Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Fungal infections are ignored by social and political communities. However, they are estimated to affect more than a billion people, resulting in approximately 11.5 million life-threatening infections in the 'at risk' population and more than 1.5 million deaths annually. Though there have been huge advances in diagnostics and antifungal drug development over the past two decades, however, resource limited settings have not benefited from these advances. The aim of this research was to determine the burden of serious fungal infections in Nigerians with the appropriate underlying diseases. This epidemiological research was conducted across four study populations. Study 1; HIV-infected patients with CD4+ counts < 250 cells/mm³, irrespective of their ART status, a CrAg lateral flow assay was used for detecting cryptococcal antigenaemia (n=214). Study 2; a cross-sectional multicentre survey of TB patients being managed for smear negative or treatment failure TB irrespective of their HIV status (n=208). Study 3; a multicentre histoplasmin skin sensitivity survey amongst healthy HIV-infected and non-HIV infected participants; intradermally; induration ≥ 5 mm was considered to be histoplasmin positive (n=750). Study 4; a prospective cohort study of critically ill patients in a Nigerian ICU (n=71). Two retrospective studies to analyse the clinical picture of serious fungal infections in two at risk populations (HIV/AIDS and neonatal intensive care babies) in Nigerians was also conducted (n=7034; n=2712 respectively). Results revealed an overall seroprevalence of cryptococcal antigenemia of 8.9% with 6 (9.8%) in those with CD4+ cell counts < 100cells/mm³, 4 (5.0%) in the 100-200 group and 9 (12.3%) in 200-250 cells/mm³ group; a CPA prevalence of 8.7% (6.5% had HIV infection and 14.5% were HIV-negative) and a prior subclinical histoplasmosis of 4.4%. The ICU study revealed a 45% healthcare associated infection rate representing an incidence rate of 79/1000 patient-days in the ICU. The retrospective studies revealed a 2.3% rate of neonatal ICI with a case fatality rate of 18.5%. In the 12 years retrospective study 18% had a fungal OI with 88% of patients having initiated ART. In conclusion, serious fungal infections do occur in the at risk population in Nigeria and they constitute a significant public health challenge. Our findings demonstrate that there has been an underestimation of the burden of the problem in Nigerians. There is a dire need to design guidelines for the management of fungal infections in at risk population.

Health care-associated and hospital-acquired infections are two entities associated with increased morbidity and mortality. They are highly costly and constitute a great burden to the health care system. Vitamin D deficiency (< 20 ng/ml) is prevalent and may be a key contributor to both acute and chronic ill health. Vitamin D deficiency is associated with decreased innate immunity and increased risk for infections. Vitamin D can positively influence a wide variety of microbial infections. Herein we discuss hospital-acquired infections, such as pneumonia, bacteremias, urinary tract and surgical site infections, and the potential role vitamin D may play in ameliorating them. We also discuss how vitamin D might positively influence these infections and help contain health care costs. Pending further studies, we think it is prudent to check vitamin D status at hospital admission and to take immediate steps to address existing insufficient 25-hydroxyvitamin D levels.

Paediatric human immunodeficiency virus (HIV) infection has become a major socio-economic health problem in recent years as the number of HIV-1 infected children steadily increases. The majority of these infants are infected through mother-to-child transmission, with the frequency of vertical transmission varying between 12,9% and 65%. In order to implement appropriate management and possible treatment of these infected neonates, it is essential to have reliable laboratory tests for the early diagnosis of an HIV infection. At the time that this study was initiated, the diagnosis of HIV-1 infection in the Groote Schuur Hospital Virology Laboratory depended almost exclusively on serological assays. Such assays are of limited value for infants under 18 months of age, as maternal lgG antibody to HIV-1 is transferred via the placenta and may persist in the baby for up to 18 months. Available lgG antibody tests do not distinguish reliably between passively acquired maternal antibody and that produced by the infant itself. A valuable method of establishing the presence of true infection is provided by the polymerase chain reaction (PCR) technique which allows the identification, and subsequent exponential amplification of low levels of specific viral nucleic acid using specific oligonucleotide primers. A major aim of this study was to develop and instigate a (PCR) assay for the early diagnosis of HIV infection in infected infants. This was successfully achieved by the adaptation and optimization of an existing standard PCR protocol to suit the specific needs of a routine diagnostic service. Preliminary requirements involved the selection of primers and probes and establishing optimal parameters for: ionic strength, Taq DNA polymerase concentration, primer concentration, deoxynucleotide triphosphate concentration, and hybridization conditions for most efficient functioning of the test. The devised method entailed the extraction of proviral DNA from peripheral blood mononuclear cells, amplification of HIV-1 specific sequences by PCR, and identification by Southern blot hybridization with digoxigenin (DIG)-labelled probes. Thereafter the efficacy of the assay was tested on 45 infants (under 15 months of age) all born to seropositive mothers and therefore at risk for HIV infection. Forty-two of these infants had antibodies to HIV-1 and the remaining 3 were seronegative. The latter 3 also tested negative for HIV proviral DNA when PCR was performed, using at least 2 different HIV-1 primer pairs and their respective DIG-labelled probes. However, 27 (64%) of the 42 seropositive infants were also HIV-PCR positive and the remaining 15 (36%) seropositive infants were negative for HIV proviral DNA. Positive PCR tests correlated well with clinical data indicative of active HIV-1 infection for the majority of infants in the neonatal period, although it could not provide proof of infection in newborn babies (less than 1 week of age). The development of an in-house PCR protocol specific for HIV-1 has not only provided a valuable diagnostic assay for neonatal infection, but has also given insight into the parameters required for high sensitivity and the stringent precautionary measures that need to be applied to avoid contamination problems. The second part of this study was devoted to DNA sequence analysis of cloned HIV isolates from an infected mother and her 3-month-old infant. Nucleotide sequence variation between isolates of HIV-1 has been well documented. Examination of the third variable region (particularly the V3- loop) in the env gene of HIV-1 of our mother-infant pair confirmed this variation and provided the first genetic epidemiological data of this nature in the local community. Proviral DNA from both mother and baby was amplified using V3-specific degenerate primers and cloned. Clones containing the insert DNA were 2 identified by colony-blot hybridization. Their nucleotide and amino acid sequences were analyzed by using various computer programs. The degree of similarity between variants from the mother and infant in this study differed to a large extent from previous studies. The virus population harboured by the mother displayed highly homogeneous V3 sequences (1,04% variation) compared to the isolates from her 3-month-old infant, which showed a higher degree (1,8%) of heterogeneity. Phylogenetic analysis of the different isolates from mother and infant demonstrated that an HIV-1 subtype C virus was the infectious agent. This classification was confirmed by the characteristic amino-acid sequence of the tetrapeptide motif of the V3 loop present in the isolates from both mother and infant as well as the absence of a potential N-linked glycosylation site proximal to the first cysteine of the V3 loop, which is characteristic of subtype C viruses. Based on the amino acids present at positions 306 and 320 of the V3 loop, it could also be concluded that isolates from both the mother and her baby were consistent with the non-syncytium inducing (NSI) phenotype of HIV-1, thus indicating that, contrary to popular belief, NSI variants can be responsible for initiating infection. Data obtained from these genetic investigations of variants involved in vertical transmission of HIV-1 can form a useful basis for future comparative studies.

Plus de deux millions d’enfants dans le monde vivent actuellement avec le virus d’immunodéficience humaine de type 1 (le VIH-1). De plus, les femmes, particulièrement celles en âge de procréer, sont plus vulnérables à cette infection. Or, 90% des infections par ce rétrovirus chez l’enfant sont attribuables à la transmission de la mère à l’enfant (TME). Quoique des traitements antirétroviraux soient disponibles pour la prévenir, seulement une infime proportion des femmes séropositives y a accès encore aujourd’hui. On estime donc que la transmission verticale du VIH-1 est un problème de santé public alarmant, non seulement pour les générations d’aujourd’hui, mais aussi pour celles de demain. La contamination fœtale est l’une des voies par laquelle la TME peut se produire. Cependant, les mécanismes qui y sont associés demeurent peu connus, particulièrement en ce qui concerne l’infection directe des trophoblastes, éléments structuraux du placenta. Afin d’éclaircir ce sujet, nous avons étudié, dans cette thèse, les évènements précoces du cycle réplicatif du VIH-1 dans les trophoblastes, première étape conduisant à l’infection d’une cellule cible. Nous avons découvert que le mécanisme d’infection des trophoblastes est inhabituel pour ce rétrovirus. En effet, le VIH-1, au contact de ces cellules, est internalisé par celles-ci et se retrouve alors dans les endosomes. Nous avons établi que l’endocytose du VIH-1 se fait par une voie indépendante de la clathrine, des cavéoles et de la dynamine-2, mais requérant toutefois que le cholestérol membranaire soit libre. Nous avons suivi le parcours intracellulaire des particules virales et noté qu’elles se rendaient principalement aux endosomes tardifs, transit contrôlé par les protéines Rab5 et Rab7. Quoique ce transport entraîne la dégradation d’une grande partie des virions, il est de façon étonnante essentiel à leur processus infectieux dans les trophoblastes. Finalement, l’accès du VIH-1 au cytoplasme cellulaire se fait en l’absence des protéines de l’enveloppe virale, la gp120 et la gp41, suggérant que le virus fusionne dans les endosomes grâce à la machinerie cellulaire présente. Les données présentées dans cette thèse décrivent donc une nouvelle voie d’infection pour le VIH-1. La compréhension de ce processus est essentielle si l’on veut mieux contrôler un jour la transmission mère-enfant du VIH-1 durant la grossesse et/ou trouver des solutions alternatives aux antirétroviraux existants. / More than two million children under fifteen years of age are currently living with the human immunodeficiency virus type 1 (HIV-1) worldwide and 90% of these infections are associated with mother-to-child transmission (MTCT) of this retrovirus. Women, particularly those of child-bearing age, are highly susceptible to HIV-1 infection. In spite of available antiretroviral treatments to prevent MTCT, only a minority of infected women have access to these treatments. Hence, vertical transmission of HIV-1 is an alarming public health issue for both current and future generations. One of the postulated models for how HIV-1 is transmitted by the mother is foetal contamination. However, the mechanisms underlying such an event are poorly understood. In particular, the process whereby HIV-1 may directly infect trophoblasts, the structural cells of the placenta, is unknown. In this thesis, we have studied the early events associated with HIV-1 life cycle in trophoblasts, the first step towards infecting a target cell. Our data demonstrate that the mechanism whereby HIV-1 infects trophoblasts is unusual for this retrovirus. Upon contact with these cells, HIV-1 is rapidly and massively endocytosed. We have tracked the step-by-step movements of incoming particles and found that HIV-1 traffics primarily towards late endosomes, via Rab5 and Rab7. Surprisingly, although this transit leads to the degradation of the majority of the internalized virions, it is necessary for HIV-1 to establish a productive infection in these cells. In addition, we found that endocytosis of HIV-1 in these placental cells relies on a clathrin-, caveolae- and dynamin-independent pathway that requires free membrane cholesterol. Finally, viral entry occurs in the absence of the viral envelope glycoproteins, gp120 and gp41, suggesting that HIV-1 undergoes fusion within the endosomes via the host cell machinery. Collectively, the data presented in this thesis describe a novel infection pathway for HIV-1. An understanding of this unique process is essential if we are to learn how to control MTCT and/or find alternate solutions to existing antiretroviral drugs.

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 5 uppsatser.

Since 1988 when the first HIV positive drug user was identified in Poland, for close to two decades, the predominant route of HIV transmission has been through injecting drug use. In mid 2000s, Polish officials reported that injecting drug use no longer contributed to incrasing HIV incidence. The consequences of such a statement are that many of the structural and personal risks associated with HIV infection go unaddressed, that drug users are neglected by HIV prevention efforts, that HIV treatment is not made available to drug users and that the policy environment does not adequately support effective public health initiatives. This case study is based on documentation, archival records, interviews, participant observation, and physical artifacts shows that these assertions were made, and continue to be repeated, in a highly political context. Poland is a post-socialist state with strong neoliberal leanings, and it is highly invested in successful integration with the European Union. Powerful Catholic Church serves as an important backdrop. While people considered "at risk" now have more freedom to conduct their lives, they also have a set of neoliberal expectations and religious pressures placed on them. Country's geographic location adds to this complexity - situated between "Old Europe" where HIV problem has been successfully contained and the former Soviet Union, where the HIV incidence among drug users is the highest in the world, Poland attempts to align itself with the success of the West. Furthermore, examination of the available data suggests that the assertions made by Polish officials omit numerous variables. My research shows that even though Polish leadership in the area of HIV and drug policy wishes to resemble Western Europe, Poland does not meet international standards for the prevention of HIV transmission. The interviews I conducted, as well as the review of the literature on drug and HIV policies and programs suggest that these services are scattered, often unavailable, and that their number is stagnating, at best, and in some cases, even decreasing. This maybe a direct result of lack of engagement of drug users in their design. Excluded from the discussion of risk, drug users are thus not the focus of prevention efforts. Based on gathered data, there are seven crucial issues that require immediate action if Poland is to manage HIV prevention and care for people who use drugs in a manner consistent with the international standards. The areas requiring action are: a change in the drug policy from the current very punitive approach, expansion of needle and syringe programs and other harm reduction services, improved data collection and an increase in the availability of HIV testing, scaled-up substitution treatment, improved quality of other forms of drug treatment, greater investment in civil society organizations, improved access to HIV treatment, and educational and training efforts that encourage greater attention to HIV related matters across disciplines.

Thesis (M. Cur.) --University of Limpopo, 2011. / HIV/AIDS is one of the major challenges facing South Africa today. Over 5.5 million people are infected with HIV and the majority of these infections are in the reproductive age group. Since the start of the epidemic, over 12.2 million women worldwide have been infected with HIV (WHO, 2000:10). The risk of women contracting HIV is rising globally. HIV seems to be a major cause of infant mortality. It is estimated that approximately 55% of women in South Africa are HIV-positive (National Department of Health, 2007:7). It is, therefore, important that knowledge and attitudes of women regarding mother-to-child transmission (MTCT) of HIV infection are explored to reduce the high infant mortality rate and the incidence of MTCT of HIV infections, and to develop preventive programmes on HIV and AIDS. In view of these considerations, the objectives of this study were to explore and describe the knowledge and attitudes of women with regard to MTCT of HIV infection and to provide guidelines for the prevention of MTCT of HIV infection. The study was conducted in the rural area of the Ehlanzeni District in the Mpumalanga Province, South Africa at Bourke’s Luck and Elandsfontein clinics. An explorative, descriptive, qualitative research design that is contextual in nature was used. The population consisted of all pregnant women and those in pueperium between 25-40 years of age. Non-probability purposive sampling was used. Participants were selected according to inclusion criteria. Data were collected using semi-structured interviews. The research findings revealed that some participants had knowledge and understanding regarding MTCT of HIV infection while others lacked knowledge and understanding which could impact on MTCT of HIV infection.

This dissertation examines the political economy of HIV biomedical prevention research—largely designed in the global North but conducted in the global South—and its implications for people of diverse genders and sexualities. As a recognized global leader in HIV biomedical prevention research among people categorized as men who have sex with men (MSM) and transgender women, Peru offers a key site in which to explore the increasing focus on gender and sexual identity as a strategic area for extractive research practices. This phenomenon has become particularly visible in the epidemic’s 4th decade, which has emphasized the pursuit of biomedical prevention strategies. Building on nine years of previous experience working inside HIV biomedical prevention studies, this project involved 24 months of ethnographic research, including participant observation; 110 interviews with scientists, study staff, and research subjects; 10 focus groups; and analyses of relevant scientific publications. This study presents four key findings. First, US and Peruvian researchers’ historical and continued entanglement primed Peru to become a hotbed of HIV biomedical prevention research. In this context, population categories imported from the global North have served as powerful tools to sustain a booming local research market, which produces data that aligns with the global demands of the HIV industry. Second, on the ground, research begets more research rather than institutionalized HIV prevention technologies, creating a sustained enterprise in which issues of compensation, value, and labor shape the science. The commodification of gender and sexually diverse identities operates here in two ways: as a mechanism to access particular kinds of bodies and associated HIV risk data, and as a mechanism by which to claim expertise in the HIV prevention research industry for both researchers and community members. Third, Peruvians classified as MSM and transgender women are afforded only temporary access to cutting-edge strategies to prevent HIV, limited to study participation. The result is a sustained pool of people in need of HIV care primed to support the HIV biomedical research economy. Finally, this project illuminates a key paradox within the industry’s contemporary focus on gender and sexual diversity in HIV prevention science. This focus creates the impression that progressive health politics marked the field, while obscuring and absolving ongoing forms of exploitation and unequal gains embedded within it.

Abstract not available