Detection of Transversions and Transitions in HBG2 Cis-Elements Associated with Sickle Cell Allele in Ghanaians.

Short tandem repeats located 5' prime to the ß-globin gene, have been observed to be in linkage disequilibrium with the HbS allele, and thought to affect the severity of sickle cell disease. Here, we report on new mutants within the HBG2 region that may impact sickle cell disease. To determine the cis-acting elements microsatellites, indels and single nucleotide polymorphisms (SNPs), within the HBG2 region by sequencing, in subjects with sickle cell disease. The case-control study was located at the Center for Clinical Genetics, Sickle cell unit, Korle-Bu Teaching Hospital. A questionnaire was used for demographic data and clinical information. Hematological profile (red blood cell, white blood cell, platelet, hemoglobin and mean corpuscular volume) were assessed in 83 subjects. A set of 45 samples comprising amplified DNA on the HBG2 gene from HbSS (22), HbSC (17) and 6 controls (HbAA) were sequenced. Differences in the microsatellite region between sickle cell disease (SCD) (HbSS and HbSC) genotypes and control subjects were identified by counting and assessed by Chi-square analysis. Red blood cells, hematocrit, platelets, white blood cells and hemoglobin indices differed in genotypic groups. HbSS subjects were affirmed to have severer hemolytic anemia than HbSC subjects. Two indels (T1824 and C905) were seen in both SS and SC genotypes. Two peculiar SNPs: G:T1860 (transition) and A:G1872 transversions were found within the HBG2 gene that were significantly associated with the HbSS genotype (Fisher's exact test, p = 0.006) and HbS allele respectively (Fisher's exact test, p = 0.006). Cis-acting elements in HbSS and HbSC were different and may contribute to the phenotype seen in the disease state.

Haematological Changes among HIV-Positive Persons on Antiretroviral Therapy at a Tertiary Hospital in Ghana.

BACKGROUND: Haematological abnormalities such as anaemia, leucopenia, and thrombocytopenia are common complications of Human Immunodeficiency Virus (HIV) infection. Few researchers have studied the changes in HIV positive patients before and during antiretroviral therapy (ART) in Ghana. This study is aimed at determining the haematological profile of people living with HIV (PLHIV) at baseline and whilst on ART in a tertiary facility in Cape Coast, Ghana. METHODS: This was an analytical cross-sectional study with a retrospective component among PLHIV assessing ART services at the Cape Coast Teaching Hospital, Ghana. Full blood count (FBC) test was performed on blood samples and the results were analyzed and categorized based on WHO definitions. RESULTS: A total of 440 participants were included. The mean haemoglobin level (g/dL) for females at baseline, 6 months after ART and during this study were 9.6 (±1.8), 10.9 (±1.4) and 11.6 (±1.4); and 10.2 (±2.1), 11.6 (±1.7) and 11.8 (±1.6) for males. At baseline, the commonest type of anaemia for both females and males was microcytic hypochromic anaemia. The mean platelet count was 382 x 109/l at baseline but reduced to 298 x 109/L after 6 months on ART. Among male participants in this study, the main factor associated with being anaemic after 6 months on ART was the ART regimen with non-Zidovudine based regimen, having reduced odds of anaemia of OR 0.3 (95%CI 0.1 - 0.9), p-value of 0.04. Among females, having plasma viral load >1000 copies per ml was found to have increased odds of being anaemic (OR 1.4, 95%CI 0.7 - 2.6), though not statistically significant (P-value of 0.32). CONCLUSION: The prevalence of anaemia, though improved on ART, was high among PLHIV. It is essential to ensure that full blood count of PLHIV in Ghana are done regularly, at all levels of service provision, with appropriate referral systems in place. The change to the current TDF based preferred first line ART regimen must also be enforced to reduce the potential risks associated with AZT use. This will improve outcome for PLHIV.

CUTANEOUS INVOLVEMENT OF HODGKIN LYMPHOMA IN A CHILD--CASE REPORT.

Specific cutaneous involvement in Hodgkin Lymphoma is rare and has not been reported in the younger paediatric age group. We report a case of a ten year old girl who presented with specific cutaneous involvement, confirmed using immunohistochemical stains. Treatment with combination chemotherapy resulted in rapid disappearance of the lesions and contrary to the generally poor prognosis associated with most other such reported cases in adults, she has clinically remained disease free two and a half years post treatment. Obtaining an accurate pathological diagnosis is essential to ensure appropriate treatment even in resource limited settings as illustrated by this case.

Second Trimester Anaemia in Pregnant Ghanaians.

BACKGROUND: Anaemia is considered a severe public health problem by WHO and is seen as such in Ghana. Its prevalence in pregnancy has remained high despite improved antenatal care. The main purpose of this study was to determine the current anaemia prevalence and aetiology other than iron deficiency. METHODS: This was a cross-sectional study. A total of 214 pregnant women were studied. Women were administered a questionnaire related with the subject and blood samples were drawn. Full blood count was performed within four hours and serum iron, folate and vitamin B12 were studied. Other tests done included sickling and Hb electrophoresis , stool routine examination for hookworm infestation, thick and thin film for malaria parasitaemia. Dietary intake was also looked at to determine whether it contributed to anaemia seen in these subjects. RESULTS: Anaemia was detected in 150 (70%) of the 214 pregnant women studied. Using the World Health Organisation criteria for anaemia, 81 subjects had mild, 66 moderate and 3 had severe anaemia. Anaemia was more prevalent in young adults (82%) than in teenagers and subjects above 35years (p=0.018). Primigravidae (21%) and multigravidae (67%) were more likely to be anaemic than grandmultigravidae (12%). Anaemia was more prevalent in the low social class group (94%). Nutritional intake of both anaemic and non-anaemic subjects was found to be adequate and thus iron deficiency anaemia, which was found to be the commonest cause of anaemia, was probably due to intake of diet low in bioavailable iron. There was very little consumption of fruits and vegetables that facilitate iron absorption. Twenty seven anaemic subjects had low serum iron levels. Transferrin saturation was low in 39 subjects; 24 of these also had low serum iron, which was suggestive of iron deficiency. Folate and vitamin B12 deficiency did not play significant role in the aetiology of anaemia. Malaria and hookworm infestation were also not found to be significant in the causation of anaemia. CONCLUSIONS: The prevalence of anaemia (70%) in pregnant Ghanaians in their second trimester is unacceptably high. Twenty seven (18%) of the 70% anaemic subjects had low serum iron and six (4%) had low serum folate levels. None of the subjects had vitamin B12 deficiency. Generally dietary intake in pregnant women in this study was adequate, but significant proportion of their meals was of the type low in bioavailable iron as more cereals and tubers were consumed. The kind of diet, which most people can afford in Africa is low in proteins and vitamins, but high in carbohydrate with high phytate contents and this reduces iron absorption. Iron and folic acid prophylaxis for all women of child bearing age is recommended and emphasis on a more balanced nutritional intake at antenatal clinics should be encouraged.

ORBITAL AND ADNEXAL LYMPHOMAS AMONG ADULT PATIENTS IN GHANA.

BACKGROUND: Non Hodgkin's lymphomas (NHLs) present variously in different ethnic communities. Orbital and adnexal disorders have been reported among NHLs in Africa. They can involve the orbit, the eyelid, the conjunctiva, alone or in combinations. To our knowledge there are no reports in the literature about the clinical presentation of lymphomas in Ghana. AIM: To explored orbital and adnexal disorders among adult patients attending the Korle-Bu Teaching hospital, Accra. METHODOLOGY: Histological case notes of patients reporting to the orbital clinic of Korle-Bu Teaching Hospital, Eye Department from November 2004 to October 2016 with orbital and adnexial lympho-proliferative tumors were retrieved. Histopathology was performed at Sheffield Teaching hospital. Data collected included age, sex, symptoms at presentation and anatomic site of involvement. Histology and immune histochemistry data were generated. RESULTS: A total of 18 patients were examined and entered into the study. The male to female ratio was 1.25:1. Twelve patients (70.6) presented with proptosis and 14 (77.8%) had orbital involvement. Two patients had isolated eyelid disease. Of those with orbital disease, three had simultaneously upper eyelid involvement. Out of the 18 cases, 11 (61.1%) were mucosa-associated lymphoid tissue (MALT) lymphomas. Only males 40 years and above were affected, compared with females who presented at any age. Patients above 60 years reported early (i.e. <3 months) compared with patients below 40 years who mostly reported after 1 year. CONCLUSION: This study reports pattern of epidemiological and clinical presentation of orbital and adnexal lymphomas as seen in Ghana, West Africa. Though there were some variations in the clinical presentation the histological subtypes represented seem to be similar to those reported in other parts of the world.

The Orthodontic Management of an Adult with Sickle Cell Disease.

Sickle cell disease (SCD) is a hereditary blood disorder characterized by abnormally shaped red cells. SCD frequently exhibits multisystemic manifestations including oral and craniofacial disorders. Craniofacial features such as maxillary protrusion and more forward growth of the mandible with significantly retruded maxillary and mandibular incisors are common. When a patient with Sickle Cell Disease (SCD) needs orthodontic treatment, it is important for the practitioner involved to know about the disease and the respective treatment because of the importance of complete blood supply after application of intraoral and extraoral forces. This article describes a sickle cell HbSS patient with orthodontic problems and how she was successfully managed at the University of Ghana Dental School.

Sickle Cell Disease: Reappraisal of the Role of Foetal Haemoglobin Levels in the Frequency of Vaso-Occlusive Crisis.

BACKGROUND: Foetal haemoglobin has been implicated in the modulation of sickle cell crisis. Its level is generally inversely proportional to the severity of sickle cell disease (SCD) for a given sickle cell phenotypes. The main aim of therapy for vaso-occlusive crisis (VOC), which is the hallmark of SCD, is to reduce the chances of sickling through the prevention of polymerization of HbS. One way of preventing this polymerization is by increasing foetal haemoglobin levels. OBJECTIVES: To determine the relationship between HbF levels and the frequency of crisis in SCD patients in Ghana. METHOD: A longitudinal retrospective survey covering a period of 30 months was carried out on adult SCD patients at the Sickle Cell Clinic of the Korle-Bu Teaching Hospital. RESULTS: Eighty-three adults aged 15 to 65 years made up of 40 males and 43 femalea were studied. Analysis of variance (ANOVA) gave significant results in Hb and HbF levels. Higher HbF levels were positively related to less frequent crisis and were significantly high in SCD patients than in controls. HbF effects on the clinical manifestations on SCD were variable. CONCLUSION: Threshold values of HbF play a role in reducing the frequency of vaso-occlusive crisis in SCD patients and this finding contributes to the body of available literature on SCD severity. However our work does not give the apparent threshold level of helpful HBF Level in SCD.

Childhood acute lymphoblastic leukaemia (ALL) in Ghanaians and Germans--a comparative study.

The records of 20 ALL patients aged 12 years and below seen at Korle-Bu Teaching Hospital(KBTH) between December 1982 and May 1990 were examined as well as that of their counterparts in Hamburg University Children's Hospital(HHOG) matched by age, sex and as closely as possible date of presentation. Data on clinical and laboratory findings, treatment and outcomes were taken and analysed using binomial proportions and paired samples T-tests. It was found that KBTH patients presented with lower haemoglobin levels, bigger organ enlargements, received less intensive treatment and defaulted more often than HHOG patients. White blood cell(WBC) counts were statistically the same. Achievability of remission was 75% and 100% for KBTH and HHOG patients respectively. Average follow up was 6 months for KBTH patients and 69 months for HHOG. 60% of KBTH patients had defaulted at the time of the study. 75% of HHOG patients were alive at the time of study with the longest follow up being 114 months. It is concluded that in spite of the bigger organ enlargement for the KBTH patients, WBC count which is the single most important prognostic factor was the same for both groups, and with less intensive therapy, achievability of remission for KBTH was 75%--reasonably good. More work need to be done in Africa on prognostic features and treatment.

Multicentric Castleman's disease in a Ghanaian adult.

Castleman's disease is a rare cause of lymphoid hyperplasia that may result in localized symptoms or an aggressive, multisystem disorder that can mimic other diseases like lymphoma or tuberculosis. We describe a case of a 55-year-old Ghanaian male who was successfully diagnosed and managed for multicentric Castleman's disease with combination chemotherapy.

A-61C and C-101G Hp gene promoter polymorphisms are, respectively, associated with ahaptoglobinaemia and hypohaptoglobinaemia in Ghana.

We have investigated the genetic basis for the Hp0 phenotype amongst 123 randomly selected Ghanaians. A total of 17 individuals were determined to be Hp0 phenotype, based on the classical method for Hp phenotyping of Hb-supplemented plasma. Out of the 17 Hp0 individuals, nine subjects were further classified as ahaptoglobinaemic and eight as hypohaptoglobinaemic by Western blots and double immunodiffusion. We identified three previously known base substitutions (A-55G, A-61C and T-104A) and three new ones (C-101G, T-191G and C-242T) within the 5' flanking region of the Hp gene. The A-61C base substitution significantly decreased transcriptional activity and was associated strongly with Hp2 allele and ahaptoglobinaemia. The C-101G substitution was similar in transcriptional activity to the wild-type and was associated with Hp1S allele and hypohaptoglobinaemia. The Hpdel allele seen in Asian populations was absent. We conclude that the Hp0 phenotype in Ghana has a genetic basis that differs significantly from that seen in Asia.