Differential antibody responses to Plasmodium falciparum merozoite proteins in Malawian children with severe malaria

Cerebral malaria (CM) and severe malarial anemia (SMA) are 2 major causes of death in African children infected with Plasmodium falciparum. We investigated levels of naturally acquired antibody to conserved and variable regions of merozoite surface protein (MSP)-1 and MSP-2, apical membrane antigen (AMA)-1, and rhoptry-associated protein 1 in plasma samples from 126 children admitted to the hospital with CM, 59 with SMA, and 84 with uncomplicated malaria (UM) in Malawi. Children with SMA were distinguished by very low levels of immunoglobulin (Ig) G to the conserved C-terminus of MSP-1 and MSP-2 and to full-length AMA-1. Conversely, children with CM had significantly higher levels of IgG to the conserved regions of all antigens examined than did children with UM (for MSP-1 and AMA-1, P< .005; for MSP-2, P< .05) or SMA (for MSP-1 and MSP-2, P<.001; for AMA-1, P< .005). These distinct IgG patterns might reflect differences in age, exposure to P. falciparum, and/or genetic factors affecting immune responses

Field Evaluation of Calypte’s AWARE™ Blood Serum Plasma (BSP) and Oral Mucosal Transudate (OMT) Rapid Tests for Detecting Antibodies to HIV-1 and 2 in Plasma and Oral Fluid

As programs to prevent and care for HIV-infected persons are scaled-up in Africa, there is the need for continuous evaluation of the performance of test kits that could best support these programs. The present study evaluated the sensitivity, specificity, ease of use, and cost of AWARE ™ Blood Serum Plasma (BSP) and Oral Mucosal Transudate (OMT) Rapid HIV-1/2 test kits using real-time and archived samples of HIV-infected persons from Cameroon. Matched whole blood and OMT specimens were collected prospectively from HIV-positive and HIV-negative persons from different regions of Cameroon and tested using the AWARE ™ BSP and OMT test kits, respectively. These results were compared to the gold standard that included a combination of Determine HIV-1/2 and Enzygnost HIV-1/2. The BSP Rapid test kit was further evaluated using well characterized panels of HIV-2 and HIV-1 group O samples. Cost and end-user analysis of the OMT test kit was done by comparing its actual cost, consumables, safety, bench time and manipulation with other test kits. Of the 732 matched samples, 412 (56.3%) and 320 (43.7%) were from females and males, respectively. Of these samples, 23 (3.1%) gave discordant results between Determine HIV-1/2 and Enzygnost HIV1/2 and were excluded from the analysis. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the AWARE™ BSP were 100%. The AWARE™ OMT had 98.8% sensitivity, 98.9% specificity, 98.0% PPV and 99.4% NPV. The results of a well-characterized archived panel of HIV-2 (n=7) and HIV-1 group O (n=3) samples using the AWARE™ BSP Rapid test kit gave 100% concordance. Total per patient cost of the AWARE OMT rapid test kit was US$4.72 compared to a mean cost of US$7.33 ± 0.11 for the other test kits. Both the AWARE™ BSP and OMT Rapid test kits demonstrated high sensitivities and specificities on all samples tested and were well adapted for use in resource-constrained settings with high HIV heterogeneity such as Cameroon. The AWARE ™ HIV-1/2 OMT Rapid test kit appears to be the cheapest, safest and easiest to use compared with other available test kits

IgG antibody responses to Plasmodium falciparum merozoite antigens in Kenyan children have a short half-life

BACKGROUND: Data suggest that antibody responses to malaria parasites merozoite antigens are generally short-lived and this has implications for serological studies and malaria vaccine designs. However, precise data on the kinetics of these responses is lacking. METHODS: IgG1 and IgG3 responses to five recombinant Plasmodium falciparum merozoite antigens (MSP-119, MSP-2 type A and B, AMA-1 ectodomain and EBA-175 region II) among Kenyan children were monitored using ELISA for 12 weeks after an acute episode of malaria and their half-lives estimated using an exponential decay model. RESULTS: The responses peaked mainly at week 1 and then decayed rapidly to very low levels within 6 weeks. Estimation of the half-lives of 40 IgG1 responses yielded a mean half-life of 9.8 days (95% CI: 7.6-12.0) while for 16 IgG3 responses it was 6.1 days (95% CI: 3.7-8.4), periods that are shorter than those normally described for the catabolic half-life of these antibody subclasses. CONCLUSION: This study indicates antibodies against merozoite antigens have very short half-lives and this has to be taken into account when designing serological studies and vaccines based on the antigens

The role of recombination in the emergence of a complex and dynamic HIV epidemic

<p>Abstract</p> <p>Background</p> <p>Inter-subtype recombinants dominate the HIV epidemics in three geographical regions. To better understand the role of HIV recombinants in shaping the current HIV epidemic, we here present the results of a large-scale subtyping analysis of 9435 HIV-1 sequences that involve subtypes A, B, C, G, F and the epidemiologically important recombinants derived from three continents.</p> <p>Results</p> <p>The circulating recombinant form CRF02_AG, common in West Central Africa, appears to result from recombination events that occurred early in the divergence between subtypes A and G, followed by additional recent recombination events that contribute to the breakpoint pattern defining the current recombinant lineage. This finding also corrects a recent claim that G is a recombinant and a descendant of CRF02, which was suggested to be a pure subtype. The BC and BF recombinants in China and South America, respectively, are derived from recent recombination between contemporary parental lineages. Shared breakpoints in South America BF recombinants indicate that the HIV-1 epidemics in Argentina and Brazil are not independent. Therefore, the contemporary HIV-1 epidemic has recombinant lineages of both ancient and more recent origins.</p> <p>Conclusions</p> <p>Taken together, we show that these recombinant lineages, which are highly prevalent in the current HIV epidemic, are a mixture of ancient and recent recombination. The HIV pandemic is moving towards having increasing complexity and higher prevalence of recombinant forms, sometimes existing as "families" of related forms. We find that the classification of some CRF designations need to be revised as a consequence of (1) an estimated > 5% error in the original subtype assignments deposited in the Los Alamos sequence database; (2) an increasing number of CRFs are defined while they do not readily fit into groupings for molecular epidemiology and vaccine design; and (3) a dynamic HIV epidemic context.</p

Natural antibody response to Plasmodium falciparum Exp-1, MSP-3 and GLURP long synthetic peptides and association with protection

A longitudinal study was undertaken in Burkina Faso among 293 children aged 6 months to 9 years in order to determine the correlation between an antibody response to several individual malarial antigens and malarial infection. It was found that the presence of a positive antibody response at the beginning of the rainy season to three long synthetic peptides corresponding to Plasmodium falciparum Exp-1 101-162, MSP-3 154-249 and GLURP 801-920 but not to CSP 274-375 correlated with a statistically significant decrease in malarial infection during the ongoing transmission season. The simultaneous presence of an antibody response to more than one antigen is indicative of a lower frequency of malarial infection. This gives scientific credibility to the notion that a successful malaria vaccine should contain multiple antigens

Decentralised paediatric HIV care in Ethiopia: a comparison between outcomes of patients managed in health centres and in a hospital clinic

Background: In order to increase access to antiretroviral therapy (ART) in HIV-infected children, paediatric HIV care has been introduced in health centres in Ethiopia, where patients are managed by health professionals with limited training. Objective: To compare outcomes of paediatric HIV care in hospital and health centre clinics and to determine risk factors for death and loss to follow-up (LTFU). Design: Retrospective comparison of patient characteristics and outcomes among children managed in a public hospital and all five public health centres in the uptake area. Results: Among 1,960 patients (health centres 572, hospital clinic 1,388), 34% were lost to follow-up, 2% died, 14% were transferred out, and 46% remained in care. Children initiating ART in the hospital clinic had lower median CD4 cell counts (age &#60;1 year: 575 vs. 1,183 cells/mm3, p=0.024; age 1&#x2013;5 years: 370 vs. 598 cells/mm3, p&#60;0.001; age &#x003E;5 years: 186 vs. 259 cells/mm3, p&#60;0.001), and a higher proportion were &#60;1 year of age (22% vs. 15%, p=0.025). ART initiation rates and retention in care were similar between children managed in health centres and in the hospital clinic (36% vs. 37% and 47% vs. 46%, respectively). Among patients starting ART, mortality was associated with age &#60;1 year [hazard ratio (HR) 12.0; 95% confidence interval (CI): 3.5, 41]. LTFU was associated with CD4 cell counts &#60;350 cells/mm3 (HR 1.8; 95% CI: 1.2, 3.0), weight-for-age z-scores below &#x2212;4 (HR 2.8; 95% CI: 1.4, 5.6), and age &#60;5 years (1&#x2013;5 years: HR 1.6; 95% CI: 1.0, 2.5; &#60;1 year: HR 3.3; 95% CI: 1.6, 6.6). Conclusions: Outcomes of HIV care were similar for Ethiopian children managed in a hospital clinic or in health centres. However, patients treated at the hospital clinic had characteristics of more advanced disease. Rates of LTFU were high in both types of health facility