**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 [27–29].

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].
