Towards an odour-baited trap to control Musca sorbens, the putative vector of trachoma.

Musca sorbens is a synanthropic filth fly that aggressively attacks people to feed from mucous membranes of the eyes, nose or mouth, from open sores, or from sweat. It has long been suspected that this fly contributes to the transmission of eye infections, particularly trachoma, and recent work has added to the evidence base that M. sorbens is a trachoma vector in Ethiopia. There are few options to control M. sorbens, largely due to a lack of evidence. Space spraying with insecticides is effective, but an environmentally sound and long-term sustainable solution would be better, for example, mass trapping. We tested commercially available and homemade trap types in a pilot (laboratory) study and three field studies. A homemade design, built from a bucket and two empty water bottles, baited with a commercially available lure, The Buzz, was found to be most effective. This trap caught 3848 M. sorbens over 26 trap 'events' (3- or 4-day periods); mean/median per 24 h 43.6 (standard deviation 137.10)/2.25 (IQR 0.25-12.67). The Buzz lure is cheap and effective for 4 weeks, and trap components cheap and locally available. Further studies are needed to understand the impact of this trap on local fly populations and the local transmission of trachoma.

Strengthening data collection for neglected tropical diseases: What data are needed for models to better inform tailored intervention programmes?

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.

Viability PCR shows that non-ocular surfaces could contribute to transmission of Chlamydia trachomatis infection in trachoma.

BACKGROUND: The presence of Chlamydia trachomatis (Ct) DNA at non-ocular sites suggests that these sites may represent plausible routes of Ct transmission in trachoma. However, qPCR cannot discriminate between DNA from viable and non-viable bacteria. Here we use a propodium monoazide based viability PCR to investigate how long Ct remains viable at non-ocular sites under laboratory-controlled conditions. METHODS: Cultured Ct stocks (strain A2497) were diluted to final concentrations of 1000, 100, 10 and 1 omcB copies/µL and applied to plastic, woven mat, cotton cloth and pig skin. Swabs were then systemically collected from each surface and tested for the presence Ct DNA using qPCR. If Ct DNA was recovered, Ct viability was assessed over time by spiking multiple areas of the same surface type with the same final concentrations. Swabs were collected from each surface at 0, 2, 4, 6, 8 and 24 hours after spiking. Viability PCR was used to determine Ct viability at each timepoint. RESULTS: We were able to detect Ct DNA on all surfaces except the woven mat. Total Ct DNA remained detectable and stable over 24 hours for all concentrations applied to plastic, pig skin and cotton cloth. The amount of viable Ct decreased over time. For plastic and skin surfaces, only those where concentrations of 100 or 1000 omcB copies/µL were applied still had viable loads detectable after 24 hours. Cotton cloth showed a more rapid decrease and only those where concentrations of 1000 omcB copies/µL were applied still had viable DNA detectable after 24 hours. CONCLUSION: Plastic, cotton cloth and skin may contribute to transmission of the Ct strains that cause trachoma, by acting as sites where reservoirs of bacteria are deposited and later collected and transferred mechanically into previously uninfected eyes.

Selecting behaviour change priorities for trachoma 'F' and 'E' interventions: A formative research study in Oromia, Ethiopia.

BACKGROUND: Trachoma is the leading infectious cause of blindness. However, little is known about the behavioural and environmental determinants of transmission of the causative organism, Chlamydia trachomatis. We conducted formative research in a trachoma hyper-endemic area of Ethiopia to explore the behaviours which are likely to contribute to trachoma transmission and map their determinants. METHODOLOGY/PRINCIPAL FINDINGS: Data on water use, hygiene, defecation, and sleeping arrangements were collected from five communities during the dry and rainy seasons in 2016. Data collection involved direct observation in households (n = 20), interviews with caregivers (n = 20) and focus group discussions (n = 11). Although several behaviours that likely contribute to trachoma transmission were identified, no single behaviour stood out as the dominant contributor. Hygiene practices reflected high levels of poverty and water scarcity. Face washing and soap use varied within and between households, and were associated with other factors such as school attendance. Children's faces were rarely wiped to remove nasal or ocular discharge, which was not perceived to be socially undesirable. Bathing and laundry were performed infrequently due to the amount of time and water required. Open defecation was a normative practice, particularly for young children. Latrines, when present, were poorly constructed, maintained and used. Young children and parents slept closely together and shared bedding that was infrequently washed. CONCLUSIONS/SIGNIFICANCE: Existing norms and enabling factors in this context favour the development of interventions to improve facial cleanliness as more feasible than those that reduce unsafe faeces disposal. Interventions to increase the frequency of bathing and laundry may also be infeasible unless water availability within the home is improved.

Perceptions and practices of community members relating to trachoma in Africa: a qualitative systematic review protocol.

OBJECTIVE: The objective of this systematic review is to synthesize and present the best available evidence on community perceptions and practices relating to trachoma in Africa. INTRODUCTION: Globally, trachoma is the leading cause of blindness and is responsible for about 1.4% of all cases of blindness. The African continent is the worst affected, with about 1.9 million cases of trichiasis (61%). While interventions are currently being implemented to combat the disease in Africa, very little is known by decision makers about community perceptions and practices relating to trachoma, which may hinder successful implementation. INCLUSION CRITERIA: Studies with participants, regardless of their health status, gender, religion and ethnicity, aged 14 and over conducted in any African country, will be considered. Studies on Africans, conducted out of the continent and those involving healthcare professionals, will not be included in this review. METHODS: Qualitative studies, published in English from 1996 onwards. will be considered. Databases to be searched will include, but not be limited to: PubMed, CINAHL, Embase and PsycINFO. Study selection, critical appraisal and data extraction will be conducted by two independent reviewers, using the appropriate JBI methodology and any disagreement will be resolved by discussion or with a third reviewer. Qualitative findings will be synthesized using the appropriate JBI methodology, following the meta-aggregation approach. Where textual pooling is not possible, the findings will be presented in narrative form. The ConQual approach will be used to grade synthesized findings, and these will be presented in a Summary of Findings.

Discrepancies between observed data and predictions from mathematical modelling of the impact of screening interventions on Chlamydia trachomatis prevalence.

Mathematical modelling studies of C. trachomatis transmission predict that interventions to screen and treat chlamydia infection will reduce prevalence to a greater degree than that observed in empirical population-based studies. We investigated two factors that might explain this discrepancy: partial immunity after natural infection clearance and differential screening coverage according to infection risk. We used four variants of a compartmental model for heterosexual C. trachomatis transmission, parameterized using data from England about sexual behaviour, C. trachomatis testing, diagnosis and prevalence, and Markov Chain Monte Carlo methods for statistical inference. In our baseline scenario, a model in which partial immunity follows natural infection clearance and the proportion of tests done in chlamydia-infected people decreases over time fitted the data best. The model predicts that partial immunity reduced susceptibility to reinfection by 68% (95% Bayesian credible interval 46-87%). The estimated screening rate was 4.3 (2.2-6.6) times higher for infected than for uninfected women in 2000, decreasing to 2.1 (1.4-2.9) in 2011. Despite incorporation of these factors, the model still predicted a marked decline in C. trachomatis prevalence. To reduce the gap between modelling and data, advances are needed in knowledge about factors influencing the coverage of chlamydia screening, the immunology of C. trachomatis and changes in C. trachomatis prevalence at the population level.

The utility of serology for elimination surveillance of trachoma.

Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, we analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low-transmission and post-elimination settings. Analyses with sero-catalytic and antibody acquisition models provide insights into transmission history within each population. To accurately estimate sero-conversion rates (SCR) for trachoma in populations with high-seroprevalence in adults, the model accounts for secondary exposure to Chlamydia trachomatis due to urogenital infection. We estimate the population half-life of sero-reversion for anti-Pgp3 antibodies to be 26 (95% credible interval (CrI): 21-34) years. We show SCRs below 0.015 (95% confidence interval (CI): 0.0-0.049) per year correspond to a prevalence of trachomatous inflammation-follicular below 5%, the current threshold for elimination of active trachoma as a public health problem. As global trachoma prevalence declines, we may need cross-sectional serological survey data to inform programmatic decisions.

Serological and PCR-based markers of ocular Chlamydia trachomatis transmission in northern Ghana after elimination of trachoma as a public health problem.

BACKGROUND: Validation of elimination of trachoma as a public health problem is based on clinical indicators, using the WHO simplified grading system. Chlamydia trachomatis (Ct) infection and anti-Ct antibody responses (anti-Pgp3) have both been evaluated as alternative indicators in settings with varying levels of trachoma. There is a need to evaluate the feasibility of using tests for Ct infection and anti-Pgp3 antibodies at scale in a trachoma-endemic country and to establish the added value of the data generated for understanding transmission dynamics in the peri-elimination setting. METHODOLOGY/PRINCIPAL FINDINGS: Dried blood spots for serological testing and ocular swabs for Ct infection testing (taken from children aged 1-9 years) were integrated into the pre-validation trachoma surveys conducted in the Northern and Upper West regions of Ghana in 2015 and 2016. Ct infection was detected using the GeneXpert PCR platform and the presence of anti-Pgp3 antibodies was detected using both the ELISA assay and multiplex bead array (MBA). The overall mean cluster-summarised TF prevalence (the clinical indicator) was 0.8% (95% CI: 0.6-1.0) and Ct infection prevalence was 0.04% (95%CI: 0.00-0.12). Anti-Pgp3 seroprevalence using the ELISA was 5.5% (95% CI: 4.8-6.3) compared to 4.3% (95%CI: 3.7-4.9) using the MBA. There was strong evidence from both assays that seropositivity increased with age (p<0.001), although the seroconversion rate was estimated to be very low (between 1.2 to 1.3 yearly events per 100 children). CONCLUSIONS/SIGNIFICANCE: Infection and serological data provide useful information to aid in understanding Ct transmission dynamics. Elimination of trachoma as a public health problem does not equate to the absence of ocular Ct infection nor cessation in acquisition of anti-Ct antibodies.

Identifying a sufficient core group for trachoma transmission.

BACKGROUND: In many infectious diseases, a core group of individuals plays a disproportionate role in transmission. If these individuals were effectively prevented from transmitting infection, for example with a perfect vaccine, then the disease would disappear in the remainder of the community. No vaccine has yet proven effective against the ocular strains of chlamydia that cause trachoma. However, repeated treatment with oral azithromycin may be able to prevent individuals from effectively transmitting trachoma. METHODOLOGY/PRINCIPAL FINDINGS: Here we assess several methods for identifying a core group for trachoma, assuming varying degrees of knowledge about the transmission process. We determine the minimal core group from a completely specified model, fitted to results from a large Ethiopian trial. We compare this benchmark to a core group that could actually be identified from information available to trachoma programs. For example, determined from the rate of return of infection in a community after mass treatments, or from the equilibrium prevalence of infection. CONCLUSIONS/SIGNIFICANCE: Sufficient groups are relatively easy for programs to identify, but will likely be larger than the theoretical minimum.

One round of azithromycin MDA adequate to interrupt transmission in districts with prevalence of trachomatous inflammation-follicular of 5.0-9.9%: Evidence from Malawi.

BACKGROUND: As highly trachoma-endemic countries approach elimination, some districts will have prevalences of trachomatous inflammation-follicular in 1-9-year-olds (TF1-9) of 5.0-9.9%. The World Health Organization (WHO) previously recommended that in such districts, TF prevalence be assessed in each sub-district (groupings of at least three villages), with three rounds of azithromycin treatment offered to any sub-district in which TF≥10%. Given the large number of endemic districts worldwide and the human and financial resources required to conduct surveys, this recommendation may not be practical. In a group of 8 Malawi districts with baseline TF prevalences of 5.0-9.9%, the Malawi Ministry of Health administered one round of azithromycin mass treatment, to the whole of each district, achieving mean coverage of ~80%. Here, we report impact surveys conducted after that treatment. METHODS: We undertook population-based trachoma surveys in 18 evaluation units of the 8 treated districts, at least 6 months after the MDA. The standardized training package and survey methodologies of Tropical Data, which conform to WHO recommendations, were used. RESULTS: Each of the 18 evaluation units had a TF1-9 prevalence <5.0%. CONCLUSION: The study demonstrates that in Malawi districts with TF of 5.0-9.9%, one round of azithromycin MDA with ~80% coverage associates with a reduction in TF prevalence to <5%. Further evidence for this approach should be collected elsewhere.

Models of Trachoma Transmission and Their Policy Implications: From Control to Elimination.

Despite great progress in eliminating trachoma from the majority of worldwide districts, trachoma control seems to have stalled in some endemic districts. Can mathematical models help suggest the way forward? We review specific achievements of models in trachoma control in the past. Models showed that, even with incomplete coverage, mass drug administration could eliminate disease through a spillover effect, somewhat analogous to how incomplete vaccine campaigns can eliminate disease through herd protection. Models also suggest that elimination can always be achieved if enough people are treated often enough with an effective enough drug. Other models supported the idea that targeting ages at highest risk or continued improvements in hygiene and sanitation can contribute meaningfully to trachoma control. Models of intensive targeting of a core group may point the way to final eradication even in areas with substantial transmission and within-community heterogeneity.

Coverage, social mobilization and challenges of mass Zithromax administration campaign in South and South East zones of Tigray, Northern Ethiopia: A cross sectional study.

BACKGROUND: The antibiotic treatment of people with trachoma helps to prevent transmission the disease in a community. Currently, Zithromax is the drug recommended for mass drug administration (MDA). MDA should be carried out annually for three to five years in trachoma endemic areas. Coverage survey is essential to track progress towards program goals and to identify communities with poor coverage in order to permit timely and appropriate actions. We assessed mass Zithromax administration coverage, social mobilization and campaign challenges in south and southeast zones of Tigray, Ethiopia. METHOD: We conducted a survey in community in Southern and South East zones of Tigray region from August 15 to August 31, 2016. The survey included nine Woredas. It was supported by qualitative methods. A total of 3741 individuals were enrolled from 933 households using multistage sampling. We used structured questionnaire. In-depth interview and focus group discussion were also applied. Descriptive statistics was performed using SPSS version 20.We thematically analyzed the qualitative data using Atlas 7. RESULT: The overall coverage of Zithromax MDA was 93.3%. It ranges from 90.0% in Seharti Samre to 97.9% in Endamokoni. The coverage was 93.4% for males and 93.1% for females. A higher proportion (98.3%) of children aged 5 to 15 years and 409 (87.8%) under five children took Zithromax. The coverage was 94% in rural and 91.2% in urban. Women development army (43.3%) and health extension workers (32.5%) were the main source of information. Frequent occurrence of drug side effects, rumors, lack of community and leaders' engagement in the campaign, fasting, shortage of human power and short term unavailability of supplies were barriers during the campaign. CONCLUSION: The Zithromax MDA coverage in the study zones was higher than the minimum WHO set criteria of 80%. There was a wide difference in coverage among Woredas and Kebeles. The MDA coverage was lower in urban than rural. Misconceptions and poor mobilization were common challenges. Thus, proper planning, community mobilization and uniform training will need to be done ahead of the campaign in the future.

Sanitation and water supply coverage thresholds associated with active trachoma: Modeling cross-sectional data from 13 countries.

BACKGROUND: Facial cleanliness and sanitation are postulated to reduce trachoma transmission, but there are no previous data on community-level herd protection thresholds. We characterize associations between active trachoma, access to improved sanitation facilities, and access to improved water sources for the purpose of face washing, with the aim of estimating community-level or herd protection thresholds. METHODS AND FINDINGS: We used cluster-sampled Global Trachoma Mapping Project data on 884,850 children aged 1-9 years from 354,990 households in 13 countries. We employed multivariable mixed-effects modified Poisson regression models to assess the relationships between water and sanitation coverage and trachomatous inflammation-follicular (TF). We observed lower TF prevalence among those with household-level access to improved sanitation (prevalence ratio, PR = 0.87; 95%CI: 0.83-0.91), and household-level access to an improved washing water source in the residence/yard (PR = 0.81; 95%CI: 0.75-0.88). Controlling for household-level water and latrine access, we found evidence of community-level protection against TF for children living in communities with high sanitation coverage (PR80-90% = 0.87; 95%CI: 0.73-1.02; PR90-100% = 0.76; 95%CI: 0.67-0.85). Community sanitation coverage levels greater than 80% were associated with herd protection against TF (PR = 0.77; 95%CI: 0.62-0.97)-that is, lower TF in individuals whose households lacked individual sanitation but who lived in communities with high sanitation coverage. For community-level water coverage, there was no apparent threshold, although we observed lower TF among several of the higher deciles of community-level water coverage. CONCLUSIONS: Our study provides insights into the community water and sanitation coverage levels that might be required to best control trachoma. Our results suggest access to adequate water and sanitation can be important components in working towards the 2020 target of eliminating trachoma as a public health problem.

Dicas em Saúde: Tracoma

Informações de utilidade pública sobre sintomas, transmissão e prevenção do tracoma.

Probabilistic forecasts of trachoma transmission at the district level: A statistical model comparison.

The World Health Organization and its partners are aiming to eliminate trachoma as a public health problem by 2020. In this study, we compare forecasts of TF prevalence in 2011 for 7 different statistical and mechanistic models across 9 de-identified trachoma endemic districts, representing 4 unique trachoma endemic countries. We forecast TF prevalence between 1-6 years ahead in time and compare the 7 different models to the observed 2011 data using a log-likelihood score. An SIS model, including a district-specific random effect for the district-specific transmission coefficient, had the highest log-likelihood score across all 9 districts and was therefore the best performing model. While overall the deterministic transmission model was the least well performing model, although it did comparably well to the other models for 8 of 9 districts. We perform a statistically rigorous comparison of the forecasting ability of a range of mathematical and statistical models across multiple endemic districts between 1 and 6 years ahead of the last collected TF prevalence data point in 2011, assessing results against surveillance data. This study is a step towards making statements about likelihood and time to elimination with regard to the WHO GET2020 goals.

Mathematical Modelling of Trachoma Transmission, Control and Elimination.

The World Health Organization has targeted the elimination of blinding trachoma by the year 2020. To this end, the Global Elimination of Blinding Trachoma (GET, 2020) alliance relies on a four-pronged approach, known as the SAFE strategy (S for trichiasis surgery; A for antibiotic treatment; F for facial cleanliness and E for environmental improvement). Well-constructed and parameterized mathematical models provide useful tools that can be used in policy making and forecasting in order to help to control trachoma and understand the feasibility of this large-scale elimination effort. As we approach this goal, the need to understand the transmission dynamics of infection within areas of different endemicities, to optimize available resources and to identify which strategies are the most cost-effective becomes more pressing. In this study, we conducted a review of the modelling literature for trachoma and identified 23 articles that included a mechanistic or statistical model of the transmission, dynamics and/or control of (ocular) Chlamydia trachomatis. Insights into the dynamics of trachoma transmission have been generated through both deterministic and stochastic models. A large body of the modelling work conducted to date has shown that, to varying degrees of effectiveness, antibiotic administration can reduce or interrupt trachoma transmission. However, very little analysis has been conducted to consider the effect of nonpharmaceutical interventions (and particularly the F and E components of the SAFE strategy) in helping to reduce transmission. Furthermore, very few of the models identified in the literature review included a structure that permitted tracking of the prevalence of active disease (in the absence of active infection) and the subsequent progression to disease sequelae (the morbidity associated with trachoma and ultimately the target of GET 2020 goals). This represents a critical gap in the current trachoma modelling literature, which makes it difficult to reliably link infection and disease. In addition, it hinders the application of modelling to assist the public health community in understanding whether trachoma programmes are on track to reach the GET goals by 2020. Another gap identified in this review was that of the 23 articles examined, only one considered the cost-effectiveness of the interventions implemented. We conclude that although good progress has been made towards the development of modelling frameworks for trachoma transmission, key components of disease sequelae representation and economic evaluation of interventions are currently missing from the available literature. We recommend that rapid advances in these areas should be urgently made to ensure that mathematical models for trachoma transmission can robustly guide elimination efforts and quantify progress towards GET 2020.

The impact of climate on the abundance of Musca sorbens, the vector of trachoma.

BACKGROUND: To assess the extent to which climate may affect the abundance of Musca sorbens, a putative vector of trachoma. DATA SOURCES: Studies were identified by systematically searching online databases including CAB abstracts, Embase, Global Health, Medline, Web of Science and BIOS Online, references from key articles, and the websites of relevant international agencies. METHODS: A systematic literature review was conducted of field and laboratory studies that reported the impact of climate factors (e.g., temperature, humidity) on the synanthropic fly Musca sorbens. Data were systematically extracted and studies assessed for quality by two readers. Study results were reported narratively. RESULTS: A total of 16 studies met the inclusion criteria but only three evaluated associations between climatic/abiotic factors and M. sorbens. Limited evidence indicates that M. sorbens abundance has an optimal temperature and humidity range. Thirteen studies reported seasonal patterns but no consistent pattern was found between season and the abundance of M. sorbens. CONCLUSIONS: The evidence base regarding the effect of climatic factors on M. sorbens is limited, so it is difficult to construct a biological model driven by climate for this species. A multivariate statistical approach based on the climate of sites where M. sorbens is found may better capture its complex relationship with climatic factors as well as aid in mapping the global range of M. sorbens.

Short-term forecasting of the prevalence of clinical trachoma: utility of including delayed recovery and tests for infection.

BACKGROUND: The World Health Organization aims to control blinding trachoma by 2020. Decisions on whether to start and stop mass treatments and when to declare that control has been achieved are currently based on clinical examination data generated in population-based surveys. Thresholds are based on the district-level prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years. Forecasts of which districts may and may not meet TF control goals by the 2020 target date could affect resource allocation in the next few years. METHODS: We constructed a hidden Markov model fit to the prevalence of two clinical signs of trachoma and PCR data in 24 communities from the recent PRET-Niger trial. The prevalence of TF in children in each community at 36 months was forecast given data from earlier time points. Forecasts were scored by the likelihood of the observed results. We assessed whether use of TF with additional TI and PCR data rather than just the use of TF alone improves forecasts, and separately whether incorporating a delay in TF recovery is beneficial. RESULTS: Including TI and PCR data did not significantly improve forecasts of TF. Forecasts of TF prevalence at 36 months by the model with the delay in TF recovery were significantly better than forecasts by the model without the delay in TF recovery (p = 0.003). A zero-inflated truncated normal observation model was better than a truncated normal observation model, and better than a sensitivity-specificity observation model. CONCLUSION: The results in this study suggest that future studies could consider using just TF data for forecasting, and should include a delay in TF recovery. TRIAL REGISTRATION: Clinicaltrials.gov NCT00792922.