Ending tuberculosis: the cost of missing the World Health Organization target in a low-incidence country.

BACKGROUND: Ending tuberculosis (TB) is a global priority and targets for doing so are outlined in the World Health Organization (WHO) End TB Strategy. For low-incidence countries, eliminating TB requires high levels of wealth, low levels of income inequality and effective TB programmes and services that can meet the needs of people who have not benefited from these and are still at risk of TB. In Ireland, numerous reports have noted a need for more funding for TB prevention and control. AIM: The aim of this research was to estimate the cost of not meeting the WHO End TB target of a 90% reduction in TB incidence in Ireland between 2015 and 2035. METHODS: The cost of projected TB cases between 2022 and 2035 is estimated based on trends in surveillance data for the period 2015 to 2019 and outcomes reported in the literature. RESULTS: Between 2022 and 2035, it is projected that a failure to meet the WHO End TB Strategy target will result in an additional 989 cases of TB, 577.3 disability-adjusted life years and 35 deaths with TB in Ireland. The cost of this is estimated to be €70.779 million. CONCLUSION: Given the estimated cost, Ireland's current prospects of eliminating TB and the tendency towards programmatic funding internationally, greater investment in TB prevention and control in Ireland is justifiable. A national elimination strategy with actions at the levels of the social determinants of health, the health system and the TB programme should be funded.

Factors Associated With Intimate Partner Violence Perpetration and Victimization in Asylum Seeking and Refugee Populations: A Systematic Review.

Intimate partner violence (IPV) is a common and serious health and justice problem. Asylum seekers and refugees are generally vulnerable to violence and may be particularly vulnerable to IPV. The aim of this study is to identify factors associated with IPV perpetration and victimization in asylum seeking and refugee populations through a systematic review of the literature. PubMed, Web of Science, Scopus, Embase, Global Health, PsycINFO, Westlaw, and Social Science Research Network databases were searched. Quantitative studies were included according to a population, exposure, outcome framework. Studies were critically appraised with the Joanna Briggs Institute's System for the Unified Management, Assessment and Review of Information tool and quality assessed according to the Grading of Recommendations, Assessment, Development, and Evaluations approach. Meta-analysis was not possible due to heterogeneity. A complex multitude of factors associated with IPV perpetration and victimization in asylum seeking and refugee populations was found. Narrative synthesis of 23 studies showed an inverse association between both perpetrator and victim education level and IPV. Relationship factors, legal status, and age were also important factors associated with IPV. The majority of studies had a cross-sectional design. Heterogeneity in definitions of IPV, sample, methods, statistical procedures, and outcomes was reported. Low education level is a consistent modifiable factor associated with IPV in asylum seeking and refugee populations. This work points to a testable intervention that stakeholders could trial to address the unjust and unhealthy problem of IPV. More and better quality research using standardized definitions, longitudinal design, and sensitive tools is needed in this area.

An integrated multidisciplinary model of COVID-19 recovery care.

BACKGROUND: In January 2020, the WHO declared the SARS-CoV-2 outbreak a public health emergency; by March 11, a pandemic was declared. To date in Ireland, over 3300 patients have been admitted to acute hospitals as a result of infection with COVID-19. AIMS: This article aims to describe the establishment of a COVID Recovery Service, a multidisciplinary service for comprehensive follow-up of patients with a hospital diagnosis of COVID-19 pneumonia. METHODS: A hybrid model of virtual and in-person clinics was established, supported by a multidisciplinary team consisting of respiratory, critical care, infectious diseases, psychiatry, and psychology services. This model identifies patients who need enhanced follow-up following COVID-19 pneumonia and aims to support patients with complications of COVID-19 and those who require integrated community care. RESULTS: We describe a post-COVID-19 service structure together with detailed protocols for multidisciplinary follow-up. One hundred seventy-four patients were discharged from Beaumont Hospital after COVID-19 pneumonia. Sixty-seven percent were male with a median age (IQR) of 66.5 (51-97). Twenty-two percent were admitted to the ICU for mechanical ventilation, 11% had non-invasive ventilation or high flow oxygen, and 67% did not have specialist respiratory support. Early data suggests that 48% of these patients will require medium to long-term specialist follow-up. CONCLUSIONS: We demonstrate the implementation of an integrated multidisciplinary approach to patients with COVID-19, identifying those with increased physical and mental healthcare needs. Our initial experience suggests that significant physical, psychological, and cognitive impairments may persist despite clinical resolution of the infection.

Readability of online COVID-19 health information: a comparison between four English speaking countries.

BACKGROUND: The internet is now the first line source of health information for many people worldwide. In the current Coronavirus Disease 2019 (COVID-19) global pandemic, health information is being produced, revised, updated and disseminated at an increasingly rapid rate. The general public are faced with a plethora of misinformation regarding COVID-19 and the readability of online information has an impact on their understanding of the disease. The accessibility of online healthcare information relating to COVID-19 is unknown. We sought to evaluate the readability of online information relating to COVID-19 in four English speaking regions: Ireland, the United Kingdom, Canada and the United States, and compare readability of website source provenance and regional origin. METHODS: The Google® search engine was used to collate the first 20 webpage URLs for three individual searches for 'COVID', 'COVID-19', and 'coronavirus' from Ireland, the United Kingdom, Canada and the United States. The Gunning Fog Index (GFI), Flesch-Kincaid Grade (FKG) Score, Flesch Reading Ease Score (FRES), Simple Measure of Gobbledygook (SMOG) score were calculated to assess the readability. RESULTS: There were poor levels of readability webpages reviewed, with only 17.2% of webpages at a universally readable level. There was a significant difference in readability between the different webpages based on their information source (p < 0.01). Public Health organisations and Government organisations provided the most readable COVID-19 material, while digital media sources were significantly less readable. There were no significant differences in readability between regions. CONCLUSION: Much of the general public have relied on online information during the pandemic. Information on COVID-19 should be made more readable, and those writing webpages and information tools should ensure universal accessibility is considered in their production. Governments and healthcare practitioners should have an awareness of the online sources of information available, and ensure that readability of our own productions is at a universally readable level which will increase understanding and adherence to health guidelines.

TRANSVAC research infrastructure - Results and lessons learned from the European network of vaccine research and development.

TRANSVAC was a collaborative infrastructure project aimed at enhancing European translational vaccine research and training. The objective of this four year project (2009-2013), funded under the European Commission's (EC) seventh framework programme (FP7), was to support European collaboration in the vaccine field, principally through the provision of transnational access (TNA) to critical vaccine research and development (R&D) infrastructures, as well as by improving and harmonising the services provided by these infrastructures through joint research activities (JRA). The project successfully provided all available services to advance 29 projects and, through engaging all vaccine stakeholders, successfully laid down the blueprint for the implementation of a permanent research infrastructure for early vaccine R&D in Europe.

A phase Ia study to assess the safety and immunogenicity of new malaria vaccine candidates ChAd63 CS administered alone and with MVA CS.

BACKGROUND: Plasmodium falciparum (P. falciparum) malaria remains a significant cause of mortality and morbidity throughout the world. Development of an effective vaccine would be a key intervention to reduce the considerable social and economic impact of malaria. METHODOLOGY: We conducted a Phase Ia, non-randomized, clinical trial in 24 healthy, malaria-naïve adults of the chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient viral vectored vaccines encoding the circumsporozoite protein (CS) of P. falciparum. RESULTS: ChAd63-MVA CS administered in a heterologous prime-boost regime was shown to be safe and immunogenic, inducing high-level T cell responses to CS. With a priming ChAd63 CS dose of 5×109 vp responses peaked at a mean of 1947 SFC/million PBMC (median 1524) measured by ELIspot 7 days after the MVA boost and showed a mixed CD4+/CD8+ phenotype. With a higher priming dose of ChAd63 CS dose 5×1010 vp T cell responses did not increase (mean 1659 SFC/million PBMC, median 1049). Serum IgG responses to CS were modest and peaked at day 14 post ChAd63 CS (median antibody concentration for all groups at day 14 of 1.3 µg/ml (range 0-11.9), but persisted throughout late follow-up (day 140 median antibody concentration groups 1B & 2B 0.9 µg/ml (range 0-4.7). CONCLUSIONS: ChAd63-MVA is a safe and highly immunogenic delivery platform for the CS antigen in humans which warrants efficacy testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT01450280.

Maternal proviral load and vertical transmission of human T cell lymphotropic virus type 1 in Guinea-Bissau.

The relative importance of routes of transmission of human T cell lymphotropic virus type 1 (HTLV-1) in Guinea-Bissau is largely unknown; vertical transmission is thought to be important, but there are very few existing data. We aimed to examine factors associated with transmission in mothers and children in Guinea-Bissau, where HTLV-1 is endemic (prevalence of 5% in the adult population). A cross-sectional survey was performed among mothers and their children (aged <15 years) in a rural community in Guinea-Bissau. A questionnaire to identify risk factors for infection and a blood sample were obtained. HTLV-1 proviral load in peripheral blood was determined and PCR was performed to compare long terminal repeat (LTR) sequences in mother-child pairs. Fourteen out of 55 children (25%) of 31 HTLV-1-infected mothers were infected versus none of 70 children of 30 uninfected mothers. The only factor significantly associated with HTLV-1 infection in the child was the proviral load of the mother; the risk of infection increased significantly with the log(10) proviral load in the mother's peripheral blood (OR 5.5, 95% CI 2.1-14.6, per quartile), adjusted for weaning age and maternal income. HTLV-1 sequences of the LTR region obtained from mother-child pairs were identical within pairs but differed between the pairs. Vertical transmission plays an important role in HTLV-1 transmission in this community in Guinea-Bissau. The risk of transmission increases with the mother's proviral load in the peripheral blood. Identical sequences in mother-child pairs give additional support to the maternal source of the children's infection.

Partially randomized, non-blinded trial of DNA and MVA therapeutic vaccines based on hepatitis B virus surface protein for chronic HBV infection.

BACKGROUND: Chronic HBV infects 350 million people causing cancer and liver failure. We aimed to assess the safety and efficacy of plasmid DNA (pSG2.HBs) vaccine, followed by recombinant modified vaccinia virus Ankara (MVA.HBs), encoding the surface antigen of HBV as therapy for chronic HBV. A secondary goal was to characterize the immune responses. METHODS: Firstly 32 HBV e antigen negative (eAg(-)) participants were randomly assigned to one of four groups: to receive vaccines alone, lamivudine (3TC) alone, both, or neither. Later 16 eAg(+) volunteers in two groups received either 3TC alone or both 3TC and vaccines. Finally, 12 eAg(-) and 12 eAg(+) subjects were enrolled into higher-dose treatment groups. Healthy but chronically HBV-infected males between the ages of 15-25 who lived in the western part of The Gambia were eligible. Participants in some groups received 1 mg or 2 mg of pSG2.HBs intramuscularly twice followed by 5×10(7) pfu or 1.5×10(8) pfu of MVA.HBs intradermally at 3-weekly intervals with or without concomitant 3TC for 11-14 weeks. Intradermal rabies vaccine was administered to a negative control group. Safety was assessed clinically and biochemically. The primary measure of efficacy was a quantitative PCR assay of plasma HBV. Immunity was assessed by IFN-γ ELISpot and intracellular cytokine staining. RESULTS: Mild local and systemic adverse events were observed following the vaccines. A small shiny scar was observed in some cases after MVA.HBs. There were no significant changes in AST or ALT. HBeAg was lost in one participant in the higher-dose group. As expected, the 3TC therapy reduced viraemia levels during therapy, but the prime-boost vaccine regimen did not reduce the viraemia. The immune responses were variable. The majority of IFN-γ was made by antigen non-specific CD16(+) cells (both CD3(+) and CD3(-)). CONCLUSIONS: The vaccines were well tolerated but did not control HBV infection. TRIAL REGISTRATION: ISRCTN ISRCTN67270384.

Virological response to highly active antiretroviral therapy in patients infected with human immunodeficiency virus type 2 (HIV-2) and in patients dually infected with HIV-1 and HIV-2 in the Gambia and emergence of drug-resistant variants.

Drug design, antiretroviral therapy (ART), and drug resistance studies have focused almost exclusively on human immunodeficiency virus type 1 (HIV-1), resulting in limited information for patients infected with HIV-2 and for those dually infected with HIV-1 and HIV-2. In this study, 20 patients, 12 infected with HIV-2 and 8 dually infected with HIV-1 and HIV-2, all treated with zidovudine (ZDV), lamivudine (3TC), and lopinavir-ritonavir (LPV/r), were followed up longitudinally for about 3 years. For 19/20 patients, viral loads were reduced to undetectable levels; the patient whose viral load remained detectable reported adverse effects associated with LPV/r that had caused him to stop taking all the drugs. HIV-2 strains containing mutations in both the protease and the reverse transcriptase gene that may confer drug resistance were observed in two patients with viral rebound, as early as 130 days (4.3 months) after the initiation of therapy. We conclude that the combination of ZDV, 3TC, and LPV/r is able to provide efficient and durable suppression of HIV-1 and HIV-2 for as long as 3 years in HIV-2-infected and dually infected patients. However, the emergence of HIV-1 and HIV-2 strains containing drug-resistant mutations can compromise the efficacy of this highly active ART.

Changes in viral load and HBsAg and HBeAg status with age in HBV chronic carriers in The Gambia.

BACKGROUND: Little is known about changes in hepatitis B viral load (HBV DNA) in relation to age in Africa. The aim of this study is to determine the natural course of HBV chronic infection, particularly in relation to sequential changes in serum HBV DNA levels and hepatitis B surface (HBsAg) antigen/hepatitis e antigen (HBeAg) status by age. METHODS: The study was conducted on 190 HBV chronic carriers, aged 1-19 years who were followed for 19 years. 160, 99 and 123 were traced at 5, 9 and 19 years later. All available samples were tested for HBsAg and HBeAg, whilst 170, 61, 63 and 81 were tested for HBV DNA at the baseline, and at 5, 9 and 19 years following recruitment. RESULTS: In general HBeAg which correlated with high levels of HBV DNA was lost at a much faster rate than HBsAg. 86% of the carriers who were recruited at the age of 1-4 yrs lost HBeAg by the age of 19 years compared to 30% who lost HBsAg. HBeAg negative carriers had serum HBV DNA levels of < 105 copies per mL, HBV DNA positivity declined from 100% in 1-4 yrs old carriers at recruitment to 62.5%,60% and 88% at 5, 9 and 19 years respectively following recruitment. CONCLUSION: After 19 years of follow up, the majority of HBV surface antigen carriers had lost HBeAg positivity and had low levels of viral replication. However small proportions (10-20%) retained HBeAg and continue to have high levels of viral replication.

Mycobacterial T cell responses in HIV-infected patients with advanced immunosuppression.

Antimycobacterial T cell reactivity at different stages of HIV infection was investigated. Subjects were screened with purified protein derivative (PPD), early secreted antigenic target (ESAT)-6, and culture filtrate protein (CFP)-10 antigens for interferon (IFN)-gamma-producing effector T cell responses by direct ex vivo enzyme-linked immunospot (ELISpot) assay. The proportion of responders to PPD tuberculin decreased with a reduction in CD4 T cell count, whereas the proportion of responder to ESAT-6 and CFP-10 did not. The main sources of IFN-gamma secretion were CD4 cells, and the relative responses to ESAT-6 and CFP-10 significantly increased in HIV-infected patients with decreasing CD4 cell count. This may reflect early signs of reactivation, reinfection, or a restricted, inefficient immune response to Mycobacterium tuberculosis.

Long-term protection against HBV chronic carriage of Gambian adolescents vaccinated in infancy and immune response in HBV booster trial in adolescence.

BACKGROUND: Chronic infection with hepatitis B virus (HBV) arising in childhood is associated with hepatocellular carcinoma in adult life. Between 1986 and 1990, approximately 120,000 Gambian newborns were enrolled in a randomised controlled trial to assess the effectiveness of infant HBV vaccination on the prevention of hepatocellular carcinoma in adulthood. These children are now in adolescence and approaching adulthood, when the onset of sexual activity may challenge their hepatitis B immunity. Thus a booster dose in adolescence could be important to maintain long-term protection. METHODS: Fifteen years after the start of the HBV infant vaccination study, 492 vaccinated and 424 unvaccinated children were identified to determine vaccine efficacy against infection and carriage in adolescence. At the same time, 297 of the 492 infant-vaccinated subjects were randomly offered a booster dose of HBV vaccine. Anti-HBs was measured before the booster, and two weeks and 1 year afterwards (ISRCTN71271385). RESULTS: Vaccine efficacy 15 years after vaccination was 67.0% against infection as manifest by anti-HBc positivity (95% CI 58.2-74.6%), and 96.6% against HBsAg carriage (95% CI 91.5-100%). 31.2% of participants had detectable anti-HBs with a GMC of 32 IU/l. For 168 boosted participants GMC anti-HBs responses were 38 IU/l prior to vaccination, 524 IU/l two weeks after boosting, and 101 IU/l after 1 year. CONCLUSIONS: HBV vaccination in infants confers very good protection against carriage up to 15 years of age, although a large proportion of vaccinated subjects did not have detectable anti-HBs at this age. The response to boosting persisted for at least a year. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN71271385.

Risk factors for and clinical outcome of congenital cytomegalovirus infection in a peri-urban West-African birth cohort.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide. Epidemiology and clinical outcomes are known to vary with socio-economic background, but few data are available from developing countries, where the overall burden of infectious diseases is frequently high. METHODOLOGY/PRINCIPAL FINDINGS: As part of an ongoing birth cohort study in The Gambia among term infants, urine samples were collected at birth and tested by PCR for the presence of CMV DNA. Risk factors for transmission and clinical outcome were assessed, including placental malaria infection. Babies were followed up at home monthly for morbidity and anthropometry, and at one year of age a clinical evaluation was performed. The prevalence of congenital CMV infection was 5.4% (40/741). A higher prevalence of hepatomegaly was the only significant clinical difference at birth. Congenitally infected children were more often first born babies (adjusted odds ratio (OR) 5.3, 95% confidence interval (CI) 2.0-13.7), more frequently born in crowded compounds (adjusted OR 2.9, 95%CI 1.0-8.3) and active placental malaria was more prevalent (adjusted OR 2.9, 95%CI 1.0-8.4). These associations were corrected for maternal age, bed net use and season of birth. During the first year of follow up, mothers of congenitally infected children reported more health complaints for their child. CONCLUSIONS/SIGNIFICANCE: In this study, the prevalence of congenital CMV among healthy neonates was much higher than previously reported in industrialised countries, and was associated with active placental malaria infection. There were no obvious clinical implications during the first year of life. The effect of early life CMV on the developing infant in the Gambia could be mitigated by environmental factors, such as the high burden of other infections.

Development and evaluation of an oligonucleotide ligation assay for detection of drug resistance-associated mutations in the human immunodeficiency virus type 2 pol gene.

Human immunodeficiency virus type 2 (HIV-2) is naturally resistant to several antiretroviral drugs, including all of the non-nucleoside reverse transcriptase inhibitors and the entry inhibitor T-20, and may have reduced susceptibility to some protease inhibitors. These resistance properties make treatment of HIV-2 patients difficult, with very limited treatment options. Therefore, early detection of resistance mutations is important for understanding treatment failures and guiding subsequent therapy decisions. With the Global Fund Initiative, a substantial number of HIV-2 patients in West Africa will receive antiretroviral therapy. Therefore, development of cheaper and more sustainable resistance assays, such as the oligonucleotide ligation assay (OLA), is a priority. In this study, we designed oligonucleotide probes to detect the Q151M mutation, associated with phenotypic resistance to zidovudine, didanosine, zalcitabine, and stavudine, and the M184V mutation, associated with phenotypic resistance to lamivudine and emtricitabine, in HIV-2. The assay was successfully developed and evaluated with 122 samples from The Gambia, Guinea Bissau, The Netherlands, and Sweden. The overall sensitivity of the assay was 98.8%, with 99.2% for Q151M and 98.4% for M184V. OLA results were compared with sequencing to give high concordances of 98.4% (Q151M) and 97.5% (M184V). OLA demonstrated a higher sensitivity for detection of minor variants as a mixture of wild-type and mutant viruses in cases when sequencing detected only the major population. In conclusion, we have developed a simple, easy-to-use, and economical assay for genotyping of drug resistance in HIV-2 that is more sustainable for use in resource-poor settings than is consensus sequencing.

Is HIV-2- induced AIDS different from HIV-1-associated AIDS? Data from a West African clinic.

BACKGROUND: Although AIDS is less frequent following HIV-2 than HIV-1 infection, it is unclear whether the clinical picture and clinical course of AIDS are similar in the two infections. OBJECTIVES: To compare the pattern of AIDS-defining events, CD4 cell count at the time of AIDS diagnosis, survival from time of AIDS, and CD4 cell count near time of death in HIV-1 and HIV-2-infected patients. METHODS: Adult patients with AIDS who attended the clinics of the MRC in The Gambia were enrolled. AIDS was diagnosed according to the expanded World Health Organization case definition for AIDS surveillance (1994). RESULTS: Three hundred and forty-one AIDS patients with HIV-1 and 87 with HIV-2 infection were enrolled. The most common AIDS-defining events in both infections were the wasting syndrome and pulmonary tuberculosis. The median CD4 cell count at AIDS was 109 cells/microl in HIV-1 and 176 in HIV-2 (P = 0.01) and remained significantly higher in HIV-2 after adjustment for age and sex (P = 0.03). The median time to death was 6.3 months in HIV-1 and 12.6 months in HIV-2-infected patients (P = 0.03). In a multivariable analysis adjusting for age, sex and CD4 cell count, the mortality rates of HIV-1 and HIV-2-infected patients were similar (P = 0.25). The median CD4 cell count near time of death was 62 and 120 cells/microl in HIV-1 and HIV-2-infected patients, respectively (P = 0.02). CONCLUSIONS: HIV-2 patients have a higher CD4 cell count at the time of AIDS, and a longer survival after AIDS. The mortality after an AIDS diagnosis is more influenced by CD4 cell count than HIV type.

A relational database for management of flow cytometry and ELISpot clinical trial data.

BACKGROUND: Although relational databases are widely used in bioinformatics with deposited and finalized data, they have not received widespread usage among immunologists for managing raw laboratory data such as that generated by ELISpot or flow cytometry assays. Almost no published guidance exists for immunologists to design appropriate and useful data management systems. METHODS: We describe the design and implementation of a Microsoft Access relational database used in a clinical trial in which the primary immunogenicity measures were ELISpot and intracellular cytokine staining. RESULTS: Our data management system enabled us to perform sophisticated queries and to interpret our data as quantitatively as possible. It could easily be used without modification by other researchers using automated plate reading of ELISpot plates or four color flow cytometry. CONCLUSION: We illustrate in detail the use of a flexible data management system for two of the most widely used immunological techniques. Minor modifications for more colors or other outputs can easily be implemented. Based on this example, other modifications could be easily envisaged for any other quantitative output.

Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection.

Unlike HIV-1-infected people, most HIV-2-infected subjects maintain a healthy CD4+ T cell count and a strong HIV-specific CD4+ T cell response. To define the cellular immunological correlates of good prognosis in HIV-2 infection, we conducted a cross-sectional study of HIV Gag-specific T cell function in HIV-1- and HIV-2-infected Gambians. Using cytokine flow cytometry and lymphoproliferation assays, we show that HIV-specific CD4+ T cells from HIV-2-infected individuals maintained proliferative capacity, were not terminally differentiated (CD57-), and more frequently produced IFN-gamma or IL-2 than CD4+ T cells from HIV-1-infected donors. Polyfunctional (IFN-gamma+/IL-2+) HIV-specific CD4+ T cells were found exclusively in HIV-2+ donors. The disparity in CD4+ T cell responses between asymptomatic HIV-1- and HIV-2-infected subjects was not associated with differences in the proliferative capacity of HIV-specific CD8+ T cells. This study demonstrates that HIV-2-infected donors have a well-preserved and functionally heterogeneous HIV-specific memory CD4+ T cell response that is associated with delayed disease progression in the majority of infected people.

Application of real-time PCR to quantify hepatitis B virus DNA in chronic carriers in The Gambia.

BACKGROUND/AIM: The study aimed at developing a real-time quantitative PCR assay to monitor HBV serum virus load of chronic carriers enrolled in therapeutic trials. METHOD: Quantitative real-time PCR assay was carried out using SYBR-Green signal detection and primers specific to the S gene. Thermal cycling was performed in an ABi 5700 sequence detection system. The assay was calibrated against an international HBV DNA standard and inter- and intra-assay reproducibility determined. Levels of viral load were monitored for 1-year in lamivudine treated carriers. Correlation between HBV DNA levels and HBeAg sero-status was determined in untreated carriers. RESULTS: The qPCR assay showed good intra- and inter-assay reproducibility over a wide dynamic range (1.5 x 103 to 1.5 x 108 copies/mL) and correlated well with those from a commercial assay (r = 0.91, (p < 0.001). Viral load levels dropped dramatically but temporarily during and after a short course of lamivudine therapy. HBV DNA was a more reliable indicator of the presence of virus than HBe antigen and was detected in 77.0% (161/209) of HBeAg negative and in all HBeAg positive carriers. CONCLUSION: This method is reliable, accurate, and reproducible. HBV DNA Quantification by qPCR can be used to monitor the efficacy of HBV therapy and useful in understanding the natural history of HBV in an endemic area.

Sixteen years of HIV surveillance in a West African research clinic reveals divergent epidemic trends of HIV-1 and HIV-2.

BACKGROUND: The HIV-1 epidemic in West Africa is characterized by a slower rise than that in Eastern and Southern Africa. The HIV-2 epidemic in West Africa may be declining, but few long-term data exist. METHODS: In a research clinic in The Gambia, HIV-1 and HIV-2 prevalence trends among all new patients being tested for HIV were examined over a 16 year period (1988 till 2003). In newly diagnosed patients a baseline CD4 count was done. RESULTS: An HIV test was done in 23 363 patients aged 15 years or older. The prevalence of HIV-1 was 4.2% in 1988-91 and rose to 17.5% in 2001-03 (P < 0.0001, chi(2)-test for trend). The prevalence of HIV-2 was 7.0% in 1988-91 and declined to 4.0% in 2001-03 (P < 0.0001). HIV-1 prevalence increased and HIV-2 prevalence decreased with time in logistic regression models adjusting for age, sex, and indication for test (P < 0.0001). Baseline CD4 counts were available for 65% of patients. The median CD4 count was 215 cells/mm3 [interquartile range (IQR) 72-424] for HIV-1, and 274 (IQR 100-549) for HIV-2 infected patients. There was no marked trend of rise or decline in baseline CD4 count in either HIV-1 or HIV-2 infected patients over the study period. Forty-five per cent of newly diagnosed HIV patients had a CD4 count <200 cells/mm3. CONCLUSIONS: These data suggest that HIV-1 prevalence is rising in The Gambia, and that HIV-2 is declining. HIV patients in The Gambia present late and almost half of patients would qualify for anti-retroviral treatment at their first visit.