The safety and efficacy of itraconazole for the treatment of patients with eumycetoma due to Madurella mycetomatis

This prospective study aimed to determine the safety and efficacy of itraconazole for the treatment of patients with mycetoma due to Madurella mycetomatis. The study consisted of 13 patients with confirmed disease; all were treated with oral itraconazole in a dose of 400mg daily for three months after which the dose was reduced to 200mg daily for nine months. All patients showed good clinical response to 400mg itraconazole daily, but when the dose was reduced to 200mg daily, the clinical response was gradual and slow. Post-treatment surgical exploration showed that, in all patients, the lesions were well localized, encapsulated with thick capsule and they were easily removed surgically. In all these lesions, grains colonies were encountered and they were viable on culture. Post-operative biopsies showed no significant changes in the morphology of the grains. A constant finding was the presence of between 5-7 grains in a single cavity walled by fibrous tissue. The reaction surrounding the grains was a Type I tissue reaction characterized by a neutrophil zone around grains. Patients were followed up post-operatively for variable periods (range 18-36 months) and only one patient had recurrence. Initial pre-operative treatment with itraconazole may be recommended for eumycetoma patients to enhance lesions encapsulation and localization which can facilitate wide local excision to avoid unnecessary massive mutilating surgery and recurrence.     

Mycetoma: a thorn in the flesh

Mycetoma is a chronic, granulomatous, subcutaneous, inflammatory disease caused by true fungi (eumycetoma) or filamentous bacteria (actinomycetoma). It occurs in the mycetoma belt stretching between the latitudes of 15 degrees South and 30 degrees North and is endemic in relatively arid areas. The organisms are present in the soil and may enter the subcutaneous tissue by traumatic inoculation. Mycetoma commonly affects adults aged 20 to 40 years, predominantly males. The foot is most commonly affected. Both forms of mycetoma present as a progressive, subcutaneous swelling, although actinomycetoma has a more rapid course. Multiple nodules develop which may suppurate and drain through sinuses, discharging grains during the active phase of the disease. Diagnosis may involve radiology, ultrasonic imaging, cytology, culture, histology or immunodiagnosis. Actinomycetoma is amenable to treatment by antibiotics, preferably by combined drug therapy for long periods. Eumycetoma is usually treated by aggressive surgical excision combined with medical treatment.     

Uncommon clinical presentations of cutaneous leishmaniasis in Sudan

Cutaneous leishmaniasis in Sudan is caused by Leishmania major zymodeme LON1. Self-healing usually occurs within 1 year but occasionally its duration is prolonged and treatment is required. The clinical forms are ulcers, nodules and noduloulcerative lesions. Here we describe seven patients with uncommon lesions that were difficult to recognize as Leishmania infections. These included mycetoma-like lesions, lesions that resembled L. tropica infection and others. One HIV/AIDS patient had Kaposi's sarcoma with Leishmania parasites in the Kaposi lesions. Most of these uncommon clinical forms were difficult to treat. The diagnosis depended on a high degree of suspicion and the demonstration of parasites in smears or culture. PCR was used to characterize parasites from the patients described here. Leishmania major was found by kDNA PCR in all patients, except one, who had a leishmanioma due to L. donovani. In three patients, including one with a L. tropica like-lesion, the parasites were confirmed as L. major by gp63 PCR-RFLP.     

Quinine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan

An observational clinical trial was conducted in New Halfa, eastern Sudan, in November and December 2003. Sixty-two patients with uncomplicated Plasmodium falciparum malaria were treated with oral quinine (10 mg/kg thrice daily for 7 d); 47 (76%) of these patients were followed-up to day 28, and 5 (10.6%) of them appeared to have late treatment failures. The parasitological failures were early R1 in two (4.3%) patients and late R1 in three (6.4%) patients. The reappearance of parasites in three of these five patients were true recrudescences rather than a re-infection, based on genetic evidence. The present results and those of earlier investigations indicate that the response to quinine in this area may be faltering.     

Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations

Both northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria (artesunate+sulfadoxine-pyrimethamine [AS+SP] in the north, artesunate+amodiaquine [AS+AQ] in the south). In 2003, we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the isolated, seasonally endemic Nuba Mountains region (the first study of AS combinations in southern Sudan). We also analysed pre-treatment blood samples for mutations at the P. falciparum chloroquine transporter (Pfcrt) gene (associated with CQ resistance), and at the dihydrofolate reductase (Dhfr) gene (associated with pyrimethamine resistance). Among 161 randomized children under 5 years, PCR-corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7-97.1) for AS+SP and 92.7% (51/55, 95% CI 82.4-98.0) for AS+AQ, with equally rapid parasite and fever clearance. The Pfcrt K76T mutation occurred in 90.0% (144/160) of infections, suggesting CQ would work poorly in this region. Overall, 82.5% (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but triple mutants (more predictive of in vivo SP failure) were rare (3.1%). CQ use should be rapidly discontinued in this region. SP resistance may propagate rapidly, and AS+AQ is likely to be a better long-term option, provided AQ use is limited to the combination.     

Isolation and propagation of Trypanosoma brucei gambiense from sleeping sickness patients in south Sudan

This study aimed at isolating Trypanosoma brucei gambiense from human African trypanosomiasis (HAT) patients from south Sudan. Fifty HAT patients identified during active screening surveys were recruited, most of whom (49/50) were in second-stage disease. Blood and cerebrospinal fluid samples collected from the patients were cryopreserved using Triladyl as the cryomedium. The samples were stored at -150 degrees C in liquid nitrogen vapour in a dry shipper. Eighteen patient stabilates could be propagated in immunosuppressed Mastomys natalensis and/or SCID mice. Parasitaemia was highest in SCID mice. Further subpassages in M. natalensis increased the virulence of the trypanosomes and all 18 isolates recovered from M. natalensis or SCID mice became infective to other immunosuppressed mouse breeds. A comparison of immunosuppressed M. natalensis and Swiss White, C57/BL and BALB/c mice demonstrated that all rodent breeds were susceptible after the second subpassage and developed a parasitaemia >10(6)/ml by Day 5 post infection. The highest parasitaemias were achieved in C57/BL and BALB/c mice. These results indicate that propagation of T. b. gambiense isolates after initial isolation in immunosuppressed M. natalensis or SCID mice can be done in a range of immunosuppressed rodents.     

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.     

Médecins Sans Frontières interventions against kala-azar in the Sudan, 1989-2003

Since 1989, Médecins Sans Frontières (MSF) has provided medical humanitarian assistance duringoutbreaks of visceral leishmaniasis (VL, kala-azar) in Sudan. First, in western Upper Nile in southern Sudan, where a VL epidemic occurred after the resumption of the civil war in Sudan in 1983, with an estimated 100 000 deaths. Later, MSF started interventions in eastern Upper Nile and Gedaref State. In these 2 endemic regions VL incidence has risen markedly since 2001, which could be the start of a new epidemic cycle. Outbreaks of VL in Sudan remain unpredictable, and access to affected populations in war-torn southern Sudan is often hampered by insecurity. Therefore, MSF takes a flexible approach, establishing treatment centres where patients can be accessed. From 1989 to 2002, MSF treated > 51 000 VL cases in Sudan. Despite very basic field conditions, high cure rates of 95% are being achieved. Lack of diagnostics is a major obstacle to treatment, especially during epidemic situations. Therefore, development of simple and rapid technologies is required, allowing reliable diagnosis under field conditions. For treatment of VL there is a limited choice of effective, affordable drugs. There are strong indications of an emerging resistance to antimonials in Malakal. Introduction of combination therapies is urgently needed to prevent the further emergence and spread of resistance to antimonials, which are still the mainstay of VL treatment in eastern Africa. Experience with combination therapy with sodium stibogluconate (SSG) and paromomycin is promising, and combinations of SSG with liposomal amphotericin B and miltefosine are currently being explored.     

Scedosporium apiospermum mycetoma with bone involvement successfully treated with voriconazole

Treatment of Scedosporium apiospermum mycetoma usually requires limb amputation. A 49-year-old woman, from Ivory Coast, was diagnosed with Madura foot in 1995. She failed to respond to several treatments including itraconazole, fluconazole and co-trimoxazole, and refused limb amputation. In December 2002 she was admitted to hospital in France with a painful, swollen right leg and foot. She had no fever and C-reactive protein was 120 mg/l. Magnetic resonance imaging (MRI) confirmed the destruction of tarsus bones with a tibia extension. Voriconazole (400 mg/day) treatment was initiated in March 2003; a significant clinical improvement was observed within 4 months as confirmed by C-reactive protein (16 mg/l) and MRI. Voriconazole was maintained for 18 months with good tolerance. Cholestasis appeared after the first month and remained stable. In October 2004 voriconazole was discontinued due to side effects on the liver (alanine aminotransferase 17 times the normal level); MRI showed impressive regression of bone lesions. As of July 2005, the patient remains clinically well. Voriconazole appears to be a promising drug for the treatment of S. apiospermum mycetomas.     

Risk factors for trachomatous trichiasis in children: cross-sectional household surveys in Southern Sudan

We have previously documented blinding trachoma to be a serious public health problem in Southern Sudan, with an unusually high prevalence of trachomatous trichiasis (TT) among children. We aimed to investigate risk factors for TT in children in Southern Sudan. Cross-sectional surveys were undertaken in 11 districts between 2001 and 2006, and eligible participants were examined for trachoma signs. Risk factors were assessed through interviews and observations. Using logistic regression, associations between TT in children and potential risk factors were investigated. In total, 11155 children aged 1-14 years from 3950 households were included in the analysis. Overall prevalence of TT was 1.5% (95% CI 1.1-2.1). Factors independently associated with increased odds of TT in children aged 1-14 years were: increasing age (P(trend)<0.001); female gender (odds ratio=1.5; 95% CI 1.1-2.1); increasing proportion of children in the household with trachomatous inflammation-intense (TI) (P(trend)=0.002); and increasing number of adults in the household with TT (P(trend)<0.001). Our study revealed risk factors for TT in children consistent with those previously reported for TT in adults. While the associations of TT in children with TI in siblings and TT in adult relatives merit further investigation, there is an urgent need for trachoma prevention interventions and trichiasis surgery services that are tailored to cater for young children in Southern Sudan.     

Severe malaria attack is associated with high prevalence of Ascaris lumbricoides infection among children in rural Senegal

In human populations, the concomitance of various parasitic infections can induce modifications of the specific immune response to each pathogen and thus induce changes in their clinical expression. Several studies, however, have produced conflicting results. To study the hypothesis that there is an association between helminthiasis and the occurrence of severe malaria a prospective case-control study was carried out in a rural zone of Senegal where 105 presumptive severe malaria attacks were studied in 2001 and 2002. Following parasitological control the cases were divided into two groups: A (severe malaria) with severe symptoms and parasite density >5000 parasites/microl (n = 64) and B (other causes) with severe symptoms and negative or weak parasite density (n = 41). In group A the prevalence of Ascaris lumbricoides infection was higher in cases of severe malaria than in controls, odds ratio (OR) = 9.95 (95% CI 3.03-32.69). Similar but not significantly different results were observed between patients in group B and their controls, OR = 2.47 (95% CI 0.95-6.38).     

Kala-azar epidemiology and control, southern Sudan

Southern Sudan is one of the areas in eastern Africa most affected by visceral leishmaniasis (kala-azar), but lack of security and funds has hampered control. Since 2005, the return of stability has opened up new opportunities to expand existing interventions and introduce new ones.     

Chloroquine, sulfadoxine-pyrimethamine and amodiaquine efficacy for the treatment of uncomplicated Plasmodium falciparum malaria in Upper Nile, south Sudan

The current first-line and second-line drugs for Plasmodium falciparum malaria in South Sudan, chloroquine and sulfadoxine-pyrimethamine (SP), were evaluated and compared with amodiaquine, in an MSF-Holland-run clinic in eastern Upper Nile, South Sudan from June to December 2001. Patients with uncomplicated malaria and fever were stratified by age group and randomly allocated to one of 3 treatment regimes. A total of 342 patients was admitted and followed for 14 d after treatment. The dropout rate was 10.2%. Of those who completed the study, 104 were treated with chloroquine (25 mg/kg, 3 d), 102 with SP (25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine, single dose) and 101 with amodiaquine (25 mg/kg, 3 d). Adequate clinical response was observed in 88.5% of patients treated with chloroquine, 100% of patients treated with SP and 94.1% of patients treated with amodiaquine. In children aged < 5 years, the success rate was lower: 83.3% for chloroquine and 93.0% for amodiaquine. In adults no treatment failures were found, but children aged 5-15 years showed intermediate levels. In addition, we determined the initial genotypes of dhfr and dhps of 44 isolates from the SP-treated group and > 80% were found to be wild type for dhfr and 100% for dhps. Two percent of isolates had a single mutation and 16% had double mutations of dhfr. These data are in full agreement with the clinical effectiveness of SP. A change in malaria treatment protocols for South Sudan is recommended.     

Prevalence and risk factors for anaemia in pregnant women of eastern Sudan

The prevalence and possible risk factors for anaemia were investigated in 744 pregnant Sudanese women attending the antenatal clinic of New Halfa teaching hospital, eastern Sudan between October 2003 and April 2004. Of those, 466 (62.6%) had anaemia (haemoglobin [Hb]: <11 gm/dl); 52.4% had mild anaemia (Hb: 9.0-10.9 gm/dl); 8.1% had moderate anaemia (Hb: 7.0-8.9 gm/dl); and 2.2% had severe anaemia (Hb: <7 gm/dl), respectively. The prevalence of anaemia (73.2%) was significantly high in grandmultigravidae. Univariate and multivariate analysis showed that age and parity were not significantly associated with anaemia. Malaria (OR = 4.5, 95% CI 2.5-8.1; P < 0.0001) and pica (OR = 1.6, 95% CI 1.05-2.6; P = 0.03) were the risk factors for anaemia. Thus, preventive measures against malaria (chemoprophylaxis and insecticide-treated bednets) may be needed for all pregnant women irrespective of their age or parity.     

Carriage of diarrhoeagenic Escherichia coli by older children and adults in Accra, Ghana

Diarrhoeagenic Escherichia coli (DEC) were sought in stool specimens from 72 adults and children aged over 3 years, who presented with diarrhoea at a hospital in Accra, Ghana, and 72 matched controls. Only diffusely-adherent E. coli were significantly associated with disease in these older individuals (P = 0.029). We additionally tested 53 specimens from infants among whom DEC were collectively associated with disease (P = 0.012). Enteropathogenic, enterotoxigenic and enteroaggregative E. coli, the most commonly isolated pathotypes from infants with diarrhoea, were frequently recovered from healthy adults. Asymptomatic carriage of DEC by older individuals in Accra may place young children at risk for diarrhoea.     

LC/MS/MS法分析食品中微量苏丹红I、II、III、IV

目的:建立快速、准确、高灵敏度的测定食品中苏丹红I、II、III、IV的分析方法。方法:采用超高效液相色谱-串联质谱联用法,以乙腈-0.1%甲酸进行梯度洗脱,流速0.3 ml/min,采用C18柱分离,以多反应监测(MRM)方式进行检测,分析时间仅为5 min。苏丹红I、II、III、IV用于定量分析的离子分别为m/z249→93、277→120、353→197、381→224。结果:苏丹红I、II、III、IV的线性范围分别为1.1616~290.4、1.2608~315.2、1.184~296.0、1.1664~291.6 ng/ml,25份食品中有3份检出苏丹红I、II、III、IV含量超过50μg/kg,其余检出均微量。结论:此方法选择性强,灵敏度高,可作为含各种辣椒的食品中苏丹红I、II、III、IV的有效分析检测方法。