Clinical aspects and management of cutaneous leishmaniasis in rheumatoid patients treated with TNF-α antagonists.

Patients under immunosuppressive therapy with tumor necrosis factor alpha (TNF-α) antagonists are vulnerable to various opportunistic infections including leishmaniasis. We present a case series of 8 travellers developing cutaneous leishmaniasis whilst on TNF-α antagonist treatment and review the literature on aspects of cutaneous leishmaniasis developing in patients treated with TNF-α antagonists. We make interim recommendations regarding the drug therapy used to maintain remission in travellers with rheumatoid disease travelling to leishmania prone areas. Despite having a medical condition requiring continued rheumatological review the interval to diagnosis appears not to be reduced compared to that described in non-rheumatoid patients. Rheumatologists and family doctors should be aware of the need for post-travel surveillance for leishmaniasis in rheumatoid patients on TNF-alpha antagonist treatment.

Acute febrile respiratory reaction after praziquantel treatment during asymptomatic late form of acute schistosomiasis.

Paradoxical reactions (Jarish Herxheimer-like reactions) have been described in patients treated with praziquantel (PZQ) during acute schistosomiasis (infected≤ 3 mo), while PZQ treatment of chronic schistosomiasis is generally considered to be safe. We report an acute febrile reaction with respiratory decompensation following PZQ treatment in a 17-year-old male patient who had no potential (re)exposure to infection for at least 5 months and was therefore considered to have reached the chronic stage of disease. We speculate that the clinical manifestations in our patient constitute a very late paradoxical reaction in an unusually long acute phase of infection.

Successful treatment of imported mucosal Leishmania infantum leishmaniasis with miltefosine after severe hypokalemia under meglumine antimoniate treatment.

Old World mucosal leishmaniasis is a rare but regularly reported disease in Southern Europe. We report the case of a 64-year-old woman who developed severe hypokalemia under meglumine antimoniate treatment and was successfully treated under second line therapy with miltefosine.

Clinical presentation of T.b. rhodesiense sleeping sickness in second stage patients from Tanzania and Uganda.

BACKGROUND: A wide spectrum of disease severity has been described for Human African Trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense (T.b. rhodesiense), ranging from chronic disease patterns in southern countries of East Africa to an increase in virulence towards the north. However, only limited data on the clinical presentation of T.b. rhodesiense HAT is available. From 2006-2009 we conducted the first clinical trial program (Impamel III) in T.b. rhodesiense endemic areas of Tanzania and Uganda in accordance with international standards (ICH-GCP). The primary and secondary outcome measures were safety and efficacy of an abridged melarsoprol schedule for treatment of second stage disease. Based on diagnostic findings and clinical examinations at baseline we describe the clinical presentation of T.b. rhodesiense HAT in second stage patients from two distinct geographical settings in East Africa. METHODOLOGY/PRINCIPAL FINDINGS: 138 second stage patients from Tanzania and Uganda were enrolled. Blood samples were collected for diagnosis and molecular identification of the infective trypanosomes, and T.b. rhodesiense infection was confirmed in all trial subjects. Significant differences in diagnostic parameters and clinical signs and symptoms were observed: the median white blood cell (WBC) count in the cerebrospinal fluid (CSF) was significantly higher in Tanzania (134 cells/mm(3)) than in Uganda (20 cells/mm(3); p<0.0001). Unspecific signs of infection were more commonly seen in Uganda, whereas neurological signs and symptoms specific for HAT dominated the clinical presentation of the disease in Tanzania. Co-infections with malaria and HIV did not influence the clinical presentation nor treatment outcomes in the Tanzanian study population. CONCLUSIONS/SIGNIFICANCE: We describe a different clinical presentation of second stage T.b. rhodesiense HAT in two distinct geographical settings in East Africa. In the ongoing absence of sensitive diagnostic tools and safe drugs to diagnose and treat second stage T.b. rhodesiense HAT an early identification of the disease is essential. A detailed understanding of the clinical presentation of T.b. rhodesiense HAT among health personnel and affected communities is vital, and awareness of regional characteristics, as well as implications of co-infections, can support decision making and differential diagnosis.

Cardiac alterations in human African trypanosomiasis (T.b. gambiense) with respect to the disease stage and antiparasitic treatment.

BACKGROUND: In Human African Trypanosomiasis, neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The aims of the study were to assess the frequency and characteristics of electrocardiographic findings in the first stage of HAT, to compare these findings to those of second stage patients and healthy controls and to assess any potential effects of different therapeutic antiparasitic compounds with respect to ECG changes after treatment. METHODS: Four hundred and six patients with first stage HAT were recruited in the Democratic Republic of Congo, Angola and Sudan between 2002 and 2007 in a series of clinical trials comparing the efficacy and safety of the experimental treatment DB289 to the standard first stage treatment, pentamidine. These ECGs were compared to the ECGs of healthy volunteers (n = 61) and to those of second stage HAT patients (n = 56). RESULTS: In first and second stage HAT, a prolonged QTc interval, repolarization changes and low voltage were significantly more frequent than in healthy controls. Treatment in first stage was associated with repolarization changes in both the DB289 and the pentamidine group to a similar extent. The QTc interval did not change during treatment. CONCLUSIONS: Cardiac involvement in HAT, as demonstrated by ECG alterations, appears early in the evolution of the disease. The prolongation of the QTC interval comprises a risk of fatal arrhythmias if new drugs with an additional potential of QTC prolongation will be used. During treatment ECG abnormalities such as repolarization changes consistent with peri-myocarditis occur frequently and appear to be associated with the disease stage, but not with a specific drug.

Cardiac involvement in African and American trypanosomiasis.

American trypanosomiasis (Chagas disease) and human African trypanosomiasis (HAT; sleeping sickness) are both caused by single-celled flagellates that are transmitted by arthropods. Cardiac problems are the main cause of morbidity in chronic Chagas disease, but neurological problems dominate in HAT. Physicians need to be aware of Chagas disease and HAT in patients living in or returning from endemic regions, even if they left those regions long ago. Chagas heart disease has to be taken into account in the differential diagnosis of cardiomyopathy, primarily in patients with pathological electrocardiographic (ECG) findings, such as right bundle branch block or left anterior hemiblock, with segmental wall motion abnormalities or aneurysms on echocardiography, and in young patients with stroke in the absence of arterial hypertension. In HAT patients, cardiac involvement as seen by ECG alterations, such as repolarisation changes and low voltage, is frequent. HAT cardiopathy in general is benign and does not cause relevant congestive heart failure and subsides with treatment. We review the differences between the American and African trypanosomiasis with the main focus on the heart.

Sleeping hearts: the role of the heart in sleeping sickness (human African trypanosomiasis).

OBJECTIVES: To estimate the frequency and evolution of heart involvement in human African trypanosomiasis (HAT) using electrocardiogram (ECG) findings; to describe these findings and to assess the frequency and clinical relevance of symptoms and signs before and after treatment. METHODS: In a prospective cohort study ECG findings, signs and symptoms consistent with heart failure and cardiac laboratory parameters were studied at baseline, 2 days after the end of treatment and 3 months later. RESULTS: Major ECG alterations were significantly more frequent in HAT patients than in healthy controls (71%vs. 18%; P < 0.001); 31% were low voltage changes, 34% were repolarization changes. ECG signs of necrosis and conduction problems were rare. Symptoms consistent with heart failure such as exertional dyspnoea (19%vs. 1.7%; P = 0.002) or palpitations (18%vs. 5%; P = 0.28) occurred more frequently in patients than in controls. The median NT-proBNP was significantly higher in HAT patients than in controls (85.2 vs. 28 pg/ml; P < 0.001). Troponin levels were normal. At the end of treatment repolarization changes appeared or worsened in 33.4%. Such changes improved or disappeared at follow-up in 33.1% of the patients. CONCLUSIONS: Cardiac involvement documented by ECG alterations is common in HAT patients, but cardiopathy rarely causes severe congestive heart failure and subsides after treatment. ECG alterations immediately after treatment and their improvement 3 months later may be the result of a treatment-induced inflammatory reaction.

Sleeping glands? - The role of endocrine disorders in sleeping sickness (T.b. gambiense Human African Trypanosomiasis).

Symptoms consistent with hypothyroidism or adrenal insufficiency, such as lethargy, anorexia, cold intolerance, weakness, hypotension or paraesthesia, are frequently reported in the literature in patients with Human African Trypanosomiasis (HAT), but an endocrine origin for these symptoms has not yet been demonstrated. Thyroid and adrenocortical function were assessed in 60 patients with late-stage HAT and compared to those in 60 age- and gender-matched healthy controls. Clinical assessment and endocrine laboratory examinations were performed on admission, within 2 days after the end of treatment and at follow-up 3 months later. Signs and symptoms of hypothyroidism, such as fatigue, cold sensation, constipation, paraesthesia, peripheral oedema and dry skin, were significantly more frequent in HAT patients than in the controls. However, these signs and symptoms could not be attributed to hypothyroidism due to the lack of supporting laboratory data, and thus empirical replacement therapy for the clinically suspected hypothyroidism was not warranted. Signs and symptoms consistent with adrenal insufficiency, such as weakness, anorexia, weight loss or hypotension, were significantly more frequent in HAT patients than in controls, but they could not be associated with an insufficiency of the adrenocortical axis. Higher basal levels of cortisol were found in HAT patients than in controls, which can be viewed as a stress response to the infection. However, a transitory adrenal insufficiency was suspected in 8% of HAT patients at admission and in 9% at discharge. All values were normal at follow-up 3 months later.