The beta subunits (beta1, beta2, and beta5) of 20S proteasome and HslV/ClpQ are ATP-dependent thr... more The beta subunits (beta1, beta2, and beta5) of 20S proteasome and HslV/ClpQ are ATP-dependent threonine proteases present in eukaryotes and prokaryotes, respectively that control levels of key regulatory proteins in the cell. The orthologue of prokaryotic HslV protease in Plasmodium falciparum (PfHslV) is a novel drug target candidate that has no homolog in the human host. In the present study, the PfHslV was expressed, localized and biochemically characterized. The recombinant PfHslV harbored threonine protease specific activity as well as chymotrypsin like and peptidyl glutamyl peptide hydrolase activities. All the three activities could be inhibited by respective specific inhibitors. The protein was localized in the cytosol of the parasite as a soluble protein by Western immunoblotting of parasite fractions and by immuno-fluorescence microscopy. Activity of the protease in the parasite was ascertained by following the degradation of GFP in a transgenic parasite line expressing fusion protein of GFP and Arc-repressor gene, a known target of HslV protease in the prokaryotes. A model structure of PfHslV was constructed based on the crystal structure of Escherichia coli HslV to assess the structural homology. Availability of the structure model of PfHslV may facilitate identification or designing of novel and specific drugs against PfHslV. The in vitro protease assays with recombinant PfHslV and the transgenic parasite line generated in the present study may be exploited in the screening of novel inhibitors to evaluate their anti-malarial activity.
We evaluated four decontamination methods and one nondecontamination procedure in combination wit... more We evaluated four decontamination methods and one nondecontamination procedure in combination with four egg-based media for the primary isolation of Mycobacterium ulcerans from tissue specimens. With mycobacterial recovery and contamination rates of 75.6 and 2.4%, respectively, the combination of the oxalic acid decontamination method with Lowenstein-Jensen medium supplemented with glycerol yielded the best results.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 1991
One hundred and thirteen children aged 12 years or less with cerebral malaria in Accra, Ghana wer... more One hundred and thirteen children aged 12 years or less with cerebral malaria in Accra, Ghana were treated with chloroquine either with a low dose regime of 3.5 mg/kg 8-hourly intramuscularly, or orally by nasogastric tube, in a standard regime, both to a total of 25 mg/kg body weight. There was no obvious difference in outcome in the 2 treatment groups. The overall mortality of 5.3% (5.9% and 4.4% in the oral and intramuscular treatment groups respectively) was similar to that seen 10 years ago in this hospital. The average parasite clearance time had increased to 61 h, compared to 41 h noted 10 years ago. The incidence of hypoglycaemia (3%) was very low compared to studies in other malaria endemic areas. The reason for this is not clear but it could have contributed to the low mortality. Neurological deficits were seen on day 14 in 7.8% of patients. Parasitaemia recurred within 14 d in 22% of surviving patients, confirming the presence of RI/RII chloroquine resistance in Accra.
Pattern of drug utilization for treatment of uncomplicated malaria in urban Ghana following natio... more Pattern of drug utilization for treatment of uncomplicated malaria in urban Ghana following national treatment policy change to artemisinin-combination therapy
In Ghana a baseline survey examined management practices in the Ministry of Health (MOH) resource... more In Ghana a baseline survey examined management practices in the Ministry of Health (MOH) resources in the community availability of drugs in private and public facilities and households. These data were needed to implement essential drug activities within the Bamako Initiative. Even though MOH had a primary health care (PHC) strategy since 1978 it had not fully implemented PHC at subnational levels. People perceived health facilities as a source of curative care. Supervision of facilities was top down. Poor service conditions reinforced the low morale of health workers. Most facilities received most extra funding from hospital fees. The communities did not use these fees to fund development instead taxes funded community development and welfare groups. Only a small number of communities has bank accounts. Maternal and child health indicators showed limited PHC programs e.g. trained traditional birth attendants delivered just 9.5% of births. 75% of the public lived within 1 hour of a health facility. Few people preferred just traditional medicine (8.8%) or a traditional healer as their first choice (3.5%). Chemical sellers outnumbered MOH facilities as a source of drugs. 84.8% of drug outlet clients considered drug costs to be reasonable. Public facilities did a better job of drug logistics than did private facilities. Staff at both public and private facilities asked everyone requesting drugs to pay even when clients were poor. Inappropriate use of drugs and inappropriate instruction on how to use drugs were commonplace. Staff often took drugs. Shortages occurred for the most commonly prescribed drugs (chloroquine paracetamol and multivitamins). This study found inferior managerial capacity at MOH facilities especially poor financial management. MOH must come up with a mechanism to identify the poor so as not to deny them health services and drugs. Community leaders should not receive drugs and health services at no cost. Other recommendations are a system of prescription auditing and continuous education on drug use.
The landscape of public health in many sub-Saharan African countries has been changing rapidly ov... more The landscape of public health in many sub-Saharan African countries has been changing rapidly over the past few decades. Marked changes have been seen in the demographic structure of populations, economics, lifestyle changes, social upheavals (war and migration) and these have impacted disease patterns.
Pregnant women in malaria-endemic communities are susceptible to Plasmodium falciparum infections... more Pregnant women in malaria-endemic communities are susceptible to Plasmodium falciparum infections, with adverse consequences including maternal anaemia, placental malaria parasitaemia and infant low birth weight (LBW). We sought to assess the prevalence, incidence, and clinical markers of pregnancy-associated malaria (PAM) in a rural district of Ghana. A total of 294 pregnant women were enrolled and followed passively and actively, monthly and weekly until delivery. Haemoglobin levels, malaria parasitaemia and Hb electrophoresis were done from peripheral blood samples. At delivery, placental smears were examined for malaria parasites. Prevalence of peripheral blood P. falciparum parasitaemia at enrolment was 19.7% and related to parity. Incidence rate of parasitaemia was 0.06 infections/ person/month [95% confidence interval (CI): 0.04 to 0.08]. Symptomatic infections rose sharply from the first trimester to the last. Prevalence of malaria parasites in the placenta was 35.9% (61/170...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2006
Public health laboratories in Ghana performing tuberculosis (TB) microscopy. To assess the situat... more Public health laboratories in Ghana performing tuberculosis (TB) microscopy. To assess the situation of the laboratories in terms of staff strength, technical skills, documentation, biosafety practices, equipment, supplies and disposal systems. Methods used for data collection were interviews using a structured questionnaire, informal observation of laboratory registers, disposal systems and safety measures for sputum handling. Of 114 laboratories visited between 2000 and 2001, 102 (89.5%) were performing TB microscopy. Of the staff working in the laboratories, 9% were medical technologists, 24% laboratory technicians, 37% laboratory assistants and 30% orderlies. Average false-negative and -positive rates were respectively 13% and 14%. Although most of the centres (85.3%) were using the recommended TB laboratory register for recording, in most cases they were not filled in accurately or completely. The majority of the available microscopes had mechanical or optical faults. Availabil...
A 48 h in vitro test was conducted to compare the susceptibility of two strains of Plasmodium fal... more A 48 h in vitro test was conducted to compare the susceptibility of two strains of Plasmodium falciparum to chloroquine, the two enantiomers of chloroquine, desethylchloroquine and the new antimalarial drug pyronaridine. The five compounds similarly inhibited the chloroquine sensitive strain. However, desethylchloroquine was less active and pyronaridine was much more active than chloroquine and its enantiomers against the chloroquine resistant strain.
The effects of potassium chloride (as Slow-K® 600 mg three times daily) and spironolactone (as A ... more The effects of potassium chloride (as Slow-K® 600 mg three times daily) and spironolactone (as A ldactone-A,® 25 mg four times daily) were compared in hypertensive African patients on frusemide. Mean plasma-potassium levels in patients on frusemide plus Slow-K® and frusemide plus Aldactone-A® rose from 3.6 to 3.8 mOsm/L whilst on frusemide alone mean plasma-potassium fell from 3.7 to 3.6 mOsm/L. The mean blood pressure, both systolic and diastolic, was significantly reduced in the frusemide plus Aldactone-A® group when compared with patients on frusemide alone or on frusemide plus Slow-K®.
The beta subunits (beta1, beta2, and beta5) of 20S proteasome and HslV/ClpQ are ATP-dependent thr... more The beta subunits (beta1, beta2, and beta5) of 20S proteasome and HslV/ClpQ are ATP-dependent threonine proteases present in eukaryotes and prokaryotes, respectively that control levels of key regulatory proteins in the cell. The orthologue of prokaryotic HslV protease in Plasmodium falciparum (PfHslV) is a novel drug target candidate that has no homolog in the human host. In the present study, the PfHslV was expressed, localized and biochemically characterized. The recombinant PfHslV harbored threonine protease specific activity as well as chymotrypsin like and peptidyl glutamyl peptide hydrolase activities. All the three activities could be inhibited by respective specific inhibitors. The protein was localized in the cytosol of the parasite as a soluble protein by Western immunoblotting of parasite fractions and by immuno-fluorescence microscopy. Activity of the protease in the parasite was ascertained by following the degradation of GFP in a transgenic parasite line expressing fusion protein of GFP and Arc-repressor gene, a known target of HslV protease in the prokaryotes. A model structure of PfHslV was constructed based on the crystal structure of Escherichia coli HslV to assess the structural homology. Availability of the structure model of PfHslV may facilitate identification or designing of novel and specific drugs against PfHslV. The in vitro protease assays with recombinant PfHslV and the transgenic parasite line generated in the present study may be exploited in the screening of novel inhibitors to evaluate their anti-malarial activity.
We evaluated four decontamination methods and one nondecontamination procedure in combination wit... more We evaluated four decontamination methods and one nondecontamination procedure in combination with four egg-based media for the primary isolation of Mycobacterium ulcerans from tissue specimens. With mycobacterial recovery and contamination rates of 75.6 and 2.4%, respectively, the combination of the oxalic acid decontamination method with Lowenstein-Jensen medium supplemented with glycerol yielded the best results.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 1991
One hundred and thirteen children aged 12 years or less with cerebral malaria in Accra, Ghana wer... more One hundred and thirteen children aged 12 years or less with cerebral malaria in Accra, Ghana were treated with chloroquine either with a low dose regime of 3.5 mg/kg 8-hourly intramuscularly, or orally by nasogastric tube, in a standard regime, both to a total of 25 mg/kg body weight. There was no obvious difference in outcome in the 2 treatment groups. The overall mortality of 5.3% (5.9% and 4.4% in the oral and intramuscular treatment groups respectively) was similar to that seen 10 years ago in this hospital. The average parasite clearance time had increased to 61 h, compared to 41 h noted 10 years ago. The incidence of hypoglycaemia (3%) was very low compared to studies in other malaria endemic areas. The reason for this is not clear but it could have contributed to the low mortality. Neurological deficits were seen on day 14 in 7.8% of patients. Parasitaemia recurred within 14 d in 22% of surviving patients, confirming the presence of RI/RII chloroquine resistance in Accra.
Pattern of drug utilization for treatment of uncomplicated malaria in urban Ghana following natio... more Pattern of drug utilization for treatment of uncomplicated malaria in urban Ghana following national treatment policy change to artemisinin-combination therapy
In Ghana a baseline survey examined management practices in the Ministry of Health (MOH) resource... more In Ghana a baseline survey examined management practices in the Ministry of Health (MOH) resources in the community availability of drugs in private and public facilities and households. These data were needed to implement essential drug activities within the Bamako Initiative. Even though MOH had a primary health care (PHC) strategy since 1978 it had not fully implemented PHC at subnational levels. People perceived health facilities as a source of curative care. Supervision of facilities was top down. Poor service conditions reinforced the low morale of health workers. Most facilities received most extra funding from hospital fees. The communities did not use these fees to fund development instead taxes funded community development and welfare groups. Only a small number of communities has bank accounts. Maternal and child health indicators showed limited PHC programs e.g. trained traditional birth attendants delivered just 9.5% of births. 75% of the public lived within 1 hour of a health facility. Few people preferred just traditional medicine (8.8%) or a traditional healer as their first choice (3.5%). Chemical sellers outnumbered MOH facilities as a source of drugs. 84.8% of drug outlet clients considered drug costs to be reasonable. Public facilities did a better job of drug logistics than did private facilities. Staff at both public and private facilities asked everyone requesting drugs to pay even when clients were poor. Inappropriate use of drugs and inappropriate instruction on how to use drugs were commonplace. Staff often took drugs. Shortages occurred for the most commonly prescribed drugs (chloroquine paracetamol and multivitamins). This study found inferior managerial capacity at MOH facilities especially poor financial management. MOH must come up with a mechanism to identify the poor so as not to deny them health services and drugs. Community leaders should not receive drugs and health services at no cost. Other recommendations are a system of prescription auditing and continuous education on drug use.
The landscape of public health in many sub-Saharan African countries has been changing rapidly ov... more The landscape of public health in many sub-Saharan African countries has been changing rapidly over the past few decades. Marked changes have been seen in the demographic structure of populations, economics, lifestyle changes, social upheavals (war and migration) and these have impacted disease patterns.
Pregnant women in malaria-endemic communities are susceptible to Plasmodium falciparum infections... more Pregnant women in malaria-endemic communities are susceptible to Plasmodium falciparum infections, with adverse consequences including maternal anaemia, placental malaria parasitaemia and infant low birth weight (LBW). We sought to assess the prevalence, incidence, and clinical markers of pregnancy-associated malaria (PAM) in a rural district of Ghana. A total of 294 pregnant women were enrolled and followed passively and actively, monthly and weekly until delivery. Haemoglobin levels, malaria parasitaemia and Hb electrophoresis were done from peripheral blood samples. At delivery, placental smears were examined for malaria parasites. Prevalence of peripheral blood P. falciparum parasitaemia at enrolment was 19.7% and related to parity. Incidence rate of parasitaemia was 0.06 infections/ person/month [95% confidence interval (CI): 0.04 to 0.08]. Symptomatic infections rose sharply from the first trimester to the last. Prevalence of malaria parasites in the placenta was 35.9% (61/170...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2006
Public health laboratories in Ghana performing tuberculosis (TB) microscopy. To assess the situat... more Public health laboratories in Ghana performing tuberculosis (TB) microscopy. To assess the situation of the laboratories in terms of staff strength, technical skills, documentation, biosafety practices, equipment, supplies and disposal systems. Methods used for data collection were interviews using a structured questionnaire, informal observation of laboratory registers, disposal systems and safety measures for sputum handling. Of 114 laboratories visited between 2000 and 2001, 102 (89.5%) were performing TB microscopy. Of the staff working in the laboratories, 9% were medical technologists, 24% laboratory technicians, 37% laboratory assistants and 30% orderlies. Average false-negative and -positive rates were respectively 13% and 14%. Although most of the centres (85.3%) were using the recommended TB laboratory register for recording, in most cases they were not filled in accurately or completely. The majority of the available microscopes had mechanical or optical faults. Availabil...
A 48 h in vitro test was conducted to compare the susceptibility of two strains of Plasmodium fal... more A 48 h in vitro test was conducted to compare the susceptibility of two strains of Plasmodium falciparum to chloroquine, the two enantiomers of chloroquine, desethylchloroquine and the new antimalarial drug pyronaridine. The five compounds similarly inhibited the chloroquine sensitive strain. However, desethylchloroquine was less active and pyronaridine was much more active than chloroquine and its enantiomers against the chloroquine resistant strain.
The effects of potassium chloride (as Slow-K® 600 mg three times daily) and spironolactone (as A ... more The effects of potassium chloride (as Slow-K® 600 mg three times daily) and spironolactone (as A ldactone-A,® 25 mg four times daily) were compared in hypertensive African patients on frusemide. Mean plasma-potassium levels in patients on frusemide plus Slow-K® and frusemide plus Aldactone-A® rose from 3.6 to 3.8 mOsm/L whilst on frusemide alone mean plasma-potassium fell from 3.7 to 3.6 mOsm/L. The mean blood pressure, both systolic and diastolic, was significantly reduced in the frusemide plus Aldactone-A® group when compared with patients on frusemide alone or on frusemide plus Slow-K®.
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