[The delusions of Health for All. Interview by Christian Moreau].
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Biomedical subjects
Publications and source records attributed to M Gentilini.
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The assessment of the socio-economical aspects of the human immunodeficiency virus (HIV) infection is difficult because of the relative scarcity of information. This study addresses mainly the socio-economic aspects of the AIDS pandemic in the inter-tropical zone of Africa, which, at the moment, constitutes the epicenter of the disease. In the absence of a possible radical treatment, the HIV infection prevalence should range between 25 and 30 million individuals by the year 2000 in the world, and the number of cases of AIDS, between 5 and 6 million, among which 4 to 5 million in the developing world alone. At the current rate, the overmortality rate related to AIDS in Africa is estimated at 0.1%, which should result in a drop by 30% of the Gross National Products advance (GNP). Each case of AIDS in Africa leads to a loss of productivity of 8.8 years. Already, losses caused by AIDS screening and its medical treatment in five countries of Central Africa should exceed the total amount of the foreign assistance received by each country. The estimated economic weight of the AIDS attendance is 15 to 20 times more heavy for a developing country than for an industralized one. Overcoming economically the cost of AIDS is an objective impossible to reach for deprived countries.
Two billion of persons live in regions where endemic malaria prevails or has reappeared. An estimated on hundred million infected individuals per year have been reported around the world. In front of this alarming situation, the diversity and even the incoherence of the currently proposed prophylactic regimens confuses the therapists and renders difficult the adoption of an efficacious strategy. The extension and gravity of drug resistance of P. falciparum and the withdrawal of anti-vectorial campaign constitute two reasons for the present recrudescence of malaria. The preventive strategies in 1990 are based on: rehabilitation of anti-vectorial campaign particularly against nocturnal mosquito bites, applicable to all, everywhere and at all times, by the means of individual and collective measures and mostly by impregnated nets; chemoprophylaxis for which two situations should be distinguished: the non immune traveler leaving for a short period (inferior or equal to 3 months) to an endemic area: individuals living permanently or for long periods in tropical regions. Prevention for short stays In low risk transmission zone (North Africa, Mexico, large cities of South East Asia) whatever the duration, suppression of chemoprophylaxis is acceptable. In high risk transmission zone, three strategies exist according to the intensity and frequency of drug resistance: zone 1 (P. vivax or drug sensitive P. falciparum): chloroquine at a dose of 100 mg/day for adults (1.5 mg/kg/day for children) 6 days out of 7, from the day of departure trough the whole stay and for one month after the return, is still efficacious; zone 2 (moderate frequency of drug resistance): protection is again ensured by chloroquine only, as in zone 1, or better than that by the association of chloroquine 300 mg once a week and proguanil 200 mg/day (3 mg/kg/day for children). The side effects of mefloquine and the risk of generation drug resistance argue against its general use in this zone particularly in West Africa. In one year, we have already observed three chemoprophylactic failures with mefloquine in individuals returning from this region; zone 3 (high frequency of drug resistance and multiresistance): mefloquine, if well tolerated is justified in weekly intake. In case of contraindications or intolerance to mefloquine, which are becoming more frequent, no substitution for that chemoprophylactic regimen is presently available. In view of these facts, indications, contraindications and posologies of mefloquine should be reviewed to better profit from the remarkable characteristics of this antimalarial. Mefloquine should only be prescribed (excluding curative treatment) for chemoprophylaxis of short stays in zone 3. Some contraindications of this drug should be maintained (pregnant women) or made relative (treatment with B-blockers and in the absence of pediatric studies, children weighing less than 15 kg).(ABSTRACT TRUNCATED AT 400 WORDS)
Malaria caused by P. falciparum occurred during prophylaxis with mefloquine upon return from Sierra Leone (zone II). A typical and not recognized, with negative results of initial hematological examinations. Diagnosed on D.26 with parasitemia of 0.2%. Successful treatment of clinical symptoms with halofantrine but increased anemia and positive parasitemia at D.7. Successful treatment with chloroquine. Chemosensitivity tests confirmed sensitivity to chloroquine, threshold sensitivity to quinine (IC50 = 297), resistance to mefloquine (IC50 = 76) despite high levels in bloods, and to halofantrine (IC50 = 7-laboratory normal value = 1). This cross-resistance of P. falciparum originating from Sierra Leone to mefloquine-halofantrine seems to be the first observation of this danger in Africa. Prescription of chloroquine is still imperative in zone 11 countries.
Surveys on drug sensitivity of Plasmodium falciparum carried out between 1985 and 1989 included 7-day in vitro tests and in vivo tests. 485 in vivo tests were carried out in eight surveys conducted in Brazzaville and in several inland regions. The subjects were congolese children aged between 3 months and 15 years old. They were recruited in hospital, mother-child clinics or at school. The drugs studied were chloroquine, amodiaquine and the sulfadoxine-pyrimethamine combination. 182 strains were tested in vitro in two surveys (December 1985 and January 1987); amino-4-quinolines, quinine and mefloquine were studied. Although resistance to amino-4-quinolines is a recent occurrence, by 1985 it had spread widely in the indigenous population in the Centre and South of the country. Resistance has since increased gradually, especially for chloroquine which undergoes specific surveillance. The situation is less serious in the North, a less densely populated region which is still enclosed. In an in vivo comparative study with chloroquine conducted in Brazzaville in November 1986, amodiaquine was found to be only slightly more effective at a similar dosage. At that time, certain isolated observations already seem to imply that the sulfadoxine-pyrimethamine combination was also affected by resistance. This was not corroborated in an in vivo study carried out in 1989 on 40 children presenting with a malarial attack. Although the sensitivity to quinine may probably be decreased. This drug cannot yet be considered as being truly affected by resistance. The activity of mefloquine, the use of which is still limited, was satisfactory in 1987 in two different regions of the country.
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Mefloquine (Lariam) is extensively prescribed for the prevention of malaria in chloroquine-resistant areas. However, in west Africa, most of the strains of Plasmodium falciparum are still sensitive to chloroquine. In addition, a few of these strains are inherently resistant to mefloquine. Under these conditions, we must expect to see the failure of mefloquine prophylaxis in travellers returning from west Africa. We report here 5 such failures. The in vitro susceptibility of Plasmodium falciparum isolates from 4 of these patients was evaluated and showed that all 4 had normal sensitivity to chloroquine and quinine, 3 were resistant to mefloquine and one had reduced susceptibility to mefloquine. Mefloquine blood levels (measured 3 times) were within the normal protective range. These case reports indicate that mefloquine should be used cautiously for malaria prevention in west Africa. They also point out that, regardless of the prophylactic method used, fever in a traveller returning from endemic malaria regions always dictates the analysis of a thick blood smear to rule out the diagnosis of malaria.
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Two patients with acquired immunodeficiency syndrome presented unusual keratotic cutaneous lesions with a protracted course. Pathologic examination in both patients, cultures, and DNA hybridization techniques of skin biopsy specimens in the second patient were characteristic of cytomegalovirus cutaneous infection. Cytomegalovirus skin lesions are rarely described in acquired immunodeficiency syndrome in contrast with the high frequency of ocular and visceral involvement. Skin biopsy specimens may lead to early diagnosis of cytomegalovirus disseminated disease and to specific treatment.
Space exploration carried out under visual control and in its absence (blindfolded condition) was investigated in 20 RBD patients, 10 LBD patients and 20 normal controls with a modified version of Chedru's test (pressing the keys of a keyboard). Conventional tests for visual hemi-inattention permitted to classify RBD patients in a group with visual neglect (RBD VN+) and a group without visual neglect (RBD VN-). On the visual version of the test both RBD groups showed a preference for pressing the keys ipsilateral to the lesion side, but this tendency was more marked in the RBD VN+ group than in any other brain-damaged group. On the tactile version of the test only RBD VN+ patients showed a gradient favouring the pressing of the ipsilateral half of the keyboard. This ipsilateral preference was, however, significantly less marked than that found when the performance was assisted by vision. No relation between neglect in the blindfolded condition and tactile extinction was found. The nature of space exploration in the absence of vision is discussed and the existence of tactile neglect is questioned.
In a search task where four letters were displayed to the right of a central fixation point, right brain-damaged patients with visual neglect showed the fastest response when the target was at the rightmost position and progressively slower responses as it moved towards the center of the display. This finding confirms Kinsbourne's claim that in visual neglect an important role is played by the magnetic attraction that the extreme end of the right structured space exerts on the patient's attention.
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This report describes the growth curve during adolescence in the rural area of Mali (West Africa). The authors measured the height, weight, and arm circumference in a sample of 1255 subjects over 14 years and below 20 years of age during a 2-year cross-sectional study (1984-1985). The comparison of the trend of these criteria with French data suggests that Malian adolescents present a different growth curve to those observed in industralized countries.
Twenty five patients with peripheral neuropathy at different stages of human immunodeficiency virus (HIV) infection are reported. Cerebrospinal fluid (CSF) findings were available in 17 cases, electrophysiology in all and a neuromuscular biopsy in 11. Of six otherwise asymptomatic HIV+ patients, five had chronic inflammatory demyelinating polyneuropathy (CIDP) and one acute inflammatory demyelinating polyneuropathy (AIDP). CSF showed pleocytosis in all cases. Infiltration of the endoneurium and/or the epineurium by mononuclear cells was seen in biopsies from three cases. These six patients recovered either spontaneously, or with corticosteroids or plasmaphereses. Of five patients with AIDS related complex (ARC), three had distal predominantly sensory peripheral neuropathy (DSPN), one CIDP and one mixed neuropathy. Of 14 patients with AIDS, one had mononeuropathy multiplex and 13 painful DSPN. Electrophysiological studies were consistent with an axonopathy. Nerve biopsies in six cases showed axonal changes but surprisingly associated with marked segmental demyelination in two cases. Cell infiltration was present in nerve samples in two cases. Five patients died within six months after the onset of the neuropathy.
Auditory neglect was investigated in normal controls and in patients with a recent unilateral hemispheric lesion, by requiring them to detect the interruptions that occurred in one ear in a sound delivered through earphones either mono-aurally or binaurally. Control patients accurately detected interruptions. One left brain damaged (LBD) patient missed only once in the ipsilateral ear while seven of the 30 right brain damaged (RBD) patients missed more than one signal in the monoaural test and nine patients did the same in the binaural test. Omissions were always more marked in the left ear and in the binaural test with a significant ear by test interaction. The lesion of these patients was in the parietal lobe (five patients) and the thalamus (four patients). The relation of auditory neglect to auditory extinction was investigated and found to be equivocal, in that there were seven RBD patients who showed extinction, but not neglect and, more importantly, two patients who exhibited the opposite pattern, thus challenging the view that extinction is a minor form of neglect. Also visual and auditory neglect were not consistently correlated, the former being present in nine RBD patients without auditory neglect and the latter in two RBD patients without visual neglect. The finding that in some RBD patients with auditory neglect omissions also occurred, though with less frequency, in the right ear, points to a right hemisphere participation in the deployment of attention not only to the contralateral, but also to the ipsilateral space.
Foscarnet is a pyrophosphate analogue that has been successfully used in severe cytomegalovirus (CMV) infections. Little is known of the incidence and mechanisms of foscarnet-induced nephrotoxicity as most data comes from recipients of renal allografts or from patients with severe underlying disease or with other nephrotoxic drugs. We have retrospectively analyzed the evolution of renal function after 56 courses of foscarnet. In addition, we have prospectively studied the protective effects of hydration on foscarnet nephrotoxicity (2.5 liters of saline/day during the night before the foscarnet therapy and throughout the course of treatment). Foscarnet-induced acute renal failure was defined as a rise in serum creatinine of at least 25% from the basal value. An increase in serum creatinine occurred in 37 cases out of the 56 courses of foscarnet (66%). The mean serum creatinine prior to foscarnet was 80.5 +/- 3.3 mumol/l and the mean increase was 190 +/- 28.3 mumol/l (range 80-1,000). Peak serum creatinine was higher than 200 and 300 mumol/l in 16 and 13 patients, respectively. Kidney obtained at autopsy from a 30-year-old male with AIDS, CMV pneumonitis and acute renal failure secondary to foscarnet administration showed an extensive tubular necrosis. In the group which was prospectively hydrated only 1 patient had an acute renal failure. The mean serum creatinine at the peak (96 +/- 4 mumol/l) and at the end of the treatment (83 +/- 4 mumol/l) was significantly lower (p less than 0.05) than in non hydrated patients. In conclusion, foscarnet is a highly nephrotoxic drug which induces acute tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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