Diagnosis and management of extrahepatic oesophageal variceal bleed in children in a low resourced setting

Extrahepatic portal vein obstruction (EHPVO) is a major cause of portal hypertension (PH) in children. Portal vein thrombosis (PVT) is the most common cause accounting for up to 75% of cases in developing countries. Upper gastrointestinal bleeding is the most dreaded and commonest presentation of portal hypertension. Successful treatment of paediatric PH, though challenging is performed in resource constraint countries. Cases: Five children presented over three years to a tertiary hospital in Ghana, with massive upper gastrointestinal bleeding. They had anaemia, thrombocytopaenia and four had splenomegaly. Liver function tests, INR, haemoglobin electrophoresis as well as HIV serology, hepatitis B and C screening were all normal. Abdominal doppler ultrasound scan confirmed portal vein thromboses. They were resuscitated and managed with octreotide, propranolol, antibiotics and sclerotherapy or oesophageal variceal banding in the acute setting and long term secondary prophylaxis with propranolol. Subsequently, an algorithm was developed to assist with the management of bleeding from oesophageal varices and the diagnosis of EHPVO. Conclusion: Portal hypertension due to EHPVO is an important cause of upper gastrointestinal (GI) bleeding in children. This can be successfully managed even in a resource constraint setting once the appropriate measures are taken

Time to and Predictors of CD4+ T-Lymphocytes Recovery in HIV-Infected Children Initiating Highly Active Antiretroviral Therapy in Ghana

Background. CD4+ T-lymphocyte monitoring is not routinely available in most resource-limited settings. We investigated predictors of time to CD4+ T-lymphocyte recovery in HIV-infected children on highly active antiretroviral (HAART) at Korle-Bu Teaching Hospital, Ghana. Methods. Time to CD4+ T-lymphocyte recovery was defined as achieving percent CD4+ T-lymphocytes of 25%. We used Cox proportional hazard models for identifying significant predictor variables. Results. Of the 233 children with complete CD4+ T-lymphocyte data, the mean age at HAART initiation was 5.5 (SD = 3.1) years. The median recovery time was 60 weeks (95% CL: 55–65). Evidence at baseline of severe suppression in CD4+ T-lymphocyte count adjusted for age, age at HAART initiation, gender, and having parents alive were statistically significant in predicting time to CD4+ T-lymphocyte recovery. Conclusions. A targeted approach based on predictors of CD4+ T-lymphocyte recovery can be a viable and cost-effective way of monitoring HAART in HIV-infected children in resource-limited settings

Respiratory syncytial virus genotypes circulating in urban Ghana: february to november 2006

Introduction: Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract  infection (ALRI) in young children. RSV strains have been divided into 2 major antigenic groups (A and B), which are further divided into several genotypes, but very little is known about its circulating genotypes in Ghana. This study characterized RSV genotypes detected in children with ALRI in Accra between  February and November 2006. Methods: Nasopharyngeal aspirates (NPA) were obtained from children diagnosed with ALRI between  February and November 2006. The NPA were screened for RSV using a nested multiplex reverse  transcriptase polymerase chain reaction (RT-PCR) method for genotyping RSV. Viral RNA was extracted from the NPA using guanidinium isothiocyanate method and purified with an RNAID commercial kit.  Care-givers gave their consent prior to specimen collection. Administered questionnaires captured  information on patient demographic and clinical history. Results: A total of 53 children were enrolled in the study with a male to female ratio of 3:1. Of the 53 NPA  analyzed, 60.4% (32/53) were positive for RSV. Subsequent genotypic analysis showed that 72% (23/32) of the 60.4% RSV infections were RSV B only and 28% (9/32) were co-infections of both RSV A and B. Children between the ages of 2 - 12 months were the most affected age group per an RSV infection rate of 37.5% (12/32). No significant difference was detected in the recovery rate of ALRI (98.1%) and RSV (96.9%) positive patients from the infection. One patient died resulting in a mortality rate of 3.1%. Bronchopneumonia (20 out of 32 cases) was the major diagnosis on admission. RSV infection was  seasonal dependent, described by 2 peaks in October and April-May.Conclusion: Both RSV A and RSV B genotypes co-circulated during the study period with RSV B  predominating. RSV may possibly be the main pathogen of lower respiratory tract illness during  epidemics in the wet seasons. Genotyping by the multiplex RT-PCR is one of the first attempts at  molecular diagnosis of RSV infection in Ghana.Key words: Respiratory syncytial viruses, lower respiratory tract infections, multiplex RT-PC

Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia

BACKGROUND: Severe anaemia can develop in the aftermath of Plasmodium falciparum malaria because of protracted bone marrow suppression, possibly due to residual subpatent parasites. MATERIALS AND METHODS: Blood was collected from patients with recent malaria and negative malaria microscopy. Detection of the Plasmodium antigens, lactate dehydrogenase (Optimal(®)), aldolase and histidine rich protein 2 (Now malaria(®)) were used to differentiate between patients with (1) no malaria, (2) recent cleared malaria, (3) persistent P. falciparum infection. Red cell distribution width (RDW), plasma levels of soluble transferrin receptor (sTfR) and erythropoietin (EPO) were measured as markers of erythropoiesis. Interleukin (IL) 10 and tumour necrosis factor (TNF)α were used as inflammation markers. RESULTS: EPO was correlated with haemoglobin, irrespective of malaria (R = -0.36, P < 0.001). Persistent P. falciparum infection, but not recent malaria without residual parasites, was associated with bone marrow suppression i.e., low RDW (P < 0.001 vs. P = 0.56) and sTfR (P = 0.02 vs. P = 0.36). TNF-α and IL-10 levels were not associated with bone marrow suppression. CONCLUSION: In the treatment of malaria, complete eradication of parasites may prevent subsequent development of anaemia. Severely anaemic children may benefit from antimalarial treatment if antigen tests are positive, even when no parasites can be demonstrated by microscopy

Retinopathy in severe malaria in Ghanaian children - overlap between fundus changes in cerebral and non-cerebral malaria

<p>Abstract</p> <p>Background</p> <p>In malaria-endemic areas, reliably establishing parasitaemia for diagnosis of malaria can be difficult. A retinopathy with some features unique to severe malaria with a predictive value on prognosis, has been described. Detection of this retinopathy could be a useful diagnostic tool. This study was designed to determine the diagnostic usefulness of retinopathy on ophthalmoscopy in severe malaria syndromes: Cerebral malaria (CM) and non-cerebral severe malaria (non-CM), i.e. malaria with respiratory distress (RD) and malaria with severe anaemia (SA), in Ghanaian children. Secondly, to determine any association between retinopathy and the occurrence of convulsions in patients with CM.</p> <p>Methods and subjects</p> <p>A cross-sectional study of consecutive patients on admission with severe malaria who were assessed for retinal signs, at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, from July to August 2002 was done. All children had dilated-fundus examination by direct and indirect ophthalmoscopy.</p> <p>Results</p> <p>Fifty-eight children aged between six months and nine years were recruited. Twenty six(45%) had CM, 22 with convulsion; 26(45%) had SA and six(10%) had RD.</p> <p>Any retinopathy was seen in: CM 19(73%), SA 14(54%), RD 3(50.0%), CM with convulsion 15(68%) and CM without convulsion 4(100%). Comparison between CM versus non-CM groups showed a significant risk relationship between retinal whitening and CM(OR = 11.0, CI = 2.2- 56.1, p = 0.001). There was no significant association with papilloedema(OR = 0.9, CI = 0.3 - 3.0, p = 0.9), macular whitening(OR = 1.6, CI = 0.5 - 4.8, p = 0.4), macular haemorrhage(OR = 0.28, CI = 0.03 - 2.7 p = 0.2), retinal haemorrhage(OR = 1.9, CI = 0.6 - 5.6, p = 0.3), vessel abnormality(OR = 1.9, CI = 0.6 - 6.1, p = 0.3) and cotton wool spots(OR not calculated, p = 0.08).</p> <p>Tortuous and engorged retinal veins, not previously described as a feature of CM, was the most common vascular abnormality(15/58 = 26%) and was detected even in the absence of papilloedema.</p> <p>Conclusion</p> <p>Retinal whitening, a sign suggestive of retinal ischaemia, was significantly more common in CM than in non-CM syndromes. However, the high prevalence of any retinopathy in the latter suggests that the brain and the retina may be suffering from ischaemia in both CM and non-CM.</p

Respiratory syncytial virus genotypes circulating in urban Ghana: february to

Abstract Introduction: Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infection (ALRI) in young children. RSV strain

Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory distress (RD) are severe forms of <it>Plasmodium falciparum </it>malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute <it>P. falciparum </it>infection.</p> <p>Methods</p> <p>The direct Coombs test (DCT) and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3bαβ) and the regulatory proteins [complement receptor 1 (CD35) and decay accelerating factor (CD55)] in children with discrete clinical forms of <it>P. falciparum </it>malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated.</p> <p>Results</p> <p>Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were positive for C3d alone while 16/131 (12.2%) were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2–6.7, p < 0.001). DCT correlated significantly with RD (β = -304, p = 0.006), but multiple regression analysis revealed that, Hb (β = -0.341, p = 0.012) and coma (β = -0.256, p = 0.034) were stronger predictors of RD than DCT (β = 0.228, p = 0.061). DCT was also not associated with IVH, p = 0.19, while spleen size was inversely correlated with Hb (r = -402, p = 0.001). Flow cytometry showed similar mean fluorescent intensity (MFI) values of CD35, CD55 and C3bαβ levels on the surfaces of RBC in patients and asymptomatic controls (AC). However, binding of C3bαβ correlated significantly with CD35 or CD55 (p < 0.001).</p> <p>Conclusion</p> <p>These results suggest that complement activation contributed to anaemia in acute childhood <it>P. falciparum </it>malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.</p

Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana

Background: Antiretroviral therapy (ART) scale-up in resource-limited countries, with limited capacity for CD4 and HIV viral load monitoring, presents a unique challenge. We determined the effectiveness of first-line ART in a real world pediatric HIV clinic and explored associations between readily obtainable patient data and the trajectories of change in CD4 count and HIV viral load. Methods: We performed a longitudinal study of a cohort of HIV-infected children initiating ART at the Korle-Bu Teaching Hospital Pediatric HIV clinic in Accra, Ghana, aged 0-13 years from 2009-2012. CD4 and viral load testing were done every 4 to 6 months and genotypic resistance testing was performed for children failing therapy. A mixed linear modeling approach, combining fixed and random subject effects, was employed for data analysis. Results: Ninety HIV-infected children aged 0 to 13 years initiating ART were enrolled. The effectiveness of first-line regimen among study participants was 83.3%, based on WHO criteria for virologic failure. Fifteen of the 90 (16.7%) children met the criteria for virologic treatment failure after at least 24 weeks on ART. Sixty-seven percent virologic failures harbored viruses with ≥ 1 drug resistant mutations (DRMs); M184V/K103N was the predominant resistance pathway. Age at initiation of therapy, child’s gender, having a parent as a primary care giver, severity of illness, and type of regimen were associated with treatment outcomes. Conclusions: First-line ART regimens were effective and well tolerated. We identified predictors of the trajectories of change in CD4 and viral load to inform targeted laboratory monitoring of ART among HIV-infected children in resource-limited countries

Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia

BACKGROUND: Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about the activation status of those cells in SMA patients. METHODS: The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR(+) and/or CD69(+) surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined. RESULTS: Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69(+) and HLA-DR(+) T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM (P = .003) and UM (P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower (P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM (P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P = .005) contrasting with TNF levels, which were higher (P = .001). CONCLUSIONS: These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection