Lessons Learned From Developing an Eradication Investment Case for Lymphatic Filariasis.

In the last few years, the concepts of disease elimination and eradication have again gained consideration from the global health community, with Guinea worm disease (dracunculiasis) on track to become the first parasitic disease to be eradicated. Given the many complex and interlinking issues involved in committing to a disease eradication initiative, such commitments must be based on a solid assessment of a broad range of factors. In this chapter, we discuss the value and implications of undertaking a systematic and fact-based analysis of the overall situation prior to embarking on an elimination or eradication programme. As an example, we draw upon insights gained from a series of lymphatic filariasis (LF) studies from our research group that adopted an eradication investment case (EIC) framework. The justification for EICs, and related epidemiological, geospatial and other mathematical/operational research modelling, stems from the necessity for proper planning prior to committing to disease eradication. Across all considerations for LF eradication, including: time, treatments, level of investments necessary, health impact, cost-effectiveness, and broader economic benefits, scaling-up mass drug administration coverage to all endemic communities immediately provided the most favourable results. The coherent and consistent pursuit of eradication goals, operationally tailored to a given socioecological system and based on integrated measures of available tools will lead relatively rapidly to elimination in many parts of endemic areas and provide the cornerstone towards eradication.

Comparison of technetium-99m tetrofosmin and thallium-201 single-photon emission computed tomographic imaging for detection of myocardial perfusion defects in patients with coronary artery disease.

OBJECTIVES: We compared dipyridamole technetium-99m (Tc-99m) tetrofosmin and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) imaging with respect to the detection rate of perfusion abnormalities in 26 patients with angiographic coronary artery disease (CAD). BACKGROUND: Experimental studies have shown that myocardial extraction of Tc-99m tetrofosmin is lower than that of Tl-201 at high flow rates, resulting in less severe defects with vasodilator stress. It is uncertain whether this results in a lower sensitivity than Tl-201 for detecting coronary stenoses with vasodilator stress in patients. METHODS: Twenty-six patients with CAD underwent both dipyridamole Tl-201 and Tc-99m tetrofosmin SPECT. Tomographic images were scored for initial defects and the presence of reversibility. Defect magnitude was computer quantitated. RESULTS: Of the 26 patients, 25 had defects on both Tl-201 and Tc-99m tetrofosmin SPECT images. Of 340 segments analyzed, 102 had defects by Tl-201 and 92 by Tc-99m tetrofosmin (p = NS). Whereas Tl-201 detected 27 fixed defects in 12 patients, Tc-99m tetrofosmin identified 37 fixed defects in 14 patients (p = NS). In contrast, Tl-201 identified more reversible and partially reversible defects than did Tc-99m tetrofosmin (89 vs. 55, p = 0.002). The average defect magnitude (percent normal) was similar for defects concordantly graded as fixed (38 +/- 3.0% for Tl-201 vs. 42 +/- 4% [mean +/- SEM] for Tc-99m tetrofosmin, p = NS). The average defect magnitude for defects concordantly graded as completely reversible was significantly more severe on Tl-201 than on Tc-99m tetrofosmin (49 +/- 3% vs. 58 +/- 3%) SPECT images. A significantly greater defect magnitude for Tl-201 was also found for defects concordantly classified as partly reversible (30 +/- 4% for Tl-201 vs. 45 +/- 5% for Tc-99m tetrofosmin). CONCLUSIONS: With dipyridamole stress, 1) at least one defect was seen on both Tl-201 and Tc-99m tetrofosmin SPECT images; 2) Tc-99m tetrofosmin SPECT identified fewer reversible defects than did Tl-201, but showed a similar number of fixed defects; 3) the magnitude of reversible defects seen on Tc-99m tetrofosmin images was less, whereas fixed defects were similar for both tracers; 4) reversible defects seen on Tl-201 and not on Tc-99m tetrofosmin SPECT images were predominantly regions perfused by mild coronary stenoses.

Quantitative gated single photon emission computed tomography imaging: a counts-based method for display and measurement of regional and global ventricular systolic function.

BACKGROUND: Gated single photon emission computed tomography imaging allows simultaneous determination of myocardial perfusion and function. Quantitative perfusion measurements can be based on regional tracer uptake, but function measurements ordinarily require endocardial and epicardial edge detection, which is problematic because of the inherently low spatial resolution and image noise in single photon emission computed tomography images. This article presents methods for quantification of both function and perfusion that do not require edge detection. METHODS AND RESULTS: In SPECT imaging the partial volume effect causes changes in myocardial wall thickness to be reflected as changes in pixel counts in pixels representing the myocardial wall. This effect allows an estimation of changes in myocardial wall thickness by comparing pixel counts in end-systolic images with corresponding pixel counts in end-diastolic images. This article first describes a standard method to quantify myocardial perfusion by sampling myocardial tracer activity at rest and stress. The same method is then used to sample tracer activity in diastolic and systolic images. A new method is developed to convert the diastolic and systolic samples into quantitative estimates of regional wall thickening. A method is then developed to convert the regional wall thickening fractions into a global left ventricular ejection fraction. A normal database is presented. Receiver operating characteristic analysis is used to establish normal limits. CONCLUSION: This method requires no edge detection or geometric boundary estimates. Computer results are presented in a simple and intuitive format, which is uniform for parameters of both perfusion and function. The method is robust and produces relatively few false-positive results.

Validation of a new counts-based gated single photon emission computed tomography method for quantifying left ventricular systolic function: comparison with equilibrium radionuclide angiography.

BACKGROUND: Because myocardial wall thickness is smaller than the spatial resolution of single photon emission computed tomography (SPECT) imaging, changes in myocardial wall thickness are related to changes in maximum pixel counts via the partial volume effect, allowing for quantification of regional systolic wall thickening. We have developed a new gated SPECT method for computing the global left ventricular ejection fraction (LVEF) based entirely on changes in maximum regional myocardial counts during systolic contraction. This new method is independent of endocardial edge detection or other geometric measurements. METHODS AND RESULTS: In 23 patients the gated SPECT method was validated by comparison with radionuclide angiography. The correlation between computed LVEFs was excellent (slope = 0.97, r = 0.91). The measurement of LVEF by gated SPECT was highly reproducible, with minimal intraoperator (slope = 0.97, r = 0.97) or interoperator (slope = 1.00, r = 0.97) variability. Measurements of regional thickening indexes were also reproducible, with a mean intraoperator correlation coefficient of 0.89 +/- 0.05 (range 0.79 to 0.95) for the 14 myocardial regions. Finally, the measurement of LVEF was not significantly influenced by changes in reconstruction filter parameters over a range of cutoff frequencies from 0.16 to 0.28. CONCLUSIONS: This new counts-based gated SPECT method for measuring global left ventricular systolic function correlates well with radionuclide angiography, is highly reproducible, and has theoretic advantages over geometric methods.

Pacemaker-induced superior vena cava syndrome with successful treatment by balloon venoplasty.

This is a case report of pacemaker-induced superior vena cava syndrome in which the patient was successfully treated with balloon venoplasty. Six-month follow-up demonstrates angiographic patency and resolution of symptoms.

Syphilitic osteitis in a patient with secondary syphilis and concurrent human immunodeficiency virus infection.

Destructive bone disease is a well-recognized complication of congenital and tertiary syphilis. Clinically significant osteitis and osteomyelitis are rare complications of primary or secondary syphilis in patients who are not infected with human immunodeficiency virus (HIV). We report a case of an HIV-infected man who presented with symptomatic, left ulnar osteitis as the initial manifestation of secondary syphilis. The patient's clinical course was complicated by a pathological fracture, but he responded to high-dose intravenous penicillin G therapy and surgical intervention. Results of physical examination on follow-up at 15 months were normal, and a serofast (rapid plasma reagin [RPR]) titer of 1:4 and a markedly decreased uptake on bone scintigraphy were observed. Our case report suggests that bone disease can represent an atypical manifestation of early acquired syphilis and that HIV-positive patients who present with orthopedic complaints or bone lesions should be evaluated for the presence of syphilitic bone disease.

Differentiation of substantia gelatinosa-like regions in intraspinal and intracerebral transplants of embryonic spinal cord tissue in the rat.

The differentiation of intracerebral and intraspinal transplants of fetal (E14-E15) rat spinal cord was studied to determine the extent to which myelin-free zones in these embryonic grafts exhibit cytological features and immunocytochemical characteristics of the substantia gelatinosa (SG) of the normal spinal cord. Immunocytochemical staining with antiserum to myelin basic protein (MBP) revealed myelin-free areas of varying proportions within fetal spinal cord grafts. These regions were identified in both newborn and adult recipients regardless of whether donor tissue was grafted to heterotopic (intracerebral) or homotopic (intraspinal) sites. As in the SG of the intact spinal cord, the myelin-free regions consisted mainly of small (7-15 microns) diameter neurons. At the ultrastructural level, these cells were surrounded by a neuropil composed of numerous small caliber, unmyelinated axons and intermediate-sized dendrites. Synaptic terminals in these areas were primarily characterized by the presence of clear, round vesicles, although granular vesicles were occasionally found within these terminals. Immunocytochemical staining demonstrated met- and leu-enkephalin-, neurotensin-, substance P-, and somatostatin-like immunoreactive elements within these myelin-free areas. Thus, regions within embryonic spinal cord grafts undergo some topographical differentiation which parallels that of the normal superficial dorsal horn. The presence of SG-like regions illustrates the potential capacity of fetal spinal cord transplants for replacing some intraspinal neuronal populations at the site of a spinal cord injury in neonatal and adult animals. These graft regions may serve as a source of intersegmental projection neurons or establish an extensive intrinsic circuitry similar to that seen in the normal SG. In addition, the definition of these areas provides a useful model to study the innervation patterns of host axons that typically project to the substantia gelatinosa of the normal spinal cord.