Neuroinvasion by Mycoplasma pneumoniae in Acute Disseminated Encephalomyelitis

We report the autopsy findings for a 45-year-old man with polyradiculoneuropathy and fatal acute disseminated encephalomyelitis after having Mycoplasma pneumoniae pneumonia. M. pneumoniae antigens were demonstrated by immunohistochemical analysis of brain tissue, indicating neuroinvasion as an additional pathogenetic mechanism in central neurologic complications of M. pneumoniae infection

Response of religious groups to HIV/AIDS as a sexually transmitted infection in Trinidad

BACKGROUND: HIV/AIDS-related stigma and discrimination are significant determinants of HIV transmission in the Caribbean island nation of Trinidad and Tobago (T&T), where the adult HIV/AIDS prevalence is 2.5%. T&T is a spiritually-aware society and over 104 religious groups are represented. This religious diversity creates a complex social environment for the transmission of a sexually transmitted infection like HIV/AIDS. Religious leaders are esteemed in T&T's society and may use their position and frequent interactions with the public to promote HIV/AIDS awareness, fight stigma and discrimination, and exercise compassion for people living with HIV/AIDS (PWHA). Some religious groups have initiated HIV/AIDS education programs within their membership, but previous studies suggest that HIV/AIDS remains a stigmatized infection in many religious organizations. The present study investigates how the perception of HIV/AIDS as a sexually transmitted infection impacts religious representatives' incentives to respond to HIV/AIDS in their congregations and communities. In correlation, the study explores how the experiences of PWHA in religious gatherings impact healing and coping with HIV/AIDS. METHODS: Between November 2002 and April 2003, in-depth interviews were conducted with 11 religious representatives from 10 Christian, Hindu and Muslim denominations. The majority of respondents were leaders of religious services, while two were active congregation members. Religious groups were selected based upon the methods of Brathwaite. Briefly, 26 religious groups with the largest followings according to 2000 census data were identified in Trinidad and Tobago. From this original list, 10 religious groups in Northwest Trinidad were selected to comprise a representative sample of the island's main denominations. In-depth interviews with PWHA were conducted during the same study period, 2002–2003. Four individuals were selected from a care and support group located in Port of Spain based upon their perceived willingness to discuss religious affiliation and describe how living with a terminal infection has affected their spiritual lives. The interviewer, a United States Fulbright Scholar, explained the nature and purpose of the study to all participants. Relevant ethical procedures associated with the collection of interview data were adopted: interviews were conducted in a non-coercive manner and confidentiality was assured. All participants provided verbal consent, and agreed to be interviewed without financial or other incentive. Ethics approval was granted on behalf of the Caribbean Conference of Churches Ethics Committee. Interview questions followed a guideline, and employed an open-ended format to facilitate discussion. All interviews were recorded and transcribed by the interviewer. RESULTS: Religious representatives' opinions were grouped into the following categories: rationale for the spread of HIV/AIDS, abstinence, condom use, sexuality and homosexuality, compassion, experiences with PWHA, recommendations and current approach to addressing HIV/AIDS in congregations. Religious representatives expressed a measure of acceptance of HIV/AIDS and overwhelmingly upheld compassion for PWHA. Some statements, however, suggested that HIV/AIDS stigma pervades Trinidad's religious organizations. For many representatives, HIV/AIDS was associated with a promiscuous lifestyle and/or homosexuality. Representatives had varying levels of interaction with PWHA, but personal experiences were positively associated with current involvement in HIV/AIDS initiatives. All 4 PWHA interviewed identified themselves as belonging to Christian denominations. Three out of the 4 PWHA described discriminatory experiences with pastors or congregation members during gatherings for religious services. Nonetheless, PWHA expressed an important role for faith and religion in coping with HIV. CONCLUSION: Religious groups in Trinidad are being challenged to promote a clear and consistent response to the HIV/AIDS epidemic; a response that may reflect personal experiences and respect religious doctrine in the context of sex and sexuality. The study suggests that (1) religious leaders could improve their role in the fight against HIV/AIDS with education and sensitization-specifically aimed at dismantling the myths about HIV transmission, and the stereotyping of susceptible sub-populations, and (2) a consultative dialogue between PWHAs and religious leaders is pivotal to a successful faith-based HIV intervention in Trinidad

A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice

No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals

Challenge of SARS-CoV– or Mock-Immunized Mice with the Lethal MA15 Virus

<p>Groups of eight mice (8 wk old) were immunized intranasally with 50 μL of SARS-CoV (Urbani) (10⁵TCID₅₀/mouse) or L15 tissue culture media. Four weeks after immunization, mice were challenged intranasally with 50 μL MA15 virus (10^6.9 TCID₅₀/mouse), weighed daily, and observed twice daily for morbidity and mortality. Surviving mice that lost in excess of 20% initial body weight were euthanized. Symbols represent mean values for SARS-CoV–immunized mice (triangles) and mock-immunized mice (circles). Error bars indicate standard error.</p

Histopathology and Immunohistochemical Localization of SARS-CoV Antigens in the Lungs of Mice Infected with MA15 Virus

<div><p>Abundant necrotic cellular debris (arrows) in alveoli (A) and a bronchiole lumen (B) of mice at days 2 and 3 p.i., respectively. Abundant SARS-CoV antigens (arrowheads) within alveolar pneumocytes (C) and in necrotic alveolar and bronchiolar cellular debris in mice at day 2 p.i. (D).</p><p>(A and B) Hematoxylin and eosin stain; (C and D) primary antibody, rabbit anti-SARS-CoV antibody; secondary antibody conjugated with alkaline phosphatase with naphthol fast-red and hematoxylin counterstain; original magnifications ×100. Mice were inoculated with 10^5.6 TCID₅₀ MA15 virus/mouse.</p></div

Schematic Diagram of SARS-CoV Genome Indicating Mutations Found in MA15 Virus

<div><p>(A) The 29,727 nucleotide positive-sense RNA genome of SARS-CoV is depicted in this to-scale drawing with ORFs indicated by shaded boxes (dark gray, structural and non-structural proteins; light gray, accessory genes X1–X5 [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0030005#ppat-0030005-b037" target="_blank">37</a>]; and straight lines, non-coding regions). Asterisks indicate the sites of the six nucleotide changes (compared with the published SARS-CoV (Urbani) sequence) resulting in six coding mutations found in the mouse-adapted SARS-CoV (MA15).</p><p>(B) The six mutations found in MA15. ^aORF, open reading frame. ^bCDS, coding sequence, sequence of nucleotides that corresponds with the sequence of amino acids in a protein (location includes start and stop codon). ^cnsp, non-structural protein, cleavage product of ORF 1ab; Main^pro, main 3C-like protease; Hel, helicase. ^dRBM, receptor binding motif (amino acids 424–494).</p></div

Virus Titers in Lungs of BALB/c Mice Inoculated with SARS-CoV or MA15 Virus

<p>Data represents a compilation of two experiments. In each experiment, groups of four mice were inoculated intranasally with 50 μL of SARS-CoV (Urbani) (10^5.0 TCID₅₀/mouse, black bars) or MA15 virus at lethal (10^5.6 TCID₅₀/mouse, white bars) or sub-lethal (10^3.6 TCID₅₀/mouse, light gray bars) doses. Mice were sacrificed on indicated d.p.i. Mice receiving lethal doses of MA15 virus did not survive beyond day 4. Bars represent mean viral titers; error bars indicate standard error. Asterisks indicate significant differences (<i>p</i> < 0.05) compared with titers in mice receiving lethal doses of MA15 virus. Dotted line indicates lower limit of detection (10^1.5 TCID₅₀/g).</p