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An overview of the evolution of sleeping sickness and control activities in the DRC during the period 1989-1998 is presented. A resurgence was already developing in the mid-1980s and, after a breakdown of active case-finding between 1990 and 1993, annual detection rates attained levels similar to those of the late 1920s. Although a staggering number of 150 591 new cases have been detected during the past decade, the problem is ignored by most of the international community. The major cause for the resurgence appears to be the interruption of active case-finding for a prolonged period of time. Control activities have improved considerably in recent years, but a lot remains to be done and supplementary resources are needed. [ABSTRACT FROM AUTHOR]

Background and Objectives: We assessed the agreement between prostate-specific antigen (PSA) and imaging responses using whole-body magnetic resonance imaging (wbMRI). Our aim was to explore the potential prognostic value of PSA and wbMRI responses in metastatic hormone-naïve prostate cancer (mHNPC) and castration-resistant PC (mCRPC)., Methods: wbMRI was prospectively performed in 37 patients with mHNPC and 51 with mCRPC before and after 6-12 mo of androgen deprivation therapy and an androgen receptor pathway inhibitor (ARPI). Imaging responses were defined according to the Metastasis Reporting and Data System for PC (MET-RADS-P) criteria. A PSA response was defined as PSA ≤0.2 ng/ml in mHNPC and a ≥50% decrease from the pretreatment level in mCRPC. Agreement between PSA and wbMRI responses was assessed using Cohen's κ. The association between time to subsequent treatment and overall survival (OS) was analyzed using Cox regression analysis., Key Findings and Limitations: Agreement between PSA and wbMRI responses was fair in mHNPC (κ = 0.30) but none to slight in mCRPC (κ = 0.15). In mHNPC, patients with a PSA or wbMRI response were less likely to receive subsequent treatments; wbMRI progression was associated with a significantly higher risk of death (hazard ratio 8.59; p = 0.002). In mCRPC, two-thirds of patients with a PSA response showed progression on wbMRI; neither PSA nor wbMRI progression changed the likelihood of starting a subsequent treatment or the risk of death., Conclusions and Clinical Implications: In mHNPC, wbMRI progression was associated with a higher risk of needing subsequent treatment and shorter OS., Patient Summary: We evaluated the agreement between routine PSA (prostate-specific antigen) test results and whole-body MRI (magnetic resonance imaging) scans for assessing the response of metastatic prostate cancer to treatment. There was disagreement between the PSA and MRI results, mainly for patients with cancer that was resistant to hormone-based treatment. Combining PSA with whole-body MRI might provide a more accurate picture of the response of advanced prostate cancer to treatment., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To compare the diagnostic accuracy of a single T2 Dixon sequence to the combination T1+STIR as anatomical sequences used for detecting tumoral bone marrow lesions in whole-body MRI (WB-MRI) examinations., Methods: Between January 2019 and January 2020, seventy-two consecutive patients (55 men, 17 women, median age = 66 years) with solid (prostate, breast, neuroendocrine) cancers at high risk of metastasis or proven multiple myeloma (MM) prospectively underwent a WB-MRI examination including coronal T1, STIR, T2 Dixon and axial diffusion-weighted imaging sequences. Two radiologists independently assessed the combination of T1+STIR sequences and the fat+water reconstructions from the T2 Dixon sequence. The reference standard was established by consensus reading of WB-MRI and concurrent imaging available at baseline and at 6 months. Repeatability and reproducibility of MRI scores (presence and semi-quantitative count of lesions), image quality (SNR: signal-to-noise, CNR: contrast-to-noise, CRR: contrast-to-reference ratios), and diagnostic characteristics (Se: sensitivity, Sp: specificity, Acc: accuracy) were assessed per-skeletal region and per-patient., Results: Repeatability and reproducibility were at least good regardless of the score, region, and protocol (0.67 ≤ AC1 ≤ 0.98). CRR was higher on T2 Dixon fat compared to T1 (p < 0.0001) and on T2 Dixon water compared to STIR (p = 0.0128). In the per-patient analysis, Acc of the T2 Dixon fat+water was higher than that of T1+STIR for the senior reader (Acc = +0.027 [+0.025; +0.029], p < 0.0001) and lower for the junior reader (Acc = -0.029 [-0.031; -0.027], p < 0.0001)., Conclusions: A single T2 Dixon sequence with fat+water reconstructions offers similar reproducibility and diagnostic accuracy as the recommended combination of T1+STIR sequences and can be used for skeletal screening in oncology, allowing significant time-saving., Key Points: • Replacement of the standard anatomic T1 + STIR WB-MRI protocol by a single T2 Dixon sequence drastically shortens the examination time without loss of diagnostic accuracy. • A protocol based on fat + water reconstructions from a single T2 Dixon sequence offers similar inter-reader agreement and a higher contrast-to-reference ratio for detecting lesions compared to the standard T1 + STIR protocol. • Differences in the accuracy between the two protocols are marginal (+ 3% in favor of the T2 Dixon with the senior reader; -3% against the T2 Dixon with the junior reader)., (© 2022. The Author(s).)

Over the past decade, updated definitions for the different stages of prostate cancer and risk for distant disease, along with the advent of new therapies, have remarkably changed the management of patients. The two expectations from imaging are accurate staging and appropriate assessment of disease response to therapies. Modern, next-generation imaging (NGI) modalities, including whole-body magnetic resonance imaging (WB-MRI) and nuclear medicine (most often prostate-specific membrane antigen [PSMA] positron emission tomography [PET]/computed tomography [CT]) bring added value to these imaging tasks. WB-MRI has proven its superiority over bone scintigraphy (BS) and CT for the detection of distant metastasis, also providing reliable evaluations of disease response to treatment. Comparison of the effectiveness of WB-MRI and molecular nuclear imaging techniques with regard to indications and the definition of their respective/complementary roles in clinical practice is ongoing. This paper illustrates the evolution of WB-MRI imaging protocols, defines the current state-of-the art, and highlights the latest developments and future challenges. The paper presents and discusses WB-MRI indications in the care pathway of men with prostate cancer in specific key situations: response assessment of metastatic disease, "all in one" cancer staging, and oligometastatic disease., (© 2020 International Society for Magnetic Resonance in Medicine.)

Whole-Body Magnetic Resonance Imaging (WB-MRI) is increasingly used for metastatic screening in oncology. This prospective single center study assesses the diagnostic value of WB-MRI including diffusion weighted imaging (DWI) and identifies the sufficient protocol for metastatic lymph node detection in patients with testicular germ cell cancer (TGCC). Forty-three patients underwent contrast enhanced thoraco-abdominopelvic CT (TAP-CT) and WB-MRI with DWI for metastatic lymph node screening. Two independent readers reviewed CTs and WB-MRIs. The diagnostic performance of different imaging protocols (CT, complete WB-MRI, T1W + DWI, T2W + DWI), the agreement between these protocols and the reference standard, the reproducibility of findings and the image quality (Signal and contrast to Noise Ratios, Likert scale) were studied. Reproducibility was very good regardless of both lesion locations (retroperitoneal vs distant lymph nodes, other lesions) and the reader. Diagnostic accuracy of MRI was ≥95% (regardless of the locations and imaging protocol); accuracy of CT was ≥93%. There was a strict overlap of 95% CIs associated with this accuracy between complete WB-MRI, T1W + DWI and T2W + DWI, regardless of the reader. Higher Likert score and SNR were observed for DWI, followed by T2W and T1W sequences. In conclusion, a fast WB-MRI protocol including T2W and DWI is a sufficient, accurate, non-irradiating alternative to TAP-CT for metastatic lymph node screening in TGCC.

Background: Prostate specific membrane antigen (PSMA) positron emission tomography computed tomography (PET-CT) and whole-body magnetic resonance imaging (WB-MRI) outperform standard imaging technology for the detection of metastasis in prostate cancer (PCa). There are few direct comparisons between both modalities. This paper compares the diagnostic accuracy of PSMA PET-CT and WB-MRI for the detection of metastasis in PCa. One hundred thirty-four patients with newly diagnosed PCa ( n = 81) or biochemical recurrence after curative treatment ( n = 53) with high-risk features prospectively underwent PSMA PET-CT and WB-MRI. The diagnostic accuracy of both techniques for lymph node, skeletal and visceral metastases was compared against a best valuable comparator (BVC). Overall, no significant difference was detected between PSMA PET-CT and WB-MRI to identify metastatic patients when considering lymph nodes, skeletal and visceral metastases together (AUC = 0.96 (0.92-0.99) vs. 0.90 (0.85-0.95); p = 0.09). PSMA PET-CT, however, outperformed WB-MRI in the subgroup of patients with newly diagnosed PCa for the detection of lymph node metastases (AUC = 0.96 (0.92-0.99) vs. 0.86 (0.79-0.92); p = 0.0096). In conclusion, PSMA PET-CT outperforms WB-MRI for the detection of nodal metastases in primary staging of PCa.

With its outstanding soft tissue contrast, spatial resolution, and multiplanar capacities, magnetic resonance imaging (MRI) has become a widely used technique. Whole-body MRI (WB-MRI) has been introduced among diagnostic methods for the staging and follow-up assessment in oncologic patients, and international guidelines recommend its use. In nononcologic applications, WB-MRI is as a promising imaging tool in inflammatory diseases, such as seronegative arthritis and inflammatory myopathies. Technological advances have facilitated the introduction of three-dimensional (3D) almost isotropic sequences in MRI examinations covering the whole body. The possibility to reformat 3D images in any plane with equal or almost equal resolution offers comprehensive understanding of the anatomy, easier disease detection and characterization, and finally contributes to correct treatment planning. This article illustrates the basic principles, advantages, and limitations of the 3D approach in WB-MRI examinations and provides a short review of the literature., Competing Interests: None declared., (Thieme. All rights reserved.)

Acute scrotum is characterized by intense acute scrotal pain, which may be associated with other symptoms and signs such as abdominal pain, inflammation, and fever. Many pathologic conditions can present in this way, most which involve the scrotal contents. Nonscrotal conditions, however, can rarely present clinically only as acute scrotum: among them, renal colic, aneurysm rupture or other causes of retroperitoneal hemorrhage, primary abdominal or pelvic tumors and metastases, pancreatitis, pelvic inflammation, and muscle injuries. The pathophysiologic characteristics of the clinical presentation, clues for diagnosis, and imaging features of a series of nonscrotal lesions presenting clinically with acute scrotal pain are herein reported and illustrated. In patients presenting with acute scrotal symptoms and normal scrotal ultrasound findings, nonscrotal causes of acute scrotal pain should be considered in the differential diagnosis. Therefore, an ultrasound investigation of the abdomen, groin, and thighs is indicated., (© 2020 American Institute of Ultrasound in Medicine.)

Erectile dysfunction (ED) is defined as the persistent inability to achieve and/or maintain an erection for a satisfactory sexual activity. It is secondary to several organic, psychogenic, and combined causes, and represents a serious health dilemma affecting both men and their partners. The diagnostic approach to erectile dysfunction has significantly changed in the last years with the advent of phosphodiesterase-5 (PDE5) inhibitors, and with the recognition that surgical treatment of both arterial insufficiency and penile venous leak have poor long-term clinical outcomes. Although imaging modalities have diminished in importance, differentiating among causes of erectile dysfunction remains mandatory in good medical practice, and ultrasound (US) still remains the cornerstone of the diagnostic workup. US provides an objective, minimally invasive evaluation of penile hemodynamics. Moreover, it provides an excellent depiction of the penile anatomy and of its changes in pathological conditions such as in patients with Peyronie's disease, priapism, and posttraumatic erectile dysfunction.

Purpose: To compare 3D T1-weighted fast spin echo (FSE) and 3D T1-weighted gradient echo (GE) mDixon as morphologic sequences to complement diffusion-weighted imaging (DWI) for the metastatic screening in prostate cancer (PCa) patients., Materials and Methods: Thirty PCa patients at high risk of metastases prospectively underwent both a 3D T1 FSE (14 min) and a rapid 3D T1 GE mDixon (1 min 20 s) sequences within a WB-MRI protocol. Two readers assessed the diagnostic performance of the FSE/Fat/in-phase (IP)/IP+Fat sequences in detecting bone and node metastases. The reference standard was established by a panel of four physicians on the basis of all baseline and follow-up imaging, biological and clinical information. The reproducibility of readings, predictive accuracy (Acc) from ROC curves analysis, and contrast-to-reference ratio (CRR) in lesions were assessed for each sequence., Results: In bone and lymph nodes (per-region analysis), reproducibility was at least good for all sequences/readers, except for nodes in the common iliac/inguinal regions. In bone (per-organ analysis), Acc of FSE was superior to that of mDixon (difference + 4%, p < 0.0083). In nodes (per-organ analysis), Acc of Fat was superior to that of other sequences (difference + 4% to + 6% depending on reader, p < 0.0083). In the per-patient analysis, Acc of FSE was superior to that of mDixon (difference + 4% to + 6% depending on sequence, p < 0.0083). Fat images had higher CRR compared with FSE in the thoracic spine, the bony pelvis and lymph node metastases (p < 0.025)., Conclusion: 3D T1 GE mDixon may replace 3D T1 FSE to complement DWI in WB-MRI for metastatic screening in PCa. It demonstrates an Acc ranging from + 4% to + 6% (nodes) to - 4% to - 6% (bone and patient staging) compared with FSE and considerably reduces the examination time, offering the perspective of acquiring WB-MRI examinations in less than 20 min., Key Points: • The replacement of 3D T1 FSE by the 3D T1 GE mDixon as morphologic sequence to complement DWI drastically reduces the acquisition time of WB-MRI studies. • The 3D T1 GE mDixon sequence offers similar reproducibility of image readings compared with that of the 3D T1 FSE. • Differences in diagnostic accuracy are limited (+ 4%/+ 6% in favor of mDixon to detect node metastases; + 4%/+ 6% in favor of FSE to detect bone metastases/metastatic disease in a patient).

Purpose: It is generally accepted that when metastases develop in a patient with biochemical recurrence of prostate cancer (PCa), they follow a centrifuge pattern of seeding from the pelvis and that most patients enter the disease as oligometastatic. In this study, we used whole-body magnetic resonance imaging (WB-MRI) to assess the anatomical distribution of oligo- and polymetastatic disease and the impact of the initial treatment on this distribution in patients., Materials and Methods: WB-MRI examinations of patients with a rising prostate-specific antigen (PSA) after radical treatment by surgery or/and radiotherapy were analyzed for disease recurrence. The patients were separated into three groups, based on the primary treatment: patients treated by radical prostatectomy without radiotherapy and with/without lymph node dissection (RP), patients treated only by radiotherapy or hormono-radiotherapy (RT) and patients treated with radical prostatectomy and adjuvant or salvage radiotherapy (RP + RT). Patients with ≤ 5 bone or/and node metastases were considered oligometastatic. Regional distributions of bone and lymph nodes metastases were reported using anatomical diagrams. Univariate and multivariable logistic regressions were performed to identify prognostic factors of relapse., Results: The primary treatment (RP, RT, RP + RT), Gleason score, PSA at relapse, time between first diagnosis and recurrence did not influence the metastatic status (oligo vs. polymetastatic). Oligometastatic patients showed different distribution of bone metastases compared to the polymetastatic ones and the distribution of the oligometastatic disease was not influenced by the primary treatment., Conclusions: In this WB-MRI-based study, there was no evidence that the primary treatment influenced the metastatic status of the patient or the distribution of the oligometastatic disease.

Objective: To compare prospectively the diagnostic performance of a biparametric (T2-weighted imaging [T2WI] and diffusion-weighted imaging [DWI]) 1.5-T fast magnetic resonance imaging (fMRI) protocol with the standard 3.0-T multiparametric MRI (mpMRI) protocol of the European Society of Urological Imaging (ESUR) in men referred for a prostate biopsy., Patients and Methods: Ninety patients with a prostate cancer (PCa) risk of ≥10% according to the SWOP calculator 4 underwent first fMRI and then the reference mpMRI. Patients with Prostate Imaging Reporting and Data System (PI-RADS) v.2 lesions ≥3/5 on the mpMRI were scheduled for MRI/ultrasonography (US) fusion-guided prostate biopsy. Performance of fMRI was assessed using receiver-operating characteristic curve analysis and mpMRI as reference. Calculation of inter-technique agreement on PI-RADS v.2 score by Cohen's κ., Results: The diagnostic accuracy of fMRI shown by the lesion-based analysis was excellent: area under the curve (AUC) 0.961 (P < 0.001), sensitivity 95%, specificity 97%, positive predictive value (PPV) 99%, negative predictive value (NPV) 89%. The patient-based analysis showed an AUC for fMRI of 0.975 (P < 0.001), a sensitivity of 98%, a specificity of 97%, a PPV of 98% and an NPV of 97%. Agreement on the PI-RADS score between both protocols was found to be good (κ = 0.78 [0.57; 0.99]); fMRI missing PI-RADS 4 lesions in three patients. Biopsy results showed no cancer in two patients (two cores per nodule) and Gleason 6 cancer in one patient. There was only one false-positive fMRI, with a PI-RADS score of 4, whose biopsy was negative., Conclusion: In the triage of men with a high risk of PCa for prostate biopsy, an f MRI protocol (1.5-T magnet, T2WI + DWI, <15 min) may safely replace the traditional ESUR 3.0-T mpMRI protocol, saving time and contrast injection., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Whole-body MR imaging (WB-MR imaging) has become a modality of choice for detecting bone metastases in multiple cancers, and bone marrow involvement by multiple myeloma or lymphoma. Combination of anatomic and functional sequences imparts an inherently hybrid dimension to this nonirradiating tool and extends the screening of malignancies outside the skeleton. WB-MR imaging outperforms bone scintigraphy and CT and offers an alternative to PET in many tumors by time of lesion detection and assessment of treatment response. Much work has been done to standardize procedures, optimize sequences, validate indications, confirm preliminary research into new applications, rendering clinical application more user-friendly., (Copyright © 2018 Elsevier Inc. All rights reserved.)

MRI is a very attractive approach for tumour detection and oncological staging with its absence of ionizing radiation, high soft tissue contrast and spatial resolution. Less than 10 years ago the use of Whole Body MRI (WB-MRI) protocols was uncommon due to many limitations, such as the forbidding acquisition times and limited availability. This decade has marked substantial progress in WB-MRI protocols. This very promising technique is rapidly arising from the research world and is becoming a commonly used examination for tumour detection due to recent technological developments and validation of WB-MRI by multiple studies and consensus papers. As a result, WB-MRI is progressively proposed by radiologists as an efficient examination for an expanding range of indications. As the spectrum of its uses becomes wider, radiologists will soon be confronted with the challenges of this technique and be urged to be trained in order to accurately read and report these examinations. The aim of this review is to summarize the validated indications of WB-MRI and present an overview of its most recent advances. This paper will briefly discuss how this examination is performed and which are the recommended sequences along with the future perspectives in the field.

A 68-year-old female presented with a week history of fever and generalized weakness. Clinical examination, blood work and urinalysis were compatible with sepsis due to acute pyelonephritis. Urine cultures were positive for Escherichia coli and blood cultures were negative. After 5 days of antibiotic therapy with cefuroxime, inflammatory parameters (CRP level and white blood cell count) remained highly elevated. Abdominal CT scan showed right kidney pyelonephritis with renal and perirenal abscess and right renal vein thrombosis. The patient improved after percutaneous drainage of the perirenal abscess and anticoagulation treatment. She was discharged on hospital day 14., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Developing countries face numerous barriers to conducting effective and efficient ethics reviews of international collaborative research. In addition to potentially overlooking important scientific and ethical considerations, inadequate or insufficiently trained ethics committees may insist on unwarranted changes to protocols that can impair a study's scientific or ethical validity. Moreover, poorly functioning review systems can impose substantial delays on the commencement of research, which needlessly undermine the development of new interventions for urgent medical needs. In response to these concerns, the Drugs for Neglected Diseases Initiative (DNDi), an independent nonprofit organization founded by a coalition of public sector and international organizations, developed a mechanism to facilitate more effective and efficient host country ethics review for a study of the use of fexinidazole for the treatment of late stage African Trypanosomiasis (HAT). The project involved the implementation of a novel 'pre-review' process of ethical oversight, conducted by an ad hoc committee of ethics committee representatives from African and European countries, in collaboration with internationally recognized scientific experts. This article examines the process and outcomes of this collaborative process., (© 2014 The Authors. Developing World Bioethics published by John Wiley & Sons Ltd.)

BACKGROUND. Clinical management of human African trypanosomiasis requires patient follow-up of 2 years' duration. At each follow-up visit, cerebrospinal fluid (CSF) is examined for trypanosomes and white blood cells (WBCs). Shortening follow-up would improve patient comfort and facilitate control of human African trypanosomiasis. METHODS. A prospective study of 360 patients was performed in the Democratic Republic of the Congo. The primary outcomes of the study were cure, relapse, and death. The WBC count, immunoglobulin M level, and specific antibody levels in CSF samples were evaluated to detect treatment failure. The sensitivity and specificity of shortened follow-up algorithms were calculated. RESULTS. The treatment failure rate was 37%. Trypanosomes, a WBC count of > or = 100 cells/microL, and a LATEX/immunoglobulin M titer of 1:16 in CSF before treatment were risk factors for treatment failure, whereas human immunodeficiency virus infection status was not a risk factor. The following algorithm, which had 97.8% specificity and 94.4% sensitivity, is proposed for shortening the duration of follow-up: at 6 months, patients with trypanosomes or a WBC count of > or = 50 cells/microL in CSF are considered to have treatment failure, whereas patients with a CSF WBC count of > or = 5 cells/microL are considered to be cured and can discontinue follow-up. At 12 months, the remaining patients (those with a WBC count of > or = 6-49 cells/microL) need a test of cure, based on trypanosome presence and WBC count, applying a cutoff value of > or = 20 cells/microL. CONCLUSION. Combining criteria for failure and cure allows follow-up of patients with second-stage human African trypanosomiasis to be shortened to a maximum duration of 12 months.

Background: Treatment of second-stage sleeping sickness relies mainly on melarsoprol. Nifurtimox has been successfully used to cure melarsoprol-refractory sleeping sickness caused by Trypanosoma brucei gambiense infection., Methods: An open, randomized trial was conducted to test for equivalence between the standard melarsoprol regimen and 3 other regimens, as follows: standard melarsoprol therapy (3 series of 3.6 mg/kg/day intravenously [iv] for 3 days, with 7-day breaks between the series); 10-day incremental-dose melarsoprol therapy (0.6 mg/kg iv on day 1, 1.2 mg/kg iv on day 2, and 1.8 mg/kg iv on days 3-10); nifurtimox monotherapy for 14 days (5 mg/kg orally 3 times per day); and consecutive 10-day melarsoprol-nifurtimox combination therapy (0.6 mg/kg iv melarsoprol on day 1, 1.2 mg/kg iv melarsoprol on day 2, and 1.2 mg/kg/day iv melarsoprol combined with oral 7.5 mg/kg nifurtimox twice a day on days 3-10). Primary outcomes were relapse, severe adverse events, and death attributed to treatment., Results: A total of 278 patients were randomized. The frequency of adverse events was similar between the standard melarsoprol regimen and the other regimens. Encephalopathic syndromes occurred in all groups and caused all deaths that were likely due to treatment. Relapses (n=48) were observed only with the 3 monotherapy regimens., Conclusion: A consecutive 10-day low-dose melarsoprol-nifurtimox combination is more effective than the standard melarsoprol regimen.

The efficacy and adverse effects of nifurtimox and DFMO in the treatment of sleeping sickness are reviewed. Both new substances constitute effective novel therapeutic agents for gambiense sleeping sickness, including melarsoprol-refractory disease. DFMO is not very active in rhodesiense sleeping sickness and experience with nifurtimox in this form of trypanosomiasis is too limited to draw valid conclusions. The toxicity of nifurtimox and DFMO is not negligible. Optimum dosage and duration of therapy, modes of administration and potential for large scale use are discussed. Some recent results obtained with the classical trypanocide melarsoprol are presented to facilitate comparison. The current availability of several effective late-stage drugs (melarsoprol, nifurtimox and DFMO), that show synergistic activity in experimental models, should allow the establishment of optimum combination treatment regimens.

In an area of endemic gambiense sleeping sickness in southern Sudan, the vegetation around 40 wells was categorised in terms of potential habitat for the vector, Glossina fuscipes, and the probability of repeated man/fly contact. These observations were related to the results of sleeping sickness surveys including the use of serodiagnostic (ICHA and CATT) tests which allowed the detection of the great majority of cases. Riverine woodland and gallery forest were the primary habitat of G. fuscipes and 1286 people using wells in this vegetation had an 11.1% infection rate including parasitological, clinical and serological cases. In contrast, 638 people using wells in open situations where the presence of G. fuscipes was unlikely, showed a significantly lower (4.5%) infection rate. These observations provide a basis for planning localised tsetse control, using, for example, insecticide impregnated targets, co-ordinated with mass survey and treatment of the human population.

The antitrypanosomal activity of two 5-substituted 2-nitro-imidazoles (Ro 15-0216 and benznidazole) and alpha-DL-difluoro-methylornithine (DFMO) was tested in four stocks of Trypanosoma brucei brucei in vitro. The IC50 (drug concentration which inhibits growth of trypanosome populations by 50%) values ranged from 0.27-1.0 for Ro 15-0216, 84-265 for benznidazole, and 147-691 microM for DFMO. Potentiation of antitrypanosomal activity of the combination of Ro 15-0216 and DFMO was demonstrated in a 24 h growth inhibition test. A synergistic effect was also demonstrated when benznidazole and DFMO were combined in a long term viability assay in vitro. Although 40 microM DFMO and 20 microM benznidazole were ineffective when used individually, trypanosomes of all stocks were killed when both drugs were present simultaneously at these concentrations. The combination of 40 microM DFMO and 4 microM benznidazole led to growth suppression. At an early stage of infection, a single injection of 100 mg/kg Ro 15-0216 at the end of a 3-day treatment period with DFMO (2% in drinking water) resulted in a 100% cure of T. b. brucei-infected mice, whereas monotherapy with either drug at the same dose levels was completely ineffective. Nitroimidazoles and DFMO given simultaneously might improve the therapy of human sleeping sickness.

Difluoromethylornithine (DFMO), a specific, irreversible inhibitor of polyamine biosynthesis shown to be curative in animal models inoculated with various Trypanosoma spp., was evaluated in the Southern Sudan in a preliminary open clinical field trial in patients infected with Trypanosoma brucei gambiense. 20 patients were studied including 18 with late-stage disease involving the central nervous system, 16 of whom were refractory to arsenical treatment. In late-stage disease monotherapy with oral DFMO doses of about 400 mg/kg/day for five to six weeks was associated with disappearance of parasites from cerebrospinal fluid (CSF), decreased CSF WBC counts and protein concentrations and reversal of clinical signs. Side effects associated with this dose regimen included diarrhoea, abdominal discomfort and anaemia, but were seldom sufficiently severe to prompt discontinuing therapy. In early-stage patients about 200 mg/kg/day for six weeks appears adequate to eliminate parasites and reverse clinical symptoms and is well tolerated. Three cases of late-stage sleeping sickness and two of early-stage disease followed up for approximately one and a half to two years after treatment indicated that DFMO monotherapy can be curative. Additional studies are needed to define optimal posology. Inhibition of polyamine biosynthesis is a promising new approach to therapy of trypanosomiasis.