The burden of trachoma in South Sudan: assessing the health losses from a condition of graded severity

Introduction

Trachoma is a disease that can lead to visual impairment and ultimately blindness. Previous estimates of health losses from trachoma using the Global Burden of Disease methodology have not, however, included the stage prior to visual impairment. We estimated the burden of all stages of trachoma in South Sudan and assessed the uncertainty associated with the severity and duration of stages of trachoma prior to full blindness.

Methods

The prevalence of trachoma with normal vision, low vision and blindness in the Republic of South Sudan has been estimated previously. These estimates were used to model the incidence and duration of the different stages employing DISMOD II. Different assumptions about disability weights and duration were used to estimate the Years Lived with Disability (YLD).

Results

We have estimated the total burden of trachoma in South Sudan to be between 136,562 and 163,695 YLD and trichiasis with normal vision contributes between 5% and 21% of the total depending on the disability weight applied. Women experience more of this burden than men. The sensitivity of the results to different assumptions about the disability weights is partly dependent upon the assumed duration of the different disease states.

Interpretation

A better understanding of the natural history of trachoma is critical for a more accurate burden estimate.     

The prevalence of blinding trachoma in northern states of Sudan

Background

Despite historical evidence of blinding trachoma, there have been no widespread contemporary surveys of trachoma prevalence in the northern states of Sudan. We aimed to conduct district-level surveys in this vast region in order to map the extent of the problem and estimate the need for trachoma control interventions to eliminate blinding trachoma.

Methods and Findings

Separate, population based cross-sectional surveys were conducted in 88 localities (districts) in 12 northern states of Sudan between 2006 and 2010. Two-stage cluster random sampling with probability proportional to size was used to select the sample. Trachoma grading was done using the WHO simplified grading system. Key prevalence indicators were trachomatous inflammation-follicular (TF) in children aged 1–9 years and trachomatous trichiasis (TT) in adults aged 15 years and above. The sample comprised 1,260 clusters from which 25,624 households were surveyed. A total of 106,697 participants (81.6% response rate) were examined for trachoma signs. TF prevalence was above 10% in three districts and between 5% and 9% in 11 districts. TT prevalence among adults was above 1% in 20 districts (which included the three districts with TF prevalence >10%). The overall number of people with TT in the population was estimated to be 31,072 (lower and upper bounds = 26,125–36,955).

Conclusion

Trachoma mapping is complete in the northern states of Sudan except for the Darfur States. The survey findings will facilitate programme planning and inform deployment of resources for elimination of trachoma from the northern states of Sudan by 2015, in accordance with the Sudan Federal Ministry of Health (FMOH) objectives.     

Targeting Trachoma Control through Risk Mapping: The Example of Southern Sudan

Background

Trachoma is a major cause of blindness in Southern Sudan. Its distribution has only been partially established and many communities in need of intervention have therefore not been identified or targeted. The present study aimed to develop a tool to improve targeting of survey and control activities.

Methods/Principal Findings

A national trachoma risk map was developed using Bayesian geostatistics models, incorporating trachoma prevalence data from 112 geo-referenced communities surveyed between 2001 and 2009. Logistic regression models were developed using active trachoma (trachomatous inflammation follicular and/or trachomatous inflammation intense) in 6345 children aged 1–9 years as the outcome, and incorporating fixed effects for age, long-term average rainfall (interpolated from weather station data) and land cover (i.e. vegetation type, derived from satellite remote sensing), as well as geostatistical random effects describing spatial clustering of trachoma. The model predicted the west of the country to be at no or low trachoma risk. Trachoma clusters in the central, northern and eastern areas had a radius of 8 km after accounting for the fixed effects.

Conclusion

In Southern Sudan, large-scale spatial variation in the risk of active trachoma infection is associated with aridity. Spatial prediction has identified likely high-risk areas to be prioritized for more data collection, potentially to be followed by intervention.     

Trachoma Rapid Assessments in Unity and Northern Bahr-el-Ghazal States,Southern Sudan

Background

Trachoma is thought to be endemic over large parts of Southern Sudan, but empirical evidence is limited. While some areas east of the Nile have been identified as highly endemic, few trachoma surveys have been conducted in the remainder of the country. This study aimed to determine whether trachoma constitutes a problem to public health in Northern Bahr-el-Ghazal and Unity State, both located west of the Nile.

Methods and Principal Findings

Trachoma rapid assessments (TRA) were conducted between July and September 2009. Seven villages in Northern Bahr-el-Ghazal State and 13 villages in Unity State were surveyed; an average of 50 children (age 1–9 years) and 44 women (age 15 years and above) were examined per village. Samples for analysis using the APTIMA Combo-2 nucleic acid amplification test (NAAT) were collected from participants with active trachoma in eight villages in Unity State. In Northern Bahr-el-Ghazal State, only three children with active trachoma (trachomatous inflammation follicular (TF) and/or trachomatous inflammation intense (TI)) and two women with trichiasis (TT) were found, in two of the seven villages surveyed. In Unity State, trachoma was endemic in all thirteen villages surveyed; the proportion of children with active trachoma ranged from 33% to 75% between villages, while TF in children ranged from 16% to 44%. Between 4% to 51% of examined women showed signs of TT. Samples from active trachoma cases tested using the NAAT were positive for Chlamydia trachomatis infection for 46.6% of children and 19.0% of women.

Conclusions

Trachoma presents a major problem to public health Unity State, while the disease is of low priority in Northern-Bahr-el-Ghazal State. Implementation of a population-based prevalence survey is now required in Unity State to generate baseline prevalence data so that trachoma interventions can be initiated and monitored over time.     

The Impact of Climatic Risk Factors on the Prevalence,Distribution, and Severity of Acute and Chronic Trachoma

Background and Objectives

Trachoma is the most common cause of infectious blindness. Hot, dry climates, dust and water scarcity are thought to be associated with the distribution of trachoma but the evidence is unclear. The aim of this study was to evaluate the epidemiological evidence regarding the extent to which climatic factors explain the current prevalence, distribution, and severity of acute and chronic trachoma. Understanding the present relationship between climate and trachoma could help inform current and future disease elimination.

Methods

A systematic review of peer-reviewed literature was conducted to identify observational studies which quantified an association between climate factors and acute or chronic trachoma and which met the inclusion and exclusion criteria. Studies that assessed the association between climate types and trachoma prevalence were also reviewed.

Results

Only eight of the 1751 papers retrieved met the inclusion criteria, all undertaken in Africa. Several papers reported an association between trachoma prevalence and altitude in highly endemic areas, providing some evidence of a role for temperature in the transmission of acute disease. A robust mapping study found strong evidence of an association between low rainfall and active trachoma. There is also consistent but weak evidence that the prevalence of trachoma is higher in savannah-type ecological zones. There were no studies on the effect of climate in low endemic areas, nor on the effect of dust on trachoma.

Conclusion

Current evidence on the potential role of climate on trachoma distribution is limited, despite a wealth of anecdotal evidence. Temperature and rainfall appear to play a role in the transmission of acute trachoma, possibly mediated through reduced activity of flies at lower temperatures. Further research is needed on climate and other environmental and behavioural factors, particularly in arid and savannah areas. Many studies did not adequately control for socioeconomic or environmental confounders.     

The burden of trachoma in Ayod County of Southern Sudan

Background

Blindness due to trachoma is avoidable through Surgery, Antibiotics, Facial hygiene and Environmental improvements (SAFE). Recent surveys have shown trachoma to be a serious cause of blindness in Southern Sudan. We conducted this survey in Ayod County of Jonglei State to estimate the need for intervention activities to eliminate blinding trachoma.

Methodology and Findings

A cross-sectional two-stage cluster random survey was conducted in November 2006. All residents of selected households were clinically assessed for trachoma using the World Health Organization (WHO) simplified grading scheme. A total of 2,335 people from 392 households were examined, of whom 1,107 were over 14 years of age. Prevalence of signs of active trachoma in children 1–9 years of age was: trachomatous inflammation follicular (TF) = 80.1% (95% confidence interval [CI], 73.9–86.3); trachomatous inflammation intense (TI) = 60.7% (95% CI, 54.6–66.8); and TF and/or TI (active trachoma) = 88.3% (95% CI, 83.7–92.9). Prevalence of trachomatous trichiasis (TT) was 14.6% (95% CI, 10.9–18.3) in adults over 14 years of age; 2.9% (95% CI, 0.4–5.3) in children 1–14 years of age; and 8.4% (95% CI, 5.5–11.3) overall. The prevalence of corneal opacity in persons over 14 years of age with TT was 6.4% (95% CI, 4.5–8.3). No statistically significant difference was observed in the prevalence of trachoma signs between genders. Trachoma affected almost all households surveyed: 384/392 (98.0%) had at least one person with active trachoma and 130 (33.2%) had at least one person with trichiasis.

Conclusions

Trachoma is an unnecessary public health problem in Ayod. The high prevalence of active trachoma and trichiasis confirms the severe burden of blinding trachoma found in other post-conflict areas of Southern Sudan. Based on WHO recommended thresholds, all aspects of the SAFE strategy are indicated to eliminate blinding trachoma in Ayod.     

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.     

Access to Water Source,Latrine Facilities and Other Risk Factors of Active Trachoma in Ankober,Ethiopia

Objective

This study aims to determine the prevalence and correlates of active trachoma in Ankober, Ethiopia.

Methods

A cross-sectional community-based study was conducted during July 2007. A total of 507 children (ages 1–9 years), from 232 households were included in the study. All children were examined for trachoma by ophthalmic nurses using the WHO simplified clinical grading system. Interviews and observations were used to assess risk factors. Logistic regression procedures were used to determine associations between potential risk factors and signs of active trachoma.

Results

Overall, the prevalence of active trachoma was found to be 53.9% (95%CI 49.6%–58.2%). Presence of fly-eye (fly contact with the eyelid margin during eye examination) (Odds Ratio (OR) = 4.03 95% CI 1.40–11.59), absence of facial cleanliness (OR = 7.59; 95%CI 4.60–12.52), an illiterate mother (OR = 5.88; 95%CI 2.10–15.95), lack of access to piped water (OR = 2.19; 95%CI 1.14–6.08), and lack of access to latrine facilities (OR = 4.36; 95%CI 1.49–12.74) were statistically significantly associated with increased risk of active trachoma.

Conclusion

Active trachoma among children 1–9 years of age in Ankober is highly prevalent and significantly associated with a number of risk factors including access to water and latrine facilities. Trachoma prevention programs that include improved access to water and sanitation, active fly control, and hygiene education are recommended to lower the burden of trachoma in Ankober, Ethiopia.     

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.     

Risk Factors for Active Trachoma and Ocular Chlamydia trachomatis Infection in Treatment-Na?ve Trachoma-Hyperendemic Communities of the Bijagós Archipelago,Guinea Bissau

Background

Trachoma, caused by ocular infection with Chlamydia trachomatis, is hyperendemic on the Bijagós Archipelago of Guinea Bissau. An understanding of the risk factors associated with active trachoma and infection on these remote and isolated islands, which are atypical of trachoma-endemic environments described elsewhere, is crucial to the implementation of trachoma elimination strategies.

Methodology/Principal Findings

A cross-sectional population-based trachoma prevalence survey was conducted on four islands. We conducted a questionnaire-based risk factor survey, examined participants for trachoma using the World Health Organization (WHO) simplified grading system and collected conjunctival swab samples for 1507 participants from 293 randomly selected households. DNA extracted from conjunctival swabs was tested using the Roche Amplicor CT/NG PCR assay. The prevalence of active (follicular and/or inflammatory) trachoma was 11% (167/1508) overall and 22% (136/618) in 1–9 year olds. The prevalence of C. trachomatis infection was 18% overall and 25% in 1–9 year olds. There were strong independent associations of active trachoma with ocular and nasal discharge, C. trachomatis infection, young age, male gender and type of household water source. C. trachomatis infection was independently associated with young age, ocular discharge, type of household water source and the presence of flies around a latrine.

Conclusions/Significance

In this remote island environment, household-level risk factors relating to fly populations, hygiene behaviours and water usage are likely to be important in the transmission of ocular C. trachomatis infection and the prevalence of active trachoma. This may be important in the implementation of environmental measures in trachoma control.     

Prevalence and Risk Factors for Trachoma in Central and Southern Malawi

Background

Trachoma, one of the neglected tropical diseases is suspected to be endemic in Malawi. Objectives: To determine the prevalence of trachoma and associated risk factors in central and southern Malawi.

Methodology/Principal Findings

A population based survey conducted in randomly selected clusters in Chikwawa district (population 438,895), southern Malawi and Mchinji district (population 456,558), central Malawi. Children aged 1–9 years and adults aged 15 and above were assessed for clinical signs of trachoma. In total, 1010 households in Chikwawa and 1016 households in Mchinji districts were enumerated within 108 clusters (54 clusters in each district). A total of 6,792 persons were examined for ocular signs of trachoma. The prevalence of trachomatous inflammation, follicular (TF) among children aged 1–9 years was 13.6% (CI 11.6–15.6) in Chikwawa and 21.7% (CI 19.5–23.9) in Mchinji districts respectively. The prevalence of trachoma trichiasis (TT) in women and men aged 15 years and above was 0.6% (CI 0.2–0.9) in Chikwawa and 0.3% (CI 0.04–0.6) in Mchinji respectively. The presence of a dirty face was significantly associated with trachoma follicular (TF) in both Chikwawa and Mchinji districts (P<0.001).

Conclusion/Significance

Prevalence rates of trachoma follicles (TF) in Central and Southern Malawi exceeds the WHO guidelines for the intervention with mass antibiotic distribution (TF>10%), and warrants the trachoma SAFE control strategy to be undertaken in Chikwawa and Mchinji districts.     

The Development of an Age-Structured Model for Trachoma Transmission Dynamics,Pathogenesis and Control

Background

Trachoma, the worldwide leading infectious cause of blindness, is due to repeated conjunctival infection with Chlamydia trachomatis. The effects of control interventions on population levels of infection and active disease can be promptly measured, but the effects on severe ocular sequelae require long-term monitoring. We present an age-structured mathematical model of trachoma transmission and disease to predict the impact of interventions on the prevalence of blinding trachoma.

Methodology/Principal Findings

The model is based on the concept of multiple reinfections leading to progressive conjunctival scarring, trichiasis, corneal opacity and blindness. It also includes aspects of trachoma natural history, such as an increasing rate of recovery from infection and a decreasing chlamydial load with subsequent infections that depend upon a (presumed) acquired immunity that clears infection with age more rapidly. Parameters were estimated using maximum likelihood by fitting the model to pre-control infection prevalence data from hypo-, meso- and hyperendemic communities from The Gambia and Tanzania. The model reproduces key features of trachoma epidemiology: 1) the age-profile of infection prevalence, which increases to a peak at very young ages and declines at older ages; 2) a shift in this prevalence peak, toward younger ages in higher force of infection environments; 3) a raised overall profile of infection prevalence with higher force of infection; and 4) a rising profile, with age, of the prevalence of the ensuing severe sequelae (trachomatous scarring, trichiasis), as well as estimates of the number of infections that need to occur before these sequelae appear.

Conclusions/Significance

We present a framework that is sufficiently comprehensive to examine the outcomes of the A (antibiotic) component of the SAFE strategy on disease. The suitability of the model for representing population-level patterns of infection and disease sequelae is discussed in view of the individual processes leading to these patterns.     

Rapid Assessment of Trachoma in Underserved Population of Car-Nicobar Island,India

Purpose

To determine the burden of trachoma and its related risk factors amongst the native population of Car-Nicobar Island in India.

Methods

Rapid assessment for trachoma was conducted in ten villages of Car- Nicobar Island according to standard WHO guidelines. An average of 50 children aged 1–9 years were assessed clinically for signs of active trachoma and facial cleanliness in each village. Additionally, all adults above 15 years of age in these households were examined for evidence of trachomatous trichiasis and corneal opacity. Environmental risk factors contributing to trachoma like limited access to potable water & functional latrine, presence of animal pen and garbage within the Nicobari hut were also noted in all villages.

Results

Out of a total of fifteen villages in Car-Nicobar Island, ten villages were selected for trachoma survey depending on evidence of socio-developmental indicators like poverty and decreased access to water, sanitation and healthcare facilities. The total population of the selected clusters was 7277 in the ten villages. Overall, 251 of 516 children (48.6%;CI: 46.5–55.1) had evidence of follicular stage of trachoma and 11 children (2.1%;CI:1.0–3.4) had evidence of inflammatory stage of trachoma. Nearly 15%(CI:12.1–18.3) children were noted to have unclean faces in the ten villages. Trachomatous trichiasis was noted in 73 adults (1.0%;CI:0.8–1.2). The environmental sanitation was not found to be satisfactory in the surveyed villages mainly due to the co-habitance of Nicobari people with domestic animals like pigs, hens, goats, dogs, cats etc in most (96.4%) of the households.

Conclusion

Active trachoma and trachomatous trichiasis was observed in all the ten villages surveyed, wherein trachoma control measures are needed.     

Onchocerciasis: The Pre-control Association between Prevalence of Palpable Nodules and Skin Microfilariae

Background

The prospect of eliminating onchocerciasis from Africa by mass treatment with ivermectin has been rejuvenated following recent successes in foci in Mali, Nigeria and Senegal. Elimination prospects depend strongly on local transmission conditions and therefore on pre-control infection levels. Pre-control infection levels in Africa have been mapped largely by means of nodule palpation of adult males, a relatively crude method for detecting infection. We investigated how informative pre-control nodule prevalence data are for estimating the pre-control prevalence of microfilariae (mf) in the skin and discuss implications for assessing elimination prospects.

Methods and Findings

We analyzed published data on pre-control nodule prevalence in males aged ≥20 years and mf prevalence in the population aged ≥5 years from 148 African villages. A meta-analysis was performed by means of Bayesian hierarchical multivariate logistic regression, accounting for measurement error in mf and nodule prevalence, bioclimatic zones, and other geographical variation. There was a strong positive correlation between nodule prevalence in adult males and mf prevalence in the general population. In the forest-savanna mosaic area, the pattern in nodule and mf prevalence differed significantly from that in the savanna or forest areas.

Significance

We provide a tool to convert pre-control nodule prevalence in adult males to mf prevalence in the general population, allowing historical data to be interpreted in terms of elimination prospects and disease burden of onchocerciasis. Furthermore, we identified significant geographical variation in mf prevalence and nodule prevalence patterns warranting further investigation of geographical differences in transmission patterns of onchocerciasis.     

Incidence of HIV-Associated Tuberculosis among Individuals Taking Combination Antiretroviral Therapy: A Systematic Review and Meta-Analysis

Background

Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis.

Methods

Systematic literature review and meta-analysis of tuberculosis incidence rates among HIV-infected individuals taking combination antiretroviral therapy.

Results

From PubMed, EMBASE and Global Index Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and 11 from low tuberculosis burden settings) were included in the qualitative review and 33 in the quantitative review. Cohorts from high/intermediate burden settings were smaller in size, had lower median CD4 cell counts at study entry and fewer person-years of follow up. Tuberculosis incidence rates were higher in studies from Sub-Saharan Africa and from World Bank low/middle income countries. Tuberculosis incidence rates decreased with increasing CD4 count at study entry and duration on combination antiretroviral therapy. Summary estimates of tuberculosis incidence among individuals on combination antiretroviral therapy were higher for cohorts from high/intermediate burden settings compared to those from the low tuberculosis burden settings (4.17 per 100 person-years [95% Confidence Interval (CI) 3.39–5.14 per 100 person-years] vs. 0.4 per 100 person-years [95% CI 0.23–0.69 per 100 person-years]) with significant heterogeneity observed between the studies.

Conclusions

Tuberculosis incidence rates were high among individuals on combination antiretroviral therapy in high/intermediate burden settings. Interventions to prevent tuberculosis in this population should address geographical, socioeconomic and individual factors such as low CD4 counts and prior history of tuberculosis.     

Active Trachoma and Ocular Chlamydia trachomatis Infection in Two Gambian Regions: On Course for Elimination by 2020?

Background

Trachoma has been endemic in The Gambia for decades. National trachoma control activities have been in place since the mid-1980''s, but with no mass antibiotic treatment campaign. We aimed to assess the prevalence of active trachoma and of actual ocular Chlamydia trachomatis infection as measured by polymerase chain reaction (PCR) in the two Gambian regions that had had the highest prevalence of trachoma in the last national survey in 1996 prior to planned national mass antibiotic treatment distribution in 2006.

Methodology/Principal Findings

Two stage random sampling survey in 61 randomly selected Enumeration Areas (EAs) in North Bank Region (NBR) and Lower River Region (LRR). Fifty randomly selected children aged under 10 years were examined per EA for clinical signs of trachoma. In LRR, swabs were taken to test for ocular C. trachomatis infection. Unadjusted prevalences of active trachoma were calculated, as would be done in a trachoma control programme. The prevalence of trachomatous inflammation, follicular (TF) in the 2777 children aged 1–9 years was 12.3% (95% CI 8.8%–17.0%) in LRR and 10.0% (95% CI 7.7%–13.0%) in NBR, with significant variation within divisions (p<0.01), and a design effect of 3.474. Infection with C. trachomatis was found in only 0.3% (3/940) of children in LRR.

Conclusions/Significance

This study shows a large discrepancy between the prevalence of trachoma clinical signs and ocular C. trachomatis infection in two Gambian regions. Assessment of trachoma based on clinical signs alone may lead to unnecessary treatment, since the prevalence of active trachoma remains high but C. trachomatis infection has all but disappeared. Assuming that repeated infection is required for progression to blinding sequelae, blinding trachoma is on course for elimination by 2020 in The Gambia.     

Prevalence of Trachoma at Sub-District Level in Ethiopia: Determining When to Stop Mass Azithromycin Distribution

Background

To eliminate blinding trachoma, the World Health Organization emphasizes implementing the SAFE strategy, which includes annual mass drug administration (MDA) with azithromycin to the whole population of endemic districts. Prevalence surveys to assess impact at the district level are recommended after at least 3 years of intervention. The decision to stop MDA is based on a prevalence of trachomatous inflammation follicular (TF) among children aged 1–9 years below 5% at the sub-district level, as determined by an additional round of surveys limited within districts where TF prevalence is below 10%. We conducted impact surveys powered to estimate prevalence simultaneously at the sub-district and district in two zones of Amhara, Ethiopia to determine whether MDA could be stopped.

Methodology

Seventy-two separate population-based, sub-district surveys were conducted in 25 districts. In each survey all residents from 10 randomly selected clusters were screened for clinical signs of trachoma. Data were weighted according to selection probabilities and adjusted for correlation due to clustering.

Principal Findings

Overall, 89,735 residents were registered from 21,327 households of whom 72,452 people (80.7%) were examined. The prevalence of TF in children aged 1–9 years was below 5% in six sub-districts and two districts. Sub-district level prevalence of TF in children aged 1–9 years ranged from 0.9–76.9% and district-level from 0.9–67.0%. In only one district was the prevalence of trichiasis below 0.1%.

Conclusions/Significance

The experience from these zones in Ethiopia demonstrates that impact assessments designed to give a prevalence estimate of TF at sub-district level are possible, although the scale of the work was challenging. Given the assessed district-level prevalence of TF, sub-district-level surveys would have been warranted in only five districts. Interpretation was not as simple as stopping MDA in sub-districts below 5% given programmatic challenges of exempting sub-districts from a highly regarded program and the proximity of hyper-endemic sub-districts.     

Identification of novel single nucleotide polymorphisms in inflammatory genes as risk factors associated with trachomatous trichiasis

Background

Trachoma is the leading preventable cause of global blindness. A balanced Th1/Th2/Th3 immune response is critical for resolving Chlamydia trachomatis infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT). While there are a number of environmental and behavioral risk factors for trachoma, genetic factors that influence inflammation and TT risk remain ill defined.

Methodology/Findings

We identified single nucleotide polymorphisms (SNP) in 36 candidate inflammatory genes and interactions among these SNPs that likely play a role in the overall risk for TT. We conducted a case control study of 538 individuals of Tharu ethnicity residing in an endemic region of Nepal. Trachoma was graded according to World Health Organization guidelines. A linear array was used to genotype 51 biallelic SNPs in the 36 genes. Analyses were performed using logic regression modeling, which controls for multiple comparisons. We present, to our knowledge, the first significant association of TNFA (-308GA), LTA (252A), VCAM1 (-1594TC), and IL9 (T113M) polymorphisms, synergistic SNPs and risk of TT. TT risk decreased 5 times [odds ratio = 0.2 (95% confidence interval 0.11.–0.33), p = 0.001] with the combination of TNFA (-308A), LTA (252A), VCAM1 (-1594C), SCYA 11 (23T) minor allele, and the combination of TNFA (-308A), IL9 (113M), IL1B (5′UTR-T), and VCAM1 (-1594C). However, TT risk increased 13.5 times [odds ratio = 13.5 (95% confidence interval 3.3–22), p = 0.001] with the combination of TNFA (-308G), VDR (intron G), IL4R (50V), and ICAM1 (56M) minor allele.

Conclusions

Evaluating genetic risk factors for trachoma will advance our understanding of disease pathogenesis, and should be considered in the context of designing global control programs.     

Acute Myocardial Infarction in Sub-Saharan Africa: The Need for Data

Background

Trends in the prevalence of acute myocardial infarction in sub-Saharan Africa have not been well described, despite growing recognition of the increasing burden of cardiovascular disease in low- and middle-income countries. The aim of this systematic review was to describe the prevalence of acute myocardial infarction in sub-Saharan Africa.

Methods

We searched PubMed, EMBASE, Global Health Archive, CINAHL, and Web of Science, and conducted reference and citation analyses. Inclusion criteria were: observational studies, studies that reported incidence or prevalence of acute myocardial infarction, studies conducted in sub-Saharan Africa, and studies that defined acute myocardial infarction by EKG changes or elevation of cardiac biomarkers. Studies conducted prior to 1992 were excluded. Two independent reviewers analyzed titles and abstracts, full-texts, and references and citations. These reviewers also performed quality assessment and data extraction. Quality assessment was conducted with a validated scale for observational studies.

Findings

Of 2292 records retrieved, seven studies met all inclusion criteria. These studies included a total of 92,378 participants from highly heterogeneous study populations in five different countries. Methodological quality assessment demonstrated scores ranging from 3 to 7 points (on an 8-point scale). Prevalence of acute myocardial infarction ranged from 0.1 to 10.4% among the included studies.

Interpretation

There is insufficient population-based data describing the prevalence of acute myocardial infarction in sub-Saharan Africa. Well-designed registries and surveillance studies that capture the broad and diverse population with acute myocardial infarction in sub-Saharan Africa using common diagnostic criteria are critical in order to guide prevention and treatment strategies.

Registration

Registered in International Prospective Register of Systematic Reviews (PROSPERO) Database #CRD42012003161.     

Haptoglobin and Sickle Cell Polymorphisms and Risk of Active Trachoma in Gambian Children

Background

Susceptibility and resistance to trachoma, the leading infectious cause of blindness, have been associated with a range of host genetic factors. In vitro studies of the causative organism, Chlamydia trachomatis, demonstrate that iron availability regulates its growth, suggesting that host genes involved in regulating iron status and/or availability may modulate the risk of trachoma. The objective was to investigate whether haptoglobin (Hp) haplotypes constructed from the functional polymorphism (Hp1/Hp2) plus the functional promoter SNPs -61A-C (rs5471) and -101C-G (rs5470), or sickle cell trait (HbAS, rs334) were associated with risk of active trachoma when stratified by age and sex, in rural Gambian children.

Methodology and Principal Findings

In two cross sectional surveys of children aged 6–78 months (n = 836), the prevalence of the clinical signs of active trachoma was 21.4%. Within boys, haplotype E (-101G, -61A, Hp1), containing the variant allele of the -101C-G promoter SNP, was associated with a two-fold increased risk of active trachoma (OR = 2.0 [1.17–3.44]). Within girls, an opposite association was non-significant (OR = 0.58 [0.32–1.04]; P = 0.07) and the interaction by sex was statistically significant (P = 0.001). There was no association between trachoma and HbAS.

Conclusions

These data indicate that genetic variation in Hp may affect susceptibility to active trachoma differentially by sex in The Gambia.