Search

ABSTRACTIntroductionAntimicrobial resistance (AMR) is a concern as this increases morbidity, mortality, and costs, with sub-Saharan Africa having the highest rates globally. Concerns with rising AMR have resulted in international, Pan-African, and country activities including the development of national action plans (NAPs). However, there is variable implementation across Africa with key challenges persisting.Areas coveredConsequently, there is an urgent need to document current NAP activities and challenges across sub-Saharan Africa to provide future guidance. This builds on a narrative review of the literature.Expert OpinionAll surveyed sub-Saharan African countries have developed their NAPs; however, there is variable implementation. Countries including Botswana and Namibia are yet to officially launch their NAPs with Eswatini only recently launching its NAP. Cameroon is further ahead with its NAP than these countries; though there are concerns with implementation. South Africa appears to have made the greatest strides with implementing its NAP including regular monitoring of activities and instigation of antimicrobial stewardship programs. Key challenges remain across Africa. These include available personnel, expertise, capacity, and resources to undertake agreed NAP activities including active surveillance, lack of focal points to drive NAPs, and competing demands and priorities including among donors. These challenges are being addressed, with further co-ordinated efforts needed to reduce AMR.

ABSTRACTBackgroundIntentional poisoning is becoming an important public health concern particularly among young women globally. Consequently, there is a need to analyze this further within countries to establish pertinent policies to reduce current incidence rates. This includes sub-Saharan African countries where there has been a scarcity of information. Consequently, we sought to establish the nature and sources of poisoning in patients admitted to a leading hospital in Botswana to help develop pertinent future policies for Botswana and surrounding countries.MethodsRetrospectively reviewing the medical records of all patients admitted to Princess Marina Hospital (PMH), which is a leading tertiary hospital in the capital city of Botswana, due to acute poisoning over a six-year period.ResultsThe records for 408 patients were reviewed. The majority of admissions (58%) were females, and the mean age of patients was 21(±14) years. Most poisoning cases (53%) were intentional. The 15–45 years age group was most likely to intentionally poison themselves compared to other age groups, with females four and half times more likely to intentionally poison themselves compared to males (AOR 4.53, 95% CI: 2.68–7.89, p < 0.001). Half of the patients were poisoned by medicines followed by household chemicals (22%), with females overall four times more likely to be poisoned by medicines compared to males. The medicine mostly ingested was paracetamol (30%). Failing relationships (57%) were the principal reason for intentional poisoning. Six patients died from poisoning representing a 1.5% mortality rate.ConclusionsThe findings suggest in-depth and urgent investigations on intentional poisoning are needed among young women across countries including sub-Saharan African countries to inform future policies on prevention strategies. Further, strategies for poisoning prevention should target social and family relationship problems. We will be following this up in the future.

ABSTRACTIntroduction: Appropriately managing mental disorders is a growing priority across countries in view of the impact on morbidity and mortality. This includes patients with bipolar disorders (BD). Management of BD is a concern as this is a complex disease with often misdiagnosis, which is a major issue in lower and middle-income countries (LMICs) with typically a limited number of trained personnel and resources. This needs to be addressed.Areas covered: Medicines are the cornerstone of managing patients with Bipolar II across countries including LMICs. The choice of medicines, especially antipsychotics, is important in LMICs with high rates of diabetes and HIV. However, care is currently compromised in LMICs by issues such as the stigma, cultural beliefs, a limited number of trained professionals and high patient co-payments.Expert opinion: Encouragingly, some LMICs have introduced guidelines for patients with BD; however, this is very variable. Strategies for the future include addressing the lack of national guidelines for patients with BD, improving resources for mental disorders including personnel, improving medicine availability and patients’ rights, and monitoring prescribing against agreed guidelines. A number of strategies have been identified to improve the treatment of patients with Bipolar II in LMICs, and will be followed up.

•Antimicrobial resistance (AMR) is a growing concern, especially in sub-Saharan Africa.•Antimicrobial stewardship programmes (ASPs) can reduce AMR, but little is known about them in Nigeria.•Only 24% of tertiary hospitals had an ASP, increasing to 35% with formalised structures and teams for stewardship.•Less than 25% have specific treatment recommendations, and only 12% have a formal procedure for reviewing appropriateness.•Antimicrobial susceptibility reports for the previous year were available in 18% of facilities, and 6% monitor utilisation.•The Nigerian Ministry of Health and other key stakeholders need to address the lack of ASPs to improve antimicrobial use.

ABSTRACTBackground and aims: Glycemic control among patients with diabetes mellitus is associated with a marked reduction of both macrovascular and microvascular complications; however, glycemic control remains an elusive goal worldwide. The aim of this study was to determine factors associated with glycemic control among patients attending a tertiary clinic in Botswana as limited information to date.Methods: Cross-sectional study in a tertiary clinic in Gaborone, Botswana. Patients were recruited between 21 July 2015 and 21 September 2015. The majority of the randomly recruited patients (368/380–96.8%) had documentation of glycemic control (HbA1c) within three months of study recruitment and were subsequently included in the analysis. Glycemic control was categorized as desirable, suboptimal and poor if HbA1c was <7%, 7–9% and >9%, respectively. Data were analyzed using SPSS for descriptive statistics including both bivariate and multinomial logistic regression. A value of p< 0.05 was considered statistically significant.Results: The analyzed study population consisted of 258/368 (70.1%) females with a mean age (SD) of 56.7 ± 13.6 years. Means (SDs) for diabetes duration and glycated hemoglobin were 7.2 ± 7.1 years and 7.97 ± 2.02%, respectively. Of the 368 patients, 136 (36.95%) and 132/368 (35.86%) had desirable and suboptimal glycemic control, respectively. Older age, attending the clinic for more or equal to 3 years and not being on insulin were associated with both desirable and suboptimal glycemic control whereas duration of diabetes between 5 and 10 years was associated with poor glycemic control.Conclusions: The majority of patients had poor glycemic control. Older age and not being on insulin were associated with better glycemic control. The fact that patients on insulin had poor glycemic control calls for more research to determine the timing of insulin initiations and dosing schedule factors as these will help to improve overall glycemic control in Botswana and elsewhere.

ABSTRACTObjectives: Diabetes mellitus (DM) is one of the most common contributors of chronic kidney disease (CKD). The epidemiology of CKD, a concern among patients with DM, has not been studied in Botswana. Consequently, the objective of this study was to estimate its prevalence among these patients in Botswana to provide future guidance to both government personnel and physicians.Methods: Observational cross-sectional study in a leading clinic in Botswana. Demographic and clinical data were obtained from patients through interviews and from their notes using a standard questionnaire. The study was conducted from July to October 2015. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet for Renal Disease equation. CKD was defined as an eGFR < 60 ml/min/1.73 m2. Multivariable logistic regression analyses were performed to assess the associations between CKD and potential factors.Results: The mean age and duration of DM among study participants were 54.67 years (range 21–92 years) and 5.0 years, respectively. Over half, i.e. 213/370 (57.6%) and 232/370 (62.7%), had an average blood pressure greater than 140/90 mmHg and poor glycemic control (HbA1c > 7%), respectively. 31/370 patients (8.4%) had CKD. However, only 18/370 (4.9%) had a diagnosis of CKD documented in their charts. Age, level of education, and duration of diabetes were independently associated with CKD.Conclusion: The prevalence of CKD by estimated eGFR was low compared to most previous studies. However, half of patients with CKD are not documented resulting in the potential for prescription errors and drug toxicity. A substantial number of our patients had uncontrolled hypertension and poor glycemic control. Older age, low level of education and longer duration of DM were associated with CKD. There is a need to carry out prospective studies to determine the association and role of glycemic and blood pressure control in CKD causation among patients with DM in Botswana.

ABSTRACTObjectives: Antibiotic prophylaxis in surgery is known to reduce the rate of surgical site infections (SSI) as well as shorten hospital stay. However, there is currently a scarcity of data on antibiotic prophylaxis and SSIs among African countries including Botswana. Consequently, this study aimed to address this.Methods: A prospective study involving 400 patients was carried out at a leading tertiary hospital in Botswana from 2014–2015. Patients’ demographic information, type of surgery performed and peri-operative use of antibiotics were documented. All enrolled patients were followed-up for 30 days post discharge to fully document the incidence of SSIs.Results: Median age of patients was 35.5 (25 – 50) years, with 52% female. There were 35.8% emergency and 64.2% elective surgeries. The most common operations were exploratory laparotomy (25%), appendectomy (18.3%), excision, and mastectomy (8%). Antibiotics were given in 73.3% of patients, mainly postoperatively (58.3%). The most commonly prescribed antibiotics were cefotaxime (80.7%), metronidazole (63.5%), cefradine (13.6%) and amoxicillin/clavulanate (11.6%). The incidence of SSI was 9%. The most common organisms were Pseudomonas aeruginosa, Staphylococcus aureus, and coagulase-negative staphylococci.Conclusion: The rate of SSI is a concern, and may be related to inappropriate antibiotic prophylaxis given post operatively. Interventions are in place to decrease SSI rates to acceptable levels in this leading hospital by improving for instance infection prevention practices including the timing of antibiotic prophylaxis. Research is also ongoing among other hospitals in Botswana to reduce SSI rates building on these findings.

ABSTRACTObjective: Pharmaceutical companies spend significant amount of resources on promotion influencing the prescribing behavior of physicians. Drug promotion can negatively impact on rational prescribing, which may adversely affect the quality of patient care. However, little is known about these activities in Nigeria as the most populous country in Africa. We therefore aimed to explore the nature of encounters between Nigerian physicians and pharmaceutical sales representatives (PSRs), and how these encounters influence prescribing habits.Methods: Cross-sectional questionnaire-based study conducted among practicing physicians working in tertiary hospitals in four regions of Nigeria.Results: 176 questionnaires were completed. 154 respondents (87.5%) had medicines promoted to them in the previous three months, with most encounters taking place in outpatients’ clinics (60.2%), clinical meetings (46%) and new medicine launches (17.6%). Information about potential adverse effects and drug interactions was provided in 41.5%, and 27.3% of cases, respectively. Food, in the form of lunch or dinner, was the most common form of incentive (70.5%) given to physicians during promotional activities. 61% of physicians felt motivated to prescribe the drug promoted to them, with the quality of information provided being the driving factor. Most physicians (64.8%) would agree to some form of regulation of the relationship between medical doctors and the pharmaceutical industry.Conclusion: Interaction between PSRs and physicians is a regular occurrence in Nigeria, influencing prescribing practices. Meals and cheap gifts were the most common items offered to physicians during their encounters with PSRs. The need for some form of regulation by professional organizations and the government was expressed by most respondents to address current concerns.

ABSTRACTBackground: Prescribing medicines in an off-label manner for children with chronic conditions is sparsely documented, even more so among developing countries. This needs addressing. The objective of this research was to investigate the extent of off-label prescribing among children with epilepsy, asthma, and sickle cell anaemia in Nigeria.Methods: Prescriptions for children ≤16 years documented in their case files that attended paediatric clinics in Lagos, Nigeria, for these three conditions between January and October 2015, were reviewed retrospectively to extract data on the medicines prescribed. British National Formulary for children and American Hospital Formulary Service Drug information were used as references.Results: 477 patients received 1746 prescriptions. Off-label prescriptions were seen in 7.7% of prescriptions, related to dose (93; 68.9%), indication (22; 16.3%), and age (20; 14.8%). Nervous system (525; 30.1%) and anti-infective (441; 25.2%) medicines were the most prescribed but only 9.5% and 8.2% of the respective prescriptions were off-label. Children with epilepsy received the most number (94; 69.6%) of off-label prescriptions. The three chronic conditions did not associate significantly with the category of off-label medicine prescribed (p = 0.925).Conclusion: Off-label prescribing for children with epilepsy, asthma and sickle cell anaemia occurs. Encouragingly, the overall rate appears low in Nigeria.

Aim:Hypertension is a leading global health problem requiring lifelong treatment. However, adherence to antihypertensive medicines is a problem, greater among developing countries. Consequently, there is a need to determine current adherence rates and their associations among developing countries to plan future initiatives. Materials & methods:Cross-sectional study among adult outpatients with essential hypertension in Tanzania. Predesigned questionnaires were used to gather information on adherence rates and patient-related beliefs. The main outcome measure was adherence. Results:A total of 180 participants were included, with females making up 65. High-adherence rates were seen in 54 of the patients. Patients’ belief about their medication and its necessity was higher in the high adherent group and concerns about their medicines and their necessity were higher in the low adherent group. Conclusion & recommendations:Adherence rates were low compared with a suggested level ≥80. Educational initiatives are needed to address knowledge and concerns with hypertension to improve future outcomes.

A multiple reaction monitoring liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for the simultaneous determination of five antiretroviral drugs i.e.emtricitabine, tenofovir, efavirenz, lopinavir and ritonavir using commercially sterilized human blood plasma as the matrix and a THF/water solvent system was developed for therapeutic drug monitoring purposes and partially validated using the United States Food and Drug Administration (US FDA) guidelines. The analytical performance characteristics that were examined were limits of detection (LODs), lower limits of quantification (LLOQs), upper limits of quantification (ULOQs), selectivity, percent mean recoveries, precision measured as percent relative standard deviations and accuracy. Optimized LC-MS/MS parameters were employed for this purpose. The percent mean recoveries were between 77.3 and 90.1% using solid phase extraction (SPE) for sample preparation. These recoveries were obtained at three spike levels i.e.the LOD, the LLOQ and the ULOQ. The precision of the SPE technique was within an acceptable range of <15% i.e.between 2.7 and 9.2% at the LLOQ. Accuracy was calculated as the percent deviation of the mean value from the true value and the values ranged between 9.9 and 22.7%. The SPE technique satisfied all the requirements of the US FDA guidelines except for efavirenz whose accuracy was slightly higher than recommended at the LLOQ i.e.22.7% as opposed to 20%. The limits of detection using SPE also fell below the clinically relevant therapeutic range (3–8 mg L−1) for most of the drugs and therefore the method could be useful for therapeutic drug monitoring in HIV patients.

Background: We have previously found decreased CYP2C19 activity in Tanzanians tested with mephenytoin and omeprazole in relation to genotype when compared with white and Asian subjects.Objective: We investigated the impact of CYP2C19 genotype and phenotype on chloroguanide (INN, proguanil) metabolism to its metabolites cycloguanil and 4-chlorophenylbiguanide.Methods: A single oral chloroguanide dose was given to 25 healthy Tanzanian subjects with CYP2C19 genotypes (CYP2C19*1, CYP2C19*2, and CYP2C19*3). Homozygous wild-type and mutated genotype groups were chosen randomly, but the heterozygous genotype group was chosen with a range in phenotype. We used a novel HPLC method for drug determination.Results: Pharmacokinetics of chloroguanide did not differ between groups. Maximum plasma concentration (C) and area under the plasma concentration versus time [AUC(0-∞)] for cycloguanil was significantly lower (t test P < .05) in the homozygously mutated group compared with the homozygously wild-type group. There were similar significant group differences of median urinary excretion. The chloroguanide/cycloguanil ratio closely correlated (rs= .87) with omeprazole metabolic ratio, confirming that Tanzanian subjects are generally slower CYP2C19 metabolizers. It also confirms that CYP2C19 genotype and phenotype predicts cycloguanil formation. In addition, a 3-hour plasma sample metabolic ratio also seems to be a proper time for omeprazole phenotyping in Tanzanian subjects. Because the plasma concentrations of cycloguanil and 4-chlorophenylbiguanide covary (rs= .89), it is now suggested that their formation be catalyzed by the same enzyme (ie, CYP2C19) through a common intermediate, the structure of which is also presented.Conclusions: As shown in an earlier study, also with a third substrate, Tanzanians have a lower capacity to form cycloguanil than white and Asian subjects. Individuals with two mutated alleles have lower metabolic capacity than individuals with two wild-type alleles or individuals in the heterozygous group, which may lead to chloroguanide therapeutic failure. This knowledge should be important when selecting appropriate patients and doses of chloroguanide in different populations.

The source, availability, and use of antimalarial drugs in a rural community in the Kibaha district of Tanzania were assessed. Using questionnaires, the heads of households and mothers/guardians of children under five years of age in 1000 randomly selected households were interviewed, and an inventory of antimalarials at all drug stores and shops in the area was carried out. The majority of the drugs stocked by both households and mothers/guardians were antimalarials, exclusively chloroquine. Only 20.1% of the mothers/guardians knew the correct pediatric dose regimen of the chloroquine syrup which they stocked the most. In contrast, 70.4% of the mothers/guardians stated the correct adult dose of chloroquine tablets. They had significantly (p < 0.025) higher mean ages than those who stated the dose incorrectly. Similarly, 78.6% of heads of households stated the correct adult dose of chloroquine tablets, and those with more education had better knowledge of dose regimens (p < 0.001). Drug stores were the main sources of malaria treatment for both the heads of households (72.2%) and the mothers/guardians (89.4%). Lack of drugs at public health facilities, as stated by more than 85.6% of the mothers /guardians, is a possible reason for this. Only four of the drug store sellers had professional training. Most malaria treatment in children occurs in the home and, thus, poor knowledge of pediatric chloroquine regimen by the mothers/guardians is of great concern. A simplified dose regimen, particularly the pediatric formulation for mothers/ guardians with limited education, should be developed. As these caregivers interact with the public and private health facilities, the quality of malaria management, including instructions given to them, needs to be assessed.

The cytochrome P450 2D6 (CYP2D6) genotypes and phenotypes of 106 unrelated, healthy black Tanzanians of Bantu origin were investigated. The results revealed a population with a generally decreased capacity to metabolize the CYP2D6 substrate debrisoquine with 59 of the Tanzanian extensive metabolisers having debrisoquine metabolic ratios (MRs) > 1 versus 20 in Caucasians. This decrease in metabolic capacity was not fully explained by the partially or fully detrimental CYP2D6gene mutations analysed for in this study. As many as 7 poor metabolizers of debrisoquine were identified but none was homozygous for defective CYP2D6alleles. The majority among the group of poor metabolizers had relatively low metabolic ratios. The mutational profile indicated a closer association of the Tanzanian CYP2Dlocus to that of Zimbabweans rather than to that of Ethiopians. The defective alleles CYP2D63, 4, 5and 6were found at low frequencies (0, 1, 6, 0, respectively), whereas the CYP2D617allele causing an enzyme with altered specificity was common (allele frequency = 17). It is concluded that the CYP2D6genotype in the Tanzanian Bantu population is different from that of other African populations examined to date and that further studies are required to explain the generally lower capacity to metabolize CYP2D6 substrates.

The source, availability, and use of antimalarial drugs in a rural community in the Kibaha district of Tanzania were assessed. Using questionnaires, the heads of households and mothers/guardians of children under five years of age in 1000 randomly selected households were interviewed, and an inventory of antimalarials at all drug stores and shops in the area was carried out. The majority of the drugs stocked by both households and mothers/guardians were antimalarials, exclusively chloroquine. Only 20.1% of the mothers/guardians knew the correct pediatric dose regimen of the chloroquine syrup which they stocked the most. In contrast, 70.4% of the mothers/guardians stated the correct adult dose of chloroquine tablets. They had significantly (p < 0.025) higher mean ages than those who stated the dose incorrectly. Similarly, 78.6% of heads of households stated the correct adult dose of chloroquine tablets, and those with more education had better knowledge of dose regimens (p < 0.001). Drug stores were the main sources of malaria treatment for both the heads of households (72.2%) and the mothers/guardians (89.4%). Lack of drugs at public health facilities, as stated by more than 85.6% of the mothers/guardians, is a possible reason for this. Only four of the drug store sellers had professional training. Most malaria treatment in children occurs in the home and, thus, poor knowledge of pediatric chloroquine regimen by the mothers/guardians is of great concern. A simplified dose regimen, particularly the pediatric formulation for mothers/guardians with limited education, should be developed. As these caregivers interact with the public and private health facilities, the quality of malaria management, including instructions given to them, needs to be assessed.

Abstract: Objective: Routine malaria prophylaxis with chloroquine (CQ) is recommended to pregnant semi-immune women in several countries in Africa. The dosage is empirically based. We investigated whether blood CQ concentrations and apparent oral blood clearance (CL/F) change during the course of pregnancy. We also studied whether malaria parasites could be detected together with low CQ blood levels. Methods: Forty nine semi-immune Tanzanian women were recruited in the 16th week of pregnancy. They were given 310 mg oral CQ base once per week as prophylaxis during the whole pregnancy. Capillary blood samples were taken for analysis of CQ before treatment and at weeks 26 and 36. Blood samples were dried on filter paper and analysed by HPLC. Blood was also drawn to detect occurrence of malaria parasites. Results: A total of 25 women fulfilled the sampling schedule. CL/F increased significantly from 160 ml ·  min−1 at week 26 to 180 ml · min−1 at week 36. In 7 of 25 women, CL/F increased >20%. Trough blood CQ concentrations, determined on four occasions at week 26 and at week 36 varied between 200 and 900 nmol · l−1. No statistically significant differences between occasions were seen. Malaria parasites were seen in two individuals early in pregnancy. Conclusion: Blood CQ CL/F showed a small increase during the course of pregnancy. The estimated mean blood CL/F values of 160 and 180 ml · min−1 (week 26 and 36, respectively) were higher than the mean CL/F of 125 ml · min−1 in non-pregnant individuals, published previously. Efficacy of higher dosages of CQ in malaria prophylaxis in pregnant women could, therefore, be evaluated in controlled trials in high-risk malaria areas.

Drug prescribing patterns were studied in 720 retrospective and 779 prospective outpatient prescriptions from 20 dispensaries in Dar es Salaam region, and these revealed a mean drug exposure of 2.0 and 2.3, respectively. The percentage of patients leaving the dispensaries with no prescribed drugs was 1.3% and 0.7%, respectively. Prescriptions containing antibiotics were 36.8% (retrospective) and 39.8% (prospective), while injections accounted for 24.6% and 34% of the total encounters, respectively. Over 70% of prescriptions conformed to the Tanzania essential drug list (EDP) and/or standard treatment guidelines and consisted of 83.9% and 79.1% generic prescriptions, respectively. Interestingly, only 15% of the surveyed dispensaries had an EDP book and/or calendar. Despite the consulting and dispensing times being short (2.98 min and 77.7 s, respectively), 70% of the patients could remember the dosing instructions. Only 64% of the patients had a minimum physical examination.

To investigate the CYP2C19 polymorphism in Tanzanians because this enzyme shows large interindividual differences in activity and metabolizes several drugs of importance in Africa, especially the antimalarial agent chloroguanide (INN, proguanil). Two hundred fifty‐one Tanzanian healthy volunteers were phenotyped with respect to CYP2C19 with use of a single oral dose of mephenytoin (n = 106), a single oral dose of omeprazole (n = 207), or both. Sixty‐two were phenotyped with both probe drugs. The urinary 0‐ to 8‐hour S/R‐mephenytoin ratio and the plasma omeprazole metabolic ratio (MR) (omeprazole/hydroxyomeprazole) 3 hours after drug intake were determined. The genotype was determined by analysis for CYP2C19*1(wt), CYP2C19*2(m1), and CYP2C19*3(m2). Ten subjects with high omeprazole MR were screened for new mutations in the CYP2C19gene by searching for single‐strand conformation polymorphisms (SSCP). Eight subjects were classified as mephenytoin poor metabolizers (7.5%). Only 5 of these were homozygous for mutated alleles. The S/R ratio was skewed to the right (lower CYP2C19 activity) compared with other ethnic groups studied previously. No new mutations were found with polymerase chain reaction (PCR)‐SSCP. We found 30 volunteers (14.5%) with an MR >7, which is the antimode found previously in white subjects and Asian subjects. Of the 251 volunteers genotyped, 3.2% were homozygous for mutated alleles and 66.1% were homozygous for the wild‐type allele. The allele frequencies of CYP2C19*1, *2, and *3were 81.5%, 17.9%, and 0.6%, respectively. The correlation between the S/R‐mephenytoin ratio and the omeprazole MR was significant (Spearman r= 0.59; P< .01). Tanzanians have a decreased capacity to metabolize both omeprazole and mephenytoin when their genotype is compared with metabolic capacity and genotype in other previously studied populations. We identified a low frequency of the Asian allele (CYP2C19*3). Although we did not find any new mutations, our results may be consistent with the presence of yet‐unidentified mutations of CYP2C19that causes decreased CYP2C19 activity in the Tanzanian population. Clinical Pharmacology & Therapeutics(1998) 64, 391–401; doi:

A retrospective survey of prescribing patterns in 10 church-owned primary healthcare (PHC) institutions in Dar es Salaam region, Tanzania, was carried out by trained research assistants in order to assess the prescribing practices of healthcare providers in these institutions. From a total of 15 000 prescriptions, 600 were recorded randomly from patient registers retrospectively. This work was carried out between April to September 1996. Each prescription was recorded using World Health Organization Action Programme on Essential Drugs (WHO/DAP) forms and analysed manually. The average number of drugs per prescription was 2.9; the percentage encounters for injections and antibiotics was 38 and 71, respectively. Ninety-four per cent of all drugs were prescribed according to the essential drug list of Tanzania.

The bioavailability of chloroquine from a single oral dose (10 mg/kg body weight) of a sugar-coated (DawaquinR) and a plain formulation (ShellyquineR) of chloroquine phosphate were compared in two groups of 10 volunteers each, following an overnight fast. Whole blood chloroquine concentrations were measured using high-performance liquid chromatography (HPLC) and bioavailability was determined by measuring area under the blood chloroquine concentration curve (AUC ng mL−1h) and the peak blood chloroquine concentration (Cpmaxng/mL). The AUC and Cpmaxfor Shellyquine were 4396.3 ± 833 ng mL−1h and 162 ± 14 ng/mL, respectively. The AUC and Cpmaxfor Dawaquin were 2060 ± 339 ng mL−1h and 56.6 ± 5.2 ng/mL, respectively. Shellyquine was significantly more bioavailable than Dawaquin (P<0.001). Although the Cpmaxfor Dawaquin was higher than the required therapeutic level for sensitive Plasmodium falciparumof 30 ng/mL, its blood levels may not guarantee a rapid clearance of parasites. The differences between the two formulations point to a problem in the quality of pharmaceuticals marketed in this country, whose extent need to be ascertained further. Failure of chloroquine phosphate in this country has already been declared by the Ministry of Health, and the potential contribution of poorly formulated products remains a subject of debate.

Increasing efforts are being made to improve drug-use practices and prescribing behaviour in developing countries. An essential tool for such work is an objective and standard method of assessment. We present here a set of drug-use indicators produced and tested in twelve developing countries. We describe practical applications, which include the use of indicators to increase awareness among prescribers in Malawi and Bangladesh, to identify priorities for action (eg, polypharmacy in Indonesia and Nigeria, overuse of injections in Uganda, Sudan, and Nigeria, and low percentage of patients who understood the dosage schedule in Malawi), and to quantify the impact of interventions in Yemen, Uganda, Sudan, and Zimbabwe.