Vapreotide, a somatostatin analogue, in cryptosporidiosis and other AIDS-related diarrhoeal diseases.

OBJECTIVE: To evaluate the efficacy and tolerance of vapreotide, a new somatostatin analogue, in the treatment of refractory AIDS-related diarrhoea. DESIGN: An open, non-comparative pilot trial. SETTING: The trial was conducted in 10 medical centres in France. PATIENTS, PARTICIPANTS: Thirty-four AIDS patients with chronic diarrhoea unresponsive to conventional antidiarrhoeal therapy were enrolled. Cryptosporidiosis was diagnosed in 21 out of 30 evaluable patients. Mean number of stools prior to therapy was 10.1 +/- 4.9 per day (range, 3-20 stools per day). INTERVENTION: After initial baseline studies, patients received subcutaneous vapreotide at escalating doses of 400 (23 patients) or 500 micrograms (seven patients), between two and six times daily. MAIN OUTCOME MEASURES: Efficacy was assessed after 14 days of therapy, when it was found to be effective. Responders were offered the opportunity to continue receiving therapy. RESULTS: Four patients demonstrated a complete response and 12 a partial response with greater than 50% reduction in daily stool emission. Fourteen patients did not respond to doses up to 2400 micrograms/day. Patients with conditions other than cryptosporidiosis had a significantly higher probability of response (P = 0.013), as did those with milder diarrhoea (less than 10 stools per day). Median duration of response was 1.5 months (range, 0.5-5 months); relapse occurred in five out of eight responders despite maintenance therapy. Toxicity was minimal. CONCLUSIONS: We conclude that AIDS patients with diarrhoea not caused by Cryptosporidium may benefit from vapreotide therapy.

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

Resting energy expenditure is increased in stable, malnourished HIV-infected patients.

Resting energy expenditure (REE) was measured by reference to body composition in 50 malnourished patients with human immunodeficiency virus (HIV) infection and compared with that of 14 healthy subjects. Among HIV patients, 40 had acquired immune deficiency syndrome (AIDS) and 10 had AIDS-related complex (ARC). All were in stable condition and had a previous history of progressive wasting, ie, a mean body weight loss of 14.2 +/- 8.1 kg over 16.6 mo (range 2-49 ms). The mean REE was 14% higher than estimated basal energy expenditure (EBEE), according to the Harris and Benedict formula. Thirty-four patients (68%) were classified as hypermetabolic (REE greater than 110% EBEE). The best predictable variable for REE was fat-free mass (FFM), as determined by an anthropometric method (r = 0.72; P less than 0.001). The mean REE was 12% higher in HIV patients than in the control group FFM (156 +/- 19 vs 124 +/- 17 kJ.kg FFM-1.d-1). We concluded that in stable and malnourished HIV patients, the progressive wasting may be partly related to an increase in REE. The mechanism of this hypermetabolic state remains to be established.

Resting energy expenditure in human immunodeficiency virus-infected patients: comparison between patients with and without secondary infections.

Resting energy expenditure (REE) was measured in 165 malnourished patients with human immunodeficiency virus infection and compared with that of 31 control subjects. Of these patients, 129 had no symptoms of secondary infections (NI), whereas 36 had evolving secondary infection (I) despite a body temperature < 38 degrees C. Mean REE was 11% higher in the NI group than in the control group (P < 0.05); it was 34% higher in the I group than in the control group (P < 0.001) and 21% higher than in the NI group (P < 0.01). In all cases the best predictive variable for REE was the fat-free mass (FFM) (r = 0.77, P < 0.001 in NI; r = 0.70, P < 0.001 in I; r = 0.78 in the control group. The REE-FFM ratio was 152.5 +/- 1.2 and 207 +/- 5.4 kJ.kg-1.d-1 in the NI and I groups, respectively. A high energy expenditure may be a harbinger of secondary infection in acquired immunodeficiency syndrome and may participate in accelerated weight loss.

Virus excretion in the cervicovaginal secretions of pregnant and nonpregnant HIV-infected women.

In order to estimate the prevalence of viral excretion in cervicovaginal secretions, we made a cross-sectional study of 55 HIV-infected women. The patient population was diverse, including pregnant and nonpregnant women in different disease stages from three centers. Virus replication was found in the cell-free supernatant from 12 of 55 cervicovaginal samples (21.8%) by coculture on the CD4-positive cell line CEM-C113. In addition, cell-associated virus was detected in five of a subgroup of 22 samples testing negatively on cell-free supernatant. The prevalence of HIV in the cell-free supernatant was not related to disease stage, zidovudine therapy, transmission group, or history of sexually transmitted diseases. Excretion of HIV was significantly higher in our population of pregnant women (eight of 21, 38%) compared with an unmatched group of nonpregnant women (four of 34, 11.8%; p = 0.04). These results provide evidence of cell-free virus shedding as well as the presence of cell-associated virus in the genital secretions of HIV-infected women.

Antibodies to the PF155 antigen of Plasmodium falciparum: measurement by cell-ELISA and correlation with expected immune protection.

Plasmodium falciparum polypeptide Pf155 is one of the main candidates for a vaccine against asexual blood stages of P. falciparum. Antibodies against Pf155 can be detected by a cell-ELISA technique with glutaraldehyde-fixed and air dried P. falciparum-infected erythrocytes as antigen. Using this assay, we measured the level of antibodies in sera from 230 subjects with various degrees of past exposure to P. falciparum. Significant levels of antibodies (OD492 greater than 0.5) were detected in 41/50 sera from Central African adults and in 34/50 sera from West African adults. All sera from 50 European adults suffering primary malarial attack and 28/30 sera from West African children (10 to 12 years old) were negative. Intermediate results were obtained with 50 sera from West African adults living in France for greater than or equal to 2 years (12 positive). Mean OD values of the sera of these five groups of subjects varied in the same direction as the positivity rates. These preliminary results suggest that the level of anti-Pf155 antibodies as detected by cell-ELISA might provide an assessment of protective immunity against P. falciparum which could complement clinical or epidemiological criteria.

Hepatitis B antigenaemia on Wuvulu Island.

A survey of the population of Wuvulu Island was undertaken to determine the prevalence of hepatitis B antigenaemia (HBsAg). Seventy-five percent of the population were tested, and 17.7% of those tested were positive for HBsAg. The percentage of positive sera increased with age but declined in the 5th decade of life. There was a marked difference in positivity between the two villages on the island (25.9% and 9.9%) which cannot be explained by several existing hypotheses for HBsAg transmission.

Albendazole: a new broad spectrum anthelmintic. Double-blind multicenter clinical trial.

A new anthelmintic drug, albendazole, has been tested in a multicenter double-blind placebo controlled study in 392 patients from France and West Africa in children and adults with single or mixed infections caused by roundworms, hookworms, whipworms, threadworms and tapeworms. All patients were closely observed before and after treatment for clinical side effects, hematological or clinical blood chemical changes. Fecal samples obtained before, and 7 days and 21 days after treatment were examined using a concentration technic (Ritchie), a coproculture (Harada-Mori) and an egg count (Kato). Following a single dose of 400 mg in adults, cure rates of 96% in ascaridiasis, 96% in ancylostomiasis caused by dose of 400 mg in adults, cure rates of 96% in ascaridiasis, 96% in ancylostomiasis caused by Ancylostoma duodenale, 90% in ancylostomiasis caused by Necator americanus and 76% in trichuriasis were recorded. About 48% of the patients infected by Strongyloides stercoralis were cured following administration of 400 mg per day for 3 consecutive days. The efficacy of half of the adult dose (200 mg) was much lower in children. None of the patients who received placebo were cured. The drug did not produce any significant side effects and approximately the same numbers were reported in the albendazole and the placebo groups. No variations of the hematology and clinical blood chemistry values were recorded.

Use of the Parasight-F diagnostic test for imported malaria in a travel clinic.

The Parasight-F test based on the detection of a soluble antigen specific for Plasmodium falciparum is designed for the immediate diagnosis of malaria infection. We evaluated its use by clinicians during consultations. This prospective study of its diagnostic utility in febrile patients consulting a travel clinic on their return from areas endemic for malaria was conducted between May 1996 and May 1997. The Parasight-F test was performed by the clinician with confirmation by means of standard microscopic examination of venous blood. One-hundred and forty patients were enrolled. Forty-three (31%) cases of malaria were identified by microscopic examination. Thirty-eight were due to P. falciparum. The Parasight-F tests yielded 6 false-positive and 3 false-negative results compared to the microscopic findings. The specificity and sensitivity for the diagnosis of P. falciparum malaria were 94% and 92%. These results show that the Parasight-F test alone cannot replace microscopic diagnosis of malaria in travel clinics.

Clinical efficacy and pharmacokinetics of micronized halofantrine for the treatment of acute uncomplicated falciparum malaria in nonimmune patients.

Twenty-eight nonimmune patients with acute uncomplicated falciparum malaria returning from subSaharan Africa were treated with a micronized formulation of halofantrine hydrochloride (three doses of 250 mg at 6-hr intervals) to investigate the drug's efficacy, tolerance, and pharmacokinetics. In vitro drug susceptibility patterns were determined by the isotopic semimicrotest. Twenty-four of 28 patients were cured. Two of the four patients experiencing recrudescence were associated with low absorption of the drug and parasites susceptible in vitro to halofantrine. The other two patients had adequate plasma concentrations of halofantrine and its main human metabolite, N-desbutylhalofantrine, but the isolates were also resistant in vitro to the drugs, suggesting drug resistance as the cause of treatment failure. Only mild, transitory side effects were noted. A wide interindividual variation in plasma concentrations of halofantrine and its metabolite was observed. Pharmacokinetic studies suggested that the micronized formulation of halofantrine hydrochloride may not increase drug absorption considerably. Further studies using higher doses or longer treatment periods are needed to ensure that adequate plasma concentrations of the drug are used.

Atovaquone plus proguanil versus halofantrine for the treatment of imported acute uncomplicated Plasmodium falciparum malaria in non-immune adults: a randomized comparative trial.

In endemic zones, the atovaquone-proguanil (AP) combination is well tolerated and effective in treating acute, uncomplicated malaria. Trials involving non-immune patients are lacking, however. We conducted a randomized, multicenter open-label trial to determine the efficacy and tolerability of the AP combination (1,000 mg + 400 mg once daily for 3 days) in comparison with halofantrine (HF) (1,500 mg in 3 doses) in non-immune adults with imported uncomplicated Plasmodium falciparum malaria. Follow-up visits were programmed on Days 7, 14, 21, 28, and 35 after hospital discharge. Out of 48 patients enrolled in the study, 41 were assessable for the cure rate (21 in the AP group and 20 in the HF group). All the patients were cured. The mean parasite clearance time was longer (63+/-23 hours) in the AP group than in the HF group (48+/-15 hours) (P = 0.02). The frequency of gastrointestinal adverse events was higher in the AP group. No noteworthy electrocardiographic changes were observed, particularly in the QTc interval. The AP combination appears to be a valuable alternative treatment in non-immune adults.

Risk factors for negative sputum acid-fast bacilli smears in pulmonary tuberculosis: results from Dakar, Senegal, a city with low HIV seroprevalence.

SETTING: Two teaching hospitals in Dakar, Senegal, a West African country with a low prevalence of human immunodeficiency virus (HIV) infection. OBJECTIVE: To determine whether patients with HIV-associated pulmonary tuberculosis have fewer acid-fast bacilli (AFB) in their sputum as assessed by routine microscopy, and to correlate the findings with systematically obtained clinical, radiographic and laboratory variables. DESIGN: Prospective study from November 1995 to October 1996 of 450 consecutive patients diagnosed with pulmonary tuberculosis. RESULTS: Tuberculosis was diagnosed in 380 patients (84.4%) by positive bacteriology, in 61 (13.6%) by a favorable response to anti-tuberculosis chemotherapy, and in nine (2.0%) by the presence of a miliary radiographic pattern. Forty (8.9%) patients were HIV-seropositive. AFB-negative smears were found in 14/40 (35.0%) of the HIV-seropositive patients with pulmonary tuberculosis compared with 71/410 (17.3%) of the seronegative patients (risk ratio [RR] = 2.02, 95% confidence interval [CI] 1.26-3.24, P = 0.01). Multivariate analysis revealed that AFB smear negativity was associated with absence of cavitation (P = 0.002), lack of cough (P = 0.005), the presence of HIV seropositivity (P = 0.02), a CD4+ cell count above 200/mm3 (P = 0.02), and age over 40 years (P = 0.03). CONCLUSIONS: Compared with HIV-seronegative patients with pulmonary tuberculosis, seropositive patients in Dakar, Senegal, are more likely to have negative sputum-AFB smears. This phenomenon has now been observed in seven of eight sub-Saharan African countries with varying HIV seroprevalence from which reports are available.

Treatment of imported cases of falciparum malaria in France with halofantrine.

Halofantrine is a 9-phenanthrenemethanol which is effective against multi-drug resistant strains of Plasmodium falciparum. It has been shown to be highly effective and extremely well tolerated in the treatment of imported cases of falciparum malaria in France. A total of 1,500 mg administered in three 500 mg doses at six-hour intervals results in a 100% cure rate in semi-immune subjects. This dosage should be repeated after 14 days to obtain the same cure rate in non-immune patients. Minor clinical side effects included epigastric pains, nausea and, in one case, a skin rash.

A study of the presence of circulating immune complexes in schistosomiasis.

The sera from 51 patients with schistosomiasis were studied for the presence of circulating immune complexes (IC) using two methods, inhibition of EAC rosette formation and precipitation of radio-labelled Clq. The percentage EAC rosette inhibition was significantly greater in the total group of patients compared to the control sera. The material inhibiting EAC rosette formation was precipitable by 4% polyethylene glycol, thus excluding the role of C3 fragments and suggesting that inhibition was due to immune complexes. Using precipitation of radio-labelled Clq significant high values compared to control sera were only obtained in those patients before treatment or with an active infection. The results suggests that material behaving as IC is present in the sera of patients with schistosomiasis and that measurement of the levels of IC may be important in assessing the state of the disease.

A simple clinical and paraclinical score predictive of CD4 cells counts below 400/mm3 in HIV-infected adults in Dakar University Hospital, Senegal.

In industrialized countries the decision to start co-trimoxazole (CMX) prophylaxis of HIV-related opportunistic infections is based on the CD4+ cell count. The value of CMX prophylaxis has also been demonstrated in Africa, where CD4+ cell counts are rarely available. We therefore developed a simple score predictive of a threshold CD4+ cell count (400/mm3) below which CMX prophylaxis is indicated. In a retrospective cross-sectional study, we collected clinical and biological data on 211 HIV-infected patients recruited from January 1996 through January 1998 at Fann University Hospital in Dakar, Senegal. Several variables were identified as being predictive of a CD4+ cell count below 400/mm3 by stepwise logistic regression. Each variable was weighted according to its regression coefficient, as follows: male sex (+1), weight loss (+2), body mass index < 22 (+2), herpes zoster (+4), tuberculin induration < 5 mm (+3) and haemoglobin < or = 10 g/dL (+1). A score of > or = 4 (sum of weights) selected patients with CD4+ cell counts below 400/mm3 with a sensitivity of 98% and a negative predictive value of 83%. Such a score should be applicable in the African context and should facilitate the management of HIV-infected patients, especially the prescription of CMX prophylaxis.

Albendazole: a new single dose anthelmintic. Study in 1455 patients.

Albendazole has been tested in an open trial conducted in France, seven countries of West-Africa, Martinique and the People's Republic of China in a total of 1455 patients harboring single or mixed infections caused by round-worms, pinworms, hookworms and whipworms. All patients were closely observed before and after treatment for clinical side effects and hematology and clinical chemistry values were done in about 5% of the cases. Fecal samples obtained before and approximately 15, 16 and 17 days after treatment were examined using the Kato test, and when negative, a concentration technic. In case of ancylostomiasis, a coproculture was carried out for species identification. Following a single oral dose, albendazole was highly effective in enterobiasis (100%), ascariasis (89%), ancylostomiasis caused by Necator americanus (88%) and trichuriasis (70%). The drug did not procedure any significant adverse reactions or modifications of the hematological and clinical blood chemistry values and only 6% of the 1455 patients reported minor side effects.

Nutritional status of HIV-seropositive subjects in an AIDS clinic in Paris.

OBJECTIVE: To measure the prevalence and analyse the characteristics of malnutrition among subjects attending an AIDS outpatient clinic and a day care center, to improve the nutritional management of HIV-infected subjects. DESIGN: Prospective cross-sectional study. SETTING: AIDS clinic in a University Hospital in Paris. SUBJECTS: 124 HIV-seropositive adults attending the clinic. MAIN OUTCOME MEASURES: Evaluation of nutritional status using anthropometry, impedancemetry, plasma albumin and pre-albumin assays. Degree of malnutrition, defined by the percentage of body weight loss (BWL), calculated by reference to the usual body weight. RESULTS: Among the 124 subjects recruited (M:F sex ratio: 3.3, mean age: 36.3 +/- 7.2 y), 77 (62.1%, 95%CI: 53.9-70.3) had normal nutrition status (BWL < or = 5%), 16 (12.9%, 95%CI: 7.0-18.2) moderate malnutrition (5% < BWL < or = 10%), 21 (16.9% 95%CI: 10.3-23.5) intermediate malnutrition (10% < BWL < or = 20%), and 10 (8.1%, 95%CI: 3.3-12.9) severe malnutrition (BWL > 20%). BWL was related to the CDC class (variance analysis, P < 9 x 10(-5)) and CD4 cell count (P < 3 x 10(-5)). Malnutrition was observed even among CDC class A subjects (14.9%). BWL was also related to the body mass index (P < 3 x 10(-6)), lean body mass (P < 3 x 10(-5)), body fat (P < 7 x 10(-6)), and as assessed by impedancemetry, body cell mass (P < 10(-5)) an the extra/intra cellular water ratio (P < 2 x 10(-4)). The decrease in lean body mass was related to the decrease in body cell mass. CONCLUSIONS: Given its high frequency, malnutrition should be prevented, detected, monitored and treated from the early stages of HIV infection among patients attending AIDS clinics in order to improve survival and quality of life.

Antimalarial activity and cytotoxicity of Evodia fatraina stem bark extracts.

Stem bark extracts of Evodia fatraina (Rutaceae) were tested for antimalarial activity in vitro on Plasmodium falciparum using an isotopic semi-microtest and in vivo on Plasmodium berghei in mice. Ethyl acetate extract showed moderate antimalarial activity in vitro (IC50 = 8.5 micrograms ml-1). However, ethanolic extract exhibited significant potency in vivo (65% suppression of parasitaemia). Moreover, low toxicity against HeLa cells and L 929 fibroblasts was observed with ethanolic extract (IC50 = 95 micrograms ml-1 and 60 micrograms ml-1, respectively).

[Sexually transmitted diseases and mother-infant transmission (epidemiology and prevention)]. / Les maladies sexuellement transmissibles et le couple mère-enfant. (Epidémiologie et prévention).

Gonococcal ophthalmia neonatorum may be severe with a high risk of blindness; therefore prophylaxis is mandatory. Chlamydial ophthalmia is less severe and prevention remains less effective. Both microorganisms may be responsible of preterm labour and perinatal deaths. Congenital syphilis is an important public health problem in developing countries. Some recent papers underline the decrease of infestation when mothers may be screened during pregnancy (at least two times in initially seronegative mothers) and correctly treated by beta-lactamines.