Naturally-acquired immunity to Plasmodium falciparum malaria develops after several episodes of infection. Fc gamma receptors (FcγRs) bind to immunoglobulin G (IgG) antibodies and mediate phagocytosis of opsonized microbes, thereby, linking humoral and cellular immunity. FcγR polymorphisms influence binding affinity to IgGs and consequently, can influence clinical malaria outcomes. Specifically, variations in FcγRIIA -131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 modulate immune responses through altered binding preferences to IgGs and immune complexes. Differential binding, in turn, changes ability of immune cells to respond to infection through production of inflammatory mediators during P. falciparum infection. We determined the association between haplotypes of FcγRIIA-131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 variants and severe malarial anemia (SMA; hemoglobin < 6.0 g/dL, any density parasitemia) in children (n = 274; aged 6–36 months) presenting for their first hospital visit with P. falciparum malaria in a holoendemic transmission region of western Kenya. FcγRIIA-131Arg/His and FcγRIIIA-176F/V genotypes were determined using TaqMan® SNP genotyping, while FcγRIIIBNA1/NA2 genotypes were determined using restriction fragment length polymorphism. Hematological and parasitological indices were measured in all study participants. Carriage of FcγRIIA-131Arg/FcγRIIIA-176F/FcγRIIIBNA2 haplotype was associated with susceptibility to SMA (OR = 1.70; 95% CI; 1.02–2.93; P = 0.036), while the FcγRIIA-131His/ FcγRIIIA-176F/ FcγRIIIB NA1 haplotype was marginally associated with enhanced susceptibility to SMA (OR: 1.80, 95% CI; 0.98–3.30, P = 0.057) and higher levels of parasitemia (P = 0.009). Individual genotypes of FcγRIIA-131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 were not associated with susceptibility to SMA. The study revealed that haplotypes of FcγRs are important in conditioning susceptibility to SMA in immune-naive children from P. falciparum holoendemic region of western Kenya.

Although interferon-gamma, interleukin-10, and adiponectin are key immunopathogenesis mediators of tuberculosis, their association with clinical manifestations of early stage disease is inconclusive. We determined interferon-gamma, interleukin-10, and adiponectin levels in clinically and phenotypically well-characterised non-substance using new pulmonary tuberculosis patients (n=13) and controls (n=14) from Kenya. Interferon-gamma levels (P<0.0001) and interferon-gamma to interleukin-10 (P<0.001) and interferon-gamma to adiponectin (P=0.027) ratios were elevated in tuberculosis cases. Correlation analyses in tuberculosis cases showed associations of interferon-gamma levels with body weight (ρ=-0.849;P<0.0001), body mass index (ρ=0.664;P=0.013), hip girth (ρ=-0.579;P=0.038), and plateletcrit (ρ=0.605;P=0.028); interferon-gamma to interleukin-10 ratio with diastolic pressure (ρ=-0.729;P=0.005); and interferon-gamma to adiponectin ratio with body weight (ρ=-0.560;P=0.047), body mass index (ρ=-0.604;P=0.029), and plateletcrit (ρ=0.793;P=0.001). Taken together, our results suggest mild-inflammation in early stage infection characterised by upregulation of circulating interferon-gamma production in newly infected TB patients.

Information about HBV sero-markers, infection stages and genotypes in HIV-1 infected and uninfected injection and non-injection drug users (IDUs) in Kenya remains elusive. A cross-sectional study examining HBV sero-marker, infection stages and genotypes was conducted among HIV-1 infected and uninfected, respectively, IDUs (n = 157 and n = 214) and non-IDUs (n = 139 and n = 48), and HIV-1 uninfected non-drug using controls (n = 194) from coastal, Kenya. HBV sero-marker and infection stages were based on HBV 5-panel rapid test plasma sero-reactivity. DNA was extracted from acute and chronic plasma samples and genotypes established by nested-PCR and direct sequencing. HBsAg positivity was higher in HIV-1 infected IDUs (9.6 %) relative to HIV-1 uninfected IDUs (2.3 %), HIV-1 infected non-IDUs (3.6 %), HIV-1 uninfected non-IDUs (0.0 %) and non-drug users (2.6 %; P = 0.002). Contrastingly, HBsAb positivity was higher in HIV-1 uninfected IDUs (14.6 %) and non-IDUs (16.8) in comparison to HIV-1 infected IDUs (8.3 %), and non-IDUs (8.6 %), and non-drug users (8.2 %; P = 0.023). HBcAb positivity was higher in HIV-1 infected IDUs (10.2 %) compared to HIV-1 uninfected IDUs (3.3 %), HIV-1 infected non-IDUs (6.5 %), HIV-1 uninfected non-IDUs (2.1 %) and non-drug users (4.6 %; P = 0.038). Acute (5.7 %, 1.4 %, 0.0 %, 0.0 % and 1.5 %) and chronic (5.1 %, 0.9 %, 3.6 %, 0.0 % and 1.5 %) stages were higher in HIV-1 infected IDUs, compared to HIV-1 uninfected IDUs, HIV-1 infected and uninfected non-IDUs and non-drug users, respectively. However, vaccine type response stage was higher in HIV-1 uninfected IDUs (15.4 %) relative to HIV-1 infected IDUs (6.4 %), and HIV-1 infected (6.5 %), and uninfected (10.4 %) non-IDUs, and non-drug users (5.7 %; P = 0.003). Higher resolved infection rates were also recorded in HIV-1 uninfected IDUs (11.2 %) compared to HIV-1 infected IDUs (8.3 %), and HIV-1 infected (7.2 %), uninfected (6.3 %) non-IDUs, and non-drug users (6.7 %; P = 0.479), respectively. Only A1 genotype showing minimal diversity was detected among the study participants. HBV sero-markers and infection staging are valuable in diagnosis and genotyping of HBV infections. Among IDUs, higher HBsAg and HBcAb positivity in HIV-1 infected and higher HBsAb positivity in HIV-1 negative IDUs suggests frequent exposure. Additionally, HBV genotype A is the dominant circulating genotype in both high and low risk populations of Kenya.

Substance use is increasingly becoming prevalent on the African continent, fueling the spread of HIV infection. Although socio-demographic factors influence substance consumption and risk of HIV infection, the association of these factors with HIV infection is poorly understood among substance users on the African continent. The objective of the study was to assess socio-demographic and sexual practices that are associated with HIV infection among injection drug users (IDUs), non-IDUs, and non-drug users (DUs) at an urban setting of coastal Kenya. A cross-sectional descriptive study was conducted among 451 adults comprising HIV-infected and -uninfected IDUs (n = 157 and 39); non-IDUs (n = 17 and 48); and non-DUs (n = 55 and 135); respectively at coastal, Kenya. Respondent driven sampling, snowball and makeshift methods were used to enroll IDUs and non-IDUs. Convenience and purposive sampling were used to enroll non-DUs from the hospital’s voluntary HIV testing unit. Participant assisted questionnaire was used in collecting socio-demographic data and sexual practices. Binary logistic regression analysis indicated that higher likelihood of HIV infection was associated with sex for police protection (OR, 9.526; 95% CI, 1.156-78.528; P = 0.036) and history of sexually transmitted infection (OR, 5.117; 95% CI, 1.924-13.485; P = 0.001) in IDUs; divorced, separated or widowed marital status (OR, 6.315; 95% CI, 1.334-29.898; P = 0.020) in non-IDUs; and unemployment (OR, 2.724; 95% CI, 1.049-7.070; P = 0.040) in non-drug users. However, never married (single) marital status (OR, 0.140; 95% CI, 0.030-0.649; P = 0.012) was associated with lower odds for HIV infection in non-drug users. Altogether, these results suggest that socio-demographic and sexual risk factors for HIV transmission differ with drug use status, suggesting targeted preventive measures for drug users.

Background: Plasmodium falciparummalaria remains a leading cause of morbidity and mortality among African children. Innate immunity provides the first line of defence againstP. falciparuminfections, particularly in young children that lack naturally-acquired malarial immunity, such as the population examined here. Consistent with the fact that elevated interleukin (IL)-12 is an important component of the innate immune response that provides protective immunity against malaria, we have previously shown that suppression of IL-12 in African children is associated with the development of severe malarial anaemia (SMA). Since the role ofIL12Bvariants in conditioning susceptibility to SMA remains largely unexplored, the association between a single nucleotide polymorphism (1188A→C, rs3212227), SMA (Hb<6.0g/dL), circulating IL-12p40/p70 levels, and longitudinal clinical outcomes in Kenyan children (n = 756) residing in a holoendemic falciparum malaria transmission area were investigated.Results: Multivariate logistic regression analysis in children with acute malaria (n = 544) demonstrated that carriers of the C allele had increased susceptibility to SMA (CC: OR, 1.674; 95% CI, 1.006-2.673;P= 0.047, and AC: OR, 1.410; 95% CI, 0.953-2.087;P= 0.086) relative to wild type (AA). Although children with SMA had lower IL-12p40/p70 levels than the non-SMA group (P= 0.037), levels did not differ significantly according to genotype. Longitudinal analyses in the entire cohort (n = 756) failed to show any significant relationships between rs3212227 genotypes and either susceptibility to SMA or all-cause mortality throughout the three year follow-up.Conclusion: The rs3212227 is a marker of susceptibility to SMA in children with acute disease, but does not appear to mediate functional changes in IL-12 production or longitudinal outcomes during the acquisition of naturally-acquired malarial immunity.

Although the co-burden of injection drug use and HIV is increasing in Africa, little is known about the laboratory markers of injection drug use and anti-retroviral treatment (ART) in Kenyan injection drug users. This study, therefore, aimed at determining the clinical chemistry profiles and identifying the key laboratory markers of HIV infection during ART in injection heroin users (IHUs).