Immune-complexes-mediated evasion of Plasmodium knowlesi from destruction by macrophages

The role of immune-complexes in the evasion of Plasmodium knowlesi from destruction by macrophages was studied in vitro. Incubation of macrophages with immune-complexes, prepared either by mixing total parasite antigens soluble in culture medium with normal or immune monkey serum, or by polyethylene glycol precipitation of serum from monkeys acutely infected with P. knowlesi, significantly reduced both the pool size of the macrophages that bound parasitized erythrocytes, and the number of parasitized erythrocytes bound per macrophage. Parasitized erythrocytes with mature schizonts were invariably preferred over those containing rings. These observations appear to indicate that during P. knowlesi infection in rhesus monkeys, immune-complexes may inhibit the binding of parasitized erythrocytes with mononuclear phagocytes and thus may enable them to evade the destructive mechanisms mounted by the host.     

Serum leptin levels in wild and captive populations of baboons (papio): implications for the ancestral role of leptin

Leptin has emerged as the major lipostat, regulating adiposity by affecting feeding behavior and thermogenesis. Leptin levels in normal-weight Western humans and in captive rodents are 5-15 ng/ml. But evidence suggests that these levels are abnormally high and that leptin may have evolved as a more general metabolic signal, with its most robust effects at lower levels. If this is true, then wild, healthy animal populations should have lower levels of leptin than captive populations and Western Man. We examined leptin levels in wild, East African populations of baboons (Papio anubis, P. hamadryas, and anubis/hamadryas hybrids). Serum leptin levels averaged less than 1 ng/ml, and no differences occurred in leptin levels among the species. In wild baboons, serum leptin levels were highest in the youngest baboons, with a trend toward an inverse relation between dental age and serum leptin levels. In comparison, captive baboons had levels about three times higher than wild baboons, with a clear inverse relation between age and leptin levels. These results support the view that leptin evolved to be effective at low levels.     

Treatment of schistosomiasis mansoni and japonica in baboons with tubercidin given by direct intravenous injection.

Baboons (Papio cyanocephalus and P. anubis), infected with Schistosoma mansoni or S. japonicum, were treated with single doses of tubercidin (7-deazaadenosine; Tu), 1, 3, and 5 mg per kg of body weight, administered by intravenous drip. Crystalline Tu was dissolved in sterile 0.9% NaCl solution (1 mg per ml), and the solution was delivered at a rate of 4 ml per minute. Detectable short-term host toxicity was limited to the 5 mg per kg dose, mainly in the form of reversible mild to moderate kidney damage. Only this 5 mg per kg dose administered to baboons with relatively heavy S. mansoni infections was capable of completely suppressing fecal egg excretion for 6 to 8 weeks, eliminating the female worms, and terminating active disease, as indicated by histopathological findings. Comparable effects were achieved following the administration of the 3 mg per kg dose to baboons with moderate to heavy S. japonicum infections.     

Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening.

BACKGROUND: Until recently, Plasmodium knowlesi malaria in humans was misdiagnosed as Plasmodium malariae malaria. The objectives of the present study were to determine the geographic distribution of P. knowlesi malaria in the human population in Malaysia and to investigate 4 suspected fatal cases. METHODS: Sensitive and specific nested polymerase chain reaction was used to identify all Plasmodium species present in (1) blood samples obtained from 960 patients with malaria who were hospitalized in Sarawak, Malaysian Borneo, during 2001-2006; (2) 54 P. malariae archival blood films from 15 districts in Sabah, Malaysian Borneo (during 2003-2005), and 4 districts in Pahang, Peninsular Malaysia (during 2004-2005); and (3) 4 patients whose suspected cause of death was P. knowlesi malaria. For the 4 latter cases, available clinical and laboratory data were reviewed. RESULTS: P. knowlesi DNA was detected in 266 (27.7%) of 960 of the samples from Sarawak hospitals, 41 (83.7%) of 49 from Sabah, and all 5 from Pahang. Only P. knowlesi DNA was detected in archival blood films from the 4 patients who died. All were hyperparasitemic and developed marked hepatorenal dysfunction. CONCLUSIONS: Human infection with P. knowlesi, commonly misidentified as the more benign P. malariae, are widely distributed across Malaysian Borneo and extend to Peninsular Malaysia. Because P. knowlesi replicates every 24 h, rapid diagnosis and prompt effective treatment are essential. In the absence of a specific routine diagnostic test for P. knowlesi malaria, we recommend that patients who reside in or have traveled to Southeast Asia and who have received a "P. malariae" hyperparasitemia diagnosis by microscopy receive intensive management as appropriate for severe falciparum malaria.     

The use of SIV-infected rhesus monkeys for the preclinical evaluation of AIDS drugs and vaccines.

Macaque monkeys infected with the simian immunodeficiency virus (SIV) can be used for preclinical testing of drugs and vaccines against acquired immunodeficiency syndrome (AIDS) as well as for the study of AIDS pathogenesis. A number of pathogenic SIV strains that have been well characterized molecularly and biologically are available for animal infection studies. Data generated from in vitro drug sensitivity assays have established, for many classes of compounds, a similar degree of antiviral efficacy against both HIV-1 and the SIVs, although some examples of selective inhibitors of HIV-1 now are known. A number of virus and host parameters have been defined that provide suitable biological endpoints for in vivo efficacy studies during acute and chronic infection of macaque monkeys. Vaccine studies in SIV-infected monkeys have provided hope that immune protection against lentiviruses is possible; SIV systems are playing a major role in systematically comparing various vaccine strategies to determine correlates of immunity and the protection required for mucosal versus parenteral routes of infection. Societal pressures and the expanding AIDS epidemic will continue to encourage early testing of experimental drugs and vaccines in human clinical trials, however, as more data validating the SIV system are generated, the utility of the SIV model in preclinical development likely will become apparent. Impetus to evaluate therapies in this model system will increase if the current method of testing in humans does not identify more effective AIDS therapies in the near future.     

Evidence of trapped red cells in the brain of rhesus monkey infected with Plasmodium knowlesi

59Fe-labelled normal red cells and 51Cr-labelled P. knowlesi infected red cells were used as tracers for a study on the trapped red cells in the brain of rhesus monkeys infected with P. knowlesi. After instantaneous injection into a common carotid artery, blood was sampled from both of the internal jugular veins at various intervals. Results in 6 experiments on 3 infected monkeys showed that about 17% of infected red cells given was trapped in the capillaries of the brain of the infected monkeys. The remainder of the infected red cells travelled on the same flow rate as the normal red cells. As the volume for the flow of the former was less than that of the latter, the mean transit time of the infected red cells (-ty) was therefore shorter than that of the normal red cells (-th). The mean difference in volume was estimated to be 3.4% in the present study. These findings indicated that some of the P. knowlesi infected red cells were trapped in capillaries of the brains of monkeys infected with P. knowlesi.     

The Baboon (Papio spp.) as a Model of Human Ebola Virus Infection

Baboons are susceptible to natural Ebola virus (EBOV) infection and share 96% genetic homology with humans. Despite these characteristics, baboons have rarely been utilized as experimental models of human EBOV infection to evaluate the efficacy of prophylactics and therapeutics in the United States. This review will summarize what is known about the pathogenesis of EBOV infection in baboons compared to EBOV infection in humans and other Old World nonhuman primates. In addition, we will discuss how closely the baboon model recapitulates human EBOV infection. We will also review some of the housing requirements and behavioral attributes of baboons compared to other Old World nonhuman primates. Due to the lack of data available on the pathogenesis of Marburg virus (MARV) infection in baboons, discussion of the pathogenesis of MARV infection in baboons will be limited.     

Experimental infection of baboons (Papio cynocephalus anubis) with Chlamydia pneumoniae strain 'TWAR'

Two infant baboons (Papio cynocephalus anubis) were inoculated with Chlamydia pneumoniae strain 'TWAR', one in the conjunctiva, nasopharynx and oropharynx, the other in the trachea. Both remained well during 8 weeks of observation. C. pneumoniae infection persisted for at least 8 weeks after inoculation. Chlamydia pneumoniae seems to be of low virulence in baboons and capable of causing chronic infection.     

A comparison of hemoglobin A1c in human and baboon blood.

Cation exchange chromatography was performed on hemolysates prepared from human and baboon (Papio anubis) blood. In humans with diabetes mellitus and in baboons with pancreatectomy induced diabetes mellitus there were significant increases in Hbs A1, A1c, and A1a +A1b. The quantity of Hb A1 and Hb A1c in nondiabetic baboons was approximately one-half the quantity of Hb A1 and Hb A1c in nondiabetic humans. These differences may be explained by the differences in survival time between human and baboon red cells.     

Differences in burst morphology among baboon species

Baboon species differ markedly in the proportions of fetal hemoglobin (HbF) they produce in response to hemopoietic stress. Bone marrow erythroid progenitor cells from untreated and stressed baboons of three species were cultured to determine if differences in number, size, or other characteristics of the colonies and bursts could be correlated with the HbF response. BFU-E from adult Papio cynocephalus produced high proportions of macroscopic, well-hemo-globinized bursts, whereas those from P. anubis and P. papio produced only small, moderately hemoglobinized bursts. The species-specific differences in burst characteristics did not correlate with the in vivo HbF response to stress and they were not altered by variations in culture conditions. However, bone marrow BFU-E from P. anubis and P. cynocephalus fetuses produced similar bursts, suggesting developmental regulation of progenitor cell growth patterns. The proportions of macroscopic bursts were reduced in P. cynocephalus animals undergoing hemopoietic stress, suggesting that culture is a more severe erythropoietic stress for P. anubis and P. papio BFU-E than for P. cynocephalus BFU-E.     

Virus-provoked rhinitis in patients who have allergies.

The most common illnesses in humans are the respiratory tract infections caused by viruses. When limited to the upper respiratory region, these infections often are designated as "a common cold." Viruses commonly associated with these upper respiratory infections (URI) include rhinoviruses (RVs), respiratory syncytial virus, influenza virus, parainfluenza virus, corona virus, and adenoviruses. Clinical observations have suggested that patients with allergic rhinitis and asthma experience more pronounced symptoms during a viral URI than patients who do not have allergies and who are infected with the same virus under similar circumstances. Using an experimental virus infection model in human volunteers with and without allergic rhinitis, several groups of clinical investigators have studied the effects of experimental RV infections. These observations indicate that the experimental virus infection may induce host responses that provoke enhanced immunoglobulin E (IgE) synthesis. Whether this translates into enhanced symptoms has been suggested in one study but not in another. This article will review these studies, which suggest that it is the host response to the virus and not the virus itself that plays the major role in symptom pathogenesis.     

Schistosoma mansoni: anti-SMw32 proteinase response in vaccinated and challenged baboons

Antibodies to a cysteinyl proteinase of the trematode Schistosoma mansoni have been detected in serum from infected mice and humans. We have evaluated antiproteinase responses in infected baboons and in baboons vaccinated with irradiated, cryopreserved schistosomules prior to challenge. Prechallenge sera and normal, uninfected control sera were nonreactive by ELISA and immunoblots. Serum antibodies were first detectable by ELISA at two months post-challenge in both challenged (C) and vaccinated-challenged (V-C) baboons (serum dilution 1:200). By four months post-challenge, ELISA absorbance values for subgroup C baboons were significantly higher than for V-C counterparts. The immunoblot technique provided a more sensitive means of detecting antibody early in the infection. One month post-challenge, 7 of 12 C and V-C sera (diluted 1:100) contained measurable anti-proteinase antibody. By month two, 12 of 12 were immunoblot-positive. Baboons vaccinated but not challenged (subgroup V) remained negative. The presence of the anti-proteinase antibody appears to be a sensitive and early marker for infection by S. mansoni.     

Immune response and tolerance during chronic hepatitis B virus infection

The hepatitis B virus (HBV) is a hepatotropic non-cytopathic DNA virus that despite the presence of an effective prophylactic vaccine is estimated to infect 300 million people, with a particularly high prevalence in Asia and Africa. It causes liver diseases that vary greatly in severity from person to person. Some subjects control infection efficiently and clear the virus from the bloodstream either without clinically evident liver disease or with an acute inflammation of the liver (acute hepatitis) that can resolve without long-term clinical sequelae. Other patients fail to clear the virus and develop chronic infection. Most chronically infected patients remain asymptomatic without life-threatening liver disease but 10–30% develop liver cirrhosis with possible progression to liver cancer . Outcome of infection and the pathogenesis of liver disease are determined by virus and host factors, which have been difficult tofully elucidate because the host range of HBV is limited to man and chimpanzees. However, the study of animal models of related Hepadnavirus infections and transgenic mouse able to express individual HBV genes or replicate the entire viral genome have clarified several aspects connected to HBV infection. Furthermore, the ability to analyze many immunological phenomena ex vivo through direct quantification of Ag-specific T cells in humans and chimps has considerably increased our knowledge of HBV pathogenesis. Here, we will discuss the distinctions of HBV adaptive immunity between resolved and persistently infected patients and the host/viral factors that can cause and maintain them.     

Renal plasma flow in rhesus monkeys infected with Plasmodium knowlesi

Renal plasma flow was studied in six rhesus monkeys before and during infection with Plasmodium knowlesi using 125I-sodium orthoiodohippurate (125I-OIH) as a tracer. The mean renal plasma flow and the rate constant from the intravascular compartment to the kidneys were significantly reduced in the infected monkeys. As both intravascular and extravascular compartments were slightly but not significantly elevated, which resulted in the prolonged mean transit time of 125I-OIH in monkeys infected with P. knowlesi. The parasitemia showed a reverse relationship with the renal plasma flow and a direct relationship with the mean transit time. These findings indicated that the renal plasma flow in the infected monkeys was depressed in proportion to the number of P. knowlesi parasites. The mechanism of reduced renal plasma flow was probably due to renal vasoconstriction.     

克雷伯杆菌肺炎278例的临床分析

目的 了解肺炎克雷伯杆菌肺部感染的患病情况及临床特点.方法 对我院2008年至2010年278例住院患者中肺炎克雷伯杆菌肺部感染者,从临床资料,病史、症状、体征、肺部影像学改变、痰细菌培养、药敏实验及影响预后的相关因素等方面分析肺炎克雷伯杆菌肺部感染的临床特征.结果 本组278例肺炎克雷伯杆菌肺部感染的患病率为23.1％.患者中86.0％为医院内获得性感染;有95.7％的患者存在基础疾病.肺炎克雷伯杆菌肺部感染常于基础疾病的急性期、慢性疾病的急性加重期或迁延期起病.临床症状、体征与常见医院内获得性肺炎相似.肺部X线影像学以两肺小片状浸润影多见(80.2％).结论 肺炎克雷白杆菌是医院内获得性感染的重要致病菌之一.常引起住院患者,特别是高龄、慢性基础疾病及危重症者的肺部感染.     

Speciation in the baboon and its relation to gamma-chain heterogeneity and to the response to induction of HbF by 5-azacytidine

In the baboon (Papio species), the two nonallelic gamma-genes produce gamma-chains that differ at a minimum at residue 75, where isoleucine (I gamma-chain) or valine (V gamma) may be present. This situation obtains in baboons that are sometimes designated as Papio anubis, Papio hamadryas, and Papio papio. However, in Papio cynocephalus, although the I gamma-chains are identical with those in the above mentioned types, the V gamma-chains have the substitutions ala----gly at residue 9 and ala----val at residue 23. The V gamma-chains of P. cynocephalus are called V gamma C to distinguish them from the V gamma A-chains of P. anubis, etc. A single cynocephalus animal has been found to have only normal I gamma-chains and I gamma C-chains (that is, glycine in residue 9, valine in 23, and isoleucine in 75). When HbF is produced in response to stress with 5-azacytidine, P. anubis baboons respond with greater production than do P. cynocephalus, and hybrids fall between. Minimal data on P. hamadryas and P. papio suggest an even lower response than P. cynocephalus. As HbF increases under stress, the ratio of I gamma to V gamma-chains changes from the value in the adult or juvenile baboon toward the ratio in the newborn baboon. However, it does not attain the newborn value. The V gamma A and V gamma C-genes respond differently to stress. In hybrids, the production of V gamma A- chains exceeds that of V gamma C-chains. A controlling factor in cis apparently is present and may be responsible for the species-related extent of total HbF production. It may be concluded that the more primitive the cell in the erythroid maturation series that has been subjected to 5-azacytidine, the more active is the I gamma-gene.     

Epidemiology of herpesvirus papio infection in a large captive baboon colony: similarities to Epstein-Barr virus infection in humans

The epidemiology of herpesvirus papio, a lymphocryptovirus similar to Epstein-Barr virus (EBV), was studied in a captive colony of >1900 baboons. Herpesvirus papio IgG antibody titers were measured by IFA. In total, 438 specimens from 296 baboons were assessed, including 116 serial specimens from 52 juveniles and 6 infants studied monthly for 1 year following birth and at age 18 months. Maternally derived antibody reached a nadir at 4 months of age. About 75% of animals at 12 months of age and >95% of animals after age 24 months demonstrated serologic evidence of herpesvirus papio infection. After age 3 years, the geometric mean titer was 1:60-75. The epidemiology of herpesvirus papio infection in baboons closely parallels that of EBV infection in humans. An animal model of lymphocryptovirus infection will facilitate investigations of human lymphocryptovirus biology.