[Show abstract][Hide abstract] ABSTRACT: Background:
Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored.
In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS) loci flanking the Pvmdr1 gene.
We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, São Tomé and Ecuador. We measured and diversity in four microsatellite (MS) markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles.
SNP polymorphism in the Pvmdr1 gene was largely confined to codons T958M, Y976F and F1076L. Only 2.4% of samples were wildtype at all three codons (TYF, n = 5), 13.3% (n = 28) of the samples were single mutant MYF, 63.0% of samples (n = 133) were double mutant MYL, and 21.3% (n = 45) were triple mutant MFL. Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. Significant linkage disequilibrium (LD) between Pvmdr1 and MS alleles was found in populations sampled in Ecuador, Nepal and Sri Lanka, while significant LD between Pvmdr1 and the combined 4 MS locus haplotype was only seen in Ecuador and Sri Lanka. When combining the 5 loci, high level diversity, measured as expected heterozygosity (He), was seen in the complete sample set (He = 0.99), while He estimates for individual loci ranged from 0.00-0.93. Although Pvmdr1 haplotypes were not consistently associated with specific flanking MS alleles, there was significant differentiation between geographic sites which could indicate directional selection through local drug pressure.
Our observations suggest that Pvmdr1 mutations emerged independently on multiple occasions even within the same population. In Sri Lanka population analysis at multiple sites showed evidence of local selection and geographical dispersal of Pvmdr1 mutations between sites.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The association between diabetes mellitus (DM) and tuberculosis (TB) has been established on the basis of cross-sectional studies; however, only a few longitudinal studies have been conducted, with inconsistent results.OBJECTIVE: To study the effect of ethnicity and the presence and duration of DM on the risk of incident TB based on 15 years of follow-up of the entire Danish population.DESIGN AND METHODS: Using Poisson regression analysis, we estimated TB incidence in individuals with DM vs. those without DM by linking nationwide DM and TB registers to the National Civil Register at case level.RESULTS: The TB rate ratio was 1.9 in individuals with DM compared to non-DM individuals, regardless of country of birth, with the exception of African-born individuals (rate ratio 0.5). The risk decreased drastically within the first 2 years after the diagnosis of DM; no association was found with longer durations of DM. The risk also decreased the later the year of DM diagnosis.CONCLUSIONS: The study confirmed DM as a risk factor for TB, except in the case of African-born individuals. Other non-DM risk factors for TB could act as effect-modifiers on the DM-TB association. Implementing earlier DM diagnosis and improving metabolic control may reduce the risk of DM-related TB.
Behaviour and Information Technology 10/2015; 19(10). DOI:10.5588/ijtld.14.0932 · 0.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Few studies have examined the health consequences of living in a household with a person who has been diagnosed with type 2 diabetes (T2D). We assessed the association of sharing a household with a person with diagnosed T2D and risk factors for cardio-metabolic diseases in Uganda, a low-income country.
Ninety households with 437 residents in southwestern Uganda were studied from December 2012 through March 2013. Forty-five of the households had a member with diagnosed T2D (hereafter “diabetic household”), and 45 households had no member with diagnosed T2D (hereafter “nondiabetic household”). We compared glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), hypertension, anthropometry, aerobic capacity, physical activity, nutrition, smoking, and diabetes-related knowledge of people without diagnosed T2D living in diabetic and nondiabetic households.
People living in diabetic households had a significantly higher level of diabetes-related knowledge, lower levels of FPG (5.6 mmol/L vs 6.0 mmol/L), and fewer smoked (1.3% vs 12.9%) than residents of nondiabetic households. HbA1c was significantly lower in people aged 30 years or younger (5.2% vs 5.4%) and in males (5.2% vs 5.4%) living in diabetic households compared to residents of nondiabetic households. No differences were found between the 2 types of households in overweight and obesity, upper-arm fat area, intake of staple foods or cooking oil, or physical activity.
Sharing a household with a person with T2D may have unexpected benefits on the risk factor profile for cardio-metabolic diseases, probably because of improved health behaviors and a closer connection with the health care system. Thus, future studies should consider the household for interventions targeting primary and secondary prevention of T2D.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Risk factors for breast milk transmission of HIV-1 from mother to child include high plasma and breast milk viral load, low maternal CD4 count and breast pathology such as mastitis.
To determine the impact of nevirapine and subclinical mastitis on HIV-1 RNA in maternal plasma and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine).
Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant.
HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median (interquartile range, IQR) of 1.5 μg/mL (0.75-2.20 μg/mL) and 1.04 μg/mL (0.39-1.71 μg/mL), respectively (P < 0.001). At 1 week postpartum, 93% and 98% of the women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 μg/mL (0.13-0.39 μg/mL) and 0.22 μg/mL (0.13-0.34 μg/mL), respectively. Maternal plasma and breast milk HIV-1 RNA correlated at all visits (R = 0.48, R = 0.7, R = 0.59; all P = 0.01). Subclinical mastitis was detected in 67% of the women at some time during 6 weeks, and in 38% of the breast milk samples. Breast milk samples with subclinical mastitis had significantly higher HIV-1 RNA at 1, 4 and 6 weeks (all P < 0.05).
After short-course antiretroviral prophylaxis, nevirapine was detectable in most infant cord blood samples and the concentration in maternal plasma and breast milk was high through week 1 accompanied by suppressed HIV-1 RNA in plasma and breast milk.
PLoS ONE 03/2015; 10(3):e0121111. DOI:10.1371/journal.pone.0121111 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Physical inactivity and low birth weight (LBW) may lead to an increased risk for developing type 2 diabetes. The extent to which LBW individuals may benefit from physical exercise training when compared with those with normal birth weight (NBW) controls is uncertain. We assessed the impact of an outdoor exercise intervention on body composition, insulin secretion and action in young men born with LBW and NBW in rural India. A total of 61 LBW and 56 NBW healthy young men were recruited into the study. The individuals were instructed to perform outdoor bicycle exercise training for 45 min every day. Fasting blood samples, intravenous glucose tolerance tests and bioimpedance body composition assessment were carried out. Physical activity was measured using combined accelerometry and heart rate monitoring during the first and the last week of the intervention. Following the exercise intervention, the LBW group displayed an increase in physical fitness [55.0 ml (O2)/kg min (52.0-58.0)-57.5 ml (O2)/kg min (54.4-60.5)] level and total fat-free mass [10.9% (8.0-13.4)-11.4% (8.0-14.6)], as well as a corresponding decline in the ratio of total fat mass/fat-free mass. In contrast, an increase in total fat percentage as well as total fat mass was observed in the NBW group. After intervention, fasting plasma insulin levels, homoeostasis model assessments (HOMA) of insulin resistance (HOMA-IR) and insulin secretion (HOMA-IS), improved to the same extent in both the groups. In summary, young men born with LBW in rural India benefit metabolically from exercise training to an extent comparable with NBW controls.
Journal of Developmental Origins of Health and Disease 12/2014; 6(01):1-11. DOI:10.1017/S2040174414000609 · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Even though Plasmodium vivax has the widest worldwide distribution of the human malaria species and imposes a serious impact on global public health, the investigation of genetic diversity in this species has been limited in comparison to Plasmodium falciparum. Markers of genetic diversity are vital to the evaluation of drug and vaccine efficacy, tracking of P. vivax outbreaks, and assessing geographical differentiation between parasite populations.
The genetic diversity of eight P. vivax populations (n = 543) was investigated by using two microsatellites (MS), m1501 and m3502, chosen because of their seven and eight base-pair (bp) repeat lengths, respectively. These were compared with published data of the same loci from six other P. vivax populations.
In total, 1,440 P. vivax samples from 14 countries on three continents were compared. There was highest heterozygosity within Asian populations, where expected heterozygosity (He) was 0.92-0.98, and alleles with a high repeat number were more common. Pairwise F
ST revealed significant differentiation between most P. vivax populations, with the highest divergence found between Asian and South American populations, yet the majority of the diversity (~89%) was found to exist within rather than between populations.
The MS markers used were informative in both global and local P. vivax population comparisons and their seven and eight bp repeat length facilitated population comparison using data from independent studies. A complex spatial pattern of MS polymorphisms among global P. vivax populations was observed which has potential utility in future epidemiological studies of the P. vivax parasite.
[Show abstract][Hide abstract] ABSTRACT: Objectives
To investigate the diagnostic accuracy of random blood glucose (RBG) on good glycaemic control among patients with diabetes mellitus (DM) in a rural African setting.Methods
Cross-sectional study at St. Francis' Hospital in eastern Zambia. RBG and HbA1c were measured during one clinical review only. Other information obtained was age, sex, body mass index, waist circumference, blood pressure, urine albumin–creatinine ratio, duration since diagnosis and medication.ResultsOne hundred and one patients with DM (type 1 DM = 23, type 2 DM = 78) were included. Spearman's rank correlation coefficient revealed a significant correlation between RBG and HbA1c among the patients with type 2 DM (r = 0.73, P < 0.001) but not patients with type 1 DM (r = 0.17, P = 0.44). Furthermore, in a multivariate linear regression model (R2 = 0.71) RBG (per mmol/l increment) (B = 0.28, 95% CI:0.24–0.32, P < 0.001) was significantly associated with HbA1c among the patients with type 2 DM. Based on ROC analysis (AUC = 0.80, SE = 0.05), RBG ≤7.5 mmol/l was determined as the optimal cut-off value for good glycaemic control (HbA1c <7.0% [53 mmol/mol]) among patients with type 2 DM (sensitivity = 76.7%; specificity = 70.8%; positive predictive value = 62.2%; negative predictive value = 82.9%).Conclusions
Random blood glucose could possibly be used to assess glycaemic control among patients with type 2 DM in rural settings of sub-Saharan Africa.
Tropical Medicine & International Health 10/2014; 19(12):1515-9. DOI:10.1111/tmi.12391 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether there is an association between diameter of bacille Calmette-Guérin (BCG) scars and effect of purified protein derivative (PPD) reaction and to determine whether vitamin A (VA) combined vitamin D (VD) supplementation influences the immune response to BCG revaccinated in Chinese infants.
A cross-section and 3-month community-randomised trial was conducted. A total of 5 629 infants at 3, 6 and 12 months of age in Junan County of China were examined for BCG scar formation. Then, 597 revaccinated infants were randomly assigned to supplementation (n=307) and control (n=290) groups. The supplementation group were daily assigned to 1 500 IU VA and 500 IU VD for 3 months. Then all infants were subjected to skin test with PPD.
The diameter of BCG scars was positively correlated with diameter of skin indurations of PPD (r=0.17, P<0.05) in the 5 629 infants. The rate of positive response to PPD was higher in the supplementation group than in the control group (96.1% versus 89.7%, P<0.05, prevalence ratio 1.07, 95% CI 1.02-1.12). The prevalence ratio of PPD response for the supplementation group compared with that for the control group was 1.07 (95% CI 1.01-1.13) for the males and 1.08 (95% CI 1.00-1.17) for the females. For the supplementation group, the males got larger tuberculin induration than the females [(0.73±0.21) cm versus (0.67±0.20) cm, P<0.05) after intervention.
The diameter of BCG scars was effectively correlated with PPD response, which indicates BCG scar formation may be an useful tool to evaluate the effect of tuberculosis prevention. VA combined VD supplementation may play an immuno-regulatory role in BCG revaccination. This may contribute to the prevention of childhood tuberculosis.
Asian Pacific Journal of Tropical Medicine 02/2014; 7(2):130-5. DOI:10.1016/S1995-7645(14)60008-0 · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gestational diabetes mellitus (GDM) - a transitory form of diabetes first recognised during pregnancy complicates between < 1% and 28% of all pregnancies. GDM has important short and long-term health consequences for both the mother and her offspring. To prevent adverse pregnancy outcomes and to prevent or delay, future onset of type 2 diabetes in mother and offspring, timely detection, optimum treatment, and preventive postpartum care and follow-up is necessary. However the area remains grossly under prioritised.
To investigate determinants and barriers to GDM care from initial screening and diagnosis, to prenatal treatment and postpartum follow-up, a PubMed database search to identify quantitative and qualitative studies on the subject was done in September 2012. Fifty-eight relevant studies were reviewed.
Adherence to prevailing GDM screening guidelines and compliance to screening tests seems sub-optimal at best and arbitrary at worst, with no clear or consistent correlation to health provider, health system or client characteristics. Studies indicate that most women express commitment and motivation for behaviour change to protect the health of their unborn baby, but compliance to recommended treatment and advice is fraught with challenges, and precious little is known about health system or societal factors that hinder compliance and what can be done to improve it. A number of barriers related to health care provider/system and client characteristics have been identified by qualitative studies. Immediately following a GDM pregnancy many women, when properly informed desire and intend to maintain healthy lifestyles to prevent future diabetes, but find the effort challenging. Adherence to recommended postpartum screening and continued lifestyle modifications seems even lower. Here too, health care provider, health system and client related determinants and barriers were identified. Studies reveal that sense of self-efficacy and social support are key determinants.
The paper identifies and discusses determinants and barriers for GDM care, fully recognising that these are highly dependent on the context.
[Show abstract][Hide abstract] ABSTRACT: A study of health facility (HF) data on women receiving sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria during pregnancy (IPTp) was carried out at antenatal care (ANC) clinics in Mkuranga and Mufindi districts.
A review of health management information system (HMIS) registers, interviews with health-care workers (HWs) and district and national level malaria control program managers corroborated by inter-temporal assessment through observations at HF levels. Statistical data were analyzed in Excel and interpreted in triangulation with qualitative data from interviews and observations.
Data indicated that IPTp doses administered to women were inadequate and partly inconsistent. HMIS registers lacked space for IPT records, forcing HWs to manipulate their record-keeping. The proportion/number of IPTp recipients in related to the supply of SP for free delivery, to women's attendance behaviours, showed showed variation by quarter and year of reporting.
It is impossible to achieve rational health service planning when the HMIS is weak. Whilst it is acknowledged that the HMIS is already overloaded, concerted measures are urgently needed to accommodate data on new interventions and other vertical programs if malaria programs are to achieve their goals.
Reproductive Health 01/2014; 11(1):6. DOI:10.1186/1742-4755-11-6 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Community case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs).
Sixty-one interviews and six focus group discussions were conducted nested in a cluster-randomized trial assessing the impact of combining HMM and SMC in a rural area of Senegal. Participants consisted of: (i) members of village associations, (ii) members of families who had access to the interventions as well as members of families who did not access the interventions, (iii) CHWs, and (iv) community leaders, e g, religious guides and village chiefs.
The interventions were acceptable to the local population and perceived as good strategy to make health care services available to community members and thus, to reduce the delays in access to anti-malarial treatment as well as expenses related to patients' transfer to the health post. The use of malaria rapid diagnostic test (RDT) contributed to improving CHWs diagnostic capacity as well as malaria treatment practices. Study participants notified RDT and drugs stock-out as the major risk for sustainability of the intervention at community level.
Combining CCMm and SMC is a well accepted, community-based approach that can contribute to control malaria in areas where malaria transmission is seasonal.
[Show abstract][Hide abstract] ABSTRACT: Plasmodium vivax malaria was common in Greece until the 1950s with epidemics involving thousands of cases every year. Greece was declared free of malaria by the World Health Organization in 1974. From 1974 to 2010, an average of 39 cases per year were reported, which were mainly imported. However, in 2009 and 2010 six and one autochthonous cases were reported culminating with a total of 40 autochthonous cases reported in 2011, of which 34 originated from a single region: Laconia of Southern Peloponnese. In this study the genotypic complexity of the P. vivax infections from the outbreak in Greece during 2011 is described, to elucidate the possible origin and spread of the disease.
Three polymorphic markers of P. vivax were used; Pvmsp-3alpha and the microsatellites m1501 and m3502 on P. vivax isolates sampled from individuals diagnosed in Greece. Thirty-nine isolates were available for this study (20 autochthonous and 19 imported), mostly from Evrotas municipality in Laconia region, in southern Greece, (n = 29), with the remaining representing sporadic cases originating from other areas of Greece.
Genotyping the Evrotas samples revealed seven different haplotypes where the majority of the P. vivax infections expressed two particular Pvmsp-3alpha-m1501-m3502 haplotypes, A10-128-151 (n = 14) and A10-121-142 (n = 7). These haplotypes appeared throughout the period in autochthonous and imported cases, indicating continuous transmission. In contrast, the P. vivax autochthonous cases from other parts of Greece were largely comprised of unique haplotypes, indicating limited transmission in these other areas.
The results indicate that several P. vivax strains were imported into various areas of Greece in 2011, thereby increasing the risk of re-introduction of malaria. In the region of Evrotas ongoing transmission occurred exemplifying that further control measures are urgently needed in this region of southern Europe. In circumstances where medical or travel history is scarce, methods of molecular epidemiology may prove highly useful for the correct classification of the cases.
[Show abstract][Hide abstract] ABSTRACT: Worldwide, rotavirus infections cause approximately 453 000 child deaths annually. Two licensed vaccines could be life- and cost-saving in low-income countries where the disease burden is highest. The aim of our study was to estimate the total cost of implementing the rotavirus vaccine in the national immunisation programme of a low-income country. Furthermore, the aim was to examine the relative contribution of different components to the total cost.
Following the World Health Organization guidelines, we estimated the resource use and costs associated with rotavirus vaccine implementation, using Malawi as a case. The cost analysis was undertaken from a governmental perspective. All costs were calculated for a 5-years period (2012-2016) and discounted at 5%. The value of key input parameters was varied in a sensitivity analysis.
The total cost of rotavirus vaccine implementation in Malawi amounted to US$ 18.5 million over a 5-years period. This translated into US$ 5.8 per child in the birth cohort. With GAVI Alliance financial support, the total cost was reduced to US$ 1.4 per child in the birth cohort. Approximately 83% of the total cost was attributed to vaccine purchase, while 17% was attributed to system costs, with personnel, transportation and cold chain as the main cost components.
The total cost of rotavirus vaccine implementation in Malawi is high compared with the governmental health budget of US$ 26 per capita per year. This highlights the need for new financing opportunities for low-income countries to facilitate vaccine implementation and ensure sustainable financing.
Tropical Medicine & International Health 12/2013; 19(2). DOI:10.1111/tmi.12233 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Home-based management of malaria (HMM) may improve access to diagnostic testing and treatment with artemisinin combination therapy (ACT). In the Sahel region, seasonal malaria chemoprevention (SMC) is now recommended for the prevention of malaria in children. It is likely that combinations of antimalarial interventions can reduce the malaria burden. This study assessed the feasibility, effectiveness and safety of combining SMC and HMM delivered by community health workers (CHWs).
A cluster-randomised trial was carried out during two transmission seasons in eight villages located in the south-eastern part of Senegal. Intervention communities received HMM+SMC while control communities received HMM. Primary end point was the incidence of malaria attacks during the follow up period. Secondary end points included: malaria diagnostic accuracy; access to ACT treatment; SMC coverage; safety and drug tolerability.
The adjusted rate ratio for incidence of malaria attacks in intervention and control communities was 0.15, indicating a protective effect of HMM+SMC of 85% (95% CI: 39.9-96.3%, p=0.01). Access to ACT treatment was 96.4% while SMC coverage represented 97.3% (95% CI: 91.3-100%) in 2010, and 88.8% (95% CI: 84.2-93.6%) in 2011. No serious adverse events were recorded.
It seems feasible and safe to combine SMC with HMM intervention, while achieving high coverage and effectiveness of both SMC and HMM.
Transactions of the Royal Society of Tropical Medicine and Hygiene 12/2013; 108(1). DOI:10.1093/trstmh/trt103 · 1.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.