Recent evidence suggests that eye-seeking flies are important trachoma vectors. We conducted a series of investigations to identify which species of synanthropic flies are potential vector(s) of this blinding disease in The Gambia. Several species of fly were caught in fish-baited attractant traps placed in villages throughout the year (1997/98) but only 2 species, Musca sorbens and M. domestica, were caught from the eyes of children. M. sorbens comprised < 10% of the total number of flies caught with attractant traps but was responsible for > 90% of fly-eye contacts, the remainder were made by M. domestica. All fly species were more numerous in the wet season than the dry season. Eyes of young children are considered to be the main reservoir of Chlamydia trachomatis, the causative agent of trachoma. Collections of eye-seeking flies from children showed frequent fly-eye contacts (median [interquartile range], 3 [1.5-7] every 15 min). Children with potentially infective ocular or nasal discharge had twice as many fly-eye contacts than children with no discharge (P < 0.001). There was no difference in exposure to fly-eye contacts if a child sat inside or outside a house (P = 0.273). Female flies were more commonly caught from eyes than male (P < 0.001). The presence of Chlamydia DNA was demonstrated by PCR on 2 of 395 flies caught from the eyes of children with a current active trachoma infection. Both positive flies were M. sorbens, one male and the other female. Further elucidation of M. sorbens behavioural ecology and the development of sustainable strategies to control these flies should be a priority. It is likely that M. sorbens is the principal insect vector of trachoma in The Gambia.

C57BL/6J mice were 105-fold more resistant to Chlamydia psittaci infection than DBA/2J mice by LD100 determinations. Linkage analysis using BXD recombinant inbred strains revealed a single effector locus at a 1.5-Mbp region on chromosome 11 encoding a cluster of three p47 GTPases (Irgb10, Igtp, and Iigp2). Western blots of infected tissue showed that Irgb10 was elevated in resistant mice and one of the two possible Iigp2 protein isoforms was preferentially expressed in susceptible mice. The BXD39 strain, susceptible at Irgb10 and resistant at Iigp2, had an intermediate phenotype implicating the nonredundant role of these p47 GTPases. C57BL/6J and DBA/2J exhibited a difference in IFN-γ-dependent chlamydial control, which was reversible by Iigp2 small interfering RNA knockdown. Microarrays of infected peritoneal lavage revealed &gt;10-fold up-regulation of neutrophil-recruiting chemokines in susceptible mice and &gt;100-fold increase in macrophage differentiation genes in resistant mice, indicating that the susceptibility pattern involves the stimulation of different inflammatory cell-recruiting pathways. Massive neutrophil recruitment was seen in susceptible mice by histology and flow cytometry, and neutrophil chemokine receptor (CXCR2) knockout mice on a susceptible background survived a lethal challenge, confirming that neutrophil recruitment was required for susceptibility. Congenic Igtp knockout mice also susceptible at Irgb10 and Iigp2 on a resistant background recruited neutrophils and succumbed to infection. We conclude that Irgb10 and Iigp2 act together to confer differential susceptibility against murine chlamydial infection. Data indicate that these p47 GTPases have cell-autonomous effects that result in vastly different inflammatory stimulations, leading to either recovery or death.

Precise temporal evaluation of the chlamydial developmental cycle for selected genital and ocular C. trachomatis biovars provides a means for investigating genomic differences that define chlamydial pathotype.

Objectives:The respiratory pathogen Chlamydia pneumoniae (C. pneumoniae) produces acute and chronic lung infections and is associated with asthma. Evidence for effectiveness of antichlamydial antibiotics in asthma is limited. The primary objective of this pilot study was to investigate the feasibility of performing an asthma clinical trial in practice settings where most asthma is encountered and managed. The secondary objectives were to investigate (1) whether azithromycin treatment would affect any asthma outcomes and (2) whether C. pneumoniae serology would be related to outcomes. This report presents the secondary results.Design:Randomized, placebo-controlled, blinded (participants, physicians, study personnel, data analysts), allocation-concealed parallel group clinical trial.Setting:Community-based health-care settings located in four states and one Canadian province.Participants:Adults with stable, persistent asthma.Interventions:Azithromycin (six weekly doses) or identical matching placebo, plus usual community care.Outcome Measures:Juniper Asthma Quality of Life Questionnaire (Juniper AQLQ), symptom, and medication changes from baseline (pretreatment) to 3 mo posttreatment (follow-up); C. pneumoniae IgG and IgA antibodies at baseline and follow-up.Results:Juniper AQLQ improved by 0.25 (95% confidence interval; −0.3, 0.8) units, overall asthma symptoms improved by 0.68 (0.1, 1.3) units, and rescue inhaler use decreased by 0.59 (−0.5, 1.6) daily administrations in azithromycin-treated compared to placebo-treated participants. Baseline IgA antibodies were positively associated with worsening overall asthma symptoms at follow-up (p = 0.04), but IgG was not (p = 0.63). Overall asthma symptom improvement attributable to azithromycin was 28% in high IgA participants versus 12% in low IgA participants (p for interaction = 0.27).Conclusions:Azithromycin did not improve Juniper AQLQ but appeared to improve overall asthma symptoms. Larger community-based trials of antichlamydial antibiotics for asthma are warranted.

Tumor necrosis factor alpha (TNF-␣) may play a central role in the disease pathogenesis which occurs as a consequence of chlamydial infection. To investigate the importance of TNF-␣ gene promoter polymorphisms and TNF-␣ levels in tear fluid in scarring trachoma, a large matched-pair case-control study was performed in The Gambia. The-308A allele was present in a higher proportion of patients (28.4%) than controls (18.4%), with an increasing association for homozygotes (2 for trend, P ‫؍‬ 0.032; allele frequency, 0.163 in patients and 0.099 in controls; 2 , P ‫؍‬ 0.025). For the-238A allele, the association was similar but not significant. The disease association was highly significant when the number of either-308A or-238A sites in an individual was considered (P ‫؍‬ 0.003). TNF-␣ promoter alleles are tightly linked to some HLA class I and II alleles, but multivariate analysis confirmed that the disease associations were independent of HLA, although a class I allele, A*6802, is also associated with disease. TNF-␣ was more frequently detected in tear samples from patients (27.6%) than from controls (15.9%), increasingly so for higher levels of detectable TNF-␣ (P ‫؍‬ 0.015). Among patients, detectable TNF-␣ in tears was highly associated with the presence of ocular chlamydial infection (P < 0.001). The results indicate that TNF-␣ plays a major role in the tissue damage and scarring which occurs as a consequence of Chlamydia trachomatis infection.