Publications

BACKGROUND

In sub-Saharan Africa, malnutrition and malaria remain major causes of morbidity and mortality in young children. There are conflicting data as to whether malnutrition is associated with an increased or decreased risk of malaria. In addition, data are limited on the potential interaction between HIV infection and the association between malnutrition and the risk of malaria.

METHODS

A cohort of 100 HIV-unexposed, 203 HIV-exposed (HIV negative children born to HIV-infected mothers) and 48 HIV-infected children aged 6 weeks to 1 year were recruited from an area of high malaria transmission intensity in rural Uganda and followed until the age of 2.5 years. All children were provided with insecticide-treated bed nets at enrolment and daily trimethoprim-sulphamethoxazole prophylaxis (TS) was prescribed for HIV-exposed breastfeeding and HIV-infected children. Monthly routine assessments, including measurement of height and weight, were conducted at the study clinic. Nutritional outcomes including stunting (low height-for-age) and underweight (low weight-for-age), classified as mild (mean z-scores between -1 and -2 during follow-up) and moderate-severe (mean z-scores < -2 during follow-up) were considered. Malaria was diagnosed when a child presented with fever and a positive blood smear. The incidence of malaria was compared using negative binomial regression controlling for potential confounders with measures of association expressed as an incidence rate ratio (IRR).

RESULTS

The overall incidence of malaria was 3.64 cases per person year. Mild stunting (IRR = 1.24, 95% CI 1.06-1.46, p = 0.008) and moderate-severe stunting (IRR = 1.24, 95% CI 1.03-1.48, p = 0.02) were associated with a similarly increased incidence of malaria compared to non-stunted children. Being mildly underweight (IRR = 1.09, 95% CI 0.95-1.25, p = 0.24) and moderate-severe underweight (IRR = 1.12, 95% CI 0.86-1.46, p = 0.39) were not associated with a significant difference in the incidence of malaria compared to children who were not underweight. There were no significant interactions between HIV-infected, HIV-exposed children taking TS and the associations between malnutrition and the incidence of malaria.

CONCLUSIONS

Stunting, indicative of chronic malnutrition, was associated with an increased incidence of malaria among a cohort of HIV-infected and -uninfected young children living in an area of high malaria transmission intensity. However, caution should be made when making causal inferences given the observational study design and inability to disentangle the temporal relationship between malnutrition and the incidence of malaria.

TRIAL REGISTRATION

ClinicalTrials.gov: NCT00527800.

BACKGROUND/AIMS

Although HIV-infected persons are at higher risk for acute kidney injury (AKI) during hospitalization compared with their uninfected counterparts, risk factors for AKI are not well-defined. We aimed to describe the evolving incidence of AKI among HIV-infected individuals and to identify important AKI risk factors.

METHODS

We conducted a prospective cohort study of 56,823 HIV-infected persons in the Department of Veterans Affairs Clinical Case Registry. Outcomes were: AKI (acute in-hospital serum creatinine increase of ≥0.3 mg/dl, or a relative increase by 50% or greater), and dialysis-requiring AKI. We used proportional hazards regressions to identify risk factors.

RESULTS

From its peak in 1995 at 62 per 1,000 person-years, the incidence of AKI declined after the introduction of highly active antiretroviral therapy (HAART) in 1996 to a low point of 25 per 1,000 person-years in 2006. Incidence of dialysis-requiring AKI declined in the early 1990s, but doubled between 2000 and 2006. Using multivariate proportional hazard regression, we identified the following strong risk factors for AKI: chronic kidney disease (eGFR <60 ml/min/1.73 m(2)) (5.38, 95% CI: 5.11-5.67), proteinuria (1.78, 1.70-1.87), low serum albumin (<3.7 mg/dl) (5.24, 4.82-5.71), low body mass index (<18.5 kg/m(2)) (1.69, 1.54-1.86), cardiovascular disease (1.77, 1.66-1.89), low CD4 count (<200 cells/mm(3)) (2.54, 2.33-2.77), and high viral load (≥100,000 copies/ml) (2.51, 2.28-2.75). In addition, there was substantial heterogeneity in the strengths of risk factors for dialysis-requiring AKI before and after the introduction of HAART.

CONCLUSIONS

Although AKI incidence has decreased during the HAART era, it remains common in HIV-infected persons and appears attributable to both kidney- and HIV-related factors.

Because multiple symptoms associated with "sickness behavior" have a negative impact on functional status and quality of life, increased information on the mechanisms that underlie inter-individual variability in this symptom experience is needed. The purposes of this study were to determine: if distinct classes of individuals could be identified based on their experience with pain, fatigue, sleep disturbance, and depression; if these classes differed on demographic and clinical characteristics; and if variations in pro- and anti- inflammatory cytokine genes were associated with latent class membership. Self-report measures of pain, fatigue, sleep disturbance, and depression were completed by 168 oncology outpatients and 85 family caregivers (FCs). Using latent class profile analysis (LCPA), three relatively distinct classes were identified: those who reported low depression and low pain (83%), those who reported high depression and low pain (4.7%), and those who reported high levels of all four symptoms (12.3%). The minor allele of IL4 rs2243248 was associated with membership in the "All high" class along with younger age, being White, being a patient (versus a FC), having a lower functional status score, and having a higher number of comorbid conditions. Findings suggest that LPCA can be used to differentiate distinct phenotypes based on a symptom cluster associated with sickness behavior. Identification of distinct phenotypes provides new evidence for the role of IL4 in the modulation of a sickness behavior symptom cluster in oncology patients and their FCs.

This work presents a novel method for detecting nucleic acid targets using a ligation step along with an isothermal, exponential amplification step. We use an engineered ssDNA with two variable regions on the ends, allowing us to design the probe for optimal reaction kinetics and primer binding. This two-part probe is ligated by T4 DNA Ligase only when both parts bind adjacently to the target. The assay demonstrates that the expected 72-nt RNA product appears only when the synthetic target, T4 ligase, and both probe fragments are present during the ligation step. An extraneous 38-nt RNA product also appears due to linear amplification of unligated probe (P3), but its presence does not cause a false-positive result. In addition, 40 mmol/L KCl in the final amplification mix was found to be optimal. It was also found that increasing P5 in excess of P3 helped with ligation and reduced the extraneous 38-nt RNA product. The assay was also tested with a single nucleotide polymorphism target, changing one base at the ligation site. The assay was able to yield a negative signal despite only a single-base change. Finally, using P3 and P5 with longer binding sites results in increased overall sensitivity of the reaction, showing that increasing ligation efficiency can improve the assay overall. We believe that this method can be used effectively for a number of diagnostic assays.