NUTRITIONAL STATUS AND RISK FACTORS ASSOCIATED WITH SEVERE ACUTE MALNUTRITION AMONG HIV-INFECTED CHILDREN ENROLLED IN THE PAEDIATRIC HIV CLINIC, KORLE BU TEACHING HOSPITAL, ACCRA, GHANA.

Background: Malnutrition remains a common problem among Human Immunodeficiency Virus (HIV)-infected children even while receiving antiretroviral therapy leading to disease progression and reduced survival. Aim: To assess the nutritional status and risk factors associated with severe acute malnutrition (SAM) among HIV-infected children aged 1 to 15 years attending the Paediatric HIV Clinic at Korle Bu Teaching Hospital (KBTH), Accra. Methods: A cross-sectional study was conducted from October 2018 to January 2019 at the Clinic during which 150 participants aged 15 to 179 months were systematically recruited. A structured interview, physical examination, including anthropometric measurements, data extraction from hospital records, and laboratory investigations were conducted. Weight-for- age, weight-for-length/height, length/height-for-age, body mass index Z scores, and mid-upper arm circumference-for-age were obtained. Logistic regression models were used to assess the crude and adjusted odds of the nutritional status on the socio-demographic, clinical, and HIV-related characteristics of the participants at alpha= 0.05. Results: The prevalence of SAM, moderate acute malnutrition and normal nutrition were 4.0% (6/149), 13.4% (20/149) and 80.5% (120/149), respectively, whilst 1.3% (2/149) were overweight and 0.7% (1/149) obese. Stunting and severe stunting were 18.1% (27/149) and 6.7% (10/149) prevalent, respectively. SAM was significantly associated with oral thrush among participants in the adjusted model. The prevalence of mild-, moderate- and severe-anaemia were 23.7% (33/139), 38.8% (54/139) and 1.4% (2/139), respectively. Conclusion: Malnutrition is prevalent among HIV-infected children on antiretroviral therapy at KBTH. SAM is associated with oral thrush.

Performance of a Histidine Rich Protein-2 Based (First Response) and a p-Lactate Dehydrogenase-based (Optimal) Rapid Diagnostic Test for Diagnosis of Malaria in Patients With Pediatric Sickle Cell Disease.

BACKGROUND: Rapid diagnostic tests (RDTs) have been extensively evaluated and play an important role in malaria diagnosis. However, the accuracy of RDTs for malaria diagnosis in patients with sickle cell disease (SCD) is unknown. METHODS: We compared the performance of a histidine rich protein 2 (HRP-2)-based RDT (First Response) and a lactate dehydrogenase (LDH)-based RDT (Optimal) with routine microscopy as reference standard in 445 children with SCD and an acute febrile illness in Accra, Ghana. RESULTS: The overall sensitivity, specificity, and positive and negative predictive values of the HRP-2-based RDTs were 100%, 95.7%, 73.8%, and 100%, respectively. Comparable values for the LDH-based RDTs were 91.7%, 99.5%, 95.7%, and 99.0%, respectively. A total of 423 results were true in both tests, 1 result was false in both tests, 16 results were false in the HRP-2 test only, and 5 were false in the LDH test only (McNemar test, P = .03). At follow-up, 73.7% (28/38), 52.6% (20/38), 48.6% (17/35), and 13.2% (5/38) of study participants were HRP-2 positive on days 14, 28, 35, and 42, respectively, compared with 0%, 2.6% (1/38), 2.9% (1/35), and 2.6% (1/38) for LDH. CONCLUSION: The HRP2-based RDT fulfilled World Health Organization criteria for malaria diagnosis in patients with SCD and may provide diagnostic evidence for treatment to begin in cases in which treatment would otherwise have begun presumptively based on symptoms, whereas LDH-based RDTs may be more suitable as a confirmatory test in low-parasitemic subgroups, such as patients with SCD.

Implementing newborn screening for sickle cell disease in Korle Bu Teaching Hospital, Accra: Results and lessons learned.

BACKGROUND: Early diagnosis of sickle cell disease (SCD) through newborn screening (NBS) is a cost-effective intervention, which reduces morbidity and mortality. In sub-Saharan Africa (SSA) where disease burden is greatest, there are no universal NBS programs and few institutions have the capacity to conduct NBS. We determined the feasibility and challenges of implementing NBS for SCD in Ghana's largest public hospital. PROCEDURE: The SCD NBS program at Korle Bu Teaching Hospital (KBTH) is a multiyear partnership between the hospital and the SickKids Center for Global Child Health, Toronto, being implemented in phases. The 13-month demonstration phase (June 2017-July 2018) and phase one (November 2018-December 2019) focused on staff training and the feasibility of universal screening of babies born in KBTH. RESULTS: During the demonstration phase, 115 public health nurses and midwives acquired competency in heel stick for dried blood spot sampling. Out of 9990 newborns, 4427 babies (44.3%) were screened, of which 79 (1.8%) were identified with presumptive SCD (P-SCD). Major challenges identified included inadequate nursing staff to perform screening, shortage of screening supplies, and delays in receiving screening results. Strategies to overcome some of the challenges were incorporated into phase one, resulting in increased screening coverage to 83.7%. CONCLUSIONS: Implementing NBS for SCD in KBTH presented challenges with implications on achieving and sustaining universal NBS in KBTH and other settings in SSA. Specific steps addressing these challenges comprehensively will help build on the modest initial gains, moving closer toward a sustainable national NBS program.

HIV virological non-suppression and its associated factors in children on antiretroviral therapy at a major treatment centre in Southern Ghana: a cross-sectional study.

BACKGROUND: Children living with human immunodeficiency virus (HIV) infection require lifelong effective antiretroviral therapy (ART). The goal of ART in HIV-infected persons is sustained viral suppression. There is limited information on virological non-suppression or failure and its associated factors in children in resource limited countries, particularly Ghana. METHODS: A cross-sectional study of 250 children aged 8 months to 15 years who had been on ART for at least 6 months attending the Paediatric HIV clinic at Korle Bu Teaching hospital in Ghana was performed. Socio-demographic, clinical, laboratory and ART Adherence related data were collected using questionnaires as well as medical records review. Blood samples were obtained for viral load and CD4+ count determination. Viral load levels > 1000 copies/ml on ART was considered virological non-suppression. Logistic regression was used to identify factors associated with virological non-suppression. RESULTS: The mean (±SD) age of the study participants was 11.4 ± 2.4 years and the proportion of males was 53.2%. Of the 250 study participants, 96 (38.4%) had virological non-suppression. After adjustment for significant variables, the factors associated with non-suppressed viral load were female gender (AOR 2.51 [95% CI 1.04-6.07], p = 0.041), having a previous history of treatment of tuberculosis (AOR 4.95 [95% CI 1.58-15.5], p = 0.006), severe CD4 immune suppression status at study recruitment (AOR 24.93 [95% CI 4.92-126.31], p < 0.001) and being on a nevirapine (NVP) based regimen (AOR 7.93 [95% CI 1.58-1.15], p = 0.005). CONCLUSION: The prevelance of virological non-suppression was high. Virological non-suppression was associated with a previous history of TB treatment, female gender, severe CD4 immune suppression status at study recruitment and being on a NVP based regimen. Early initiation of ART and phasing out NVP-based regimen might improve viral load suppression in children. In addition, children with a history of TB may need focused measures to maximize virological suppression.

Treatment outcomes among children treated for uncomplicated severe acute malnutrition: a retrospective study in Accra, Ghana.

OBJECTIVES: The objectives of the study were to describe outcomes of children with uncomplicated severe acute malnutrition (SAM) attending community-based management of acute malnutrition (CMAM) treatment centres in Accra Metropolitan Area (AMA) and explore factors associated with non-adherence to clinic visits and defaulting from the treatment programme. DESIGN: A retrospective cohort study analysing routinely collected data on children with uncomplicated SAM enrolled into CMAM in 2017 was conducted. SETTING: Study was conducted at seven sites comprising Princess Marie Louise Children's Hospital, three sub-metropolitan health facilities and three community centres, located in five sub-metropolitan areas in AMA. PARTICIPANTS: Children with uncomplicated SAM aged 6-59 months, enrolled from community-level facilities (pure uncomplicated SAM, PUSAM) or transferred after completing inpatient care (post-stabilisation uncomplicated SAM, PSSAM), participated in the study. RESULTS: Out of 174 cases studied (105 PUSAM, sixty-nine PSSAM), 56·3 % defaulted, 34·5 % recovered and 8·6 % were not cured by 16 weeks. No deaths were recorded. Mid-upper arm circumference (MUAC) increased by 2·2 (95 % CI 1·8, 2·5) mm/week with full compliance and 0·9 (95 % CI 0·6, 1·2) mm/week with more than two missed visits. In breast-feeding children, MUAC increased at a slower rate than in other children by 1·3 (95 % CI 1·0, 1·5) mm/week. Independent predictors of subsequent missed visits were diarrhoea and fever, while children with MUAC < 110 mm on enrolment were at increased risk of defaulting. CONCLUSION: A high default rate and a long time to recovery are challenges for CMAM in AMA. Efforts must be made to improve adherence to treatment to improve outcomes.

Neonatal near-misses in Ghana: a prospective, observational, multi-center study.

BACKGROUND: For every newborn who dies within the first month, as many as eight more suffer life-threatening complications but survive (termed 'neonatal near-misses' (NNM)). However, there is no universally agreed-upon definition or assessment tool for NNM. This study sought to describe the development of the Neonatal Near-Miss Assessment Tool (NNMAT) for low-resource settings, as well as findings when implemented in Ghana. METHODS: This prospective, observational study was conducted at two tertiary care hospitals in southern Ghana from April - July 2015. Newborns with evidence of complications and those admitted to the NICUs were screened for inclusion using the NNMAT. Incidence of suspected NNM at enrollment and confirmed near-miss (surviving to 28 days) was determined and compared against institutional neonatal mortality rates. Suspected NNM cases were compared with newborns not classified as a suspected near-miss, and all were followed to 28 days to determine odds of survival. Confirmed near-misses were those identified as suspected near-misses at enrollment who survived to 28 days. The main outcome measures were incidence of NNM, NNM:mortality ratio, and factors associated with NNM classification. RESULTS: Out of 394 newborns with complications, 341 (86.5%) were initially classified as suspected near-misses at enrollment using the NNMAT, with 53 (13.4%) being classified as a non-near-miss. At 28-day follow-up, 68 (17%) had died, 52 (13%) were classified as a non-near-miss, and 274 were considered confirmed near-misses. Those newborns with complications who were classified as suspected near-misses using the NNMAT at enrollment had 12 times the odds of dying before 28 days than those classified as non-near-misses. While most confirmed near-misses qualified as NNM via intervention-based criteria, nearly two-thirds qualified based on two or more of the four NNMAT categories. When disaggregated, the most predictive elements of the NNMAT were gestational age < 33 weeks, neurologic dysfunction, respiratory dysfunction, and hemoglobin < 10 gd/dl. The ratio of near-misses to deaths was 0.55: 1, yet this varied across the study sites. CONCLUSIONS: This research suggests that the NNMAT is an effective tool for assessing neonatal near-misses in low-resource settings. We believe this approach has significant systems-level, continuous quality improvement, clinical and policy-level implications.

Population Pharmacokinetic Estimates Suggest Elevated Clearance and Distribution Volume of Desethylamodiaquine in Pediatric Patients with Sickle Cell Disease Treated with Artesunate-Amodiaquine.

BACKGROUND: There is limited information on the safety or efficacy of currently recommended antimalarial drugs in patients with sickle cell disease (SCD), a population predisposed to worse outcomes if affected by acute malaria. Artesunate-amodiaquine (ASAQ) is the first-line treatment for uncomplicated malaria (UM) in many malaria-endemic countries and is also used for treatment of UM in SCD patients. There is, however, no information to date, on the pharmacokinetics (PK) of amodiaquine or artesunate or the metabolites of these drugs in SCD patients. OBJECTIVES: This study sought to determine the PK of desethylamodiaquine (DEAQ), the main active metabolite of amodiaquine, among paediatric SCD patients with UM treated with artesunate-amodiaquine (ASAQ). METHODS: Plasma concentration-time data (median DEAQ levels) of SCD children (n = 16) was initially compared with those of concurrently recruited non-SCD paediatric patients with acute UM (n = 13). A population PK modelling approach was then used to analyze plasma DEAQ concentrations obtained between 64 and 169 hours after oral administration of ASAQ in paediatric SCD patients with acute UM (n = 16). To improve PK modeling, DEAQ concentration-time data (n = 21) from SCD was merged with DEAQ concentration-time data (n = 169) of a historical paediatric population treated with ASAQ (n = 103) from the same study setting. RESULTS: The median DEAQ concentrations on days 3 and 7 were comparatively lower in the SCD patients compared to the non-SCD patients. A two-compartment model best described the plasma DEAQ concentration-time data of the merged data (current SCD data and historical data). The estimated population clearance of DEAQ was higher in the SCD patients (67 L/h, 21% relative standard error (RSE) compared with the non-SCD population (15.5 L/h, 32% RSE). The central volume of distribution was larger in the SCD patients compared with the non-SCD patients (4400 L, 43% RSE vs. 368 L, 34% RSE). CONCLUSIONS: The data shows a tendency towards lower DEAQ concentration in SCD patients and the exploratory population PK estimates suggest altered DEAQ disposition in SCD patients with acute UM. These findings, which if confirmed, may reflect pathophysiological changes associated with SCD on DEAQ disposition, have implications for therapeutic response to amodiaquine in SCD patients. The limited number of recruited SCD patients and sparse sampling approach however, limits extrapolation of the data, and calls for further studies in a larger population.

Polymorphisms in the Haem Oxygenase-1 promoter are not associated with severity of Plasmodium falciparum malaria in Ghanaian children.

BACKGROUND: Haem oxygenase-1 (HO-1) catabolizes haem and has both cytotoxic and cytoprotective effects. Polymorphisms in the promoter of the Haem oxygenase-1 (HMOX1) gene encoding HO-1 have been associated with several diseases including severe malaria. The objective of this study was to determine the allele and genotype frequencies of two single nucleotide polymorphisms; A(-413)T and G(-1135)A, and a (GT)n repeat length polymorphism in the HMOX1 promoter in paediatric malaria patients and controls to determine possible associations with malaria disease severity. METHODS: Study participants were Ghanaian children (n=296) admitted to the emergency room at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, Ghana during the malaria season from June to August in 1995, 1996 and 1997, classified as having uncomplicated malaria (n=101) or severe malaria (n=195; defined as severe anaemia (n=63) or cerebral malaria (n=132)). Furthermore, 287 individuals without a detectable Plasmodium infection or asymptomatic carriers of the parasite were enrolled as controls. Blood samples from participants were extracted for DNA and allele and genotype frequencies were determined with allele-specific PCR, restriction fragment length analysis and microsatellite analysis. RESULTS: The number of (GT)n repeats in the study participants varied between 21 and 46 with the majority of alleles having lengths of 26 (8.1%), 29/30 (13.2/17.9%) and 39/40 (8.0/13.8%) repeats, and was categorized into short, medium and long repeats. The (-413)T allele was very common (69.8%), while the (-1135)A allele was present in only 17.4% of the Ghanaian population. The G(-1135)A locus was excluded from further analysis after failing the Hardy-Weinberg equilibrium test. No significant differences in allele or genotype distribution of the A(-413)T and (GT)n repeat polymorphisms were found between the controls and the malaria patients, or between the disease groups, for any of the analysed polymorphisms and no associations with malaria severity were found. CONCLUSION: These results contribute to the understanding of the role of HMOX1/HO-1. This current study did not find any evidence of association between HMOX1 promoter polymorphisms and malaria susceptibility or severe malaria and hence contradicts previous findings. Further studies are needed to fully elucidate the relationship between HMOX1 polymorphisms and malarial disease.

A randomized trial of artesunate-amodiaquine versus artemether-lumefantrine in Ghanaian paediatric sickle cell and non-sickle cell disease patients with acute uncomplicated malaria.

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder common in malaria endemic areas. In endemic areas, malaria is a major cause of morbidity and mortality among SCD patients. This suggests the need for prompt initiation of efficacious anti-malarial therapy in SCD patients with acute malaria. However, there is no information to date, on the efficacy or safety of artemisinin combination therapy when used for malaria treatment in SCD patients. METHODS: Children with SCD and acute uncomplicated malaria (n=60) were randomized to treatment with artesunate-amodiaquine (AA), or artemether-lumefantrine (AL). A comparison group of non-SCD children (HbAA genotype; n=59) with uncomplicated malaria were also randomized to treatment with AA or AL. Recruited children were followed up and selected investigations were done on days 1, 2, 3, 7, 14, 28, 35, and 42. Selected clinical and laboratory parameters of the SCD patients were also compared with a group of malaria-negative SCD children (n=82) in steady state. RESULTS: The parasite densities on admission were significantly lower in the SCD group, compared with the non-SCD group (p=0.0006). The parasite reduction ratio (PRR) was lower, clearance was slower (p<0.0001), and time for initial parasitaemia to decline by 50 and 90% were longer for the SCD group. Adequate clinical and parasitological response (ACPR) on day 28 was 98.3% (58/59) in the SCD group and 100% (57/57) in the non-SCD group. Corresponding ACPR rates on day 42 were 96.5% (55/57) in the SCD group and 96.4% (53/55) in the non-SCD group. The fractional changes in haemoglobin, platelets and white blood cell counts between baseline (day 0) and endpoint (day 42) were 16.9, 40.6 and 92.3%, respectively, for the SCD group, and, 12.3, 48.8 and 7.5%, respectively, for the non-SCD group. There were no differences in these indices between AA- and AL-treated subjects. CONCLUSIONS: The parasite clearance of SCD children with uncomplicated malaria was slower compared with non-SCD children. AA and AL showed similar clinical and parasitological effects in the SCD and non-SCD groups. The alterations in WBC and platelet counts may have implications for SCD severity. TRIAL REGISTRATION: Current controlled trials ISRCTN96891086.

Diagnostic accuracy of Xpert MTB/RIF Ultra for childhood tuberculosis in West Africa - a multicenter pragmatic study.

OBJECTIVE: To evaluate the performance of Xpert Mycobacterium Tuberculosis/rifampicin (MTB/RIF) Ultra (Ultra) for diagnosis of childhood tuberculosis (TB) within public health systems. METHODS: In this cross-sectional study, children aged <15 years with presumptive pulmonary TB were consecutively recruited and evaluated for TB at tertiary-level hospitals in Benin, Mali, and Ghana. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against culture. We also estimated its diagnostic yield against a composite microbiological reference standard (cMRS) of positive culture or Ultra. RESULTS: Overall, 193 children were included in the analyses with a median (interquartile range) age of 4.0 (1.1-9.2) years, 88 (45.6%) were female, and 36 (18.7%) were HIV-positive. Thirty-one (16.1%) children had confirmed TB, 39 (20.2%) had unconfirmed TB, and 123 (63.7%) had unlikely TB. The pooled sensitivity and specificity of Ultra verified by culture were 55.0% (95% confidence interval [CI]: 28.0-79.0%) and 95.0% (95% CI: 88.0-98.0%), respectively. Against the cMRS, the diagnostic yield of Ultra and culture were 67.7% (95% CI: 48.6-83.3%) and 70.9% (95% CI: 51.9-85.8%), respectively. CONCLUSION: Ultra has suboptimal sensitivity in children with TB that were investigated under routine conditions in tertiary-level hospitals in three West African countries.

Human genetic polymorphisms in the Knops blood group are not associated with a protective advantage against Plasmodium falciparum malaria in Southern Ghana.

BACKGROUND: The complex interactions between the human host and the Plasmodium falciparum parasite and the factors influencing severity of disease are still not fully understood. Human single nucleotide polymorphisms SNPs associated with Knops blood group system; carried by complement receptor 1 may be associated with the pathology of P. falciparum malaria, and susceptibility to disease. METHODS: The objective of this study was to determine the genotype and haplotype frequencies of the SNPs defining the Knops blood group antigens; Kna/b, McCoya/b, Swain-Langley1/2 and KCAM+/- in Ghanaian patients with malaria and determine possible associations between these polymorphisms and the severity of the disease. Study participants were patients (n = 267) admitted to the emergency room at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, Ghana during the malaria season from June to August in 1995, 1996 and 1997, classified as uncomplicated malaria (n = 89), severe anaemia (n = 57) and cerebral malaria (n = 121) and controls who did not have a detectable Plasmodium infection or were symptomless carriers of the parasite (n = 275). The frequencies were determined using a post-PCR ligation detection reaction-fluorescent microsphere assay, developed to detect the SNPs defining the antigens. Chi-square/Fisher's exact test and logistic regression models were used to analyse the data. RESULTS: As expected, high frequencies of the alleles Kna, McCb, Sl2 and KCAM- were found in the Ghanaian population. Apart from small significant differences between the groups at the Sl locus, no significant allelic or genotypic differences were found between the controls and the disease groups or between the disease groups. The polymorphisms define eight different haplotypes H1(2.4%), H2(9.4%), H3(59.8%), H4(0%), H5(25.2%), H6(0.33%), H7(2.8%) and H8(0%). Investigating these haplotypes, no significant differences between any of the groups were found. CONCLUSION: The results confirm earlier findings of high frequencies of certain CR1 alleles in Africa; and shed more light on earlier conflicting findings; the alleles McCb, Sl2, Knb and KCAM- or combined haplotypes do not seem to confer any protective advantage against malaria infection or resulting disease severity. Based on these findings, in a very well-characterized population, malaria does not seem to be the selective force on these alleles.

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.

Cardiovascular physical examination as a screening tool for congenital heart disease in newborns at a teaching hospital in Ghana.

Objectives: To determine the usefulness of cardiovascular physical examination (CPE) as a screening tool in a low-resource setting for detecting congenital heart disease (CHD) in newborns delivered at the Maternity Unit of Korle Bu Teaching Hospital (KBTH), Accra, Ghana. Design: A hospital-based cross-sectional study with a comparison group component. Setting: Maternity Unit of the KBTH, Accra, Ghana. Participants: Over eight months, newborns aged 1-14 days delivered at ≥ 34 weeks' gestation at the Maternity Unit, KBTH, were recruited into the study. Intervention: Each newborn was examined using a set of CPE parameters for the presence of congenital heart disease. Those with suggestive features of CHD had a confirmatory echocardiogram test. Main Outcome Measure: Abnormal CPE features and their corresponding echocardiogram findings. Results: A total of 1607 were screened, with 52 newborns showing signs of CHD on CPE, of which 20 newborns were proven on echocardiogram to have congenital heart disease. Abnormal CPE parameter that was associated with CHD was murmur (P=0.001), dysmorphism (p=0.01), newborns with chest recessions (p=0.01) and lethargy (p=0.02). CPE's sensitivity, specificity, and positive and negative predictive values were 95%, 60.7%, 36.5% and 98,1%, respectively. The most common acyanotic CHD found was isolated atrial septal defect (ASD), followed by patent ductus arteriosus (PDA). The only cyanotic CHD found was a case of tricuspid atresia. Conclusion: Cardiovascular physical examination at birth is an effective and inexpensive screening tool for detecting CHD in newborns, which can easily be utilised in low-resource settings. Funding: None declared.

Electrocardiographic study in Ghanaian children with uncomplicated malaria, treated with artesunate-amodiaquine or artemether-lumefantrine.

BACKGROUND: Several anti-malarial drugs are associated with adverse cardiovascular effects. These effects may be exacerbated when different anti-malarials are used in combination. There has been no report yet on the potential cardiac effects of the combination artesunate-amodiaquine. METHODS: Electrocardiographic (ECG) intervals in Ghanaian children with uncomplicated malaria treated with artesunate-amodiaquine (n=47), were compared with that of children treated with artemether-lumefantrine (n=30). The ECG measurements were repeated one, two, three, seven and 28 days after treatment. The ECG intervals of artesunate-amodiaquine treated subjects were correlated with plasma concentrations of desethylamodiaquine (DEAQ), the main metabolite of amodiaquine. RESULTS: The mean ECG intervals were similar in both groups before treatment. After treatment (day 3), ECG intervals changed significantly from baseline in all subjects, but there were no differences between the two treatment groups. A significantly higher proportion of children treated with artesunate-amodiaquine developed sinus bradycardia compared with artemether-lumefantrine treated subjects (7/47 vs 0/30; χ² p=0.03). Subjects who developed bradycardia were significantly older, and had higher DEAQ concentrations than those who did not develop bradycardia. The proportion of subjects with QTc interval prolongations did not differ significantly between the groups, and no relationship between prolonged QTc intervals and DEAQ levels were observed. No clinically significant rhythm disturbances were observed in any of the subjects. CONCLUSION: Artesunate-amodiaquine treatment resulted in a higher incidence of sinus bradycardia than artemether-lumefantrine treatment in children with uncomplicated malaria, but no clinically significant rhythm disturbances were induced by combining artesunate with amodiaquine. These findings, although reassuring, may imply that non-amodiaquine based artemisinin combination therapy may be preferable for malaria treatment in patients who are otherwise at risk of cardiac effects.

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.

Childhood tuberculosis and factors associated with mortality and loss to follow-up at a major paediatric treatment centre in Southern Ghana.

Introduction: tuberculosis (TB) is a major cause of morbidity and mortality in children in low- and middle-income countries. This study described the clinical presentation and identified factors contributing to poor outcome of childhood TB at Korle Bu Teaching Hospital (KBTH), Accra, Ghana. Methods: this was a retrospective cohort study of children aged ≤ 14 years with TB registered for treatment at KBTH from 2015 to 2019. Treatment outcomes were recorded as treatment success and unsuccessful outcomes (died and loss to follow-up). Multivariable logistics regression was conducted to assess factors associated with an unsuccessful outcome. Results: of 407 children with TB registered during the period, 269 (66.1%) patients had pulmonary tuberculosis (PTB). Of the 138 patients with extra-pulmonary TB (EPTB), 68 (49.3%) had TB lymphadenitis. The TB/HIV coinfection rate was 42.8%. The overall treatment success rate was 68.3%, whilst 71(17.4%) died, and 58 (14.3%) were lost to follow-up. Factors associated with death were age below 1 year (AOR: 3.46, 95% CI: 1.48-8.10, p=0.004) and having HIV coinfection (AOR: 1.89, 95% CI: 1.04-3.43, p=0.037). Factors associated with loss to follow-up were age below 1 year (AOR: 2.91, 95% CI: 1.12-8.59, p=0.029) and having EPTB (AOR: 2.40, 95% CI: 1.24-4.65, p=0.009). Conclusion: childhood TB treatment success in our population was below the national target of 85%, with high mortality and loss to follow-up rates, especially in younger children and those with HIV coinfection or EPTB. Tailored treatment strategies may be needed for children at risk of unsuccessful treatment outcome, especially among infants.

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

BACKGROUND: 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. METHODS AND SUBJECTS: 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. RESULTS: 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.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).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. CONCLUSION: 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.

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.

Plasma Folate Levels in Acutely Ill and Steady State Pediatric Sickle Cell Disease Patients in Ghana.

BACKGROUND: Individuals with sickle cell disease (SCD) are susceptible to infective conditions that predispose them to hemolysis and anemia. Folic acid is recommended as a preventative measure against anemia in SCD patients; however, there is scarce literature on the implications of this practice. PATIENTS AND METHODS: Plasma concentrations of folate were measured in acutely ill pediatric SCD patients presenting with malaria or bacteremia and compared with those of SCD patients in steady state, or acutely ill non-SCD patients with confirmed malaria. RESULTS: The proportion of individuals with high (>45.3 nmol/L) folate concentrations was 29.5% (13/44), 18.2% (8/44), 33.3% (6/18), and 0% in the SCD-malaria, SCD steady state, SCD bacteremia, and the non-SCD malaria groups, respectively. The proportion of SCD patients with high folate levels did not vary significantly at steady state and during confirmed malaria (p = 0.216), and during acute bacteremia (p = 0.20). The median (interquartile range) plasma folate levels were 34.50 (24.40-52.00 nmol/L), 33.40 (15.83-60.85 nmol/L), 30.85 (24.68-39.65 nmol/L), and 13.30 (10.03-17.18 nmol/L), respectively, in the SCD malaria, SCD bacteremia, SCD steady state, and the non-SCD malaria sub-groups. The median folate levels of SCD steady state, SCD malaria, and SCD bacteremia sub-groups differed significantly (p < 0.0001) when compared with non-SCD patients, but the levels in the SCD bacteremia and malaria groups were not significantly different from the SCD steady state group. CONCLUSION: Elevated levels of plasma folate were found in a high proportion of pediatric SCD patients. The implications of such elevated folate levels in pediatric SCD patients are unknown but may suggest a need for review of current recommendations for prophylactic doses of folic acid in SCD patients.

Correction: The significance of human respiratory syncytial virus (HRSV) in children from Ghana with acute lower respiratory tract infection: A molecular epidemiological analysis, 2006 and 2013-2014.

[This corrects the article DOI: 10.1371/journal.pone.0203788.].