Jeffrey A Brinker, M.D.
- Professor of Medicine
- Joint Appointment in Radiology and Radiological Science
There had been a good deal of talk after High Mass purchase genuine famvir antiviral research, and he had even received a request from General Jeronimo Argote purchase famvir 250mg with mastercard hiv-1 infection cycle, on behalf of the Caribbean refugees cheap famvir 250mg with amex hiv transmission statistics female to male, that he be buried in holy ground. Urbino answered: “Gerontophobia,” the proper word although he thought he had just invented it. Olivella, attentive to the guests who were sitting closest to him, stopped listening to them for a moment to take part in his teacher’s conversation. Urbino was not surprised to recognize his own thoughts in those of his favorite disciple. Then he spoke to the Archbishop of the lay saint he had known in their long twilights of chess, he spoke of the dedication of his art to the happiness of children, his rare erudition in all things of this world, his Spartan habits, and he himself was surprised by the purity of soul with which Jeremiah de Saint-Amour had separated himself once and for all from his past. Then he spoke to the Mayor about the advantages of purchasing his files of photographic plates in order to preserve the images of a generation who might never again be happy outside their portraits and in whose hands lay the future of the city. The Archbishop was scandalized that a militant and educated Catholic would dare to think that a suicide was saintly, but he agreed with the plan to create an archive of the negatives. Fermina Daza noticed it and in a low voice made him promise that he would attend the funeral. The woodwind band began a popular tune that had not been announced on the program, and the guests strolled along the terraces, waiting for the men from Don Sancho’s Inn to finish drying the patio in case anyone felt inclined to dance. The only guests who stayed in the drawing room were those at the table of honor, who were celebrating the fact that Dr. No one recalled that he had already done the same thing with a glass of grand cru wine as accompaniment to a very special dish, but his heart had demanded it of him that afternoon, and his selfindulgence was well repaid: once again, after so many long years, he felt like singing. And he would have, no doubt, on the urging of the young cellist who offered to accompany him, if one of those new automobiles had not suddenly driven across the mudhole of the patio, splashing the musicians and rousing the ducks in the barnyards with the quacking of its horn. Marco Aurelio Urbino Daza and his wife emerged, laughing for all they were worth and carrying a tray covered with lace cloths in each hand. Other trays just like them were on the jump seats and even on the floor next to the chauffeur. Urbino Daza explained in all seriousness that before the storm broke, the Sisters of St. Clare had asked him to please bring the dessert, but he had left the King’s Highway because someone said that his parents’ house was on fire. Juvenal Urbino became upset before his son could finish the story, but his wife reminded him in time that he himself had called for the firemen to rescue the parrot. Aminta de Olivella was radiant as she decided to serve the dessert on the terraces even though they had already had their coffee. Juvenal Urbino and his wife left without tasting it, for there was barely enough time for him to have his sacred siesta before the funeral. And he did have it, although his sleep was brief and restless because he discovered when he returned home that the firemen had caused almost as much damage as a fire. In their efforts to frighten the parrot they had stripped a tree with the pressure hoses, and a misdirected jet of water through the windows of the master bedroom had caused irreparable damage to the furniture and to the portraits of unknown forebears hanging on the walls. Thinking that there really was a fire, the neighbors had hurried over when they heard the bell on the fire truck, and if the disturbance was no worse, it was because the schools were closed on Sundays. When they realized they could not reach the parrot even with their extension ladders, the firemen began to chop at the branches with machetes, and only the opportune arrival of Dr. They left, saying they would return after five o’clock if they received permission to prune, and on their way out they muddied the interior terrace and the drawing room and ripped Fermina Daza’s favorite Turkish rug. Needless disasters, all of them, because the general impression was that the parrot had taken advantage of the chaos to escape through neighboring patios. Urbino looked for him in the foliage, but there was no response in any language, not even to whistles and songs, so he gave him up for lost and went to sleep when it was almost three o’clock. But first he enjoyed the immediate pleasure of smelling a secret garden in his urine that had been purified by lukewarm asparagus. Not the sadness he had felt that morning when he stood before the corpse of his friend, but the invisible cloud that would saturate his soul after his siesta and which he interpreted as divine notification that he was living his final afternoons. Until the age of fifty he had not been conscious of the size and weight and condition of his organs. Little by little, as he lay with his eyes closed after his daily siesta, he had begun to feel them, one by one, inside his body, feel the shape of his insomniac heart, his mysterious liver, his hermetic pancreas, and he had slowly discovered that even the oldest people were younger than he was and that he had become the only survivor of his generation’s legendary group portraits. When he became aware of his first bouts of forgetfulness, he had recourse to a tactic he had heard about from one of his teachers at the Medical School: “The man who has no memory makes one out of paper. But what disturbed him most was his lack of confidence in his own power of reason: little by little, as in an ineluctable shipwreck, he felt himself losing his good judgment. Juvenal Urbino knew that most fatal diseases had their own specific odor, but that none was as specific as old age. He detected it in the cadavers slit open from head to toe on the dissecting table, he even recognized it in patients who hid their age with the greatest success, he smelled it in the perspiration on his own clothing and in the unguarded breathing of his sleeping wife. If he had not been what he was-in essence an old-style Christian-perhaps he would have agreed with Jeremiah de Saint-Amour that old age was an indecent state that had to be ended before it was too late. The only consolation, even for someone like him who had been a good man in bed, was sexual peace: the slow, merciful extinction of his venereal appetite. At eighty-one years of age he had enough lucidity to realize that he was attached to this world by a few slender threads that could break painlessly with a simple change of position while he slept, and if he did all he could to keep those threads intact, it was because of his terror of not finding God in the darkness of death. Fermina Daza had been busy straightening the bedroom that had been destroyed by the firemen, and a little before four she sent for her husband’s daily glass of lemonade with chipped ice and reminded him that he should dress for the funeral. Urbino had two books by his hand: Man, the Unknown by Alexis Carrel and the Story of San Michele by Axel Munthe; the pages of the second book were still uncut, and he asked Digna Pardo, the cook, to bring him the marble paper cutter he had left in the bedroom. But when it was brought to him he was already reading Man, the Unknown at the place he had marked with an envelope: there were only a few pages left till the end.
The Expansion of Infectious Disease In recent decades buy discount famvir 250mg on line xylitol antiviral, diseases have spread faster than ever before cheap famvir 250mg antiviral brand names, facilitated by high speed travel and trade in goods and services between countries and continents order famvir cheap antiviral quotes. Often times, diseases will spread before the signs and symptoms of the disease are visible. When a natural disaster occurs or governments or insurgent groups engage in armed conflict, a result is often the devastation or weakening of health systems. Consequently, health systems have a reduced capacity to detect, prevent, and respond to infectious disease in outbreaks, diminishing the population’s access to healthcare. Especially in recent years, a large-scale movement of human populations has been common as a result of war, conflict, or natural catastrophes. These 13 Ya-Wen Chiu, Yi-Hao Weng, Yi-Yuan Su, Ching-Yi Huang, Ya-Chen Chang, Ken Kuo, “The Nature of International Health Security,” Asia Pacific Journal of Clinical Nutrition 18 (200): 680. Migrants also may not have immunity to diseases endemic in the new area; furthermore, they may bring with them diseases that are prevalent in their previous home but are not common in the new region. These displaced people are often forced to live in crowded, insanitary, and impoverished conditions which are conducive to infectious disease epidemics. Economic migrants make the great majority of all international migrants, but still add to the pool of people who are able to spread infectious diseases. According to Manuel Carballo, director of the International Center for Migration Health and Development, disease usually spreads within the migrant community because they typically interact, live, and work with each other. Global health security is becoming progressively more important because of the emergence and re-emergence of infectious diseases. As indicated by the Center for Comparative Epidemiology at Michigan State University, “An emerging or re-emerging infectious disease is a disease whose incidence has increased in a defined time period and location If the disease was unknown in the location before, the disease is considered to be emerging. However, if the disease had been present at the location in the past and 25 was considered eradicated or controlled, the disease is considered to be re-emerging. The spread and variety of resistant bacteria are facilitated by over-prescribing or under prescribing drugs, inadequate observance of recommended dosages, and unregulated sale by 27 unqualified workers. Although antibiotics were originally developed to treat infectious diseases in people, the same medicines are used to treat animals and plants. The spread of resistance worldwide is a rising problem which increases the threat of emerging and reemerging diseases. Migration Because migration can be viewed as an illustration of the global spread of diseases, migration and global health are often analyzed together. Migration is a topic of concern when considering the spread of infectious diseases, because people who move are vectors for disease. People carry their “healthprint” with them – their immunities, history of diseases, and germs they picked up along the way. Migrants can introduce new diseases to an area or bring back diseases when they return to their homeland. Additionally, with modern technology, people are traveling faster and are able to visit what used to be remote parts of the world. As different regions of the world develop, more people are likely to migrate in search of employment of a better quality of life. As written in the Impact of Globalization on Infectious Disease Emergence and Control, “migrant populations are among the most vulnerable to emerging and reemerging infectious diseases and have been implicated as a key causal factor in the global spread of such 29 diseases. The situations that result from migration are the risk, not the people in 30 these “spaces of vulnerability. Millions of migrants face health risks including poor access to health care, poverty, and exploitation during their journeys in search of a better life. Migration does not always lead to poor health; in fact, most migrants are healthy. However, undocumented migrants, internally displaced people, refugees, and groups such as victims of human trafficking often have little access to health care and suffer from exploitation, physical, and mental abuse which exacerbates their vulnerability to infectious diseases. Many migrants, especially undocumented ones, hesitate to come forward and receive the medical assistance they deserve. The right to health applies to all people, irrespective of their migratory status. Many migrants of low socio-economic backgrounds move from poor countries to richer ones, and have poor living conditions in their new home – crowded spaces, poor ventilation, and unhygienic areas. They also often have two or three jobs to survive and be able to send money back home. A major result is that their health 32 suffers as they are exposed to high and chronic stress. Because of all the risks migration brings, post-industrial states are weary of migration and are implementing more legal and social barriers to migrants, which make the migration process more difficult and make migrants feel unwanted. However, movies and the internet among other media spread images of life in developed countries across the world, and migrants are tempted to move in search of a better life. Health inequities within and between countries exist because of discrimination and marginalization, an unequal distribution of resources, and an unequal access to education, jobs, healthcare, and other social services. Migrants are especially vulnerable to health inequities because of their living and working conditions in their home and destination countries and because of the nature of the migration cycle. Migrants may be exposed to an increased amount of health risks and negative health outcomes, especially with the increase of restrictive migration policies. Irregular means of transportation, labor and economic downturns, and anti-migrant sentiment often cause migrants to be stuck with a low socio-economic status, which gives them less access to healthcare, education, and safe working conditions. Migrants, whether internally displaced persons, refugees, asylum seekers, or victims of trafficking, have varying levels of risks and vulnerabilities based on their individual migration circumstance. The health of a migrant is shaped by experiences and situations surrounding the migrant’s journey – in the place of origin, in transit, in the place of destination, and sometimes on the return journey to the place of origin. All migrants, even those with legal documents and a higher socio-economic position, may experience challenges to accessing services due to language and cultural differences, institutional or structural obstacles, or psycho-social stressors.
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Examples of helpful soft tissue signs include the elbow fat pad sign discount famvir 250mg on-line hiv infection rate hong kong, cervical spine preverteIn a targeted approach cheap famvir 250mg with mastercard hiv infection and aids pictures, the radiographs are rst examined for bral soft tissue swelling buy famvir 250mg amex antiviral proteins secreted by t cells, and maxillary sinus air/fluid levels. Then, the radiographs are scrutinized for signs of that can have subtle radiographic manifestations. Recognition of subtle radiographic ndings is especially important for injuries that can cause signicant disability when missed (Table 4). Knowledge of the standard and supplementary radiographic views is essential for accurate radiograph interpretation (Table 1). In regions of complex anatomy such as the wrist, hand, ankle and foot, a third view (often an oblique view) is often standard. The views that are included in a standard radiographic series may vary from institution to institution. Supplementary views may include oblique views, views in a third perpendicular plane (such as an axial view), or views with special positioning (such as the scaphoid view of the wrist). In a Lateral Supination oblique (ball-catcher view) specic injury patterns are sought Pronation oblique (Table 2). Distal radius fractures are the most common fracthe ulnar shaft is displaced dorsally relative to tures of the wrist. The dislocation is “posterior” (named for disIn this patient, careful inspection of the lateral view reveals placement of the ulna relative to the radius). When treated soon slight disruption and deformity of the dorsal cortex of the disafter the injury, closed reduction is usually successful, and the tal radius (Figure 23). There are two ways to determine whether apparent malalignextending across the distal radius. It is a remnant of the growth ment of the distal radius and ulna is due to incorrect (rotated) plate (Figure 17). First, the ulnar styloid normally “points” to the dorsal surface of the triquetrum, even when the lateral view is rotated. In Patient 4F, the ulnar styloid is directed dorsal to the triquetrum (Figure 24). Second, on a correctly positioned lateral view, the apex of the radial styloid should be aligned with the long axis of the radius and located midway between the volar and dorsal surfaces of the radial shaft (Figure 24). If the lateral view positioning is rotated, the apex of the radial styloid will be either too volar or too dorsal with respect to the radial shaft (Figure 25). A fracture of the distal radial shaft with dislocation of the ulnar-carpal articulation . The injury is unstable so closed reduction alone is insufcient to maintain the reduction. Fracture of the distal radial shaft and disPostoperative radiographs showing reduction and internal xation with comlocation of the distal ulna. This patient pacted fracture of the anterior aspect of the humeral head at the point had a prior posterior shoulder dislocation. The humeral head and gle When the patient was instructed to externally rotate his arm, he noid fossa are slightly overlapping because of the posterior instead externally rotated his torso because his shoulder was fixed dislocation. A B iliac oblique view obturator oblique view “closed book” pelvis laterally directed force Lateral compression extraperitoneal bladder rupture. However, patients with nondisplaced best detected by looking for specic injury patterns (tripod fracfractures may only have nonspecic clinical ndings such as ture, blow-out fracture, isolated zygomatic arch fracture, or swelling or ecchymosis. On the other hand, in Fracture patterns are best understood by considering the patients with massive facial injuries that have a dramatic clinmain structural elements of the facial skeleton (Figure 1). Nonetheless, the anatomical landmarks and patterns of facial There are no clinical decision rules to guide the ordering of fainjury remain the same. Many facial fractures can be diagnosed clinically, and signs of specic injuries serve as a guide to ordering facial imaging. Such clinical ndings include: palpable deformity of the orbital rim or zygomatic arch (can be masked by soft tisthe facial skeleton consists of three horizontal and three vertisue swelling), malar attening, periorbital subcutaneous emcal supportive struts (Figure 1). Most facial fractures are oriphysema, infraorbital anesthesia, restriction of ocular motion ented perpendicular to these supportive struts. The walls of the maxillary sinus and orbital oor are cut away in this illustration. Furthermore, the occurrence and predictors for esophageal varices and associated gastrointestinal bleeding were assessed, the relations between liver histology and clinical outcome variables evaluated, and noninvasive follow-up tools identified. The patients whose liver fibrosis progressed had higher serum bilirubin levels at follow-up [median 15 mol/L (3-35) vs. The combination of normal serum bilirubin (<20 mol/L) and galactose half-life under 12. National centralization of biliary atresia care to an assigned multidisciplinary team provides high-quality outcomes. Endoscopic surveillance and primary prophylaxis sclerotherapy of esophageal varices in biliary atresia. These articles are reproduced with the kind permission of their copyright holders. According to the World Health Organization, over 5000 rare disorders exist and in Europe, over 30 million patients have a rare disease. Problems that affect patients with rare disorders, and medical professionals treating them, include limited information on rare diseases, limited availability of adequate treatments, and difficulties in obtaining research financing.
Niacin should be taken in multiple doses during the day discount famvir 250 mg amex examples of antiviral drugs, starting from 50–100 mg 2–3 times a day discount famvir 250 mg without prescription antivirus windows vista, and gradually increasing the dose whilst carefully checking for any side effects discount famvir 250mg free shipping antiviral krem. The reduction of triglycerides can be already observed several hours after the intake of niacin, while the effects on cholesterol decrease take a few days. The most common side effect of niacin is skin vasodilatation (ushing and itching), an annoying but harmless sensation that can be prevented by taking aspirin, ibuprofen, or indomethacin before the drug . Gastrointestinal intolerance is an effect that can be minimized by administering the drug with meals . It is advisable to avoid the simultaneous use of niacin with adrenergic blockers and vasodilators (calcium channel blockers, nitrates) as there is a greater risk of vasodilation and postural hypotension. Omega-3 Fatty Acids Omega-3 fatty acids are polyunsaturated fatty acids with a double bond at the third carbon atom from the end of the carbon chain. They become part of the cell membrane, as with other fatty acids, and thanks to their chemical–physical characteristics, they determine the uidity characteristics of membranes. Meta-analyses of omega-3 fatty acids added to optimal statin therapy suggest they give no added benet . The mechanisms by which omega-3 polyunsaturated fatty acids exert cardiovascular protective effects are both functional and metabolic: they cause greater uidity of membranes, improve endothelial function, modulate platelet aggregation, modulate the metabolism of eicosanoids, and stabilize atheromatous lesions . From a metabolic point of view, omega-3 mainly reduces serum triglycerides through an increase in the oxidation of fatty acids, further decreasing their synthesis and modulating the composition of membrane phospholipids. Highly-puried omega-3 is usually used together with other drugs for the treatment of certain forms of hypertriglyceridemia . The common side effects are: stomach problems, indigestion (dyspepsia), and nausea . Uncommon side-effects are abdominal and stomach pain, allergic reactions, dizziness, Pharmacy 2018, 6, 10 8 of 16 problems with taste, diarrhea, and vomiting. Alirocumab has near 90% bioavailability and a long half-life (around 17–20 days) . This results in an increase in target clearance and reduced systemic exposure to alirocumab. Compared to alirocumab monotherapy, alirocumab exposure is reduced by about 40% if the drug is used in combination with a statin, and about 15% if the drug is used in association with ezetimibe . Evolocumab is indicated in adult patients with primary hypercholesterolemia (familial heterozygous and non-familial) or mixed dyslipidemia, in addition dietary changes. The recommended adult dose of evolocumab is 140 mg every two weeks or 420 mg once a month for primary hypercholesterolemia and mixed dyslipidaemia; the two doses are clinically equivalent. Pharmacy 2018, 6, 10 9 of 16 For homozygous familial hypercholesterolemia in adults and adolescents aged 12 years or over, the recommended starting dose is 420 mg once a month. After 12 weeks of treatment and no clinically-relevant response, it is possible to increase the frequency of administration to 420 mg every two weeks . The pharmacokinetic interactions between statins and evolocumab have been studied. No statin dose adjustments are required when used in association with evolocumab . The absolute oral bioavailability of lomitapide is 7% due to an extensive rst pass effect. The efcacy of lomitapide, at a starting dose of 5 mg/day for the rst two weeks and then escalated to 10, 20, 40, and 60 mg/day at 4-week intervals, was evaluated in a single-arm open-label study of 29 patients with homozygous familial hypercholesterolemia, in addition to their current lipid-lowering therapy (statins, ezetimibe, and apheresis) . Lomitapide should be used in combination with a low-fat diet and other lipid-lowering drugs, administered on an empty stomach at least two hours after the evening meal, as fat content can adversely affect gastrointestinal tolerability. The starting dose is 5 mg/day, and after several weeks it is possible to gradually increase the dose up to the maximum recommended dose of 60 mg . The most common, least-serious side effects are those affecting the gastrointestinal tract (diarrhea, nausea, dyspepsia, vomiting) with an incidence of about 90%, while the most serious side effects are those affecting the liver, such as abnormal increases in liver transaminases and hepatic steatosis . Finally, the plasma concentrations of statins can also be increased by lomitapide such that constant monitoring of this association needs to be performed since it may lead to a greater risk of myopathy . Mipomersen half-life is approximately two to ve hours, and it has an elimination half-life of one to two months . Pharmacy 2018, 6, 10 10 of 16 the estimated subcutaneous bioavailability of mipomersen is between 54% and 78% after a once-weekly dose of 50 to 400 mg . The lipid-lowering effects of mipomersen in two phase three clinical trials have been shown after failed courses of standard lipid-lowering therapy . However, the protective effects of mipomersen on cardiovascular outcomes needs to be better evaluated. The recommended dose is 200 mg/mL, subcutaneously, once weekly, on the same day each week. Longer-term evaluations of transaminase elevations and hepatic steatosis are necessary. Mipomersen is not recommended for patients with severe renal dysfunction and/or liver dysfunction. Common adverse effects reported in clinical trials include injection site reactions and u-like symptoms . Injection site reactions occurred three-times more often in the treatment group than the placebo group. Most of these reactions were described as mild, erythematous, and painless, and resolved after 24 h. Flu-like symptoms, the second most common complaint that arises frequently in the rst doses, appeared shortly after the administration of mipomersen and resolved within a few days.
Also National Directorate for Water Supply and Sanitation buy 250 mg famvir with visa hiv infection rates among youth, personal communications discount famvir generic four early symptoms hiv infection. It can also be done through support for the government’s proposed microcredit schemes to discount famvir 250mg without prescription lysine antiviral encourage investments in rural sanitation projects. Received 14 January 2011 Its dynamics are highly complex owing to the coupling among multiple transmission pathways and Received in revised form 29 March 2011 differentfactorsinpathogenecology. Althoughvariousmathematicalmodelsandclinicalstudiespublished Accepted 5 April 2011 in recent years have made important contribution to cholera epidemiology, our knowledge of the disease Available online 12 April 2011 mechanism remains incomplete at present, largely due to the limited understanding of the dynamics of cholera. Inthis paper, we conduct global stability analysis for several deterministic cholera epidemic modKeywords: els. We employ three different techniques, including the monotone dynamical systems, the geometricapproach, andLyapunovfunctions,toinvestigatetheendemicglobalstabilityforseveralbiologically important cases. The analysis and results presented in this paper make building blocks towards a comprehensive study and deeper understanding of the fundamental mechanism in cholera dynamics. Introduction cholera outbreak in a Singapore psychiatric hospital indicated that the direct human-to-human transmission was a driving force . Cholera is an ancient disease that continues to cause epidemic In addition, several other aspects must be considered, including the and pandemic infection despite ongoing efforts to limit its spread pathogen ecology outside of human hosts  and climatological [1,11,16,22,35,38,41,42,53]. The present work aims to understand the global era pandemics have swept the globe since 1816 [58–60]. Most redynamics of cholera epidemiology in a general mathematical modcently, the seventh pandemic started from Indonesia in 1961, el which has a potential to incorporate these different factors into a spread into Europe, South Pacic and Japan in the late 1970s, unied framework. Such understanding is crucial for effective prereached South America in 1990s, and has continued (though much vention and intervention strategies against cholera outbreak. The last few years have witnessed Many mathematical models have already been proposed to many cholera outbreaks in developing countries, including India investigate the complex epidemic and endemic behavior of chol(2007), Congo (2008), Iraq (2008), Zimbabwe (2008–2009), Vietera. One difculty in studying cholera dynamics is the coupling nam (2009), Nigeria (2010), and Haiti (2010). In the year of 2010 between its multiple transmission pathways which involve both alone, it is estimated that cholera affects 3–5 million people and direct human-to-human and indirect environment-to-human causes 100,000–130,000 deaths in the world . Particularly, modes and which lead to combined human-environment epidemicholera represents a signicant public health burden to developing ological models. The earliest mathematical model was proposed by countries and cholera continues receiving worldwide attention. Capasso and Paveri-Fontana  to study the 1973 cholera epidemic Cholera is an infection of the small intestine caused by the in the Mediterranean region. Untreated individuals nents, the concentration of the pathogen in water, x1, and the popsuffer severely from diarrhea and vomiting. In their original notations, the dehydration and electrolyte imbalance, and can lead to death. As model is given by a water/food-borne disease, cholera is typically infected through dx1 pathogen ingestion, such as drinking sewage-contaminated water, Aa11x1 a12x2; 1:1 or eating food prepared by an individual with soiled hands. Particularly, g(x1) obeys a ‘‘saturation’’ Their model includes both environment-to-human and human-torequirement: when the pathogen concentration (x1) is high, g aphuman transmission pathways: proaches a constant representing a saturated state of the incidence. She also included the susceptible population into her model to dI B consider the long-term dynamics. The parameters b1 and b2 are rates of ingesting where S and I stand for the susceptible and infected individuals vibrios from contaminated water and through human-to-human respectively, and B is the concentration of the vibrios in water reinteraction, respectively. The incidence is a non-linear function in B, given by In addition, Tien and Earn  in 2010 published a water-borne fBa B with a being the contact rate with contaminated water KB disease model which also included the dual transmission pathand K the pathogen concentration that yields 50% chance of catchways, with bilinear incidence rates employed for both the environing cholera. This incidence represents a logistic response to the inment-to-human and human-to-human infection routes. No crease in B: when B (K, f grows linearly with B; when B) K, f saturation effect was considered in this work. Similar to the work of Capasso and Paveri-Fontana , this contribution in the study of cholera dynamics. However, the intermodel assumes the ingestion of contaminated water is the only action between V. Also, the bacterial growth Using similar non-linear incidence in Codeco’s model, Hartley outside of human hosts does not have to follow linear dynamics. Consequently, this model tries to implicitly highlight the cholera epidemics, we can lump IA and I+ as one variable. However, as pointed out in , the role of the hyper-infective As mentioned above, two major differences among these cholstage of V. Wang/Mathematical Biosciences 232 (2011) 31–41 33 among its multiple transmission pathways, but also stems from the global stability of the endemic equilibrium, however, the intricate V. In order to include these different factors inknowledge, none of the previous works on cholera modeling have volved in cholera dynamics, we recently proposed a generalized addressed the global dynamics. The model unies previous mathematical whether the long-term disease dynamics approaches an equilibmodels by introducing a general incidence function f(I,B) which rium and how this depends on the initial size of the infection, recan include multiple transmission pathways, and a general pathomain to be answered. The study of the endemic global stability is gen growth rate h(I,B) which can represent varying environmental not only mathematically important, but also essential in predicting factors such as cholera ecology in water and climatological inuthe evolution of the disease in the long run so that prevention and ence. The model consists of the following differential equations: intervention strategies can be effectively designed, and public health administrative efforts can be properly scaled. The challenge, dS bN A SfI; BAbS; 1:21 however, in the global analysis of cholera models is that due to the dt incorporation of the environmental component B, the models usudI ally constitute four-dimensional non-linear autonomous systems SfI;BAc bI; 1:22 dt for which the classical Poincare–Bendixson theory  is no longer valid. Hence, other analytical tools must be employed, and possibly dR cI A bR; 1:23 new methods need to be created, to overcome this challenge. The theories of monotone h(I,B) are assumed for I P 0, B P 0: dynamical systems and geometric approach are relatively new compared to the Poincare-Bendixson framework. These new meth(a) f(0,0) = 0, h(0,0) = 0 ods are much involved both conceptually and computationally.