Trachoma

Abstract

Trachoma is the most common infectious cause of blindness worldwide. In children, repeated episodes of infection within cohorts and family with Chlamydia trachomatis would lead to severe conjunctival inflammation, scarring, and potentially blinding trichiasis or entropion in later life. Trachoma is a disease associated with poverty, poor hygiene, and sanitation as well inadequate water supply. Collaborative control programs are implementing the “SAFE” strategy: surgery for trichiasis, mass distribution of antibiotics, promotion of facial cleanliness, and environmental improvement. The SAFE strategy has remained the cornerstone of WHO’s plan to eliminate trachoma as public health problem, and many countries and districts have eliminated trachoma by this means.

1. Introduction

Trachoma has been recognized as a cause of blindness since antiquity [1, 2, 3]. Early Egyptian and Chinese manuscripts described its manifestation, therapy, and complications. Trachoma remains the leading cause of infectious blindness worldwide [4]. The intracellular bacterium Chlamydia trachomatis (C. trachomatis) is the causative agent, and it causes chronic keratoconjunctivitis [5].

C. trachomatis can spread either directly through interpersonal contact with secretions from the eyes and noses of infected individuals or indirectly via contact with pieces of clothing or flies that have picked up the bacterium from an infected person [6]. It has been demonstrated that poor sanitation, overcrowding, and insufficient clean water and toilets significantly increase the rate of spread [4].

Episodes of repeated reinfection within cohorts and families cause intense conjunctival inflammation described as active trachoma, which leads to conjunctival scarring. Scarring from trachoma distorts the normal anatomy of the upper tarsal plate leading to entropion and trichiasis also known as cicatricial trachoma [7].

The World Health Organization (WHO) along with its partners in 1996 adopted surgery (S), antibiotics (A), facial cleanliness (F), and environmental improvement (E) strategy as the best approach for the control of trachoma [8].

The Neglected Tropical Disease Road map 2021–2030 has set 2030 as the target year for the global elimination of trachoma as a public health problem. Recently, the Global Trachoma Mapping Project and its successor Tropical Data established communities across the globe where elimination efforts should be concentrated to achieve the goal of eliminating trachoma [9].

2. Epidemiology

Trachoma is endemic in 44 countries, and the highest prevalence are in sub-Saharan Africa, Asia, Latin America, and the Middle East [4, 6, 10]. C. trachomatis infection occurs mostly in children, and in areas where trachoma is endemic, the first infection usually occurs in the first 2 years of life. Even though initial infections may resolve spontaneously, they are frequently followed by reinfection or superimposed bacterial conjunctivitis [11]. However, the prevalence generally declines to low levels in adults [12].

Complications arising from trachoma may result in severe ocular pains and loss of vision with its attendant poor quality of life and loss of economic productivity [13]. In 2021, approximately 1.9 million people were blind or suffer significant visual impairment from trachoma with over 136 million people living in communities requiring trachoma elimination programs [14].

2.1 Morbidity and mortality

Approximately, 1.9 million people are blind because of trachoma [8]. The risk of mortality in endemic communities is increased among those blinded by the disease [14].

2.2 Poverty

Trachoma is a disease of the poor and deprived [4, 15]. The risk of active trachoma is higher in households with crowed living spaces and poor sanitation. Trachoma persists in low- and middle-income countries (LMICs) where resources are scarce and shared within households [16]. Additionally, the disability that results from the sequelae of chronic infection with C. trachomatis such trichiasis and corneal opacities may lead to reduced productivity and unemployment. Demonstrably, trachoma remains a good proxy of inequality in a population [16, 17]. A study in Ethiopia found that within communities afflicted with trachoma, individuals and households affected by trachomatous trichiasis (TT) are significantly poorer economically than those that are not affected [18]. Trachoma therefore creates a vicious cycle of poverty that traps those affected.

2.3 Race and sex

Trachoma remains a disease of poverty and poor hygiene. Consequently, trachoma has no racial predilection [19]. The disease affects the marginalized and deprived members of the communities [20]. The disease persists in communities with inadequate access to water and sanitation and in dry, dusty, and hot climates [15, 21, 22]. Other agents of transmission include dirty faces, eye-seeking flies (particularly, Musca sorbens), and fomites such as clothing.

Women are usually affected by severe trachoma more than twofold compared to men [19, 23]. Because women carry the burden of childcare in most endemic communities, they tend to be more at risk. School age children harbor the active forms of the disease, thereby increasing exposure to C trachomatis [19].

2.4 Age

It has been established that active trachoma is a disease of school age children [24, 25, 26]. However, young adults especially mothers have trachomatous scarring. Older patients and grandparents tend to have trichiasis and corneal opacity [21]. In hyperendemic communities, these forms of presentation can occur concurrently [27].

3. Pathophysiology

C. trachomatis serovars A, B, Ba, and C predominate as causative agents of trachoma. Serovars D-K may rarely cause a subacute follicular conjunctivitis that except for scarring, may indistinguishable clinically from trachoma [27, 28, 29].

Trachomatous inflammation begins with the recruitment and activation of a host of leukocytes in the conjunctival tissue [30]. Increased expression of certain proteases like matrix metalloproteinases (MMPS), e.g. MMP7, MMP9, and MMP12, and pro-inflammatory agents like chemokines and cytokines are associated with severe disease. Research has shown that the predominant cellular constituents of trachoma follicles are macrophages, plasma cells with lymphocytic and monocytic infiltrate [27]. Typically, the follicles are made up of germinal centers with clumps of intense B-cell proliferation that are surrounded by multiple T cells. Scarring ensues when conjunctival epithelium lose goblet cells and compact collagen bands replace the normally freely mobile and vascular subepithelial stroma [7, 31].

3.1 Histopathology/immunology

Histology of conjunctival tissue will reveal a diffuse mixed inflammatory cell infiltrate of the conjunctiva with mild to moderate epithelial hyperplasia [32]. The hallmark of trachoma is the presence of lymphoid follicles in the stroma. In late stages of the disease known as cicatricial trachoma, the conjunctiva will show chronic inflammatory infiltrate in the substantia propria with lymphocytes predominating [27, 32, 33]. Additionally, the conjunctival epithelium may show squamous metaplasia with multiple denuded areas where the underlying stroma may be replaced with thick, compact scar tissue [34].

Trachoma evades host immune responses through intracellular invasion. Therefore, the leading sequalae are a result of inflammation rather than infection by C. Trachomatis. It is now clear that host immunity plays a significant role in clinical presentation and disease severity [34, 35]. The most likely pathway is that increased chemokine responses lead to neutrophil activation, chemotaxis, and fibrosis. This is mediated by the activities of TH1 as a pro-inflammatory as well as TH2 serving as a potent inducer of anti-inflammatory responses [27, 31].

Blindness from trachoma occurs from conjunctival scarring which is attributed to recurrent infection. Subconjunctival fibrotic bands eventually cause scar contraction leading to entropion, trichiasis, and finally corneal opacification [34].

4. Clinical presentation

Trachoma presents in two phases: the active phase and the cicatricial or scarring phase; however, both phases can coexist concurrently [6]. Active trachoma is characterized by a mucopurulent keratoconjunctivitis [36]. The conjunctival surface of the upper eyelid shows a follicular and inflammatory response. The cornea may have limbal follicles, superior neovascularization also known as pannus, and punctate keratitis [31]. C trachomatis infection may occur concurrently with that of other extraocular mucous membranes, e.g. the nasopharynx, leading to a nasal discharge.

Most patients with active trachoma are relatively asymptomatic [11].

The cicatricial phase has characteristic clinical features, which can lead to definitive diagnosis in most cases [7, 37].

4.1 Grading

The most widely used grading system for trachoma is the WHO grading (Figure 1) [38]:

Figure 1.

The simplified WHO grading system of trachoma.

4.1.1 Trachomatous inflammation Follicullar (TF)

Follicular trachoma indicates active disease. It is defined as the presence of five or more follicles at least 5 mm in diameter in the central part of the upper tarsal conjunctiva.

4.1.2 Trachomatous inflammation (TI)

Trachomatous inflammation is defined as pronounced inflammatory thickening of the upper tarsal conjunctiva that obscures more than one half of the normal deep tarsal vessels.

4.1.3 Trachomatous scarring (TS)

Trachomatous scarring is defined as the presence of easily visible scars in the tarsal conjunctiva.

4.1.4 Corneal opacity

Corneal opacity is defined as easily visible corneal opacity over the pupil that is so dense that it blurs at least part of the pupillary margin when it is viewed through the opacity.

Corneal opacity or scarring reflects the prevalence of vision loss and blindness resulting from trachoma.

4.2 Differential diagnosis

• Allergic conjunctivitis

• Viral conjunctivitis

• Bacterial conjunctivitis

• Acute chlamydial infection

• Neonatal conjunctivitis

• Toxic follicular conjunctivitis

5. Diagnosis

Trachoma diagnosis is usually determined clinically using a x2.5 binocular magnifying loupe to examine the everted upper tarsal conjunctiva. In non-endemic areas, the laboratory methods of diagnosis are usually preferred [39].

However, the laboratory detection of c trachomatis is problematic. Firstly, it requires sophisticated equipment that are hard to acquire or even maintain in trachoma endemic communities. Secondly, the services of a specialist microbiologist or pathologist is often required in order to make accurate and consistent diagnosis of C trachomatis [40]. Thirdly and most importantly is the fact that clinical signs of trachoma are poorly correlated with actual evidence of infection demonstrable in the laboratory [41, 42].

For operational purposes, any modality of C. trachomatis diagnosis will have to be cheap and reliable and provide rapid results. It becomes apparent, therefore, that trachoma control programs overwhelmingly rely on clinical signs of trachoma for diagnosis [43, 44, 45, 46].

Even though laboratory tests are not commonly used in the field of the diagnosis of C. trachoma, they are useful in non-endemic areas as well as in research laboratories. Frequently performed laboratory tests include the following:

1. Polymerase chain reaction (PCR), specifically nucleic acid amplification tests (NAATs) are most sensitive.

2. Direct fluorescent antibody assay.

3. Enzyme immunoassay.

6. Treatment and control

Trachoma remains a major public health problem in many endemic countries. A multifaceted strategy has been advocated as the best approach if success is to be had beyond the ophthalmology clinic [15]. Following a resolution by the World Health Assembly in 1998, the World Health Organization (WHO) recommended the “SAFE” strategy as the most effective means of managing trachoma [38]. It has been operationalized in all programs aimed at eliminating trachoma. Elimination has been successfully achieved in hitherto endemic countries such as Gambia, Morocco, Mexico, Laos, and Nepal [47, 48, 49]. Control programs utilize a four-step approach as follows:

S: Surgery for trichiasis.

A: Antibiotics for chlamydia trachomatis infection.

F: Facial cleanliness.

E: Environmental change to improve sanitation and increase access to clean water.

6.1 Surgery for Trichiasis

Trachomatous trichiasis (TT) afflicts about 8 million people worldwide [50]. Untreated TT will ultimately lead to blinding corneal opacity which is an irreversible sequela. Eyelid surgeries to avert complications from trichiasis have been extensively studied. Varying success rates have been reported with several surgical techniques used in several control programs. The WHO endorsed the bilamellar tarsal rotation because of its low TT recurrence rate.

6.2 Antibiotics

The WHO recommends mass distribution of antibiotics in communities where follicular trachoma is >10% in children [12]. In 1940, sulfonamide was the first antibiotic to be used at a large scale to treat trachoma. Over the ensuing decades, several other antibiotics were evaluated with little success until in 1990 when tetracycline became the drug of choice.

In more recent decades, azithromycin has been adopted as the drug of choice by many trachoma control programs because of its many advantages over tetracycline ointment [51]. For example, azithromycin is a single-dose regime and treatment can be directly observed to improve compliance significantly.

The WHO has developed guidelines for determining how community treatment of trachoma based solely on the prevalence of trachoma follicles in children aged 1–9 (Figure 2) [52]. It is recommended that trachoma control programs use either 6 weeks’ regimen of tetracycline eye ointment instilled into the lower conjunctival sacs two times a day or a single dose of azithromycin (20 mg/kg up to 1 g) [53, 54]. The duration of treatment remains a subject of debate and further research. The WHO recommends three annual rounds of mass treatment endemic communities after which a reassessment of active disease will determine whether another round of treatment will be needed or discontinued [55].

Figure 2.

WHO recommendations for initiating antibiotic treatment for trachoma.

6.3 Face washing

Face washing plays a crucial role in the control of trachoma because it disrupts the transmission of C. trachomatis by removing potentially infected ocular secretions [56].

6.4 Environmental improvements

Trachoma control programs advocate for improved water supply which is essential for face washing and sanitation as major contributors of successful control efforts. Latrine building is particularly advocated and incorporated because in trachoma control programs, because it limits the preferred breeding ground of the mechanical vector of C. trachomatis, Musca sorbens. It is to be noted that most of the changes that tend to improve the control of trachoma will also benefit the general health of the community [19, 53].

6.5 Prognosis

If the risk of reinfection is eliminated, early identification and treatment lead to resolution and full recovery [11]. Surgery may have a limited role once corneal scarring develops.

7. Conclusion

There is a real chance that trachoma will be eliminated as a public health problem in our lifetime [14, 20]. Following over two decades of sustained “SAFE” strategy, the disease burden of trachoma has been substantially reduced. As we near the end, research efforts are now geared toward accurate diagnosis of trachoma infection and monitoring of symptoms. Several studies have shown that mass distribution of azithromycin antibiotic also provides ancillary benefits such as the reduction infectious diseases and childhood mortality [55]. For these efforts to be sustainable, integrating trachoma programs with other neglected tropical diseases (NTDs) may prove cost-effective in many ways [44].

Acknowledgments

I will like to acknowledge the brilliant suggestions of Dr. Ruth J. alfin and Dr. Nievel Maigida.

Conflict of interest

“The authors declare no conflict of interest.”

Notes/thanks/other declarations

Special thanks to Prof. Caleb Mpyet for kindling my interest in ophthalmic epidemiology and being a mentor per excellence.