Haematological changes and recovery associated with treated and untreated Plasmodium falciparum infection in children in the Mount Cameroon Region

Pre-hospital antimalarial treatment of febrile children remains a significant common practice among individuals in the Mount Cameroon region. To evaluate the effect of routinely administered monotherapy sulphadoxine pyrimethamine (SP), treatment using amodiaquine artesunate (AQAS) combination therapy and untreated malaria on haematological and parasitological parameters, 332 malaria positive subjects were assigned to three groups comprising 138 children treated with AQAS, 43 treated with SP and 151 untreated. The changes and recovery in red cell indices, white blood cell and differential and platelets counts were compared. The highest haematological recovery (39.1%) occurred in the AQAS treatment group. The majority (94%) of the untreated cases never achieved haematological recovery even though there was spontaneous clearance of parasites in some cases. Haematological insult was greatest in untreated children followed by those treated with SP, the 1.1 -3 year age group whether or not they received treatment and in those with high parasitaemia. Delayed parasite clearance observed in the untreated and SP treatment group may be responsible for the occurrence of haematological insult. Treatment type and parasitological cure was associated with haematological recovery. Prompt use of effective arthemisinin combination therapy reduced the burden of malaria, hence the greater clinical and haematological benefits observed in our study

B Cell Depletion in HIV-1 Subtype A Infected Ugandan Adults: Relationship to CD4 T Cell Count, Viral Load and Humoral Immune Responses

To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001). HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb) titers against subtype A (p = 0.05) and subtype CRF02_AG (p = 0.02) viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02) and mean titer against the 10 viruses (p = 0.0002). In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001). These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection

Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients

Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4+ T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes

Editorial: Reflections on Professionalization of Education in Cameroon

No abstract

Limited variation of the 5’cis-control region of the transmission blocking vaccine candidate Pfs25 amid great genetic diversity of Plasmodium falciparum in Cameroon

Genetic recombination during sexual reproduction within Plasmodium sp. contributes to parasite diversity and altered gene expression of certain surface markers. The pfs25 gene involved in the upsetof gametocytogenesis is a candidate antigen in transmission blocking vaccine. This study investigated the polymorphism of Pfs25 within its 5’cis-control region in field isolates from different ecotypes inCameroon. Symptomatic patients and asymptomatic healthy school children with a positive smear and from different ecozones were included. Parasite DNA was extracted and polymorphisms within pfs25,cg2-, msp-1, msp-2 and glurp genes were investigated by PCR-RFLP and DNA sequencing. Putative control elements of the 5’cis control regions of Pfs25 were identified by PCGENE software andenzymes were selected whose sequences produced or abolished restriction sites by mutations. Malaria infection was mainly caused by Plasmodium falciparum with sporadic occurrence of Plasmodiummalariae and Plasmodium ovale. Analysis of the Pfs25 5’ cis-control region identified only one polymorphism (0.002%) that abolished an RsaI restriction site as part of the sequence TTTCTGTAC,located 40 bp downstream of the promoter and found at – 478 bp of the ATG. Analysis of the 5’ ciscontrol sequence of Pfs25 revealed minimal variation of the promoter region amid great zonal differences in parasite population. Altitudinal differences in parasite populations were not easily discernable

HLA-DQ haplotypes in 15 different populations

In order to understand the forces governing the evolution of the DQ molecule, PCR-based methods have been used to type the DQA1 and DQB1 loci encoding this heterodimer on 2,807 chromosomes from 15 different populations including Africans, Asians, Amerindians and Caucasians. These ethnically diverse samples represent a variety of population substructures and include small, isolated populations as well as larger populations where admixture has occurred. Nine DQA1 alleles and 18 DQB1 alleles have been identified which make up 42 distinct DQ haplotypes. Some haplotypes are found in all ethnic groups while others are confined to a single ethnic group or population. Despite evidence of recombination between the DQA1 and DQB1 loci, there are no examples of a haplotype carrying a DQw1-associated alpha chain and a DQw2-, DQw3-, or DQw4-associated beta chain in cis (and vice versa). These data suggest that these haplotypes, which encode unstable heterodimers, are rapidly removed from the population through natural selection