To characterize the immune response in haemorrhagic fever with renal syndrome, serial changes in immune effector cells were measured in 14 patients. Significant findings included initial elevations of all major leucocyte populations, increases in suppressor T cells and B cells, decreases in helper/suppressor cell ratios, and a dramatic increase in activated T cells. These changes were most marked in severely ill patients. Changes reverted to normal over approximately one week.

Adult↗

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Platelet dysfunction contributes to the haemostatic defect in haemorrhagic fever with renal syndrome.

To characterize further the nature of haemostatic impairment in haemorrhagic fever with renal syndrome, we assessed platelet function in 9 patients in whom the diagnosis was serologically confirmed. Defective platelet aggregation was demonstrated in every patient. An abnormality of the granule release reaction was demonstrated in all of 7 patients tested. Gel-filtered platelets from a normal subject showed normal aggregation in plasma from a patient with impaired aggregation, which is evidence for an intrinsic platelet defect, and against the presence of a circulating inhibitor in this patient.

Adenosine Diphosphate↗

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Viruses and hemostasis.

The great majority of viral infections are not associated with significant alterations in hemostasis. Occasionally, common viral pathogens lead to illnesses in which hemostatic impairment is an important feature. In these instances, two clinical syndromes usually are present: thrombocytopenic purpura and disseminated intravascular coagulation. Immune mechanisms are implicated in the first, while the second is associated with severe disease. Hepatitis viruses produce hemorrhage by a third mechanism. In cases of fulminant hepatitis, hepatocellular injury leads to decreased production of multiple coagulation factors and impairment of other hepatic functions that modulate hemostasis. A small number of viruses stand apart by virtue of the frequency with which they cause hemorrhage. These are the hemorrhagic fever viruses. Much more needs to be learned about how these viruses cause disease and induce hemorrhage. The first line of therapy in viral infections complicated by hemorrhage is early treatment with an antiviral agent. Unfortunately, effective antiviral therapy is usually not available. There is little useful information and no controlled studies on the efficacy of therapy aimed directly at correcting hemostatic impairment.

Blood Coagulation Factors↗

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Replication of hemorrhagic fever viruses in monocytic cells.

Monocytes play a central role in protection against many viruses. In some infections they are target cells for viral replication. There is increasing evidence that these cells may also be important in regulation of hemostasis. The part played by monocytic cells in the pathogenesis of hemorrhage in the viral hemorrhagic fevers is presently uncertain. Monocytes and monocytic cell lines have been used to investigate the ability of viruses to infect these cells in vitro. Several factors may affect the ability of a particular virus to infect monocytic cells, including specific antiserum to virus and the degree of cellular maturation. The effect of cellular maturation on the replication of Rift Valley fever virus in the U937 cell line is discussed in light of studies on the infectivity of other viruses for monocytic cells. Data supporting the ability of specific antibody to enhance the infectivity of Pichinde virus and Lassa fever virus for U937 cells are presented.

Antibodies, Viral↗

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Hemostatic derangement produced by Rift Valley fever virus in rhesus monkeys.

Rift Valley fever (RVF) is an important cause of disease in animals and humans in sub-Saharan Africa. In a small percentage of human cases, the disease is complicated by hemorrhage, which often is associated with a fatal outcome. Inoculation of rhesus monkeys with the Zagazig Hospital strain of RVF virus produced a clinical picture similar to illness in humans. Ten of 17 monkeys developed clinical evidence of hemostatic impairment. When coagulation tests were performed, this group of monkeys had significant abnormalities, including evidence for disseminated intravascular coagulation. These abnormalities were much less pronounced in the remaining seven monkeys-whose only sign of illness was transient fever-and, in general, they paralleled the level of viremia and the degree of elevation in levels of serum hepatic enzymes. Autopsy of the three monkeys with severe disease revealed hepatic necrosis.

Animals↗

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Prevention of Rift Valley fever in rhesus monkeys with interferon-alpha.

Prophylactic and therapeutic efficacy of recombinant leukocyte A interferon (rIFN-alpha A) and Sendai virus-induced human leukocyte interferon (HuIFN-alpha) administered intramuscularly to Rift Valley fever virus (RVFV)-infected rhesus monkeys was studied. Clinical, virologic, immunologic, and hemostatic parameters were monitored. Five daily inoculations of 5 X 10(5) units of either interferon product per kilogram of body weight, initiated 24 hours before or 6 hours after RVFV infection, prevented or greatly suppressed viremia. No clinical signs of disease or laboratory evidence of impaired hemostasis was observed. Serum neutralizing antibody to RVFV was detected within 6 days of virus inoculation. Prophylactic administration of 5 X 10(4) or 5 X 10(3) units of rIFN-alpha A per kilogram also limited viremia, hepatocellular damage, and hemostatic derangement. Untreated, RVFV-infected, control monkeys developed high-titered viremia, clinical disease, and impaired hemostasis. These data suggest that rIFN-alpha A and HuIFN-alpha are effective in protecting RVFV-infected rhesus monkeys from viremia and hepatocellular damage and may be beneficial in human RVF infection.

Animals↗

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Hemorrhage in hemorrhagic fever with renal syndrome in China.

Hemorrhage is a prominent feature of hemorrhagic fever with renal syndrome (HFRS) in China. It occurs in all phases of the disease and is an important cause of death. Petechiae involving skin and oropharyngeal mucosa are the commonest manifestation of hemorrhage, occurring in more than 90% of patients. Gastrointestinal hemorrhage is the next commonest manifestation, occurring in approximately 50% of patients. Suggested mechanisms of hemorrhage include vascular injury, thrombocytopenia and platelet dysfunction, disseminated intravascular coagulation, circulating heparin-like activity, and uremia. Controlled trials of treatment regimens for hemostatic impairment in HFRS have not been performed. Support of blood pressure can lessen hemorrhage by limiting the adverse consequences of hypotension and shock. Dialysis is of benefit in patients with hemorrhage and significant renal failure.

Cerebral Hemorrhage↗

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The reemergence of dengue in China.

In 1978, dengue was reported in China for the first time in 32 years. Since then, epidemics involving hundreds of thousands of people have occurred in Guangdong and Guangxi provinces and on Hainan Island. These epidemics were caused by all four types of dengue virus. Aedes aegypti was the vector in coastal areas, while Aedes albopictus was the vector in inland regions. During these epidemics, case rates were very high (greater than 50%) in some areas. Case-fatality rates were generally less than 0.1% except during the 1986 outbreak on Hainan Island, when the rate was 0.25%. Hemorrhagic disease occurred in both children and adults. On Hainan Island, hemorrhagic disease was more than three times as common in the 1986 outbreak as in the 1980 outbreak; the 1980 outbreak was caused by dengue virus type 3 and the 1986 outbreak by dengue virus type 2. The weight of the evidence suggests that the reemergence of dengue in China resulted from the introduction of the infection by travelers and refugees from areas of Asia where dengue is endemic.

Aedes↗

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Mechanisms of disease in Hantavirus infection: pathophysiology of hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease that occurs over wide areas of Europe and Asia. Hantaviruses are the cause of this syndrome. The hallmark of HFRS is the triad of fever, hemorrhage, and renal failure. In its severe form it is associated with significant mortality. The syndrome evolves through five phases: febrile, hypotensive, oliguric, diuretic, and convalescent. The central physiologic derangement in HFRS is vascular dysfunction, manifested by impaired vascular tone and increased vascular permeability. The systemic effects of this dysfunction account for the occurrence of hypotension and shock, while local effects are probably important in the development of renal failure. Shock in HFRS has distributive and oligemic features, while renal failure has features of acute tubular necrosis. Hemorrhage is a consequence of vascular injury and a deficit of functional platelets. Vascular and platelet dysfunction are both compounded by uremia. Disseminated intravascular coagulation contributes to hemorrhage in some patients. Although hantaviruses are infectious for endothelial cells and may cause direct injury, a large body of evidence suggests that immune mechanisms play an important role in the pathogenesis of HFRS.

Acute Kidney Injury↗

PubMedDate not supplied

Long-term survival in Wiskott-Aldrich syndrome: case report and literature review.

The case reported concerns a 29-year-old man who was seen because of clinical and laboratory features consistent with Wiskott-Aldrich Syndrome. While an infant he underwent splenectomy for thrombocytopenia. Evaluation revealed small platelets, abnormal immunoglobulin levels, impaired delayed hypersensitivity, and mildly reduced neutrophil chemotaxis. His response to vaccination with polyvalent pneumococcal vaccine was subnormal. Possible factors accounting for his long-term survival are discussed.

Adult↗