Ingrid Peterson

Observational Study of Vaccine Efficacy 24 Years after the Start of Hepatitis B Vaccination in Two Gambian Villages: No Need for a Booster Dose

Objectives To determine the duration of protection from hepatitis B vaccine given in infancy and early childhood and asses risk factors for HBV infection and chronic infection. Methods In 1984 infant HBV vaccination was started in two Gambian villages. Cross sectional serological surveys have been undertaken every 4 years to determine vaccine efficacy. In the current survey 84.6% of 1508 eligible participants aged 1–28 years were tested. A spouse study was conducted in females (aged 14 years and above) and their male partners. Results Vaccine efficacy against chronic infection with hepatitis B virus was 95.1% (95% confidence interval 91.5% to 97.1%), which did not vary significantly between age groups or village. Efficacy against infection was 85.4% (82.7% to 87.7%), falling significantly with age. Concentrations of hepatitis B antibody fell exponentially with age varying according to peak response: 20 years after vaccination only 17.8% (95% CI 10.1–25.6) of persons with a low peak response (10–99 mIU/ml) had detectable HBs antibody compared to 27% (21.9% to 32.2%) of those with a high peak response (>999 mIU/ml). Time since vaccination and a low peak response were the strongest risk factors for HBV infections; males were more susceptible, marriage was not a significant risk for females. Hepatitis B DNA was not detected after infection, which tested soley core antibody positive. An undetectable peak antibody response of <10 mIU/ml and a mother who was hepatitis B e antigen positive were powerful risk factors for chronic infection. Conclusions Adolescents and young adults vaccinated in infancy are at increased risk of hepatitis B infection, but not chronic infection. Married women were not at increased risk. There is no compelling evidence for the use of a booster dose of HBV vaccine in The Gambia.

Two Distinct Epidemics: The Rise of HIV-1 and Decline of HIV-2 Infection Between 1990 and 2007 in Rural Guinea-Bissau

Objectives:To assess changes in HIV incidence and prevalence in Caió, a rural area of Guinea-Bissau, between 1990 and 2007. Design:Three cross-sectional community surveys. Methods:In 1990, 1997, and 2007, surveys were conducted among adults. The prevalence of HIV-1 and of HIV-2 was estimated for each survey, and incidence rates were calculated for the first (1990-1997) and second period (1997-2007). Results:The HIV-1 incidence was approximately 4.5/1000 person-years in the two periods, whereas the HIV-2 incidence decreased from 4.7 (95% confidence interval 3.6-6.2) in the first to 2.0 (95% confidence interval 1.4-3.0) per 1000 person-years in the second period (P < 0.001). HIV-1 prevalence rose from 0.5% in 1990 to 3.6% in 2007, and HIV-2 prevalence decreased from 8.3% in 1990 to 4.7% in 2007. HIV-1 prevalence was less than 2% in 15 to 24 year olds in all surveys and was highest (7.2%) in 2007 among 45 to 54 year olds. The HIV-2 prevalence was fivefold higher in older subjects (≥45 yr) compared with those less than 45 years in both sexes in 2007. Conclusions:HIV-1 incidence is stable, and its prevalence is increasing, whereas HIV-2 incidence and prevalence are both declining. In contrast with what has been observed in other sub-Saharan countries, HIV-1 prevalence is lower in younger age groups than older age groups.

Seroprevalence of hepatitis B and C virus in HIV-1 and HIV-2 infected Gambians

BackgroundThe prevalence of HIV/hepatitis co-infection in sub-Saharan Africa is not well documented, while both HIV and HBV are endemic in this area.ObjectiveThe aim of this study is to determine the seroprevalence of HBV and HCV virus in HIV-infected subjects in the Gambia.MethodsPlasma samples from HIV infected patients (190 individuals with clinically defined AIDS and 382 individuals without AIDS) were tested retrospectively for the presence of HBV sero-markers and for serum HBV DNA, screened for HCV infection by testing for anti-HCV antibody and HCV RNA.ResultsHBsAg prevalence in HIV-positive individuals is 12.2%. HIV/HBV co-infected individuals with CD4 count of <200 cells uL-1 have a higher HBV DNA viral load than patients with higher CD4 count (log 4.0 vs. log 2.0 DNA copies/ml, p < 0.05). Males (OR = 1.8, 95% CI: 1.0, 3.2) were more likely to be HBsAg positive than female. HCV seroprevalence was 0.9% in HIV-positive individuals.ConclusionThe prevalence of HBsAg carriage in HIV- infected Gambians is similar to that obtained in the general population. However co-infected individuals with reduced CD4 levels, indicative of AIDS had higher prevalence of HBeAg retention and elevated HBV DNA levels compared to non-AIDS patients with higher CD4 count.

Mortality and immunovirological outcomes on antiretroviral therapy in HIV-1 and HIV-2-infected individuals in the Gambia.

Objectives:This studys objective was to assess outcomes in HIV-1 and HIV-2 infected antiretroviral therapy (ART)-naïve patients starting ART in the Gambia, West Africa. Design:A cohort design was used to estimate survival in ART patients and determine whether survival and time to virologic failure varied across patient subgroups. Methods:Mortality, virologic failures and CD4+ cell recovery were assessed in a clinical cohort of patients from the Genito-Urinary Medicine (GUM) clinic of the MRC Laboratories in the Gambia. Kaplan–Meier estimates of survival were determined for mortality and virologic failure. A Cox proportional hazards model was used to identify baseline demographic, clinical, immunologic and virologic factors associated with increased risk of death. Results:The overall Kaplan–Meier estimate of survival to 36 months was 73.4% (66.5, 80.3). Survival was marginally higher in HIV-2-infected patients compared to HIV-1-infected patients; it was significantly higher in patients with a baseline CD4+ lymphocyte cell count of greater than 50 cells/&mgr;l compared to those with a baseline CD4+ count of less than 50 cells/&mgr;l. CD4+ cell recovery was faster in HIV-1-infected individuals compared to HIV-2-infected patients up to 24 months, although this did not result higher mortality in the latter group. No differences in virologic failure were observed by HIV type. Conclusion:HIV-1 and HIV-2-infected patients receiving ART in a clinical setting in the Gambia had good survival to 36 months. HIV-2-infected patients did as well as HIV-1-infected patients in terms of long-term immunological and virological responses and overall survival.

A temporal-spatial analysis of malaria transmission in Adama, Ethiopia.

Urban malaria is a growing problem in Africa. Small-scale spatial studies are useful in identifying foci of malaria transmission in urban communities. A population-based cohort study comprising 8,088 individuals was conducted in Adama, Ethiopia. During a single malaria season, the Kulldorff scan statistic identified one temporally stable spatial malaria cluster within 350 m of a major Anopheles breeding site. Factors associated with malaria incidence were residential proximity to vector breeding site, poor house condition (incidence rate ratio [IRR] = 2.0, 95% confidence interval [CI] = 1.4, 2.9), and a high level of vegetation (IRR = 1.8, 95% CI = 1.0, 3.3). Maximum (IRR = 1.4, 95% CI = 1.1, 1.9) and minimum daily temperatures (degrees C; IRR = 1.3, 95% CI = 1.2, 1.5) were positively associated with malaria incidence after a 1-month delay. Rainfall was positively associated with malaria incidence after a 10-day delay. Findings support the use of small scale mapping and targeted vector control in urban malaria control programs in Africa.

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.

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

BackgroundHTLV-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.ResultsHTLV-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).ConclusionsTo 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.

Emergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa

BackgroundLamivudine ( 3TC) is a potent inhibitor of both Hepatitis B virus (HBV) and Human Immunodeficiency Virus (HIV) replication and is part of first-line highly active antiretroviral therapy (HAART) in the Gambia. Unfortunately, the effectiveness of 3TC against HBV is limited by the emergence of resistant strains.AimThe aim of this retrospective study was to characterise 3TC-resistant mutations in HBV from co-infected patients receiving HAART, by generating HBV polymerase sequence data and viral loads from HBV genotype E infected patients, both at initiation and during a course of 3TC therapy.MethodSamples from 21 HBV chronic carriers co-infected with HIV-1 (n = 18), HIV-2 (n = 2) and HIV-dual (n = 1) receiving HAART for a period of 6-52 months were analysed for the emergence of 3TC-resistance mutations.FindingsSixteen out of 21 HBV/HIV co-infected patients responded well to HAART treatment maintaining suppression of HBV viraemia to low (≤ 104 copies/mL) (n = 5) or undetectable levels (< 260 copies/ml) (n = 11). Out of the 5 non-responders, 3 had developed 3TC-resistant HBV strains showing mutations in the YMDD motif at position 204 of the RT domain of the HBV polymerase. One patient showed the M204V+ L180M+ V173L+ triple mutation associated with a vaccine escape phenotype, which could be of public health concern in a country with a national HBV vaccination programme. All except one patient was infected with HBV genotype E.ConclusionsOur findings confirm the risk of 3TC mutations in HAART patients following monotherapy. This is a novel study on 3TC resistance in HBV genotype E patients and encourage the use of tenofovir (in association with 3TC), which has not shown unequivocally documented HBV resistance to date, as part of first-line therapy in HIV/HBV co-infected patients in West Africa.HBV- hepatitis B infection; HIV- human immunodeficiency virus; HAART- antiretroviral therapy.

Declining trend of serological syphilis among genitourinary medicine patients in the Gambia West Africa.

Background: Syphilis is a common disease in Africa and may be an important contributor to the HIV epidemic. Trends in syphilis prevalence are important in their own right and because syphilis is a cofactor for HIV infection. In this study we analyzed trends in serological syphilis prevalence at a sexually transmitted infections (STI) clinic in The Gambia. Methods: At the Genitourinary Medicine clinic of the Medical Research Council in The Gambia patients were routinely screened for syphilis using a 2-test algorithm, measuring rapid plasma reagin followed by the Treponema pallidum haemagglutination assay. Serological syphilis was defined as both tests being positive. We determined year to year trends in serological syphilis. Logistic regression was used to identify risk factors. Results: Over the period 1994–2007, 23,674 people were tested for syphilis. The prevalence of serological syphilis dropped from 11.2% in 1994 to 1.5% in 2007 (P <0.0001; &khgr;2 test for trend). Significant risk factors for serological syphilis in women were found to be ethnicity, commercial sex work, and HIV infection. No associations between serological syphilis and possible risk factors in men were found. Conclusions: This study identified a strong and significant downward trend in the prevalence of serological syphilis among patients attending the Genitourinary Medicine clinic in The Gambia in the period 1994–2007. These results suggest that syphilis prevalence may be declining in the general population, in the absence of a targeted control program. Research is needed to identify the reasons for this decline.

Respiratory Virus–Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition

Background We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering. Methods From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection. Results Hospital-attended influenza virus–positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged <1 year (6.3 cases per 10 000), and human immunodeficiency virus (HIV)–infected children aged 5–9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4–3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3–3.0) and rainy season (aRR, 2.4; 95% CI, 1.6–3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs. Conclusions Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance.