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.

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.

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.

Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal.

OBJECTIVES: To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults. DESIGN: Randomized, double-blind, placebo-controlled clinical trial in the urban community of Dakar, Senegal. METHODS: Eligibility criteria were age greater than 15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, no progressive infection, no previous history of intolerance to sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia, infectious enteritis, bacterial meningitis, urinary tract infection, bacterial otitis and sinusitis, and pyomyositis. RESULTS: Between September 1996 and March 1998, 297 patients were screened, and 100 were randomized in the study. Demographic, clinical, and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2). CONCLUSION: Our study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar, Senegal.

Cutaneous larva migrans in travelers: a prospective study, with assessment of therapy with ivermectin.

The purpose of this prospective study was to update epidemiological data on cutaneous larva migrans (CLM) and to assess the therapeutic efficacy of ivermectin. We performed the study between June 1994 and December 1998 at our travel clinic. Ivermectin (a single dose of 200 microg/kg) was offered to all the patients with CLM, and its efficacy and tolerability were assessed by a questionnaire. Sixty-four patients were enrolled. All were European and had stayed in tropical areas. After the patients had returned from their destinations, 55% had lesions occur within a mean of 16 days (range, 1-120 days; >1 month in 7 patients). The initial diagnosis was wrong in 55% of patients. The mean number of lesions was 3 (range, 1-15), and the main sites were the feet (48%) and buttocks (23%). The cure rate after a single dose of ivermectin was 77%. In 14 patients, 1 or 2 supplementary doses were necessary, and the overall cure rate was 97%. The median time required for pruritus and lesions to disappear was 3 and 7 days, respectively. No systemic adverse effects were reported. Physicians' knowledge of CLM, which can have a long incubation period, is poor. Single-dose ivermectin therapy appears to be effective and well tolerated, even if several treatments are sometimes necessary.

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.

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.

[Invasive aspergillosis sinusitis in patients infected by the human immunodeficiency virus]. / Sinusites aspergillaires invasives chez les patients infectés par le virus de l'immunodéficience humaine.

Invasive aspergillus sinusitis invasive is a rare, life threatening infection observed in immunocompromised patients. We report three cases of patients with AIDS. Diagnosis was based on surgical biopsy specimen performed on patients with unilateral sinusitis with facial pain and osteolysis on CT scanning, associated in one patient with neurological disorders. One patient with frontal sinusitis and meningeal involvement died despite therapy. One patient with limited maxillary sinusitis who underwent surgical satisfactory resection and antifungal therapy was successfully treated without relapse 12 months later. One patient with orbital and cavernous sinus extension of ethmoiditis was successfully cured with antifungal therapy by itraconazole. Our results confirm the necessity of early diagnosis when clinical and CTscanning are suggestive and the curability of aspergillus sinusitis.

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.

[Malaria prophylaxis]. / Prophylaxie du paludisme.

Malaria, occurring in 1 to 2% of unprotected travellers to sub-Saharian Africa, remains a real risk because of its potential severity. In Asia or Latin America, the risk appears to be much lower, and in some cases, prevention can be limited to measures to avoid mosquito bites. Chemoprophylaxis by chloroquine-proguanil, mefloquine or, less frequently cyclines, is efficacious but poor compliance and frequent adverse events limits its interest. No regimen is totally effective and malaria must be considered in any traveller coming back from an endemic area with fever, even still receiving an appropriate prophylaxis.

Prospective evaluation of a flow chart using a risk assessment for the diagnosis of STDs in primary healthcare centres in Libreville, Gabon.

BACKGROUND: The serious impact of STDs on women and children in particular, and the linkage between STDs and HIV infection are a profound concern to public health worldwide. One of the main strategies against STDs is based on early diagnosis and treatment. However, this approach is limited by the lack of appropriate laboratory facilities. A syndromic approach has been recommended by the WHO but needs to be evaluated under field conditions. A preliminary cross sectional study on STD prevalence and risk factors in Libreville showed that 13.5% of pregnant women had gonococcal and/or chlamydial infection which justifies systematic screening of STDs. Based on the results of this study, different flow charts with or without a risk factor assessment (score) were designed. The flow chart with the best performances for diagnosing chlamydial or gonococcal cervical infection and routinely acceptable, was a score algorithm, based on two risk factors (age and marital status) and four simple clinical signs (pelvic or lumbar pain, vaginal discharge and its characteristics). Sensitivity and specificity were 76.9% and 40.4% respectively. Thus, the objective of this study was to evaluate this strategy under field conditions. METHODS: A prospective study among pregnant women attending antenatal clinics was done. The score was applied to each woman by a midwife and a physician, and specimens were collected for the reference laboratory tests. Validation of the algorithm was done by comparing the performances with the gold standard laboratory diagnosis. RESULTS: 646 pregnant women were enrolled. The prevalence of cervical infection was 11.3. The sensitivity and specificity of this algorithm recorded by the midwives were 73.3% and 54.8%, respectively and by the physician 76.7% and 50.6%. The proportion of women correctly classified by the midwives and by the physician was not significantly different. CONCLUSION: The score applied was well accepted by healthcare workers and patients, and was routinely practised. Results obtained by the midwives and by the physician were similar. Thus, the use of flow charts which adds a risk assessment to the syndromic approach for diagnosing cervical infections is feasible. However, the performances of such flow charts need to be improved before being used routinely.

[Treatment of CMV retinitis with intravitreal foscarnet]. / Traitement de la rétinite à CMV par foscarnet intravitréen.

PURPOSE: To assess the tolerability and efficacy of intravitreal injections of foscarnet in cytomegalovirus (CMV) retinitis in acquired immunodeficiency syndrome (AIDS). METHODS: Patients with CMV retinitis resistant and/or intolerant to intravenous foscarnet and ganciclovir and resistant to intravitreal ganciclovir were included. The induction therapy consisted of intravitreal injections of 2,400 micrograms of foscarnet twice a week. The assessment was performed by clinical examination and photographies of the fundus. RESULTS: Three patients (four eyes) have been included. Three eyes were administered seven and one eye eight intravitreal injections. The tolerability was good, but the efficacy was mere: the retinal lesions became less edematous, but they still extended. CONCLUSION: In these four eyes with CMV retinitis resistant to intravitreal ganciclovir, intravitreal injections of foscarnet were well tolerated but did not stop the progression of the retinitis.

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.

Randomized comparison of amphotericin B deoxycholate dissolved in dextrose or Intralipid for the treatment of AIDS-associated cryptococcal meningitis.

We conducted a randomized, open-labeled clinical trial to compare the tolerability and efficacy of amphotericin B deoxycholate, prepared in 5% dextrose or Intralipid (Kabi Pharmacia, Saint-Quentin-en-Yvelines, France), in the treatment of AIDS-associated cryptococcal meningitis in Burundi. Forty-four patients were assigned to receive amphotericin B/dextrose (0.7 mg/[kg.d]) for 14 days; the dose was then reduced to 1 mg/kg every other day for 28 days (infused over 6 hours). Forty-six patients were assigned to receive Intralipid/amphotericin B at a 50% higher dosage (1 mg/[kg.d]) for 14 days; the dose was then reduced to 1.5 mg/kg every other day for 28 days (infused over 2 hours). Intralipid significantly decreased the incidence of fever (P = .02) and chills (P = .0001) related to the infusion of amphotericin B deoxycholate. Analysis of the time to the onset of increased levels of serum creatinine (creatinine level, > 150 mumol/L) showed that Intralipid/amphotericin B was more nephrotoxic (P = .03). The percentage of patients who were clinically cured or had improvement in their conditions and successful mycological outcome was similar in both therapeutic groups, but analysis of the time to the first negative cerebrospinal fluid culture showed a nearly significant difference that favored Intralipid/amphotericin B (P = .07). Intralipid reduced the infusion-related toxicity of amphotericin B deoxycholate without altering its antifungal efficacy but did not confer substantial benefit against renal toxicity that would allow the unitary dosage of amphotericin B deoxycholate to be increased safely.

Herpes simplex esophagitis in patients with AIDS: report of 34 cases. The Cooperative Study Group on Herpetic Esophagitis in HIV Infection.

Herpetic esophagitis (HE) associated with human immunodeficiency virus (HIV) is a rare condition mainly reported as isolated cases. We thus decided to study this association and analyze the possible predisposing factors, clinical and endoscopic presentations, and clinical response to treatment. Thirty-four HIV-1-infected patients were identified: 27 had histologically or virologically confirmed HE and seven had probable HE, a retrospective diagnosis based on the efficacy of acyclovir given alone. The median CD4 cell count was 15/mm3. Recent predisposing factors (such as nasogastric procedures, steroid therapy, and anticancer therapy) were noted with regard to 16 of the 34 patients (47%). Odynophagia and/or chest pain occurred in 30 patients (88%). At the time of diagnosis of HE, extraesophageal herpes was found in only 13 patients (38%). Superficial ulcers of the distal third of the esophagus were present in 17 (50%). Among 20 of the 27 patients with confirmed HE that could be evaluated, therapy with acyclovir led to complete resolution in 16 and partial response in 3; 1 patient died of HE. Five patients (15%) suffered confirmed or possible relapses. The mean interval between the diagnosis of HE and death was 8.8 months. Herpes simplex virus may be responsible for ulcerated esophagitis that occurs in the advanced stages of AIDS and that can be safely treated with acyclovir before a definitive diagnosis is made.