A Series of Haemophilus parainfluenzae Surgical Infections and Review of the Literature.

Background: Haemophilus parainfluenzae (HPI) is a rare and underreported pathogen. Haemophilus parainfluenzae causes respiratory, soft tissue, and central nervous system (CNS) infections, and endocarditis. Little data on HPI surgical infections are available, especially for intra-abdominal infections (IAI). Patients and Methods: Haemophilus parainfluenzae isolates were recovered from patients treated at a rural hospital during a two-year period. Isolation and identification of the pathogen was done according to standard guidelines. A literature review with regard to HPI IAI was done. Results: A total of 273 HPI isolates were analyzed, 15 patients had double isolates; HPI was commonly part of a mixed infection. Respiratory tract infections accounted for 64.8%, ear-nose-throat (ENT)/eye infections for 17.9%, genital/urologic infections for 3%, blood stream infections for 1% of cases and 13.2% of HPI isolates involved surgical infections. Thirty-four patients (36 isolates) had HPI surgical infections including 28 skin/soft tissue infections, two bone infections, two perirectal abscesses, one infected hemodialysis catheter, and three IAIs including perforated appendicitis, perforated diverticulitis, and a pelvic abscess 10 days after laparoscopic appendectomy. All three IAIs were mixed infections and successfully managed with percutaneous drainage and antibiotic therapy. More than 90% of HPI isolates in our hospital tested negative for ß-lactamase production. A literature review revealed 32 reported cases of HPI IAI including biliary infections (12), peritonitis (9), liver abscess (7), and IA abscess (4) with the majority being monomicrobial; treatment included antibiotic agents and surgery/intervention in most cases. Outcomes were generally favorable. Conclusions: Our study confirms data from the literature that HPI is capable of causing a variety of severe surgical infections. More research with regard to this pathogen is warranted.

Yellow fever 17-D vaccine is neurotropic and produces encephalitis in immunosuppressed hamsters.

Immunosuppressed (cyclophosphamide) adult golden hamsters inoculated intraperitoneally (i.p.) with wild-type Asibi yellow fever virus (YFV) developed a rapidly fatal illness. Histopathologic and immunohistochemical studies of tissues from these animals showed typical hepatic changes of severe yellow fever (inflammation, hepatocyte necrosis, and steatosis) without brain involvement. In contrast, 50% of immunosuppressed hamsters receiving the YFV-17D-attenuated vaccine developed a slowly progressive encephalitic-type illness. Brain tissue from these latter animals revealed focal neuronal changes, inflammation, and YFV antigen-positive neurons; however, the liver and spleen appeared normal. YFV was isolated from brain cultures of many of these animals. Immunocompetent (non-immunosuppressed) hamsters inoculated with both viruses developed a subclinical infection. Results of this study indicate that wild-type YFV is hepatotropic in immunosuppressed hamsters, whereas the attenuated YFV-17 is primarily neurotropic. These findings support current recommendations against yellow fever vaccination of immunosuppressed/immunocompromised people and suggest that this hamster model might be useful for monitoring the safety of other live-attenuated YFV vaccines.

Efficacy of the antipoxvirus compound ST-246 for treatment of severe orthopoxvirus infection.

Efficacy of the new antipoxvirus compound ST-246 was evaluated as treatment of monkeypox (MPX) virus infection in a ground squirrel model of the disease. Ground squirrels were given a lethal dose of MPX virus and were then treated orally at various times post-inoculation (pi) with 100 mg/kg/day of ST-246. Morbidity and mortality, clinical laboratory results, viral load, and pathology of placebo and treatment groups were compared. All animals that started treatment with ST-246 on days 0, 1, 2, and 3 pi survived lethal challenge with MPX virus; 67% of animals treated on day 4 pi also survived. In contrast, 100% of the placebo group died. Most of the ST-246-treated animals showed no evidence of clinical disease or alteration of baseline clinical laboratory values and had minimal histopathologic changes. These results suggest that ST-246 is a promising candidate for early treatment of severe orthopoxvirus infection.

Dhori virus (Orthomyxoviridae: Thogotovirus) infection in mice: a model of the pathogenesis of severe orthomyxovirus infection.

After intranasal, subcutaneous, or intraperitoneal infection with Dhori virus (DHOV), adult mice developed a fulminant and uniformly fatal illness with many of the clinical and pathologic findings seen in mice infected with H5N1 highly pathogenic avian influenza A virus. Histopathologic findings in lungs of DHOV-infected mice consisted of hemorrhage, inflammation, and thickening of the interstitium and the alveolar septa and alveolar edema. Extra-pulmonary findings included hepatocellular necrosis and steatosis, widespread severe fibrinoid necrosis in lymphoid organs, marked lymphocyte loss and karyorrhexis, and neuronal degeneration in brain. Similar systemic histopathologic findings have been reported in the few fatal human H5N1 cases examined at autopsy. Because of the relationship of DHOV to the influenza viruses, its biosafety level 2 status, and its similar pathology in mice, the DHOV-mouse model may offer a low-cost, relatively safe, and realistic animal model for studies on the pathogenesis and management of H5N1 virus infection.

Effects of immunosuppression on West Nile virus infection in hamsters.

A research study, comparing the pathogenesis of experimental West Nile virus (WNV) infection in immunocompetent and immunosuppressed golden hamsters, is described. Cyclophosphamide was used to immunosuppress the animals. The immunosuppressed hamsters had a prolonged period of viremia, depressed humoral immune response, more extensive and severe pathology, and higher fatality rate than the untreated immunocompetent animals. Histopathological and immunohistochemical studies of tissues from the two groups showed that pathologic changes in the untreated infected animals were confined to the brain and spinal cord, whereas the histopathological changes and WNV antigen distribution in the immunosuppressed animals were much more extensive and diffuse, involving the adrenal, kidney, heart and lung, and brain and spinal cord. Results of this study in the hamster model provide insight into the increased severity of WNV infection observed in immunosuppressed people.

Clinical laboratory, virologic, and pathologic changes in hamsters experimentally infected with Pirital virus (Arenaviridae): a rodent model of Lassa fever.

The clinical laboratory, virologic, and pathologic changes occurring in hamsters after infection with Pirital virus (Arenaviridae) are described. Pirital virus infection in the hamsters was characterized by high titered viremia, leukocytosis, coagulopathy, pulmonary hemorrhage and edema, hepatocellular and splenic necrosis, and marked elevation of serum transaminase levels. All of the animals died within 9 days. The clinical and histopathological findings in the Pirital virus-infected hamsters were very similar to those reported in severe human cases of Lassa fever, suggesting that this new animal model could serve as a low-cost and relatively safe alternative for studying the pathogenesis and therapy of Lassa fever.