HIV-1 Subtype C Vpr Amino Acid Residue 45Y and Specific Conserved Fragments Are Associated with Neurocognitive Impairment and Markers of Viral Load.

There is increasing evidence that HIV-1 viral protein R (Vpr) plays an important role in the pathogenesis of cognitive impairment. We investigated the relationship between HIV-1 subtype C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) in treatment-naive individuals. We used different bioinformatic tools and statistical models to correlate vpr variation and cognitive function. We identified a tyrosine at position 45 (45Y) as a signature for neurocognitive impairment and histidine (45H) as a signature in the non-impaired individuals. The presence of signature 45Y was associated by 3.66 times higher GDS, 525 times higher plasma viral load, 15.84 times higher proviral load, and 60% lower absolute CD4-T cell count compared with those without the signature. Additionally, we identified four conserved Vpr fragment sequences, PEDQGPQREPYNEWTLE (5-21), LGQYIY (42-47), TYGDTW (49-54), and PEDQGPQREPYNEW (5-18), that were associated with higher plasma viral load and proviral load. The implication of these findings is that variation of Vpr leads to neurocognitive impairment in HIV infection and worsens the progression of disease in general by promoting the production of provirus, promoting HIV replication and depletion of CD4+ T cells in the periphery.

HIV-1 subtype C Tat exon-1 amino acid residue 24K is a signature for neurocognitive impairment.

Variation and differential selection pressures on Tat genes have been shown to alter the biological function of the protein, resulting in pathological consequences in a number of organs including the brain. We evaluated the impact of genetic variation and selection pressure on 147 HIV-1 subtype C Tat exon 1 sequences from monocyte-depleted peripheral lymphocytes on clinical diagnosis of neurocognitive impairment. Genetic analyses identified two signature amino acid residues, lysine at codon 24 (24K) with a frequency of 43.4% and arginine at codon 29 (29R) with a frequency of 34.0% in individuals with HIV-associated neurocognitive impairment. The analyses also revealed two signature residues, asparagine, 24 N (31.9%), and histidine, 29H (21.3%), in individuals without neurocognitive impairment. Both codons, 24 and 29, were associated with high entropy but only codon 29 was under positive selection. The presence of signature K24 increased by 2.08 times the risk of neurocognitive impairment, 3.15 times higher proviral load, and 69% lower absolute CD4 T-cell count compared to those without the signature. The results support a linkage between HIV-1 C Tat N24K polymorphism, proviral load, immunosuppression, and neurocognitive impairment. The signature may induce more neurotoxic effects, which contributes to establishment and severity of HIV-associated neurocognitive impairment.

Plasma Cytokine Biomarker Cutoff Values for HIV-Associated Neurocognitive Impairment in Adults.

Diagnosing HIV-associated neurocognitive impairment in most high-burden, but resource-constrained, settings is difficult due to the unavailability of specialist neurologists and neuropsychologists in primary health care centers. New tests that are easy to perform, based on virological and host immune response biomarkers, may be valuable in the diagnosis of HIV-associated neurocognitive disorder. The receiver operator characteristic curve analysis was used to investigate the diagnostic accuracy of threshold/cutoff concentrations for the peripheral lymphocyte proviral load and plasma biomarkers as diagnostic candidates for neurocognitive impairment in 133 HIV-infected individuals, using global deficit scores as the clinical gold standard. Forty-five (33.83%) of the participants had HIV-associated neurocognitive impairment, with 17.29% being mildly impaired and 16.54% moderately impaired. IL-2 had the best performance as a diagnostic tool for neurocognitive impairment with sensitivity of 67% and specificity of 52%, while the lowest performance was IL-6 with 65% sensitivity and 39% specificity. MIP-1α had the highest precision for the cutoff value, as indicated by the narrow 95% confidence interval (CI) (2.23-3.27), followed by IL-2 with 95% CI (3.02-5.12). RANTES had least precision, as shown by the widest 95% CI (135-9,487.61). For clinical markers of HIV diagnosis and monitoring, the lymphocyte proviral load cutoff value of 145 genome copies/million cells had the highest accuracy with 60% sensitivity and 51% specificity. The plasma viral load had an imperfect balance of 46% sensitivity and 78% specificity. The study demonstrated low to medium diagnostic accuracy of plasma cytokine biomarker cutoff values for defining neurocognitive impairment in people living with HIV.

Predictors of mortality and treatment success of multi-drug resistant and Rifampicin resistant tuberculosis in Zimbabwe: a retrospective cohort analysis of patients initiated on treatment during 2010 to 2015.

INTRODUCTION: Zimbabwe is one of the 30 countries globally with a high burden of multidrug-resistant TB or rifampicin-resistant TB. The World Health Organization recommended that patients diagnosed with multidrug-resistant TB be treated with 20-24 month standardized second-line drugs since 2010. However, factors associated with mortality and treatment success have not been systematically evaluated in Zimbabwe. The Objective of the study was to assess factors associated with Mortality and treatment success among multidrug-resistant-TB patients registered and treated under the National Tuberculosis programme in Zimbabwe. METHODS: the study was conducted using secondary data routinely collected from the National tuberculosis (TB) programme. Categorical variables were summarised using frequencies and a generalized linear model with a log-link function and a Poisson distribution was used to assess factors associated with mortality and treatment success. The level of significance was set at P-Value < 0.05. RESULTS: patient antiretroviral therapy (ART) status was a significant associated factor of treatment success or failure (RRR = 3.92, p < 0.001). Patients who were not on ART had a high risk of death by 3.92 times compared to patients who were on ART. In the age groups 45 - 54 years (relative risk ratios (RRR) = 1.41, p = 0.048), the risk of death was increased by 1.41 times compared to other age groups. Patients aged 55 years and above (RRR = 1.55, p = 0.017), had a risk of dying increased by 1.55 times compared to other age groups. Diagnosis time duration of 8 - 30 days (RRR = 0.62, p = 0.022) was found to be protective, a shorter diagnosis time duration between 8 to 30 days reduced the risk of TB deaths by 0.62 times compared to longer periods. Missed TB doses of > 10% (RRR = 2.03, p < 0.001) increased the risk of MDR/RR-TB deaths by 2.03 times compared to missing TB doses of ≤ 10%. CONCLUSION: not being on ART when HIV positive was a major significant predictor of mortality. Improving ART uptake among those ART-naïve and strategies aimed at improving treatment adherence are important in improving treatment success rates.

The role of bacteriological monitoring using culture and drug susceptibility tests (CDST) on treatment outcomes among MDR/RR-TB patients on treatment: a cohort analysis of patients enrolled on treatment 2010-2015 in Zimbabwe.

INTRODUCTION: an estimated 25% of the world population is infected with Mycobacterium tuberculosis. In 2017, new tuberculosis cases were estimated at 10 million, while 1.6 million tuberculosis related deaths were recorded, 25% residing in Africa. Treatment outcomes of multi drug resistant Tuberculosis patients in Zimbabwe has been well documented but the role of bacteriological monitoring on treatment outcomes has not been systematically evaluated. The objective of the study was to determine the role of bacteriological monitoring using culture and drug susceptibility tests on treatment outcomes among patients with multi drug resistant tuberculosis. METHODS: a retrospective, secondary data analysis was conducted using routinely collected data of patients with multi drug resistant TB in Zimbabwe. Frequencies were used to summarize categorical variables and a generalized linear model with a log-link function and a Poisson distribution was used to assess factors associated with unfavourable outcomes. The level of significance was set at P-Value<0.05. RESULTS: about the study collected data from 473 records of patients with an average age of 36.35 years. Forty-nine percent (49%) were male and 51% were female. Results showed that when a patient has baseline culture result missing, has no culture conversion result, regardless of having a follow up culture and drug susceptibility test result, the risk of developing unfavourable outcomes increase by 3.9 times compared to a patient who has received all the three (3) bacteriological monitoring tests. CONCLUSION: results highlights the need for consistent bacteriological monitoring of patients to avert unfavourable treatment outcomes.

Plasma Cytokine Levels As Predictors of Global and Domain-Specific Human Immunodeficiency Virus-Associated Neurocognitive Impairment in Treatment-Naive Individuals.

Central nervous system dysfunction, associated with human immunodeficiency virus (HIV) infection, remains a significant clinical concern, affecting at least 50% of infected people. Imbalances in cytokine expression levels have been linked to HIV-associated neurocognitive disorders. The aim of this study was to evaluate plasma cytokine levels as predictor neurocognitive impairment in HIV infection using a multiplex profiling kit. Stepwise regression model was used to identify cytokine biomarkers of overall and domain-specific cognitive performance. Higher interleukin (IL)-2 (ß = 0.04; P = 0.001) and eotaxin (ß = 0.01; P = 0.017) were predictors of global neurocognitive, whereas higher IL-5 (ß = 0.005; P = 0.007) was negative predictor of global cognitive deficit. IL-2 was a negative predictor of most cognitive domain functions, including recall (ß = 0.24; P = 0.005), recognition (ß = 0.04; P = 0.026), mental control (ß = 0.38; P = 0.005), symbol search (ß = -0.55; P = 0.001), and digital symbol (ß = -0.79; P = 0.019). IL-6 was associated with 3 impaired domains, mental processing (ß = -0.468; P = 0.027), recognition (ß = -0.044; P = 0.012), and learning (ß = 0.02668; P = 0.020) These results show that plasma cytokines/chemokines may serve as markers of neurocognitive impairment in HIV infection.

Impact of Plasma IP-10/CXCL10 and RANTES/CCL5 Levels on Neurocognitive Function in HIV Treatment-Naive Patients.

Immune activation, which is accompanied by the production of proinflammatory cytokines, is a strong predictor of disease progression in HIV infection. Inflammation is critical in neuronal damage linked to HIV-associated neurocognitive disorders. We examined the relationship between plasma cytokine levels and deficits in neurocognitive function. Multiplex profiling by Luminex® technology was used to quantify 27 cytokines/chemokines from 139 plasma samples of people living with HIV (PLWH). The relationship of plasma cytokine markers, clinical parameters, and cognitive impairment, was assessed using Spearman correlations. Partial least squares regression and variable importance in projection scores were used for further evaluation of the association. Forty-nine (35.3%) participants exhibited neurocognitive impairment based on a global deficit score (GDS) of at least 0.5 and 90 (64.7%) were classified as nonimpaired. Twenty-three (16.5%) initiated on combination antiretroviral therapy for 4 weeks before cognitive assessment and 116 (83.5%) were not on treatment. We identified five proinflammatory cytokines that were significant predictors of GDS namely, IP-10 (ß = 0.058; p = .007), RANTES (ß = 0.049; p = .005), IL-2 (ß = 0.047, p = .006), Eotaxin (ß = 0.042, p = .003), and IL-7 (ß = 0.039, p = .003). IP-10 and RANTES were the strongest predictors of GDS. Both cytokines correlated with plasma viral load and lymphocyte proviral load and were inversely correlated with CD4+ T cell counts. IP-10 and RANTES formed a separate cluster with highest proximity. Study findings describe novel associations among IP-10, RANTES, cognitive status, plasma viral load, and cell-associated viral load.

Peripheral blood lymphocyte proviral DNA predicts neurocognitive impairment in clade C HIV.

It is not known if proviral DNA in the periphery corresponds to cognitive status in clade C as it does in clade B and recombinant forms. A cross-sectional study was conducted on participants investigated for HIV-associated neurocognitive impairment in South Africa. HIV-1 proviral DNA was quantified using a PCR assay targeting a highly conserved HIV-1 LTR-gag region. Fifty-four (36.7%) participants were cognitively impaired and 93 (63.3%) were not impaired. Forty-three (79.6%) of the cognitively impaired participants were female and 11 (20.4%) were male. There was no significant age difference between cognitively impaired and unimpaired participants (p = 0.42). HIV-1 DNA in cognitively impaired PLWH was significantly higher than in cognitively normal individuals (p = .016). Considering impaired participants, lymphocyte HIV-1 DNA was significantly higher in males than females (p = 0.02). There was a modest positive correlation between lymphocyte HIV-1 DNA and global deficit scores (GDS) r = 0.176; p = 0.03). The two measures of viral load, lymphocyte HIV-1 DNA copies/million and plasma RNA copies/ml, were positively correlated (r = 0.39; p < .001). After adjusting for other covariates, age, sex, treatment status, and the interactions between impairment and treatment, the multivariate regression showed association between proviral load and neurocognitive impairment; omega effect size was 0.04, p value = 0.010. The burden of HIV-1 peripheral blood lymphocyte proviral DNA corresponds to neurocognitive impairment among individuals infected with clade C disease. Therefore, therapeutic strategies to reduce the HIV-1 proviral DNA reservoir in lymphocytes may improve neurocognitive outcomes in PLWH.

Assessment of quality of obstetric care in Zimbabwe using the standard primipara.

BACKGROUND: To improve maternity services in any country, there is need to monitor the quality of obstetric care. There is usually disparity of obstetric care and outcomes in most countries among women giving birth in different obstetric units. However, comparing the quality of obstetric care is difficult because of heterogeneous population characteristics and the difference in prevalence of complications. The concept of the standard primipara was introduced as a tool to control for these various confounding factors. This concept was used to compare the quality of obstetric care among districts in different geographical locations in Zimbabwe. METHODS: This was a substudy of the Zimbabwe Maternal and Perinatal Mortality Study. In the main study, cluster sampling was done with the provinces as clusters and 11 districts were randomly selected with one from each of the nine provinces and two from the largest province. This database was used to identify the standard primipara defined as; a woman in her first pregnancy without any known complications who has spontaneous onset of labour at term. Obstetric process and outcome indicators of the standard primipara were then used to compare the quality of care between rural and urban, across rural and across urban districts of Zimbabwe. RESULTS: A total of 45,240 births were recruited in the main study and 10,947 women met the definition of standard primipara. The maternal mortality ratio (MMR) and the perinatal mortality rate (PNMR) for the standard primiparae were 92/100000 live births and 15.4/1000 total births respectively. Compared to urban districts, the PNMR was higher in the rural districts (11/1000 total births vs 19/ 1000 total births, p < 0.001). In the urban to urban and rural to rural districts comparison, there were significant differences in most of the process indicators, but not in the PNMR. CONCLUSIONS: The study has shown that the standard primipara can be used as a tool to measure and compare the quality of obstetric care in districts in different geographical areas. There is need to explore further how the quality of obstetric care can be improved in rural districts of Zimbabwe.

Women's dietary diversity scores and childhood anthropometric measurements as indices of nutrition insecurity along the urban-rural continuum in Ouagadougou, Burkina Faso.

BACKGROUND: Malnutrition is still prevalent worldwide, and its severity, which differs between regions and countries, has led to international organisations proposing its inclusion in the global development framework that will succeed the Millennium Development Goals (post-2015 framework). In Sub-Saharan Africa, malnutrition is particularly severe, among women and children under 5 years. The prevalence of malnutrition has been reported worldwide, differing from region to region and country to country. Nevertheless, little is known about how malnutrition differs between multiple locations along an urban-rural continuum. OBJECTIVE: A survey was carried out in and around Ouagadougou, Burkina Faso, between August and September 2014 to map household nutrition insecurity along the urban-rural continuum, using a transect approach to guide the data collection. DESIGN: Transects of 70 km long and 2 km wide directed radially from the city centre outwards were laid, and data were collected from randomly selected households along these transects. Women's dietary diversity scores (WDDSs) were calculated from a sample of 179 women of reproductive age (15-49 years) from randomly selected households. Additionally, anthropometric data (height/length and weight) of 133 children under 5 years of age were collected along the same transects for the computation of anthropometric indices. RESULTS: We found that relative proportions of the nutrition indices such as stunting, wasting and underweight varied across the urban-rural continuum. Rural households (15%) had the highest relative proportion of WDDS compared with urban households (11%) and periurban households (8%). There was a significant association between children under 5 years' nutritional status (wasting, stunting and underweight) and spatial location (p=0.023). The level of agricultural activities is a possible indicator of wasting in children aged 6-59 months (p=0.032). CONCLUSION: Childhood undernutrition certainly has a spatial dimension that is highly influenced by the degree of urbanity, which should be taken into consideration in policy formulation and implementation.

Drying kinetics of syrup of Parinari curatellifolia fruit and cereal based product, zvambwa.

Drying properties of syrup prepared from Parinari curatellifolia fruit and cereal based product, zvambwa prepared from the syrup and finger millet (Eleusine coracana) meal were studied using a convective tray drier at temperatures ranging from 30 to 80 °C and air velocity of 0.72 m/s. Nine mathematical models namely Henderson and Pabis, Lewis, Midilli et al., Modified Page, Page, Two Term, Weibull, Modified Page Equation (II) and Wang and Singh were fitted to data for thin layer drying of the products using non-linear regression analysis. Thin layer drying processes for the syrup and zvambwa were best described by the Modified Page model. Effective moisture diffusivities for drying of syrup were higher than those for drying of zvambwa. The activation energies for drying of syrup and zvambwa were 21.0 ± 2.0 kJ/mol and19.0 ± 2.0 kJ/mol respectively.

Adherence to tuberculosis infection control guidelines by nurses in Lesotho.

BACKGROUND: Lesotho has a high prevalence rate of tuberculosis (TB) that has been exacerbated by high prevalence of HIV. Adherence to the TB infection control guidelines recommended by the World Health Organization is pivotal in TB infection control. OBJECTIVES: We assessed the level of adherence to the TB infection control guidelines by nurses in TB wards and outpatient departments and the factors associated with nonadherence to the guidelines in Lesotho. METHODS: This was an analytical study based on a semistructured questionnaire administered on 55 purposively sampled nurses working in TB wards and outpatient departments at Motebang and Mafeteng Hospitals. Logistic regression analysis was used to determine the variables associated with nonadherence to TB infection control guidelines. RESULTS: Fear of occupational exposure (P = .026), female gender (P = .03), lack of equipment (P = .02), inadequate staff (P = .005), and the keeping of guidelines by certain nurses (P = .02) were significantly associated with nonadherence. Overall, 43.6% of the respondents had poor adherence to the guidelines. Adherence to the guidelines was not influenced significantly by age, TB ward work experience, and qualifications of nursing staff. CONCLUSIONS: There is poor adherence to World Health Organization TB infection control guidelines by nurses in Lesotho. There is need to improve access to equipment, increase accessibility of guidelines, and ensure adequate staff to increase adherence to TB infection control guidelines.

Occurrence of HBV/HIV coinfection by laboratory values in Roma, Lesotho.

OBJECTIVE: This study was an assessment of the coinfection status of patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Lesotho, and this has been rarely reported. METHODS: This was a retrospective study, in a laboratory setting, on HBV/HIV coinfection among 304 HIV-positive patients who were screened for HBsAg in St Joseph's Hospital records between March 2011 and December 2013. Demographic characteristics, HIV status, indications for HBsAg screening, HBsAg results and liver function test results including alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase were reviewed from the patient and laboratory registers. RESULTS: In this study 10.5% of 304 HIV-positive patients had HBV/HIV coinfection. With respect to gender, males had a significantly higher (p=0.048) rate of HBV/HIV coinfection in this study. Increased levels of ALT (p=0.013) and AST (p=0.014) were significantly associated with HBV/HIV coinfection status. CONCLUSION: Gender and liver function tests are important predictors for HBV/HIV coinfection. Screening for HBV coinfection in HIV-positive patients is recommended.

Human parasitic protozoa in drinking water sources in rural Zimbabwe and their link to HIV infection.

OBJECTIVE: We aimed to perform a risk assessment in a rural setting, where drinking water is obtained from both protected and unprotected deep or shallow wells, boreholes and springs. Water is consumed untreated and this poses a risk of acquiring waterborne infections that may cause diarrhea. METHODS: The study included 113 study participants who volunteered in Chiweshe rural community (Musarara village) in Mashonaland Central Province in Zimbabwe. There were 34 (30%) males and 79 (70%) females with ages ranging from 2 to 89 years. HIV counseling was carried out at the communal meeting and testing was done at home visits. Stool and drinking water samples were collected from 104 subjects. Routine laboratory methods were used to examine for parasitic infections. RESULTS: Only 29 (25.7%) of participants were confirmed HIV positive using 2 rapid serology tests; eighty-four (74.3%) were negative. Diarrheic stool samples were observed in 17 (16.3%) participants and of these 5 (29.4%) were HIV seropositive. Several parasites were isolated from stool samples: G. duodenalis 6 (5.7%), E. histolytica/dispar 19 (18.2%), C. parvum, 8 (7.6%) and C. cayetanensis 23 (22.1%). Eleven out of 30 (36.6%) water bodies had protozoan parasites: G. duodenalis 2 (6.6%), E. histolytica 4 (13.3%), C. parvum 1 (3.3%), C. cayetanensis 3 (10%), E. coli 1 (3.3%). CONCLUSION: The water sources were being used without treatment and were shown to pose a risk for acquiring diarrheagenic protozoan parasites.

Cardiovascular effects of Boophone disticha aqueous ethanolic extract on early maternally separated BALB/C mice.

ETHNOPHARMACOLOGICAL RELEVANCE: There are a number of reports from traditional medical practice in Zimbabwe and neighboring countries and few in vitro studies suggesting an effect with extracts of Boophone disticha in some forms of anxiety disorder. AIM OF THE STUDY: In order to validate the use of Boophone disticha in treatment of anxiety, this study was set to determine the effects of the plant extracts on blood pressure (BP) and heart rate (HR) in adult BALB/c mice subjected to repeated early maternal separation (MS) stress. MATERIALS AND METHODS: To test whether early life stress increases anxiety in mice, non-invasive tail cuff method was used to examine the autonomic nervous system activity by assessing cardiovascular reactivity and response to acute mixing stress (AMS) and restraint stress (RS) in adult mice subjected to early postnatal stress as compared to control. AMS-induced cardiovascular response was then evaluated in adult MS mice treated with Boophone disticha as compared to vehicle and diazepam. RESULTS: Comparisons of the BP and HR measurements indicated that MS significantly reduced AMS-induced HR responses in BALB/c mice when compared with control. Boophone disticha treatment significantly reduced AMS-induced BP response in BALB/c MS mice as compared to vehicle and diazepam treatments. CONCLUSIONS: Our findings demonstrate for the first time that postnatal stress can induce short-term changes in the sensitivity of the cardiovascular system to subsequent stress which can be reduced by treatment with a freeze dried aqueous ethanolic extract of Boophone disticha.