Health-Related Quality of Life in Patients with Osteoarthritis of the Knee attending two Outpatient Clinics in Jos, Nigeria: A Cross-Sectional Descriptive Study.

BACKGROUND: It appears particularly suitable to measure healthrelated quality of life (HRQoL) in patients with knee osteoarthritis (OA) because the chronic debilitating nature of this disease likely takes a considerable toll on HRQoL. The study aims to assess the health-related quality of life in patients with symptomatic knee osteoarthritis attending the two outpatient clinics. The study also aimed to determine factors affecting the HRQoL in patients with knee OA. METHODS: A facility based, cross sectional descriptive study using the abbreviated World Health Organisation Quality of Life (WHOQOL-BREF) (26-item) questionnaire was carried out in two out-patient (general and orthopaedic) clinics of the University Teaching Hospital, Jos, Nigeria over a period of two months. The medical assistants, record staffs and nurses were involved in recruiting the patients while the Family Physicians performed the interview. RESULTS: A total of 120 participants were recruited. The mean age was 58.41±13.03 years and the majority of the respondents were female, constituting 102 (85%) of the participants. The mean body mass index (BMI) was 30.83±7.12 kg/m2 and more than half of the participants were obese. The most common associated chronic disease was hypertension, reported by 93(77.5%). A majority, 86(72%) of the respondents reported their overall QoL and General Health (GH) as poor or fair and all the domains (physical, psychological, social relationships, and environmental) of the QoL were low. QoL scores were relatively low for domain due to psychological health and environment with that of psychological health being more severely affected. Epilepsy was found to affect QoL in patients with knee OA (p= 0.022). There was no significant effect of age, sex, educational status, employment status, marital status, and family income on QoL. CONCLUSION: This study has shown that patients with knee OA attending the outpatient clinics in JUTH, Jos have relatively poor HRQoL with the domain due to psychological health being more severely affected.

CONTEXTE: Il semble particulièrement approprié de mesurer la qualité de vie liée à la santé (QVLS) chez les patients souffrant d'arthrose du genou, car la nature chronique et débilitante de cette maladie a probablement un impact considérable sur la QVLS. L'étude vise à évaluer la qualité de vie liée à la santé des patients souffrant d'arthrose symptomatique du genou qui fréquentent les deux centres de soins ambulatoires. L'étude vise également à déterminer les facteurs affectant la QVLS chez les patients souffrant d'arthrose du genou. MÉTHODES: Une étude descriptive transversale basée sur l'établissement et utilisant le questionnaire abrégé de l'Organisation mondiale de la santé sur la qualité de vie (WHOQOL-BREF) (26 éléments) a été réalisée dans deux cliniques ambulatoires (générale et orthopédique) de l'hôpital universitaire de Jos, au Nigeria, sur une période de deux mois. Les assistants médicaux, le personnel chargé des dossiers et les infirmières ont participé au recrutement des patients, tandis que les médecins de famille ont mené les entretiens. RÉSULTATS: Au total, 120 participants ont été recrutés. L'âge moyen était de 58,41±13,03 ans et la majorité des répondants étaient des femmes, constituant 102 (85%) des participants. L'indice de masse corporelle (IMC) moyen était de 30,83±7,12 kg/m2 et plus de la moitié des participants étaient obèses. La maladie chronique associée la plus fréquente était l'hypertension, signalée par 93 (77,5 %). Une majorité, 86 (72%) des personnes interrogées ont déclaré que leur qualité de vie globale et leur état de santé général étaient mauvais ou moyens et que tous les domaines (physique, psychologique, relations sociales et environnement) de la qualité de vie étaient faibles. Les scores de qualité de vie étaient relativement bas dans les domaines de la santé psychologique et de l'environnement, la santé psychologique étant plus gravement affectée. On a constaté que l'épilepsie affectait la qualité de vie des patients souffrant d'arthrose du genou (p = 0,022). L'âge, le sexe, le niveau d'éducation, la situation professionnelle, la situation matrimoniale et le revenu familial n'avaient pas d'effet significatif sur la qualité de vie. CONCLUSION: Cette étude a montré que les patients atteints d'arthrose du genou qui fréquentent les services de consultation externe de l'hôpital JUTH de Jos ont une qualité de vie relativement médiocre, le domaine de la santé psychologique étant le plus gravement touché. Mots-clés: Qualité de vie liée à la santé, Arthrose du genou, Questionnaire WHOQOL-BREF, Consultations externes.

Giant congenital pigmented naevus with unusual presentation and early malignant transformation in a Nigerian infant: case report and review of the literature.

A six month-old female infant with a giant congenital pigmented naevus is reported because of the rarity and unusual presentation and early malignant transformation. It was the first case to be documented in our centre. There was an extensive giant, darkly pigmented naevus of the "bathing trunk" distribution noted at birth, associated with multiple darkly pigmented smaller naevi scattered over the trunk and limbs. Bv the third month of life large pigmented lesion began to demonstrate small papillomatous projections studding the entire surface and at age six months nodular and warty excrescences appeared including a large pedunculated spherical mass attached to the anal verge. The labia majora became anatomically disfigured by these nodular, warty lesions of various sizes associated with the large pigmented hairy naevus. Histological examination of the excised large perianal and vulvar nodules showed the typical picture of an intradermal naevus consistent with giant congenital pigmented (melanocytic) naevus. The deeper portions of the lesion showed features of malignant transformation. The rapidity of evolution of the lesions including histologic features of early malignant transformation and the gross disfiguring of the genitalia and perineum are uncommon presentation of this melanocytic naevus. In view of the early malignant transformation immediate surgical treatment was indicated. Unfortunately the patient was lost to follow-up. The case report is complimented with a review of the literature.

Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques.

Prolonged antiretroviral therapy (ART) is not likely to eradicate human immunodeficiency virus type I (HIV-I) infection. Here we explore the effect of therapeutic immunization in the context of ART during primary infection using the simian immunodeficiency virus (SIV251) macaque model. Vaccination of rhesus macaques with the highly attenuated poxvirus-based NYVAC-SIV vaccine expressing structural genes elicited vigorous virus-specific CD4 + and CD8+ T cell responses in macaques that responded effectively to ART. Following discontinuation of a six-month ART regimen, viral rebound occurred in most animals, but was transient in six of eight vaccinated animals. Viral rebound was also transient in four of seven mock-vaccinated control animals. These data establish the importance of antiretroviral treatment during primary infection and demonstrate that virus-specific immune responses in the infected host can be expanded by therapeutic immunization.

Cross-protection in NYVAC-HIV-1-immunized/HIV-2-challenged but not in NYVAC-HIV-2-immunized/SHIV-challenged rhesus macaques.

OBJECTIVES: Immunization with attenuated poxvirus-HIV-1 recombinants followed by protein boosting had protected four of eight rhesus macaques from HIV-2SBL6669 challenge. The present study was designed to confirm this result and to conduct the reciprocal cross-protection experiment. METHODS: Twenty-four macaques were primed with NYVAC (a genetically attenuated Copenhagen vaccinia strain) recombinants with HIV-1 and HIV-2 env and gag-pol or NYVAC vector alone and boosted with homologous, oligomeric gp160 proteins or adjuvant only. Binding and neutralizing antibodies, cytotoxic T-lymphocytes (CTL) and CD8 T cell antiviral activity (CD8AA) were evaluated. One half of each immunization and control group were intravenously challenged with SHIV(HXB2) the other half was challenged with HIV-2SBL6669,. Protective outcome was assessed by monitoring virus isolation, proviral DNA and plasma viral RNA. RESULTS: Both immunization groups developed homologous binding antibodies; however, homologous neutralizing antibodies were only observed in NYVAC-HIV-2-immunized macaques. While no cross-reactive neutralizing antibodies were detected, both immunization groups displayed cross-reactive CTL. Significant CD8AA was observed for only one NYVAC-HIV-2-immunized macaque. Virological assessments verified that both NYVAC-HIV-1 and NYVAC-HIV-2 immunization significantly reduced viral burdens and partially protected against HIV-2 challenge, although cross-protection was not at the level that had been previously reported. Humoral antibody and/or CTL and CD8AA were associated with protection against homologous HIV-2 challenge, while cellular immune responses seemed more important for cross-protection. No significant protection was observed in the SHIV-challenged macaques, although NYVAC-HIV-1 immunization resulted in significantly lower viral burdens compared with controls. CONCLUSIONS: Further delineation of cross-reactive mechanisms may aid in the development of a broadly protective vaccine.

Targeting the mucosa: genetically engineered vaccines and mucosal immune responses.

The discovery that inoculation of DNA leads to strong and long lasting immune responses generated enthusiasm to assess the efficacy of various genetically engineered vaccines against mucosally acquired infections. Various techniques have been used to generate the most suitable DNA vaccines, ranging from immunization with naked DNA to utilizing genetically engineered recombinant viruses and bacteria to deliver the DNA. Different DNA vaccine modalities and mucosal immune responses to them have been discussed. It has been shown that even though intramuscular and intradermal immunization with these vaccines generates strong systemic responses, mucosal responses are not induced. It has been proposed that the site of immunization determines mucosal immune responses and that primed lymphocytes preferentially accumulate at sites where they have been induced thus generating the strongest cellular and antibody responses at the site of vaccination. The impact of the site of induction on mucosal immune responses to vaccines is discussed. It is possible to enhance desired vaccine effects in the mucosa and to modify the undesirable side effects. Cytokines such as IL-2, IL-12, IL-15 and IL-18 have been used to enhance CTL activity while IL-5, IL-6 and the chemokine MIP-1 alpha have shown the capacity to increase IgA responses to vaccines.

A comprehensive panel of near-full-length clones and reference sequences for non-subtype B isolates of human immunodeficiency virus type 1.

Non-subtype B viruses cause the vast majority of new human immunodeficiency virus type 1 (HIV-1) infections worldwide and are thus the major focus of international vaccine efforts. Although their geographic dissemination is carefully monitored, their immunogenic and biological properties remain largely unknown, in part because well-characterized virological reference reagents are lacking. In particular, full-length clones and sequences are rare, since subtype classification is frequently based on small PCR-derived viral fragments. There are only five proviral clones available for viruses other than subtype B, and these represent only 3 of the 10 proposed (group M) sequence subtypes. This lack of reference sequences also confounds the identification and analysis of mosaic (recombinant) genomes, which appear to be arising with increasing frequency in areas where multiple sequence subtypes cocirculate. To generate a more representative panel of non-subtype B reference reagents, we have cloned (by long PCR or lambda phage techniques) and sequenced 10 near-full-length HIV-1 genomes (lacking less than 80 bp of long terminal repeat sequences) from primary isolates collected at major epicenters of the global AIDS pandemic. Detailed phylogenetic analyses identified six that represented nonrecombinant members of HIV-1 subtypes A (92UG037.1), C (92BR025. 8), D (84ZR085.1 and 94UG114.1), F (93BR020.1), and H (90CF056.1), the last two comprising the first full-length examples of these subtypes. Four others were found to be complex mosaics of subtypes A and C (92RW009.6), A and G (92NG083.2 and 92NG003.1), and B and F (93BR029.4), again emphasizing the impact of intersubtype recombination on global HIV-1 diversification. Although a number of clones had frameshift mutations or translational stop codons in major open reading frames, all the genomes contained a complete set of genes and three had intact genomic organizations without inactivating mutations. Reconstruction of one of these (94UG114.1) yielded replication-competent virus that grew to high titers in normal donor peripheral blood mononuclear cell cultures. This panel of non-subtype B reference genomes should prove valuable for structure-function studies of genetically diverse viral gene products, the generation of subtype-specific immunological reagents, and the production of DNA- and protein-based subunit vaccines directed against a broader spectrum of viruses.

Highly attenuated HIV type 2 recombinant poxviruses, but not HIV-2 recombinant Salmonella vaccines, induce long-lasting protection in rhesus macaques.

Immunization schemes employing priming with vector-based vaccine candidates followed by subunit booster administrations have been explored and shown to have merit in the human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus systems. In this study, we have assessed the priming capacity of highly attenuated poxvirus vector (NYVAC and ALVAC)-based HIV-2 recombinants, as well as Salmonella typhimurium HIV-2 recombinants in rhesus macaques. ALVAC- and NYVAC-based vaccine candidates expressing the HIV-2 gag, pol, and env genes or NYVAC-based recombinants expressing either gp160 or gp120 were used to immunize rhesus macaques in combination protocols with alum-adjuvanted HIV-2 rgp160. Following intravenous challenge exposure with 100 infectious doses of the HIV-2SBL6669 parental virus genotype mixture, seven of eight animals were protected from infection. The seven protected animals were rechallenged 6 months postprimary challenge, without additional booster inoculations, with the same dose of the HIV-2SBL6669 parental virus. Five of the seven animals remained protected against HIV-2 infection at 6 months following the second challenge. In contrast, oral immunization with recombinant Salmonella expressing the HIV-2 gag and the gp120 portion of the envelope either alone or in combination with alum-adjuvanted rgp160 failed to confer protection. These results suggest that the NYVAC- and ALVAC-based recombinants may confer long-lasting protection and that these two highly attenuated poxvirus vaccine vectors may represent promising candidates for developing an acquired immunodeficiency syndrome vaccine.

HIV-1 recombinant poxvirus vaccine induces cross-protection against HIV-2 challenge in rhesus macaques.

Rhesus macaques were immunized with attenuated vaccinia or canarypox human immunodeficiency virus type 1 (HIV-1) recombinants and boosted with HIV-1 protein subunits formulated in alum. Following challenge with HIV-2SBL6669, three out of eight immunized macaques resisted infection for six months and another exhibited significantly delayed infection, whereas all three naive controls became infected. Immunizations elicited both humoral and cellular immune responses; however, no clear correlates of protection were discerned. Although more extensive studies are now called for, this first demonstration of cross-protection between HIV-1 and -2 suggests that viral variability may not be an insurmountable problem in the design of a global AIDS vaccine.

Humoral and cellular immune responses in rhesus macaques infected with human immunodeficiency virus type 2.

Eighteen rhesus macaques were inoculated with either an infectious molecularly cloned human immunodeficiency virus type 2 (HIV-2)SBL/ISY, or with one of eight mutants defective in one or more accessory genes. The immune responses generated by the macaques were monitored for up to 2 years postinfection. All the macaques except those that received mutants lacking the vpr or vif genes demonstrated low to moderate antibody titers. Macaques inoculated with vpx- mutants exhibited a persistent serological response, suggesting continuous virus expression even in the absence of detectable virus in the peripheral blood mononuclear cells (PBMCs). Neutralizing antibodies developed in only four macaques. In general, low-level cytotoxic T lymphocyte (CTL) activity, not clearly HIV-2 specific, was detected in PBMCs. However, one virus-negative macaque exhibited significant HIV-2-specific CTL activity in an enriched CD8+ cell population from PBMCs, suggesting clearance of the viral infection. In addition, CTL activity against the Env and Gag/Pol epitopes of HIV-2 by CD8+ lymphocytes from the spleens and lymph nodes of two infected macaques, in one case requiring CD8+ T cell enrichment and in the other clearly evident in unfractionated tissue lymphocytes, was demonstrated for the first time. This sequestration of tissue CTLs occurred in the absence of significant levels of circulating CTLs in the blood. Our results suggest that routine monitoring of PBMCs may sometimes be inadequate for detecting cell-mediated immune responses. Elucidation of immune correlates of vaccine protection may therefore require sampling of lymphoid tissues and assessment of enriched CD8+ populations.

Subgroup G HIV type 1 isolates from Nigeria.

PIP: Nucleotide sequences were obtained for portions of the envelope and gag genes of 4 HIV-1 isolates from Nigeria. The gag gene sequences clustered with previously described gag sequences from Gabon, Zaire, and Taiwan, which form the G clade of HIV-1. This documented for the first time the presence of subgroup G viruses in Nigeria. The env gene sequences were most closely related to env sequences reported from 2 isolates previously classified as gag subgroup G and, with those 2 env sequences, defined the subgroup G env genotype. Virus isolates were obtained by cocultivation of peripheral blood mononuclear cells (PBMCs) from Nigerian AIDS patients (isolates JV1018 and JP88) or healthy prostitutes (G3 and G9) with normal uninfected PBMCs (JV1083, JP88, and G3) or GEM-SS, a T cell line (G9). Clones containing env and gag gene sequences were obtained by polymerase chain reaction amplification, using DNA from these cultures. The region of gag amplified by primers SK37 and SK39 containing BamHI and KpnI sites, respectively, in 5' tails, was cloned into the KpnI-BamHI site of pKSBluescript and sequenced. When the gag sequences from 2 of the Nigerian viruses were subtyped by weighted parsimony, both viruses grouped with others of the gag G subgroup. A similar analysis of env sequences from all 4 Nigerian isolates showed that they were most closely related to 2 env sequences that had been assigned to env subgroup G. The Nigerian env sequences clustered more closely with each other than they did with the other 2 subgroup G viruses. Consensus of the inferred amino acid sequences of the 4 env genes showed that the V3 loop closely resembled the A to F consensus. 8 positions in the Nigerian consensus sequence appeared to be unique. However, whether these are signature residues for Nigerian subgroup G isolates or for subgroup G isolates will require the characterization of more isolates.^ieng

Comparison of different vaccines and induced immune response against Campylobacter jejuni colonization in the infant mouse.

The degree of protection conferred by vaccinated dams on infant mice against colonization by Campylobacter jejuni depended on the bacterial strain, preparation, and route of administration of the vaccine. In some instances of homologous protection, serum bactericidal titres correlated well with protection. However, boiled C. jejuni vaccine, which was non-protective, also elicited a strong bactericidal antibody response. Conversely, bactericidal activity could not be demonstrated against strains capable of cross-protection. There was a good correlation between high campylobacter-specific IgG response and bactericidal activity.

Cross-protection of infant mice against intestinal colonisation by Campylobacter jejuni: importance of heat-labile serotyping (Lior) antigens.

An association of the heat-labile antigens detected by the Lior serotyping scheme with ability to protect infant mice against gastrointestinal colonisation with Campylobacter jejuni has been established. Overall, 39 (57%) of 68 infant mice challenged with a heterologous strain of the same Lior serotype as the vaccine strain were protected, compared with 40 (85%) of 47 infants protected against a homologous challenge. In contrast, none of the infant mice challenged with a strain carrying the same heat-stable antigens (i.e., of the same Penner serotype as the vaccine strain) were protected.

The mechanism of protection of infant mice from intestinal colonisation with Campylobacter jejuni.

BALB/c mice, vaccinated intraperitoneally with a heat-killed (62 degrees C) suspension of Campylobacter jejuni before mating, completely protect c. 90% of their own infants from intestinal colonisation. This protection has now been investigated further in fostering experiments. Fostering by vaccinated dams within the first 24 h of life prevented intestinal colonisation in 50% of infants from non-vaccinated dams, and reduced colonisation in a further 25%. Infants from vaccinated dams, even if allowed to receive their own mothers' colostrum and milk, became susceptible to challenge when subsequently fostered by non-vaccinated dams. Immunity in experimentally infected infant mice depended upon the consumption of immune milk at and after the time of challenge. High concentrations of IgG antibodies specific for C. jejuni were found in the serum and mammary secretion of vaccinated dams, but there was very little specific IgA antibody.