Evolving epidemiology of HIV infection among adults.

Whereas new, or changes in existing, routes of transmission of HIV have not been identified in the 11 years since AIDS was identified as a clinical syndrome, changes in the epidemiology of HIV infection in the US have been identified during that period. The role of injection drug use as a risk for both parenteral and sexual transmission of HIV has increased substantially during this period. Heterosexual transmission is becoming more prominent as the epidemic continues to "mature" in the US. The likelihood that heterosexual transmission will become progressively more important in the spread of HIV in the US in the next several years seems high. The ability of individuals in some populations at risk for infection to modify risk behaviors has led to a reduction in transmission of HIV in those populations. The addition of nucleoside analog antiretrovirals and effective chemoprophylaxis for Pneumocystis carinii pneumonia has led to increases in both the quality and duration of life for some populations of HIV-infected patients. Neither a chemotherapeutic cure nor a vaccine is on the immediate horizon; education and behavior modification remain the cornerstones of current prevention efforts. For a variety of complex reasons, inappropriate scrutiny has been focused on the remote risks of health-care provider-to-patient transmission of HIV. In the past 11 years medical science has made remarkable progress in understanding the etiology, biology, epidemiology, pathogenesis, and prevention of HIV infection. Despite this progress, a great deal of work remains to be done not only in the medical and basic science arenas but also in the behavioural and sociological sciences.     

Nosocomial HIV infection: epidemiology and prevention--a global perspective

Because, globally, HIV is transmitted mainly by sexual practices and intravenous drug use and because of a long asymptomatic period, healthcare-associated HIV transmission receives little attention even though an estimated 5.4% of global HIV infections result from contaminated injections alone. It is an important personal issue for healthcare workers, especially those who work with unsafe equipment or have insufficient training. They may acquire HIV occupationally or find themselves before courts, facing severe penalties for causing HIV infections. Prevention of blood-borne nosocomial infections such as HIV differs from traditional infection control measures such as hand washing and isolation and requires a multidisciplinary approach. Since there has not been a review of healthcare-associated HIV contrasting circumstances in poor and rich regions of the world, the aim of this article is to review and compare the epidemiology of HIV in healthcare facilities in such settings, followed by a consideration of general approaches to prevention, specific countermeasures, and a synthesis of approaches used in infection control, injury prevention, and occupational safety. These actions concentrated on identifying research on specific modes of healthcare-associated HIV transmission and on methods of prevention. Searches included studies in English and Russian cited in PubMed and citations in Google Scholar in any language. MeSH keywords such as nosocomial, hospital-acquired, iatrogenic, healthcare associated, occupationally acquired infection and HIV were used together with mode of transmission, such as "HIV and hemodialysis". References of relevant articles were also reviewed. The evidence indicates that while occasional incidents of healthcare-related HIV infection in high-income countries continue to be reported, the situation in many low-income countries is alarming, with transmission ranging from frequent to endemic. Viral transmission in health facilities occurs by unexpected and unusual as well as more frequent modes. HIV can be transmitted to patients and to donors of blood products by specific vehicles and vectors during blood transfusion, plasma donation, and artificial insemination, by improperly sterilized sharps, by medical equipment during activities such as dialysis and organ transplantation, and by healthcare workers infected by occupational exposure to hazards such as blood-contaminated sharps. Personal, equipment, and environmental factors predispose to acquisition of nosocomial HIV and all are pertinent for prevention. For infection and injury control, poverty is often an underlying determinant. While sophisticated new tests offer improved HIV detection, increasingly higher marginal costs limit their feasibility in many settings. Modest investment in safer equipment and appropriate integrated training in infection control, injury prevention, and occupational safety should provide greater benefit.     

A cluster of HIV infection among heterosexual people without apparent risk factors

Human immunodeficiency syndrome (HIV) epidemiology in Belgium shows that 66% of all acquired immunodeficiency syndrome patients were infected heterosexually. Since 1985, all HIV-seropositive patients in Brussels and Antwerp who have been heterosexually infected have been offered participation in a partner notification program; this article reports the case study of 1 HIV infected male and his 19 identified previous women sexual partners. This report describes the patient's background and the type and frequency of sexual intercourse he had with each partner. The characteristics of each of the sexual partners were also described. An important consideration of this case was that 11 of the tested partners (56%) were HIV seropositive. Several factors were discussed concerning the cause of this high rate of transmission (e.g. high disseminator patient, highly virulent HIV strain, and presence of genital herpes). This study emphasizes the fact that middle class women with low risk sexual practices were infected with AIDS from as little as 1 sexual encounter with this infected individual. To stop a false sense of security among people with few sexual partners, it was advised that a program of partner notification targeted to heterosexuals be implemented along with other public health policies.     

Tuberculosis and HIV infection: epidemiology, immunology, and treatment

Tuberculosis and HIV have combined to present a major threat to global public health. Each disease has a negative effect on the other, and mortality in patients with both tuberculosis and HIV is higher than that caused by either condition alone. In regions such as sub-Saharan Africa, as many as a third or more of all patients with tuberculosis have concomitant HIV infection. In urban centers in developed nations, HIV co-infection may also be quite common. Treatment of latent tuberculosis infection in persons with HIV is successful in preventing many cases of active disease, and newer ultra-short course regimens, such as those consisting of 2 months of rifampin and pyrazinamide, should aid in this effort. Diagnosis and treatment of active tuberculosis in HIV-infected patients may be difficult. Although treatment of active tuberculosis is generally successful in patients with HIV, drug interactions between anti-tuberculosis medications and antiretrovirals often complicate the matter, and expert guidance should be sought for proper management.     

Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study

ObjectivesTo determine the viral epidemiology and clinical characteristics of patients with and without clinically apparent respiratory tract infection.MethodsThis prospective cohort study was conducted during the 2018 winter influenza season. Adult patients with fever/respiratory symptoms (fever/RS group) were age- and sex-matched with patients without fever/RS (non-fever/RS group) in a 1:1 ratio. Respiratory viruses were tested using NxTAG? Respiratory Pathogen Panel IVD, a commercially-available multiplex PCR panel.ResultsA total of 214 acutely hospitalized patients were included in the final analysis, consisting of 107 with fever/RS (fever/RS group), and 107 age- and sex-matched patients without fever/RS (non-fever/RS group). Respiratory viruses were detected in 34.1% (73/214) of patients, and co-infection occurred in 7.9% (17/214) of patients. The incidence of respiratory virus was higher in the fever/RS group than in the non-fever/RS group (44.9% (48/107) versus 23.4% (25/107), p 0.001). Influenza B virus, enterovirus/rhinovirus and coronaviruses were detected more frequently in the fever/RS group, whereas parainfluenza virus 4B and adenovirus were detected more frequently in the non-fever/RS group. Among the non-fever/RS group, chest discomfort was more common among patients tested positive for respiratory viruses than those without respiratory virus detected (44% (11/25) versus 22% (18/82), p 0.04).ConclusionsRespiratory viruses can be frequently detected among hospitalized patients without typical features of respiratory tract infection. These patients may be a source of nosocomial outbreaks.     

The macrophage in HIV infection

Macrophages play a key role in several critical aspects of HIV disease. They appear to be the first cells infected by HIV and perhaps the very source of HIV production when CD4⁺ cells are markedly depleted in the patient. Macrophages and microglial cells are the cells infected by HIV in the CNS. In tonsils and adenoids of HIV-infected patients, macrophages fuse into multinucleated giant cells that produce copious amounts of virus. Finally, opportunistic pathogens can cause an upregulation of HIV production by macrophages, often in the multinucleated form.     

Genetic susceptibility to symptomatic norovirus infection in Nicaragua

Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo‐blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody‐prevalence and titer to NoV among individuals with different histo‐blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non‐secretors in the population and nil non‐secretors among patients infected with NoV, suggesting that non‐secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le^a?b?). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le^{a + b?}) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18‐Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non‐secretors resistant. The overall antibody‐prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody‐negative. Among secretors, 63% were antibody‐positive compared to 33% among non‐secretors (P = 0.151). This study extends previous knowledge about the histo‐blood group antigens role in NoV disease in a population with different genetic background than North American and European. J. Med. Virol. 81:728–735, 2009 © 2009 Wiley‐Liss, Inc.     

The epidemiology of human immunodeficiency virus infection

The epidemiology and natural history of infection with the human immunodeficiency virus (HIV) is reviewed. HIV is associated with a broad spectrum of disease, including AIDS. In presenting the natural history, early and late clinical manifestations, diagnosis of infection, incubation and latency periods, and survival time are discussed. Data from the published literature on the distribution of HIV infection in the adult U.S. population and factors that affect the acquisition and spread of the virus are also reviewed. Understanding of the epidemiology of this infection in certain high-risk groups is substantial and has provided a clear focus for preventive efforts and counseling. Many questions about spread in heterosexuals and about factors that may affect the natural history of the disease await completion of ongoing and planned studies.     

Emerging trends of HIV epidemiology in Asia

The main molecular trait of HIV-1 is the inherent capacity to vary, recombine, and diversify, which gives it a clear edge to evade the human immune system and survive through the generation of complex molecular forms, termed recombinants. In a setting of coinfection, molecular and biological interactions between diverse HIV-1 subtypes may promote the emergence of circulating recombinant forms through the shuffling of viral genomes, which results in increased intra- and inter- host viral variation and altered biological properties. The focus of this review is on Asia, which has the highest proportion of HIV-1 recombinants circulating worldwide, with the top in South and Southeast Asia, amounting to 89% of its total HIV-1 infection. The HIV-1 strains which are spreading in this geographic area are CRF01_AE, subtypes B and C. Given the rapid spread and active establishment of some of the recombinant forms in Asia, it is essential to understand how they differ from their parental strains, the acquisition of certain molecular traits, and their biological attributes upon recombination, which give these strains an epidemiologic edge. The current epidemic provides strong evidence that the parental subtypes are being replaced via competition with possibly more versatile HIV-1 recombinant forms. This appears to be an ongoing phenomenon and has resulted in an HIV-1 epidemic shift, with the expansion and dissemination of a wide variety of HIV-1 forms within this geographic region.     

Angiostrongylus costaricensis natural infection in Vaginulus plebeius in Nicaragua.

A study of 94 slugs, collected from urban and rural areas in and around Léon, Nicaragua, was carried out in order to confirm the role of Vaginulus plebeius as an intermediate host of Angiostronglylus costaricensis. Third-stage larvae of A. costaricensis were obtained from these molluscs. Some of these larvae were then orally inoculated into two laboratory-bred rats Sigmodon hispidus and adult worms of A. costaricensis were recovered two months later. The infection rate of these slugs ranged from 4% in urban areas to 85% in rural areas. These data suggest that contamination to man is a major risk especially in rural areas and that abdominal angiostrongyliasis could be a health problem in Nicaragua.     

The molecular epidemiology of hepatitis E virus infection

Molecular characterization of various hepatitis E virus (HEV) strains circulating among humans and animals (particularly swine, deer and boars) in different countries has revealed substantial genetic heterogeneity. The distinctive four-genotype distribution worldwide of mammalian HEV and varying degrees of genetic relatedness among local strains suggest a long and complex evolution of HEV in different geographic regions. The population expansion likely experienced by mammalian HEV in the second half of the 20th century is consistent with an extensive genetic divergence of HEV strains and high prevalence of HEV infections in many parts of the world, including developed countries. The rate and mechanisms of human-to-human transmission and zoonotic transmission to humans vary geographically, thus contributing to the complexity of HEV molecular evolution.     

The pathobiology of HIV infection.

The follicular dendritic cells (FDCs) of the germinal center are known to absorb antigens in the form of immune complexes and to express them on the cell surface for long periods of time. Here, Cecil Fox and Michele Cottler-Fox propose that, as a result of FDC binding of immune-complexed viruses, lymphoid organs are the major reservoirs of HIV, and that FDCs play a key role in infection of CD4+ T cells.     

The role of neutralizing antibodies in HIV infection

Neutralizing antibodies against HIV-1 play an important role in preventing viral infections. Less clear is their role in the containment of viral replication in infected individuals. However, evidence is accumulating that neutralizing antibodies may help the cellular arm of the immune response to prevent or delay the progression to AIDS. Detection of neutralizing antibodies depends on the in vitro neutralization assays used, and standardization of the assays is essential in order to be able to compare the magnitude and quality of a neutralizing antibody response in sera or other fluids from HIV-infected patients, uninfected HIV-1 exposed persons, or vaccinated animals/persons. Viral mechanisms to prevent neutralization include high variability and extensive glycosylation of the Envelope proteins, Envelope trimerization and shedding as well as late exposure of functionally important entry domains by conformational changes induced upon CD4 binding. These are also the difficulties encountered in the design of immunogens able to induce neutralizing antibodies upon vaccination.     

The epidemiology of human papillomavirus infection and cervical cancer

Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI). The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs). The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC), the adenocarcinomas and the vast majority (i.e. > 95%) of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL)/Cervical Intraepithelial Neoplasia 3 (CIN3)/Carcinoma in situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC) for five or more years, smoking, high parity (five or more full term pregnancies) and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT) and Herpes Simplex Virus type 2 (HSV-2). Women exposed to the Human Immunodeficiency Virus (HIV) are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.     

Hemoglobin Beth Israel. A mutant causing clinically apparent cyanosis.

We found that an abnormal hemoglobin with a very low oxygen affinity was responsible for overt cyanosis in an otherwise healthy adolescent. Hemoglobin Beth Israel, in which serine replaces the asparagine residue normally present at position 102 (G4) of the beta-polypeptide chain, was associated with normal blood counts and no apparent exercise intolerance in the heterozygous carrier. Cyanosis resulted from a drastically right-shifted oxygen dissociation curve, whose position and shape could account for the absence of "physiologic" anemia. The whole-blood oxygen tension at 50 per cent oxygen saturation was 88 mm Hg (normally 26 +/- 1 mm Hg), and the arterial blood was only 63 per cent saturated with oxygen despite a normal oxygen tension of 97 mm Hg. The hemolysate showed a low oxygen affinity but normal Bohr effect. Unexplained cyanosis, particularly in association with normal arterial oxygen tension should prompt a search for an abnormal hemoglobin, which may obviate the need for invasive diagnostic procedures.     

Current HIV epidemiology and revised recommendations for HIV testing in health-care settings

The Centers for Disease Control and Prevention (CDC) estimates that about one quarter of the 1-1.2 million persons living with HIV/AIDS in the United States are unaware they are infected. Persons who do not know they are HIV infected are unable to access effective treatment and, compared with those who know they are infected with HIV, are more likely to transmit HIV to others. Pregnant women need to know if they are HIV infected so they can take steps to avoid transmitting HIV to their infants and access medical care for themselves. Despite past CDC recommendations for routine, voluntary HIV testing of all persons in acute-care hospitals with high HIV prevalence and those with risks for HIV, many HIV-infected persons who encounter the health-care system are not tested. Promoting HIV testing as a routine part of medical care is a key strategy of the CDC's Advancing HIV Prevention initiative launched in 2003. The CDC has recently revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings to help increase the number of HIV-infected Americans who are aware they are infected so they can receive prevention, care, and treatment. The new recommendations advocate voluntary "opt-out" HIV screening in health-care settings, with appropriate follow-up care and treatment; eliminating requirements for separate, written consent for HIV testing; annual retesting for persons with known risk factors; and expanded rescreening in the third trimester for women who test negative for HIV early in pregnancy. The CDC issued the revised recommendations on September 22, 2006, and is now engaged with numerous professional organizations on practical strategies for implementation.