that adult women are at much greater risk
of developing the blinding complications of trachoma
than are adult men (42, 55). This increased risk has
been explained by the women's close contact with
small children, who are the main reservoir of infection,
and active disease in adults is almost entirely confined
to caretakers of children with trachoma (52). However,
a case-control study of risk factors for trichiasis in
women by Turner et al. (88) did not find any association with years of exposure to child care activities,
although exposure to children with active trachoma
could not be ascertained retrospectively.
The same study found that trichiasis cases were
more likely than controls to report poor living conditions during childbearing years. Having no adult education, living in poor housing, sleeping in rooms with
a cooking fire, and having five or more deaths among
their children were all associated with an increased
risk of developing trichiasis (88). The association with
cooking fire is of interest because others have found
carbon particles imbedded in the fibrotic conjunctiva
of entropion cases undergoing surgery in South Africa
(89). Whether dust or smoke from the cooking fire
could act as a mechanical irritant in the development
of trichiasis is unclear.
MATHEMATICAL MODELS FOR TRACHOMA
The development of quantitative models that will
integrate a variety of information from epidemiologic
studies into a single system is currently underway.
These models must identify optimal communityspecific intervention strategies that have the potential
to control or eradicate trachoma as a public health
problem. Early catalytic models were developed in the
late 1960s to evaluate reductions of trachoma (90, 91);
however, these models describe rates of incidence and
recovery for a given epidemiologic situation, without
the characterization of the dynamics of transmission
needed to understand the contribution of different
types of interventions. Currently, simulation models
are being developed that take into consideration population structure as well as environmental conditions
to estimate the force of infection, likelihood of chronic
sequelae, and effect of interventions (92, 93).
STRATEGIES FOR TRACHOMA CONTROL
Trachoma must be viewed as a community disease,
not as a series of cases, in order to develop effective
public health measures for control. As with other inEpidemiol Rev Vol. 19, No. 2, 1997
213
fectious diseases that have been controlled, a vaccine
against Chlamydia would be ideal; however, efforts to
date to create a vaccine against chlamydial infection
have been unsuccessful. Attempts were made to develop chlamydial vaccines by using killed elementary
bodies, but these first generation vaccines resulted in
even more severe disease than naturally acquired infection; any protection conferred was against the immunizing serovar (94). Apparently, the vaccine acted
to potentiate the effects of infection by sensitizing the
subjects. The evidence in humans is not convincing,
and researchers are again raising the issue of the value
of killed vaccines in conferring immunity (95).
Clearly, an effective vaccine will have to elicit a
protective immune response across multiple serovars,
without sensitizing the recipient. Rational approaches
to the design of a vaccine await further research on the
development of genetic systems for chlamydia and
studies clarifying human correlates of protective immunity (95).
Based on our current knowledge, a public health
approach to trachoma control for hyperendemic areas
should consist of three components: first, the provision
of safe, effective, and inexpensive antibiotics to reduce
the pool of infection in the community; second, health
education about face washing to decrease transmission; third, the provision of surgery for trichiasis to
prevent visual impairment. Trachoma control programs that do not have all three components will be
unsuccessful in ultimately reducing the burden of visual impairment in the community for the long run.
Although antibiotics are effective in combating infection, reinfection is very likely to occur if only cases
are treated. Antibiotic treatment of either whole communities or selected groups considered at high risk has
been used in an attempt to reduce the risk of blinding
disease. These approaches are effective in reducing
infection and transmission in the short term. However,
a long-lasting effect has not been attained when they
are used as the only mode of control (71, 81, 86).
Eradication failures have been attributed to poor compliance with the treatment regimen, the fact that the
topical treatment may not be effective if extraocular
sites of infection exist, the lack of treatment of infectious but clinically inapparent cases, and the reintroduction of trachoma through in-migration of active
cases.
Recently, Bailey and coworkers (86) found that a
new antibiotic, azithromycin, taken orally in a single
dose, is as effective against ocular Chlamydia infection as 6 weeks of topical tetracycline. There are
several advantages of this new drug: First, a single
dose is effective and easy to administer, so there is the
potential for achieving the high levels of compliance
214
Munoz and West
required for successful control programs. Second, systemic therapy with minimal side effects would be
more effective than topical treatment for the eradication of infection in any extraocular reservoir. However, even with systemic antibiotics, a control program
that must plan for the constant provision of medicine
because reemergence occurs does not constitute a sustainable approach.
The disappearance of blinding trachoma from several countries in the Western world occurred before
the availability of effective drug therapy. The disappearance paralleled economic development and improvement in housing, sanitation, and personal
hygiene (69). Thus, it appears that environmental
changes and alterations in lifestyle have a more sustainable impact on trachoma and point to the need for
health education strategies for trachoma control. After
the identification of key environmental and personal
factors that are involved in maintaining transmission
of active disease, community intervention programs
that are culturally appropriate and targeted to the modification of these key factors should be developed and
implemented.
In the transmission of trachoma, the role played by
factors such as towel sharing, frequency of face washing, and presence of flies around the home appears to
be understood by members of communities with trachoma. Therefore, Sutter and Ballard (96) in South
Africa introduced the idea of "self-help" in the prevention of disease and found it could be very effective
in areas where trachoma is hyperendemic. The formation of local women's groups that not only were able
to identify and treat the clinical signs of active trachoma but also were motivated to improve personal
hygiene in their communities was the key element of
the success of trachoma control in the Transvaal region of South Africa (97).
A community intervention trial carried out in Tanzania aimed to improve facial cleanliness in children
after one mass treatment campaign was successful in
reducing the levels of severe active trachoma up to a
year after intervention (84, 85). In this trial, the key
element was the active participation of the entire community through an intense education campaign to create awareness of first, the blinding consequences of
the trachoma; second, the role that hygiene factors
play in the transmission of the disease; and third, the
importance of keeping children's faces clean to avoid
cycles of infection and reinfection with Chlamydia.
The sustainability of this type of intervention requires
a high level of involvement and support from the
entire community (83).
Control strategies incorporating health education
and antibiotics together are effective in reducing active
trachoma in children, but the third arm—surgical intervention—must also be available because trichiasis
will continue to exist in the adult population as a result
of previous years of exposure to trachoma (55, 98). A
number of different surgical techniques have been
used to correct trichiasis (99). In particular, Reacher et
al. (99) showed that tarsal rotation, when performed by
an ophthalmologist, was effective in correcting 80
percent of minor and major cases of trichiasis studied
for up to 1 year. However, in areas in which trachoma
is endemic, patients with trichiasis often have very
limited, if any, access to an ophthalmologist, so other
health personnel should be trained. In Tanzania, after
proper training by an ophthalmologist, eye nurses can
successfully perform trichiasis surgery using the tarsal
rotation technique in makeshift theaters in the local
communities (100). Ophthalmic nurses or medical assistants can be trained to perform trichiasis surgery,
and training manuals and videos are available from the
World Health Organization (101).
Availability of trained personnel does not necessarily ensure that patients will use the services. In Tanzania, even after patients were aware that surgery was
available and could prevent vision loss, compliance
with surgery was very low: Only 18 percent of women
with trichiasis to whom surgery was offered opted to
have the operation in a 2-year period. The main barriers were perceived cost and lack of accessibility to
the health facilities (102). In this environment, cost
includes transportation, food, and expenses of an accompanying person who acts as a caretaker. Such
factors must be considered when implementing an
effective surgical program.
This three-pronged public health approach to sustainable trachoma control does not offer a quick and
easy solution to trachoma. Unlike vitamin A capsules
for xerophthalmia or ivermectin for onchocerciasis,
there is no "magic bullet" for trachoma. Clearly, more
research is needed on the immunopathology of trachoma, risk factors for the blinding complications, and
strategies for effective intervention. Because trachoma
afflicts the least empowered members of communities
who are the most resource poor, the disease continues
to be the most important, if forgotten, infectious cause
of blindness in the world.
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