HIV Treatments Have Malaria Gametocyte Killing and Transmission Blocking Activity.

HIV Treatments have Malaria Gametocyte Killing and Transmission Blocking Activity.

J Infect Dis. 2013 Mar 28;
Hobbs CV, Tanaka TQ, Muratova O, Van Vliet J, Borkowsky W, Williamson KC, Duffy PE

Background.?Millions of individuals being treated for HIV live in malaria endemic areas, but the effects of these treatments on malaria transmission are unknown. While drugs like HIV protease inhibitors (HIV PIs) and trimethoprim-sulfamethoxazole (TMP-SMX) have known activity against parasites during liver or asexual blood stages, their effects on transmission stages requires further study.Methods.?The HIV PIs, lopinavir and saquinavir, the non-nucleoside reverse transcriptase inhibitor (NNRTI), nevirapine, and the antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX) were assessed for activity against Plasmodium falciparum transmission stages. Drug effects on gametocytes were investigated using the alamarBlue® assay for viability and exflagellation assessment for maturation. Drug effects on transmission were assessed by examining mosquito oocyst count as a marker for infectivity with standard membrane feeding assays.Results.?The HIV PIs lopinavir and saquinavir have gametocytocidal and transmission blocking effects at clinically relevant treatment levels, while the NNRTI, nevirapine, does not. TMP-SMX is not gametocytocidal, but does block transmission, at prophylaxis levels.Conclusion.?Specific HIV treatments have gametocyte killing and transmission blocking effects. Clinical studies are warranted to evaluate these findings and their potential impact on eradication efforts. HubMed – drug


Humoral and Cellular Immunity to Plasmodium falciparum Merozoite Surface Protein 1 and Protection from Blood-stage Infection.

J Infect Dis. 2013 Mar 28;
Moormann AM, Sumba PO, Chelimo K, Fang H, Tisch DJ, Dent AE, John CC, Long CA, Vulule J, Kazura JW

Background.?Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria infection would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts.Methods.?The relationship between IgG antibody and IFN-? and IL-10 responses to the 42 kD C-terminal fragment of Plasmodium falciparum Merozoite Surface Protein 1 (MSP142) and risk-of-(re)infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in a holoendemic area of western Kenya.Results.?Positive IFN-? ELISA and ELISPOT responses to MSP-142 3D7 were associated with delayed time-to-(re)infection whereas high-titer IgG antibodies to MSP-142 3D7 or FVO alleles were not independently predictive of risk-of-(re)infection. When IFN-? and IL-10 responses were both present, the protective effect of IFN-? was abrogated. A Cox proportional hazard model including IFN-?, IL-10, MSP142 3D7 IgG antibody responses, hemoglobin S genotype, age and infection status at baseline, showed time to blood-stage infection correlated positively with IFN?+ responses and negatively with IL-10+ responses, younger age, and asymptomatic parasitemia.Conclusion.?Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to either measure alone. HubMed – drug


CD26/DPP4 levels in Peripheral Blood and T cells in Patients with Type 2 Diabetes Mellitus.

J Clin Endocrinol Metab. 2013 Mar 28;
Lee SA, Kim YR, Yang EJ, Kwon EJ, Kim SH, Kang SH, Park DB, Oh BC, Kim J, Heo ST, Koh G, Lee DH

Context:Dipeptidyl peptidase 4 (CD26/DPP4) is expressed on blood T cells and also circulates in a soluble form (sCD26/DPP4).Objective:We aimed to evaluate blood T cell and circulating CD26/DPP4 and its association with metabolic parameters in patients with type 2 diabetes (T2DM).Designs:We measured CD26/DPP4 expression (% of CD26(+) cells using flow cytometry) on CD4(+) and CD8(+) T cells, serum CD26/DPP4 level and activity, and various metabolic parameters in T2DM patients not on DPP4 inhibitor therapy (n=148). Non-diabetic control subjects (n= 50) were included as a control group.Results:Compared with the healthy controls, CD26/DPP4 expression on CD4(+) T cells and CD8(+) T cells was higher in T2DM patients. Serum CD26/DPP4 levels and enzymatic activities were also higher in patients with T2DM than in the control group, only when metformin and/or thiazolidinedione (TZD)-treated T2DM patients were excluded; metformin and/or TZD-treated T2DM patients had lower those values compared with other T2DM patients. Various parameters in T2DM patients were related to CD26/DPP4 expression on the T cells [hemoglobin A1c (HbA1c)], serum sCD26/DPP4 [HbA1c and HOMA2-IR (insulin resistance assessed by updated homeostasis model assessment)], and serum CD26/DPP4 activity [HOMA2-IR, ?-glutamyl transferase (?GT) and ALT] by multivariate analyses. After active glucose control for 12 weeks in drug-naïve T2DM patients (n=50), CD26/DPP4 expression on blood T cells was significantly decreased.Conclusions:Our results suggest that the CD26/DPP4 level on blood T cells was associated with glucose control status in patients with T2DM. HubMed – drug


Choice of drugs in the treatment of chronic hepatitis B in pregnancy.

World J Gastroenterol. 2013 Mar 14; 19(10): 1671-2
Guclu E, Karabay O

The selection of antiviral drugs for chronic hepatitis B (CHB) treatment in pregnancy is very difficult since none of the drugs have been approved for use in pregnancy. Transmission from mother to newborn remains the most frequent route of infection in mothers with high viral load and positive hepatitis B e antigen status, even with the use of appropriate prophylaxis with hepatitis B virus (HBV) immunoglobulin and HBV vaccination. We read from the article written by Yi et al that lamivudine treatment in early pregnancy was safe and effective. However, we could not understand why adefovir dipivoxil (ADV) was used in three pregnancy cases, since ADV has been classified as pregnancy category C. In pregnancy, telbivudine or tenofovir should be selected when the treatment of CHB is necessary, since these drugs have been classified as Food and Drug Administration pregnancy risk category B. HubMed – drug