Changing antibiotics prescribing practices in health centers of Khartoum State, Sudan.

OBJECTIVE: A major problem with inappropriate use of antibiotics is the emergence of resistance. Thus, cost-effective interventional strategies are required to improve their use. This study aimed to evaluate the effect of multifaceted interventions on prescribing practices of antibiotics in health centers of Khartoum State, Sudan. METHODS: Twenty health centers were randomly assigned to receive: (1) no intervention; (2) audit and feedback; (3) audit and feedback + seminar; or (4) audit and feedback + academic detailing. A total of 1,800 patient encounters, 30 from each health center, were randomly collected. The total number of encounters with antibiotics prescribed were determined in each health center and they were evaluated with regard to antibiotic choice, dose and duration of therapy before the study and at 1 and 3 months post-intervention. RESULTS: In comparison to the control group, the prescriber targeted interventions involving audit and feedback, together with academic detailing (4), reduced the mean number of encounters with an antibiotic prescribed by 6.3 and 7.7 (p<0.001) at 1 and 3 months post-intervention, respectively. In addition, the mean number of encounters with an inappropriate antibiotic with respect to diagnosis, doses and/ or duration of therapy was reduced by 5.3 and 5.9 (p<0.001) at 1 and 3 months post-intervention, respectively. For audit and feedback together with seminars (3) and for audit and feedback alone (2), the corresponding reductions were 5.3, 7.1, 4.4 and 5.1 (p<0.001) and 1.4, 2.8, 1.8 and 1.9 (p>0.05), respectively. CONCLUSION: Inappropriate prescribing patterns of antibiotics in health centers of Khartoum State, Sudan, are alarmingly high. Multifaceted interventions involving audit and feedback combined with either academic detailing or seminars appear more effective in changing prescribing practices of antibiotics than audit and feedback alone.

Clinical pattern of severe Plasmodium falciparum malaria in Sudan in an area characterized by seasonal and unstable malaria transmission.

A hospital-based study was carried out in Gedarif town, eastern Sudan, an area of markedly unstable malaria transmission. Among the 2488 diagnosed malaria patients, 4.4% fulfilled the WHO criteria for severe malaria, and seven died of cerebral malaria. The predominant complication was severe malarial anemia (45.4%), followed by convulsions (21%), cerebral malaria (16. 4%) and hypotension (11.8%). Severe malaria was recognized in all age groups, but 44.5% of patients were aged 2 to 4 years. The mean ages of patients with severe anemia (5.6 years) and convulsions (5.9 years) were significantly lower than the mean ages of patients with cerebral malaria (14.1 years) or hypotension (35.2 years). Patients with convulsions and cerebral malaria had significantly higher mean parasite count (69972 and 56110 parasites/microL, respectively) than patients with severe anemia (24637 parasites/microL) or hypotension (13667 parasites/microL). The mean blood glucose level was higher in patients with cerebral malaria than in patients with anemia, and higher in patients who died than in patients who survived. In this setting, the clinico-epidemiological pattern of severe malaria varies considerably from that of hyperendemic regions in sub-Saharan Africa, and there is considerable variation between the individual complications of severe malaria.

Pharmacokinetics of artesunate following oral and rectal administration in healthy Sudanese volunteers.

The aims of this study were to determine the pharmacokinetic parameters of a single dose of 200 mg oral and rectal artesunate in healthy volunteers, and to suggest a rational dosage regimen for rectal administration. The study design was a randomized open cross-over study of 12 healthy volunteers; the analytical method used was a reversed phase high performance liquid chromatography with post column derivatization and subsequent ultraviolet detection. Pharmacokinetic parameters were derived from the main metabolite alpha-dihydroartemisinin data due to the rapid disappearance of artesunate from the plasma. Dihydroartemisinin following oral administration of artesunate had a significantly higher AUC(0-infinity) (P<0.05 95% confidence interval (CI) -1168.73, -667.61 ng x h/mL(-1)) and Cmax (P<0.05; 95% CI -419.73, -171.44 ng/mL(-1)), and had shorter tmax (P<0.05; 95% CI -0.97, -0.10 h) than that following rectal artesunate. There was no statistically significant difference in the elimination half-life between both routes of administration (P>0.05; 95% CI -0.14, 0.53 h). The relative bioavailability of rectal artesunate was [mean (coefficient of variation %) 54.9 (24.8%) %]. On the basis of these data an 8 hourly dosing regimen per day with rectal artesunate is proposed.

Symptoms in patients attending services for diagnosis of pulmonary tuberculosis in Sudan.

OBJECTIVE: To describe the variation in clinical features of individuals presenting to a health facility with chest symptoms according to their ultimate diagnosis. METHODS: Of 16735 patients (52.6% males and 47.4% females) presenting at respiratory centres in seven states in Sudan, 5338 patients were identified with respiratory tract symptoms: 2917 (54.6%) men and 2421 (45.4%) women, with a mean age of 32 years. Those who had cough for more than 3 weeks that was not responsive to a course of antibiotics were screened by microscopy of two or three sputum specimens and chest radiography. RESULTS: A total of 504 (9.44%) were smear-positive, 259 (4.85%) were smear-negative, and 166 (3.11%) had extra-pulmonary tuberculosis, of whom 59 (1.11%) had pleural involvement; the remaining 4409 suspects (82.6%) were non-tuberculous. CONCLUSION: Tuberculosis patients had a constellation of presenting symptoms, with the principal symptom being cough for more than 3 weeks. The accompanying symptoms with greatest predicted significance were weight loss, tiredness and night sweats.

The effect of decentralisation on tuberculosis services in three states of Sudan.

SETTING: Referral hospitals and primary health care (PHC) facilities in Khartoum, Red Sea and Gadaref States. OBJECTIVES: To measure the effect of the decentralisation of the tuberculosis (TB) services on the clinical profile and treatment outcome of tuberculosis. DESIGN: A cohort study of case detection and treatment outcome using information routinely collected comparing patients attending PHC facilities and referral hospitals in selected locations in Sudan. RESULTS: Two-thirds of all TB patients were diagnosed in referral hospitals and one-third in PHC facilities. In PHC facilities, women represented 46% of notified cases, compared to 37.9% in referral hospitals (OR 1.398, 95%CI 1.343-1.455). Older age groups were more likely to prefer PHC facilities to referral hospitals. In referral hospitals, 38% were cured, 29.3% completed treatment without smear examination and 17.3% defaulted, while in PHC facilities 58% were cured, 17.8% completed treatment without smear examination and 11.6% defaulted. CONCLUSION: PHC facilities provide care for a higher proportion of women and older age groups of tuberculosis patients, suggesting a higher level of accessibility for these groups. A higher cure rate and a lower default rate were noted in PHC facilities, possibly reflecting better conditions for directly observed treatment and follow-up.

Descriptive study on the efficacy and safety of artesunate suppository in combination with other antimalarials in the treatment of severe malaria in Sudan.

Documentation on the efficacy of artesunate in Africa is limited, and no experience of artesunate use in Sudan is documented. Severe malaria in rural areas of Sudan, where facilities for the safe and effective use of parenteral quinine are lacking, is a frequent problem. Early treatment with artesunate suppositories would provide a simple method for use by unskilled staff and would be an alternative approach to treat malaria in settings with poor resources. We describe a hospital-based study of rectal artesunate in 100 adult patients with severe falciparum malaria with a dose derived from pharmacokinetic data (200 mg every 8 hours) over 3 days, which halted progression of severe disease and had a low fatality rate. The dosage schedule led to a rapid clinical response and reduced parasite clearance and fever subsidence times of (31.5 +/- 10.1 hours) and (31.4 +/- 11.1 hours). The sequential treatment of rectal artesunate with either doxycycline or pyrimethamine/sulfadoxine or mefloquine resulted in similar clinical cure rates of around 100%, and the combination of artesunate with either doxycycline or pyrimethamine/sulfadoxine was equally effective as mefloquine in preventing recrudescence. There were no significant adverse effects or signs of toxicity related to the treatment observed during the 28-day follow-up. The combination regimens could be used in areas where there is limited access to parenteral therapy for malaria.

Onchocerca volvulus: genetic diversity of parasite isolates from Sudan.

Onchocerciasis in Sudan exists in three distinct foci which exhibit differing clinical presentations. Previous studies have demonstrated that a tandemly repeated Onchocerca sequence family with a unit repeat length of 150 bp (the O-150 family) is a useful marker for deducing relationships among different O. volvulus populations. In the current study, the O-150 repeat families of O. volvulus from Sudan were analyzed and compared to each other and to those of parasites from West Africa. Similar to West African and American O. volvulus, the O-150 families of the Sudanese parasites could be divided into clusters within which little or no intracluster variation was evident, suggesting that the O-150 family in these parasites was subject to the forces of concerted evolution. Statistical analysis of the O-150 families from the different Sudanese parasite isolates, employing a nested algorithm based on an analysis of variance, revealed that O. volvulus endemic to the northern focus at Abu Hamed were significantly different from all other O. volvulus populations examined to date. In contrast, parasites from the southern and eastern foci of Sudan were indistinguishable from those endemic to the West African savanna. The significance of these data are discussed in light of knowledge of the biogeography and biology of transmission of O. volvulus in Africa.

Cytotaxonomic and molecular analysis of Simulium (Edwardsellum) damnosum sensu lato (Diptera: Simuliidae) from Abu Hamed, Sudan.

The northernmost focus for Onchocerca volvulus Leuckhart (Nematoda: Onchocercidae), the causative agent of human onchocerciasis, is found along the Nile near the town of Abu Hamed in Sudan. The vector for O. volvulus at this focus is a single monomorphic population of Simulium (Edwardsellum) damnosum Theobald. This black fly population is limited to a small area between the fourth and fifth cataracts of the Nile River that is isolated geographically from all other populations of S. damnosum sensu lato. Phylogenies produced from cytological analyses and sequence data derived from the NADH dehydrogenase subunit 4 and 16S rRNA genes indicate that Abu Hamed black flies are similar to, but distinct from, the savanna-dwelling sibling species of S. damnosum s.l., Simulium (Edwardsellum) damnosum sensu strictu Theobald, and S. (Edwardsellum) sirbanum Vajime & Dunbar. The DNA sequence and the cytological data support the hypothesis that the black fly population present in Abu Hamed may represent a new sibling species of S. damnosum s.l. We propose that this population be informally designated as the hamedense form of the Simulium damnosum complex.

A study of the urban malaria transmission problem in Khartoum.

A study of malaria prevalence and transmission was carried out in Khartoum, the capital of Sudan. The sentinel sites were El manshia, an urban area on the Blue Nile and Ed dekheinat, a lower-income peri-urban area bordering the White Nile. Anopheles arabiensis, the only malaria vector encountered, was present throughout the year although vector density varied seasonally. Plasmodium falciparum was the only species found in El manshia. In Ed dekheinat P. falciparum, Plasmodium ovale and Plasmodium vivax constituted 84.9, 8.2 and 6.9% of the cases, respectively. Plasmodium ovale appears to have recently spread into Khartoum since it has not previously been reported there. We conclude that focal transmission of malaria in the districts bordering both Niles has become established and that the reservoir of human infections has increased in recent years leading to increased risk of malaria epidemics, particularly in the aftermath of seasonal flooding.

Effects of single-dose praziquantel on morbidity and mortality resulting from intestinal schistosomiasis.

The long-term effect of single-dose praziquantel on morbidity and mortality from Schistosoma mansoni was investigated in surveys in 1987 and 1994 in central Sudan. Prevalence of infection dropped from 53% to 34%, and intensity of infection (> or = 400 eggs/g of faeces) from 31% to 18%. There was a reduction in hepatomegaly and hepatosplenomegaly, although splenomegaly alone was unchanged. Prevalence of periportal fibrosis decreased from 14% to 10%. Endoscopic investigation of patients with fibrosis showed a reduction in oesophageal varices from 47% to 30%. Mortality due to bleeding varices was high (community-wide, up to 11/100 infected patients with bleeding). Thus praziquantel mass treatment can be spaced to a much longer period, reducing the expense of treatment, delivery and distribution.

Mortality due to schistosomiasis mansoni: a field study in Sudan.

Although schistosomiasis affects 200 million persons, 20 million of whom have advanced disease, little is known about the mortality pattern in areas of endemic schistosomiasis mansoni. In an attempt to assess the mortality rates in an endemic area in Sudan, we conducted two demographic surveys in a village in the Gezira area. Clinical, sonographic, and parasitologic examinations were performed in a randomly selected sample of 25% of the population in 1987 and 1994. One of us asked each head of household about the names, sex, and age of family members. Particularly, we asked about death in the family if any, history of schistosomiasis, abdominal swelling, and hematemesis. Possible causes of death were ascertained by reviewing medical records in the village dispensary and the district hospital. There were 42 deaths in the village. Four males died of hematemesis secondary to portal fibrosis. The crude mortality rate of schistosomiasis was is 51/100,000/year. The overall schistosomiasis fatality rate per year was 1/1,000 infected persons, but was as high as 11/100/infected patients with bleeding varices. These findings showed the impact of schistosomiasis on public health in this economically important region of Sudan.

The burden of Onchocerca volvulus in Sudan.

Onchocerciasis has been reported in Sudan since 1908 and now prevails in three endemic regions known as the southern, northern and eastern foci. The southern focus is the largest, with nodule and blindness rates exceeding 80% and 12%, respectively, in certain villages. Onchocercal infection in this region causes only a mild skin reaction although microfilarial loads in the skin are high. In contrast, those with onchocerciasis in the northern focus, located between the fourth and fifth Nile cataracts, present with limited but severe skin reactions, low nodule rates (16%), low microfilarial loads in the skin and no ocular involvement. The characteristics of patients from the eastern focus, close to the border with Ethiopian border are similar to those in the north, although most onchocercal skin disease in this area comprises the severe localized pruritus known as sowda.

Blood supply and vasculature of mycetoma.

The blood supply to the mycetoma lesion and its vasculature were studied in patients with various types of mycetoma using histological, ultrastructural, angiographic and sonographic techniques. The mycetoma lesion proved to be well vascularized. However, certain vascular abnormalities were demonstrated. In histological sections, the small arteries and arterioles showed medial muscular hypertrophy in 83%, intimal fibrosis in 33%, arteritis in 7% and endarteritis obliterans with narrowed lumen in 7% of the patients. No vascular occlusion, ischaemic changes or arteriovenous shunts were observed. These changes were confirmed ultrastructurally. Angiography of the lesion showed a brisk pathological circulation which was more evident in eumycetoma. The vascular Doppler study showed normal blood flow pattern in the affected limb. Regional intra-arterial chemotherapy for mycetoma is suggested as a possible treatment modality.

Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus.

OBJECTIVE: To determine the distribution of ivermectin in plasma and tissues of onchocerciasis patients following a single oral dose of 150 micrograms kg-1. SETTING: Medical Department at Soba University Hospital, Khartoum. PATIENTS: Twenty five patients and fourteen healthy volunteers. METHODS: Serial blood samples were obtained from both groups. Tissue samples were removed from various patients as full thickness skin punch biopsies or during nodulectomy. Ivermectin concentration was determined by radioimmunoassay. RESULTS: The plasma pharmacokinetic variables for patients were; maximum plasma concentration 52.0 ng ml-1; time to achieve maximum concentration, 5.2 h.; elimination half life, 35.0 h; and the area under the plasma concentration curve versus time, 2852 ng.h.ml-1. In healthy volunteers, the plasma ivermectin distribution was similar to that in patients, and both groups showed a tendency for a second rise in plasma concentration of the drug suggestive of enterohepatic recirculation. Ivermectin was detected in tissues obtained from patients. Fat showed the highest and most persistent levels, whilst values for skin, nodular tissues, and worms were comparable. Subcutaneous fascia contained the lowest concentrations. CONCLUSIONS: Infection with O. volvulus does not affect the pharmacokinetics of ivermectin, and filarial infected tissues and parasites themselves do take up the drug. There may be prolonged retention of ivermectin because of depot formation in fat tissue.

Community based distribution of ivermectin in eastern Sudan: acceptability and early post-treatment reactions.

A study to monitor ivermectin acceptability and post-treatment reactions during mass community distribution was carried out in eastern Sudan, where severe reactive onchodermatitis is prevalent. Of 1081 individuals eligible for treatment, 1076 (99.5%) accepted the ivermectin. Post-treatment reactions were monitored by self reporting, 5 d after a single dose of about 150 micrograms/kg (range 103-200 micrograms/kg); 230 persons reported adverse events (21.4%). No reaction was rated as severe. The most common problem was itching with cutaneous papular eruptions (16.2%). Local oedematous swelling was the second most common and the most slowly resolving complaint (5.4%), followed by musculoskeletal pain. There was a high acceptance rate of the treatment and remarkable tolerance of the post-treatment effects, probably due to efforts made to prepare the community to expect reactions to ivermectin, widespread awareness of the beneficial effects of treatment by villagers who had participated in clinical trials previously, and the encouragement we gave to the population to become involved in improvement of their health care services. Single doses of ivermectin resulted in good clinical responses and created much goodwill among villagers. Improvements in physical fitness, ability to work, and freedom from musculoskeletal pain were reported at the 3 months' follow-up. We recommend that, during mass distribution of ivermectin, community involvement in planning overall health improvement should be included, since the treatment initiates the process well. In areas where sowda syndrome is prevalent, medical surveillance for 3 d or more should be considered.

Ivermectin treatment in severe asymmetric reactive onchodermatitis (sowda) in Sudan.

Ivermectin efficacy and post-treatment reactions in asymmetric severe reactive ochodermatitis (sowda) were studied in 8 patients with sowda syndrome and 6 with mild generalized onchodermatitis in Sudan. Initial skin snips from 12 patients contained microfilariae (1-9 per mg skin). Patients were treated in hospital with a single oral dose of c. 150 micrograms/kg ivermectin (103-200 micrograms/kg) and monitored for frequency and severity of post-treatment reactions for 4 weeks. Serial samples of heparinized blood were collected over the first 24 h after treatment for determination of ivermectin pharmacokinetics. Skin snips from all patients on days 3 and 28 revealed no microfilariae. Post-treatment reactions were more common and severe in individuals with sowda; they consisted mainly of musculoskeletal pain, local swellings with pitting oedema, and lymph gland tenderness and enlargement. No relation was established between these reactions, the microfilarial infection intensity, or the plasma pharmacokinetic profiles. A single oral dose of ivermectin cleared the skin of microfilariae and led to improvement of symptoms and dermatological signs of sowda, but resulted in more marked reactions than in cases of generalized onchodermatitis.

Pneumatosis cystoid intestinalis: a case report.

A case of pneumatosis cystoid intestinalis associated with duodenal ulcer and pyloric stenosis is reported. Review of literature revealed that, this is the first reported case in the Sudan and in Africa at large. The clinical presentation of this patient was confusing and it seems reasonable to consider pneumatosis in the differential diagnosis of pneumoperitonium associated with duodenal ulcer to avoid unnecessary laparotomy.

The effect of propranolol on paracetamol metabolism in man.

Ten healthy volunteers were treated for 4 days with 160 mg propranolol HCl and placebo in random order. At the end of each treatment salivary antipyrine kinetics and the plasma kinetics and urinary excretion of paracetamol and its major metabolites were measured following a 1500 mg oral dose. Propranolol prolonged the half-life of antipyrine by 11 +/- 5% (mean +/- s.e. mean) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol increased the half-life of paracetamol by 25 +/- 12% (P less than 0.05) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol decreased the partial clearance of paracetamol to its cysteine and mercapturate derivatives by 16 +/- 3% (P less than 0.05) and 32 +/- 7% (P less than 0.05), respectively. The partial clearance to the glucuronide conjugate was decreased by 27 +/- 6% (P less than 0.05), whereas that to sulphate was not changed significantly. Propranolol inhibits paracetamol metabolism predominantly through inhibition of the oxidation and glucuronidation pathways.