Correlation of clinical trachoma and infection in Aboriginal communities

Background

Trachoma is the leading infectious cause of blindness due to conjunctival infection with Chlamydia trachomatis. The presence of active trachoma and evidence of infection are poorly correlated and a strong immunologically-mediated inflammatory response means that clinical signs last much longer than infection. This population-based study in five Aboriginal communities endemic for trachoma in northern Australia compared a fine grading of clinical trachoma with diagnostic positivity and organism load.

Methods

A consensus fine grading of trachoma, based on clinical assessment and photograding, was compared to PCR, a lipopolysacharide (LPS)-based point-of-care (POC) and a 16S RNA-based nucleic acid amplification test (NAAT). Organism load was measured in PCR positive samples.

Results

A total of 1282 residents, or 85.2% of the study population, was examined. Taking the findings of both eyes, the prevalence of trachomatous inflammation-follicular (TF) in children aged 1–9 years was 25.1% (96/383) of whom 13 (13.7%) were PCR positive on the left eye. When clinical data were limited to the left eye as this was tested for PCR, the prevalence of TF decreased to 21.4% (82/383). The 301 TF negative children, 13 (4.3%) were PCR positive. The fine grading of active trachoma strongly correlated with organism load and disease severity (rs = 0.498, P = 0.0004). Overall, 53% of clinical activity (TF₁ or TF₂) and 59% of PCR positivity was found in those with disease scores less than the WHO simplified grade of TF.

Conclusion

Detailed studies of the pathogenesis, distribution and natural history of trachoma should use finer grading schemes for the more precise identification of clinical status. In low prevalence areas, the LPS-based POC test lacks the sensitivity to detect active ocular infection and nucleic acid amplification tests such as PCR or the 16S-RNA based NAAT performed better. Trachoma in the Aboriginal communities requires specific control measures.     

Risk of seroconversion and seroreversion of antibodies to Chlamydia trachomatis pgp3 in a longitudinal cohort of children in a low trachoma prevalence district in Tanzania

BackgroundSerologic testing for chlamydial antibodies is one potential tool for trachoma monitoring. Understanding the dynamics of seroconversion and seroreversion in low endemic districts is critical for determining the value of using serology.Methodology/Principal findingsWe surveyed a random sample of 2536 children aged 1–9 years in Kongwa, Tanzania, over three years; 1719 (67.8%) participants had all three follow-ups. Surveys assessed trachomatous inflammation—follicular (TF), Chlamydia trachomatis infection, and anti-pgp3 antibodies. Mass drug administration occurred immediately after the first and second follow-up surveys. The cohort was classified into trajectories of change in serostatus, and risk factors were evaluated for seroconversion and seroreversion. We found that 86.2% of seropositives remained seropositive throughout the study, whereas 12.1% seroreverted. Seroreverters were younger (Odds Ratio [OR] = 0.88 for every one-year increase in age, 95% CI = 0.79–0.99). 84.5% of seronegatives remained seronegative, and 13.0% seroconverted. Seroconverters were also younger (OR = 0.92, 95% CI = 0.87–0.98). Seroconversion and seroreversion were not explained by indeterminate values for the intensity of antibody response. Less than 1% of the cohort had unstable changes in serostatus, mostly explained by values in the indeterminate range. TF and infection in the cohort declined over time, while seropositivity increased from 31.5% to 36.4%.Conclusions/SignificanceAntibody status is relatively stable over time. Both seroconversion and seroreversion occurred over the three years in this low endemic district, especially in younger children. Modeling seroreversion is important for accurate determination of seroconversion. The use of serology as a monitoring tool should target the younger aged children as they will most likely capture recent changes in serostatus.     

Prevalence of trachoma in unity state, South Sudan: results from a large-scale population-based survey and potential implications for further surveys

Background

Large parts of South Sudan are thought to be trachoma-endemic but baseline data are limited. This study aimed to estimate prevalence for planning trachoma interventions in Unity State, to identify risk factors and to investigate the effect of different sampling approaches on study conclusions.

Methods and Findings

The survey area was defined as one domain of eight counties in Unity State. Across the area, 40 clusters (villages) were randomly selected proportional to the county population size in a population-based prevalence survey. The simplified grading scheme was used to classify clinical signs of trachoma. The unadjusted prevalence of trachoma inflammation-follicular (TF) in children aged 1–9 years was 70.5% (95% CI: 68.6–72.3). After adjusting for age, sex, county and clustering of cases at household and village level the prevalence was 71.0% (95% CI: 69.9–72.1). The prevalence of trachomatous trichiasis (TT) in adults was 15.1% (95% CI: 13.4–17.0) and 13.5% (95% CI: 12.0–15.1) before and after adjustment, respectively. We estimate that 700,000 people (the entire population of Unity State) require antibiotic treatment and approximately 54,178 people require TT surgery. Risk factor analyses confirmed child-level associations with TF and highlighted that older adults living in poverty are at higher risk of TT. Conditional simulations, testing the alternatives of sampling 20 or 60 villages over the same area, indicated that sampling of only 20 villages would have provided an acceptable level of precision for state-level prevalence estimation to inform intervention decisions in this hyperendemic setting.

Conclusion

Trachoma poses an enormous burden on the population of Unity State. Comprehensive control is urgently required to avoid preventable blindness and should be initiated across the state now. In other parts of South Sudan suspected to be highly trachoma endemic, counties should be combined into larger survey areas to generate the baseline data required to initiate interventions.     

The spread of HB virus infection in familial foci in a territory hyperendemic for hepatitis B

Epidemiological surveillance with the use of highly sensitive techniques for the indication of markers of hepatitis B (HB) virus infection in their dynamics has made it possible to find out that at a territory, hypersensitive for HB, along the existing high risk of this infection as the result of parenteral medical manipulations the intensive natural transmission of HB virus infection occurs under the conditions of everyday contacts with sources of the infection, patients with chronic forms of HB virus infection being of the highest epidemic importance. Under these conditions, children aged up to 7 years have been found to belong to the highest risk group. As a consequence, children of this age should be covered in future by specific preventive measures against HB. The spread of the epidemic process of HB virus infection in family foci is usually manifested by anicteric (usually not diagnosed) forms of this infection. All these circumstances make it expedient to develop antiepidemic and prophylactic measures in the foci of HB.     

Risk factors for the progression of trachomatous scarring in a cohort of women in a trachoma low endemic district in Tanzania

BackgroundTrachoma, a chronic conjunctivitis caused by Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. Trachoma has been targeted for elimination as a public health problem which includes reducing trachomatous inflammation—follicular prevalence in children and reducing trachomatous trichiasis prevalence in adults. The rate of development of trachomatous trichiasis, the potentially blinding late-stage trachoma sequelae, depends on the rate of trachomatous scarring development and progression. Few studies to date have evaluated the progression of trachomatous scarring in communities that have recently transitioned to a low trachomatous inflammation—follicular prevalence.Methodology/Principal findingsWomen aged 15 and older were randomly selected from households in 48 communities within Kongwa district, Tanzania and followed over 3.5 years for this longitudinal study. Trachomatous inflammation—follicular prevalence was 5% at baseline and at follow-up in children aged 1–9 in Kongwa, Tanzania. 1018 women aged 15 and older had trachomatous scarring at baseline and were at risk for trachomatous scarring progression; 691 (68%) completed follow-up assessments. Photographs of the upper tarsal conjunctiva were obtained at baseline and follow-up and graded for trachomatous scarring using a previously published four-step severity scale. The overall cumulative 3.5-year progression rate of scarring was 35.3% (95% CI 31.6–39.1). The odds of TS progression increased with an increase in age in women younger than 50, (OR 1.03, 95% CI 1.01–1.05, p = 0.005) as well as an increase in the household poverty index (OR 1.29, 95% CI 1.13–1.48, p = 0.0002).Conclusions/SignificanceThe 3.5-year progression of scarring among women in Kongwa, a formerly hyperendemic now turned hypoendemic district in central Tanzania, was high despite a low active trachoma prevalence. This suggests that the drivers of scarring progression are likely not related to on-going trachoma transmission in this district.     

A slow spread of adenovirus type 7 infection after its re-emergence in Yamagata, Japan, in 1995

We have continued the epidemiological study on adenovirus type 7 (Ad7), which re-emerged in 1995 in Yamagata, Japan. Between 1999 and 2004, we isolated only four strains from 10,778 throat swab specimens among children with acute respiratory infections. A serological survey of 303 specimens revealed the antibody-positive rate against Ad7 to be 0-7.4% in children under 10 years of age in 2005, although it was 3.3-16.7% in 1997 and 0% in 1993. Our results suggest that a re-emergence does not always provoke a sudden major outbreak, even if the antibody-positive rate against Ad7 is low in the local community.     

Synthesis and evaluation of Ciprofloxacin derivatives as diagnostic tools for bacterial infection by Staphylococcus aureus

Development of target-specific diagnostic radiopharmaceuticals has always been a challenging task. For this purpose, design and development of the imaging-friendly variant of a potent antibiotic could aid in treatment planning and follow-up of patients with hard-to-diagnose bacterial infections. Fluoroquinolone analogues were synthesized taking the lead from Ciprofloxacin (the broad spectrum antibiotic) molecule. The idea of modifying fluoroquinolones, and subsequently labeling them, was to preserve their capacity to bind bacteria and thereby enable the compound to specifically target those microorganisms. Three compounds were thus synthesized as derivatives of Ciprofloxacin. The fluoroquinolone analogues were labeled with (99m)Tc by using (99m)Tc pertechnetate with high labeling efficiency for all the formulations. The complexes formed by chelation of (99m)Tc with our synthesized fluoroquinolone analogues showed good in vitro serum stability. The blood clearance study performed in New Zealand White rabbits exhibited a curve indicating the initial fast phase in which radiocomplexed drugs cleared from blood very quickly followed by a slow phase. The in vivo evaluation showed that fluoroquinolone-based radiopharmaceuticals bind to the bacteria present at the site of infection, which results in the retention of the agent at sites of active bacterial infection. The biodistribution data and the scintigrams demonstrated that Staphylococcus aureus bacteria in animal infection models took up the radiopharmaceutical formulations, confirming our hypothesis that (99m)Tc fluoroquinolone derivatives might be useful as diagnostic agents for targeted delivery in bacterial infections.     

Experimental field study of problem-solving using tools in free-ranging capuchins (Sapajus nigritus, formerly Cebus nigritus)

Some populations of capuchins are reported to use tools to solve foraging problems in the wild. In most cases, this involves the act of pounding and digging. The use of probing tools by wild capuchins is considerably less common. Here we report on the results of an experimental field study conducted in southern Brazil designed to examine the ability of wild black-horned capuchins (Sapajus nigritus) to use a wooden dowel as a lever or a probe to obtain an embedded food reward. A group of eight capuchins was presented with two experimental platforms, each housing a clear Plexiglas box containing two bananas on a shelf and four inserted dowels. Depending on the conditions of the experiment, the capuchins were required either to pull (Condition I) or push (Conditions II and III) the dowels, in order to dislodge the food reward from the shelf so that it could be manually retrieved. In Condition I, four individuals spontaneously solved the foraging problem by pulling the dowels in 25% (72/291) of visits. In Conditions II and III, however, no capuchin successfully pushed the dowels forward to obtain the food reward. During these latter two experimental conditions, the capuchins continued to pull the dowels (41/151 or 27% of visits), even though this behavior did not result in foraging success. The results of these field experiments are consistent with an identical study conducted on wild Cebus capucinus in Costa Rica, and suggest that when using an external object as a probe to solve a foraging problem, individual capuchins were able to rapidly learn an association between the tool and the food reward, but failed to understand exactly how the tool functioned in accomplishing the task. The results also suggest that once a capuchin learned to solve this tool-mediated foraging problem, the individual persisted in using the same solution even in the face of repeated failure (slow rate of learning extinction).     

Predicting future community-level ocular Chlamydia trachomatis infection prevalence using serological,clinical, molecular,and geospatial data

Trachoma is an infectious disease characterized by repeated exposures to Chlamydia trachomatis (Ct) that may ultimately lead to blindness. Efficient identification of communities with high infection burden could help target more intensive control efforts. We hypothesized that IgG seroprevalence in combination with geospatial layers, machine learning, and model-based geostatistics would be able to accurately predict future community-level ocular Ct infections detected by PCR. We used measurements from 40 communities in the hyperendemic Amhara region of Ethiopia to assess this hypothesis. Median Ct infection prevalence among children 0–5 years old increased from 6% at enrollment, in the context of recent mass drug administration (MDA), to 29% by month 36, following three years without MDA. At baseline, correlation between seroprevalence and Ct infection was stronger among children 0–5 years old (ρ = 0.77) than children 6–9 years old (ρ = 0.48), and stronger than the correlation between active trachoma and Ct infection (0-5y ρ = 0.56; 6-9y ρ = 0.40). Seroprevalence was the strongest concurrent predictor of infection prevalence at month 36 among children 0–5 years old (cross-validated R² = 0.75, 95% CI: 0.58–0.85), though predictive performance declined substantially with increasing temporal lag between predictor and outcome measurements. Geospatial variables, a spatial Gaussian process, and stacked ensemble machine learning did not meaningfully improve predictions. Serological markers among children 0–5 years old may be an objective tool for identifying communities with high levels of ocular Ct infections, but accurate, future prediction in the context of changing transmission remains an open challenge.     

The prevalence of non-breeders in raptor populations: evidence from rings, radio-tags and transect surveys

Age-specific survival and breeding (ASSAB) models were developed with data from 146 common buzzards ( Buteo buteo ) radio-tagged in southern Britain during 1990–1998, in a 120-km2 study area that had on average 25 egg-laying pairs. Survival checks were aided by philopatric behaviour and a maximum annual tag failure rate of 7%: minimum survival rates, that were estimated by assuming death of buzzards with lost tags, were close to maximum rates that were estimated using only the recorded deaths. First-year survival rate estimates for 35 buzzards fitted in 1990–1991 with 25–30-g backpack radios were 69–74% (minimum-maximum), close to the 61–71% for 16 buzzards with 12-g tail-mount radios; the backpacks transmitted for 2–4 yr. Overall survival rates were 66–73% in the first year, 91–97% in the second and 88–91% thereafter. Survival estimates from 288 recent British ring recoveries were lower in the first and second years, at 55% and 75%, but similar (88%) thereafter. Most deaths were from natural causes (40%) or interaction with artefacts (36%). ASSAB models, from radio-tracking and the observed 1.71 young clutch−1, predicted breeding by 16–21% of all the buzzards present in spring, or up to 25% with the minimum likely productivity of 1.4 young clutch−1 or 12% net emigration. Ringing data predicted breeding rates of 33–38%. The models were tested with density data from nest surveys and new radio-corrected-transect and truncation-mark-resighting estimates of buzzard numbers. Surveys in autumn and late winter estimated breeding rates of 21–25%. The high non-breeder density in spring, of three other buzzards for each paired bird with eggs, has important implications for understanding evolutionary fitness, predation and population ecology.     

Community risk factors for ocular Chlamydia infection in Niger: pre-treatment results from a cluster-randomized trachoma trial

Background

Trachoma control programs utilize mass azithromycin distributions to treat ocular Chlamydia trachomatis as part of an effort to eliminate this disease world-wide. But it remains unclear what the community-level risk factors are for infection.

Methods

This cluster-randomized, controlled trial entered 48 randomly selected communities in a 2×2 factorial design evaluating the effect of different treatment frequencies and treatment coverage levels. A pretreatment census and examination established the prevalence of risk factors for clinical trachoma and ocular chlamydia infection including years of education of household head, distance to primary water source, presence of household latrine, and facial cleanliness (ocular discharge, nasal discharge, and presence of facial flies). Univariate and multivariate associations were tested using linear regression and Bayes model averaging.

Findings

There were a total of 24,536 participants (4,484 children aged 0–5 years) in 6,235 households in the study. Before treatment in May to July 2010, the community-level prevalence of active trachoma (TF or TI utilizing the World Health Organization [WHO] grading system) was 26.0% (95% CI: 21.9% to 30.0%) and the mean community-level prevalence of chlamydia infection by Amplicor PCR was 20.7% (95% CI: 16.5% to 24.9%) in children aged 0–5 years. Univariate analysis showed that nasal discharge (0.29, 95% CI: 0.04 to 0.54; P = 0.03), presence of flies on the face (0.40, 95% CI: 0.17 to 0.64; P = 0.001), and years of formal education completed by the head of household (0.07, 95% CI: 0.07 to 0.13; P = 0.03) were independent risk factors for chlamydia infection. In multivariate analysis, facial flies (0.26, 95% CI: 0.02 to 0.49; P = 0.03) and years of formal education completed by the head of household (0.06, 95% CI: 0.008 to 0.11; P = 0.02) were associated risk factors for ocular chlamydial infection.

Interpretation

We have found that the presence of facial flies and years of education of the head of the household are risk factors for chlamydia infection when the analysis is done at the community level.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00792922","term_id":"NCT00792922"}}NCT00792922     

Urogenital schistosomiasis infection prevalence targets to determine elimination as a public health problem based on microhematuria prevalence in school-age children

BackgroundRecent research suggests that schistosomiasis targets for morbidity control and elimination as a public health problem could benefit from a reanalysis. These analyses would define evidence-based targets that control programs could use to confidently assert that they had controlled or eliminated schistosomiasis as a public health problem. We estimated how low Schistosoma haematobium infection levels diagnosed by urine filtration in school-age children should be decreased so that microhematuria prevalence was at, or below, a “background” level of morbidity.MethodologyData obtained from school-age children in Burkina Faso, Mali, Niger, Tanzania, and Zambia who participated in schistosomiasis monitoring and evaluation cohorts were reanalyzed before and after initiation of preventive chemotherapy. Bayesian models estimated the infection level prevalence probabilities associated with microhematuria thresholds ≤10%, 13%, or 15%.Principal findingsAn infection prevalence of 5% could be a sensible target for urogenital schistosomiasis morbidity control in children as microhematuria prevalence was highly likely to be below 10% in all surveys. Targets of 8% and 11% infection prevalence were highly likely to result in microhematuria levels less than 13% and 15%, respectively. By contrast, measuring heavy-intensity infections only achieves these thresholds at impractically low prevalence levels.Conclusions/significanceA target of 5%, 8%, or 11% urogenital schistosomiasis infection prevalence in school-age children could be used to determine whether a geographic area has controlled or eliminated schistosomiasis as a public health problem depending on the local background threshold of microhematuria.     

Screening strategies for tuberculosis prevalence surveys: the value of chest radiography and symptoms

Background

We conducted a tuberculosis (TB) prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding.

Methods

All participants with a positive screen on either a symptom questionnaire, chest radiography (CXR) and/or sputum smear microscopy submitted sputum for culture. HIV status was obtained from prevalent cases. We estimated the accuracy of modified screening strategies with bacteriologically confirmed TB as the gold standard, and compared these with other survey reports. We also assessed whether sequential rather than parallel application of symptom, CXR and HIV screening would substantially reduce the number of participants requiring CXR and/or sputum culture.

Results

Presence of any abnormality on CXR had 94% (95%CI 88–98) sensitivity (92% in HIV-infected and 100% in HIV-uninfected) and 73% (95%CI 68–77) specificity. Symptom screening combinations had significantly lower sensitivity than CXR except for ‘any TB symptom’ which had 90% (95%CI 84–95) sensitivity (96% in HIV-infected and 82% in HIV-uninfected) and 32% (95%CI 30–34) specificity. Smear microscopy did not yield additional suspects, thus the combined symptom/CXR screen applied in the survey had 100% (95%CI 97–100) sensitivity. Specificity was 65% (95%CI 61–68). Sequential application of first a symptom screen for ‘any symptom’, followed by CXR-evaluation and different suspect criteria depending on HIV status would result in the largest reduction of the need for CXR and sputum culture, approximately 36%, but would underestimate prevalence by 11%.

Conclusion

CXR screening alone had higher accuracy compared to symptom screening alone. Combined CXR and symptom screening had the highest sensitivity and remains important for suspect identification in TB prevalence surveys in settings where bacteriological sputum examination of all participants is not feasible.     

Purification and characterization of a 60-kDa protein from oat, formerly known as a TCP1-related chaperone

Recently, Mummertet al. [Nature 363, 644–648 (1993)] isolated a proposed TCP1-related chaperone. Here we report several findings concerning the protein which they sequenced. Two similar N-terminal sequences were obtained from this abundant 60-kDa protein. Internal sequences were also acquired by protease digestion. Initially it was believed the protein was able to completely inhibit citrate synthase aggregation, but later purifications demonstrated that the 60-kDa polypeptide lacked both chaperone activity and the previously reported kinase activity [Grimmet al., Planta 178, 199–206 (1989)]. It is now our belief that this protein is neither a chaperone nor a kinase.     

Prediction tools for unfavourable outcomes in Clostridium difficile infection: a systematic review

Context

Identifying patients at risk for adverse outcomes of Clostridium difficile infection (CDI), including recurrence and death, will become increasingly important as novel therapies emerge, which are more effective than traditional approaches but very expensive. Clinical prediction rules (CPRs) can improve the accuracy of medical decision-making. Several CPRs have been developed for CDI, but none has gained a widespread acceptance.

Methods

We systematically reviewed studies describing the derivation or validation of CPRs for unfavourable outcomes of CDI, in medical databases (Medline, Embase, PubMed, Web of Science and Cochrane) and abstracts of conferences.

Results

Of 2945 titles and abstracts screened, 13 studies on the derivation of a CPR were identified: two on recurrences, five on complications (including mortality), five on mortality alone and one on response to treatment. Two studies on the validation of different severity indices were also retrieved. Most CPRs were developed as secondary analyses using cohorts assembled for other purposes. CPRs presented several methodological limitations that could explain their limited use in clinical practice. Except for leukocytosis, albumin and age, there was much heterogeneity in the variables used, and most studies were limited by small sample sizes. Eight models used a retrospective design. Only four studies reported the incidence of the outcome of interest, even if this is essential to evaluate the potential usefulness of a model in other populations. Only five studies performed multivariate analyses to adjust for confounders.

Conclusions

The lack of weighing variables, of validation, calibration and measures of reproducibility, the weak validities and performances when assessed, and the absence of sensitivity analyses, all led to suboptimal quality and debatable utility of those CPRs. Evidence-based tools developed through appropriate prospective cohorts would be more valuable for clinicians than empirically-developed CPRs.     

Serological surveys of Corynebacterium kutscheri infection in mice and rats

Serological surveys of mice and rats naturally infected with Corynebacterium kutscheri were performed by examining serum samples collected from breeder and laboratory colonies between 1981 and 1983. Among 756 mice from 73 conventional colonies, only 4 animals (0.5%) from 3 colonies (4.1%) developed C. kutscheri antibody of 1:40 to 1:2, 560 titers. Three of them suffered from abscess caused by the organism. Regarding a titer of 1:40 or higher as reliably positive, 87 (13.0%) of 669 conventional rats or 20 (32.8%) of 61 colonies were found to be infected with the organism. The antibodies were detected in both types of animals older than 6 months of age. No lesions caused by C. kutscheri were found in almost all the rats examined. Germ-free and SPF mice and rats were all negative for antibody at 1:5 serum dilution.