Effects of factor v Leiden polymorphism on the pathogenesis and outcomes of preeclampsia.

BACKGROUND: Factor V Leiden polymorphism is a well-recognized genetic factor in the etiology of preeclampsia. Considering that Ghana is recording high incidence of preeclampsia, we examined if factor V Leiden is a contributory factor to its development and pregnancy outcomes. METHODS: STROBE consensus checklist was adopted to recruit eighty-one (81) consenting subjects after ethical clearance. Subjects were followed up till delivery to obtain outcomes of PE. Routine blood chemistry and proteinuria were done on all samples. Factor V Leiden was characterized by polymerase chain reaction and restriction fragment length polymorphism (RFLP). The data was captured as protected health information (PHI) and analyzed with SPSS version 22. RESULTS: Overall allelic frequencies found in FVL exon 10 were 0.67 and 0.33 for G and A alleles respectively. The FVL mutation was more in PE and hypertensive patients. Increased white blood cells, increased uric acid and a three - fold increment of AST / ALT ratio was observed in PE cases when stratified by FVL exons (exon 8 and 10). Significant differences were also observed between FVL and age, systolic blood pressure (SBP), diastolic blood pressure (DBP), liver enzymes, white blood cells (wbc), hemoglobin levels. CONCLUSION: FVL mutation allele frequency was 0.33, a first report. The mutation was associated with increased uric acid, liver enzymes and blood cell indices suggestive of acute inflammation.

Endomyocardial fibrosis associated with Schistosoma haematobium infection.

Endomyocardial fibrosis (EMF) is a form of restrictive cardiomyopathy common in the tropics and subtropics. The aetiology of EMF is unknown but helminth infestations such as schistosomiasis have been implicated. Two boys aged 8 and 10 years with EMF associated with Schistosoma haematobium, are described. The schistosomes in both cases may have been acquired from contact with contaminated water collected and stored in containers and subsequently used for bathing. Both patients were managed conservatively. Overall prognosis of EMF is poor and this report emphasizes the importance of public health interventions in the control of schistosomiasis.

Kawasaki disease in ghana: case reports from Korle Bu teaching hospital.

Kawasaki disease, an acute febrile vasculitis, predominantly affects children under the age of 5 years and is thought to be a rare disease in the developing world. It has previously never been reported in Ghana. We report 3 cases from February, 2007 to February, 2008. This potentially serious disease has no definitive diagnostic test and it is not unusual for diagnosis to be delayed with serious consequences. Any child with irritability and persisting fever (>5 days) not responding to antipyretics and antibiotics, accompanied by a rash and non purulent conjunctivitis should be suspected to have Kawasaki disease.

Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malaria.

We have examined IgG and complement factor C3d deposition on erythrocytes by means of the direct Coombs' test (DAT) and looked for an association with the anaemia seen in falciparum malaria in children living in an area of hyperendemic malaria transmission (in Ghana). In one study (in 1997), 53 out of 199 patients had a positive DAT. Of these, 45 samples reacted with anti-C3d antibodies, 2 with anti-IgG and 6 with both reagents. There were significantly lower haemoglobin (Hb)-levels and higher prevalence of spleen enlargement in DAT-positive than in DAT-negative patients. Hb-levels were independently associated with DAT and age. This initial study was designed to investigate the role of intravascular haemolysis (IVH), but we found no association between IVH and either DAT result or anaemia. Because of the risk of selection bias we repeated the study using consecutive enrollment of malaria patients and were able to confirm the results in a total of 49 DAT-positive and 183 DAT-negative patients. This second study (in 1998) was designed to look at the importance of erythrophagocytosis through measurement of plasma neopterin levels and total nitrite and nitrate as markers of NO-release. Both parameters were significantly higher in DAT-positive than in DAT-negative patients (P < 0.001), indicating that complement binding to erythrocytes was associated with macrophage activation. Plasma levels of haptoglobin, interleukin-10 and tumour necrosis factor-alpha did not vary between the groups. The studies support the role of complement activation and erythrophagocytosis in the pathogenesis of anaemia in falciparum malaria in African children.

Comparison of chloroquine with artesunate in the treatment of cerebral malaria in Ghanaian children.

Despite previously reported chloroquine-resistant forms of PF falciparum in Ghana, chloroquine remains the drug of choice in severe malaria. Artemisinin derivatives have been shown to be effective against chloroquine-resistant strains in other endemic areas. This open randomized study was conducted to compare the efficacy of chloroquine and artesunate in the treatment of childhood cerebral malaria. Out of 82 subjects that fulfilled the inclusion criteria, 36 were randomized to receive chloroquine and 46 to receive artemisinin. Blantyre coma scores, temperature and parasitaemia were monitored. Mortality and neurological deficits were documented. There was no difference in mortality rates (chloroquine, 16.7 per cent; artesunate, 21.7 per cent; p = 0.6), neurological deficit at day 14 (chloroquine, 0 per cent; artesunate, 4.3 per cent; p = 0.3), resolution of fever (p = 0.55), and coma recovery time (p = 0.8), between the two groups. The results suggest that syrup chloroquine and intramuscular/oral artesunate currently give comparable clinical responses in the treatment of cerebral malaria in Ghana. Possible reasons for this are discussed, and suggestions are made for future antimalarial drug policy.

HIV-1 and HIV-2 in Ghana, west Africa: community surveys compared to surveys of pregnant women.

We conducted a population-based serosurvey of HIV-1/2 in 2,410 residents of two urban and two rural areas of southern Ghana, West Africa and compared the results to serosurveys of 1,417 pregnant women. Using conservative criteria, we found the prevalence of HIV-1/2 in community survey adults (> 15 years old) to be 1.5% in women and 1.0% in men. Among pregnant women, the prevalence was 9.3% in one rural area but only 1.0% in other areas. Many samples, especially among the pregnant women were HIV-1 and -2 dual reactive on serology. We attribute the disparity between prevalence in the community survey participants and pregnant women to local socio-economic factors. Women in this area have a tradition of working throughout West Africa as trader/ commercial sex workers. When pregnant or ill, they return to their home villages to be with their families. HIV surveillance programs which rely on pregnant women need to be sure that sampled populations are truly typical of the communities they are intended to represent.

PIP: HIV prevalence in urban and rural southern Ghana was investigated in a community-based serosurvey of 2410 people conducted in 1989-90 and an analysis of serum samples collected in 1987 from 1330 pregnant women attending antenatal clinics in the Eastern Region. None of the 906 children in the community-based survey was HIV-positive, including 6 born to HIV-infected women. Among the 1329 adults, 5 men (1.0%) and 12 women (1.5%) were infected. Among pregnant women, 100 (7.1%) were HIV-positive. At the four antenatal centers, HIV prevalence ranged from 0.6% to 10.3%. The high HIV prevalence recorded among pregnant women in the Manya-Krobo District (10.3%), a rural area away from major travel routes, likely reflects the tendency for ill women to return home to be cared for by their families. HIV surveillance programs that focus on pregnant women should be aware of this social phenomenon.

Acute hepatitis in recurrent hereditary polyserositis (familial Mediterranean fever).

The clinical features of two cases of Hereditary Recurrent Polyserositis HRP (Familial Mediterranean Fever) in related Yemeni children resident in Saudi Arabia are described. One presented with recurrent acute hepatitis, which has not been previously documented. These are the first cases of HRP reported in Arabs originating from the Arabian Peninsula.

The prevalence of antibodies to the human T lymphotropic virus (HTLV) in Ghana, West Africa.

We conducted a population-based serosurvey of urban areas and rural regions of southern Ghana, West Africa. Subjects (3763) of all ages were enrolled from 25 city and village sites and in studies of groups of special interest. "Positive" results were difficult to define because of a high frequency of results that were indeterminate on immunoblotting, the current standard for confirmation of HTLV-I. However, polymerase chain reaction results and HTLV type-specific discriminatory tests proved HTLV-I was present in Ghana. No HTLV-2 positivity was observed. By using strict criteria that considered indeterminate results as negative, the overall prevalence was found to be between 1 and 2% in all areas, with no difference by geographic location. Prevalence rose with age and was higher in adult women than men. However, in substudies of selected populations, we found HTLV prevalence among 124 persons with lymphomas and hematological malignancies was not different from that in the general population. Furthermore, the prevalence in prostitutes was similar to that in the general population and in pregnant women. HTLV-I is present in West Africa, but we were unable to associate HTLV-I seropositivity with malignancy or with prostitution.

Will genetic counselling be effective in controlling sickle cell disease in Ghana?

The knowledge; attitude and practices regarding birth control were studied in 183 adults with sickle cell disease and 61 parents of affected children in Accra. Knowledge of the aetiology of sickle cell disease was poor. Only 30 per cent of respondents volunteered that it is hereditary while 74 per cent attributed it to environmental causes or disease. When prompted; 75 per cent agreed it was hereditary but 20 per cent thought it came from relatives other than parents. Thirty-three per cent (33 per cent) of parents did not know their genotype; while 36 per cent of married patients and 51 per cent of parents did not know the genotype of their spouses. Only 10 per cent of patients knew their spouses' genotype before marriage. The possibility of transmitting the disease had limited the desired family size in half of married patients; and in 18 per cent of parents. However; 37 and 46 per cent respectively already had 4 or more children. A third of married respondents were using birth control methods. Fifty-eight per cent of unmarried patients were worried about transmitting the disease; and 48 per cent would test a prospective spouse and not marry a carrier. However; 22 per cent stated that the partner's genotype would not alter the decision to marry. While 38 per cent of married patients and 27.8 per cent of parents would consider changing their spouses because of the disease; 3.8 per cent of the married patients and none of the parents had actually done so. It is suggested that better education of the general public and patients about sickle cell disease is necessary for genetic counselling to have an impact on the control of the disease

Agglutination of Plasmodium falciparum-infected erythrocytes from east and west African isolates by human sera from distant geographic regions.

Plasmodium falciparum-infected erythrocytes (PfE) were collected from acutely infected children in The Gambia and Tanzania and cultured for more than 30 hr until the parasites were mature trophozoites. Sera collected from these countries, other African countries, Asia, and South America were used in the PfE microagglutination test to determine whether PfE from East and West Africa share surface antigens. From the patterns of agglutination reactivity, we identified extensive antigenic diversity in surface antigens, but obtained no evidence for greater differences between isolates from East or West Africa and those within one region. The majority of sera from immune adults from The Gambia, Tanzania, Sudan, Nigeria, or Ghana were pan-agglutinating, and agglutinated all PfE isolates from The Gambia and Tanzania. Some sera from immune adults of Irian Jaya also agglutinated each of the seven African isolates, while others agglutinated many but not all of the isolates, similar to sera from immune adults of Flores, Indonesia. In contrast, sera from nonimmune adults from Colombia agglutinated few of the African isolates. It was remarkable, however, that sera from nonimmune Colombians agglutinated any African isolates. Our results are consistent with the following conclusions: some PfE surface antigen(s) are very diverse; this diversity is a feature of the parasite worldwide; the repertoire of isolate-specific surface antigens, although large, includes antigens that are either identical or antigenically cross-reactive in geographically very distant parasite populations; and African adults have pan-agglutinating antibodies that may contribute to protective immunity. Such pan-agglutinating antibodies could reflect the accumulation of a large repertoire of isolate-specific antibodies. The contribution of antibody against any shared PfE surface antigen to the pan-agglutinating reactivities is unknown and awaits development of the appropriate reagents.

Geographic/ethnic differences in human herpesvirus-6 antibody patterns.

Serum samples from healthy adults in four geographic/ethnic groups (Ghanaian Blacks, Malaysian Chinese, Malaysian Indians and United States Caucasians) were tested under code for antibodies to human herpesvirus-6 (HHV-6). The prevalence and titer of HHV-6 antibody in the healthy Ghanaians were significantly higher than in the Malaysian Chinese; United States Caucasians and Malaysian Indians had intermediate prevalence and titer of antibodies. Thus far, no specific differences in HHV-6-associated diseases have been noted between geographic/ethnic groups with these marked variations in antibody patterns.

Comparative trial of oral versus intramuscular chloroquine in children with cerebral malaria.

One hundred and thirteen children aged 12 years or less with cerebral malaria in Accra, Ghana were treated with chloroquine either with a low dose regime of 3.5 mg/kg 8-hourly intramuscularly, or orally by nasogastric tube, in a standard regime, both to a total of 25 mg/kg body weight. There was no obvious difference in outcome in the 2 treatment groups. The overall mortality of 5.3% (5.9% and 4.4% in the oral and intramuscular treatment groups respectively) was similar to that seen 10 years ago in this hospital. The average parasite clearance time had increased to 61 h, compared to 41 h noted 10 years ago. The incidence of hypoglycaemia (3%) was very low compared to studies in other malaria endemic areas. The reason for this is not clear but it could have contributed to the low mortality. Neurological deficits were seen on day 14 in 7.8% of patients. Parasitaemia recurred within 14 d in 22% of surviving patients, confirming the presence of RI/RII chloroquine resistance in Accra.

Sero-epidemiological investigations on human herpesvirus 6 (HHV-6) infections using a newly developed early antigen assay.

Monoclonal antibodies (MAbs) were developed against immunodominant HHV-6 (GS isolate) late and early proteins. The major late protein was identified as a probable glycoprotein with a molecular weight of approximately 110 kDa (gp 110). Immunoblotting of the early antigen yielded proteins of 41 and 38 kDa (p41/38). The MAb to the early protein reacted with cells infected with 14 different HHV-6 isolates. In contrast, the MAb against the late protein reacted with only 10 of these isolates, indicating that there was strain variation in this glycoprotein. The percentage of antibody-positive sera reactive with gp110 in the ELISA ranged from 56% to 96% among the different serum donor categories. In contrast, only 10-30% of the sera were positive for antibodies to p41/38 with the exception of sera from patients with African Burkitt's lymphoma (ABL) and Hodgkin's disease (HD). These antibody patterns denote the presence of active HHV-6 replication in patients with ABL and HD.

Characterization and localization of Plasmodium falciparum surface antigens on infected erythrocytes from west African patients.

The malaria-induced surface antigens on Plasmodium falciparum-infected erythrocytes from West African patients were characterized by agglutination of infected cells by human sera, surface immunofluorescence of live infected cells, inhibition of cytoadherence to C32 melanoma cells by human sera, immunoelectron microscopy (immunoEM), and immunoprecipitation. In a nonimmune individual, serum antibody reactivity to surface antigens of infected cells was acquired during convalescence, as tested by all five methods, and was generally parasite isolate-specific. By contrast, adult hyperimmune West African sera reacted with many isolates, including isolates from geographically distinct regions. A quantitative correlation was established between agglutination and surface immunofluorescence assay titers, and between surface immunofluorescence assay and immunoEM reactivity, suggesting that a single antigen or a set of coexpressed antigens is being detected. Surface iodination of infected cells identified trypsin-sensitive high M, antigens in the sodium dodecyl sulfate extract. All sera tested that agglutinated infected cells also immunoprecipitated these antigens. The same surface antigens were immunoprecipitated by the homologous convalescent serum as by adult sera. By immunoEM these antigens were localized exclusively at the knob-like protrusions of infected cells, where they may participate in adherence to vascular endothelium.

Patterns of chromosomal breakpoint locations in Burkitt's lymphoma: relevance to geography and Epstein-Barr virus association.

We have examined, by Southern blotting, the patterns of chromosomal breakpoint locations in 55 cases of Burkitt's lymphoma (BL) with respect to geography and Epstein-Barr virus (EBV) association. We have confirmed the association between chromosome 8 breakpoint and geography: 74% of endemic (eBL) but only 9% of sporadic BL (sBL) had breakpoints outside the HindIII fragment encompassing the c-myc gene (P2 less than .00001). Conversely, not only did 91% of sBL manifest a rearranged HindIII fragment, but at least 56% of these cases, in contrast to 17% of eBL cases, had a breakpoint within the first exon or intron of c-myc (P2 less than .004). Breakpoints outside the switch mu (S mu) region (ie, the HindIII fragment encompassing S mu) on chromosome 14 were twice as common overall (73%) as those within S mu (27%), but in the 15 tumors with S mu breakpoints, 13 (87%) had a rearranged c-myc gene. Breakpoints outside the HindIII fragment encompassing c-myc on chromosome 8 were predominantly associated with non-S mu breakpoints on chromosome 14 (85%) and this was the combination most frequently associated with eBL (65%; 6% of sBL, P2 less than .00001). In sBL, the most frequent breakpoint combination was a rearranged c-myc gene with a non-S mu breakpoint (63%; 13% of eBL). Twenty-eight percent of sBL and 13% of eBL had breakpoints both within c-myc and within S mu. EBV DNA was present in 19 of 20 tumors with breakpoints outside c-myc, in none of 7 with a breakpoint in the immediate 5' region of c-myc, in 4 of 5 tumors with breakpoints in the first exon, and in 7 of 12 tumors with breakpoints in the first intron. These data suggest that the pathogeneses of eBL and sBL differ with regard to the mechanism of c-myc deregulation, and probably also with regard to the state of differentiation of the target cell for malignant transformation. We have formulated a testable hypothesis regarding the potential role of EBV in pathogenesis: that it is required to contribute to the deregulation of c-myc in the presence of some, but not all, types of c-myc damage arising from the chromosomal translocations.

Epstein-Barr virus infection precedes clonal expansion in Burkitt's and acquired immunodeficiency syndrome-associated lymphoma.

The Epstein-Barr virus (EBV) is associated with distinct forms of human lymphoid malignancies, including the endemic (eBL) and sporadic forms of Burkitt's lymphoma (sBL) and acquired immunodeficiency syndrome-associated non-Hodgkin lymphoma (AIDS-NHL). However, whether EBV has a pathogenetic role in these tumors or is a passenger virus has not been conclusively demonstrated. One element to distinguish between these two possibilities is to determine whether EBV infection has preceded and, thus, possibly contributed to clonal expansion, or whether infection has occurred after clonal expansion and thus is unlikely to contribute to pathogenesis. Toward this end we analyzed the structure of the heterogeneous genomic termini of EBV as markers of clonal infection in a panel of eBL (11 cases), sBL (9 cases), and AIDS-NHL (10 cases) biopsies. We show that EBV termini are uniformly clonal in sBL, eBL, and AIDS-NHL, strongly suggesting that EBV infection has preceded and, thus, most likely contributed to clonal expansion in these malignancies.

Factors that could influence the spread of AIDS in Ghana, West Africa: knowledge of AIDS, sexual behavior, prostitution, and traditional medical practices.

Ghana is a West African nation in the early stages of the human immunodeficiency virus (HIV) epidemic. In a series of surveys done between 1987 and 1989, we examined factors related to the spread of HIV infection, including knowledge about the acquired immune deficiency syndrome (AIDS), sexual habits, use of prostitutes, traditional healer practices, and skin-piercing customs. Although a polygamous society, three-fourths of married men had only one wife. The number of sexual partners at any one time was generally low. However, the divorce rate was more than 29% and 55% of married men had current sexual partners in addition to their wives. Knowledge about AIDS was widespread, yet 4% of men interviewed had had a sexual encounter with a prostitute within the last month. Use of condoms was very limited and 66% of customers of high-class prostitutes refused to use a condom even after a request to do so by the prostitute. Skin piercing, including scarification, was done by an unsterile instrument by 39% of 74 rural traditional healers, many of whom had more than one patient per day. To combat the spread of AIDS, Ghanaians will have to apply their knowledge of AIDS risk factors to their actual behavior. Many of the social customs are products of poverty and its ensuing social consequences. Funds are needed for specific AIDS prevention programs as well as improved education and health care throughout the country.

Specific transfer factor with activity against Epstein-Barr virus reduces late relapse in endemic Burkitt's lymphoma.

Twenty-seven children with abdominal Burkitt's lymphoma (stage III), who had achieved complete remission, were entered into a prospective controlled trial of adjunct treatment with Epstein-Barr virus (EBV)-specific transfer factor (TF). Two patients treated with TF and 2 controls relapsed early (less than or equal to 12 weeks). Two out of 12 TF-treated patients and 5 out of 11 controls subsequently suffered relapses. Time to first late relapse was longer among TF-treated patients (p = 0.08), and no late relapse occurred while a patient was receiving TF treatment. Thus it seems that specific TF might be useful in the management of endemic Burkitt's lymphoma and also in the treatment of other virus-associated cancers and diseases.

Genes for Plasmodium falciparum surface antigens cloned by expression in COS cells.

Two genes encoding membrane antigens of Plasmodium falciparum were isolated by transient expression in mammalian cells and selection with human immune sera from African adults exposed to P. falciparum malaria. COS-7 cells were transfected with a plasmid expression library constructed from P. falciparum genomic DNA, and cells expressing reactive malaria antigens on their surface were enriched by adherence to antibody-coated dishes. One of the genes isolated is distinctive in that it does not contain repeat sequences typical of many malarial genes cloned by immunoscreening of bacterial expression libraries. The second gene apparently encodes a polymorphic version of the P. falciparum merozoite surface antigen Ag513, since the two sequences are identical in the 5' and 3' coding regions but diverge completely in the center. The COS-7 expression system provides an alternate means for cloning genes encoding malarial membrane antigens by using those antibodies in complex immune sera that bind membrane-associated, nondenatured molecules.