Browsing by Author "Kalingonji, Ayam R."
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Item The burden and early neonatal outcome of infants born to HIV positive women in a tertiary centre.(Hubert Kairuki Memorial University, 2015) Kalingonji, Ayam R.Introduction: Tanzania is one of the 22 countries with the highest estimated numbers of pregnant women living with HIV, and as such a focus country for MTCT elimination. HIV prevalence among pregnant women is 6.8%, compared to an overall population prevalence of 5.1%. The neonatal mortality rate was 40.4/1,000 live births in 1999, 32/1,000 live births in 2004/05 and 26/ 1,000 live birth in 2010. Currently i.e. in 2012 Tanzania neonatal mortality is reported to be 21.4/per 1,000 live birth. Up to 50% of all neonatal deaths occur in the first 24 hours of life, with over 75% of them taking place in the first week of life. HIV exposure of the neonates may be associated with higher mortality, this way contributing to high mortality of neonates. Objectives: To determine the early health problems and proportion/burden of HIV Exposed neonates in a tertiary institution, and to determine the knowledge and perception of breast feeding counselling to the mothers, co-morbidity conditions of a mothers that contribute to the early neonatal health problems and to determine the early neonatal outcome of HIV exposed infants. Methods: The study was a six month cross sectional descriptive hospital-based study covering all neonates exposed to IV/AIDS mothers, conducted at the neonatal unit of Muhimbili National Hospital. Results: A total of 384 neonates, males 186(90.7%) and females were 165(92.2%) were studied. Number of HIV exposed neonates were 33(8.5%), males 19(9.3%) and females 14(7.8%). Total number of death were 45 neonates, males 21(46.7%) and 3 females 24(53.3%). Among neonates who died HIV exposed were 6(13.3%) and Non HIV exposed were 39(86.7. %). HIV-positive women who received ARV prophylaxis during pregnancy 6(18.18%) and 27(81.81%) were on ARV therapy. In this study, the HIV positive mothers had 35.2 fold increased risk of PROM when compared to HIV negative mothers (95% CI 3-409, P=0.04 ). The study also showed HIV exposed neonates to have 20.1 increased risk of being unconscious when they were sick(95%CI 3.2-123,P=0.001). The study revealed HIV exposed to stay much longer in the wards, i.e. twice as much as the unexposed neonates (OR 2.3, 95% CI 1.1-4.8,P=0.025). Six (66.7%) of the HIV unexposed neonates were found to have Anaemia with COR of 5.7( 95% CI 1.3-24.1, P=0.007)which isstatistically significant. However, when adjusted to potential confounders, it was found to be insignificant. All mothers received breast feeding counselling except one HIV positive mother who died immediately after delivery. Most mothers following the breastfeeding counselling opted for exclusive breast feeding. DISCUSSION /CONCLUSION: This study shows that, the prevalence of HIV exposed neonates is higher than the community prevalence, based on the feeding counselling done as per PMTCT national guideline. HIV infected mothers were found to be at higher risk of having premature rupture of membrane compared to non HIV infected mothers while HIV exposed neonates were found to have higher risk of becoming unconscious when sick as compared to the unexposed neonates. Appropriate infections control measures during pregnancy should be given more priority in order to minimize early neonatal morbidity and mortality in HIV exposed infants. The program should be strengthened and expanded to cover the entire country for the comprehensive management of HIV exposed neonates.Item Decreased Microvascular Function in Tanzanian Children With Severe and Uncomplicated Falciparum Malaria(Open Forum Infectious Diseases, 2017) Kalabamu, Florence S.; Kalingonji, Ayam R.; Mwaikambo, Esther D.Microvascular function and oxygen consumption affect oxygen homeostasis but have not been assessed in African children with malaria. Microvascular function in Tanzanian children with severe malaria (SM) or uncomplicated malaria were 39% and 72%, respectively, of controls (P < .001). Uncomplicated malaria (P = .04), not SM (P = .06), children had increased oxygen consumption compared with controls. A major pathogenic mechanism in severe falciparum malaria is microcirculatory obstruction due to parasite sequestration [1]. However, several studies suggest that sequestration alone may not impair microcirculatory flow in malaria [1–3]. The normal microvasculature matches oxygen delivery and demand, with a major mediator being nitric oxide (NO) [2, 4]. In malaria, NO pathway dysregulation impairs host NO production and bioavailability [5–8]. In Indonesian children, vascular NO and microvascular function was decreased in severe and uncomplicated falciparum malaria [3]. Oxygen demand may exacerbate tissue hypoxia and was increased in Indonesian adults and children with malaria [2, 3]. However, microvascular function and oxygen demand have not been assessed in African children, the group with the highest burden of malaria. We assessed skeletal muscle microvascular function and oxygen consumption in Tanzanian children with severe malaria (SM) or uncomplicated malaria (UM) and compared these to controls.Item Evidence of Degradation of Endothelial Glycocalyx in African Children with Falciparum Malaria(The FASEB Journal, 2020-04-19) Mwaikambo, Esther D.; Kalingonji, Ayam R.; Kalabamu, Florence S.Abstract The microvasculature and endothelium play a pivotal role in pathophysiology of malaria. The endothelial glycocalyx (eGC) is a layer on the luminal side of vascular endothelial cells with involvement in homeostatic functions including regulation of vascular permeability, cellular adhesion and blood flow‐mediated nitric oxide formation. Breakdown products of eGC degradation include glycosaminoglycans (GAG) and syndecan‐1, a core protein. The objective of this study was to evaluate a possible role of eGC breakdown in the pathogenesis of malaria. We prospectively evaluated measures of endothelial glycocalyx integrity in children with severe and moderately severe malaria and healthy controls, and determined the relationship between glycocalyx integrity and markers of malaria severity, microvascular reactivity, and endothelial activation. At the Hubert Kairuki Medical Center in Dar es Salaam, Tanzania we studied 146 subjects, aged 2–11 years, including 60 healthy controls (HC), 49 patients with moderately severe malaria (MSM) and 37 patients meeting WHO criteria for severe malaria (SM). Ethics committee approvals were obtained prior to study initiation. We assessed eGC integrity biochemically by measuring plasma syndecan‐1 (ELISA) and total urinary glycosaminoglycan (GAG) breakdown products (dimethylmethylene blue assay). Angiopoietin‐2 has been reported to cause breakdown of eGC and was measured by ELISA. Quantitative measures of eGC were assessed using non‐invasive, side‐stream dark field (SDF) microscopy of the pinna and axilla. Levels of urinary GAG were increased in malaria patients compared with HC (mean±SEM 4.3±0.4 g/mol creatinine); MSM (12.4±1.0); SM (13.4±1.0); p<0.0001. Plasma levels of angiopoietin‐2 and syndecan‐1 were also elevated in MSM and SM compared with HC (p<0.0001), and significantly correlated with each other. For HC compared with MSM, imaging results showed eGC degradation [an increase in the perfused boundary region (mean±SEM 1.55±0.04 microns vs.1.68±0.05; p<0.05)], increased microvascular density (549± 34 μm/mm2 vs. 649 ±38; p<0.05)], and a decrease in the extent of RBC filling (79.1± 0.98% vs. 74.9±1.02%; p<0.01). In conclusion, these results provide evidence for degradation of the eGC that could contribute to pathogenesis of vascular dysfunction in malaria. Decreased nitric oxide formation, endothelial activation and increased adhesion of infected RBC are potential consequences of the eGC degradation and vascular dysfunction. Administration of an agent that prevents or repairs eGC degradation may be helpful as adjunctive therapy for malaria. Support or Funding Information National Institutes of Health (R01 HL130783)Item Kinetic and Cross-Sectional Studies on the Genesis of Hypoargininemia in Severe Pediatric Plasmodium falciparum Malaria(Infection and immunity, 2019) Kalabamu, Florence S.; Kalingonji, Ayam R.; Mwaikambo, Esther D.The low bioavailability of nitric oxide (NO) and its precursor, arginine, contributes to the microvascular pathophysiology of severe falciparum malaria. To better characterize the mechanisms underlying hypoargininemia in severe malaria, we measured the plasma concentrations of amino acids involved in de novo arginine synthesis in children with uncomplicated falciparum malaria (UM; n = 61), children with cerebral falciparum malaria (CM; n = 45), and healthy children (HC; n = 109). We also administered primed infusions of l-arginine uniformly labeled with 13C6 and 15N4 to 8 children with severe falciparum malaria (SM; age range, 4 to 9 years) and 7 healthy children (HC; age range, 4 to 8 years) to measure the metabolic flux of arginine, hypothesizing that arginine flux is increased in SM. Using two different tandem mass spectrometric methods, we measured the isotopic enrichment of arginine in plasma obtained at 0, 60, 90, 120, 150, and 180 min during the infusion. The plasma concentrations of glutamine, glutamate, proline, ornithine, citrulline, and arginine were significantly lower in UM and CM than in HC (P ≤ 0.04 for all pairwise comparisons). Of these, glutamine concentrations were the most markedly decreased: median, 457 μM (interquartile range [IQR], 400 to 508 μM) in HC, 300 μM (IQR, 256 to 365 μM) in UM, and 257 μM (IQR, 195 to 320 μM) in CM. Arginine flux during steady state was not significantly different in SM than in HC by the respective mass spectrometric methods: 93.2 μmol/h/kg of body weight (IQR, 84.4 to 129.3 μmol/h/kg) versus 88.0 μmol/h/kg (IQR, 73.0 to 102.2 μmol/h/kg) (P = 0.247) by the two mass spectrometric methods in SM and 93.7 μmol/h/kg (IQR, 79.1 to 117.8 μmol/h/kg) versus 81.0 μmol/h/kg (IQR, 75.9 to 88.6 μmol/h/kg) (P = 0.165) by the two mass spectrometric methods in HC. A limited supply of amino acid precursors for arginine synthesis likely contributes to the hypoargininemia and NO insufficiency in falciparum malaria in children.Item Monocyte polarization in children with falciparum malaria: relationship to nitric oxide insufficiency and disease severity(Scientific reports, 2016) Kalabamu, Florence S.; Kalingonji, Ayam R.; Mwaikambo, Esther D.Abstract We earlier established that nitric oxide (NO) is protective against severe malaria and that arginine and NO levels are reduced in malaria patients. We now show that an M2-like blood monocyte phenotype is significantly associated with hypoargininemia, NO insufficiency, and disease severity in Tanzanian children with falciparum malaria. Compared to control children (n = 106), children with moderately severe (n = 77) and severe falciparum malaria (n = 129) had significantly higher mononuclear cell arginase 1 mRNA, protein, and enzyme activity; lower NOS2 mRNA; lower plasma arginine; and higher plasma IL-10, IL-13, and IL-4. In addition, monocyte CD206 and CD163 and plasma soluble CD163 were elevated. Multivariate logistic regression analysis revealed a significant correlation of risk of severe malaria with both plasma IL-10 and soluble CD163 levels. Monocyte M2 skewing likely contributes to NO bio insufficiency in falciparum malaria in children. Treatments that reverse the M2 polarization may have potential as adjunctive treatment for malaria.