Education, outreach and the future of remote sensing in human health.

The human health community has been slow to adopt remote sensing technology for research, surveillance, or control activities. This chapter presents a brief history of the National Aeronautics and Space Administration's experiences in the use of remotely sensed data for health applications, and explores some of the obstacles, both real and perceived, that have slowed the transfer of this technology to the health community. These obstacles include the lack of awareness, which must be overcome through outreach and proper training in remote sensing, and inadequate spatial, spectral and temporal data resolutions, which are being addressed as new sensor systems are launched and currently overlooked (and underutilized) sensors are newly discovered by the health community. A basic training outline is presented, along with general considerations for selecting training candidates. The chapter concludes with a brief discussion of some current and future sensors that show promise for health applications.

Remote sensing and human health: new sensors and new opportunities.

Since the launch of Landsat-1 28 years ago, remotely sensed data have been used to map features on the earth's surface. An increasing number of health studies have used remotely sensed data for monitoring, surveillance, or risk mapping, particularly of vector-borne diseases. Nearly all studies used data from Landsat, the French Système Pour l'Observation de la Terre, and the National Oceanic and Atmospheric Administration's Advanced Very High Resolution Radiometer. New sensor systems are in orbit, or soon to be launched, whose data may prove useful for characterizing and monitoring the spatial and temporal patterns of infectious diseases. Increased computing power and spatial modeling capabilities of geographic information systems could extend the use of remote sensing beyond the research community into operational disease surveillance and control. This article illustrates how remotely sensed data have been used in health applications and assesses earth-observing satellites that could detect and map environmental variables related to the distribution of vector-borne and other diseases.

Prediction of villages at risk for filariasis transmission in the Nile Delta using remote sensing and geographic information system technologies.

Remote sensing and geographic information system (GIS) technologies were used to discriminate between 130 villages, in the Nile Delta, at high and low risk for filariasis, as defined by microfilarial prevalence. Landsat Thematic Mapper (TM) data were digitally processed to generate a map of landcover as well as spectral indices such as NDVI and moisture index. A Tasseled Cap transformation was also carried out on the TM data which produced three more indices: brightness, greenness and wetness. GIS functions were used to extract information on landcover and spectral indices within one km buffers around the study villages. The relationship between satellite data and prevalence was investigated using discriminant analysis. The analysis indicated that the most important landscape elements associated with prevalence were water and marginal vegetation, while wetness and moisture index were the most important indices. Discriminant functions generated for these variables were able to correctly predict 80% and 74% of high and low prevalence villages, respectively, with an overall accuracy of 77%. The present approach provides a promising tool for regional filariasis surveillance and helps direct control efforts.

Properties of optical data from activated partial thromboplastin time and prothrombin time assays.

Changes in characteristics of optical transmittance data from coagulation assays were examined as a function of concentration of coagulation proteins or anticoagulants. Transmittance data were collected for activated partial thromboplastin time (APTT) and prothrombin time (PT) assays from: 1) plasmas prepared by mixing normal plasmas with deficient plasmas to give varying levels of coagulation proteins; 2) plasmas containing added heparin; and 3) 200 specimen plasmas that were also assayed for fibrinogen, coagulation factors, and other components. Optical profiles were characterized using a set of parameters describing onset and completion of coagulation, magnitude of signal change, rate of coagulation and other properties. Results indicated that parameters other than those typically reported for APTT and PT are associated with individual deficiencies, but that diagnosis of specimen status on the basis of optical data is complex. These results suggest possibilities for expanded interpretation of PT/APTT optical data for clinical or research applications.

Assessment of a remote sensing-based model for predicting malaria transmission risk in villages of Chiapas, Mexico.

A blind test of two remote sensing-based models for predicting adult populations of Anopheles albimanus in villages, an indicator of malaria transmission risk, was conducted in southern Chiapas, Mexico. One model was developed using a discriminant analysis approach, while the other was based on regression analysis. The models were developed in 1992 for an area around Tapachula, Chiapas, using Landsat Thematic Mapper (TM) satellite data and geographic information system functions. Using two remotely sensed landscape elements, the discriminant model was able to successfully distinguish between villages with high and low An. albimanus abundance with an overall accuracy of 90%. To test the predictive capability of the models, multitemporal TM data were used to generate a landscape map of the Huixtla area, northwest of Tapachula, where the models were used to predict risk for 40 villages. The resulting predictions were not disclosed until the end of the test. Independently, An. albimanus abundance data were collected in the 40 randomly selected villages for which the predictions had been made. These data were subsequently used to assess the models' accuracies. The discriminant model accurately predicted 79% of the high-abundance villages and 50% of the low-abundance villages, for an overall accuracy of 70%. The regression model correctly identified seven of the 10 villages with the highest mosquito abundance. This test demonstrated that remote sensing-based models generated for one area can be used successfully in another, comparable area.

Landscape surrounding human settlements and Anopheles albimanus (Diptera: Culicidae) abundance in Southern Chiapas, Mexico.

Landscape characteristics that may influence important components of the Anopheles albimanus Wiedemann life cycle, including potential breeding sites, suitable diurnal resting sites, and possible sources of blood meals, were analyzed at 14 villages in a malarious area of southern Mexico. An. albimanus adults were collected weekly in each village using UV-light traps between July 1991 and August 1992. Based on rainfall, the study was divided into 6 seasonal periods. Villages were considered to have high mosquito abundance when >5 mosquitoes per trap per night were collected during any 1 of the 6 seasonal periods. The extension and frequency of 11 land cover types surrounding villages were determined using aerial photographs and subsequently verified through field surveys. Elevation was the main landscape feature that separated villages with low and high mosquito abundance. All villages with high mosquito abundance were below 25 m. Transitional and mangrove land cover types were found only in the high mosquito abundance group. Flooded areas as potential breeding sites and potential adult resting sites in unmanaged pastures were significantly more frequent in areas surrounding villages with high mosquito abundance. No significant differences in density of cattle and horses were found among village groups. Overall, surrounding breeding sites located at low elevations in flooded unmanaged pastures seemed to be the most important determinants of An. albimanus adult abundance in the villages.

Remote sensing as a landscape epidemiologic tool to identify villages at high risk for malaria transmission.

A landscape approach using remote sensing and geographic information system (GIS) technologies was developed to discriminate between villages at high and low risk for malaria transmission, as defined by adult Anopheles albimanus abundance. Satellite data for an area in southern Chiapas, Mexico were digitally processed to generate a map of landscape elements. The GIS processes were used to determine the proportion of mapped landscape elements surrounding 40 villages where An. albimanus abundance data had been collected. The relationships between vector abundance and landscape element proportions were investigated using stepwise discriminant analysis and stepwise linear regression. Both analyses indicated that the most important landscape elements in terms of explaining vector abundance were transitional swamp and unmanaged pasture. Discriminant functions generated for these two elements were able to correctly distinguish between villages with high and low vector abundance, with an overall accuracy of 90%. Regression results found both transitional swamp and unmanaged pasture proportions to be predictive of vector abundance during the mid-to-late wet season. This approach, which integrates remotely sensed data and GIS capabilities to identify villages with high vector-human contact risk, provides a promising tool for malaria surveillance programs that depend on labor-intensive field techniques. This is particularly relevant in areas where the lack of accurate surveillance capabilities may result in no malaria control action when, in fact, directed action is necessary. In general, this landscape approach could be applied to other vector-borne diseases in areas where 1) the landscape elements critical to vector survival are known and 2) these elements can be detected at remote sensing scales.

Preparation and pharmacokinetic evaluation of a modified long-acting injectable norethisterone microsphere.

Prototype long-acting formulations of norethisterone in the form of injectable microspheres made of biodegradable co-polymer of polylactic acid and glycolic acid have been successfully used as injectable contraceptives in women. Second-generation formulations with improved in vitro and in vivo norethisterone-release profiles have been developed and tested in baboons. A cyclic pattern of norethisterone release has been achieved by modification of the surface properties of the prototype formulation. One such modification, and the resulting effects on the in vitro and in vivo norethisterone release profiles will be presented and discussed.

A baboon model for pregnancy-associated antigens (PAPP-A, PP5, PP14).

By radioimmunoassays established on human derived antigens, PAPP-A, PP5 and PP14 immunoreactivity was detected in placental extracts and blood of pregnant baboons. None of the serial dilution curves suggested parallelism between respective human and baboon samples. Based on slopes of regressed logit-log transformed binding data, PAPP-A demonstrated the greatest degree of interspecies immunological crossreactivity. PP14 showed the least conservation of antigenic determinants. Physicochemical characterization on heparin, zinc chelate and bovine thrombin affinity matrices could not distinguish human from baboon-derived antigens. As in the human, baboon PAPP-A and PP5 were not detected in blood of male or non-pregnant animals. PP14 was detected in baboon follicular fluid, and only PP5 immunoreactivity was measured in culture media of baboon embryos. Of the three antigens, PAPP-A was detected in pregnant baboons at about 61 days gestation, that is, 4 weeks before PP5 and PP14. With the exception of PP14 which attained peak concentration at 118 days of pregnancy, PAPP-A and PP5 concentrations were greatest at term. In conjunction with physicochemical and immunological criteria, these physiological kinetics clearly support a role for developing a baboon model to serve for further studies into feto-maternal signals, particularly antigens such as PAPP-A and PP5.

Home traction in the management of congenital dislocation of the hips.

A total of 14 patients with congenital dislocation of the hip have used our home traction frame and program over a 2-year period. The newly designed frame is made of polyvinyl chloride tubing and consists of two parts: a Bradford frame and a roller base. The frame is lightweight, portable, and inexpensive to make. Traction can be maintained for 3 weeks at home, with a significant cost savings of more than $5,000/child. In our patients, there have been no cases of avascular necrosis of the hip or neurovascular problems to the legs. There is decreased psychological stress to the child and family when the care can be provided at home.

Cryopreservation and transfer of baboon embryos.

The feasibility of modifying bovine cryopreservation methods for use with baboon embryos was evaluated. Twenty-six baboon embryos at the eight-cell to blastocyst stage of development were transferred after being frozen using glycerol as cryoprotectant. Either a two-step fast of a controlled linear temperature depression was achieved to -40 degrees C, followed by plunging into liquid nitrogen. After thawing, embryos were rehydrated in medium containing sucrose (0.5 to 1.0 M) using various methods of glycerol dilution. Embryos were transferred nonsurgically to anesthetized recipient baboons. Two term pregnancies resulted from six embryos frozen using the controlled linear cooling method and rehydrated by dropwise dilution of the sucrose (0.8 M) medium. Later cell stages had a greater morphological integrity postthaw than did earlier developmental stages, and embryos frozen by the linear cooling-rate method had less cell damage than those frozen by the fast method.

Long-acting injectable microsphere formulation for the parenteral administration of levonorgestrel.

The pharmacokinetic and pharmacodynamic effects of a long-acting formulation of levonorgestrel microencapsulated in a biodegradable polymer poly(DL-lactide-CO-glycolide) was tested in baboons. The polymer microspheres provided continuous release of levonorgestrel for up to 6 months following a single intramuscular injection. The treatment inhibits ovarian function for 3-6 months, depending on the dose. The duration and pattern of levonorgestrel release varies according to the quality and size of the microspheres. The microsphere delivery system offers a promising new approach to developing a long-acting injectable contraceptive based on levonorgestrel.

Long-acting injectable norethisterone contraceptive system: review of clinical studies.

PIP: This report summarizes research supported by the Program for Applied Research on Fertility Regulation (PARFR) to develop a long-acting, injectable, biodegradable miscrosphere delivery system for norethisterone (NET). This delivery system consists of microspheres composed of a biodegradable polymer and NET. The polymer 1st evaluated for making NET microspheres was dl-polylactic acid (PLA). This prototype system was tested in clinical trials involving 63 women at 3 centers. The results of these studies indicated that PLA microspheres are capable of delivering NET continously for about 6 months. The duration of ovarian suppression was dose dependent with a given microsphere formulation and size limit. The average number of bleeding and spotting days decreased with increasing time from injection. Up to 12 months was required for the PLA microspheres to completely degrade, however, and there was concern that repeated injections at 6-month intervals might allow an undesirable build-up of PLA in muscle tissues. Research efforts then centered on developing a polymer formulation that offered better synchronization between duration of NET release and biodegradation of the polymer. In the 2nd generation formulation, polyglycolic acid (PGA) was incorporated to achieve faster biodegradation. Phase II studies were based on a formulation that demonstrated improvements in the manufacturing process, pharmacokinetics of the NET microspheres, biodegradation kinetics of the polymer, and injectability. More precise control of release has been obtained, the drug loading and size distribution of the microspheres have been optimized, and the molar ratios of PLA and PGA have been changed. Although Phase II studies are still in progress, higher NET-loaded microspheres have been shown to product substantially faster release rates during the 1st 30 days post-treatment. In addition, increasing the NET concentration to 50% substantially improved formulation injectability. Few obstacles to eventual approval and widescale use of this injectable contraceptive system are anticipated. Studies are currently underway to provide better bleeding control.^ieng

SP-I secretion by baboon embryos in vitro.

Baboon embryos cultured to postimplantation stages have been shown to secrete the placental protein SP-I into the culture medium in quantities of up to almost 5 micrograms/day, based on a rhesus monkey standard. Twelve embryos, for which spent media samples have been assayed, have been shown to secrete this protein, with measurable quantities usually being present on day four following attachment of the zonaless embryo to the culture dish. Secretion has continued for up to 14 days, with over 26 micrograms total SP-I secretion from one embryo. These observations further enhance the utility of the baboon embryo culture system as a model for studying early placental development in the primate.

Controlled-release delivery systems for hormones. A review of their properties and current therapeutic use.

Biomedical engineering approaches used to develop controlled-release delivery systems for hormones are here reviewed regarding system design and therapeutic applications. The biomedical engineering approach uses a system of non-drug components to control the rate and duration of hormone delivery. The non-drug components vary from system to system, but generally include: a reservoir for the hormone; a barrier or regulator to contain the hormone within the reservoir and to control its release; an energy source to remove the hormone from the reservoir; and a pathway for egress of the hormone from the system. Controlled-release delivery systems for hormones discussed in this review include mechanical and osmotic pumps; intraocular, intravaginal and intrauterine platform devices; biodegradable and non-biodegradable subcutaneous implants; and small particulate systems including microcapsules, microspheres and liposomes. Examples of the therapeutic application of the various systems are given along with a discussion of design factors and pharmacological aspects relevant to their clinical use.

Clinical evaluation of an improved injectable microcapsule contraceptive system.

Pharmacokinetics and pharmacodynamics of a long-acting injectable microcapsule, poly(DL-lactide-co-glycolide), delivery system were tested in 10 women. Two doses (75 or 100 mg of norethindrone) were administered by intramuscular injection. Treatment suppressed ovarian function and inhibited ovulation for 3 months in all subjects. Levels of norethindrone in subjects who received the 100 mg dose were proportionately higher than those in subjects who received the 75 mg dose. Subsequent to the injection, there was a rapid rise in the serum levels of norethindrone followed by a gradual decline until 8 to 10 weeks. Between 10 and 20 weeks after treatment, there was a secondary rise and fall in the serum levels of norethindrone. Treatment caused suppression of the endometrium for 3 months, and, except for spotting and irregular menstrual cycles, there were no adverse side effects. Treatment had no significant effect on serum lipids.

Poly(DL-lactide-co-glycolide)/norethisterone microcapsules: an injectable biodegradable contraceptive.

Microcapsules made from a biocompatible, biodegradable polymeric excipient, poly(DL-lactide-co-glycolide) (DL-PLGA) that contained 22 weight percent (wt %) norethisterone (NET), were prepared by a solvent-evaporation microencapsulation process. The effects of changing both the lactide-to-glycolide ratio of the DL-PLGA and the size of the microcapsules on the rate of NET release and the rate of excipient biodegradation were determined in vivo. NET release rates were determined in baboons after injecting the microcapsule formulations intramuscularly. Serum samples obtained at various times following treatment were analyzed for NET, progesterone, and estrogen by radioimmunoassay (RIA). Biodegradation kinetics were determined by injecting NET microcapsules made from radiolabeled DL-PLGA intramuscularly into the hind legs of rats. Residual radioactivity at the injection site was determined at various times after treatment by combustion analysis of the muscle tissue. Changing the ratio of the comonomers to include more glycolide (DL-lactide:glycolide-96:4, 92:8, 87:13, 74:26) increased the rate of NET release and accelerated the biodegradation of the copolymer excipient. Decreasing the size of the microcapsules increased the rate of NET release. On the basis of these studies a NET microcapsule formulation has been identified for clinical testing which releases NET for 3 months and biodegrades completely within 6 months.

The abortifacient effect of synthetic androstane derivatives in the baboon.

Synthetic androstane derivatives have been tested for their ability to induce abortion during early pregnancy in primates. Two compounds were studied following intramuscular (IM) and oral treatment in fourteen baboons. A five-day treatment regimen was started at approximately day 20 of pregnancy in 12 baboons, with treatment delayed until after day 40 in two baboons. All seven baboons treated IM with either compound aborted following intramuscular treatment, although three required a second treatment series beginning on approximately day 40 of pregnancy. Two of five baboons treated orally aborted following the single treatment series initiated around day 20 of pregnancy. The two baboons treated only after day 40 continued to term and delivered healthy infants. These compounds are therefore effective at terminating pregnancy when given around the time of the missed menstrual period. Further studies are necessary to determine optimal dose and treatment schedule.

A 4-year summary of the nonsurgical recovery of baboon embryos: A report on 498 eggs.

A nonsurgical embryo recovery procedure, developed to allow the economical acquisition of cleavage stage baboon embryos, has been successfully used for 4 years. With this technique, 498 eggs have been recovered from 979 uterine flushes (50.9%) on 71 baboons. Of 467 eggs recovered from mated baboons, 290 (62.1%) were fertilized. Papio anubis females provided a higher percentage of fertilized eggs (75.3%) than did Papio hamadryas (47.8%) or Papio cynocephalus (44.3%) females following exposure to males during estrus, although sexual preference may be responsible for the reduced fertilization rate in the P. cynocephalus females. Recovery rates from individual baboons ranged from 0% (n = 11) to between 66% and 93% for ten baboons from each of which 12-33 eggs have been recovered. Fertilized eggs were at the two-cell (n = 23) to blastocyst (n = 53) stage at recovery 1-6 days postdeturgescence (PD) of the sex skin, with morulae (n = 84) being the most frequent cell stage recovered (30%). The optimum time for performing the procedure was the third day PD, when 113 (40%) embryos were recovered. The abilities of baboons to become pregnant and to provide fertilized embryos were significantly related (P < 0.005), allowing the embryo recovery technique to be used as a screening procedure for evaluating baboon fertility.