Diagnosis patterns of sickle cell disease in Ghana: a secondary analysis.

BACKGROUND: Despite having the highest prevalence of sickle cell disease (SCD) in the world, no country in Sub-Saharan Africa has a universal screening program for the disease. We sought to capture the diagnosis patterns of SCD (age at SCD diagnosis, method of SCD diagnosis, and age of first pain crisis) in Accra, Ghana. METHODS: We administered an in-person, voluntary survey to parents of offspring with SCD between 2009 and 2013 in Accra as a part of a larger study and conducted a secondary data analysis to determine diagnosis patterns. This was conducted at a single site: a large academic medical center in the region. Univariate analyses were performed on diagnosis patterns; bivariate analyses were conducted to determine whether patterns differed by participant's age (children: those < 18 years old whose parents completed a survey about them, compared to adults: those > = 18 years old whose parents completed a survey about them), or their disease severity based on SCD genotype. Pearson's chi-squared were calculated. RESULTS: Data was collected on 354 unique participants from parents. Few were diagnosed via SCD testing in the newborn period. Only 44% were diagnosed with SCD by age four; 46% had experienced a pain crisis by the same age. Most (66%) were diagnosed during pain crisis, either in acute (49%) or primary care (17%) settings. Children were diagnosed with SCD at an earlier age (74% by four years old); among the adults, parents reflected that 30% were diagnosed by four years old (p < 0.001). Half with severe forms of SCD were diagnosed by age four, compared to 31% with mild forms of the disease (p = 0.009). CONCLUSIONS: The lack of a robust newborn screening program for SCD in Accra, Ghana, leaves children at risk for disease complications and death. People in our sample were diagnosed with SCD in the acute care setting, and in their toddler or school-age years or thereafter, meaning they are likely being excluded from important preventive care. Understanding current SCD diagnosis patterns in the region can inform efforts to improve the timeliness of SCD diagnosis, and improve the mortality and morbidity caused by the disease in this high prevalence population.

Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial.

BACKGROUND: The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient. METHODS: This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia. Six hundred and four children 2-59 months of age presenting with severe pneumonia at six urban and rural health care facilities in The Gambia were individually randomised to receive placebo (n = 301) or zinc (n = 303) for seven days. To determine if the study children were zinc deficient, supplementation was continued in a randomly selected subgroup of 121 children from each arm for six months post-enrolment, and height-gain, nutritional status, plasma zinc concentrations, and immune competence were compared. RESULTS: Percentage of treatment failure were similar in placebo and zinc arms both on day 5 (14.0% vs 14.1%) and day 10 (5.2% vs 5.9%). The time to recovery from lower chest wall indrawing and sternal retraction was longer in the placebo compared to zinc arm (24.4 vs 23.0 hours; P = 0.011 and 18.7 vs 11.0 hours; P = 0.006 respectively). The time to resolution for all respiratory symptoms of severity was not significantly different between placebo and zinc arms (42.3 vs 30.9 hours respectively; P = 0.242). In the six months follow-up sub-group, there was no significant difference in height gain, height-for-age and weight-for-height Z-scores, mid upper arm circumference, plasma zinc concentrations, and anergy at six months post-enrolment. CONCLUSIONS: In this population, zinc given as an adjunct treatment for severe pneumonia showed no benefit in treatment failure rates, or clinically important benefit in time to recovery from respiratory symptoms and showed marginal benefit in rapidity of resolution of some signs of severity. This finding does not support routine use of zinc as an adjunct treatment in severe pneumonia in generally zinc replete children. TRIAL REGISTRATION: ISRCTN33548493.

Identification of OP354-like human rotavirus strains with subtype P[8]b in Ghanaian children with diarrhoea.

BACKGROUND: Rotaviruses with the P[8] genotype have been associated with majority of infections. Recent improvements in molecular diagnostics have delineated the P[8] genotype into P[8]a and P[8]b subtypes. P[8]a is the previously known P[8] genotype which is common whilst P[8]b subtype also known as OP354-like strain is genetically distinct, rarely detected and reported from a few countries. In a previous study, the P-types could not be determined for 80 RVA-positive samples by conventional RT-PCR genotyping methods with the recommended pool of P-genotype specific primers used in the WHO Regional Rotavirus Reference Laboratory in Ghana. The present study employed sequence-dependent cDNA amplification method to genotype previously non-typeable P-types. METHODS: Viral RNAs were extracted and rotavirus VP4 genes amplified by one step RT-PCR using gene specific primers. PCR amplicons were purified, sequenced and sequences aligned with cognate gene sequences available in GenBank using the ClustalW algorithm. Phylogenetic analysis was performed using the Neighbour-Joining method in MEGA v6.06 software. Phylogenetic tree was statistically supported by bootstrapping with 1000 replicates, and distances calculated using the Kimura-2 parameter model. RESULTS: Of the 80 RVA-positive samples, 57 were successfully sequenced and characterized. Forty-eight of these were identified as P[8] strains of which 5 were characterized as the rare P[8]b subtype. Phylogenetic analysis of the VP8* fragment of the VP4 genes of these P[8]b strains revealed a close relationship with prototype OP354-like P[8]b strain and P[8]b strains of Russian and South African P[8]b origin. CONCLUSION: The study highlights the importance of regularly updating the primers employed for molecular typing of rotaviruses.

Rotavirus Infection in Children with Diarrhea at Korle-Bu Teaching Hospital, Ghana.

Human rotavirus infection was studied over a 13-month period (January 2004 to January 2005) in children <5 years of age admitted with severe diarrhea at the Korle-Bu Teaching Hospital in Accra, Ghana. During this period, 206 hospitalizations for diarrhea were recorded, with 34.0% (70/206) being positive for rotavirus infection. Infection occurred throughout the year, with peak rotavirus infection occurring during the month of March. Hospitalization associated with rotaviruses was most common in the 6-8 month age group. The case fatality rate of rotavirus infection was 2.9% (2/70) and occurred in children <12 months of age. Four rotavirus VP7 genotypes (G1, G2, G3, and G9) were detected. The predominant genotypes were G2 (22.9%), G1 (17.1%), G9 (17.1%) and G3 (12.9%). Mixed G types were also detected. The predominant VP4 genotypes (P types) were P[6] (38.6%), P[8] (21.4%), P[4] (4.3%) and P[9] (1.4%). The predominant rotavirus strains infecting children in Accra were G9P[6] (10.0%) and G1P[8] (8.6%). Strains with unusual genotypes such as G2P[8] and G(2/3)P[6] were also detected.

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.

Aetiology of Acute Lower Respiratory Infections among Children Under Five Years in Accra, Ghana.

The study aimed to investigate the aetiological agents and clinical presentations associated with acute lower respiratory infections (ALRI) among children under five years old at the Korle-Bu Teaching Hospital in Ghana. This was a cross-sectional study carried from February to December 2001. Nasopharyngeal aspirates and venous blood specimens obtained from 108 children with features suggestive of ALRI, were cultured and the isolated bacterial organisms were identified biochemically. Nasopharyngeal aspirates were also tested for Respiratory Syncitial Virus (RSV) antigen using a commercial kit (Becton Dickinson Directigen RSV test kit). A multiplex reverse transcription-PCR (RT-PCR) was also used to detect and characterize RSV using extracted RNA. Socio-demographic and clinical data were also obtained from the study subjects. Bronchopneumonia (55.5%), bronchiolitis (25%), lobar pneumonia (10.2), non-specific ALRI (4.6%), TB, bronchitis and respiratory distress (0.67%) were diagnosed. The prevalence of septicaemia was 10% and bacteria isolated were Staphylococcus aureus, Streptococcus pneumoniae and enteric bacteria, including Salmonella spp., Enterobacter spp and Klebsiella spp, were isolated. Out of the 108 cases, 18% tested positive for RSV, with two cases having RSV as the only aetiological pathogen detected. The subtyping analysis of RSV strains by a multiplex RT-PCR showed that subgroups A and B circulated in the season of analysis.

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.

Reversible audiometric threshold changes in children with uncomplicated malaria.

Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs, is associated with hearing impairment in adults. There is little information, however, on the extent, if any, of this effect in children, and the evidence linking artemisinin combination therapies (ACTs) with hearing is inconclusive. Methods. Audiometry was conducted in children with uncomplicated malaria treated with artesunate-amodiaquine (n = 37), artemether-lumefantrine (n = 35), or amodiaquine (n = 8) in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days later and after 9 months. Audiometric thresholds were compared with those of a control group of children (n = 57) from the same area. Findings. During the acute stage, hearing threshold levels of treated children were significantly elevated compared with controls (P < 0.001). The threshold elevations persisted up to 28 days, but no differences in hearing thresholds were evident between treated children and controls after 9 months. The hearing thresholds of children treated with the two ACT regimens were comparable but lower than those of amodiaquine-treated children during acute illness. Interpretation. Malaria is the likely cause of the elevated hearing threshold levels during the acute illness, a finding that has implications for learning and development in areas of intense transmission, as well as for evaluating potential ototoxicity of new antimalarial drugs.

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.

Attitudes of Ghanaian women toward genetic testing for sickle cell trait.

OBJECTIVE: To explore the attitudes of Ghanaian women toward genetic testing for the sickle cell trait and to investigate key factors that promote or impede the decision to pursue knowledge of the carrier status. METHODS: A survey, administered in person to Ghanaian women, collected demographic information and information on the participants' knowledge about their carrier status, their attitudes toward genetic testing, and their perceptions of the implications of being a carrier. The results for women who had previously undergone testing and those who had not were compared. RESULTS: Of 124 participants, 75 had been tested for the sickle cell trait and 49 had not. Some 53% of the women who had been tested did not know their carrier status. Most women agreed that getting a prenatal genetic test was important. However, nontested women were more likely to lack the financial resources to undergo testing, to think that testing is futile because sickle cell disease is not curable, and to believe that the outcome of their child's health is determined by God. CONCLUSION: The women tended to have favorable attitudes toward genetic testing, but numerous barriers remained that precluded knowledge of their carrier status or the pursuit of this knowledge.

Motor development in 9-month-old infants in relation to cultural differences and iron status.

Motor development, which allows infants to explore their environment, promoting cognitive, social, and perceptual development, can be influenced by cultural practices and nutritional factors, such as iron deficiency. This study compared fine and gross motor development in 209 9-month-old infants from urban areas of China, Ghana, and USA (African-Americans) and considered effects of iron status. Iron deficiency anemia was most common in the Ghana sample (55%) followed by USA and China samples. Controlling for iron status, Ghanaian infants displayed precocity in gross motor development and most fine-motor reach-and-grasp tasks. US African-Americans performed the poorest in all tasks except bimanual coordination and the large ball. Controlling for cultural site, iron status showed linear trends for gross motor milestones and fine motor skills with small objects. Our findings add to the sparse literature on infant fine motor development across cultures. The results also indicate the need to consider nutritional factors when examining cultural differences in infant development.

Ocular manifestations of sickle cell disease at the Korle-bu Hospital, Accra, Ghana.

PURPOSE: To determine the magnitude and pattern of ocular manifestations in sickle cell disease at Korle-bu Hospital, Accra, Ghana. METHODS: Hospital-based cross-sectional study including all patients with sickle cell disease reporting for routine follow-up at the Sickle Cell Clinic at Korle-bu Hospital, Accra, Ghana. RESULTS: A total of 201 patients with sickle cell disease (67 male and 134 female) were enrolled, comprising 114 subjects with genotype HbSS, aged 6-58 years, mean 19.26 (SD 11.70), and 87 with genotype HbSC, aged 6-65 years, mean 31.4 (SD 16.76). Visual impairment was found in 5.6% of eyes examined. Causes were cataract, proliferative sickle retinopathy (PSR), optic atrophy, phthisis bulbi, and central retinal artery occlusion. Common anterior segment signs of sickle cell disease, which were more common in HbSC patients, were tortuous corkscrew conjunctival vessels, iris atrophy, and cataract. Eyes with iris atrophy or depigmentation were 1.8 times more at risk of PSR than eyes without. Overall, PSR was found in 12.9% of subjects examined (3.5% of HbSS, 25.3% of HbSC; 15.9% of males and 11.2% of females). The prevalence of proliferative sickle retinopathy increased with age and increased systemic severity of sickle cell disease; sex did not have an influence. CONCLUSIONS: There is a high prevalence of ocular morbidity in sickle cell disease patients at Korle-bu Hospital. Prevalence increased with age, systemic severity of sickle cell disease, and HbSC genotype.

Effect of concomitant artesunate administration and cytochrome P4502C8 polymorphisms on the pharmacokinetics of amodiaquine in Ghanaian children with uncomplicated malaria.

Artesunate (AS) is used in combination with amodiaquine (AQ) as first-line treatment for uncomplicated malaria in many countries. We investigated the effect of concomitant AS administration on the pharmacokinetics of AQ and compared concentrations of desethylamodiaquine (DEAQ), the main metabolite of AQ, in plasma between patients with different variants of the cytochrome P4502C8 (CYP2C8) gene. A two-compartment model was fitted to 169 plasma DEAQ concentrations from 103 Ghanaian children aged 1 to 14 years with uncomplicated malaria treated either with AQ alone (n = 15) or with AS plus AQ (n = 88). The population clearance of DEAQ appeared to increase nonlinearly with body weight, and the central volume of distribution of DEAQ was higher (P < 0.001) in the AS-plus-AQ group than in the AQ-only group. The maximum plasma DEAQ concentration was higher (P < 0.001), and the population distribution half-life was shorter (P < 0.01), in the AQ-only group than in the AS-plus-AQ group. The total areas under the plasma DEAQ concentration-time curves (P = 0.68) and elimination half-lives (P = 0.39) were similar for the two groups. There was a high frequency (0.179) of the non-wild-type allele of CYP2C8, but no differences between CYP2C8 genotypes with regard to AQ efficacy or safety were evident. The sample size, however, was limited, so monitoring of AQ toxicity in the study area is still indicated. The nonlinear clearance of DEAQ and the wide variability in kinetic parameters have safety implications for weight-based dosing of higher-body-weight children with AQ. The pharmacokinetics of artemisinin combination therapies should be studied in malaria patients, because the rapid parasite clearance caused by the artemisinin may affect the kinetics of the partner drug and the combination.

Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up.

BACKGROUND: Artesunate-amodiaquine (AS+AQ) and artemether-lumefantrine (AM-L) are efficacious artemisinin combination therapy (ACT) regimens that have been widely adopted in sub-Saharan Africa. However, there is little information on the efficacy of these regimens on subsequent episodes beyond 28 days, or on the safety of repeated treatments. METHODS: Children aged six months to 14 years with uncomplicated malaria were randomly assigned to treatment with AS+AQ (n = 116), or AM-L (n = 111). Recruited subjects were followed-up, initially for 28 days, and then monthly for up to one year. All subsequent attacks of uncomplicated malaria after 28 days were treated with the same regimen as at randomization. Investigations aimed at determining efficacy and side effects were conducted. RESULTS: Adequate clinical and parasitological response in subjects with evaluable end-points were, 97.1% (100/103) and 98.2% (107/109) on day 14, and 94.2% (97/103) and 95.3% (102/107) on day 28 in the AM-L and AS+AQ groups, respectively. Similar results were obtained after PCR correction. The incidence of malaria attacks in the year following recruitment was similar between the two treatment groups (p = 0.93). There was a high incidence of potentially AQ-resistant parasites in the study area. The incidence of adverse events, such as pruritus, fatigue and neutropaenia were similar in the two treatment groups. No patient showed signs of hearing impairment, and no abnormal neurological signs were observed during one year of follow-up. Other adverse events were mild in intensity and overlapped with known malaria symptomatology. No adverse event exacerbation was observed in any of the subjects who received multiple treatment courses with these ACT regimens during one year follow-up. CONCLUSION: AS+AQ and AM-L were efficacious for treatment of children with uncomplicated malaria in Ghana and drug-related adverse events were rare in treated subjects during one year of follow-up. The high prevalence of potentially AQ resistant parasites raises questions about the utility of AQ as a partner drug for ACT in Ghana. The efficacy of AS+AQ in Ghana requires, therefore, continuous monitoring and evaluation. TRIAL REGISTRATION: NCT 00406146 http://www.clinicaltrials.gov.

Cryptosporidium Spp., a frequent cause of diarrhea among children at the Korle-Bu Teaching Hospital, Accra, Ghana.

This report presents the results of a study conducted at the Child Health Department, Korle-Bu Teaching Hospital, Accra, Ghana, between the months of October 2001 and June 2002. Stool samples from 227 children with diarrhea and 77 children without diarrhea, aged less than 5 years, were tested for Cryptosporidium spp. Prevalence rates were 27.8 and 15.6% in children with and without diarrhea, respectively. Cryptosporidium infection was found to be high in children between the ages of 6 and 24 months. Cryptosporidium spp. was more common in malnourished children, but was not isolated in children under 6 months of age who were exclusively breastfed. Neither the presence of domestic animals, abdominal pain, blood in stool, nausea, vomiting, nor the consumption of untreated water was associated with Cryptosporidium spp. infection. Shigella, Salmonella, and yeast-like organisms were the most frequently identified enteropathogenic bacteria. In summary, this study demonstrates the prevalence of Cryptosporidium spp. among Ghanaian children.