The East Africa Consortium for human papillomavirus and cervical cancer in women living with HIV/AIDS.

The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer, and to encourage collaborations between researchers in North America and East African countries. To date, studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on the persistence of HPV, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP. It will now be determined how HPV testing fits into cervical cancer screening programs in Kenya and Uganda, how aflatoxin influences immunological control of HIV, how HPV alters certain genes involved in the growth of tumours in HIV-infected women. Although there have been challenges in performing this research, with time, this work should help to reduce the burden of cervical cancer and other cancers related to HIV infection in people living in sub-Saharan Africa, as well as optimized processes to better facilitate research as well as patient autonomy and safety. KEY MESSAGESThe East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer.Collaborations have been established between researchers in North America and East African countries for these studies.Studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on HPV detection, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP.

A cross-sectional analysis of factors associated with detection of oncogenic human papillomavirus in human immunodeficiency virus-infected and uninfected Kenyan women.

BACKGROUND: Cervical cancer is caused by oncogenic human papillomaviruses (HPV) and is one of the most common malignancies in women living in sub-Saharan Africa. Women infected with the human immunodeficiency virus (HIV) have a higher incidence of cervical cancer, but the full impact on HPV detection is not well understood, and associations of biological and behavioral factors with oncogenic HPV detection have not been fully examined. Therefore, a study was initiated to investigate factors that are associated with oncogenic HPV detection in Kenyan women. METHODS: Women without cervical dysplasia were enrolled in a longitudinal study. Data from enrollment are presented as a cross-sectional analysis. Demographic and behavioral data was collected, and HPV typing was performed on cervical swabs. HIV-uninfected women (n = 105) and HIV-infected women (n = 115) were compared for demographic and behavioral characteristics using t-tests, Chi-square tests, Wilcoxon sum rank tests or Fisher's exact tests, and for HPV detection using logistic regression or negative binomial models adjusted for demographic and behavioral characteristics using SAS 9.4 software. RESULTS: Compared to HIV-uninfected women, HIV-infected women were older, had more lifetime sexual partners, were less likely to be married, were more likely to regularly use condoms, and were more likely to have detection of HPV 16, other oncogenic HPV types, and multiple oncogenic types. In addition to HIV, more lifetime sexual partners was associated with a higher number of oncogenic HPV types (aIRR 1.007, 95% CI 1.007-1.012). Greater travel distance to the clinic was associated with increased HPV detection (aOR for detection of ≥ 2 HPV types: 3.212, 95% CI 1.206-8.552). Older age (aOR for HPV 16 detection: 0.871, 95% CI 0.764-0.993) and more lifetime pregnancies (aOR for detection of oncogenic HPV types: 0.706, 95% CI, 0.565-0.883) were associated with reduced detection. CONCLUSION: HIV infection, more lifetime sexual partners, and greater distance to health-care were associated with a higher risk of oncogenic HPV detection, in spite of ART use in those who were HIV-infected. Counseling of women about sexual practices, improved access to health-care facilities, and vaccination against HPV are all potentially important in reducing oncogenic HPV infections.

Bacteremia in Kenyan children presenting with malaria.

Since the etiologies and clinical outcomes of bacteremia in children with Plasmodium falciparum infections, particularly in areas of holoendemic malaria transmission, are largely unexplored, blood cultures and comprehensive clinical, laboratory, hematological, and nutritional parameters for malaria-infected children (aged 1 to 36 months, n = 585 patients) were investigated at a rural hospital in western Kenya. After the exclusion of contaminant microorganisms, the prevalence of bacteremia was 11.7% in the cohort (n = 506), with nontyphoidal Salmonella spp. being the most common isolates (42.4%). Bacteremia was found to occur in a significantly higher proportion of females than males and was associated with elevated blood glucose concentrations and lowered malaria parasite and hemoglobin (Hb) levels compared to those in abacteremic participants. In addition, the incidences of respiratory distress and severe malarial anemia (SMA; Hb level of <6.0 g/dl) were nonsignificantly greater in children with bacteremia. Mortality was 8.5-fold higher in children with bacteremia. Multivariate logistic regression analyses revealed that bacteremia was significantly associated with reduced incidences of high-density parasitemia (HDP; ≥ 10,000/µl) and increased incidences of malnutrition (i.e., underweight; weight-for-age Z score of <-2 using the NCHS system). Since previous studies showed that bacteremia caused by Gram-negative organisms is associated with enhanced anemia and mortality, multivariate logistic regression was also performed separately for randomly age- and gender-matched children with bacteremia caused by Gram-negative organisms (n = 37) and for children found to be abacteremic (n = 74). These results revealed that the presence of bacteremia caused by Gram-negative organisms was significantly associated with reduced HDP, enhanced susceptibility to respiratory distress, SMA (Hb level of <6.0 g/dl), and being underweight (Z score, <-2). Data presented here from a region of holoendemic P. falciparum transmission demonstrate that although bacteremia is associated with reduced malaria parasitemia, a number of unfavorable clinical outcomes, including malnutrition, respiratory distress, anemia, and mortality, are elevated in children with bacteremia, particularly in cases of Gram-negative origin.

A macrophage migration inhibitory factor promoter polymorphism is associated with high-density parasitemia in children with malaria.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that regulates innate and adaptive immune responses to bacterial and parasitic infections. Functional promoter variants in the MIF gene influence susceptibility to inflammatory diseases in Caucasians. As the role of genetic variation in the MIF gene in conditioning malaria disease outcomes is largely unexplored, the relationship between a G to C transition at MIF -173 and susceptibility to high-density parasitemia (HDP) and severe malarial anemia (SMA) was examined in Kenyan children (aged 3-36 months; n=477) in a holoendemic Plasmodium falciparum transmission region. In a multivariate model, controlling for age, gender, HIV-1 status, and sickle-cell trait, MIF -173CC was associated with an increased risk of HDP compared to MIF -173GG. No significant associations were found between MIF -173 genotypic variants and susceptibility to SMA. Additional studies demonstrated that homozygous G alleles were associated with lower basal circulating MIF levels relative to the GC group. However, stimulation of cultured peripheral blood mononuclear cells with malarial pigment (hemozoin) increased MIF production in the GG group and decreased MIF production in the GC group. Thus, variability at MIF -173 is associated with functional changes in MIF production and susceptibility to HDP in children with malaria.