A model would suggest what conditions must be met for archival antigenic variation to be an eective strategy to avoid host immune memory purchase innopran xl 80mg mastercard heart attack 64 lyrics. Eectsovermorethan one step are obtained by multiplying the signs along the paths effective innopran xl 40 mg jugular pulse pressure. For example cheap innopran xl 40mg with mastercard heart attack high 3000 miles from the south, an increase in y has a negative eect on R buy innopran xl 80mg with amex blood pressure medication muscle weakness,whichinturnhas a positive eect on x,whichhas apositive eect on Ix. Thus, an increase in y depresses Ix becausetheproduct of the two positive arrows and one negative arrow is negative. Thepath to Iy from y is positive, and the return path to y is negative, yielding a net negative eect. Continuing on from y to Ix produces another negativecomponent, so the product of the entire indirect pathway is positive. A decline in x lowers stimulation and causes Ix to fall, which allows x to rise, and so on. A similar cycle happens with the predatory immune type, Iy,preyingontheantigenic type, y. For example, the parasite types x and y may com- pete for a host resource, R,suchashostcells to infect or the uptake of alimiting nutrient (Smith and Holt 1996). Direct competition between the parasite variants creates indirect in- teractions between the specic immune types. Overall, if we ignore all feedbacks, an increase in y enhances Iy,anddepresses x and Ix. For this particular example, it turns out that resource competition by itself typically reduces the potential for coexistence of antigenic variants compared with the case in which no competition occurs. If Iy drives y to extinction in the absence of competition, then additional competition for resources will usually not save y. Several studies suggest that resource competition between parasites may sometimes inuence the within-host dynamics of infection. In per- sistent malaria infections, competition between Plasmodium for suscep- tible erythrocytes apparently playsanimportant role (Gravenor et al. These studies did not directly discuss antigenic variation, but they suggest that resource com- petition may be important. To the extent that antigenic variants do dier in their use of host resources, coexistence becomes easier to maintain by reducing the direct competition between the variants. Variation in tissue tropism appearstobeassociated with antigenically variable surface molecules in Neisseria gonorrhoeae (Gray-Owen et al. In Neisseria,variablecelltropism may be impor- tant in sequentially colonizing dierent tissues as invasion and spread develop, with little direct competition between the antigenic variants. The population of early viruses used a narrow range of coreceptors, whereas the late viruses were highly polymorphic for a diverse array of host coreceptors. As the population of viruses builds and depresses the abundance of commonly infected cell types, diversication to dierent cell tropisms reduces competition. The rst has a sur- face antigen that provides superior entry into host cells, but this variant is cleared at a higher rate. The second variant has a lower rate of entry into host cells, but is cleared at a lower rate. For example, host compartments with low resource lev- els cannot sustain the rst typelimitedhostcells reduce the produc- tion rate below the high clearance rate. By contrast, in compartments with high resource levels, the stronger type dominates by outcompeting the weaker type. The immunogenicity of the anti- genic types may dier, varying the rate of parasite killing and the stimu- latory signals to the immune cells. Mathematical studies show that even rather simple interactions often lead to uctuat- ing abundances because of the nonlinear processes inherent in popula- tion dynamics. Thus, uctuating abundances of antigenic variants and matching immune specicities may often occur in persistent infections (Nowak and May 2000). How many amino acid sub- stitutions are needed for new variants to escape immunity against the original epitope? Does escape usually arise from a single substitution, or are multiple substitutions often required? If laboratory mice can be used as a model, it would be interesting to infect replicates of a common host genotype by a cloned pathogen genotype. One could then study the relative eect of genotype and stochastic factors on the number of sub- stitutions in escape variants and the genetic pattern of diversication in escape. I discuss relevant preliminary studies in later chapters on experimental evolution. Epitopes often occur in key surface molecules used for attachment or in important enzymes such as replication polymerases. Escape variants gain by avoiding specic immunity but may impose costs by lowering other components of par- asite tness. The glycosylation also reduced the degree to which vi- ruses stimulated an antibody response when injected into new hosts. It would be interesting to know if glycosylation reduces transmissibility or some other component of viral tness. Escape within a host does not necessarily reduce transmissibility or othercomponents of tness. Mothers can transmit this escape variant to their ospring, who then target a subdominant B27 epitope and fail to contain the infection. These escape variants remain stable and do not revert to the original type when passaged in cell culture. Antigenic switching from archival libraries generates inter- esting dynamics within the host. Typically, the rst variants increase rapidly, causing a high density of parasites within the host. Specic im- munity then rises against those initial variants, causing a decline in the parasite population within the host. The variants rise in abundance during or after the decline of the rst parasite burst. What is the basic tim- ing for the initial growth of the parasite population, the rise in specic immune cells, and the decline in the initial parasitemia? What are the densities and the diversity of antigenic variants during the initial para- sitemia? What are the timings and theshapesofthe growth curves for the populations of antigenic variants? At what parasite density do the variants begin to stimulate a specic immune response? That stimulatory threshold sets the pace at which the host can raise a new wave of immunity to combat the second parasite wave. What is the timing and pattern of new variants generated by parasites in the second wave? How do the coupled dynamics of specic immune cell populations and matching parasite variants together determine the total length of infec- tion and the uctuating density of parasites available for transmission? What determines the order in which parasite variants rise in successive parasitemias? Dierent par- asite surface molecules may cause infection of dierent body compart- ments. The surface molecules that aect tissue tropism may also be strong antigenic determinants. I mentioned that diversifying tissue tro- pisms during the course of an infectioncandiversifyantigenic variation within the host.
Two small preliminary unblinded studies showed an anti-inflammatory effect of curcumin (90 buy 80 mg innopran xl with amex blood pressure good range,91) 40 mg innopran xl free shipping blood pressure 78 over 48. No large order 40 mg innopran xl overnight delivery arrhythmia guideline, double- blind purchase 80mg innopran xl with visa arteria auricular posterior, placebo-controlled studies have been performed to evaluate the clinical efficacy of this agent in rheumatic diseases. A Phase I clinical trial of curcumin in patients with premalignant disease in Taiwan showed that curcumin is well tolerated even in doses up to 8 g per day (89). Patient interest and use are high, as are the number of available products and practitioners, as well as the costs. The discussion in this chapter highlighted the evidence as it pertains to only a fraction of this vast topic: diets, dietary supplements, and herbal products and their role as therapies in rheumatic diseases. Scientific evidence does not support a substantial role of special diets or dietary manipulations in the treatment of the majority of patients suffering from arthritis and rheumatic diseases. The level of available evidence has not yet risen to the standards expected for pharmacological interventions However, taken broadly, vegetarian diets and those high in n-3 fatty acids are more likely to be beneficial than the traditional American diet. Laboratory data indicate that long-chain fatty acids play a role in inflam- mation, suggesting a credible pathophysiological pathway through which beneficial effects in inflammatory diseases might be mediated. However, the role of vitamin supplementation is not clear in the treatment of rheumatic diseases. There have not been adequate prospective observations to support the notion that vitamin supplementation beyond current federal recommendations is warranted in rheumatology patients. A considerable amount of work has been published regarding the effects of glucosamine and chondroitin. A variety of small, short-term trials of a variety of herbal supplements have appeared in the literature. Results of short-term trials may only reflect fluctuations in natural disease activity rather than representing true differences in long-term outcome. Unconventional medicine in the United States: prevalence, costs, and patterns of use. Trends in alternative medicine use in the United States, 19901997: results from a national survey. Advance Data From Vital and Health Statistics, Centers for Disease Control and Prevention 2004;343:120. Glucosamine, chondroitin sulfate and the two in combination for painful knee osteoarthritis. Placebo-controlled, blind study of dietary manipulation therapy in rheumatoid arthritis. Epidemiological studies in the Upernavik district, Greenland: incidence of some chronic diseases 19501974. Eicosapentaenoic acid inhibits antigen-presenting cell function of murine splenocytes. Effects of high-dose fish oil on rheumatoid arthritis after stopping non-steroidal anti-inflammatory drugs. Pathological indicators of degradation and inflammation in human osteoarthritis cartilage are abrogated by exposure to n-3 fatty acids. Effects of fish oil supplementation on non-steroidal anti-inflammatory requirement in patiens with mild rheumatoid arthritisa double-blind placebo-controlled trial. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects. Gammalinolenic acid treatment of fatigue associated with primary Sjogrens syndrome. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham study. Vitamin D is inversely associated with rheumatoid arthritis: results from the Iowa Womens Health Study. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Experimentally induced osteoarthritis in guinea pigs: metabolic responses in articular cartilage to developing pathology. Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model. Do antioxidant micronutrients protect against the devel- opment and progression of knee osteoarthritis? Review: oxygen and reactive oxygen species in cartilage degredation: friend or foes? A case-control study of serum tocopherol levels and the alpha- to gamma-tocopherol ratio in radiographic knee osteoarthritis: the Johnston County Osteoarthritis Project. Coordinated expression of matrix Gla protein is required during endochondral ossification for chondrocyte survival. Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability for peripheral effectiveness. Effects of glucosamine and chondroitin sulfate on mediators of osteoarthritis in cultured equine chondrocytes stimulated by use of recombinant equine interleukin-1b. Long-term effects of glucosamine sulphate on osteoarthrtitis progression: a randomized, placebo-controlled clinical trial. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind multicenter study versus placebo. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial. Advising patients who seek complementary and alternative medical therapies for cancer. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial. Ginger extract components suppress induction of chemokine expression in human synoviocytes. A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis. Benefit of an extract of Tripterygium Wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study. Avocado/soybean unsaponifiables increase aggrecan synthesis and reduce catabolic and proinflammatory mediator production by human osteoarthritic chondrocytes. Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip. Structural effects of avocado/soybean unsaponifiables on joint-space loss in osteoarthritis of the hip. Modulation of arachidonic acid metabolism by curcumin and related b-diketone derivatives: effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase. Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells.
Wear clothing that is appropriate to the climate and type of exercise you are doing (usually loose clothing is preferable) 80mg innopran xl fast delivery how is pulse pressure used as a diagnostic tool. Complete a few warm-up exercises to get your body ready to exercisethis may include some stretching or flexibility exercises order innopran xl 40mg line hypertension journal article, too generic innopran xl 40 mg overnight delivery arrhythmia flutter. As the pain or swelling settles innopran xl 40 mg with mastercard heart attack 720p movie, resume exercising gently, gradually building up the exercises as before and taking care to monitor the quality of the exercises. Leave out any specific activities that caused pain initially then add them back into the exercise program cautiously. A persons current activity level, fitness, and general health should be considered when setting realistic and achievable goals. The level of exercising and 72 Part I / Introduction to Rheumatic Diseases and Related Topics these goals should be low at first and then gradually increased, for comfort, safety, and to prevent the patient from becoming disillusioned if he or she does not quickly reach unrealistic targets. Assessment Existing levels of physical activity can be assessed using measurement tools such as the Minnesota Leisure Time Physical Activity Questionnaire (12) or the Rapid Assessment of Physical Activity (13). Alternatively, a simple way to estimate current activity levels is to keep a record of daily activities in an activity diary. However, the need to assess cardiorespiratory fitness depends on an individuals cardiovascular risk (see Practitioner Point 1). In general, men under age 50 and women under age 40 who have more than one risk factor should have a formal assessment of cardiorespiratory function before beginning a program involving moderate intensity exercise or physical activity. Practitioner Point 1: Assessing Cardiovascular Risk Men over age 50 and women over age 40 who have two or more of the following risk factors for cardiovascular disease should have their cardiorespi- ratory function assessed before undertaking a moderate exercise program: Hypertension (blood pressure > 160/90 mmHg) Serum cholesterol > 240 mg/dL (6. These determine the heart rate response to a submaximal work rate from which a prediction of aerobic fitness (i. Self-Monitoring People need to appreciate the difference between moderate and vigorous exercise so that they can exercise at an intensity that is suitable for their level of fitness. There are simple measures that can be used to gauge whether they are exercising appropriately. The Rating of Perceived Exercise requires individuals to rate their perception of intensity of exercise on a 15-point scale. This scale relates well to the physio- logical and psychological responses to exercise (16,17). In the initial stages of an exercise program, adhering to the talk test (a person should be able to carry on a conversation with someone else while exercising) indicates an appropriate intensity of exercise (18). Once baseline information has been collected and the goals of the exercise program identified between the health practitioner and the patient, a series of exercises may be prescribed and agreed on to achieve these aims. Exercise for Improving Joint Movement (see Patient Point 2, Practitioner Point 2) An adequate range of motion in all joints is needed to maintain function, balance, and agility. Loss of joint movement is often associated with pain, muscle weakness, functional limitations, and increased risk of falls. In arthritic joints, restriction of movement may result from the following: capsular distension from increased amounts of synovial fluid or synovial tissue; contraction of the capsule, periarticular ligaments, or tendons; or loss of articular cartilage with varying amounts of fibrosis or osseous ankylosis. Exercise and physical activity can help to reverse or minimize these effects, and intuitively, people realize that movement is beneficial for joints. However, concern and confusion may result if physical activity causes joint pain; even more so if rest eases it. In the absence of adequate education and advice, patients may interpret this as movement damaging the joint and surmise that reducing activity will prolong the life of the joint and modify (minimize) the disease process. In fact, movement helps reduce joint effusion (19) and protects the smooth joint cartilage covering the bones involved in articulation. Regular motion, compression, and decompression are required to stimulate remodeling and repair (20). Each day, weight- bearing and non-weight-bearing exercises and activities that move a joint through its full range of movement are necessary to maintain cartilage health (21). Movement maintains and restores adequate compliance and flexibility of the periarticular structures (joint capsule, ligaments, tendons, muscles) which are important for protecting joints from damaging stresses. People with rheumatic conditions should perform stretching exercises at least two to three times per week. Stretches should be performed in a slow, controlled manner (without bouncing) and be specific to a joint or muscle group (24). Stretches should be performed after warm-up exercises, which are low-intensity exercises that prepare the body for more vigorous activity by increasing circulation, body temperature, and tissue extensibility. By doing so, warm-up exercises help to minimize the risk of musculoskeletal injury (e. Each stretch should be held for 10 to 30 seconds at the end of the range of movement and gradually progressed to greater joint range. Joints that are hypermobile, deformed or subluxed, or vulnerable to injury as a result of effusion are easily overstretched and should be protected and exercised with care. Patient Point 2: Stretching Exercises Stretching or flexibility exercises improve joint mobility. There are several guidelines that should be followed when stretching: Stretching exercises should be completed after some gentle warm-up exercises. These are low-intensity exercises that prepare the body for exercise by increasing body temperature and increasing the extensibility of the tissues, thus preventing injury. Exercise for Improving Strength and Endurance (see Practitioner Point 3) Inactivity leads to muscle weakness and wasting owing to a reduction in muscle fiber size, capillary density, and deposition of fat and connective tissue in muscles that are often not used enough (2527). Considerable weakness has been shown in people with early arthritic disease (28) as well as in those with long-standing disease (5,6,29). Therefore, it is important for those with rheumatic disease to try to preserve or enhance their muscle strength by remaining as active as possible and/or completing strengthening exercises. The static stretch is held at or beyond initial limit to stretch periarticular structures and muscles to the point of mild discomfort (for 1030 seconds). This can produce muscle soreness if the forces produced by the bouncing movement are too great. Practitioner Point 3: Muscle Strengthening There are several types of muscle actions that can be used when prescribing strengthening exercises. Any changes in muscle force production in the initial stages of training (6 10 weeks) are attributed to neural changes that result in a higher numbers of motor units being recruited and/or a higher rate of motor unit firing (64). Asthe activation of the agonists is increased, a reduction of the antagonists occurs and coactivation of the synergists is improved. Different types of muscle actions (isometric, isotonic, and isokinetic) can be used to improve muscle functioning. The principle of overloadwhen the training load exceeds the daily load levelsshould also be employed to achieve the changes in the structure and function of the muscles needed. Additionally, the frequency and a progressive increase in the overall amount (volume) of each training session are important variables to optimize training stimuli (specificity of training). Strength-training specificity is important to consider, as different types of strength- ening exercises produce different results. Typically, the maximum load an individual can lift once through range before fatiguing is determined (i. This hypertrophic strength training increases muscle fiber size and is aimed at preventing muscle wasting and increasing muscle mass. This type of training can be used to improve functional activities such as standing up from a chair. This type of exercise improves repetitive activities such as stair climbing, or enhances the ability to hold static postures for a long time. Prescription of resistance exercises for patients with rheumatic disease should be based on careful assessment of an individuals current motor function (i.
Blood smears are usually nega- important in maintaining the cycle in some tive in all stages of infection with T generic innopran xl 80mg without a prescription heart attack yahoo answers. At some point innopran xl 40mg overnight delivery arrhythmia or panic attack, trypanosomes enter the central nervous system 40 mg innopran xl amex blood pressure of 130/80, but remain extracel- Cellular and Molecular Pathogenesis lular generic 80mg innopran xl visa hypertension renal failure, with serious pathological consequences for humans. Both male and female tsetse fies become contrast, humans and the numerous mam- infected by ingesting a blood meal from an mals introduced into Africa from Europe, 34 infected host. African trypanosomes have evolved 35 diately after they are ingested by the vector. The trypanosomes then develop into procy- clic trypomastigotes in the midgut of the fy, and continue to divide for approximately 10 days. When the division cycles are completed, the organisms migrate to the salivary glands, and transform into epimastigotes. This form, in turn, divides and transforms further into the metacyclic try- panosome stage, and is infective for humans and reservoir hosts. Impala, one of many reservoirs for Try- takes 25-50 days, depending upon the species panosoma brucei rhodesiense. African Trypanosomiasis 65 several molecular strategies enabling them to ertoire of antigenic variants of the blood- avoid elimination from the mammalian host; stream trypomastigotes is large, numbering varying the antigenicity of its surface protein in the hundreds. Antigenic variation is against a membrane-associated antigen of the one reason why vaccine development against 45 trypanosome referred to as the variant surface this pathogen has not progressed. Specifc IgG antibod- In addition to antigenic variation, certain ies destroy all clonal organisms sharing the genotypes of trypanosomes have the ability same surface protein (e. This antigen-antibody and the immune capabilities of the infected battle between parasite and host continues, individual. All nodes become enlarged, but until the infected individual is overcome by enlargement of the posterior cervical nodes 47 exhaustion due to glucose depletion and the is the most noticeable. This cervical lymph buildup of metabolic wastes from the parasite node enlargement is known as Winterbot- (Fig. Dysregulated infammation is the chief pathological correlate, with perivascular cuff- ing consisting of infltrates of glial cells, lym- phocytes, and plasma cells (Fig. Each peak of parasitemia represents loose their effectiveness during the chronic a new antigenic variant. Some patients develop rash, generalized pruritus, weight loss, and facial 55 Winterbottoms sign is charac- swelling. Masterman Winterbottom was an English physician and abolitionist who travelled to Clinical Disease the colony of the Sierra Leone Company and spent 4 years in Africa. Upon returning The disease caused by the two species of to England to take over his fathers medi- trypanosomes, although both called African cal practice, Dr. Winterbottom published a sleeping sickness, are very different in many description of diseases he had seen including ways. Infection rapidly progresses on to dis- West African trypanosomiasis and noted that ease with T. Central nervous system involve- When trypanosomes invade the central ment occurs some 3-4 weeks after infection. Focal seizures, tremors, may not involve the brain for months or even and palsies are also common. During the early stage there is intermittent fever, malaise, and joint pain that probably correlates with waves of parasitemia. It is during this time that gen- eralized enlargement of the lymph nodes 53 occurs and hepatosplenomegaly may occur. African Trypanosomiasis 67 Anemia is a complication of infection malarial parasites in the blood of a patient with T. Criti- tures are more sensitive than smears, since cal for selection of appropriate treatment for thick blood smears miss a large percent- both East African and West African trypano- 57 A number of screening age of infections. Antigen detection For treatment of West African sleeping testing is currently not routinely employed sickness, infection with T. An alternative therapy for early hemo- but this approach is still not widely used in lymphatic stage infection with T. Since parasites often are biense is suramin, which is equal in effcacy 70 present at only low concentrations, even in to pentamidine. Suramin as also frst line a patient dying of the disease, techniques to therapy for early stage East African sleep- improve the sensitivity of diagnosis such ing sickness. Large plasma cells containing eosinophilic inclusions, Mott cells, are uncommon but characteristic and likely represent cells with large amounts 66, 67 of IgM that they are unable to secrete. History of travel to endemic area, recall- ing a painful fy bite, and the presence of a chancre can lead the clinician to the diag- nosis. In early hemolymphatic stage East African sleeping sickness sura- migration of millions of individuals, placing 72, 73 them at high risk from a number of parasitic min is the preferred therapeutic agent. Tsetse fy control programs are of the infection as it does not cross the blood- also compromised in these same regions due 68 to political and economic instability, exac- brain barrier. For West African try- that a latent human reservoir and reactiva- panosomiasis, infection with T. Unfortunately, melarsoprol is the ing conficted areas cannot keep up with the only effective drug for treatment of T. Tsetse fies and mosquitoes do toxic drug is associated with encephalopathy not obey political boundaries, and thrive in 75 79 in about 3% of cases. Other protein antigens, particularly Previously, periods of political upheaval transporters on the membrane of the fagellar 83 in different parts of Africa have resulted in pocket and tubulin offer promise. Diagnos- dramatic increases in human cases of sleep- tic tests, other than microscopy, would help 77 in earlier patient diagnosis and control efforts ing sickness. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 2001, 4 (1), 50-65. Proceedings of the National Academy of Sciences of the United States of America 1985, 82 (10), 3380-4. Proceedings of the National Academy of Sciences of the United States of America 1993, 90 (16), 7809-13. Biology of the cell / under the auspices of the European Cell Biology Organization 1988, 64 (2), 109-19. Bulletin et memoires de lAcademie royale de medecine de Belgique 1996, 151 (2), 203-10. Discussion of the relevance of the trypanosome survey to the biology of large mammals in the Serengeti. Transactions of the Royal Society of Tropical Medicine and Hygiene 1990, 84 (6), 795-9. Control of Chagas disease requires constant vigilance Trypanosoma cruzi and has now re-emerged in countries that (Chagas 1909) previously reported that they had eliminated 19 transmission of the disease. Despite con- Introduction certed efforts at the clinical level to lower the mortality rate of chronic Chagas Disease, Trypanosoma cruzi is the causative agent acute Chagas disease can have a case fatal- of American trypanosomiasis, also known as 20 ity rate as high as 5%. Oral transmission to humans of this parasite often leads to life-threatening American trypanosomiasis has transformed disease. Chagas disease is one of the worlds this disease from one restricted to certain geo- 7-9 leading causes of cardiomyopathy. Oral transmission is likely the most ica, where according to the Global Burden of frequent mechanism in non-human mam- Disease study it infects approximately 9-10 mals, and is now linked to several outbreaks 10-12 million people. Still another results in over $7 billion in economic losses transmission route of increasing importance 13 annually. In Texas, there is strong evidence that transmis- sion occurs within the state, where a high 16 percentage of dogs is also infected. Through globalization, Chagas disease cases are also now found in Southern Europe (especially Spain and Portugal), and even Australia and Japan, although there is no disease transmis- 17 sion in these areas. Thatched roofs speculated that humans were likely to be of rural houses can harbor large numbers of infected as well.