Abstract Around 3% of pregnant women in Finland have genital Chlamydia trachomatis infection, which can be transmitted from mother to newborn at birth. The risk of transmission has been reported to be 10–70% in vaginal deliveries resulting in conjunctivitis in 10–30% of cases and lower respiratory tract infection in 0–20% of cases. Although usually benign, Chlamydia trachomatis infections in infancy may result in long-term consequences, including conjunctival and corneal scarring, chronic cough and abnormal lung function. Based on the transmission rates published in prior studies, chlamydial conjunctivitis should occur in approximately 200 infants and chlamydial lower respiratory tract infection in 100 infants each year in our country, but in clinical practice we rarely encounter or diagnose infants with Chlamydia trachomatis infections. To investigate the reason for this discrepancy and to improve the recognition of Chlamydia trachomatis-infected infants, we set out to study the risk of vertical transmission of Chlamydia trachomatis in a population-based setting, to describe the typical features of Chlamydia trachomatis infections in infants and to evaluate the occurrence of Chlamydia trachomatis in both neonatal conjunctivitis and lower respiratory tract infections in infants. When studying the probability of vertical transmission of Chlamydia trachomatis a search through two national health registers for 1996–2011 yielded 206 children aged less than four years with a possible Chlamydia trachomatis infection. In a cohort of 933 823 births this represented an occurrence of 0.22 per 1000 live births (95% confidence interval 0.19–0.25). The risk of vertical transmission of Chlamydia trachomatis leading to a symptomatic infection in infancy was 0.8–1.8%. A review of patient charts to evaluate the typical features of Chlamydia trachomatis infections in infants (124/206) revealed that one-third of the infants with chlamydial conjunctivitis (33/124) had spontaneous bloody discharge from the infected eyes. Almost half of the infants with chlamydial lower respiratory tract infection (15/32) had wheezing, but the characteristic staccato cough was not recorded in any of them. The median diagnostic delay from the onset of symptoms was 13 (range 4–374) days for conjunctivitis and 25 (range 10–149) days for lower respiratory tract infection. One neglected child developed bilateral corneal scars due to untreated chlamydial conjunctivitis. To investigate the occurrence of Chlamydia trachomatis in neonatal conjunctivitis, 173 neonates with clinical conjunctivitis at child health clinics were examined prospectively during 2010–2015 and none of the 163 cases tested had chlamydial or gonococcal conjunctivitis (0%; 95% confidence interval 0%–2.2%). Viral conjunctivitis was diagnosed in 8/167 cases (4.8%; 95% confidence interval 2.1%–9.2%) and non-chlamydial bacterial conjunctivitis in 58/160 (36%; 95% confidence interval 29%–44%). To investigate the occurrence of Chlamydia trachomatis in lower respiratory tract infections, 228 infants aged less than six months with lower respiratory tract infection presenting at the paediatric emergency department of Oulu University Hospital were examined prospectively over a period of a complete epidemiological year. One infant (0.4%; 95% confidence interval 0.01%–2.4%) had lower respiratory tract infection caused by Chlamydia trachomatis and another was diagnosed with whooping cough (0.4%; 95% confidence interval 0.01%–2.4%). The majority of the infants with lower respiratory tract infection (203/228) had a respiratory viral infection. It may be concluded that the risk of mother-to-child transmission of Chlamydia trachomatis leading to a clinical illness in the infant in this era of nucleic acid-based diagnostics was less than 2%, which is significantly lower than in earlier studies. The population-based prevalence of neonatal chlamydial conjunctivitis in primary care was less than 2% and that of chlamydial lower respiratory tract infection in a hospital setting less than 2.5%. The long-term prognosis for Chlamydia trachomatis infections in infancy was good. Common respiratory viruses were detected in 5% of the neonatal conjunctivitis cases. / Tiivistelmä Noin 3 %:lla suomalaisista raskaana olevista naisista on klamydian (Chlamydia trachomatis) aiheuttama sukupuolitauti, joka voi tarttua äidistä lapseen synnytyksessä. Tartuntariskin on raportoitu olevan alatiesynnytyksessä noin 10–70 %. Noin 10–30 % tartunnan saaneista lapsista sairastuu silmätulehdukseen ja 0–20 % keuhkokuumeeseen. Vaikka imeväisten klamydiainfektiot ovat useimmiten lieviä tauteja, imeväisiällä sairastettu klamydiainfektio voi aiheuttaa silmän side- ja sarveiskalvon arpeutumista, pitkittynyttä yskää ja keuhkofunktion alenemaa. Aiempien tutkimusten perusteella arvioimme, että Suomessa sairastuu vuosittain noin 200 imeväistä klamydian aiheuttamaan silmätulehdukseen ja noin 100 imeväistä klamydiakeuhkokuumeeseen. Kliininen kokemuksemme on kuitenkin, että kohtaamme klamydiaa sairastavia imeväisiä varsin harvoin. Tämän ongelman ratkaisemiseksi ja klamydiaa sairastavien imeväisten paremmaksi tunnistamiseksi suunnittelimme tutkimuksen, jonka tarkoituksena on selvittää väestöpohjainen riski klamydian tarttumiselle äidistä vastasyntyneeseen, kuvata imeväisten klamydiainfektioiden tyypilliset piirteet sekä selvittää klamydian osuus imeväisten silmätulehduksissa ja alle kuuden kuukauden ikäisten imeväisten alahengitystieinfektioissa. Klamydian sairastaneet lapset poimittiin kahdesta suomalaisesta terveydenhuoltorekisteristä vuosina 1996–2011. Tuona aikana 206 lasta oli sairastanut mahdollisen klamydiainfektion, joten klamydian ilmaantuvuus oli 0,22/1000:tta elävänä syntynyttä kohti (95 % luottamusväli 0,19–0,25). Väestöpohjainen riski äidin sukupuoliklamydian tarttumiselle vastasyntyneeseen niin että lapselle aiheutuu oireinen infektio oli 0,8–1,8 %. Saatavilla olevien potilasasiakirjojen (124/206) perusteella kolmasosalla (33/124) imeväisistä, jotka sairastivat klamydian aiheuttamaa silmätulehdusta, oli oireena spontaani verinen kyynel- tai rähmäerite. Klamydiakeuhkokuumetta sairastavista puolella (15/32) esiintyi hengityksen vinkumista, mutta klamydiakeuhkokuumeelle tyypillistä hakkaavaa yskää (”staccato-yskä”) ei todettu yhdelläkään imeväisellä. Diagnostinen viive oli verrattain pitkä: 13 päivää (vaihteluväli 4–374) silmätulehduksessa ja 25 päivää (vaihteluväli 10–149) keuhkokuumeessa. Yhdelle laiminlyödylle lapselle kehittyi molemminpuoliset sarveiskalvoarvet hoitamattoman klamydiainfektion seurauksena. Vastasyntyneen silmätulehdustutkimukseen rekrytoitiin 173 alle 30 päivän ikäistä lasta Oulun kaupungin lastenneuvoloissa vuosina 2010–2015. Klamydian tai tippurin aiheuttamaa silmätulehdusta ei todettu yhdelläkään 163:sta tutkitusta vauvasta (0 %; 95 % luottamusväli 0 %–2,2 %). Viruksen aiheuttama silmätulehdus todettiin kahdeksalla vauvalla (4,8 %; 95 % luottamusväli 2,1 %–9,2 %) ja jonkin muun bakteerin kuin klamydian aiheuttama silmätulehdus 58:lla vauvalla (36 %; 95 % luottamusväli 29 %–44 %). Imeväisten alahengitystieinfektiotutkimukseen rekrytoitiin 228 alle kuuden kuukauden ikäistä imeväistä yliopistosairaalan lastenpäivystyksessä yhden epidemiologisen vuoden aikana. Klamydian aiheuttama hengitystieinfektio diagnosoitiin yhdellä imeväisellä (0,4 %; 95 % luottamusväli 0,01 %–2,4 %) ja hinkuyskä niin ikään yhdellä (0,4 %; 95 % luottamusväli 0,01 %–2,4 %). Valtaosalla (203/228) alahengitystieinfektio-oireisista imeväisistä oli viruksen aiheuttama infektio. Yhteenvetona voimme todeta, että klamydia tarttui äidistä lapseen alle 2 %:ssa synnytyksistä, mikä on huomattavasti harvinaisempaa kuin aiemmin on luultu. Klamydian aiheuttamien silmätulehdusten esiintyvyys oli alle 2 % ja alahengitystieinfektioiden alle 2,5 % alueemme lapsiväestössä. Klamydian aiheuttamat pitkäaikaishaitat olivat harvinaisia. Tavallisten hengitystievirusten osuus vastasyntyneiden silmätulehduksissa oli 5 %.

Introduction International guidelines endorse the screening of patients for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and Chlamydia trachomatis before assisted reproductive techniques (ART). At present no such guidelines exists in South Africa. At the Reproductive and Endocrine Unit (referred to as “the Unit”) of Steve Biko Academic Hospital, all patients with unknown HIV status are counselled and a blood sample is collected during the initial visit for automated laboratory based HIV screening. These HIV results are not available before semen samples are processed. Furthermore, patients are not screened for HBV, HCV and Chlamydia trachomatis. Couples attending the Unit are of a low to middle socio-economic status and experience financial constraints. Moreover, automated laboratory based assays are expensive to perform. Rapid testing is a cost effective and practical method from screening patients, with a 20–30 minute result turnover time. Until screening at the Unit is improved, the possible identification of semen characteristics that could indicate HIV infection would be a useful tool. Materials and Methods The following rapid point-of-care assays were evaluated: Determine® HIV-1/2 combo test (n=100), Determine® HBsAg test (n=100), DIAQUICK HCV kit (n=74), and the DIAQUICK Chlamydia trachomatis kit (n=30). For profiling, parameters from a basic semen analysis of HIV-positive males (n=60) were compared with HIV-negative males (n=60). Information pertaining to CD4 count, antiretroviral treatment and plasma viral load of HIV-positive males were analysed. Results From all patients included in the study, 8% tested positive for HIV. The risk of a female being HIV-positive was 3.73 times higher than for males. In the pilot study to explore rapid testing for HBV and HCV, 1% and 1.4% of patients tested positive respectively. When testing for Chlamydia trachomatis 31.3% of females, but no males tested positive. Comparing semen profiles, no significant differences were found between samples from HIV positive and negative males or between HIV positive males categorised by CD4 cell count (p>0.05). For the HIV-positive group with a detectable plasma HIV viral load (>40 copies/ml), a significant difference was observed in the semen viscosity (p=0.0460). Significant differences were noted in the sperm motility (immotile sperm p=0.0456, progressive sperm p=0.0192) of patients receiving antiretroviral (ARV) therapy. Discussion and Conclusion The use of rapid testing is an acceptable and feasible option for improving current screening protocols at the Unit. The absence of definite alterations in the semen characteristics of HIV-positive men further motivates the need for a simpler, point-of-care screening protocol. The prevalence of HBV was lower than that reported in the general population of South Africa and further investigation is needed. Although the sample size was small, HCV prevalence was similar to that of the general population. One third of females tested positive for Chlamydia trachomatis. The methodology used was possibly not appropriate for males. This study highlighted the need for guidelines that address the specialised needs of ART clinics in resource-limited and developing countries with a high HIV prevalence. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Obstetrics and Gynaecology / unrestricted

Chlamydiae growing in target mucosal human epithelial cells in vitro can transition from their normal developmental cycle progression, alternating between infectious but metabolically inactive elementary bodies to metabolically active but noninfectious reticulate bodies (RBs) and back to elementary bodies, into a state of persistence. Persistence in vitro is defined as viable but noncultivable chlamydiae involving morphologically enlarged, aberrant, and nondividing RBs. The condition is reversible, yielding infectious elementary bodies after removal of the inducers, including penicillin, interferon-gamma, iron or nutrient starvation, concomitant herpes infection, or maturation of the host cell into its physiologically differentiated state. All aberrant RB phenotypes are not the same, owing to differing up- or down-regulated chlamydial gene sets and subsequent host responses. Although all persistence-inducing conditions exist in vivo, key questions include (1) whether or not aberrant chlamydial RBs occur in vivo during the alternating acute-silent chronic-acute chlamydial infection scenario that exists in infected patients and animals and (2) whether such aberrant RBs can contribute to prolonged, chronic inflammation, fibrosis, and scarring.