COVID-19 and the Unfinished Agenda of VISION 2020.

PURPOSE: To critically evaluate the potential impact of the coronavirus disease (COVID-19) pandemic on global ophthalmology and VISION 2020. DESIGN: Perspective supplemented with epidemiologic insights from available online databases. METHODS: We extracted data from the Global Vision Database (2017) and Global Burden of Disease Study (2017) to highlight temporal trends in global blindness since 1990, and provide a narrative overview of how COVID-19 may derail progress toward the goals of VISION 2020. RESULTS: Over 2 decades of VISION 2020 advocacy and program implementation have culminated in a universal reduction of combined age-standardized prevalence of moderate-to-severe vision impairment (MSVI) across all world regions since 1990. Between 1990 and 2017, low-income countries observed large reductions in the age-standardized prevalence per 100,000 persons of vitamin A deficiency (25,155 to 19,187), undercorrected refractive disorders (2,286 to 2,040), cataract (1,846 to 1,690), onchocerciasis (5,577 to 2,871), trachoma (506 to 159), and leprosy (36 to 26). Despite these reductions, crude projections suggest that more than 700 million persons will experience MSVI or blindness by 2050, principally owing to our growing and ageing global population. CONCLUSIONS: Despite the many resounding successes of VISION 2020, the burden of global blindness and vision impairment is set to reach historic levels in the coming years. The impact of COVID-19, while yet to be fully determined, now threatens the hard-fought gains of global ophthalmology. The postpandemic years will require renewed effort and focus on vision advocacy and expanding eye care services worldwide.

Spatial distribution of leprosy in India: an ecological study.

BACKGROUND: As leprosy elimination becomes an increasingly realistic goal, it is essential to determine the factors that contribute to its persistence. We evaluate social and economic factors as predictors of leprosy annual new case detection rates within India, where the majority of leprosy cases occur. METHODS: We used correlation and linear mixed effect regressions to assess whether poverty, illiteracy, nighttime satellite radiance (an index of development), and other covariates can explain district-wise annual new case detection rate and Grade 2 disability diagnoses. RESULTS: We find only weak evidence of an association between poverty and annual new case detection rates at the district level, though illiteracy and satellite radiance are statistically significant predictors of leprosy at the district level. We find no evidence of rapid decline over the period 2008-2015 in either new case detection or new Grade 2 disability. CONCLUSIONS: Our findings suggest a somewhat higher rate of leprosy detection, on average, in poorer districts; the overall effect is weak. The divide between leprosy case detection and true incidence of clinical leprosy complicates these results, particularly given that the detection rate is likely disproportionately lower in impoverished settings. Additional information is needed to distinguish the determinants of leprosy case detection and transmission during the elimination epoch.

The distribution of district-level leprosy incidence in India is geometric-stable, consistent with subcriticality.

Mathematical models predict that the community-level incidence of a controlled infectious disease across a region approaches a geometric distribution. This could hold over larger regions, if new cases remain proportional to existing cases. Leprosy has been disappearing for centuries, making an excellent candidate for testing this hypothesis. Here, we show the annual new case detection rate of leprosy in Indian districts to be consistent with a geometric distribution. For 2008-2013, goodness-of-fit testing was unable to exclude the geometric, and the shape parameter of the best fit negative binomial distribution was close to unity (0.95, 95% CI 0.87-1.03). Ramifications include that a district-level cross-sectional survey may reveal whether an infectious disease is headed towards elimination, that apparent outliers are expected and not necessarily representative of program failure, and that proportion 1/e of a small geographical unit may not meet a control threshold even when a larger area has.

Correction: Short-term leprosy forecasting from an expert opinion survey.

[This corrects the article DOI: 10.1371/journal.pone.0182245.].

Short-term leprosy forecasting from an expert opinion survey.

We conducted an expert survey of leprosy (Hansen's Disease) and neglected tropical disease experts in February 2016. Experts were asked to forecast the next year of reported cases for the world, for the top three countries, and for selected states and territories of India. A total of 103 respondents answered at least one forecasting question. We elicited lower and upper confidence bounds. Comparing these results to regression and exponential smoothing, we found no evidence that any forecasting method outperformed the others. We found evidence that experts who believed it was more likely to achieve global interruption of transmission goals and disability reduction goals had higher error scores for India and Indonesia, but lower for Brazil. Even for a disease whose epidemiology changes on a slow time scale, forecasting exercises such as we conducted are simple and practical. We believe they can be used on a routine basis in public health.

Robotic-Assisted Inferior Vena Cava Filter Retrieval.

Although anticoagulation remains the mainstay of therapy for patients with venous thromboembolism, guidelines recommend the use of inferior vena cava (IVC) filters in those who fail anticoagulation or have contraindications to its use. Short-term use of filters has proven effective in reducing the rate of pulmonary embolism. However, their extended use is associated with a variety of complications such as thrombosis, filter migration, or caval perforation, thus making a case for timely filter retrieval. This is the case of a 68-year-old female with a history of chronic oral anticoagulation use for multiple deep venous thrombi (DVT) and pulmonary emboli (PE) who required cervical and thoracic spinal intervention for spondylosis and foramina stenosis. Given her increased risk of recurrent DVT and PE perioperatively, we elected to place a Cook Celect™ IVC filter (Cook Medical, Bloomington, IN) after oral anticoagulation was stopped for the procedure. Her treatment course was prolonged due to wound-healing complications. We elected to use the Magellan Robotic Catheter System (Hansen Medical, Mountain View, CA) for filter retrieval when she presented 6 months later with caval perforation from the filter struts. With its ease of use, superior mechanical stability, and maneuverability, robot-assisted IVC filter retrieval may be a safer and more reliable substitute for traditional navigation techniques when presented with challenging filter retrievals.

Robotic-Assisted Coil Embolization of Ascending Aortic Pseudoaneurysm.

A 62-year-old man with coronary artery disease and ischemic cardiomyopathy after coronary artery bypass grafting and insertion of a HeartMate II (Thoratec, Pleasanton, CA) left ventricular assist device (LVAD) presented with spontaneous incisional bleeding and an ascending aortic pseudoaneurysm. Aortic angiography revealed an anomalous connection between the pseudoaneurysm and the LVAD conduit. We were able to partially embolize the tract with standard techniques, but the patient returned with repeated bleeding. Using the additional stability and control afforded by the Magellan Robotic System (Hansen Medical, Mountain View, CA), a remotely steerable catheter, we were able to cannulate and completely embolize the pseudoaneurysm and occlude the anomalous tract.

Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases.

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination 'as a public health problem' when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models' predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020.

Spatial heterogeneity in projected leprosy trends in India.

BACKGROUND: Leprosy is caused by infection with Mycobacterium leprae and is characterized by peripheral nerve damage and skin lesions. The disease is classified into paucibacillary (PB) and multibacillary (MB) leprosy. The 2012 London Declaration formulated the following targets for leprosy control: (1) global interruption of transmission or elimination by 2020, and (2) reduction of grade-2 disabilities in newly detected cases to below 1 per million population at a global level by 2020. Leprosy is treatable, but diagnosis, access to treatment and treatment adherence (all necessary to curtail transmission) represent major challenges. Globally, new case detection rates for leprosy have remained fairly stable in the past decade, with India responsible for more than half of cases reported annually. METHODS: We analyzed publicly available data from the Indian Ministry of Health and Family Welfare, and fit linear mixed-effects regression models to leprosy case detection trends reported at the district level. We assessed correlation of the new district-level case detection rate for leprosy with several state-level regressors: TB incidence, BCG coverage, fraction of cases exhibiting grade 2 disability at diagnosis, fraction of cases in children, and fraction multibacillary. RESULTS: Our analyses suggest an endemic disease in very slow decline, with substantial spatial heterogeneity at both district and state levels. Enhanced active case finding was associated with a higher case detection rate. CONCLUSIONS: Trend analysis of reported new detection rates from India does not support a thesis of rapid progress in leprosy control.

Nanocrystal superlattices that exhibit improved order on heating: an example of inverse melting?

Grazing incidence small angle X-ray scattering (GISAXS) measurements reveal that superlattices of 1.7 nm diameter, gold (Au) nanocrystals capped with octadecanethiol become significantly more ordered when heated to moderate temperatures (50-60 °C). This enhancement in order is reversible and the superlattice returns to its initially disordered structure when cooled back to room temperature. Disorder-order transition temperatures were estimated from the GISAXS data using the Hansen-Verlet criterion. Differential scanning calorimetry (DSC) measurements of the superlattices exhibited exotherms (associated with disordering during cooling) and endotherms (associated with ordering during heating) near the transition temperatures. The superlattice transition temperatures also correspond approximately to the melting and solidification points of octadecanethiol. Therefore, it appears that a change in capping ligand packing that occurs upon ligand melting underlies the structural transition of the superlattices. We liken the heat-induced ordering of the superlattices to an inverse melting transition.

Type I reaction in leprosy--a histopathological analysis.

Even though type 1 lepra reaction (TIR) is a commonly encountered clinical problem, its histology has not yet been clearly delineated. This study attempts to enumerate the most sensitive parameters for the histological diagnosis of TIR. Case records between March 2007 and September 2007 of patients with TIR were reviewed and the biopsies were evaluated by a pathologist blinded to the previous diagnoses. Twenty three patients were included in the study. The most sensitive parameters in our study were dermal edema, intra-granuloma edema and giant cell size. Though clinical findings should remain the mainstay of diagnosis of TIR, the above mentioned parameters should be evaluated in biopsies of leprosy to look for signs of reaction which might otherwise be missed.

A study of histopathology of clinically normal appearing skin in the tuberculoid spectrum of leprosy.

Histological changes suggestive of leprosy in clinically normal skin have been well documented in the lepromatous spectrum and rarely in the tuberculoid spectrum of the disease. This study attempts to evaluate the histology of clinically normal appearing skin in cases of borderline tuberculoid and tuberculoid leprosy. Biopsies from lesional and a clinically normal appearing skin from newly diagnosed patients with BT or TT leprosy seen in the outpatient department over a period of one year were evaluated by a blinded pathologist. Sixty five patients were included in the study. Six patients had granulomas in the normal skin, six others showed a histological pattern consistent with indeterminate leprosy in the biopsies taken from normal skin. The clinicians must be aware that a small percentage of cases in the TT spectrum also have involvement of normal appearing skin. These patients are at a high risk of under-treatment and may be a cause for paucibacillary relapse. This is a pilot study and a larger sample size is recommended to evaluate the real scenario.

Short-term follow-up of chagasic patients after benzonidazole treatment using multiple serological markers.

BACKGROUND: Conventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from T. cruzi as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value. METHODS: We analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of T. cruzi (15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole. RESULTS: Regardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients. CONCLUSIONS: The recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients' sera at any clinical stage of the disease. Shortly after benznidazole treatment, a drop in reactivity against three of these antigens is produced in an antigen-specific manner. Most likely, analysis of the reactivity against these recombinant antigens may be useful for monitoring the effectiveness of benznidazole treatment.

[Amputation in low-income countries: particularities in epidmiological features and management practices]. / Les amputations dans les pays à faibles revenus: particularités de l'épidémiologie, de l'appareillage et de la rééducation.

The epidemiological features and management practices associated with amputation in low-income countries, generally synonymous with the tropics, are different from those observed in Western countries. Unlike developed countries, amputation most frequently involves traumatic injury in young active people. However, Westernization of the lifestyle is leading to an increasing number of cases involving diabetes and atherosclerotic disease. In the developing world, leprosy and Buruli ulcer are still significant etiologic factors for amputation. In war-torn countries, use of antipersonnel landmines is another major cause of amputation with characteristic features. Management of amputees in the developing world is hindered by the lack of facilities for rehabilitation and prosthetic fitting. Many international organizations are supporting national programs to develop such facilities. In addition to being affordable, prosthetics and orthotics must be adapted to the living conditions of a mostly rural amputee population, i.e., heat, humidity, and farm work. The rehabilitation process must be part of a global handicap policy aimed at changing attitudes about disability and reintegrating amputees both socially and professionally.

A case of advanced lepromatous leprosy with rhino-oro-laryngological involvement in the post-elimination era.

A patient presenting with symptoms and signs of congestive heart failure was incidentally found to be in advanced stage of leprosy. He had multiple lepromatous nodules over the entire body. The oral mucosa was yellowish with a matte appearance and the palate had a site ready to perforate. Nasal cavity revealed a small septal perforation with overlying crusts suggesting advanced rhinitis. Diagnosis of lepromatous leprosy was confirmed on histology. This case report emphasizes the existence of pockets of highly bacilliferous cases that continue to be a source of infection within the community and highlights the need for enhanced health education.

Refining criteria for diagnosis of cutaneous infections caused by herpes viruses through correlation of morphology with molecular pathology.

BACKGROUND: Infections of the skin by herpes viruses do not always present themselves in typical fashion. Early diagnosis, however, is crucial for appropriate treatment. Polymerase chain reaction (PCR) allows diagnosis and differential diagnosis of herpes virus infections, but the method is not yet available in large parts of the world, where diagnosis is made based on morphology alone. AIM: To refine criteria for the diagnosis of herpes virus infections of the skin by way of correlation of clinical and histopathologic findings with results of PCR studies. METHODS: We studied 75 clinically diagnosed patients of "zoster," "varicella," and "herpes simplex", to correlate clinical and histopathological findings with results of PCR studies on paraffin embedded biopsy specimens. RESULTS: Clinical suspicion of infection by herpes viruses was confirmed by histopathology in 37% of the cases and by PCR studies in 65% of the cases. Zoster was frequently misdiagnosed as infection with herpes simplex viruses (30%). When diagnostic signs of herpes virus infection were encountered histopathologically, PCR confirmed the diagnosis in 94%. By way of correlation with results of PCR studies, initial lesions of herpes virus infections could be identified to have a distinctive histopathological pattern. Herpetic folliculitis appeared to be a rather common finding in zoster, it occurring in 28% of the cases. CONCLUSION: We conclude that correlation of clinical and histopathological features with results of PCR studies on one and the same paraffin embedded specimen permits identification of characteristic morphologic patterns and helps to refine criteria for diagnosis both clinically and histopathologically.

Leprosy affected beggars as a hidden source for transmission of leprosy.

BACKGROUND & OBJECTIVES: Despite the large scale implementation of multidrug therapy (MDT), the incidence rates of leprosy have not declined in several hyperendemic countries. Before searching for non-human reservoirs of leprosy it would be necessary to look for hidden human sources. This would include destitute leprosy affected persons who resort to begging and operate in congested areas. Hence this study was undertaken. METHODS: One major town and three semi-urban areas in Vellore district of Tamil Nadu and Chittoor town in Andhra Pradesh were purposefully selected for the study. All beggars in these towns were systematically identified and examined by allopathic doctors. Skin smears were examined for bacteriological index. RESULTS: Among the 193 beggars screened, 58 had leprosy. Of these 10 were smear positive. Several beggars, although living separately, were in touch with their relatives. Most beggars were pavement dwellers and regularly begged at places of worship, bus stands and shopping centres. INTERPRETATION & CONCLUSION: The fact that nearly 20 per cent of the leprosy affected beggars were skin smear positive highlights the need for regular screening and treatment of such beggars. Those positive should be actively treated and their close contacts frequently screened. This hidden reservoir should be completely eliminated.