Objective To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers. Design Randomised, double blind, study with placebo run-in phase. Setting Travel clinics in Switzerland, Germany, and Israel. Main outcome measure Proportion of participants in each treatment arm with subjectively moderate or severe adverse events. Participants 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil. Results A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013).Conclusions Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.
Compared with HIV-uninfected individuals, HIV-infected patients respond to 17DV with lower reactive NTs, more often demonstrate nonprotective NTs, and may experience a more rapid decline in NTs during follow-up. Vaccination with 17DV appears to be safe in HIV-infected individuals who have high CD4 cell counts, although rate of serious adverse events of up to 3% cannot be excluded.
HIV-infected patients' long-term immune response up to 10 years to YFV is primarily dependent on the control of HIV replication at the time of vaccination. For those on successful cART, immune response up to 10 years is comparable to that of non-HIV-infected adults. We recommend a single YFV booster after 10 years for patients vaccinated on successful cART, whereas those vaccinated with uncontrolled HIV RNA may need an early booster.
Summary Loiasis, caused by the filarial parasite Loa loa, is endemic in West and Central Africa. Ivermectin has been shown to be an effective treatment of loiasis. We report the case of a 20-year-old woman originally from Cameroon who was infected by the L. loa parasite and developed severe hepatitis, identified 1 month after a single dose of ivermectin. Liver biopsy showed intralobular inflammatory infiltrates, confluent necrosis and apoptosis, compatible with drug-induced liver disease. To our knowledge, this is the first case of ivermectin-induced severe liver disease published in the literature. © 2006 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. Case reportIn October 2000, a 20-year-old woman was referred to the Swiss Tropical Institute, Basle, Switzerland, for evaluation of a migrating worm in the sclera of her right eye ( Figure 1). She reported general body itching over several years, headache and dizziness. She had lived in Cameroon until the age of 15; she had moved to Switzerland 5 years previously and had not visited Africa since then. She had had meningitis with subsequent persistent deafness and a history of hepatitis A and B. Initial physical examination was inconspicuous except for moderate abdominal pain.The worm that was removed from the patient's right eye was identified as an adult Loa loa, with a length of 2 cm. Initial L. loa microfilaraemia was 820/ml of whole * Corresponding author. blood. There was an eosinophilia of 18.5% (absolute count 350/l), and liver enzymes were normal. The patient was treated with albendazole (600 mg/d) for 21 d. One month after the end of therapy, the microfilaraemia dropped to 250/ml and was still at this level 3 months thereafter (Table 1). Clinical signs and liver enzymes remained normal, and no abdominal pain was reported. A single dose of 15 mg (300 g/kg) ivermectin, a dosage previously reported as having no major side effects (Kombila et al., 1998), was given to reduce the microfilaraemia further. At a routine follow-up 1 month after administration of ivermectin, the patient reported moderate new diffuse abdominal pain. Physical examination showed a new tenderness in the upper right quadrant; the liver was not enlarged. Laboratory investigation revealed elevated liver enzymes: ALAT 907 IU/l (normal range 7-42), ASAT 279 IU/l (normal range 5-39) and ␥GT 66 IU/l (normal range 8-78); bilirubin, alkaline phosphatase, C-reactive protein, and red and white blood cell counts were in the normal range. Viral hepatitides were ruled out by means of serology (HAV, HBV, HCV, CMV, EBV).
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