CCN1 mutation is associated with atrial septal defect.

The genetic basis of congenital heart disease remains unknown in most of the cases. Recently, a novel mouse model shed new light on the role of CCN1/CYR61, a matricellular regulatory factor, in cardiac morphogenesis. In a candidate gene approach, we analyzed a cohort of 143 patients with atrial septal defects (ASD) by sequencing the coding exons of CCN1. In addition to three frequent polymorphisms, we identified an extremely rare novel heterozygous missense mutation (c.139C > T; p.R47W) in one patient with severe ASD. The mutation leads to an exchange of residues with quite different properties in a highly conserved position of the N-terminal insulin-like growth factor binding protein module. Further bioinformatic analysis, exclusion of known ASD disease genes as well as the exclusion of the mutation in a very high number of ethnically matched controls (more than 1,000 individuals) and in public genetic databases, indicates that the p.R47W variant is a probable disease-associated mutation. The report about ASD in mice in heterozygous Ccn 1 +/- animals strongly supports this notion. Our study is the first to suggest a relationship between a probable CCN1 mutation and ASD. Our purpose here was to draw attention to CCN1, a gene that we believe may be important for genetic analysis in patients with congenital heart disease.

The amount and value of work time of community medicine distributors in community case management of malaria among children under five years in the Ejisu-Juaben District of Ghana.

BACKGROUND: The contribution of community medicine distributors (CMD) to prompt health service delivery in areas described as "hard-to-reach" is important but the value of their work time remains unknown and thus makes it difficult to design appropriate regular financial incentives to motivate them. This makes CMDs feel their efforts are not recognized. An attempt to estimate the value of 54 CMDs' work time involved in community case management of malaria (CCMm) in a rural district in Ghana is presented. METHODS: Time spent by CMDs on CCMm activities were recorded for a period of 12 months to determine the work-time value. Cost analysis was performed in Microsoft Excel with data from CMD records and at 2007 market price in Ghana. RESULTS: A CMD spent 4.8 hours, [95% CI: 3.9; 5.3] on all CCMm-related activities per day. The time value of CMD work ranged from GH¢ 2.04 (US$ 2.24) to GH¢ 4.1 [US$ 4.6] per week and GH¢ 19.2 - 86.4 (US$ 21.10-94.95) per month. The gross wage outside CCMm as reported by CMD was GH¢ 58.4 [US$ 64.69] and value of foregone income of GH¢ 86.40 (US$ 94.95) per month, about 14-times higher than the monthly incentives of GH¢ 6.0 given by the CCMm programme. CONCLUSION: The value of work time and the foregone income of CMDs in CCMm are high and yet there are no regular and sustainable incentives provided for them. The results are significant to policy in designing incentives to motivate CMDs in large-scale implementation of CCMm.

MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa.

Current endeavour focuses on human genetic factors that contribute to susceptibility to or protection from tuberculosis (TB). Monocytes are crucial in containing Mycobacterium tuberculosis infection, and the monocyte chemoattractant protein-1 (MCP-1) cytokine plays a role in their recruitment to the site of infection. The G allele of the MCP-1 promoter polymorphism at position -2581 relative to the ATG transcription start codon has been described to be associated in Mexican and Korean TB patients with increased susceptibility to TB. We genotyped this and additional MCP-1 variants in sample collections comprising more than 2000 cases with pulmonary TB and more than 2300 healthy controls and 332 affected nuclear families from Ghana, West Africa, and more than 1400 TB patients and more than 1500 controls from Russia. In striking contrast to previous reports, MCP-1 -2581G was significantly associated with resistance to TB in cases versus controls [odds ratio (OR) 0.81, corrected P-value (P(corr)) = 0.0012] and nuclear families (OR 0.72, P(corr) = 0.04) and not with disease susceptibility, whereas in the Russian sample no evidence of association was found (P = 0.86). Our and other results do not support an association of MCP-1 -2581 with TB. In the Ghanaian population, eight additional MCP-1 polymorphisms were genotyped. MCP-1 -362C was associated with resistance to TB in the case-control collection (OR 0.83, P(corr) = 0.00017) and in the affected families (OR 0.7, P(corr) = 0.004). Linkage disequilibrium (LD) and logistic regression analyses indicate that, in Ghanaians, the effect results exclusively from the MCP-1 -362 variant, whereas the effect of -2581 may in part be explained by its LD with -362.

Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains.

The human immunity-related GTPase M (IRGM) has been shown to be critically involved in regulating autophagy as a means of disposing cytosolic cellular structures and of reducing the growth of intracellular pathogens in vitro. This includes Mycobacterium tuberculosis, which is in agreement with findings indicating that M. tuberculosis translocates from the phagolysosome into the cytosol of infected cells, where it becomes exposed to autophagy. To test whether IRGM plays a role in human infection, we studied IRGM gene variants in 2010 patients with pulmonary tuberculosis (TB) and 2346 unaffected controls. Mycobacterial clades were classified by spoligotyping, IS6110 fingerprinting and genotyping of the pks1/15 deletion. The IRGM genotype -261TT was negatively associated with TB caused by M. tuberculosis (OR 0.66, CI 0.52-0.84, P(nominal) 0.0009, P(corrected) 0.0045) and not with TB caused by M. africanum or M. bovis (OR 0.95, CI 0.70-1.30. P 0.8). Further stratification for mycobacterial clades revealed that the protective effect applied only to M. tuberculosis strains with a damaged pks1/15 gene which is characteristic for the Euro-American (EUAM) subgroup of M. tuberculosis (OR 0.63, CI 0.49-0.81, P(nominal) 0.0004, P(corrected) 0.0019). Our results, including those of luciferase reporter gene assays with the IRGM variants -261C and -261T, suggest a role for IRGM and autophagy in protection of humans against natural infection with M. tuberculosis EUAM clades. Moreover, they support in vitro findings indicating that TB lineages capable of producing a distinct mycobacterial phenolic glycolipid that occurs exclusively in strains with an intact pks1/15 gene inhibit innate immune responses in which IRGM contributes to the control of autophagy. Finally, they raise the possibility that the increased frequency of the IRGM -261TT genotype may have contributed to the establishment of M. africanum as a pathogen in the West African population.

The clinical impact of combining intermittent preventive treatment with home management of malaria in children aged below 5 years: cluster randomised trial.

OBJECTIVE: To investigate the impact of seasonal intermittent preventive treatment (IPTc) on malaria-related morbidity in children <5 years of age who already had access to home-based management of malaria (HMM) for presumptive treatment of fevers. METHOD: Thirty community-based drug distributors (CDDs) from all 13 communities of a rural subdistrict in Ghana were trained to provide prompt treatment for presumptive malaria using artesunate-amodiaquine (AS+AQ) to all children under 5 years of age. Six communities were randomised to also receive bimonthly courses of seasonal IPTc with AS+AQ in May, July and September of 2007. The primary outcome was the incidence rate of febrile episodes diagnosed presumptively as malaria by the CDDs in the communities in each intervention group. Cross-sectional surveys were conducted to determine the prevalence of parasitaemia and anaemia among the study children. RESULTS: During the 6 months in which IPTc was delivered, incidence of fevers in communities given HMM+IPTc was lower than in communities given HMM alone, but this difference was not statistically significant (protective efficacy: 37.0%(95% CI: -9.7 to 63.8; P = 0.14). However, incidence of presumptive malaria was significantly lower in IPTc communities when only children who received all three courses of IPTc were included in the analysis: protective efficacy 61.5% (95% CI:31.2-78.5; P = 0.018). Protection with IPTc was not followed by rebound morbidity in the following year. At the end of the intervention period, prevalence of asymptomatic parasitaemia was lower in communities that had received IPTc, but there were no differences in anaemia or haemoglobin concentration. CONCLUSION: In this study area, incidence of fevers was lower in communities given three courses of IPTc during the time of peak transmission than in communities that received only HMM. However, high levels of coverage for IPTc will be necessary for maximum impact.

The effectiveness and perception of the use of sulphadoxine-pyrimethamine in intermittent preventive treatment of malaria in pregnancy programme in Offinso district of Ashanti region, Ghana.

BACKGROUND: Malaria in pregnant women has been shown to be associated with low birth weight, stillbirth and mortality in newborns. The WHO has adopted the use of sulphadoxine-pyrimethamine (SP) to control malaria, a disease which worsens the plight of pregnant women leading to low birth weight, stillbirths and increased neonatal mortality. The present study assessed the effectiveness of SP and perception of its use in pregnant women in Offinso district (Ashanti Region), Ghana. METHOD: Pregnant women, gestational age 32 weeks prior to term, were studied from November 2006 to October 2007. Their haemoglobin levels (Hb), parasitaemia and other quantitative determinants were assessed. In-depth interviews (IDIs) and focus group discussions (FGDs) were used to assess the perception of SP usage and its effectiveness. RESULTS: Of the 306 study participants, 92 (30%) took one dose, 100 (33%) two doses and 114 (37%) three doses of SP, respectively. There was significant association between gravidity and SP dosage taken (Pearson χ2 = 18.9, p < 0.001). Although adverse effects were produced in 113 (i.e. 37%) of the pregnant women, no significant difference was observed with regard to the dosage of SP taken (Pearson's χ2 = 2.3, p ≥ 0.32). Peripheral parasitaemia was present in 47 (15%) of the subjects. There was a poor negative relationship of doses of SP with parasitaemia (r = -0.07, p ≥ 0.24). Mean Hb was 11.3 ± 1.6 g/dl, with 118 (39%) of the subjects anaemic (Hb < 11.0 g/dl), whilst 187 (61%) were normal (Hb ≥11.0 g/dl). Significant positive correlation of SP use with Hb level (r = 0.15, p < 0.008) was observed. SP use reduced malaria and anaemia prevalence, contributed to reduced maternal morbidity with mild side effects being reported. CONCLUSIONS: This study points to the effectiveness of IPTp using SP as an evidence-based measure for control of malaria and malaria-related anaemia in pregnancy. Therefore, the Ghana Health Service should improve current programme strategies to increase the proportion of pregnant women who take three doses of SP, paying attention to improved face-to-face health education, focussed antenatal care and better social mobilization.

Feasibility and acceptability of ACT for the community case management of malaria in urban settings in five African sites.

BACKGROUND: The community case management of malaria (CCMm) is now an established route for distribution of artemisinin-based combination therapy (ACT) in rural areas, but the feasibility and acceptability of the approach through community medicine distributors (CMD) in urban areas has not been explored. It is estimated that in 15 years time 50% of the African population will live in urban areas and transmission of the malaria parasite occurs in these densely populated areas. METHODS: Pre- and post-implementation studies were conducted in five African cities: Ghana, Burkina Faso, Ethiopia and Malawi. CMDs were trained to educate caregivers, diagnose and treat malaria cases in < 5-year olds with ACT. Household surveys, focus group discussions and in-depth interviews were used to evaluate impact. RESULTS: Qualitative findings: In all sites, interviews revealed that caregivers' knowledge of malaria signs and symptoms improved after the intervention. Preference for CMDs as preferred providers for malaria increased in all sites.Quantitative findings: 9001 children with an episode of fever were treated by 199 CMDs in the five study sites. Results from the CHWs registers show that of these, 6974 were treated with an ACT and 6933 (99%) were prescribed the correct dose for their age. Fifty-four percent of the 3,025 children for which information about the promptness of treatment was available were treated within 24 hours from the onset of symptoms.From the household survey 3700 children were identified who had an episode of fever during the preceding two weeks. 1480 (40%) of them sought treatment from a CMD and 1213 of them (82%) had received an ACT. Of these, 1123 (92.6%) were administered the ACT for the correct number of doses and days; 773 of the 1118 (69.1%) children for which information about the promptness of treatment was available were treated within 24 hours from onset of symptoms, and 768 (68.7%) were treated promptly and correctly. CONCLUSIONS: The concept of CCMm in an urban environment was positive, and caregivers were generally satisfied with the services. Quality of services delivered by CMDs and adherence by caregivers are similar to those seen in rural CCMm settings. The proportion of cases seen by CMDs, however, tended to be lower than was generally seen in rural CCMm. Urban CCMm is feasible, but it struggles against other sources of established healthcare providers. Innovation is required by everyone to make it viable.

The new Powerplex® ESX17 and ESI17 kits in paternity and maternity analyses involving people from Africa--including allele frequencies for three African populations.

Paternity and maternity investigations in immigration procedures are frequently done in Germany. Since mostly only one parent and one or more children are investigated, the occurrence of possible mutational events has to be interpreted with great care and the analysis of as many STRs as possible is recommended. The new Powerplex® ESX17 and Powerplex® ESI17 kits from Promega comprising both eleven established STRs and additionally the loci D1S1656, D2S441, D10S1248, D12S391, and D22S1045 (in different order) are potential tools in such paternity or maternity analyses, but only few allele frequency data for the five new loci exist. Here, we provide allele frequencies for the five additional STRs from three different populations from Africa. In addition, we present two maternity cases and one paternity case in which a clear inclusion or exclusion of the alleged parent could only be achieved by the additional application of the new Powerplex® ESX17 kit.

ALOX5 variants associated with susceptibility to human pulmonary tuberculosis.

The 5-lipoxygenase (ALOX5)-derived lipid mediators leukotrienes and lipoxins have regulatory functions in inflammation by modulating activities of immune cells and cytokine production. Recently, it was shown in ALOX5-/- mice that host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase (5-LO). ALOX5 polymorphisms were genotyped in 1916 sputum-positive patients with pulmonary tuberculosis (TB) from Ghana and in 2269 exposed, apparently healthy controls. Polymorphisms of a variable number of tandem repeats (VNTR) of the ALOX5 promoter and of the exonic non-synonymous variant g.760G>A were analysed by fragment length determination and fluorescence resonance energy transfer, respectively, and DNA sequencing. Mycobacterial lineages of >1400 isolates were differentiated biochemically and genetically. Carriers of one variant (n repeats not equal 5) and one wild-type VNTR allele (n = 5) or of the exonic allele g.760A had a higher risk of TB [P(corrected) = 0.026, odds ratio (OR) 1.19 (95% CI 1.04-1.37) and P(corrected) = 0.026, OR 1.21 (95% CI 1.04-1.41), respectively]. The association of the exonic variant was stronger in infections caused by the mycobacterial lineage M. africanum West-African 2 [P(corrected) = 0.024, OR 1.70; (95% CI 1.2-2.6)]. Determination of haplotypes revealed the strongest associaton with TB for the 'non-5/760A' haplotype compared with the 'non-5/760G' haplotype (P = 0.003, OR 1.50). Our observation of an association of ALOX5 variants with susceptibility to TB contributes evidence of the importance of 5-LO products to the regulation of immune responses to M. tuberculosis.

Unequal distribution of resistance-conferring mutations among Mycobacterium tuberculosis and Mycobacterium africanum strains from Ghana.

Isoniazid (INH) and rifampicin (RMP) resistance in Mycobacterium tuberculosis complex (MTC) isolates are mainly based on mutations in a limited number of genes. However, mutation frequencies vary in different mycobacterial populations. In this work, we analyzed the distribution of resistance-associated mutations in M. tuberculosis and M. africanum strains from Ghana, West Africa. The distribution of mutations in katG, fabG1-inhA, ahpC, and rpoB was determined by DNA sequencing in 217 INH-resistant (INH(r)) and 45 multidrug-resistant (MDR) MTC strains isolated in Ghana from 2001 to 2004. A total of 247 out of 262 strains investigated (94.3%) carried a mutation in katG (72.5%), fabG1-inhA (25.1%), or ahpC (6.5%), respectively. M. tuberculosis strains mainly had katG 315 mutations (80.1%), whereas this proportion was significantly lower in M. africanum West-African 1 (WA1) strains (43.1%; p<0.05). In contrast, WA1 strains showed more mutations in the fabG1-inhA region (39.2%, p<0.05) compared to M. tuberculosis strains (20.9%). In 44 of 45 MDR strains (97.8%) mutations in the 81-bp core region of the rpoB gene could be verified. Additionally, DNA sequencing revealed that 5 RMP-susceptible strains also showed mutations in the rpoB hotspot region. In conclusion, although principally the same genes were affected in INH(r)M. tuberculosis and M. africanum strains, disequilibrium in the distribution of mutations conferring resistance was verified that might influence the efficiency of molecular tests for determination of resistance.

Reporting on road traffic injury: content analysis of injuries and prevention opportunities in Ghanaian newspapers.

In order to analyse traffic injury reporting in Ghanaian newspapers and identify opportunities for improving road safety, the content of 240 articles on road traffic injury was reviewed from 2005 to 2006 editions of two state-owned and two privately owned newspapers. The articles comprised reports on vehicle crashes (37%), commentaries (33%), informational pieces (12%), reports on pedestrian injury (10%), and editorials (8%). There was little coverage of pedestrian injuries, which account for half of the traffic fatalities in Ghana, but only 22% of newspaper reports. Only two articles reported on seatbelt use. Reporting patterns were similar between public and private papers, but private papers more commonly recommended government action (50%) than did public papers (32%, p=0.006). It is concluded that Ghanaian papers provide detailed coverage of traffic injury. Areas for improvement include pedestrian injury and attention to preventable risk factors such as road risk factors, seatbelt use, speed control, and alcohol use.

Genome-wide linkage analysis of malaria infection intensity and mild disease.

Although balancing selection with the sickle-cell trait and other red blood cell disorders has emphasized the interaction between malaria and human genetics, no systematic approach has so far been undertaken towards a comprehensive search for human genome variants influencing malaria. By screening 2,551 families in rural Ghana, West Africa, 108 nuclear families were identified who were exposed to hyperendemic malaria transmission and were homozygous wild-type for the established malaria resistance factors of hemoglobin (Hb)S, HbC, alpha(+) thalassemia, and glucose-6-phosphate-dehydrogenase deficiency. Of these families, 392 siblings aged 0.5-11 y were characterized for malaria susceptibility by closely monitoring parasite counts, malaria fever episodes, and anemia over 8 mo. An autosome-wide linkage analysis based on 10,000 single-nucleotide polymorphisms was conducted in 68 selected families including 241 siblings forming 330 sib pairs. Several regions were identified which showed evidence for linkage to the parasitological and clinical phenotypes studied, among them a prominent signal on Chromosome 10p15 obtained with malaria fever episodes (asymptotic z score = 4.37, empirical p-value = 4.0 x 10(-5), locus-specific heritability of 37.7%; 95% confidence interval, 15.7%-59.7%). The identification of genetic variants underlying the linkage signals may reveal as yet unrecognized pathways influencing human resistance to malaria.

Allele frequencies of 11 X-chromosomal loci in a population sample from Ghana.

Eleven X-chromosomal short tandem repeats (STRs) from two multiplex PCR approaches (DXS6807, DXS8378, DXS7132, DXS6800, DXS9898, DXS7424, DXS101, DXS7133, HPRTB, DXS8377, and DXS7423), located in four different X-chromosomal linkage groups, were typed in a population sample from Ghana, Africa. After genotyping unrelated men (129) and women (114) from the Ashanti population, forensic efficiency parameters such as polymorphism information content and mean exclusion chance were calculated. A deviation from the Hardy-Weinberg equilibrium could not be found. The investigation of 11 father-daughter and seven mother-son meioses revealed no mutations in any STR analyzed. Our data were compared with European, African-American, and Asian populations from the literature.

Malaria in pregnancy in an area of stable and intense transmission: is it asymptomatic?

OBJECTIVE: To report a study of the signs and symptoms of malarial infection during pregnancy in an area of stable and intense transmission. METHODS: As part of a clinical trial, to assess the efficacy and safety of four antimalarial drug regimens in pregnant women, we collected clinical and laboratory data from 900 parasitaemic pregnant women and 223 non-parasitaemic pregnant women who attended an antenatal clinic at a district hospital in Ghana. Frequencies of signs and symptoms were calculated and their association with the level of parasitaemia was assessed using multivariate logistic regression. RESULTS: History of fever (7.8%vs. 44.4%; P < 0.0001), headache (12.5%vs. 43.9%; P < 0.0001), vomiting (0 vs. 11.5%; P = 0.01), malaise (1.6%vs. 31.6%; P < 0.0001) dizziness (0%vs. 23%; P < 0.0001) and fatigue (0%vs. 22.5%; P < 0.0001) was substantially higher in parasitaemic primigravidae than in aparasitaemic primigravid women. Similar differences in the distribution of the symptoms and signs were observed between parasitaemic and aparasitaemic multigravid women. The proportion of women with elevated concentrations of aspartate aminotransferase, alanine aminotransferase and total bilirubin and its fractions was also higher in parasitaemic than in non-parasitaemic women. CONCLUSION: In areas of stable malarial transmission, malaria in pregnancy is often symptomatic. Although the symptoms are mostly non-specific, careful recording of history may be useful to identify women who need a confirmatory test and an effective antimalarial treatment.

Feasibility and acceptability of artemisinin-based combination therapy for the home management of malaria in four African sites.

BACKGROUND: The Home Management of Malaria (HMM) strategy was developed using chloroquine, a now obsolete drug, which has been replaced by artemisinin-based combination therapy (ACT) in health facility settings. Incorporation of ACT in HMM would greatly expand access to effective antimalarial therapy by the populations living in underserved areas in malaria endemic countries. The feasibility and acceptability of incorporating ACT in HMM needs to be evaluated. METHODS: A multi-country study was performed in four district-size sites in Ghana (two sites), Nigeria and Uganda, with populations ranging between 38,000 and 60,000. Community medicine distributors (CMDs) were trained in each village to dispense pre-packaged ACT to febrile children aged 6-59 months, after exclusion of danger signs. A community mobilization campaign accompanied the programme. Artesunate-amodiaquine (AA) was used in Ghana and artemether-lumefantrine (AL) in Nigeria and Uganda. Harmonized qualitative and quantitative data collection methods were used to evaluate CMD performance, caregiver adherence and treatment coverage of febrile children with ACTs obtained from CMDs. RESULTS: Some 20,000 fever episodes in young children were treated with ACT by CMDs across the four study sites. Cross-sectional surveys identified 2,190 children with fever in the two preceding weeks, of whom 1,289 (59%) were reported to have received ACT from a CMD. Coverage varied from 52% in Nigeria to 75% in Ho District, Ghana. Coverage rates did not appear to vary greatly with the age of the child or with the educational level of the caregiver. A very high proportion of children were reported to have received the first dose on the day of onset or the next day in all four sites (range 86-97%, average 90%). The proportion of children correctly treated in terms of dose and duration was also high (range 74-97%, average 85%). Overall, the proportion of febrile children who received prompt treatment and the correct dose for the assigned duration of treatment ranged from 71% to 87% (average 77%). Almost all caregivers perceived ACT to be effective, and no severe adverse events were reported. CONCLUSION: ACTs can be successfully integrated into the HMM strategy.

Effectiveness of artemisinin-based combination therapy used in the context of home management of malaria: a report from three study sites in sub-Saharan Africa.

BACKGROUND: The use of artemisinin-based combination therapy (ACT) at the community level has been advocated as a means to increase access to effective antimalarial medicines by high risk groups living in underserved areas, mainly in sub-Saharan Africa. This strategy has been shown to be feasible and acceptable to the community. However, the parasitological effectiveness of ACT when dispensed by community medicine distributors (CMDs) within the context of home management of malaria (HMM) and used unsupervised by caregivers at home has not been evaluated. METHODS: In a sub-set of villages participating in a large-scale study on feasibility and acceptability of ACT use in areas of high malaria transmission in Ghana, Nigeria and Uganda, thick blood smears and blood spotted filter paper were prepared from finger prick blood samples collected from febrile children between six and 59 months of age reporting to trained CMDs for microscopy and PCR analysis. Presumptive antimalarial treatment with ACT (artesunate-amodiaquine in Ghana, artemether-lumefantrine in Nigeria and Uganda) was then initiated. Repeat finger prick blood samples were obtained 28 days later for children who were parasitaemic at baseline. For children who were parasitaemic at follow-up, PCR analyses were undertaken to distinguish recrudescence from re-infection. The extent to which ACTs had been correctly administered was assessed through separate household interviews with caregivers having had a child with fever in the previous two weeks. RESULTS: Over a period of 12 months, a total of 1,740 children presenting with fever were enrolled across the study sites. Patent parasitaemia at baseline was present in 1,189 children (68.3%) and varied from 60.1% in Uganda to 71.1% in Ghana. A total of 606 children (51% of infected children) reported for a repeat test 28 days after treatment. The crude parasitological failure rate varied from 3.7% in Uganda (C.I. 1.2%-6.2%) to 41.8% in Nigeria (C.I. 35%-49%). The PCR adjusted parasitological cure rate was greater than 90% in all sites, varying from 90.9% in Nigeria (C.I. 86%-95%) to 97.2% in Uganda (C.I. 95%-99%). Reported adherence to correct treatment in terms of dose and duration varied from 81% in Uganda (C.I. 67%-95%) to 97% in Ghana (C.I. 95%-99%) with an average of 94% (C.I. 91%-97%). CONCLUSION: While follow-up rates were low, this study provides encouraging data on parasitological outcomes of children treated with ACT in the context of HMM and adds to the evidence base for HMM as a public health strategy as well as for scaling-up implementation of HMM with ACTs.

Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial.

BACKGROUND: The widespread increase in resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine threatens the use of these drugs for malaria treatment in pregnancy. We aimed to assess the safety and efficacy of amodiaquine alone or in combination with sulphadoxine-pyrimethamine as alternative regimens. METHODS: Pregnant women with a gestational age of 16 weeks or more who attended antenatal clinics at a district hospital in Ghana were screened for malaria with OptiMAL dipsticks. 900 pregnant women who had a positive test result and P falciparum asexual stage parasitaemia were enrolled and randomly assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, or amodiaquine plus sulphadoxine-pyrimethamine. The primary outcome was parasitological failure by day 28 of treatment. Women were seen on days 3, 7, 14, and 28 after the start of treatment to assess the effect of treatment on peripheral parasitaemia, haemoglobin concentration, white-blood-cell count, and liver function. Additionally, reports of adverse effects were solicited and monitored during follow-up visits. Analysis was by intention to treat. This trial is registered with the US National Institute of Health clinical trials database number NCT00131703. FINDINGS: PCR-corrected parasitological failure by day 28 was 14%, 11%, 3%, and 0% in the women assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, and amodiaquine plus sulphadoxine-pyrimethamine, respectively (p<0.0001). No serious liver toxic effects or white-blood-cell dyscrasias were noted. Minor side-effects were reported more often on day 3 by women receiving amodiaquine (86%) or amodiaquine plus sulphadoxine-pyrimethamine (90%) than those receiving sulphadoxine-pyrimethamine (48%) or no antimalarial drugs (34%; p<0.0001 for every comparison). INTERPRETATION: Amodiaquine alone or in combination with sulphadoxine-pyrimethamine, although associated with minor side-effects, is effective when used to treat malaria in pregnancy.

Comparison of the therapeutic efficacy of chloroquine and sulphadoxine-pyremethamine in children and pregnant women.

OBJECTIVE: To compare the parasitological failure rates of under-fives and pregnant women with parasitaemia treated with chloroquine (CQ) or sulphadoxine-pyrimethamine (SP). METHODS: During a clinical trial of CQ, SP, amodiaquine (AQ) and SP plus AQ combination for malaria treatment in pregnant women in Ghana, a parallel study of treatment of children below 5 years of age with symptomatic malaria with CQ and SP was undertaken. Four hundred and fifty pregnant women with malaria parasitaemia and 203 children with malaria parasitaemia were randomized to receive CQ or SP. They were followed up and parasitological failure by days 14 and 28 after the start of treatment was assessed. RESULTS: Polymerase chain reaction (PCR)-uncorrected parasitological failure rates by day 28 after the start of treatment with CQ were 58.5% (55/94), 38.5% (45/117), 31% (13/42) and 8.2% (4/49) in children, primigravidae, secundigravidae and multigravidae, respectively. For those treated with SP the rates by day 28 were 36.4% (32/88), 27.1% (29/107), 6.1% (3/49) and 3.8% (2/52) in children, primigravidae, secundigravidae and multigravidae, respectively. In both CQ and SP treatment arms, children were twice as likely to experience recrudescence as pregnant women (RR 2.1 [95% CI 1.6-2.6] P < 0.0001) by day 28 after the start of treatment. CONCLUSIONS: Parasitological failure rates were significantly lower in asymptomatic pregnant women, particularly in multigravidae, compared with symptomatic children. Reliance on drug sensitivity results observed in children only to decide on antimalarial regimes for pregnant women may not be appropriate.

Perception and risk factors for cervical cancer among women in northern Ghana.

OBJECTIVE: This study assessed the perception of risk of cervical cancer and existence of risk factors for cervical cancer based on five known risk factors among women attending the Tamale Teaching Hospital in Tamale, Ghana. METHODS: A consecutive sample of 300 women was interviewed using a semi-structured questionnaire to inquire about risk factors and perception of risk of cervical cancer. Specific risk factors that were explored included early coitarche, multiple sexual partners, polygamous relationships, history of smoking, and having a current partner who had multiple sexual partners. RESULTS: Sixty-one per cent of women reported that they had no personal risk for cervical cancer. 27% of respondents were in polygamous relationships, and of those, more than half didn't think they were at an increased risk of cervical cancer. 2 women had a total of ≥ 5 sexual partners in their lifetime and neither believed they were at any risk for cervical cancer. 23% said their current partner had had at least 2 sexual partners in his lifetime, and of those, (61%) thought they were at no risk for cervical cancer. 46% of respondents reported not having any of the risk factors listed in the study. 23% of respondents reported having one risk factor while 21% had two risk factors and 11% had three or more risk factors. CONCLUSION: Women's perception of personal risk for cervical cancer is lower than their actual risk based on the five behavioural risk factors assessed and a lack of knowledge of the personal factors for the disease. FUNDING: This project was supported by NIH Research Training Grant #R25 TW009345 funded by the Fogarty International Centre, in partnership with several NIH Institutes (NIMH, NIGMS, NHLBI, OAR and OWH).

Impact of combined intermittent preventive treatment of malaria and helminths on anaemia, sustained attention, and recall in Northern Ghanaian schoolchildren.

BACKGROUND: The benefits of integrated control of malaria, schistosomiasis, and soil-transmitted helminth infections have not been fully explored in Ghanaian schoolchildren. OBJECTIVE: To assess the impact of co-administered artemether-lumefantrine plus albendazole, and artemether-lumefantrine plus albendazole plus praziquantel compared to albendazole plus praziquantel on anaemia, sustained attention, and recall in schoolchildren. DESIGN: This three-arm, open-label intervention study was carried out in Ghana among class three schoolchildren. Artemether-lumefantrine and albendazole were co-administered to 131 schoolchildren in Study Arm 1; artemether-lumefantrine, albendazole, and praziquantel to 90 children in Study Arm 2 versus albendazole and praziquantel to 127 children in Control Arm 3. Medicines were administered to all children at least 30 min after a meal. A HemoCue(®) photometer was used to measure haemoglobin (Hb), while the code transmission test (CTT), adapted from the Test of Everyday Attention for Children (TEA-Ch), was used to measure sustained attention and recall before-and-after interventions in June 2011 and June 2012. RESULTS: We observed significant malaria parasite prevalence reductions of 62.8 and 59.2% in Study Arm 1 from 24.2 to 9.0%, p<0.01, and 59.2% in Study Arm 2 from 26.7 to 10.9%, p<0.01), respectively, compared to 8.93% in Control Arm 3 (from 34.7 to 31.6%, p>0.05). Meanwhile, anaemia prevalence reduced significantly (p<0.01) in all three study arms after interventions by 38.4% (from 19.8 to 12.2%), 20.7% (from 26.6 to 21.1%), and 36.0% (from 28.3 to 18.1%) in Study Arms 1, 2, and 3, respectively. Although the interventions had no significant effects on Hb levels, anaemia prevalence reduced insignificantly by 38.4 and 20.7% in Study Arms 1 and 2, respectively, compared to 36.0% in Control Arm 3. Among schoolchildren in Study Arms 1 and 2, mean CTT score improved significantly after interventions by 10.4% (from 3.18 to 3.55, p=0.01) and 20.5% (from 2.83 to 3.56, p=0.01) respectively, compared to 5.75% in Control Arm 3 (from 2.95 to 3.13, p=0.09). Likewise, mean recall test score improvements after interventions were 16.9% (from 2.07 to 2.49, p=0.01) and 27.9% (from 1.91 to 2.65, p=0.01) in Study Arms 1 and 2, respectively, compared to 18.3% (from 1.92 to 2.35, p=0.01) in Control Arm 3. CONCLUSION: Combined intermittent preventive treatment of malaria and deworming reduced prevalence of anaemia and improved sustained attention and recall in schoolchildren. Best results for sustained attention and recall were seen in Study Arm 2.