Decreased Chronic Morbidity but Elevated HIV Associated Cytokine Levels in HIV-Infected Older Adults Receiving HIV Treatment: Benefit of Enhanced Access to Care?

Background

The association of HIV with chronic morbidity and inflammatory markers (cytokines) in older adults (50+years) is potentially relevant for clinical care, but data from African populations is scarce.

Objective

To examine levels of chronic morbidity by HIV and ART status in older adults (50+years) and subsequent associations with selected pro-inflammatory cytokines and body mass index.

Methods

Ordinary, ordered and generalized ordered logistic regression techniques were employed to compare chronic morbidity (heart disease (angina), arthritis, stroke, hypertension, asthma and diabetes) and cytokines (Interleukins-1 and -6, C-Reactive Protein and Tumor Necrosis Factor-alpha) by HIV and ART status on a cross-sectional random sample of 422 older adults nested within a defined rural South African population based demographic surveillance.

Results

Using a composite measure of all morbidities, controlling for age, gender, BMI, smoking and wealth quintile, HIV-infected individuals on ART had 51% decreased odds (95% CI:0.26-0.92) of current morbidity compared to HIV-uninfected. In adjusted regression, compared to HIV-uninfected, the proportional odds (aPOR) of having elevated inflammation markers of IL6 (>1.56pg/mL) was nearly doubled in HIV-infected individuals on (aPOR 1.84; 95%CI: 1.05-3.21) and not on (aPOR 1.94; 95%CI: 1.11-3.41) ART. Compared to HIV-uninfected, HIV-infected individuals on ART had >twice partial proportional odds (apPOR=2.30;p=0.004) of having non-clinically significant raised hsCRP levels(>1ug/mL); ART-naïve HIV-infected individuals had >double apPOR of having hsCRP levels indicative of increased heart disease risk(>3.9ug/mL;p=0.008).

Conclusions

Although HIV status was associated with increased inflammatory markers, our results highlight reduced morbidity in those receiving ART and underscore the need of pro-actively extending these services to HIV-uninfected older adults, beyond mere provision at fixed clinics. Providing health services through regular community chronic disease screening would ensure health care reaches all older adults in need.     

Influences of seasons and dietary composition on diurnal raptor habitat use in Chembe Bird Sanctuary,Zambia: Implications for conservation

Diurnal raptor habitat use has conservation implications due to environmental and anthropogenic interactions. Three tree-nesting diurnal raptors, black kites (Milvus milvus), steppe buzzards (Buteo vulpinus) and African fish eagles (Haliaeetus vocifer), were studied from December 2016 to October 2017. The objective was to determine factors influencing diurnal raptor habitat selection and use in and around Chembe Bird Sanctuary of Kalulushi district, Zambia. We surveyed for birds in ten randomly selected 200 × 200 m sample plots in each of the five stratified sampling units (miombo woodland, grasslands, human settlements, Lake Chembe and marsh). Seasons and dietary composition variably influenced the distribution, habitat selection and use by raptors. The three raptors devised a suit of behaviours to curtail challenges associated with seasonal food and water availability, and anthropogenic disturbances. There is a need to promote multi-stakeholder engagement and involvement in raptor conservation.     

Adjusting HIV Prevalence for Survey Non-Response Using Mortality Rates: An Application of the Method Using Surveillance Data from Rural South Africa

Background

The main source of HIV prevalence estimates are household and population-based surveys; however, high refusal rates may hinder the interpretation of such estimates. The study objective was to evaluate whether population HIV prevalence estimates can be adjusted for survey non-response using mortality rates.

Methodology/Principal Findings

Data come from the longitudinal Africa Centre Demographic Information System (ACDIS), in rural South Africa. Mortality rates for persons tested and not tested in the 2005 HIV surveillance were available from routine household surveillance. Assuming HIV status among individuals contacted but who refused to test (non-response) is missing at random and mortality among non-testers can be related to mortality of those tested a mathematical model was developed. Non-parametric bootstrapping was used to estimate the 95% confidence intervals around the estimates. Mortality rates were higher among untested (16.9 per thousand person-years) than tested population (11.6 per thousand person-years), suggesting higher HIV prevalence in the former. Adjusted HIV prevalence for females (15–49 years) was 31.6% (95% CI 26.1–37.1) compared to observed 25.2% (95% CI 24.0–26.4). For males (15–49 years) adjusted HIV prevalence was 19.8% (95% CI 14.8–24.8), compared to observed 13.2% (95% CI 12.1–14.3). For both sexes (15–49 years) combined, adjusted prevalence was 27.5% (95% CI 23.6–31.3), and observed prevalence was 19.7% (95% CI 19.6–21.3). Overall, observed prevalence underestimates the adjusted prevalence by around 7 percentage points (37% relative difference).

Conclusions/Significance

We developed a simple approach to adjust HIV prevalence estimates for survey non-response. The approach has three features that make it easy to implement and effective in adjusting for selection bias than other approaches. Further research is needed to assess this approach in populations with widely available HIV treatment (ART).     

TLR2 stimulation drives human naive and effector regulatory T cells into a Th17-like phenotype with reduced suppressive function

Naturally occurring CD4(+)CD25(+)FOXP3(+) regulatory T cells suppress the activity of pathogenic T cells and prevent development of autoimmune responses. There is growing evidence that TLRs are involved in modulating regulatory T cell (Treg) functions both directly and indirectly. Specifically, TLR2 stimulation has been shown to reduce the suppressive function of Tregs by mechanisms that are incompletely understood. The developmental pathways of Tregs and Th17 cells are considered divergent and mutually inhibitory, and IL-17 secretion has been reported to be associated with reduced Treg function. We hypothesized that TLR2 stimulation may reduce the suppressive function of Tregs by regulating the balance between Treg and Th17 phenotype and function. We examined the effect of different TLR2 ligands on the suppressive functions of Tregs and found that activation of TLR1/2 heterodimers reduces the suppressive activity of CD4(+)CD25(hi)FOXP3(low)CD45RA(+) (naive) and CD4(+)CD25(hi)FOXP3(hi)CD45RA(-) (memory or effector) Treg subpopulations on CD4(+)CD25(-)FOXP3(-)CD45RA(+) responder T cell proliferation while at the same time enhancing the secretion of IL-6 and IL-17, increasing RORC, and decreasing FOXP3 expression. Neutralization of IL-6 or IL-17 abrogated Pam3Cys-mediated reduction of Treg suppressive function. We also found that, in agreement with recent observations in mouse T cells, TLR2 stimulation can promote Th17 differentiation of human T helper precursors. We conclude that TLR2 stimulation, in combination with TCR activation and costimulation, promotes the differentiation of distinct subsets of human naive and memory/effector Tregs into a Th17-like phenotype and their expansion. Such TLR-induced mechanism of regulation of Treg function could enhance microbial clearance and increase the risk of autoimmune reactions.     

Significance of variation and evaluation of potential characters in three morphologically similar species of <Emphasis Type="Italic">Barleria</Emphasis> sect. <Emphasis Type="Italic">Barleria</Emphasis> (Acanthaceae) in southern Africa

The variation exhibited within three species of Barleria (B. bechuanensis, B. irritans and B. jubata) was studied to establish whether it was discrete or continuous. Morphological characters were examined and recorded in matrices. Cluster analysis was employed to impose a hierarchical non-overlapping association among operational taxonomic units (OTUs) while ordination was used to establish whether the variation was discrete or continuous. Discrete characters were determined from quantitative morphological data using box and whisker plots. Locality information for the OTUs was obtained from herbarium labels and used to generate maps to illustrate geographic distribution of taxa. Cluster analysis and ordination demonstrated that there was discrete variation within Barleria bechuanensis, B. irritans and B. jubata, which each split into two distinct clusters, although box and whisker plots illustrated that many quantitative characters overlapped within and between species. Since clear morphological gaps between clusters are assumed to be indicators of breaks in gene flow, the distinct clusters were recognised at species level.     

Mycobacterium tuberculosis resides in nonacidified vacuoles in endocytically competent alveolar macrophages from patients with tuberculosis and HIV infection

Alveolar macrophages (AM) are the first professional phagocytes encountered by aerosols containing infections in the lungs, and their phagocytic capacity may be affected by these infections or environmental particles. The aim of this study was to evaluate the innate endocytic and phagocytic properties of human AM obtained from patients with pulmonary tuberculosis and to characterize the vacuoles in which Mycobacterium tuberculosis bacilli reside in vivo. AM were obtained by bronchoalveolar lavage from patients with suspected tuberculosis and from asymptomatic volunteers (controls). Clinical case definitions were based on mycobacterial culture of respiratory specimens and HIV serology. To assess phagocytosis, endocytosis, and acidification of the endosomal system, AM were cultured with IgG-coated polystyrene beads, dextran, and a pH-sensitive reporter (3-(2,4-dinitroanilino)-3-amino-N-methyldipropylamine) and were evaluated by light and immunoelectron microscopy. Cells from 89 patients and 10 controls were studied. We found no significant difference between the two groups in the ability of AM either to ingest beads and dextran or to deliver them to acidified lysosomes. In AM from patients with tuberculosis, the bacilli were located in vacuoles that failed to accumulate endocytosed material and were not acidified. We concluded that AM from patients with tuberculosis and HIV infections were competent to endocytose and phagocytose material and to deliver the material to functional, acidified lysosomes. M. tuberculosis residing in these AM arrests the progression of their phagosomes, which fail to fuse with acidified lysosomes. This confirms, for the first time in humans with tuberculosis and HIV, the conclusions from previous animal and in vitro studies.     

Respiratory cryptosporidiosis in Malawian children with diarrheal disease

BackgroundRespiratory cryptosporidiosis has been documented in children with diarrhea. We sought to describe the dynamics of respiratory involvement in children hospitalized with gastrointestinal (GI) diarrheal disease.MethodsWe conducted a prospective, observational longitudinal study of Malawian children 2–24 months hospitalized with diarrhea. Nasopharyngeal (NP) swabs, induced sputum and stool specimens were collected. Participants that were positive by Cryptosporidium PCR in any of the three compartments were followed up with fortnightly visits up to 8 weeks post-enrollment.ResultsOf the 162 children recruited, participants had mild-moderate malnutrition (mean HAZ -1.6 (SD 2.1)), 37 (21%) were PCR-positive for Cryptosporidium at enrollment (37 stool, 11 sputum, and 4 NP) and 27 completed the majority of follow-up visits (73%). Cryptosporidium was detected in all compartments over the 4 post-enrollment visits, most commonly in stool (100% at enrollment with mean cycle thresholds (Ct) of 28.8±4.3 to 44% at 8 weeks with Ct 29.9±4.1), followed by sputum (31% at enrollment with mean Ct 31.1±4.4 to 20% at 8 weeks with Ct 35.7±2.6), then NP (11% with mean Ct 33.5±1.0 to 8% with Ct 36.6±0.7). Participants with Cryptosporidium detection in both the respiratory and GI tract over the study period reported respiratory and GI symptoms in 81% and 62% of study visits, respectively, compared to 68% and 27%, respectively, for those with only GI detection, and had longer GI shedding (17.5±6.6 v. 15.9±2.9 days).ConclusionCryptosporidium was detected in both respiratory and GI tracts throughout the 8 weeks post-enrollment. The development of therapeutics for Cryptosporidium in children should target the respiratory as well as GI tract.