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  • Gustafson, Per, et al. (författare)
  • Tuberculosis in Bissau: incidence and risk factors in an urban community in sub-Saharan Africa
  • 2004
  • Ingår i: International Journal of Epidemiology. - Oxford : Oxford University Press. - 1464-3685 .- 0300-5771. ; 33:1, s. 163-172
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Despite the long history of tuberculosis (TB) research, population-based studies from developing countries are rare. Methods In a prospective community study in Bissau, the capital of Guinea-Bissau, we assessed the impact of demographic, socioeconomic and cultural risk factors on active TB. A surveillance system in four districts of the capital identified 247 adult (greater than or equal to15 years) cases of intrathoracic TB between May 1996 and June 1998. Risk factors were evaluated comparing cases with the 25 189 adults living in the area in May 1997. Results The incidence of intrathoracic TB in the adult population was 471 per 100 000 person-years. Significant risk factors in a multivariate analysis were increasing age (P < 0.0001), male sex (odds ratio [OR] = 2.58, 95% CI: 1.85, 3.60), ethnic group other than the largest group (Pepel) (OR = 1.64, 95% CI: 1.20, 2.22), adult crowding (OR = 1.68, 95% CI: 1.18, 2.39 for >2 adults in household), and poor quality of housing (OR = 1.66, 95% CI: 1.24, 2.22). Household type was important; adults living alone or with adults of their own sex only, had a higher risk of developing TB than households with husband and wife present, the adjusted OR being 1.76 (95% CI: 1.11, 2.78) for male households and 3.80 (95% CI: 1.69, 8.56) for female households. In a multivariate analysis excluding household type, child crowding was a protective factor, the OR being 0.68 (95% CI: 0.51, 0.90) for households with >2 children per household. Conclusions Bissau has a very high incidence of intrathoracic TB. Human immunodeficiency virus (HIV), increasing age, male sex, ethnicity, adult crowding, family structure, and poor housing conditions were independent risk factors for TB. Apart from HIV prevention, TB control programmes need to emphasize risk factors such as socioeconomic inequality, ethnic differences, crowding, and gender.
  • Gustafson, Per, et al. (författare)
  • Tuberculosis mortality during a civil war in Guinea-Bissau
  • 2001
  • Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association. - 1538-3598. ; 286:5, s. 599-603
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Tuberculosis (TB) is an increasing global problem, despite effective drug therapies. Access to TB therapy during conflict situations has not been studied. OBJECTIVE: To determine the effect of irregular TB treatment due to an armed conflict in Guinea-Bissau, West Africa. DESIGN, SETTING, AND PATIENTS: Ongoing retrospective cohort study conducted in the capital city of Bissau among 101 patients with TB who received irregular or no treatment during the civil war (war cohort; June 7-December 6, 1998) and 108 patients with TB who received treatment 12 months earlier (peace cohort; June 7-December 6, 1997) and comparison of an additional 42 patients who had completed treatment before June 6, 1998, and 69 patients who had completed treatment before June 6, 1997. MAIN OUTCOME MEASURE: Mortality rates, compared by irregular (war cohort) vs regular (peace cohort) access to treatment, by intensive vs continuation phase of treatment, and by those who had previously completed treatment for TB. RESULTS: Irregular treatment was associated with an increased mortality rate among patients with TB. The mortality rate ratio (MR) was 3.12 (95% confidence interval [CI], 1.20-8.12) in the war cohort, adjusting for age, sex, human immunodeficiency virus (HIV) infection, residence, and length of treatment. Each additional week of treatment before the war started increased probability of survival by 5% (95% CI, 0%-10%). In the intensive phase of treatment, the adjusted MR was 3.30 (95% CI, 1.04-10.50) and in the continuation phase it was 2.26 (95% CI, 0.33-15.34). Increased mortality among the war cohort was most marked in HIV-positive patients, who had an adjusted MR of 8.19 (95% CI, 1.62-41.25). Mortality was not increased in HIV-positive or HIV-negative patients who had completed TB treatment when the war started. CONCLUSIONS: Interruption of treatment had a profound impact on mortality among patients with TB during the war in Guinea-Bissau. Regular treatment for TB was associated with significantly improved survival for HIV-infected individuals. In emergencies, it is crucial to ensure availability of TB drugs.
  • Norrgren, Hans R., et al. (författare)
  • Increased prevalence of HTLV-1 in patients with pulmonary tuberculosis coinfected with HIV, but not in HIV-negative patients with tuberculosis
  • 2008
  • Ingår i: Journal of Acquired Immune Deficiency Syndromes. - Philadelphia, PA : Lippincott Williams & Wilkins. - 1525-4135 .- 1944-7884. ; 48:5, s. 607-610
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Few and inconclusive results have been presented regarding the influence of human T-lymphotropic virus 1 (HTLV-1) infection on the risk of acquiring tuberculosis (TB). Methods: In 1994-1997, we performed a prospective study on hospitalized adult patients with pulmonary TB in Guinea-Bissau and compared the clinical outcome in HIV-2 and HIV-negative patients. We determined the prevalence of HTLV-1 in all patients screened and diagnosed with TB in that study and compared the infection rate with a serosurvey of HTLV-1 in a population sample from a community-based study conducted at the same time and in the same city. Results: In the TB group, a total of 32 (11.4%) of 280 patients were positive for HTLV-1. This was significantly higher compared with the population-based group in which 74 (3.5%) of 2117 were HTLV-1 positive [crude odds ratio (OR) = 3.6; 95% confidence interval (CI) 2.2 to 5.6, P < 0.001]. However, in a logistic regression analysis controlling for age, gender, and HIV result, the difference was no longer significant (OR = 1.61; 95% CI 0.95 to 2.70, P = 0.074). In HIV-negative patients, no association was found between HTLV-1 and TB (OR = 1.18; 95% CI 0.48 to 2.89, P = 0.71), whereas a significant association was found in HIV-positive patients (OR = 2.41; 95% CI 1.26 to 4.61, P = 0.008). Conclusions: The immunosuppressive effect of HTLV-1 alone was not enough to increase the risk of TB in a highly endemic country, but HTLV-1 increased the risk of TB among HIV-infected individuals.
  • Nowroozalizadeh, Salma, et al. (författare)
  • Microbial Translocation Correlates with the Severity of Both HIV-1 and HIV-2 Infections
  • 2010
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 1537-6613. ; 201:8, s. 1150-1154
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbial translocation has been linked to systemic immune activation during human immunodeficiency virus (HIV) type 1 infection. Here, we show that an elevated level of microbial translocation, measured as plasma lipopolysaccharide (LPS) concentration, correlates with AIDS in both individuals infected with HIV type 1 and individuals infected with HIV type 2. LPS concentration also correlates with CD4(+) T cell count and viral load independently of HIV type. Furthermore, elevated plasma LPS concentration was found to be concomitant with defective innate and mitogen responsiveness. We suggest that microbial translocation may contribute to loss of CD4(+) T cells, increase in viral load, and defective immune stimuli responsiveness during both HIV type 1 and HIV type 2 infections.
  • Nowroozalizadeh, Salma, et al. (författare)
  • Studies on toll-like receptor stimuli responsiveness in HIV-1 and HIV-2 infections
  • 2009
  • Ingår i: Cytokine. - : Academic Press. - 1096-0023. ; 46:3, s. 325-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: HIV-1 and HIV-2 are two related viruses with distinct clinical outcomes, where HIV-1 is more pathogenic and transmissible than HIV-2. The pathogenesis of both infections is influenced by the dysregulation and deterioration of the adaptive immune system. However, their effects on the responsiveness of innate immunity are less well known. Here, we report on toll-like receptor (TLR) stimuli responsiveness in HIV-1 or HIV-2 infections. Methods: Whole blood from 235 individuals living in Guinea-Bissau who were uninfected, infected with HIV-1, infected with HIV-2, and/or infected with HTLV-1, was stimulated with TLR7/8 and TLR9 agonists, R-848 and unmethylated CpG DNA. After TLR7/8 and TLR9 stimuli, the expression levels of IL-12 and IFN-alpha were related to gender, age, infection status, CD4(+) T cell counts. and plasma viral load. Results: Defective TLR9 responsiveness was observed in the advanced disease stage, along with CD4(+) T cell loss in both HIV-1 and HIV-2 infections. Moreover, TLR7/8 responsiveness was reduced in HIV-1 infected individuals compared with uninfected controls. Conclusions: Innate immunity responsiveness can be monitored by whole blood stimulation. Both advanced HIVA and HIV-2 infections may cause innate immunity dysregulation. (C) 2009 Elsevier Ltd. All rights reserved.
  • Ursing, Johan, et al. (författare)
  • Malaria Transmission in Bissau, Guinea-Bissau between 1995 and 2012 : Malaria Resurgence Did Not Negatively Affect Mortality
  • 2014
  • Ingår i: PLOS ONE. - 1932-6203. ; 9:7, s. e101167-
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: As Plasmodium falciparum prevalence decreases in many parts of Sub-Saharan Africa, so does immunity resulting in larger at risk populations and increased risk of malaria resurgence. In Bissau, malaria prevalence decreased from ?50% to 3% between 1995 and 2003. The epidemiological characteristics of P. falciparum malaria within Bandim health and demographic surveillance site (population similar to 100000) between 1995 and 2012 are described. METHODS AND FINDINGS: The population was determined by census. 3603 children aged <15 years that were enrolled in clinical trials at the Bandim health centre (1995-2012) were considered incident cases. The mean annual malaria incidence per thousand children in 1995-1997, 1999-2003, 2007, 2011, 2012 were as follows; age <5 years 22 -> 29 -> 4 -> 9 -> 3, age 5-9 years 15 -> 28 -> 4 -> 33 -> 12, age 10-14 years 9 -> 15 -> 1 -> 45 -> 19. There were 4 campaigns (2003-2010) to increase use of insecticide treated bed nets (ITN) amongst children <5 years. An efficacious high-dose chloroquine treatment regime was routinely used until artemisinin based combination therapy (ACT) was introduced in 2008. Long lasting insecticide treated bed nets (LLIN) were distributed in 2011. By 2012 there was 1 net per 2 people and 97% usage. All-cause mortality decreased from post-war peaks in 1999 until 2012 in all age groups and was not negatively affected by malaria resurgence. CONCLUSION: The cause of decreasing malaria incidence (1995-2007) was probably multifactorial and coincident with the use of an efficacious high-dose chloroquine treatment regime. Decreasing malaria prevalence created a susceptible group of older children in which malaria resurged, highlighting the need to include all age groups in malaria interventions. ACT did not hinder malaria resurgence. Mass distribution of LLINs probably curtailed malaria epidemics. All-cause mortality was not negatively affected by malaria resurgence.
  • Özkaya Sahin, Gülsen, et al. (författare)
  • Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent
  • 2013
  • Ingår i: Journal of Virology. - : American Society for Microbiology. - 1098-5514. ; 87:1, s. 273-281
  • Tidskriftsartikel (refereegranskat)abstract
    • Human immunodeficiency virus type-2 (HIV-2) infected individuals develop immunodeficiency with a considerable delay and transmit the virus at a lower rate as compared to HIV-1 infected. Conceivably, comparative studies on immune responsiveness of the HIV-1 and HIV-2 infected hosts may help to explain differences in pathogenesis and transmission between the two types of infection. Previous studies have shown that the neutralizing antibody response is more potent and broader in HIV-2 than HIV-1 infection. In the present study we have further examined the function of the humoral immune response and studied the potentiating effect of complement (C') on antiviral activity of plasma from singly HIV-1 or HIV-2 infected, as well as HIV-1/HIV-2 dually infected individuals. Neutralization and antibody-dependent complement-mediated inactivation of HIV-1 and HIV-2 isolates were tested in a plaque reduction assay using U87.CD4-CCR5 cells. Results showed that addition of C' increased intra-type antiviral activity of both HIV-1 and HIV-2 plasma, although the C' effect was more pronounced with HIV-2 than HIV-1 plasma. Using the area-under-curve (AUC)-based readout, multivariate statistical analysis confirmed that type of HIV infection was independently associated with the magnitude of the C' effect. Analysis carried out with purified IgG indicated that the C' effect was largely exerted through the classical C' pathway involving IgG in both HIV-1 and HIV-2 infections. In summary, these findings suggest that antibody binding to HIV-2 structures facilitates efficient use of C', and may thereby be one factor contributing to a strong antiviral activity present in HIV-2 infection.
  • Özkaya Sahin, Gülsen, et al. (författare)
  • Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1
  • 2012
  • Ingår i: Journal of Virology. - : American Society for Microbiology. - 1098-5514. ; 86:2, s. 961-971
  • Tidskriftsartikel (refereegranskat)abstract
    • HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1, 20 HIV-2 and 11 dually HIV-1/2 (HIV-D) seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2, were tested in a plaque reduction assay using U87.CD4-CCR5 cells as targets. Intratype NAc in HIV-2 plasma was found to be considerably more potent, and also broader, than intratype NAc in HIV-1 plasma. This indicates that HIV-2 infected individuals display potent type-specific neutralizing antibodies, whereas such a strong type-specific antibodies are absent in HIV-1 infection. Furthermore, potency of intratype NAc was positively associated with viral load of HIV-1, but not HIV-2, suggesting that NAc in HIV-1 infection is more antigen stimulation-dependent than in HIV-2 infection where plasma viral loads typically are at least tenfold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infected was instead of low potency. HIV-D subjects had NAc to HIV-2 with similar high potency as singly HIV-2 infected individuals, whereas neutralization of HIV-1 remained poor, indicating that the difference in NAc between HIV-1 and HIV-2 infections depends on the virus itself. We suggest that immunogenicity and/or antigenicity, meaning the neutralization phenotype, of HIV-2 is distinct from HIV-1, and that HIV-2 may display structures that favour triggering of potent neutralizing antibody responses.
  • Aaby, Peter, et al. (författare)
  • Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial
  • 2012
  • Ingår i: Archives of Disease in Childhood. - : BMJ Publishing Group. - 0003-9888. ; 97:8, s. 685-691
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants. Methods 2320 LBW newborns were visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. The authors examined survival until the 6-month visit for children who were DTP vaccinated and DTP unvaccinated at the 2-month visit. Results Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits. DTP vaccinated children had a better anthropometric status for all indices than DTP unvaccinated children. Small mid-upper arm circumference (MUAC) was the strongest predictor of mortality. The death rate ratio (DRR) for DTP vaccinated versus DTP unvaccinated children differed significantly for girls (DRR 2.45; 95% CI 0.93 to 6.45) and boys (DRR 0.53; 95% CI 0.23 to 1.20) (p=0.018, homogeneity test). Adjusting for MUAC, the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); DRR was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls. Conclusion Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.
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