Ecology of hantaviruses in Mexico: Genetic identification of rodent host species and spillover infection

In our recent epidemiological survey conducted in Mexico for hantavirus infection, we identified three distinct viruses circulating in Mexican wild rodents, namely Montano virus (MTNV), Huitzilac virus (HUIV), and Carrizal virus (CARV). To gain a detailed understanding of hantavirus epidemiology and its associated hosts, 410 rodents were captured at eight collecting points in Morelos and Guerrero, Mexico, and examined for hantavirus seroprevalence, the presence of viral RNA, and rodent host species identification using cytochrome b gene sequences. Of the 32 species captured, seven species were positive for hantavirus: Peromyscus beatae (31/127; 24.4%), Reithrodontomys sumichrasti (6/15; 40%), Reithrodontomys megalotis (2/25; 8%), Peromyscus aztecus evides (1/1; 100%), Peromyscus megalops (1/41; 2.4%), Megadontomys thomasi (1/9; 11.1%), and Neotoma picta (1/6; 16.7%), with an overall prevalence of 10.5%; virus genome persisted in the majority of seropositive rodents. Nucleotide sequence and phylogenetic analysis showed that the viruses belonged mainly to the three lineages previously identified. The data showed that MTNV and CARV were primarily carried by P. beatae and R. sumichrasti, respectively. In addition, the data revealed an apparent complex interaction between hantaviruses and their hosts, suggesting active transmission and/or spillover infections within sympatric rodent species.     

Rheumatoid factor is correlated with disease activity and inflammatory markers in antineutrophil cytoplasmic antibody-associated vasculitis

Background

Some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) also have positivity of rheumatoid factor (RF). However, the clinical significance of this occurrence remains unknown in AAV patients. The aim of this study was to clarify an association between the presence of RF and clinical features in patients with AAV.

Results

Forty-seven patients diagnosed with AAV who were not complicated with RA were enrolled in this study. We compared clinical manifestations of AAV between an RF-positive subset (n?=?29) and an RF-negative subset (n?=?18). The Birmingham Vasculitis Activity Score (BVAS) was higher (P?=?0.026) in the RF-positive subset than in the RF-negative subset. The levels of CRP and ESR were higher in the RF-positive patients (P?=?0.020 and P?=?0.007, respectively) compared to the RF-negative subset. IgM-RF titers were significantly correlated with the BVAS (r?=?0.50, P?=?0.0004). In addition, the IgM-RF titers had significant correlations with the levels of CRP (r?=?0.41, P?=?0.004), ESR (r?=?0.39, P?=?0.016), IgM (r?=?0.36, P?=?0.016) and IgG (r?=?0.37, P?=?0.015). The frequency of commencement of dialysis therapy, usage of mechanical ventilation and mortality were higher in the RF-positive subset than in the RF-negative subset.

Conclusions

In patients with AAV, RF titers were significantly correlated with disease activity and the levels of inflammatory markers. The presence of RF could be a poor prognostic factor in patients with AAV.

     

Efficacy and safety of combination therapy with mizoribine and methotrexate for rheumatoid arthritis resistant with methotrexate

Background. MZB is a purine analog, and is used as a disease modifying anti-rheumatic drug (DMARD). We conducted an open label uncontrolled clinical trial to evaluate the efficacy and safety of combination therapy with methotrexate (MTX) and mizoribine (MZB). Methods. Thirty one RA patients (9 males, 22 females, 68±12 year-old) who fulfilled ACR criteria of RA and did not show sufficient clinical response to MTX were included. MZB (150 mg/day, once a day) were added to MTX. DAS28-CRP was measured at day 0 and 1, 3, 6, and 12 months after the treatment. Adverse events were recorded. Results. Overall DAS28-CRP was significantly decreased from 4.4±1.0 to 3.1±1.3 at 3 months (p<0.01), 2.7±0.68 at 6 months (p<0.01), 2.4±1.4 at 12 months (p<0.01). Seventeen patients (55%) achieved significant improvement of DAS28-CRP. Number of swollen joints of responders before the treatment was significantly fewer than that of non-responders. Improvement of DAS28-CRP was significantly different between the responders (0.91±0.74) and non-responders (0.18±0.66) at 1 month (p<0.01). Nine patients (29%) could achieve remission Four patients experienced adverse events. Conclusions. MTX and MZB combination therapy was effective and relatively safety.     

Acute intrahepatic cholestasis accompanied with Chlamydophila pneumoniae infection

We report a case of Chlamydophila (C.) pneumoniae infection presenting with fever and rapid intrahepatic cholestasis. A 63-year-old man had a week-long history of intermittent high fever and rapidly progressive jaundice with atypical erythema. The results of liver function tests were recorded. The results of all serological tests were negative; the IgM, IgG, and IgA titers for C. pneumoniae had increased, which indicates a C. pneumoniae infection. The patient's fever and liver dysfunction improved upon administration of minocycline. Light microscopic findings showed the presence of enlarged liver cells with clear cytoplasm, a few mitotic figures, multinucleated cells, and bile cholestasis. The electron microscopic appearance of liver biopsy showed that bile canaliculi exhibited intrahepatic forms of cholestasis. From the results of light and electron microscopy, we inferred atypical intrahepatic cholestasis, probably resulting from the C. pneumoniae infection.     

Seroepidemiological study in a Puumala virus outbreak area in South-East Germany

Puumala virus (PUUV) is the cause of the majority of haemorrhagic fever with renal syndrome cases in Germany. In 2004, a nephropathia epidemica outbreak was recorded in Lower Bavaria, South-East Germany. For a seroepidemiological study in this region including the resident population at four locations (n = 178) and soldiers from one location (n = 208) indirect immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assays (ELISAs) and immunoblot tests based on a yeast-expressed PUUV nucleocapsid protein were established. The validation using human serum panels originating from Germany revealed a diagnostic sensitivity and specificity of 98/100% for the IgM ELISA, 99/99% for the IgG ELISA, 99/100% for the IgM immunoblot test and 100/96% for the IgG immunoblot test. Using the novel IgG assays as well as a commercial IgG ELISA and an immunofluorescence assay for the resident population an average prevalence of 6.7% (12 of 178) with a range of 0% (0 of 21) to 11.9% (7 of 59) was observed. Positive serological results were equally distributed between males and females with an average age of 63 for males and 52 for females. The seroprevalence in the soldier group was found to be about 1% with one positive male of 203 (age 46 years) and one positive female of five (age 47 years). In conclusion, the PUUV seroprevalence in the residents of the outbreak region in Lower Bavaria was found to be up to fivefold higher than the average hantavirus seroprevalence of the German population.     

Atypical metastatic carcinoid of the uterine cervix and review of the literature

Atypical carcinoid tumors of the uterine cervix represent rare neuroendocrine tumors and are highly aggressive, showing early lymphatic invasion and hematogenous distant metastases. Because of the small number of cases, there are currently no recommendations regarding treatment, and little is known about the response to chemotherapeutic agents. A 39-year-old woman was diagnosed with a primary atypical carcinoid of the uterine cervix with numerous metastases to the liver. After radical hysterectomy, she underwent hepatic arterial chemoembolization with streptozotocin and 5-fluorouracil. Complete response was achieved in numerous liver metastases. At the 2-year follow up of chemotherapy, the patient remains alive. Treatment for atypical carcinoid tumors remains elusive, however hepatic arterial chemoembolization with streptozotocin and 5-fluorouracil was effective in the present primary atypical carcinoid with liver metastases. A review of the previous reports is also presented.     

An anatomic study of the attachments on the condylar process of the mandible: muscle bundles from the temporalis

Purpose

The aim of this study was to evaluate anatomically the relationship between bone and muscles by detailed observation of the bone shape and the structure of muscles to facilitate an understanding of the function of the muscles involved in jaw movement.

Methods

36 specimens of 24 Japanese cadavers were examined. The insertion areas were marked using a radiopaque marker and examined by micro-computed tomography. For morphological observation, we used 101 condylar processes. In addition, we made histological sections in some specimens to observe the detailed attachments of the muscle.

Results

Based on the micro-CT images and dissection findings, the lateral pterygoid muscle was found to be most frequently inserted into the anterior impression and attached to the medial impression of the process. According to the histological observations, the lateral pterygoid muscle mainly inserted to the condylar process. The micro-CT images indicated that the obvious bony ridge was lateral to the pterygoid fovea on the condylar process in all specimens. The midmedial muscle bundle of the temporalis was attached to the ridge. Based on the morphological observations, the ridge was situated on the lateral area of the condylar process.

Conclusions

Since dysfunction of the temporomandibular joint is likely closely related to both the lateral pterygoid muscle and also the temporalis, further studies are necessary to evaluate the function of these muscles and consider jaw movement.

     

Isolation of vaccine-derived type 1 polioviruses displaying similar properties to virulent wild strain Mahoney from sewage in Japan

Type 1, 2, and 3 vaccine-derived polioviruses were isolated from a sewage disposal plant located downstream of the Oyabe River in Toyama Prefecture, Japan, between October 1993 and September 1995. Neurovirulence was analyzed in 13 type 1 vaccine-derived strains, using mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC). Nine strains (69%) were estimated to have marked neurovirulence. Some of the neutralizing antigenic sites, temperature sensitivity, and plaque-forming ability of two virulent vaccine-derived poliovirus strains were similar to Mahoney strain. The neutralizing activity of human sera obtained after oral poliomyelitis vaccine (OPV) administration against one of the virulent vaccine-derived polioviruses was examined. Although all human sera showed sufficient neutralizing activity for the prevention of poliomyelitis by vaccine-derived poliovirus strains, a lower titer than that against Sabin type 1 strain was observed. Vaccination against virulent vaccine-derived poliovirus will be effective. However, the environmental presence of viruses that have properties similar to those Mahoney strain is a threat. The introduction of inactivated poliovirus vaccine (IPV), and well-maintained herd immunity, together with reinforced environmental surveillance is important for the final phase of the polio eradication program by the World Health Organization (WHO).     

Neutralizing antibody responses to human herpesviruses 6 and 7 do not cross-react with each other, and maternal neutralizing antibodies contribute to sequential infection with these viruses in childhood

Seroprevalence of human herpesvirus 6 (HHV-6) and HHV-7 infections is very high throughout the world, and almost all people are exposed first to HHV-6 and second to HHV-7 in their childhood. However, it is not clear whether the neutralizing (NT) antibody response between each virus is cross-reactive or not. To elucidate the NT antibody response between each virus, 55 serum samples from an adult group (subjects 22 to 88 years old) and 60 serum samples from a young group (subjects 2 to 18 years old) were examined by a dot blot method for detecting viral late antigen. Thirty-nine serum samples obtained from cord bloods and a few serum samples obtained from pediatric patients with exanthem subitum were also examined to assess the maternal transferred NT antibodies against each virus. The NT antibody titers against HHV-7 in the adult group remained high throughout all the individuals, and none were negative. Those against HHV-6 were high values in the young group but low values, including negative values (three samples), in the adult group. These results suggested that the NT antibody response to either HHV-6 or HHV-7 in each individual was specific to each virus and did not cross-react with each other. In the adult group, the NT antibody response to HHV-6 decreased, while that to HHV-7 remained high throughout all the individuals. Maternal transferred NT antibody titers against HHV-7 were higher and remained longer after birth than those of HHV-6, and these findings were in accord with the clinical observation that HHV-6 infection usually occurs earlier than HHV-7 infection.