Measuring the Impact of Malaria on the Living Human Retina.

Retinal examination and imaging are relatively simple methods for studying the dynamic impact of cerebral malaria on the microcirculation of the central nervous system. Retina and brain are affected similarly by Plasmodium falciparum. Unlike the brain, the human retina can be directly observed using commercially available clinical instruments in the setting of a critical care unit, and this can be done repeatedly and non-invasively. Additional information about blood-tissue barriers can be gained from fluorescein angiography. Non-ophthalmologist clinician scientists are usually unfamiliar with ophthalmoscopy and retinal imaging, and some readers may feel that these techniques are beyond them. This chapter aims to quell these fears by providing a step-by-step description of how to examine and photograph the human retina in children with cerebral malaria.

Automated Detection of Malarial Retinopathy in Retinal Fundus Images obtained in Clinical Settings.

Cerebral malaria (CM) is a life-threatening clinical syndrome associated with 5-10% of malarial infection cases, most prevalent in Africa. About 23% of cerebral malaria cases are misdiagnosed as false positives, leading to inappropriate treatment and loss of lives. Malarial retinopathy (MR) is a retinal manifestation of CM that presents with a highly specific set of lesions. The detection of MR can reduce the false positive diagnosis of CM and alert physicians to investigate for other possible causes of the clinical symptoms and apply a more appropriate clinical intervention of underlying diseases. In order to facilitate easily accessible and affordable means of MR detection, we have developed an automated software system that detects the retinal lesions specific to MR, whitening and hemorrhages, using retinal color fundus images. The individual lesion detection algorithms were combined into an MR detection model using partial least square classifier. The classifier model was trained and tested on retinal image dataset obtained from 64 patients presenting with clinical signs of CM (44 with MR, 20 without MR). The MR detection model yielded specificity of 92% and sensitivity of 68%, with an AUC of 0.82. The proposed MR detection system demonstrates potential for broad screening of MR and can be integrated with a low-cost and portable retinal camera, to provide a bed-side tool for confirming CM diagnosis.

Prevalence of blindness and cataract surgical coverage in Narayani Zone, Nepal: a rapid assessment of avoidable blindness (RAAB) study.

BACKGROUND: The 1981 Nepal Blindness Survey first identified the Narayani Zone as one of the regions with the highest prevalence of blindness in the country. Subseuqently, a 2006 survey of the Rautahat District of the Narayani Zone found it to have the country's highest blindness prevalence. This study examines the impact on blind avoidable and treatable eye conditions in this region after significant increase in eye care services in the past decade. METHODS: The rapid assessment of avoidable blindness (RAAB) methodology was used with mobile data collection using the mRAAB smartphone app. Data analysis was done using the standard RAAB software. Based on the 2011 census, 100 clusters of 50 participants aged 50 years or older were randomly sampled proportional to population size. RESULTS: Of the 5000 participants surveyed, 4771 (95.4%) were examined. The age-adjusted and sex-adjusted prevalence of bilateral blindness, severe visual impairment (SVI) and moderate visual impairment (MVI) were 1.2% (95% CI 0.9% to 1.5%), 2.5% (95% CI 2.0% to -3.0%) and 13.2% (95% CI 11.8% to 14.5%), respectively. Cataract remains the primary cause of blindness and SVI despite cataract surgery coverage (CSC) of 91.5% for VA<3/60. Women still account for two-thirds of blindness. CONCLUSION: The prevalence of blindness in people over the age of 50 years has decreased from 6.9% in 2006 to 1.2%, a level in keeping with the national average; however, significant gender inequity persists. CSC has improved but continues to favour men.

Trachoma in Viet Nam: results of 11 surveillance surveys conducted with the Global Trachoma Mapping Project.

PURPOSE: Following interventions against trachoma in Viet Nam, impact surveys conducted in 2003-2011 suggested that trachoma was no longer a public health problem. In 2014, we undertook surveillance surveys to estimate prevalence of trachomatous inflammation-follicular (TF) and trichiasis. METHODS: A population-based prevalence survey was undertaken in 11 evaluation units (EUs) encompassing 24 districts, using Global Trachoma Mapping Project methods. A two-stage cluster sampling design was used in each EU, whereby 20 clusters and 60 children per cluster were sampled. Consenting eligible participants (children aged 1-9 years and adults aged ≥50 years) were examined for trachoma. RESULTS: A total of 9391 households were surveyed, and 20,185 participants (98.8% of those enumerated) were examined for trachoma. EU-level TF prevalence in 1-9-year-olds ranged from 0% to 1.6%. In one cluster (in Hà Giang Province), the percentage of children with TF was 10.3%. The overall pattern of cluster-level percentages of children with TF, however, was consistent with an exponential distribution, which would be consistent with trachoma disappearing. Among people aged ≥50 years, prevalence of trichiasis by EU ranged from 0% to 0.75%; these estimates are equivalent to 0-0.13% in all ages. The prevalence of trichiasis unknown to the health system among people aged ≥50 years, by EU, ranged from 0% to 0.17%, which is equivalent to 0-0.03% in all ages. CONCLUSION: Findings suggest that trachoma is no longer a public health problem in any of the 11 EUs surveyed. However, given the high proportion of children with TF in one cluster in Hà Giang Province, further investigations will be undertaken.

Magnitude and Determinants of the Ratio between Prevalence of Low Vision and Blindness in Rapid Assessment of Avoidable Blindness Surveys.

PURPOSE: To determine the magnitude and determinants of the ratio between prevalence of low vision and prevalence of blindness in rapid assessment of avoidable blindness (RAAB) surveys globally. METHODS: Standard RAAB reports were downloaded from the repository or requested from principal investigators. Potential predictor variables included prevalence of uncorrected refractive error (URE) as well as gross domestic product (GDP) per capita, health expenditure per capita of the country across World Bank regions. Univariate and multivariate linear regression were used to investigate the correlation between potential predictor variables and the ratio. RESULTS: The results of 94 surveys from 43 countries showed that the ratio ranged from 1.35 in Mozambique to 11.03 in India with a median value of 3.90 (Interquartile range 3.06;5.38). Univariate regression analysis showed that prevalence of URE (p = 0.04), logarithm of GDP per capita (p = 0.01) and logarithm of health expenditure per capita (p = 0.03) were significantly associated with the higher ratio. However, only prevalence of URE was found to be significant in multivariate regression analysis (p = 0.03). CONCLUSION: There is a wide variation in the ratio of the prevalence of low vision to the prevalence of blindness. Eye care service utilization indicators such as the prevalence of URE may explain some of the variation across the regions.

The Use of Key Informant Method for Identifying Children with Blindness and Severe Visual Impairment in Developing Countries.

PURPOSE: An estimated 19 million children are visually impaired; of these, 1.4 million are irreversibly blind. A key challenge is to identify them early in life to benefit maximally from visual rehabilitation, and/or treatment. This aggregative review and structured literature analysis summarizes evidence of what it is about the key informant (KI) approach that works to identify children with blindness or severe visual impairment (B/SVI) in the community (for whom, to what extent, in what circumstances, in what respect, how and why). METHODS: Peer-reviewed (PubMed, hand search) and grey literature (Google, World Health Organization website, academic theses, direct requests) were included, and methods and criteria used for identification, productivity (number of children referred per KI), accuracy of referrals (positive predictive value, PPV), age of children with B/SVI, KI definition, sex, information about cost and comparisons aggregated. RESULTS: We included 31 documents describing 22 unique KI programs. Mostly KIs identified children with B/SVI in 1-3 weeks, i.e. "campaign mode." In 60%, KIs were community volunteers, others formal health sector workers (FHSW). Around 0.02-1.56 children per KI (median = 0.25) were successfully recruited. PPV ranged from 12 to 66%. In two studies comparing FHSWs and community KIs, the latter were 8 and 10 times more productive. CONCLUSION: KIs working in campaign mode may provide an effective approach to identifying children with B/SVI in communities. Including identification of ocular problems and/or other impairments has been recommended. Research on factors that influence effectiveness and on whether KIs continue to contribute could inform programs.

Automated Detection of Malarial Retinopathy in Digital Fundus Images for Improved Diagnosis in Malawian Children with Clinically Defined Cerebral Malaria.

Cerebral malaria (CM), a complication of malaria infection, is the cause of the majority of malaria-associated deaths in African children. The standard clinical case definition for CM misclassifies ~25% of patients, but when malarial retinopathy (MR) is added to the clinical case definition, the specificity improves from 61% to 95%. Ocular fundoscopy requires expensive equipment and technical expertise not often available in malaria endemic settings, so we developed an automated software system to analyze retinal color images for MR lesions: retinal whitening, vessel discoloration, and white-centered hemorrhages. The individual lesion detection algorithms were combined using a partial least square classifier to determine the presence or absence of MR. We used a retrospective retinal image dataset of 86 pediatric patients with clinically defined CM (70 with MR and 16 without) to evaluate the algorithm performance. Our goal was to reduce the false positive rate of CM diagnosis, and so the algorithms were tuned at high specificity. This yielded sensitivity/specificity of 95%/100% for the detection of MR overall, and 65%/94% for retinal whitening, 62%/100% for vessel discoloration, and 73%/96% for hemorrhages. This automated system for detecting MR using retinal color images has the potential to improve the accuracy of CM diagnosis.

National Trachoma Assessment in the Lao People's Democratic Republic in 2013-2014.

PURPOSE: Population-based prevalence surveys were undertaken to determine whether trachoma is a public health problem in Laos requiring implementation of the SAFE strategy (surgery, antibiotics, facial cleanliness, environmental improvement). METHODS: The country was divided into 19 evaluation units (EUs), each containing a population of roughly 100,000-350,000 people. Of these, 16 were believed most likely to harbor trachoma (based on historical evidence), and were mapped using the Global Trachoma Mapping Project methods. A 2-stage cluster sampling was used to sample approximately 1222 children aged 1-9 years in each EU, as well as all adults aged 15 years and older resident in households with children. The presence or absence of trachomatous inflammation - follicular (TF) and of trichiasis was documented in each subject, and prevalences (adjusted for age and sex) estimated. RESULTS: The adjusted prevalence of TF in 1-9-year-olds ranged from 0.2% to 2.2% across the 16 EUs. Adjusted all-ages prevalence of trichiasis was 0.00% in 13 EUs, 0.06% in two EUs, and 0.12% in one EU. The trichiasis prevalence in adults in the last EU was 0.19%. CONCLUSIONS: The assessment included all areas of Laos suspected of ever harboring trachoma and most of the rural population of the country. The low prevalence of TF and trichiasis do not warrant any special programs against trachoma at this time.

Assessment of Trachoma in Cambodia: Trachoma Is Not a Public Health Problem.

PURPOSE: To determine whether trachoma is a public health problem requiring intervention in Cambodia. METHODS: Based on historical evidence and reports, 14 evaluation units (EUs) in Cambodia, judged to be most likely to harbor trachoma, were selected. The Global Trachoma Mapping Project methodology was used to carry out rigorous surveys to determine the prevalence of trachomatous inflammation-follicular (TF) and trichiasis in each EU. RESULTS: The EU-level prevalence of TF among 25,801 1-9-year-old children examined ranged from 0% to 0.2%. Among the 24,502 adults aged 15+ years examined, trichiasis was found in 59 people. Age- and sex-adjusted prevalences of trichiasis in all ages in the EUs studied ranged from 0% to 0.14%; five EUs had a prevalence of trichiasis ≥0.1%. CONCLUSIONS: There appears to be no need nor justification at this time for implementing public health measures to control trachoma in Cambodia.

Safety of lumbar puncture in comatose children with clinical features of cerebral malaria.

OBJECTIVE: We assessed the independent association of lumbar puncture (LP) and death in Malawian children admitted to the hospital with the clinical features of cerebral malaria (CM). METHODS: This was a retrospective cohort study in Malawian children with clinical features of CM. Allocation to LP was nonrandom and was associated with severity of illness. Propensity score-based analyses were used to adjust for this bias and assess the independent association between LP and mortality. RESULTS: Data were available for 1,075 children: 866 (80.6%) underwent LP and 209 (19.4%) did not. Unadjusted mortality rates were lower in children who underwent LP (15.3% vs 26.7% in the no-LP group) but differences in covariates between the 2 groups suggested bias in LP allocation. After propensity score matching, all covariates were balanced. Propensity score-based analyses showed no change in mortality rate associated with LP: by inverse probability weighting, the average risk reduction was 2.0% at 12 hours (95% confidence interval -1.5% to 5.5%, p = 0.27) and 1.7% during hospital admission (95% confidence interval -4.5% to 7.9%, p = 0.60). Undergoing LP did not change the risk of mortality in subanalyses of children with severe brain swelling on MRI or in those with papilledema. CONCLUSION: In comatose children with suspected CM who were clinically stable, we found no evidence that LP increases mortality, even in children with objective signs of raised intracranial pressure.

Setting targets for human resources for eye health in sub-Saharan Africa: what evidence should be used?

With a global target set at reducing vision loss by 25% by the year 2019, sub-Saharan Africa with an estimated 4.8 million blind persons will require human resources for eye health (HReH) that need to be available, appropriately skilled, supported, and productive. Targets for HReH are useful for planning, monitoring, and resource mobilization, but they need to be updated and informed by evidence of effectiveness and efficiency. Supporting evidence should take into consideration (1) ever-changing disease-specific issues including the epidemiology, the complexity of diagnosis and treatment, and the technology needed for diagnosis and treatment of each condition; (2) the changing demands for vision-related services of an increasingly urbanized population; and (3) interconnected health system issues that affect productivity and quality. The existing targets for HReH and some of the existing strategies such as task shifting of cataract surgery and trichiasis surgery, as well as the scope of eye care interventions for primary eye care workers, will need to be re-evaluated and re-defined against such evidence or supported by new evidence.

Comparison of the effectiveness of three retinal camera technologies for malarial retinopathy detection in Malawi.

The purpose of this study was to test the suitability of three available camera technologies (desktop, portable, and i-phone based) for imaging comatose children who presented with clinical symptoms of malaria. Ultimately, the results of the project would form the basis for a design of a future camera to screen for malaria retinopathy (MR) in a resource challenged environment. The desktop, portable, and i-phone based cameras were represented by the Topcon, Pictor Plus, and Peek cameras, respectively. These cameras were tested on N=23 children presenting with symptoms of cerebral malaria (CM) at a malaria clinic, Queen Elizabeth Teaching Hospital in Malawi, Africa. Each patient was dilated for binocular indirect ophthalmoscopy (BIO) exam by an ophthalmologist followed by imaging with all three cameras. Each of the cases was graded according to an internationally established protocol and compared to the BIO as the clinical ground truth. The reader used three principal retinal lesions as markers for MR: hemorrhages, retinal whitening, and vessel discoloration. The study found that the mid-priced Pictor Plus hand-held camera performed considerably better than the lower price mobile phone-based camera, and slightly the higher priced table top camera. When comparing the readings of digital images against the clinical reference standard (BIO), the Pictor Plus camera had sensitivity and specificity for MR of 100% and 87%, respectively. This compares to a sensitivity and specificity of 87% and 75% for the i-phone based camera and 100% and 75% for the desktop camera. The drawback of all the cameras were their limited field of view which did not allow complete view of the periphery where vessel discoloration occurs most frequently. The consequence was that vessel discoloration was not addressed in this study. None of the cameras offered real-time image quality assessment to ensure high quality images to afford the best possible opportunity for reading by a remotely located specialist.

Grading fluorescein angiograms in malarial retinopathy.

BACKGROUND: Malarial retinopathy is an important finding in Plasmodium falciparum cerebral malaria, since it strengthens diagnostic accuracy, predicts clinical outcome and appears to parallel cerebral disease processes. Several angiographic features of malarial retinopathy have been described, but observations in different populations can only be reliably compared if consistent methodology is used to capture and grade retinal images. Currently no grading scheme exists for fluorescein angiographic features of malarial retinopathy. METHODS: A grading scheme for fluorescein angiographic images was devised based on consensus opinion of clinicians and researchers experienced in malarial retinopathy in children and adults. Dual grading were performed with adjudication of admission fluorescein images from a large cohort of children with cerebral malaria. RESULTS: A grading scheme is described and standard images are provided to facilitate future grading studies. Inter-grader agreement was >70 % for most variables. Intravascular filling defects are difficult to grade and tended to have lower inter-grader agreement (>57 %) compared to other features. CONCLUSIONS: This grading scheme provides a consistent way to describe retinal vascular damage in paediatric cerebral malaria, and can facilitate comparisons of angiographic features of malarial retinopathy between different patient groups, and analysis against clinical outcomes. Inter-grader agreement is reasonable for the majority of angiographic signs. Dual grading with expert adjudication should be used to maximize accuracy.

Baseline Trachoma Mapping in Malawi with the Global Trachoma Mapping Project (GTMP).

PURPOSE: To determine the prevalence of trachoma in all suspected endemic districts in Malawi. METHODS: A population-based survey conducted in 16 evaluation units from 12 suspected endemic districts in Malawi (population 6,390,517), using the standardized Global Trachoma Mapping Project (GTMP) protocol. A 2-stage cluster-random sampling design selected 30 households from each of 30 clusters per evaluation unit; all residents aged 1 year and older in selected households were examined for evidence of follicular trachoma (TF), intense trachomatous inflammation (TI), and trachomatous trichiasis (TT). RESULTS: Four of the 16 evaluation units were found to be endemic for trachoma, with a prevalence range of 10.0-13.5% for TF and 0.2-0.6% for TT. Nine evaluation units had a TF prevalence between 5.0% and 9.9% while three evaluation units had a TF prevalence <5.0%. CONCLUSION: The prevalence rates of active trachoma in Malawi were not uniform among suspected endemic evaluation units, with rates higher than the World Health Organization (WHO) threshold for implementation of community-based control measures (TF ≥ 10.0%) in only 4 of the 16 evaluation units. Trachoma remains a disease of public health importance in some parts of Malawi and adjoining (unmapped) districts should be prioritized for mapping. According to the survey, an additional 3,169,362 people require intervention to reduce active disease and 1557 trichiasis surgeries are needed to reduce the prevalence of TT below WHO recommended thresholds.

The Global Trachoma Mapping Project: Methodology of a 34-Country Population-Based Study.

PURPOSE: To complete the baseline trachoma map worldwide by conducting population-based surveys in an estimated 1238 suspected endemic districts of 34 countries. METHODS: A series of national and sub-national projects owned, managed and staffed by ministries of health, conduct house-to-house cluster random sample surveys in evaluation units, which generally correspond to "health district" size: populations of 100,000-250,000 people. In each evaluation unit, we invite all residents aged 1 year and older from h households in each of c clusters to be examined for clinical signs of trachoma, where h is the number of households that can be seen by 1 team in 1 day, and the product h × c is calculated to facilitate recruitment of 1019 children aged 1-9 years. In addition to individual-level demographic and clinical data, household-level water, sanitation and hygiene data are entered into the purpose-built LINKS application on Android smartphones, transmitted to the Cloud, and cleaned, analyzed and ministry-of-health-approved via a secure web-based portal. The main outcome measures are the evaluation unit-level prevalence of follicular trachoma in children aged 1-9 years, prevalence of trachomatous trichiasis in adults aged 15 + years, percentage of households using safe methods for disposal of human feces, and percentage of households with proximate access to water for personal hygiene purposes. RESULTS: In the first year of fieldwork, 347 field teams commenced work in 21 projects in 7 countries. CONCLUSION: With an approach that is innovative in design and scale, we aim to complete baseline mapping of trachoma throughout the world in 2015.

Task Shifting for Eye Care in Eastern Africa: General Nurses as Trichiasis Surgeons in Kenya, Malawi, and Tanzania.

PURPOSE: There are approximately 8 million people with trachomatous trichiasis globally; in the year 2009, less than 160,000 people had surgery. These numbers are too low in order to achieve the goal of elimination of blinding trachoma by the year 2020. Task shifting approaches have led to the training of general nurses in trichiasis surgery in eastern Africa. The overall aim of this study was to determine the attrition and productivity (and the factors associated with productivity) of trichiasis surgeons in Kenya, Tanzania, and Malawi. METHODS: A 3-year cohort study of trichiasis surgeons. RESULTS: The overall response rate was 86%. Defining high productivity as 50+ operations per year per surgeon, only 16.1% of the trichiasis surgeons were highly productive. Among the surgeons, 27.9% were no longer at their site and ceased providing surgery (attrition) over the 3 years of study. High productivity was associated with having been trained by an experienced trainer, supervised by a clinical officer, having more than three surgical sets, and having an outreach program. CONCLUSION: Attrition of general nurses trained in trichiasis surgery was high. Surgical productivity of trichiasis surgeons remained too low. It is likely that other approaches are needed to address the burden of trichiasis in the three countries. In terms of recommendations, training of trichiasis surgeons should be done in a "package," including a plan for provision of surgical equipment, continuous support and supervision, and outreach.

Factors affecting cataract surgical coverage and outcomes: a retrospective cross-sectional study of eye health systems in sub-Saharan Africa.

BACKGROUND: Recently there has been a great deal of new population based evidence on visual impairment generated in sub-Saharan Africa (SSA), thanks to the Rapid Assessment of Avoidable Blindness (RAAB) survey methodology. The survey provides information on the magnitude and causes of visual impairment for planning services and measuring their impact on eye health in administrative "districts" of 0.5-5 million people. The survey results describing the quantity and quality of cataract surgeries vary widely between study sites, often with no obvious explanation. The purpose of this study was to examine health system characteristics that may be associated with cataract surgical coverage and outcomes in SSA in order to better understand the determinants of reducing the burden of avoidable blindness due to cataract. METHODS: This was a descriptive study using secondary and primary data. The outcome variables were collected from existing surveys. Data on potential district level predictor variables were collected through a semi-structured tool using routine data and key informants where appropriate. Once collected the data were coded and analysed using statistical methods including t-tests, ANOVA and the Kruskal-Wallis analysis of variance test. RESULTS: Higher cataract surgical coverage was positively associated with having at least one fixed surgical facility in the area; availability of a dedicated operating theatre; the number of surgeons per million population; and having an eye department manager in the facility. Variables that were associated with better outcomes included having biometry and having an eye department manager in the facility. CONCLUSIONS: There are a number of health system factors at the district level that seem to be associated with both cataract surgical coverage and post-operative visual acuity outcomes. This study highlights the needs for better indicators and tools by which to measure and monitor the performance of eye health systems at the district level. It is unlikely that epidemiological data alone is sufficient for planning eye health services within a district and health managers and study coordinators need to consider collecting supplementary information in order to ensure appropriate planning can take place.