74 research outputs found
Human leukocyte antigen (HLA) class I and class II allelic diversity in the Sudanese population and their association with HIV/AIDS disease susceptibility and progression
No full textThe study was carried out in Khartoum Teaching Hospital, Khartoum; in the period of August
2003-April 2004. The objectives of the present study were to determine the distribution of the
host polymorphic genes; HLA class I and class II alleles and haplotypes and chemokine
receptor CCR5, in order to study their impact on the susceptibility to HIV-1 infection and to
evaluate the contribution of the genetic background to the variability of disease progression.
This study is the first report on the association of HLA class I and class II alleles distribution
with HIV in Sudanese population, as well as on HLA distribution in the population at highresolution
molecular typing level. The Sudanese information is important, because it
represents a gap between the understanding of African and Eurasian HLA alleles and
haplotypes frequencies.
The present study showed that A*3101, Cw*0202, Cw*0304. DRB1*0301, and DQB1*0604
alleles were significantly associated with protection from HIV-1 infection, whereas A*2902,
Cw*0705 alleles were associated with susceptibility to HIV-1 infection. On the other hand
A*2601, A*2902, and DRB1*1102 were associated with rapid progression, while Cw*1203,
DRB1*1503, and DQB1*0602 were associated with slow progression.
At the population level, the study showed that the Sudanese have a unique HLA genes
distribution pattern. Several HLA alleles, A*0202, A*3004; B*1503, Cw*0804, DRB1*0804
which were African-specific alleles were found in similar frequencies in the Sudanese
population, as well as some other alleles which were highly distributed in Arabs, North
African, and Caucasians population such as DQB1*0201, DQB1*0301, DPB1*0401, and
DPB1*0402. This may reflect a high degree of admixture of the study population.
This study has identified several additional alleles and haplotypes, not previously reported or
tested in other populations, so far, namely Cw*0418, Cw*0214, Cw*0410104, and
Cw*070105, and haplotypes A*0201-B*3910, A*3004-B*4101, A*3201-B*4101, B*4101-
Cw*1203, A*3004-Cw*0401, A*3002-Cw*0701, A*2402-Cw*1203, DRB1*0301-
DQB1*0301, DRB1*0804-DQB1*0201, DRB1*1302-DQB1*0301, and DRB1*0804-
DPB1*0201 . They might be considered as markers for this population.
Our results clearly demonstrated that common and unique HLA alleles and haplotypes
contributed to genetic susceptibility and protection from HIV- infection. However, the present
data have given information supporting the role of HLA as genetic markers predicting HIV
disease progression. Furthermore, our results show that the presence of common alleles and
haplotypes in our population is consistent with historical data showing that the Sudanese
population is an admixture of various ethnicities, and that they have a unique HLA genes
pattern.
Regarding CCR5, the CCR5-Δ32 allele frequency in Sudanese was found to be similar to that
reported in African populations (0.6%). One of those who carried the mutant allele was HIV-1
positive; which suggest that the CCR5-Δ32 receptor does not play an important role in HIV
infection in Sudanese population
Molecular Characterization of Severe Plasmodium falciparum Malaria Parasitemia and Antimalarial Drug-resistance in Eastern Sudan
No full textA hospital-based study was carried out in Gedarif town, an area of markedly unstable malaria
transmission in eastern Sudan during the two malaria transmission seasons (2000-2002),.
Among the 2488 diagnosed malaria patients, 110 fulfilled the WHO (2000) criteria for severe
malaria (SM), and seven died of cerebral malaria (CM). The predominant complication was
severe malarial anemia (SMA, 45.45%), followed by convulsions associated malaria (CAM,
20.9%), cerebral malaria (16.4%) and hypotension (HTN, 11.8%).
DNA was extracted from 616 parasites obtained from 231 donors with asymptomatic
submicroscopic malaria (ASUM), uncomplicated malaria (UM) and SM. The MSP2 locus
was exploited for determination of parasite genotype. 51 parasite genotypes were detected.
There was no correlation between the number of infectious clones and initial parasite count or
patient age. In all infections, the mean clone number (MCN) was 1.5 clone/infection, and it
was comparable between SM and UM. However detailed analysis revealed that; individuals
with ASUM had significantly lower MCN compared with UM, SMA, and non-fatal CM. The
frequency of IC1 and FC27 allele families was comparable between SM and UM and the
distribution of the individual allele sizes was correlated. Further analysis showed that, 1.
FC27 was associated with the mildest form of malaria and was not recognized in fatal CM, 2.
Faster clearance of IC1 genotype in the multi-clone infections after quinine treatment 3.
Multi-clone infections with different genotype families (IC1 and FC27) were far more
frequent than that with the same genotype family, suggesting stronger cross-immunity within
rather than between MSP2 gene families.
The diversity of infection (DOI) was estimated by using different molecular markers (pfcrt76,
pfmdr1 86, glurp and MSP2) separately and by considering them together to generate a multilocus
genetic profile for each isolate. pfcrt and pfmdr1, are not usually used for parasite
genotyping, here they revealed DOI of 0.043 and 0.064, respectively. However, when used in
combination with the most polymorphic markers (MSP2 and GLURP) they disclosed a
hidden diversity that would have not been detected. The DOI as estimated by MSP2 and
GLURP was, 0.553 and 0.435, respectively. However, combining all 4 molecular markers
(multi-locus genetic profile), had revealed a finger print pattern of diversity, DOI of 0.936,
which almost indicated that there were one unique strain for each patient, and that was
comparable between SM and UM (although for UM, GLURP was not analyzed). Not only,
the genetic make up of parasites were different, but clinical data suggest that the virulence
markers should also be extremely diverse.
Another hospital-based study was carried out in New Halfa town, where 120 individuals were
enrolled in the study, including febrile patients with and without microscopically detectable
parasitemia, and apparently healthy individuals. PCR for parasite detection and ELISA tests
for measuring serum antibody levels were carried out on all blood samples. A majority of the
febrile patients, who were parasite negative by microscopy, showed the presence of a P.
falciparum infection by PCR. The occurrence of P. falciparum infection with parasitemia
below the detection level of microscopy was recognized more often in patients with CM
symptoms than SMA, and in older rather than younger patients. Patients clinically suspected
to have cerebral malaria (CSCM) mostly had a single clone infection and a large proportion of
them acquired antibodies against MSP antigens. The therapeutic response to quinine
treatment was comparable between patients with CSCM and CM.
In a 28-days in-vivo study of pyrimethamine/sulfadoxine (SP) and SP plus chloroquine (CQ)
efficacy, 260 patients with uncomplicated P. falciparum malaria were enrolled in rural
Eastern Sudan. The results revealed a comparable treatment failure (TF) for SP alone
(32.99%) or with CQ (31.7%). Patients who achieved adequate clinical response (ACR), were
significantly older than patients who had TF. Regarding gametocytogenesis; a. the
microscopic gametocyte productivity was significantly higher in patients with TF when
compared to ACR. Thus, gametocytemia was more associated with younger age b.
gametocyte counts were comparable between TF and ACR groups of patients until Day7 of
follow up, thereafter, at D14, D21 and D28, gametocytes count was significantly higher in
patients with TF. However, the longevity of gametocytes in patients with TF and ACR were
comparable.
Parasite isolates from 168 patients (including all patients with TF) were genotyped at the
dhfr, dhps and pfcrt loci. The molecular image of the in-vivo phenotype, revealed the
following findings: the prevalence of dhfr mutations c51-I, c108-N, and double mutant
c51I/108N, were estimated to be 91.9%, 92.3% and 79.7%, respectively, while only one
isolate (0.6%) was found carrying c59R and no c164L mutation was recognized. The dhps
mutations; c437G, c540E and double mutant c437/c540 had a prevalence rate of 90.2%,
79.3% and 58.5%, respectively, while those of c436F and c581G were, 0.6% and 13%,
respectively. For pfcrt gene at c72-76, 92.26% were the mutant type CVIET, only 6.55%
were the wild type CVMNK and 2 patients harbored mixed infection. Based on the
multiplicity of mutation score (MOM) ranging from 1 to 5, the prevalence according to the
MOM score were; 0.97, 0.931, 0.866, 0.719, 0.121, respectively
Prevalence and risk factors for <it>Plasmodium falciparum </it>malaria in pregnant women of eastern Sudan
No full textAbstract Background Pregnant women are more susceptible to malaria, which is associated with serious adverse effects on pregnancy. The presentation of malaria during pregnancy varies according to the level of transmission in the area. Our study aimed to demonstrate the prevalence and risk factors for malaria (age, parity and gestational age) among pregnant women of eastern Sudan, which is characterized by unstable malaria transmission. Methods The prevalence and possible risk factors for Plasmodium falciparum malaria were investigated in 744 pregnant Sudanese women attending the antenatal clinic of New Haifa Teaching Hospital, eastern Sudan, during October 2003-April 2004. Results A total 102 (13.7%) had P. falciparum malaria, 18(17.6%) of these were severe cases (jaundice and severe anaemia). Univariate and multivariate analysis showed that, age and parity were not associated with malaria. Women who attended the antenatal clinic in the third trimester were at highest risk for malaria (OR = 1.58, 95% CI = 1.02–2.4; P Women with malaria had significantly lower mean haemoglobin (9.4 g/dl, 95% CI 9.1–9.7 versus 10.7, CI 10.6–10.8, P Conclusion The results suggest that P. falciparum malaria is common in pregnant women attending antenatal care and that anaemia is an important complication. Preventive measures (chemoprophylaxis and insecticide-treated bednets) may be beneficial in this area for all women irrespective of age or parity.</p
Global Call to Action: maximize the public health impact of intermittent preventive treatment of malaria in pregnancy in sub-Saharan Africa.
No full textIntermittent preventive treatment of malaria in pregnancy is a highly cost-effective intervention which significantly improves maternal and birth outcomes among mothers and their newborns who live in areas of moderate to high malaria transmission. However, coverage in sub-Saharan Africa remains unacceptably low, calling for urgent action to increase uptake dramatically and maximize its public health impact. The 'Global Call to Action' outlines priority actions that will pave the way to success in achieving national and international coverage targets. Immediate action is needed from national health institutions in malaria-endemic countries, the donor community, the research community, members of the pharmaceutical industry and private sector, along with technical partners at the global and local levels, to protect pregnant women and their babies from the preventable, adverse effects of malaria in pregnancy
The safety of artemisinins during pregnancy: a pressing question.
No full textBACKGROUND: An increasing number of countries in sub-Saharan Africa are changing to artemisinins combination therapy (ACT) as first or second line treatment for malaria. There is an urgent need to assess the safety of these drugs in pregnant women who may be inadvertently exposed to or actively treated with ACTs. OBJECTIVES: To examine existing published evidence on the relationship between artemisinin compounds and adverse pregnancy outcomes and consider the published evidence with regard to the safety of these compounds when administered during pregnancy. METHODS: Studies on ACT use in pregnancy were identified via searches of MEDLINE, EMBASE, Cochrane and Current Contents databases. Data on study characteristics, maternal adverse events, pregnancy outcomes and infant follow up were extracted. RESULTS: Fourteen relevant studies (nine descriptive/case reports and five controlled trials) were identified. Numbers of participants in these studies ranged from six to 461. Overall there were reports on 945 women exposed to an artemisinin during pregnancy, 123 in the 1st trimester and 822 in 2nd or 3rd trimesters. The primary end points for these studies were drug efficacy and parasite clearance. Secondary endpoints were birth outcomes including low birth weight, pre-term birth, pregnancy loss, congenital anomalies and developmental milestones. While none of the studies found evidence for an association between the use of artemisinin compounds and increased risk of adverse pregnancy outcomes, none were of sufficient size to detect small differences in event rates that could be of public health importance. Heterogeneity between studies in the artemisinin and comparator drugs used, and in definitions of adverse pregnancy outcomes, limited any pooled analysis. CONCLUSION: The limited data available suggest that artemisinins are effective and unlikely to be cause of foetal loss or abnormalities, when used in late pregnancy. However, none of these studies had adequate power to rule out rare serious adverse events, even in 2nd and 3rd trimesters and there is not enough evidence to effectively assess the risk-benefit profile of artemisinin compounds for pregnant women particularly for 1st trimester exposure. Methodologically rigorous, larger studies and post-marketing pharmacovigilance are urgently required
Systematic review: Impact of meningococcal vaccination on pharyngeal carriage of meningococci.
No full textOBJECTIVE: To investigate the effect of meningococcal vaccines on pharyngeal carriage of meningococci. METHODS: Systematic review. MEDLINE and EMBASE were searched for relevant studies. Controlled trials and observational studies which used comparison groups or compared carriage rates before and after vaccination were included in the review. RESULTS: Twenty-nine studies satisfied the inclusion criteria. Twenty-five studies reported the effect of a polysaccharide vaccine, one the effect of a serogroup C conjugate vaccine and three the impact of serogroup B outer-membrane vaccines on overall and/or serogroup-specific meningococcal carriage rates. Ten studies of meningococcal polysaccharide vaccines found reduced serogroup-specific carriage; seven of these focussed on high-risk groups and had a short follow-up period. Only one of five studies of civilian populations in Africa showed a significantly reduced carriage. Many studies had methodological shortcomings. The one study which assessed the effect of a meningococcal conjugate vaccine on carriage showed a significant impact. Three studies of serogroup B outer-membrane protein vaccines showed no effect on carriage. CONCLUSIONS: A few well-designed trials of the impact of meningococcal vaccines on carriage have been undertaken. Such studies should be an essential component of the evaluation of new meningococcal vaccines, particularly those introduced to control epidemic meningococcal disease in Africa
Leptin, insulin like growth factor-I levels and histology-diagnosed placental malaria in an area characterized by unstable malaria transmission in central Sudan
No full textBackground: There are few published data on the association between leptin, insulin like growth factor-1 (IGF-1) and malaria during pregnancy. This study aimed to investigate maternal and umbilical cord leptin and IGF-1 levels and malaria during pregnancy, and their association - if any - with birth weight.Methods: A cross-sectional study was conducted at Medani, Sudan. Medical and obstetrics history was gathered from each parturient woman (n=175) and malaria was investigated by blood film and placental histology. Maternal and umbilical cord leptin and IGF-1 levels were measured using ELISA.Results: Upon histological examination, 48 women were infected with placental malaria, and 127 were found free from the disease. Out of the 48, 2 of the patients showed signs of active infection, 3 of chronic infection and 43 of previous infection. Placental malaria and preterm delivery were associated with low birth weight (< 2500 g). Younger mothers and primigravidae had a higher risk for placental malaria infection. There was no significant difference in maternal and umbilical cord leptin and IGF-1 levels between women infected with placental malaria and those free from the disease.Conclusions: The current study showed that low birth weight was significantly associated with placental malaria. Young mothers and primigravidae had a higher risk to develop the infection. There was no significant difference in the levels of maternal and umbilical cord leptin and IGF-1 levels between women infected with placental malaria and those free from the disease. Both the levels of maternal and cord leptin and IGF-1were found not to be associated with birth weight.Abbreviations: IGF-1: Insulin like growth factor-1; LBW: Low birth weight; ELISA: Enzyme-linked immunosorbent assay; PM: Placental malaria.</ns4:p
Malaria and pre-eclampsia in an area with unstable malaria transmission in Central Sudan
No full textAbstract Background Placental malaria and pre-eclampsia occur frequently in women in tropics and are leading causes of maternal and perinatal morbidities and mortality. Few data exist concerning the interaction between placental malaria and pre-eclampsia. Methods A case control study was conducted in Medani Hospital, which locates in an area of unstable malaria transmission in Central Sudan. Case (N = 143) were women with pre-eclampsia, which was defined as systolic blood presure≥140 mm Hg or diastolic blood pressure ≥ 90 mm Hg and proteinuria. Controls were parturient women (N = 143) without any blood pressure values > 139/89 mm Hg or proteinuria. Obstetrical and medical characteristics were gathered from both groups through structured questionnaires. Placental histopathology examinations for malaria were performed. Results Twenty-eight (19.6%) vs. 16 (11.2%); P = 0.04 of the cases vs. controls, had placental malaria infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae showed acute, chronic and past infection on histopathology examination in the two groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no infection, P = 0.04. In multivariate analysis, while there were no associations between age, parity, educational level, lack of antenatal care, blood groups and body mass index and pre-eclampsia; family history of hypertension and placental malaria (OR = 2.3, 95% CI = 1.0-5.2; P = 0.04) were significantly associated with pre-eclampsia. Conclusion Placental malaria was associated with pre-eclampsia. Further research is needed.</p
Coagulation profile of Sudanese children with homozygous sickle cell disease and the effect of treatment with omega-3 fatty acid on the coagulation parameters
No full textBackground:
It has been reported that patients with SCD do have an abnormal coagulation profile. Coagulopathy is thought to be one of the key factors that contribute to the vaso-occlusive crisis that characterises sickle cell disease (SCD). In this study, we investigated whether Sudanese sickle cell patients have an abnormal coagulation profile. In addition, the effect of treatment with either omega-3 fatty acids or hydroxyurea on coagulation profile was assessed.
Methods:
Homozygous SCD patients untreated (n = 52), omega-3 treated (n = 44), hydroxyurea (HU) treated (n = 8) and healthy (HbAA) controls (n = 52) matched for age (4–20 years), gender and socioeconomic status were enrolled. Patients on omega-3 fatty acids, according to age, received one to four capsules containing 277.8 mg DHA and 39.0 mg eicosapentnoic. Patients on Hydroxyurea were in on dosage more than 20 mg/kg/day. The steady state levels of the coagulation parameters and the effect of the treatments with either HU or omega-3 fatty acids on markers of coagulation were investigated.
Results:
Compared to the healthy controls, treated and untreated HbSS patients had lower hemoglobin, plasma Protein C, proteins S and higher white blood cell count (WBC), platelets count (PLTs) and plasma D-dimer levels,(p 0.05). HU treated group had a lower PLTs count compared to HbSS untreated group (p < 0.5). The prothrombin and activated partial thromboplastin times and international normalized ratio (INR) of untreated patients are significantly higher than n-3 treated, HU-treated patients and health controls, (p < 0.05). Patients treated with omega-3 had lowered D-dimer levels in comparison to HU-treated and untreated HbSS patients, (p < 0.001).
Conclusion:
This study provides evidence that Sudanese patients have abnormal coagulation profile and treatment with either HU or omega-3 fatty acids might partially ameliorate SCD-associated chronic coagulopathic state. Keywords: Sickle cell disease, Coagulation, Omega-3 fatty acids, D-dimer, Protein C, Protein
Severe anaemia is associated with a higher risk for preeclampsia and poor perinatal outcomes in Kassala hospital, eastern Sudan
No full textAbstract Background Anaemia during pregnancy is major health problem. There is conflicting literature regarding the association between anaemia and its severity and maternal and perinatal outcomes. Methods This is a retrospective case-control study conducted at Kassala hospital, eastern Sudan. Medical files of pregnant women with severe anaemia (haemoglobin (Hb) 11 g/dl, n = 303). Logistic regression analysis was performed separately for each of the outcome measures: preeclampsia, eclampsia, preterm birth, low birth weight (LBW) and stillbirth. Results There were 9578 deliveries at Kassala hospital, 4012 (41.8%) women had anaemia and 303 (3.2%) had severe anaemia. The corrected risk for preeclampsia increased only in severe anaemia (OR = 3.6, 95% CI: 1.4-9.1, P = 0.007). Compared with women with no anaemia, the risk of LBW was 2.5 times higher in women with mild/moderate anaemia (95% CI: 1.1-5.7), and 8.0 times higher in women with severe anaemia (95% CI: 3.8-16.0). The risk of preterm delivery increased significantly with the severity of anaemia (OR = 3.2 for women with mild/moderate anaemia and OR = 6.6 for women with severe anaemia, compared with women with no anaemia). The corrected risk for stillbirth increased only in severe anaemia (OR = 4.3, 95% CI: 1.9-9.1, P Conclusions The greater the severity of the anaemia during pregnancy, the greater the risk of preeclampsia, preterm delivery, LBW and stillbirth. Preventive measures should be undertaken to decrease the prevalence of anaemia in pregnancy.</p
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