Hepatitis A outbreak linked to imported frozen strawberries by sequencing, Sweden and Austria, June to September 2018.

Between June-September 2018, 20 hepatitis A cases were notified in six counties in Sweden. Combined epidemiological and microbiological investigations identified imported frozen strawberries produced in Poland as the source of the outbreak. Sequence analysis confirmed the outbreak strain IB in the strawberries with 100 % identity and the respective batch was withdrawn. Sharing the sequence information internationally led to the identification of 14 additional cases in Austria, linked to strawberries from the same producer.

Effect of complement on HIV-2 plasma antiviral activity is intratype specific and potent.

Human immunodeficiency virus type 2 (HIV-2)-infected individuals develop immunodeficiency with a considerable delay and transmit the virus at rates lower than HIV-1-infected persons. Conceivably, comparative studies on the immune responsiveness of HIV-1- and HIV-2-infected hosts may help to explain the 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 in HIV-1 infection. In the present study, we have examined further the function of the humoral immune response and studied the effect of complement on the antiviral activity of plasma from singly HIV-1- or HIV-2-infected individuals, as well as HIV-1/HIV-2 dually infected individuals. The 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. The results showed that the addition of complement increased intratype antiviral activities of both HIV-1 and HIV-2 plasma samples, although the complement effect was more pronounced with HIV-2 than HIV-1 plasma. Using an area-under-the-curve (AUC)-based readout, multivariate statistical analysis confirmed that the type of HIV infection was independently associated with the magnitude of the complement effect. The analyses carried out with purified IgG indicated that the complement effect was largely exerted through the classical complement pathway involving IgG in both HIV-1 and HIV-2 infections. In summary, these findings suggest that antibody binding to HIV-2 structures facilitates the efficient use of complement and thereby may be one factor contributing to a strong antiviral activity present in HIV-2 infection.

Potent intratype neutralizing activity distinguishes human immunodeficiency virus type 2 (HIV-2) from HIV-1.

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 the 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 isolates, 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 strong type-specific antibodies are absent in HIV-1 infection. Furthermore, the potency of intratype NAc was positively associated with the 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 10-fold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infections 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 that of HIV-1 and that HIV-2 may display structures that favor triggering of potent neutralizing antibody responses.

HTLV-1 and HIV-2 infection are associated with increased mortality in a rural West African community.

BACKGROUND: Survival of people with HIV-2 and HTLV-1 infection is better than that of HIV-1 infected people, but long-term follow-up data are rare. We compared mortality rates of HIV-1, HIV-2, and HTLV-1 infected subjects with those of retrovirus-uninfected people in a rural community in Guinea-Bissau. METHODS: In 1990, 1997 and 2007, adult residents (aged ≥15 years) were interviewed, a blood sample was drawn and retroviral status was determined. An annual census was used to ascertain the vital status of all subjects. Cox regression analysis was used to estimate mortality hazard ratios (HR), comparing retrovirus-infected versus uninfected people. RESULTS: A total of 5376 subjects were included; 197 with HIV-1, 424 with HIV-2 and 325 with HTLV-1 infection. The median follow-up time was 10.9 years (range 0.0-20.3). The crude mortality rates were 9.6 per 100 person-years of observation (95% confidence interval 7.1-12.9) for HIV-1, 4.1 (3.4-5.0) for HIV-2, 3.6 (2.9-4.6) for HTLV-1, and 1.6 (1.5-1.8) for retrovirus-negative subjects. The HR comparing the mortality rate of infected to that of uninfected subjects varied significantly with age. The adjusted HR for HIV-1 infection varied from 4.0 in the oldest age group (≥60 years) to 12.7 in the youngest (15-29 years). The HR for HIV-2 infection varied from 1.2 (oldest) to 9.1 (youngest), and for HTLV-1 infection from 1.2 (oldest) to 3.8 (youngest). CONCLUSIONS: HTLV-1 infection is associated with significantly increased mortality. The mortality rate of HIV-2 infection, although lower than that of HIV-1 infection, is also increased, especially among young people.

Sequence analysis of HIV-1 isolates from Guinea-Bissau: selection of vaccine epitopes relevant in both West African and European countries.

For a CD8 epitope-based vaccine to match different geographic locations, the targeted epitopes for cytotoxic T-lymphocytes (CTLs) must be present in the local circulating HIV-1 strains. Secondly, the vaccine epitopes should match the host population HLA types. We characterized two new HIV-1 isolates from Guinea-Bissau. Also, we have identified 15 subdominant CD8 epitopes representing common HLA super-types theoretically covering most HLA alleles in any population. Herein we demonstrate that the selected vaccine epitopes are well conserved and simultaneously present in sequences from West Africa and Denmark. Use of the selected epitopes will likely ensure ≥10 immune targets in the majority of candidates for experimental therapeutic vaccination in both geographic regions. Our results warrant testing of the selected vaccine epitopes in both geographic locations.

HTLV-1 in rural Guinea-Bissau: prevalence, incidence and a continued association with HIV between 1990 and 2007.

BACKGROUND: HTLV-1 is endemic in Guinea-Bissau, and the highest prevalence in the adult population (5.2%) was observed in a rural area, Caió, in 1990. HIV-1 and HIV-2 are both prevalent in this area as well. Cross-sectional associations have been reported for HTLV-1 with HIV infection, but the trends in prevalence of HTLV-1 and HIV associations are largely unknown, especially in Sub Saharan Africa. In the current study, data from three cross-sectional community surveys performed in 1990, 1997 and 2007, were used to assess changes in HTLV-1 prevalence, incidence and its associations with HIV-1 and HIV-2 and potential risk factors. RESULTS: HTLV-1 prevalence was 5.2% in 1990, 5.9% in 1997 and 4.6% in 2007. Prevalence was higher among women than men in all 3 surveys and increased with age. The Odds Ratio (OR) of being infected with HTLV-1 was significantly higher for HIV positive subjects in all surveys after adjustment for potential confounding factors. The risk of HTLV-1 infection was higher in subjects with an HTLV-1 positive mother versus an uninfected mother (OR 4.6, CI 2.6-8.0). The HTLV-1 incidence was stable between 1990-1997 (Incidence Rate (IR) 1.8/1,000 pyo) and 1997-2007 (IR 1.6/1,000 pyo) (Incidence Rate Ratio (IRR) 0.9, CI 0.4-1.7). The incidence of HTLV-1 among HIV-positive individuals was higher compared to HIV negative individuals (IRR 2.5, CI 1.0-6.2), while the HIV incidence did not differ by HTLV-1 status (IRR 1.2, CI 0.5-2.7). CONCLUSIONS: To our knowledge, this is the largest community based study that has reported on HTLV-1 prevalence and associations with HIV. HTLV-1 is endemic in this rural community in West Africa with a stable incidence and a high prevalence. The prevalence increases with age and is higher in women than men. HTLV-1 infection is associated with HIV infection, and longitudinal data indicate HIV infection may be a risk factor for acquiring HTLV-1, but not vice versa. Mother to child transmission is likely to contribute to the epidemic.

Microbial translocation correlates with the severity of both HIV-1 and HIV-2 infections.

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.

Studies on toll-like receptor stimuli responsiveness in HIV-1 and HIV-2 infections.

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-I, 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 HIV-1 and HIV-2 infections may cause innate immunity dysregulation.

Decline in human T-cell lymphotropic virus-1 prevalence in urban areas of Bissau, Guinea-Bissau: exploring the association with HIV infections.

In 2006, a cross-sectional survey of 384 randomly selected houses within a community-based follow-up study was conducted to assess the human T-cell lymphotropic virus (HTLV) prevalence in Bissau. Changes in prevalence and incidence rates were assessed based on a similar survey carried out 10 years earlier. The prevalence of HTLV-1 declined significantly from 3.5% in 1996 to 2.3% in 2006. The incidence between 1996 and 2006 was only 0.9/1000 person-years and tended to be higher for women than for men.

Changes in prevalence and incidence of HIV-1, HIV-2 and dual infections in urban areas of Bissau, Guinea-Bissau: is HIV-2 disappearing?

OBJECTIVES: To assess the changes in HIV prevalence and incidence between 1996 and 2006 in urban areas of Bissau. DESIGN: A cross-sectional survey of 384 randomly selected houses within a community-based follow-up study of HIV-1 and HIV-2. METHODS: A total of 3242 individuals aged at least 15 years were eligible for inclusion. Participants were interviewed about behavioral and socio-economic factors and had a blood sample drawn. A total of 2548 individuals were tested for antibodies to HIV-1 and HIV-2, of whom 649 had taken part in a similar survey in 1996. RESULTS: With 0.5% HIV dual reactions included, the overall HIV-1 prevalence was 4.6% (118 out of 2548) and the HIV-2 prevalence was 4.4% (112 out of 2548). The prevalence of HIV-1 increased more for women than men especially in the 25-34-year age group. HIV-2 prevalence decreased below 45 years of age but not for individuals more than 45 years old. The incidence rate between 1996 and 2006 was 0.5 per 100 person-years for HIV-1 and 0.24 per 100 person-years for HIV-2. Compared with a previous period from 1987 to 1996, the incidence of HIV-2 is declining whereas no significant increase in the incidence of HIV-1 was observed. CONCLUSIONS: The present study shows an increasing prevalence of HIV-1 and a decreasing prevalence of HIV-2 in Guinea-Bissau. HIV is generally a bigger problem for women. Despite the general decline in prevalence, HIV-2 may continue as an infection in older people, especially women.

Mortality associated with HIV-1, HIV-2, and HTLV-I single and dual infections in a middle-aged and older population in Guinea-Bissau.

BACKGROUND: In Guinea-Bissau HIV-1, HIV-2, and HTLV-I are prevalent in the general population. The natural history of HIV/HTLV-I single and dual infections has not been fully elucidated in this population. Previous studies have shown that combinations of these infections are more common in older women than in men. The present study compares mortality associated with HIV-1, HIV-2, and HTLV-I single and dual infections in individuals over 35 years of age within an urban community-based cohort in Guinea-Bissau. RESULTS: A total of 2,839 and 1,075 individuals were included in the HIV and HTLV-I mortality analyses respectively. Compared with HIV-negative individuals, adjusted mortality rate ratios (MRRs) were 4.9 (95% confidence interval (CI): 2.3, 10.4) for HIV-1, 1.8 (95%CI: 1.5, 2.3) for HIV-2, and 5.9 (2.4, 14.3) for HIV-1/HIV-2 dual infections. MRR for HTLV-I-positive compared with HTLV-I-negative individuals was 1.7 (1.1, 2.7). Excluding all HIV-positive individuals from the analysis, the HTLV-I MRR was 2.3 (1.3, 3.8). The MRR of HTLV-I/HIV-2 dually infected individuals was 1.7 (0.7, 4.3), compared with HIV/HTLV-I-negative individuals. No statistically significant differences were found in retrovirus-associated mortality between men and women. CONCLUSION: HIV-1-associated excess mortality was low compared with community studies from other parts of Africa, presumably because this population was older and the introduction of HIV-1 into the community recent. HIV-2 and HTLV-I-associated mortality was 2-fold higher than the mortality in uninfected individuals. We found no significant differences between the mortality risk for HIV-2 and HTLV-I single infection, respectively, and HIV-2/HTLV-I dual infection. The higher prevalence of retroviral dual infections in older women is not explained by differential retrovirus-associated mortality for men and women.

Vaccinia scars associated with better survival for adults. An observational study from Guinea-Bissau.

BACKGROUND: Live vaccines including BCG and measles may have non-targeted beneficial effects on childhood survival in areas with high mortality. The authors therefore undertook a survey of vaccinia scars to evaluate subsequent mortality. SUBJECTS: Based on a population census, a cohort of 1893 adults in urban Guinea-Bissau was examined in 1998 and followed until 2002. MAIN OUTCOME MEASURE: All cause mortality, excluding accidents. RESULTS: The median age of vaccinia vaccinations had been 16-18 years. Adults with a vaccinia scar had a mortality ratio (MR) of 0.60 (0.41-0.87) compared to those without any scar. The effect was stronger for women. Mortality decreased with each additional vaccinia scar (MR=0.73 (0.56-0.95)). Among 502 individuals with information on HIV infection, the age-adjusted HIV-2 prevalence was 2.45 (1.06-5.65) for those with a vaccinia scar. Control for district, ethnic group, schooling, place of birth, quality of housing and HIV status had little effect on the estimate. Since vaccinia and BCG scars could have been confused, mortality for adults with vaccinia and/or BCG scar was compared to those without, the MR being 0.61 (0.41-0.89). CONCLUSION: Known cultural or socio-economic factors possibly associated with access to vaccination had no influence on the mortality ratio for having a vaccinia scar. Hence, vaccinia vaccination may have a prolonged beneficial effect on adult survival.

Dual infections with HIV-1, HIV-2 and HTLV-I are more common in older women than in men in Guinea-Bissau.

OBJECTIVES: To investigate the association between the three human retroviruses, HIV-1, HIV-2 and HTLV-I. DESIGN: Community-based follow-up studies of retrovirus infections in two cohorts. METHODS: A total of 2057 individuals aged 35 years and over were eligible for inclusion. Participants were interviewed and had a blood sample drawn. Samples were analysed for HIV-1, HIV-2 and HTLV infections. Uni- and multivariate analyses that included behavioural and socio-economic factors were performed using logistic regression and Poisson regression models. RESULTS: A total of 1686 individuals participated with a blood sample in the HIV prevalence analyses and 1581 individuals participated in the HTLV-I prevalence analyses. The overall prevalence was 2.1% for HIV-1, 13.5% for HIV-2 and 7.1% for HTLV-I. Comparing the < 45 year age group with 45+ year age groups, the female : male (F : M) prevalence ratio increased with age for all three retroviruses. Dual infections were more common in women than in men. Assuming independent distribution of the viruses, the observed prevalence of dual infections in women was significantly higher than expected, while the prevalence was not increased in men. The prevalence of dual infections increased with age in women, the odds ratio (OR) being 3.4 [95% confidence interval (CI), 1.0-11.3] for any combination of dual infection, while the prevalence decreased with age in men (OR, 0.3; 95% CI, 0.1-2.0) (test of interaction, P = 0.033). Control for behavioural factors did not modify these patterns. CONCLUSIONS: The pattern of increased prevalence among older women could have public health implications; women of older age groups should be regarded as a potential vulnerable group and included in HIV/AIDS prevention programmes.

Increased prevalence of HTLV-1 among HIV-2-infected women but not HIV-2-infected men in rural Guinea-Bissau.

OBJECTIVE: To assess the prevalence of HTLV infection and its association with HIV and other potential risk factors. DESIGN AND SETTING: A cross-sectional survey and a case-control study in a rural community in Guinea-Bissau. METHODS: A total of 2770 people were included in an HIV and HTLV seroepidemiologic survey. Three hundred of these participants were selected for a case-control study on HIV-2. Sera from both studies were tested for HTLV. RESULTS: In all, 2501 and 298 subjects in the survey and case-control study, respectively, were tested for HTLV. Overall HTLV-1 prevalence was 5.2% and it was higher in women (odds ratio [OR], 1.36; confidence interval [CI], 0.92-2.02). Apart from an infected spouse, no significant risk factors could be identified for men. In women, HIV-2 infection (adjusted OR, 5.58; CI, 3.09-10.1), having an infected spouse, and area of residence were significantly associated with HTLV-1 infection. The association between HTLV-1 and HIV-2 was significantly different for men and women (test of interaction, p =.002). CONCLUSIONS: In women, the most important determinant of HTLV-1 seropositivity was HIV-2 infection. Because the pattern was significantly different for men and women, common sexual risk factors may not be sufficient to explain the co-occurrence of HIV-2 and HTLV-1 in women. These observations may have implications in geographic areas where both types of retroviruses are prevalent.