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Biomedical subjects

N French

Publications and source records attributed to N French.

At least 19 recordsLinked to original sources
PubMed2005

Immunocontraceptive effects on female rabbits infected with recombinant myxoma virus expressing rabbit ZP2 or ZP3.

Recombinant myxoma viruses expressing rabbit zona pellucida 2 (rZP2) or rabbit zona pellucida 3 (rZP3) glycoproteins were constructed and tested in domestic rabbits to assess their potential to induce autoimmune infertility. The recombinant virus expressing rZP2 had no effect on fertility or ovarian histology, despite all animals developing antibodies against the rZP2 antigen. However, recombinant viruses expressing rZP3 induced infertility in 70% of animals at the first breeding. Serum antibodies were relatively short-lived, but antibody was bound to zona pellucida of all rabbits from Day 10 onward. There was no obvious correlation between infertility and rZP3 antibody titer. There was a transient inflammatory response in the ovaries of rZP3-immunized rabbits at Day 15 but no T-cell response to rZP3 could be detected at any time. Dysfunctional follicular formation was present in ovaries from rabbits infected with rZP3-expressing viruses 15-40 days postinfection but this had disappeared at later time points. A recombinant myxoma virus expressing a modified rZP3 antigen with the C-terminal hydrophobic putative anchor sequence deleted was also tested. This virus did not induce either infertility or an antibody response against the zona pellucida. Thus, the context of antigen presentation was crucial for an autoimmune response.

Animals↗
PubMed2004

Quantitative estimates of the risk of new outbreaks of foot-and-mouth disease as a result of burning pyres.

The risk of dispersing foot-and-mouth disease virus into the atmosphere, and spreading it to susceptible holdings as a result of burning large numbers of carcases together on open pyres, has been estimated for six selected pyres burned during the 2001 outbreak in the UK. The probability of an animal or holding becoming infected was dependent on the estimated level of exposure to the virus predicted from the concentrations of virus calculated by the Met Office, Bracknell. In general, the probability of infection per animal and per holding decreased as their distance from the pyre increased. In the case of two of the pyres, a holding under the pyre plumes became infected on a date consistent with when the pyre was lit. However, by calculating their estimated probability of infection from the pyres it was concluded that it was unlikely that in either case the pyre was the source of infection.

Animals↗
PubMed2004

Polyuria in association with Plasmodium falciparum malaria in a region of unstable transmission.

During a recent epidemic of Plasmodium falciparum malaria in Hlabisa district, KwaZulu Natal, polyuria was recognized in a subset of adults presenting to hospital with severe disease. In January to May 2000, following consent, cases of severe malaria provided blood spots for HIV testing, clinical data, and blood and urine samples for investigation of the polyuria. Four hundred and eleven adults with malaria were admitted, of whom 175 had severe malaria and 37 had polyuria (21% of severe cases). In those with polyuria the mean 24-h urine output was 3018 ml or 2.85 ml/kg/h. Ten of 15 (66%) patients investigated had urine and plasma osmolalities consistent with diabetes insipidus. There was no significant association between polyuria and sex, age, HIV status or features of severe malaria. Whether the polyuria in these non-immune adults is a localized problem unrelated to malaria, or a hitherto unrecognized complication of severe malaria is not clear. Physicians are alerted to this observation, and the need for more clinical and pathophysiological studies.

Adult↗
PubMed2004

Other bacteria and HIV disease.

HIV-infected individuals are predisposed to infection with bacteria, in particular Streptococcus pneumoniae and non-typhi Salmonella. Other bacteria also complicate HIV disease, either because they are inherently pathogenic--Staphylococcus aureus, Enterobacteraciae, bacterial agents of enteritis--or they take advantage of advanced immunosuppression--Rhodococcus spp, Nocardia spp. An understanding of the role of bacteria is essential to the care of HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed2002

Diarrhea, CD4 counts and enteric infections in a community-based cohort of HIV-infected adults in Uganda.

OBJECTIVES: To examine relationships between diarrhoea, CD4 cell counts and stool pathogens in a community-based cohort of HIV-infected adults in Uganda. PATIENTS AND METHODS: Stool specimens, obtained between October 1995 and December 1997, were linked to patients' symptoms and laboratory results. The relationship between CD4 counts and symptoms was tested using the Wilcoxon rank-sum test and those between organisms and diarrhoea using first a univariate Mantel-Haenszel analysis and then a logistic regression model adjusted for CD4 count and multiple organisms. RESULTS: 1,213 HIV-infected individuals (70% women, median CD4 cell count at enrollment 215 cells/microl) were followed for 1,224 person years of observation (pyo). 484 stool samples were examined, 357 from patients with diarrhoea. The rate of diarrhoea was 661 episodes per 1,000 pyo. CD4 counts were significantly lower in individuals with diarrhoea than those without (P < 0.001, Wilcoxon rank-sum test). Forty-nine percent of diarrhoeal stools and 39% of stools from asymptomatic patients contained enteric pathogens. The most frequent isolates were helminths (29.5% of all stools), followed by bacteria (19.2%) and then protozoa (8.9%). Rates of isolation of diarrhoea-associated pathogens were 29% from diarrhoeal stools and 17% from asymptomatic stools (P = 0.01, chi(2) test). The association between diarrhoea and infection with bacteria or protozoa was weak and there was no association with helminths. Cryptosporidium parvum infection alone was associated with low CD4 counts. CONCLUSIONS: Diarrhoea was common and most strongly associated with low CD4 counts. Bacteria were frequently found, even in stools from asymptomatic individuals. Over two-thirds of diarrhoeal episodes were undiagnosed, suggesting that unidentified agents or primary HIV enteropathy are important causes of diarrhoea in this population.

AIDS-Related Opportunistic Infections↗
PubMed2002

Operational assessment of isoniazid prophylaxis in a community AIDS service organisation in Uganda.

SETTING: Isoniazid therapy was shown to be 70% effective at preventing tuberculosis in HIV-infected, PPD-positive Ugandan adults, but the feasibility of implementation outside an efficacy trial has not been established. OBJECTIVE: To study uptake, adherence and feasibility of a 6-month course of isoniazid preventive therapy in community-based HIV clinics in Uganda. DESIGN: Observational cohort study describing selection of patients and adherence to isoniazid 300 mg daily. Adherence was measured by clinic attendance, pill counts and urine isoniazid metabolite testing. Implementation was costed on a service delivery basis. RESULTS: Of 1597 cohort members, 22% were PPD-positive. Over 18 months, 193 PPD-positive individuals were assessed for prophylaxis and 98 (51%) were enrolled. Of those enrolled, 74 (76%) completed their course of isoniazid therapy, and 80% were fully adherent. Symptoms or previous treatment for tuberculosis and suspicion of tuberculous lymphadenopathy were the main reasons for exclusion. The additional cost of providing this service was US $14,549. CONCLUSION: Clinics specialising in the care of persons with HIV/AIDS can successfully implement isoniazid prophylaxis. Difficulties in excluding active tuberculosis and the costs of running the programme may limit its widespread implementation.

AIDS-Related Opportunistic Infections↗
PubMed2001

Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults.

BACKGROUND: Falciparum malaria and HIV-1 infection are two of the most important health problems facing sub-Saharan Africa. No convincing evidence of an association between symptomatic malaria and HIV-1 infection has been found. OBJECTIVE: To investigate the effect of HIV-associated immunosuppression on malarial fever rates. DESIGN: An observational cohort study in HIV-specific, primary healthcare clinics in Entebbe, Uganda, on 1371 HIV-1-infected adults participating in a randomized trial of 23-valent pneumococcal vaccine. METHODS: Cohort members underwent routine 6 monthly surveillance and had open clinic access when sick. Episodes of fever were assessed according to standardized protocols. Rates of malaria are described according to HIV immune status determined by CD4 T cell counts. RESULTS: Incidence rates of Plasmodium falciparum malarial fever showed a marked inverse relationship with CD4 T cell count; 140, 93 and 57 cases per 1000 pyo for CD4 T cell groups < 200, 200--499 and > 500 respectively, P < 0.001. Malarial fever definitions incorporating parasite density criteria (derived from asymptomatic surveillance) to correct for chance findings of fever and P. falciparum parasitaemia, did not affect the association of incidence rates with immunosuppression. CONCLUSION: These data support an interaction between symptomatic P. falciparum and HIV. Emphasis on mosquito avoidance measures should be an important component of education and counselling of HIV/AIDS patients in malaria-endemic areas, and suggests an additional HIV-related public health problem in Africa.

AIDS-Related Opportunistic Infections↗
PubMed2001

Genetic variation in Australian isolates of myxoma virus: an evolutionary and epidemiological study.

Myxoma virus and the European rabbit have been coevolving in Australia since the introduction of the Standard Laboratory Strain (SLS) of myxoma virus as a biological control agent for rabbits in 1950. To examine the degree of genetic variation that has occurred in the virus between 1950 and 1995 and to find genetic markers to use for epidemiological studies, we have examined 37 recent field isolates of myxoma virus for restriction fragment length polymorphisms (RFLPs) by comparision with the progenitor SLS released in 1950. Fifteen RFLPs in Australian isolates have been identified and characterized by mapping and partial DNA sequence analysis. The RFLPs that are most common are deletion and insertion events in regions of tandem repeats. Some of these RFLPs have been investigated by using polymerase chain reaction to identify them in archival tissue samples. In epidemiological studies we characterized two polymorphisms which occur in the Lausanne strain of myxoma virus (widely introduced into Australia from the 1970s) but not in SLS and showed that all of the viruses we isolated were derived from the SLS.

Amino Acid Sequence↗
PubMed2000

23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial.

BACKGROUND: Infection with Streptococcus pneumoniae is a frequent and serious problem for HIV-immunosuppressed adults. Vaccination is recommended in the USA and Europe, but there are no prospective data that show vaccine efficacy. METHODS: 1392 (937 female) HIV-1-infected adults in Entebbe, Uganda, were enrolled. 697 received 23-valent pneumococcal polysaccharide vaccine and 695 received placebo. The primary endpoint was first event invasive pneumococcal disease. Secondary endpoints included vaccine serogroup-specific invasive disease, all (probable and definite) pneumococcal events, all-cause pneumonia, and death. FINDINGS: First invasive events occurred in 25 individuals (24 bacteraemias, one pyomyositis), 15 in the vaccine arm and ten in the placebo arm (hazard ratio [HR] 1.47; 95% CI 0.7-3.3). 22 isolates (88%) were of vaccine-specific serogroups with 15 events in the vaccine arm compared with seven in the placebo arm (HR 2.10; 0.9-5.2). All pneumococcal events had a similar distribution (20 vs 14; HR 1.41; 0.7-2.8) though all-cause pneumonia was significantly more frequent in the vaccine arm (40 vs 21; HR 1.89; 1.1-3.2). Mortality was unaffected by vaccination. INTERPRETATION: 23-valent pneumococcal polysaccharide vaccination is ineffective in HIV-1-infected Ugandan adults and probably has little, or no, public health value elsewhere in sub-Saharan Africa. Increased rates of pneumococcal disease in vaccine recipients may necessitate a reappraisal of this intervention in other settings.

AIDS-Related Opportunistic Infections↗
PubMed2000

An improved algorithm for determining HIV type 1 subtypes in a primary laboratory in Uganda.

A pilot study was undertaken with the objective of developing a simple, economical, and efficient algorithm through which to subtype HIV-1 in a large epidemiological cohort study in Uganda. A peptide enzyme immunoassay (PEIA) employing both V3 and gp41 regions and a heteroduplex mobility assay (HMA) were evaluated in comparison with DNA sequencing. Of 146 samples selected, 115 (79%) were successfully sequenced. Taking sequence data as the "gold standard," other assays were compared with these data. The HMA correctly identified 95 (83%) of the samples, and only 1 sample was wrongly identified. The V3 PEIA alone and in combination with gp41 peptides correctly identified 76 and 78% of the samples, respectively; however, the number of wrongly identified samples was four times less with the combination compared with V3 peptides alone (4 versus 16%). The sensitivity, specificity, and positive and negative predictive values for serotype A and D samples were greater for the combination than V3 peptides alone. We have described a new algorithm to segregate subtypes A and D. This algorithm uses the two peptide assays followed by HMA and then DNA sequencing for untypable samples, giving an accuracy of 95% at a cost of 37 and 21% for consumables compared with subtyping all the samples by HMA or DNA sequencing, respectively. This proposed approach is suitable for epidemiological studies in Uganda and other regions with a predominance of A and D subtypes.

Algorithms↗
PubMed2000

Rhodococcus equi and HIV-1 infection in Uganda.

OBJECTIVES: To describe three cases of Rhodococcus equi infection in a cohort of HIV-1 infected adults in Entebbe, Uganda and to compare this to the rates and presentation of tuberculosis in this cohort. METHODS: Consecutive HIV-1 infected adults registering with a community HIV/AIDS clinic in Entebbe were enrolled in a cohort between October 1995 and June 1998 as part of an intervention trial of pneumococcal polysaccharide vaccine. Participants were routinely reviewed every 6 months and had open access to the clinic when unwell. Standard protocols were followed for investigation and management of illness. Microbiological investigations followed standard procedures. RESULTS: 1372 (71% female) study participants were followed for 2141 person years of observation (pyo). Rhodococcus equi was isolated from three study participants from blood, a lymph node aspirate and stool. The individuals were undergoing investigation of acute pneumonia, acute cough with cervical lymphadenopathy and chronic fever with wasting, respectively. The clinical features of these cases are described. All had a CD4 T-cell count of <300/ml. The rate of R. equi infection in the cohort was 1.4/1000 pyo. There were 132 cases of pulmonary and extrapulmonary tuberculosis in the cohort which were diagnosed either microbiologically or clinically. The rate of laboratory confirmed mycobacterial disease was 50.1/1000 pyo. The ratio of mycobacterial disease to R. equi disease was 36:1 (95% CI 11-113:1). CONCLUSIONS: Rhodococcus equi infection occurs in HIV-1 infected adults in Africa. The infection is clinically indistinguishable from pulmonary and extra-pulmonary tuberculosis in the cohort described here. Although the rate of R. equi disease is much less than that of tuberculosis, it is important to consider it in the differential diagnosis of tuberculous infection in cases which are smear negative. Rhodococcus equi infection is probably underdiagnosed in Africa due to a lack of microbiological facilities and its resemblance to common commensal organisms.

AIDS-Related Opportunistic Infections↗
PubMed2000

Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum.

Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0.3-0.4) were less than half those observed in African locations (0. 76-0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples (0.51-0.65). Furthermore, variation was distributed among locations in South America (F:(ST) = 0.364) and within locations in Africa (F:(ST) = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.

Africa↗
PubMed1999

Immunologic and clinical stages in HIV-1-infected Ugandan adults are comparable and provide no evidence of rapid progression but poor survival with advanced disease.

Clear understanding of the natural history of HIV-1 disease is critical for planning and developing appropriate therapeutic strategies for HIV-1-infected populations in the developing world. Present knowledge about Africa is based on very limited data that largely use clinical staging as the prognostic marker; this approach has not been prospectively validated. Our objectives were to compare clinical staging and CD4+ T-cell counts as prognostic tools and to describe survival and cause of death in seroprevalent HIV-1-infected Ugandan adults by means of a prospective cohort study. Consecutive HIV-1-infected adults registering with a community HIV/AIDS clinic in Entebbe, Uganda were enrolled between October 1994 to January 1995 and observed during follow-up until the end of December 1997. Baseline CD4+ T-cell count distribution showed clear and appropriate associations with clinical stage in the 201 participants. Both provided equivalent prognostic information: median survival with CD4+ T-cell count <200 cells/microl was 9 months (95% confidence interval [CI], 7-15 months) compared with 19 and 7 months (95% CI, 10-28 and 0-8 months, respectively) in clinical stages 3 and 4, respectively; survival at 3 years with CD4+ T-cell count > or =200 cells/microl was 68% and for clinical stage 1 and 2, 80% and 60%, respectively. Clinical stage 3 and 4 were 76% sensitive and 65% specific for predicting a CD4+ T-cell count <200 cells/microl, positive predictive value of 56%, negative predictive value 78%. In all, 82 participants died (41%; mortality rate 216 of 1000 person-years) and was strongly associated with low CD4+ T-cell counts. In conclusion, clinical staging is valid and comparable with staging by CD4 T-cell counts for epidemiologic measurements. Mortality with early disease in Entebbe appears equivalent to that found in the developed world but there is poor survival with advanced disease.

Adolescent↗
PubMed1999

Infertility in female rabbits (Oryctolagus cuniculus) alloimmunized with the rabbit zona pellucida protein ZPB either as a purified recombinant protein or expressed by recombinant myxoma virus.

Development of immunocontraceptives for wild rabbit populations requires selection of both effective antigens and effective delivery systems. Recombinant rabbit zona pellucida glycoprotein B (ZPB) produced in eukaryotic cells in vitro was an effective antigen and induced sustained infertility in 70% of female rabbits. This required two boosts and serum antibody titers of 12 800 or greater. Antibody titers in females were low after the initial immunization, as might be expected with a self-antigen; however, male rabbits had a strong antibody response, indicating that the protein was immunologically foreign. To develop a delivery system, ZPB was delivered by infection with a recombinant myxoma virus. In contrast to the results with ZPB protein, infection of rabbits induced a similar serum antibody response to ZPB in both sexes. This indicated that presentation of ZPB in the context of a virus infection was able to overcome tolerance in females. However, the antibody titers were lower than 12 800, and only 25% of female rabbits were infertile. This antibody response was boosted by injections of recombinant ZPB protein, after which 80% of female rabbits were infertile. Infertility was associated with antibody binding to zonae and varying degrees of ovarian pathology characterized by follicular degeneration and substantial depletion of primordial follicles. Oocyte and follicular degeneration appeared to be the principal mechanism of infertility and may be primarily induced by antibodies to ZPB.

Animals↗
PubMed1999

HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5 and DQB1 polymorphism detected by PCR-SSP in a semi-urban HIV-positive Ugandan population.

PCR-SSP was used to HLA-type a cohort of Ugandan HIV-positive individuals. The results represent a more comprehensive description of HLA in an African population than previously described and are in concordance with data from a general Black population. Substantial differences exist between this population and Caucasoid populations in which immunological responses to HIV have been investigated; this emphasises that the main HLA-restrictive elements for HIV-specific cytotoxic T lymphocytes will most likely be different for each population.

Base Sequence↗