John T. Sinnott

Rapidly Progressive Herpetic Retinal Necrosis: A Blinding Disease Characteristic of Advanced AIDS

Eleven patients with rapidly progressive herpetic retinal necrosis (RPHRN) complicating AIDS were investigated retrospectively to study the disease spectrum, systemic involvement, and therapy. The mean CD4 cell count was 24/microL. There was a characteristic disease pattern with rapid progression, 82% bilaterality, relative resistance to intravenous antiviral therapy, and 70% retinal detachment. Varicella-zoster virus was the probable cause in 10 patients (detected by polymerase chain reaction in two eyes investigated), and herpes simplex virus was the probable cause in one. Cutaneous zoster occurred previously in 73% but was not concurrent. Seventy-three percent had central nervous system disease, possibly virus-related. RPHRN may be a local herpetic recrudescence in an immune-privileged site with transneural spread. Only four of 20 affected eyes retained useful vision. Poor ocular bioavailability, retinal ischemia, acquired drug resistance, and strain pathogenicity may underlie treatment failure. Acyclovir therapy appears relatively ineffective. Combined intravenous and intravitreal therapy with foscarnet and ganciclovir may be the best current management. Research advances are needed urgently.

Editorial NeuroAIDS review

NeuroAIDS is a disease that incorporates both infectious and degenerative pathophysiologic pathways. It has a known cause, has several animal models, and is under investigation and treatment using multiple avenues, in vivo and in vitro [1–7]. Select highlights from the spectrum of NeuroAIDS research predominantly related to human immunodeficiency virus-1 clade B (HIV-1B) are reviewed below.

Rural Indian tribal communities: an emerging high-risk group for HIV/AIDS.

BackgroundRural Indian tribes are anthropologically distinct with unique cultures, traditions and practices. Over the years, displacement and rapid acculturation of this population has led to dramatic changes in their socio-cultural and value systems. Due to a poor health infrastructure, high levels of poverty and ignorance, these communities are highly vulnerable to various health problems, especially, communicable diseases including HIV/AIDS. Our study sought to assess knowledge, attitudes and practices regarding sexuality, and the risk factors associated with the spread of HIV/AIDS and STDs among these communities.MethodsA nested cross sectional study was undertaken as part of the on going Reproductive and Child Health Survey. A total of 5,690 participants age 18–44 were recruited for this study. Data were obtained through home interviews, and focused on socio-demographics, knowledge, attitudes and behaviors regarding sexuality, HIV/AIDS and other STDs.ResultsThe study revealed that only 22% of adults had even heard of AIDS, and 18 % knew how it is transmitted. In addition, only 5% knew that STDs and AIDS were related to each other. AIDS awareness among women was lower compared to men (14% vs.30 %). Regarding sexual practices, 35% of the respondents reported having had extramarital sexual encounters, with more males than females reporting extramarital affairs.ConclusionLack of awareness, permissiveness of tribal societies for premarital or extra-marital sexual relationships, and sexual mixing patterns predispose these communities to HIV/AIDS and STD infections. There is a dire need for targeted interventions in order to curtail the increasing threat of HIV and other STDs among these vulnerable populations.

The Influenza Pandemic of 2009

Influenza is a moving target, which evolves in unexpected directions and is recurrent annually. The 2009 influenza A/H1N1 pandemic virus was unlike the 2009 seasonal virus strains and originated in pigs prior to infecting humans. Three strains of viruses gave rise to the pandemic virus by antigenic shift, reassortment, and recombination, which occurred in pigs as ‘mixing vessels’. The three strains of viruses had originally been derived from birds, pigs, and humans. The influenza hemagglutinin (HA) and neuraminidase (NA) external proteins are used to categorize and group influenza viruses. The internal proteins (PB1, PB1-F2, PB2, PA, NP, M, and NS) are involved in the pathogenesis of influenza infection. A major difference between the 1918 and 2009 pandemic viruses is the lack of the pathogenic protein PB1-F2 in the 2009 pandemic strains, which was present in the more virulent 1918 pandemic strains. We provide an overview of influenza infection since 1847 and the advent of influenza vaccination since 1944. Vaccines and chemotherapy help reduce the spread of influenza, reduce morbidity and mortality, and are utilized by the global rapid-response organizations associated with the WHO. Immediate identification of impending epidemic and pandemic strains, as well as sustained vigilance and collaboration, demonstrate continued success in combating influenza.

Cost of treatment: The single biggest obstacle to HIV/AIDS treatment adherence in lower-middle class patients in Mumbai, India

BACKGROUND This study analyzes the social, economic and behavioral factors most frequently associated with adherence to Highly Active Antiretroviral Treatment (HAART) in urban India. MATERIALS AND METHODS Data was collected in a metropolitan teaching hospital in Mumbai using a cross-sectional survey design. Face-to-face interviews were conducted with 152 patients. The semistructured survey included both open and closed ended questions on socio-demographic, economic and behavioral factors. Factors affecting treatment adherence were analyzed. RESULTS The median age of patients was 40.5 years, 73% were males and all were heterosexual. Patients had been given ART from six months to five years (median is equal to 3.5). Ninety per cent lived at home and commuted to the clinic by bus or train. Behaviorally, 37% were sexually active, but only 55% used condoms. In assessing adherence, income, education, knowledge of their drugs, transportation, side effects, cost of treatment, distance from clinic and personal clinic satisfaction were analyzed. We found that 75% of patients reported cost of HAART to be the single greatest obstacle to adherence (p less than 0.01). Additionally, those claiming knowledge of their drugs were 2.3 times more likely to be adherent (p less than 0.03), while those who abused drugs or alcohol were 53% less likely to be adherent (p less than 0.03). There was no correlation with other factors. CONCLUSIONS Our study population was representative of the lower middle class of India. It found that an educated, employed group considered the cost of treatment to be a significant obstacle for successful therapy. Additionally, it showed a significant increase in adherence when patients had knowledge of their HAART medications. Therefore, reducing the cost of medication as well as teaching about antiretroviral medications are both likely to improve adherence.

Maternal death from postpartum necrotizing fasciitis arising in an episiotomy: A case report

Background: Necrotizing fasciitis is a rare condition. We report a fatal case arising from an episiotomy in a previously healthy woman. Case: A healthy 23-year-old prima gravida white female underwent vaginal delivery with repair of a proctoepisiotomy. Eighty-four hours postpartum, she developed increasing perineal swelling with severe pain. She presented on the 4th postpartum day with edema, erythema localized to the perineum, and vital signs significant only for tachycardia of 120/min. With a leukocytosis of 45,000/μl (87%) neutrophils, she was admitted to the hospital with an initial diagnosis of perineal cellulitis and empirically started on broad-spectrum intravenous antibiotic therapy. The patients condition continued to deteriorate and she was then transferred to our facility on postpartum day 9 where a team performed two radical debridements of all necrotic tissue. Despite this and a broadened antibiotic coverage, the patient eventually experienced cardiopulmonary arrest and died on postpartum day 12. Conclusion: Necrotizing fasciitis must be considered in the differential diagnosis of the postpartum patient presenting with severe vulvar pain and erythema. Our patient exemplifies the obscure presentation with seemingly minimal skin changes. Any delay in diagnosis and treatment, which must include expeditious aggressive surgical debridement, will likely result in severe morbidity or mortality.

Blastoschizomyces capitatus pneumonia in an immunocompetent male

Blastoschizomyces capitatus is an emerging fungal pathogen. It has been well characterized as a cause of local and disseminated disease in immunocompromised hosts, especially in the setting of neutropenia. We describe a case of B capitatus pneumonia in an otherwise healthy man and review the clinical presentation, microbiologic characteristics, and treatment strategies for B capitatus infections.

Structural inferences for Cholera toxin mutations in Vibrio cholerae

Cholera is a global disease that has persisted for millennia. The cholera toxin (CT) from Vibrio cholerae is responsible for the clinical symptoms of cholera. This toxin is a hetero-hexamer (AB5) complex consisting of a subunit A (CTA) with a pentamer (B5) of subunit B (CTB). The importance of the AB5 complex for pathogenesis is established for the wild type O1 serogroup using known structural and functional data. However, its role is not yet documented in other known serogroups harboring sequence level residue mutations. The sequences for the toxin from different serogroups are available in GenBank (release 177). Sequence analysis reveals mutations at several sequence positions in the toxin across serogroups. Therefore, it is of interest to locate the position of these mutations in the AB5 structure to infer complex assembly for its functional role in different serogroups. We show that mutations in the CTA are at the solvent exposed regions of the AB5 complex, whereas those in the CTB are at the CTB/CTB interface of the homo-pentamer complex. Thus, the role of mutations at the CTB/CTB interface for B5 complex assembly is implied. It is observed that these mutations are often non-synonymous (e.g. polar to non-polar or vice versa). The formation of the AB5 complex involves inter-subunit residue-residue interactions at the protein-protein interfaces. Hence, these mutations, at the structurally relevant positions, are of importance for the understanding of pathogenesis by several serogroups. This is also of significance in the improvement of recombinant CT protein complex analogs for vaccine design and their use against multiple serogroups.

The effect of treating bacterial vaginosis on preterm labor

Objective: Multiple studies suggest that bacterial vaginosis (BV) causes preterm labor; yet its routine treatment remains controversial. In order to help to elucidate this controversy, we performed a thorough review of studies with levels of evidence ranging from I to II–II. Methods: We searched for all of the studies from the years 1994 to 2001 via Medline’s database, including MD Consult and Ovid Mednet. Results: Several trials discovered a decrease in the incidence of preterm labor when BV was treated, but most of those trials were performed on women with a history of preterm labor. However, the majority of trials reviewed advise against treatment of a general low-risk obstetric population, as there was no significant decrease in preterm labor. Conclusions: Therefore, based on the above studies and the current guidelines of the Centers for Disease Control and Prevention (CDC), treating pregnant women in high-risk populations who are diagnosed with BV provides the clinician with an opportunity to possibly prevent preterm labor in this population. In nulliparous women without a history of preterm birth, treatment is recommended if other risk factors are present (e.g. gonorrhea or chlamydia). However, in the general low-risk populations, routine screening is not indicated.

The Treatment of Advanced Cardiac Allograft Rejection

Severe cardiac allograft rejection remains a serious problem despite the advances of cyclosporine-based immunosuppression. This study analyzes our experience with 202 recipients of cardiac allografts who were treated primarily with cyclosporine and prednisone. Failure of such therapy in 86 patients (43%) resulted in 105 episodes of advanced cardiac allograft rejection as diagnosed by endomyocardial biopsy. Of 101 rejection episodes that were initially treated with intravenous pulse therapy, 48 (48%) were successfully resolved, yet 60% of these successes were associated with major infections. Patients in whom steroid therapy failed or was contra-indicated received intravenous antithymocyte globulin (ATG) or intravenous monoclonal antibody (OKT3). ATG and OKT3 successfully reversed severe rejection in 26 (81%) of 32 and in 13 (93%) of 14 episodes, respectively. Infectious complication rates were 54% and 21%, respectively. Because the majority (87%) of these rejection episodes occurred within the first 30 days after treatment, many of them may have resulted from inadequate immunosuppressive induction therapy. Based on our results, we believe that advanced cardiac allograft rejection may be managed best by individualizing immunosuppressive therapy, thus enhancing prevention, and by adding OKT3 to the regimen when rejection occurs.