Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test

All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system.From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%.As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition

Predominance of the heterozygous CCR5 delta‐24 deletion in African individuals resistant to HIV infection might be related to a defect in CCR5 addressing at the cell surface

Introduction The chemokine receptor CCR5 is the main co-receptor for R5-tropic HIV-1 variants. We have previously described a novel 24-base pair deletion in the coding region of CCR5 among individuals from Rwanda. Here, we investigated the prevalence of hCCR5 Delta 24 in different cohorts and its impact on CCR5 expression and HIV-1 infection in vitro. Methods We screened hCCR5 Delta 24 in a total of 3232 individuals which were either HIV-1 uninfected, high-risk HIV-1 seronegative and seropositive partners from serodiscordant couples, Long-Term Survivors, or HIV-1 infected volunteers from Africa (Rwanda, Kenya, Guinea-Conakry) and Luxembourg, using a real-time PCR assay. The role of the 24-base pair deletion on CCR5 expression and HIV infection was assessed in cell lines and PBMC using mRNA quantification, confocal analysis, flow and imaging cytometry. Results and Discussion Among the 1661 patients from Rwanda, 12 individuals were heterozygous for hCCR5 Delta 24 but none were homozygous. Although heterozygosity for this allele may not confer complete resistance to HIV-1 infection, the prevalence of the mutation was 2.41% (95%CI: 0.43; 8.37) in 83 Long-Term Survivors (LTS) and 0.99% (95%CI: 0.45; 2.14) in 613 HIV-1 exposed seronegative members as compared with 0.35% (95% Cl: 0.06; 1.25) in 579 HIV-1 seropositive members. The prevalence of hCCR5 Delta 24 was 0.55% (95%CI: 0.15; 1.69) in 547 infants from Kenya but the mutation was not detected in 224 infants from Guinea-Conakry nor in 800 Caucasian individuals from Luxembourg. Expression of hCCR5 Delta 24 in cell lines and PBMC showed that the hCCR5 Delta 24 protein is stably expressed but is not transported to the plasma membrane due to a conformational change. Instead, the mutant receptor was retained intracellularly, colocalized with an endoplasmic reticulum marker and did not mediate HIV-1 infection. Co-transfection of hCCR5 Delta 24 and wtCCR5 did not indicate a transdominant negative effect of CCR5 Delta 24 on wtCCR5. Conclusions Our findings indicate that hCCR5 Delta 24 is not expressed at the cell surface. This could explain the higher prevalence of the heterozygous hCCR5 Delta 24 in LTS and HIV-1 exposed seronegative members from serodiscordant couples. Our data suggest an East-African localization of this deletion, which needs to be confirmed in larger cohorts from African and non-African countries

Diagnosis and management of antiretroviral-therapy failure in resource-limited settings in sub-Saharan Africa: challenges and perspectives.

Despite the enormous progress made in scaling up antiretroviral therapy (ART) in sub-Saharan Africa, many challenges remain, not least of which are the identification and management of patients who have failed first-line therapy. Less than 3% of patients are receiving second-line treatment at present, whereas 15-25% of patients have detectable viral loads 12 months or more into treatment, of whom a substantial proportion might have virological failure. We discuss the reasons why virological ART failure is likely to be under-diagnosed in the routine health system, and address the current difficulties with standard recommended second-line ART regimens. The development of new diagnostic tools for ART failure, in particular a point-of-care HIV viral-load test, combined with simple and inexpensive second-line therapy, such as boosted protease-inhibitor monotherapy, could revolutionise the management of ART failure in resource-limited settings

Liver Disease and Treatment Needs of Asymptomatic Persons Living With Hepatitis B in Senegal.

The prevalence of active hepatitis B among asymptomatic persons remains unclear in Africa. Of 1206 newly diagnosed persons in Senegal, 12.3% had significant fibrosis and 31.3% had hepatitis B virus (HBV) DNA levels >2000 IU/mL. Overall, 128 (12.9%) were eligible for antiviral therapy. Generalized HBV screening allowed the identification of a large population requiring HBV care

HIV outbreaks among people who inject drugs in Europe, North America and Israel

During 2011–16, HIV outbreaks occurred among people who inject drugs (PWID) in Canada (southeastern Saskatchewan), Greece (Athens), Ireland (Dublin), Israel (Tel Aviv), Luxembourg, Romania (Bucharest), Scotland (Glasgow), and USA (Scott County, Indiana). Factors common to many of these outbreaks included community economic problems, homelessness, and changes in drug injection patterns. The outbreaks differed in size (from under 100 to over 1000 newly reported HIV cases among PWID) and in the extent to which combined prevention had been implemented before, during, and after the outbreaks. Countries need to ensure high coverage of HIV prevention services and coverage higher than the current UNAIDS recommendation might be needed in areas in which short acting drugs are injected. In addition, monitoring of PWID with special attention for changing drug use patterns, risk behaviours, and susceptible subgroups (eg, PWID experiencing homelessness) needs to be in place to prevent or rapidly detect and contain new HIV outbreaks

Validation of a SARS-CoV-2 Surrogate Neutralization Test Detecting Neutralizing Antibodies against the Major Variants of Concern.

peer reviewedSARS-CoV-2 infection and/or vaccination elicit a broad range of neutralizing antibody responses against the different variants of concern (VOC). We established a new variant-adapted surrogate virus neutralization test (sVNT) and assessed the neutralization activity against the ancestral B.1 (WT) and VOC Delta, Omicron BA.1, BA.2, and BA.5. Analytical performances were compared against the respective VOC to the reference virus neutralization test (VNT) and two CE-IVD labeled kits using three different cohorts collected during the COVID-19 waves. Correlation analyses showed moderate to strong correlation for Omicron sub-variants (Spearman's r = 0.7081 for BA.1, r = 0.7205 for BA.2, and r = 0.6042 for BA.5), and for WT (r = 0.8458) and Delta-sVNT (r = 0.8158), respectively. Comparison of the WT-sVNT performance with two CE-IVD kits, the "Icosagen SARS-CoV-2 Neutralizing Antibody ELISA kit" and the "Genscript cPass, kit" revealed an overall good correlation ranging from 0.8673 to -0.8773 and a midway profile between both commercial kits with 87.76% sensitivity and 90.48% clinical specificity. The BA.2-sVNT performance was similar to the BA.2 Genscript test. Finally, a correlation analysis revealed a strong association (r = 0.8583) between BA.5-sVNT and VNT sVNT using a double-vaccinated cohort (n = 100) and an Omicron-breakthrough infection cohort (n = 91). In conclusion, the sVNT allows for the efficient prediction of immune protection against the various VOCs

The HIV/AIDS epidemic in sub-Saharan Africa: thinking ahead on programmatic tasks and related operational research

Until now, we have all been desperately trying to run behind the HIV/AIDS epidemic and catch up with it, but despite all our efforts, the epidemic remains well ahead of us. In 2010, the antiretroviral treatment (ART) gap was about 60%, AIDS-related deaths were almost two million a year, and on top of these figures, for every one person started on ART, there were two new HIV infections. What is needed to change this situation is to think ahead of the epidemic in terms of the programmatic tasks we will be faced with and try to act boldly in trying to implement those tasks. From a programmatic perspective, we: a) highlight what needs to fundamentally change in our thinking and overall approach to the epidemic; and b) outline a number of key task areas for implementation and related operational research

Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test

All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system.From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%.As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition

Screening migrants in the early Cold War: the geopolitics of U.S. immigration policy

The main elements of U.S. immigration policy date back to the early Cold War. One such element is a screening process initially designed to prevent infiltration by Communist agents posing as migrants from East-Central Europe. The development of these measures was driven by geopolitical concerns, resulting in vetting criteria that favored the admission of hardline nationalists and anti-Communists. The argument proceeds in two steps. First, the article demonstrates that geopolitics influenced immigration policy, resulting in the admission of extremist individuals. Second, it documents how geopolitical concerns and the openness of U.S. institutions provided exiles with the opportunity to mobilize politically. Although there is little evidence that the vetting system succeeded in preventing the entry of Communist subversives into the United States, it did help to create a highly mobilized anti-Communist ethnic lobby that supported extremist policies vis-à-vis the Soviet Union during the early Cold War

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe