A review of the physiology of fever in birds

While fever is known to occur in invertebrates and vertebrates, the mechanisms of fever in animals other than mammals have received scant attention. We look initially at the recognition, by the avian immune system, of pathogen associated molecular patterns and the likely role of toll-like receptors in signaling the presence of bacteria and viruses. Several mediators of fever are subsequently released by immune cells, including interleukin-6 and interleukin-1β, that eventually reach the brain and alter thermoregulatory function. As is the case in mammals, prostaglandins appear to be the ultimate mediators of fever in birds, since the febrile response is attenuated when prostaglandin synthesis is inhibited. Ambient temperature modulates the fever response, with larger fevers at higher, and smaller fevers at lower ambient temperatures. Glucocorticoid levels are increased during fever and seem to play an important role by modulating the extent of fever generation, possibly playing a role in the attenuation of fever after repeated exposure to a pathogen in a process termed tolerance, suggesting that the fever process can be phenotypically adapted to likely future conditions. While fever has an ancient phylogenetic history and many of the underling mechanisms in birds appear similar to mammals, there are several important differences that suggest fever has evolved quite differently in these two homeothermic classes.     

Fever: is it beneficial?

Data obtained in lizards infected with live bacteria suggest that fever may be beneficial to their survival. An adaptive value of fever has also been inferred in mammals, but the results are equivocal. Findings that certain leukocyte functions are enhanced in vitro at high temperatures have provided a possible explanation for the alleged benefits of fever. However, serious questions exist as to whether results from experiments in ectotherms and in vitro can properly be extrapolated to in vivo endothermic conditions. Indeed, various studies have yielded results inconsistent with the survival benefits attributed to fever, and fever is not an obligatory feature of all infections under all conditions. Certainly, the widespread use of antipyretics, without apparent adverse effects on the course of disease, argues against fever having great benefit to the host. In sum, although fever is a cardinal manifestation of infection, conclusive evidence that it has survival value in mammals is still lacking.     

Serotyping Coxiella burnetii isolates from acute and chronic Q fever patients by using monoclonal antibodies

Abstract Four mouse monoclonal antibodies reacting with Coxiella burnetii lipopolysaccharide antigens were produced and used in serotyping 17 C. burnetii isolates from acute Q fever and Q fever endocarditis patients in France. Two monoclonal antibodies (1B2 and 3B6) were considered specific for the Priscilla strain, a representative of Q fever endocarditis isolates, and did not react with the Nine Mile strain, which is representative of acute Q fever isolates. Monoclonal antibodies Nos. 1B2 and 3B6 reacted with 75% (3/4) acute Q fever isolates and 85% (11/13) of endocarditis isolates from France. It is reasonable to conclude that Priscilla-like strains cause both acute Q fever and Q fever endocarditis. The hypothesis that Priscilla-like strains only are associated with Q fever endocarditis should be reconsidered.     

Visceral Leishmaniasis without Fever in an 11-Month-Old Infant: a Rare Clinical Feature of Kala-azar

Visceral leishmaniasis or kala-azar is an endemic parasitic disease in some parts of the world which is characterized by fever, splenomegaly, and pancytopenia in most of the cases. Herein we report an 11 month-old male infant with diagnosis of kala-azar who presented with pallor, hepatosplenomegaly, failure to gain weight, and no history of fever. Surprisingly, fever started after beginning of meglumine antimoniate treatment in this patient. As far as we are aware of, this is a rare presentation of visceral leishmaniasis. Therefore, clinicians especially in endemic areas are highly recommended to include kala-azar among differential diagnosis of unexplained anemia without fever to prevent misdiagnosis of this potentially fatal, but treatable condition.     

Discriminating Fever Behavior in House Flies

Fever has generally been shown to benefit infected hosts. However, fever temperatures also carry costs. While endotherms are able to limit fever costs physiologically, the means by which behavioral thermoregulators constrain these costs are less understood. Here we investigated the behavioral fever response of house flies (Musca domestica L.) challenged with different doses of the fungal entomopathogen, Beauveria bassiana. Infected flies invoked a behavioral fever selecting the hottest temperature early in the day and then moving to cooler temperatures as the day progressed. In addition, flies infected with a higher dose of fungus exhibited more intense fever responses. These variable patterns of fever are consistent with the observation that higher fever temperatures had greater impact on fungal growth. The results demonstrate the capacity of insects to modulate the degree and duration of the fever response depending on the severity of the pathogen challenge and in so doing, balance the costs and benefits of fever.     

A role for natriuretic peptide in lipopolysaccharide-induced fever in Pekin ducks (Anas platyrhynchos): is natriuretic peptide an endogenous antipyretic in birds?

The febrile mechanism in all vertebrates involves endogenous molecules which mediate and attenuate the fever response. This mechanism is considered phylogenetically conserved, and the molecules are thought to be analogous in different species. The above notion is supported by evidence which show avian and mammalian fevers to have similar mediators. There is, however, a paucity of information regarding the modulators of the avian febrile response. Natriuretic peptides were shown to modulate mammalian fevers and, although natriuretic peptides are also present in birds, they have never been investigated in the context of fever. We induced fever in Pekin ducks with lipopolysaccharide and, at the same time, treated the animals with natriuretic peptide antiserum at a dose that effectively inhibited the known renal actions of endogenously secreted natriuretic peptide. We compared fever responses after ducks received either the antiserum or an appropriate control along with the lipopolysaccharide. The antiserum did not attenuate the fever responses of ducks. Our results differ from the results of a study in rats, which demonstrated natriuretic peptides to be potently antipyretic. This molecule seems to be antipyretic in mammals but not in ducks. We suggest a species variation regarding the ability of natriuretic peptides to modulate fever.     

RHEUMATIC FEVER IN COLLEGE STUDENTS

The results of three independent surveys concerned with rheumatic fever and heart disease in students at the University of California were assembled and found to be in close agreement. A full 2 per cent of all students believed they had had rheumatic fever; and several times that proportion gave a history of one of the rheumatic manifestations. Only 0.25 per cent had demonstrable rheumatic heart disease and 0.1 per cent had congenital heart disease.Physiologic murmurs may occur in 3 per cent or more of students entering college.Penicillin prophylaxis is important in persons with rheumatic heart disease, but it is important not to put a label of rheumatic heart disease on persons who think they have had rheumatic fever but who have no demonstrable heart disease. Long term penicillin prophylaxis or other long term prophylactic procedures directed against rheumatic fever are not indicated unless the diagnostic criteria for rheumatic fever are clearly met or unless rheumatic heart involvement is definitely present.     

Acute rheumatic fever

While rheumatic fever is relatively uncommon except where there are poor and crowded living conditions, sporadic acute attacks continue to occur in a family or pediatric medical practice. The physician''s role in management of the sore throat in the diagnosis of suspected cases of rheumatic fever and in follow-up for continued prophylaxis is discussed. The frequency of admissions and presenting features of 159 patients with acute rheumatic fever is reviewed. Continued surveillance is required if we are to achieve a further reduction in attack rate and complications.     

Diverse and atypical manifestations of Q fever in a metropolitan city hospital: Emerging role of next-generation sequencing for laboratory diagnosis of Coxiella burnetii

Although Q fever has been widely reported in the rural areas of China, there is a paucity of data on the epidemiology and clinical characteristics of this disease in large metropolitan cities. In this study, we profile the epidemiology and clinical manifestations of Q fever from a tertiary hospital in Shenzhen, a Southern Chinese metropolitan city with a large immigrant population from other parts of China. A total of 14 patients were confirmed to have Q fever during a nine-year-and-six-month period, five of whom were retrospectively diagnosed during case review or incidentally picked up because of another research project on unexplained fever without localizing features. Some patients had the typical exposure histories and clinical features, while a few other patients had rare manifestations of Q fever, including one with heart failure and diffuse intracapillary proliferative glomerulonephritis, a patient presenting with a spontaneous bacterial peritonitis-like syndrome, and another one with concomitant Q fever and brucellosis. Using a combination of clinical manifestation, inflammatory marker levels, echocardiographic findings and serological or molecular test results, nine, three and two patients were diagnosed to have acute, chronic and convalescent Q fever, respectively. Seven, five and two patients were diagnosed to have Q fever by serological test, nested real-time PCR and next-generation sequencing respectively. Diverse and atypical manifestations are associated with Q fever. The incidence of Q fever is likely to be underestimated. Next-generation sequencing is becoming an important diagnostic modality for culture-negative infections, particularly those that the physicians fail to recognize clinically, such as Q fever.     

Infective endocarditis caused by Arcanobacterium haemolyticum: a case report

Typhoid fever is a very common infectious disease, particularly in developing countries such as Sri Lanka. Although multiple organs are known to be affected by the disease, hepatic involvement could be considered the most important as studies have showed that it is associated with a higher relapse rate. We report a young patient who presented with fever and jaundice and found to have cholestatic hepatitis secondary to typhoid fever.     

Cells That Trigger Fever

Bacterial lipopolysaccharide (LPS) is recognized by several receptors, including the toll-like receptor (TLR) 4, on various cells. Among many biological responses to LPS is fever, an often polyphasic rise in body temperature that is thought to be mediated by prostaglandin (PG) E2. Which receptors on which cells are linked to fever production is unknown. It is also unknown which cells produce PGE2 that triggers the earliest (first) phase of fever. Two recent studies from our group answer these questions. In the first one, we studied LPS-induced fever in mouse chimeras selectively lacking the TLR4 in hematopoietic or nonhematopoietic cells. We found that the first phase of fever is triggered via the TLR4 on hematopoietic cells. In the second study, we investigated LPS fever in rats. We found that the number of cells expressing cyclooxygenase (COX)-2, a PGE2-synthesizing enzyme, surged at the onset of fever in the lung and liver (but not in the brain), and that most of these cells were macrophages. Because LPS-induced PGE2 production in macrophages is TLR4-dependent, it is tempting to speculate that the TLR4-bearing, bone marrow-derived cells implicated in fever pathogenesis by the first study are the same as the COX-2-positive macrophages identified in the second study. Hence, pulmonary and hepatic macrophages that recognize LPS via the TLR4 and rapidly produce PGE2 are likely triggers of the fever response.     

Infektionsgefahr aus dem Süden. Globale Erwärmung

The import of infectious diseases from the Mediterranean region is a possible effect of global warming. At the moment, vector‐borne diseases represent the most important threat. These include tick‐borne Mediterranean spotted fever as well as visceral Leishmaniasis and Pappataci‐fever, which are transmitted by sand flies. Dogs act as main reservoir hosts for the first two diseases; therefore, these pathogens are constantly imported to Germany with unregulated dog transports. In the same way, the vector of Mediterranean spotted fever, the “Brown dog tick”, is imported and may establish in the future. Sandflies, in contrast, are already endemic in the Rhine valley, the warmest region of Germany. Autochthonous cases of Leishmaniasis and Pappataci‐fever indicate that these diseases are already present in Germany.     

神经外科重症监护室发热及其治疗

发热是神经外科重症监护室(Neurosurgical intensive care unit,NICU)最常见的症状之一,它是人体对损伤的保护性反应,但同时又加重了机体的负担,从而恶化临床结局。NICU发热起因复杂并相互交错,仅少部分有特异性表现,并且总上而言处理困难。因此系统地了解发热的起因、处理以及预后是非常重要的。尽管过去的文献对于发热已有很好的研究,然而缺乏对NICU发热的系统性描述。我们通过回顾文献系统性地总结了NICU发热,旨在进一步增进对NICU发热的认识从而有利于临床诊治。     

Yellow fever in Africa: public health impact and prospects for control in the 21st century

In the last two decades, yellow fever re-emerged with vehemence to constitute a major public health problem in Africa. The disease has brought untold hardship and indescribable misery among different populations in Africa. It is one of Africa's stumbling blocks to economic and social development. Despite landmark achievements made in the understanding of the epidemiology of yellow fever disease and the availability of a safe and efficacious vaccine, yellow fever remains a major public health problem in both Africa and America where the disease affects annually an estimated 200,000 persons causing an estimated 30,000 deaths. Africa contributes more than 90% of global yellow fever morbidity and mortality. Apart from the severity in morbidity and mortality, which are grossly under reported, successive outbreaks of yellow fever and control measures have disrupted existing health care delivery services, overstretched scarce internal resources, fatigued donor assistance and resulted in gross wastage of vaccines. Recent epidemics of yellow fever in Africa have affected predominantly children under the age of fifteen years. Yellow fever disease can be easily controlled. Two examples from Africa suffice to illustrate this point. Between 1939 and 1952, yellow fever virtually disappeared in parts of Africa, where a systematic mass vaccination programme was in place. More recently, following the 1978-1979 yellow fever epidemic in the Gambia, a mass yellow fever vaccination programme was carried out, with a 97% coverage of the population over 6 months of age. Subsequently, yellow fever vaccination was added to the EPI Programme. The Gambia has since then maintained a coverage of over 80%, without a reported case of yellow fever, despite being surrounded by Senegal which experienced yellow fever outbreaks in 1995 and 1996. The resurgence of yellow fever in Africa and failure to control the disease has resulted from a combination of several factors, including: 1) collapse of health care delivery systems; 2) lack of appreciation of the full impact of yellow fever disease on the social and economic development of the affected communities; 3) insufficient political commitment to yellow fever control by governments of endemic countries; 4) poor or inadequate disease surveillance; 5) inappropriate disease control measures, and 6) preventable poverty coupled with misplaced priorities in resource allocation. Yellow fever can be controlled in Africa within the next 10 years, if African governments seize the initiative for yellow fever control by declaring an uncompromising resolve to control the disease, the governments back up their resolve with an unrelenting commitment and unwavering political will through adequate budgetary allocations for yellow fever control activities, and international organisations, such as WHO, UNICEF, GAVI, etc., provide support and technical leadership and guidance to yellow fever at risk countries. Over a ten-year period, of stage-by-stage mass yellow fever vaccination campaigns, integrated with successful routine immunisation, Africa can bring yellow fever under control. Subsequently, for yellow fever to cease being a public health problem, Africa must maintain at least an annual 80% yellow fever vaccine coverage of children under the age of 1 year, and sustain a reliable disease surveillance system with a responsive disease control programme. This can be achieved at an affordable annual expenditure of less than US$1.00 per person per year, with a reordering of priorities.     

Yellow fever and dengue—the interactions of virus,vector and host in the re-emergence of epidemic disease

The incidence of the mosquito-borne flavivirus diseases, yellow fever, dengue and dengue hemorrhagic fever has increased dramatically in recent years. Both diseases are characterized by the emergence of explosive epidemics. Yellow fever outbreaks appear to have a periodicity dependent upon fluctuations in sylvatic (enzootic) transmission cycles and the ecological factors that influence these cycles. Spread of the virus from the sylvatic cycle to human settlements, ultimately with interhuman transmission by domestic Aedes aegypti is a repeating event in Africa, and presents a renewed threat in the Americas, where effective Ae. aegypti control collapsed in the 1970s. The incidence of dengue has also increased dramatically in recent years, with up to 80 million persons living in tropical regions of the world now affected annually—an attack rate of 4%. The severe form, dengue hemorrhagic fever (DHF) has become a leading health problem throughout Asia in the last 20 years and is emerging as an epidemic disease in the Americas. Unlike yellow fever, sylvatic dengue transmission cycles are not responsible for disease emergence. The major factors underlying dengue epidemics are changes in human ecology, increasing contact with Ae. aegypti, the co-circulation of multiple dengue serotypes, and a rising prevalence of immunity and immunopathological events that underlie the pathogenesis of DHF. In this review, the complex interplay of virus, host, vector, environment and weather in the ecology of yellow fever and dengue are explored.     

Clinical and Epidemiological Features of Typhoid Fever in Pemba,Zanzibar: Assessment of the Performance of the WHO Case Definitions

Background

The gold standard for diagnosis of typhoid fever is blood culture (BC). Because blood culture is often not available in impoverished settings it would be helpful to have alternative diagnostic approaches. We therefore investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever.

Methodology/Principal Findings

Participants with a body temperature ≥37.5°C or a history of fever were enrolled over 17 to 22 months in three hospitals on Pemba Island, Tanzania. Clinical signs and symptoms of participants upon presentation as well as blood and serum for BC and Widal testing were collected. Clinical signs and symptoms of typhoid fever cases were compared to other cases of invasive bacterial diseases and BC negative participants. The relationship of typhoid fever cases with rainfall, temperature, and religious festivals was explored. The performance of the WHO case definitions for suspected and probable typhoid fever and a local cut off titre for the Widal test was assessed. 79 of 2209 participants had invasive bacterial disease. 46 isolates were identified as typhoid fever. Apart from a longer duration of fever prior to admission clinical signs and symptoms were not significantly different among patients with typhoid fever than from other febrile patients. We did not detect any significant seasonal patterns nor correlation with rainfall or festivals. The sensitivity and specificity of the WHO case definition for suspected and probable typhoid fever were 82.6% and 41.3% and 36.3 and 99.7% respectively. Sensitivity and specificity of the Widal test was 47.8% and 99.4 both forfor O-agglutinin and H- agglutinin at a cut-off titre of 1∶80.

Conclusions/Significance

Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test.     

Rheumatic fever in Southern California; problems related to diagnosis

Rheumatic fever occurs in native of Southern California and is a cause of death. The incidence of streptococcosis in Los Angeles is approximately equal to that in three other major cities in the United States where rheumatic fever is known to occur commonly. Manifestations of rheumatic fever may range from mild to severe. It is suggested that a greater percentage of patients in Southern California have symptoms of rheumatic fever that are more mild. Differentiation between prolonged, uncomplicated streptococcosis and rheumatic fever is a major problem. The judicious use of a battery of tests, acute phase reactants, on the same blood sample will frequently help to establish the diagnosis in borderline situations so common to Southern California.     

The climatic factors affecting dengue fever outbreaks in southern Taiwan: an application of symbolic data analysis

Background

Dengue fever is a leading cause of severe illness and hospitalization in Taiwan. This study sought to elucidate the linkage between dengue fever incidence and climate factors.

Results

The result indicated that temperature, accumulated rainfall, and sunshine play an important role in the transmission cycles of dengue fever. A predictive model equation plots dengue fever incidence versus temperature, rainfall, and sunshine, and it suggests that temperature, rainfall, and sunshine are significantly correlated with dengue fever incidence.

Conclusions

The data suggests that climate factors are important determinants of dengue fever in southern Taiwan. Dengue fever viruses and the mosquito vectors are sensitive to their environment. Temperature, rainfall and sunshine have well-defined roles in the transmission cycle. This finding suggests that control of mosquito by climatic factor during high temperature seasons may be an important strategy for containing the burden of dengue fever.