Benjamin K. Abuaku

Antimalarial Prescribing Practices: A Challenge to Malaria Control in Ghana

Objective: The study was conducted to determine antimalarial prescribing practices among prescribers in 2 of the 6 sentinel sites established to document antimalarial drug efficacy in Ghana in order to provide some explanation underlying chloroquine treatment failures in the country. Subjects andMethods: The study was descriptive combining both qualitative and quantitative designs. The qualitative design involved in-depth interviews of general prescribers in the Wassa West and Kassena Nankana districts using an interview guide. The quantitative design involved a review of Outpatient Department prescriptions of 100 patients clinically diagnosed as having malaria within the year 2000 in each of the 7 selected health care facilities. Results: The overall number of drugs prescribed per patient encounter was 4.3 in the Wassa West district and 3.0 in the Kassena Nankana district. The number of drugs per patient encounter was 5.4 and 3.7 in private and government health care facilities, respectively. The commonly prescribed antimalarial drug in all the health care facilities visited was chloroquine. However, only 9.8% of prescriptions in private health care facilities contained correct doses of chloroquine compared to 54% in government health care facilities (p = 0.000). Prescriptions containing chloroquine injections were least likely to have correct doses of chloroquine. Conclusion: Thefindings indicate that although chloroquine remained the first-line drug in the treatment of uncomplicated malaria in the two districts, the level of appropriateness of doses prescribed was generally low. Inappropriate doses of chloroquine prescribed were more prevalent in private than government health care facilities, and among prescriptions containing injections.

Surveillance of Molecular Markers of Plasmodium falciparum Resistance to Sulphadoxine-Pyrimethamine 5 Years after the Change of Malaria Treatment Policy in Ghana

In 2005, sulphadoxine-pyrimethamine (SP) became the drug of choice for intermittent preventive treatment of Plasmodium falciparum malaria in pregnancy (IPTp) in Ghana. Reports suggest the use of SP by others to treat uncomplicated malaria. Because of the increased use of SP, the prevalence of mutations in the genes, dihydrofolate reductase (dhfr), and dihydropteroate synthetase (dhps), linked to SP resistance in P. falciparum were determined. Blood samples from 945 children with uncomplicated malaria collected at nine sites from 2003 to 2010 were analyzed using polymerase chain reaction and restriction fragment length polymorphism. Prevalence of the dhfr triple and dhfr plus dhps quadruple mutations showed significant increase in trend from 2003 to 2010 (χ(2) = 18.78, P < 0.001, χ(2) = 15.11, P < 0.001, respectively). For dhps double mutant G437 + E540 the prevalence was low (1.12%) caused by the very low prevalence of E540. Our findings show the wide use of SP in Ghana and therefore its use for IPTp needs to be closely monitored.

Impact of passive smoking, cooking with solid fuel exposure, and MBL/MASP-2 gene polymorphism upon susceptibility to tuberculosis

BACKGROUNDnTo explore the impact of passive smoking, cooking with solid fuel, mannose-binding lectin (MBL) gene, MBL-associated serine proteases 2 (MASP-2) gene, and gene-environment interactions on the susceptibility to tuberculosis (TB) in non-smokers.nnnMETHODSnA total of 205 TB patients and 216 healthy controls were recruited to participate in this case-control study. PCR with sequence-specific primers (PCR-SSP) technology was leveraged to genotype rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes. Demographic data and information on exposures of participants were collected. Unconditioned logistic regression analysis was conducted to identify associations between the various factors and TB, and marginal structural linear odds models were used to estimate the interactions.nnnRESULTSnPassive smoking and cooking with solid fuel were associated with the risk of TB, with odds ratios (OR) of 1.58 and 2.93, respectively (p<0.05). Genotype CG at rs7096206 of MBL genes (OR 2.02) and genotype TC at rs6695096 of MASP-2 genes (OR 1.67) were more prevalent in the TB patients than in healthy controls (p<0.05). The relative excess risk of interaction (RERI) between rs7096206 of MBL genes and passive smoking or cooking with solid fuel exposure was 1.86 (95% confidence interval (CI) 0.59-3.16) and 2.66 (95% CI 1.85-3.47), respectively. The RERI between rs6695096 of MASP-2 genes and cooking with solid fuel exposure was 3.70 (95% CI 2.63-4.78), which was also a positive interaction. However, the RERI between rs6695096 of MASP-2 genes and passive smoking was not statistically significant.nnnCONCLUSIONSnPassive smoking, cooking with solid fuel, and polymorphisms of MBL (rs7096206) and MASP-2 (rs6695096) genes were associated with susceptibility to TB in non-smokers, and there were gene-environment interactions among them. Further studies are needed to explore details of the mechanisms of association.

Treatment default and death among tuberculosis patients in Hunan, China

Abstract We used the 2005 and 2006 national surveillance data to elucidate some of the risk factors for treatment default and death among tuberculosis (TB) patients in Hunan, China. Risk of default was higher in males (odds ratio (OR) 1.25; 95% confidence interval (CI) 1.08, 1.44); lowest in patients aged 15–24 y (OR 0.60; 95% CI 0.49, 0.75), and generally increased with increasing age; lower in patients living in cities with per capita gross domestic product (GDP) of less than 1000 US

Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis

(OR 0.60, 95% CI 0.49, 0.72), and increased with increasing per capita GDP of city of residence; and higher in patients with previously treated smear-positive pulmonary TB (diagnostic category II according to the World Health Organization definition; OR 1.99; 95% CI 1.22, 3.23). Risk of death was lowest in patients aged 15–24 y (OR 0.07; 95% CI 0.05, 0.10), and increased with increasing age; lower in new cases (OR 0.50; 95% CI 0.33, 0.76); and highest in patients who treated themselves (OR 3.47; 95% CI 1.27, 9.46). We conclude that male TB patients, elderly TB patients, patients resident in cities with higher per capita GDP, and patients receiving category II treatment need special attention to reduce TB treatment default in the province. Furthermore, elderly TB patients and patients with a long history of TB need special attention to reduce mortality. Self-treatment also needs to be discouraged to reduce mortality.

A SYBR Green 1-based in vitro test of susceptibility of Ghanaian Plasmodium falciparum clinical isolates to a panel of anti-malarial drugs

BackgroundMannose-binding lectin (MBL) and MBL-associated serine proteases 2 (MASP-2) are important proteins in the lectin pathway of the immune system. Polymorphism of MBL and MASP-2 genes may affect the serum concentration of MBL and MASP-2. This study explores the association between MBL and MASP-2 gene polymorphism and their interactions and the susceptibility to tuberculosis (TB).MethodA total of 503 patients with TB and 419 healthy controls were recruited to participate in this case-control study. PCR-SSP technology was applied to genotype rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes. Demographic data and some exposure information were also obtained from study participants. Unconditional logistic regression analysis was used to identify association between the various factors and TB whilst Marginal Structural Linear Odds Models were used to estimate the interactions.ResultsBoth genotype GC at rs7096206 of MBL genes and genotype TC at rs2273346 and rs6695096 of MASP-2 genes were more prevalent in the TB patient group than the healthy control group (Pu2009<u20090.05, OR 1.393, 1.302 and 1.426 respectively). The relative excess risk of interaction (RERI) between rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes was 0.897 (95% CI: 0.282, 1.513) and 1.142 (95% CI: 0.755, 1.530) respectively (Pu2009<u20090.05).ConclusionPolymorphisms of MBL (rs7096206) and MASP-2 (rs2273346 and rs6695096) were associated with the susceptibility of TB, and there were gene-gene interactions among them.

Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum.

BackgroundBased on report of declining efficacy of chloroquine, Ghana shifted to the use of artemisinin-based combination therapy (ACT) in 2005 as the first-line anti-malarial drug. Since then, there has not been any major evaluation of the efficacy of anti-malarial drugs in Ghana in vitro. The sensitivity of Ghanaian Plasmodium falciparum isolates to anti-malarial drugs was, therefore, assessed and the data compared with that obtained prior to the change in the malaria treatment policy.MethodsA SYBR Green 1 fluorescent-based in vitro drug sensitivity assay was used to assess the susceptibility of clinical isolates of P. falciparum to a panel of 12 anti-malarial drugs in three distinct eco-epidemiological zones in Ghana. The isolates were obtained from children visiting health facilities in sentinel sites located in Hohoe, Navrongo and Cape Coast municipalities. The concentration of anti-malarial drug inhibiting parasite growth by 50% (IC50) for each drug was estimated using the online program, ICEstimator.ResultsPooled results from all the sentinel sites indicated geometric mean IC50 values of 1.60, 3.80, 4.00, 4.56, 5.20, 6.11, 10.12, 28.32, 31.56, 93.60, 107.20, and 8952.50 nM for atovaquone, artesunate, dihydroartemisin, artemether, lumefantrine, amodiaquine, mefloquine, piperaquine, chloroquine, tafenoquine, quinine, and doxycycline, respectively. With reference to the literature threshold value indicative of resistance, the parasites showed resistance to all the test drugs except the artemisinin derivatives, atovaquone and to a lesser extent, lumefantrine. There was nearly a two-fold decrease in the IC50 value determined for chloroquine in this study compared to that determined in 2004 (57.56 nM). This observation is important, since it suggests a significant improvement in the efficacy of chloroquine, probably as a direct consequence of reduced drug pressure after cessation of its use. Compared to that measured prior to the change in treatment policy, significant elevation of artesunate IC50 value was observed. The results also suggest the existence of possible cross-resistance among some of the test drugs.ConclusionGhanaian P. falciparum isolates, to some extent, have become susceptible to chloroquine in vitro, however the increasing trend in artesunate IC50 value observed should be of concern. Continuous monitoring of ACT in Ghana is recommended.

Association between Posttraumatic Stress Disorder and Preflood Behavioral Characteristics among Children Aged 7-15 Years in Hunan, China

Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341 P. falciparum infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures.

Impact of tea drinking upon tuberculosis: a neglected issue

Objective: To explore the relationship between posttraumatic stress disorder (PTSD) and preflood behavioral characteristics among children aged 7–15 years in Hunan, China. Subjects and Methods: In 2000, a retrospective study was carried out among children who had been exposed to the 1998 floods in Hunan. A multistage sampling method was used to select subjects from the flood-affected areas. A structured questionnaire administered to the children selected was used to diagnose PTSD based on the DSM-IV criteria. A parent questionnaire was used to measure preflood behavioral characteristics related to health, behavioral, and habit problems. The association between PTSD and preflood behavioral characteristics was assessed using χ2-tests and multivariate logistic regression. Results: A total of 7,038 children from 13,450 households, aged 7–15 years, were investigated. The overall prevalence of PTSD was 2.05%. Generally, the PTSD-positive rate increased with increasing scores for behavioral characteristics. Conclusion: Preflood behavioral characteristics are an important factor influencing the prevalence of PTSD among children exposed to floods. It is therefore necessary to give special attention to children with behavioral problems in order to reduce the psychological impact of floods.

A Comparative Analysis of Tuberculosis Treatment Success between Hunan Province of China and Eastern Ghana

BackgroundTuberculosis (TB) is a global public health issue posing serious harm to the human health. Many studies have suggested that smoking and excessive alcohol consumption are risk factors for TB. Laboratory evidence suggests that EGCG in tea leaves can arrest the growth of tubercle bacillus. Can drinking tea lead to decreased susceptibility of TB in humans?MethodsA total of 574xa0TB patients and 582 healthy controls were recruited to participate in this case–control study. Self-designed questionnaire was used to collect data. Unconditioned logistic regression analysis was conducted to identify the associations between tea drinking and TB.ResultsTea drinking has a negative association with TB, with ORu2009=u20090.583(0.423, 0.804) and Pu2009<u20090.05. Drinking black tea, oolong and green tea are all negative association with TB, with OR being 0.683(0.517, 0.902), 0.674(0.508, 0.894) and 0.534(0.349, 0.817) respectively and Pu2009<u20090.05. Trend χ2 test indicated a decreasing risk for TB with increased tea consumption, with Pu2009<u20090.05.ConclusionThere is a significance negative association between tea drinking and TB. Promoting the consumption of tea as the daily drink among populations, particularly those with high TB risk, may reduce the incidence of TB in the populations.