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An international multicenter study of ready-to-eat foods, sandwiches, and ice creams or sorbets sold in the streets and their vendors was carried out to assess the microbiological quality of these foods and to identify characteristics of the vendors possibly associated with pathogens. Thirteen towns in Africa, America, Asia, and Oceania were involved in the study. A single protocol was used in all 13 centers: representative sampling was by random selection of vendors and a sample of foods bought from each of these vendors at a time and date selected at random. Microbiological analyses were carried out using standardized Association Française de Normalisation methods, and the use of a standardized questionnaire to collect data concerning the characteristics of the vendors. Fifteen surveys were carried out, with 3,003 food samples from 1,268 vendors. The proportion of unsatisfactory food samples was between 12.7 and 82.9% for ice creams and sorbets and between 11.3 and 92% for sandwiches. For ice creams and sorbets, the sale of a large number of units (>80 per day) increased the risk of unsatisfactory food by a factor of 2.8 (95% confidence interval [CI]: 1.5 to 5.1), lack of training in food hygiene by 6.6 (95% CI: 1.1 to 50). and by a factor of 2.8 (95% CI: 1.4 to 5.4) for mobile vendors. These risk factors were not identified for sandwiches, this difference may be due to the presence of a cooking step in their preparation. These results show that the poor microbiological quality of these street foods constitutes a potential hazard to public health, that the extent of this hazard varies between the cities studied, and that vendors' health education in food safety is a crucial factor in the prevention of foodborne infections.

In 1988, a programme of leprosy chemoprophylaxis, employing a supervised, single 25 mg/kg dose of rifampicin, was implemented in the Southern Marquesas Islands. Of the 2786 inhabitants, 2751 (98.7%) were treated. In addition, 3144 South Marquesans living elsewhere in French Polynesia were administered the same chemoprophylaxis. During the following 10 years, seven leprosy patients were detected among those who had been administered chemoprophylaxis. Of these, two were very likely missed cases of leprosy, and cannot be considered a failure of chemoprophylaxis. The epidemiometric projection model, based on cases of leprosy observed in the Southern Marquesas during the 20 years preceding implementation of the programme, predicted that 17 leprosy cases could be expected in the South Marquesan population if no chemoprophylaxis were given. In fact, only five cases were detected in the treated population, a number significantly smaller than 17, suggesting that the chemoprophylaxis was 70% effective, assuming that no change of detection rate would have occurred without chemoprophylaxis. However, during the 10 years following implementation of the chemoprophylaxis programme, the detection rate in the Polynesian population that was not administered chemoprophylaxis declined by about 50%. Therefore, the effectiveness of the chemoprophylaxis was only 35-40%.

A common problem of osteitis and septic arthritis is the recurrent bone infection after surgical debridement, a problem frequently encountered in patients with sequela leprosy. In these cases the authors propose the use of an ancient method of post surgical wound care based on the treatment with ordinary granulated sugar. The hyperosmolar climate created this way in the wounds inhibits the bacterial growth, enhances bacterial death and therefore permits the growth of granulation tissue in order to recover the debrided nude bones. At ILAD (Leprosy Institute of Dakar), 36 osteitis and septic arthritis were treated and healed during the last 2 years from March 1995 to March 1997 using this technic. All the wounds healed in the mean-time of 44 days. Only two of them needed a second debridement and healed afterwards. Up to now the method using ordinary sugar was applied in the treatment of infected wounds, eschars and postsurgical infections. Our experience shows that it also can be indicated to treat bone infections. This method is easy to apply also under often difficult field conditions and is very cheap.

The introduction of a program for the treatment of plantar ulcers (PU) in field conditions in Senegal was studied. The program was complementary to the Health Education and Protective Footwear to Prevent Disability (POD) initiatives within the Senegalese anti-leprosy program. The wound care given in health centers was coded and simplified. Access to hospitals was made easier for those patients requiring surgery. More than 30% of patients with PU were treated each year, with a mean of 62% cured. An increasing number of leprosy patients have been admitted to regional hospitals for surgery. Never before have patients with signs of leprosy had access to general hospitals. This study emphasizes the need for regular supervision of the individuals treating wounds.

In 1995, a field trial was implemented in Senegal in order to evaluate the efficacy of a regimen based on the monthly supervised intake of rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg to treat leprosy. During the first year of the trial, 220 patients with active leprosy (newly detected or relapsing after dapsone monotherapy) were recruited: 102 paucibacillary (PB) (60 males and 42 females) and 118 multibacillary (MB) (71 males and 47 females). All of them accepted the new treatment (none requested to be preferably put under standard WHO/MDT), no clinical sign which could be considered as a toxic effect of the drug was noted, and none of the patients refused to continue treatment because of any clinical trouble. The compliance was excellent: the 113 patients (PB and MB) detected during the first 6 months of the trial have taken six monthly doses in 6 months, as planned. The rate of clearance and the progressive decrease of cutaneous lesions was satisfactory. Although it is too soon to give comprehensive results, it should be noted that no treatment failure was observed in the 56 PB patients who have completed treatment and have been followed up for 6 months. The long-term efficacy of the new regimen is to be evaluated on the rate of relapse during the years following the cessation of treatment. If that relapse rate is acceptable (similar to that observed in patients after treatment with current standard WHO/ MDT), the new regimen could be a solution to treat, for instance, patients very irregular and/or living in remote or inaccessible areas since no selection of rifampin-resistant Mycobacterium leprae should be possible (a monthly dose of ofloxacin and minocycline being as effective as a dose of dapsone and clofazimine taken daily for 1 month). Nevertheless, until longer term results of this and other trials become available, there is no justification for any change in the treatment strategy, and all leprosy patients should be put under standard WHO/MDT.

Practically leprous plantar ulcers (PU) are difficult to treat and heal under field condition. Considering the important number of patients showing a PU, the directors of national leprosy control programmes are determined, within the programmes on prevention of disabilities (POD), to treat the PU in the field. Therefore it appears to be essential to codify and simplify their treatment thus enabling it to be effective. The healing of PU being the only criteria of effectiveness of the technique. Four clinical stages were defined, each corresponding to a precise way of treatment using only essential and basic products at low cost. During the trainings about the treatment techniques and attitudes much emphasize is given on the discharge of the PU, on the trimming of the wound and on the products to use according to PU's evolutionary stage.

Biopsies of the superficial sensory branch of the radial nerve are contested. Some authors mention it to be simple and without harm, but others are formally against this procedure. At ILAD, 274 biopsies were made between 1986 to 1992. We present a review of 112 leprosy patients for whom biopsy was done. On 112 reexamined patients, we observed 2 benign neuroma, hence 2%. The comparison of nerve function before biopsy and after, of 63 of the 112 patients, reexamination shows no significant modification of the functional score. Given even the occurrence of benign neuroma in only 2% of the cases, the authors do not recommend the biopsy of the superficial sensory branch of the radial nerve. For research purposes on neuritis in leprosy, as well as to assure diagnosis in primary neuritic leprosy, we propose the biopsy of the sensory branch of the musculo cutaneous nerve at elbow level.

Community treatment with ivermectin was implemented in Opoa, French Polynesia from April 1991 to October 1993. All consenting inhabitants aged 3 years or more were treated with twice-yearly single doses of ivermectin, pregnant women excepted. A dosage of 100 microgram/kg was used for the 3 first treatments and then abandoned because it did not reduce the prevalence of microfilariae (mf) carriers. With a dosage of 400 micrograms/kg dosage, this prevalence decreased dramatically from 21% to 7%, and the mf level in carriers dropped to only 0.5% of its initial value after 3 treatments. The 400 micrograms/kg dosage was well tolerated and compliance was excellent. The twice-yearly single dose strategy with ivermectin at 400 micrograms/kg is safe and highly effective for filariasis control in an endemic area.

This paper deals with the results observed in 21 ancient leprosy patients suffering from lagophthalmos (13 of whom suffered from bilateral lagophthalmos) and treated by the Edgerton-Montandon surgical procedure which associates lateral canthopexy and tarsorraphy. Eighteen of the 21 treated patients were reviewed at one month after the procedure and, overall, results could be evaluated for 30 eyes. Improvement was noted in all of the 30 eyes and, globally, the residual palpebral fissure (during voluntary closing of the eyes by the patient) decreased from 6.7 mm before the procedure to 1.8 after the procedure. The following recommendations may be proposed. For young patients with intact corneal sensation, the Gillies procedure remains the procedure of choice to correct lagophthalmos. For older patients with corneal anesthesia, at high risk of blindness, the Edgerton-Montandon procedure should be recommended.

Between 1983 and 1994, 66 Senegalese leprosy patients were seen for cauliflower growths developed in chronic plantar ulcer (CPU), (2 patients had each 2 tumors). 68 biopsies for pathological examination were taken: the diagnosis of squamous cell carcinoma was effectively made in 39 cases (38 patients) and that of pseudo-epitheliomatous hyperplasia in the remaining 29 cases (28 patients). The mean annual frequency of cauliflower growths was 0.45 per 100 CPU. Among these tumors, the percentage of carcinoma was 57%. Of the 38 patients with a carcinoma, 5 refused amputation and all of them died. The 33 others were amputated and of these 8 died as a direct result of their carcinoma (24%). In the case of the 28 patients with hyperplasia, amputation was carried out on 18 patients and local excision on 10. In the months following the operation 8 recurrences were observed in 10 of the patients on whom excision had been carried out. These recurrences were treated by amputation. This gives a total of 93% of amputations in the cases of hyperplasia. These facts lead as to conclude that at least in countries where pathological examination is not available below knee amputation is the most reasonable action to take in the proliferative tumors developed on a CPU.

In March 1991, a study on Wuchereria bancrofti (Cobbold, 1887) infection rates in its vector, Aedes polynesiensis Marks, was carried out in a village of French Polynesia. Our data were collected 10 yr after the suspension of human mass chemoprophylaxis and served as a baseline for pending ivermectin treatment scheduled in 1991-1993. In total, 1,789 biting females were collected, of which 1,740 were dissected and 1,183 (68%) were parous. Among these, 106 (8.96%) were infected with W. bancrofti and 34 (2.87%) harbored infective L3 larvae. The mean number of larvae per infected mosquito was 2.69, and the mean number of L3 larvae per L3 positive mosquito was 1.44. The Ae. polynesiensis biting index was 4.7 bites per 15 min, but varied significantly among habitats. The highest parous biting rates occurred in fields and peridomestic gardens and the lowest was close to houses. The proportion of parous infected and infective mosquitoes was higher in peridomestic habitats (0.25 infective bites per 15 min) than in domestic habitats (0.09) or in fields (0.11).

Forty-three Wuchereria bancrofti carriers were given four successive semi-annual single doses of ivermectin 100 micrograms.kg-1 (IVER 100). The geometric mean microfilaremia (mf) recurrence percentage as compared to the pre-initial treatment mf level was 35%, 21%, 17% and 17% at 6, 12, 18 and 24 months, respectively. However, the recurrence of mf 6 months after the fourth treatment remained high in several individuals: 15 have been considered as 'bad responders' and 28 as 'good responders' individuals. At month 24 (M 24), they were randomly allocated into 2 groups. A first group was treated with a fifty and a sixth dose of IVER 100, at M24 and M30, respectively; the second one was treated, at the same time, with single doses of IVER 400 micrograms.kg-1 (IVER 400). At M 36, the mf recurrence percentage (mf M36/mf M0) was significantly higher in patients treated with IVER 100 than IVER 400 (11% vs 1%, p < 10(-4). From the group IVER 100, 6 out of the 8 'bad responders' remained 'bad responders' whereas there were none of the 7 in the group IVER 400. Moreover, there were only 2 more patients in the group IVER 100 showing sustained complete zero mf, whereas they were 13 in the group IVER 400. Single doses of IVER 400 were effective on 'bad responders'; IVER 400 must be recommended for semi-annual mass treatment in bancroftian filariasis.

The age-specific patterns of microfilaremia, Og4C3 antigenemia, anti-Brugia malayi IgG and IgG4 were assessed in 3 villages of low, medium and high transmission level for Wuchereria bancrofti filariasis. The prevalence rates for each of the 4 markers were clearly age dependent and their patterns strongly associated with the transmission level. The antigenemia prevalence rate was consistently higher than the microfilaremia prevalence rate, in all age groups. The prevalences of anti-B. malayi IgG and IgG4 responses were very similar and much higher than those of microfilaremia or antigenemia. Antibody responses reached the plateau at an earlier age and at a higher prevalence with increased intensity of transmission. For all the markers, the prevalence rates were significantly higher in males than in females.

Between 1986 and 1989, in 5 departments of Senegal, 436 new cases of leprosy were detected, of whom 225 were put under dapsone monotherapy and 211 under multidrug therapy (MDT). Of them, 190 could be followed-up during 2 years by means of annual bacteriological and clinical examination, including neurological assessment. In 2 years, the onset of 10 (5.3%) chronic plantar ulcers (CPU) was observed: 4 (4%) among the 99 patients under dapsone monotherapy and 6 (6.6%) among the 91 under MDT (no significant difference). Of the 10 CPU, 3 (2%) appeared among the 149 patients without any disability at detection while 7 (17%) were observed among the 41 others who presented a grade 1 disability at detection (p < 0.01). Of the 6 CPU appeared in the patients under MDT, 5 (22%) were observed among the 23 who presented a grade 1 disability at detection and 1 (1.5%) among the 68 who did not (p < 0.01). This difference was not noted in the patients under dapsone monotherapy. Our results need to be confirmed by other studies including a higher number of patients followed-up during a longer period of time. Nevertheless, they suggest that MDT could prevent the onset of CPU, but only in patients without any disability at detection. Therefore, they reemphasize the importance of early detection of the disease in leprosy control programmes.

Of 584 leprosy patients known at the Institut de Léprologie Appliquée de Dakar because they suffered a nerve lesion with or without chronic plantar ulcer (CPU), 242 (41%) could be followed-up during a mean period of time of 8.2 years (range: 5 and 10 years) by the means of the mobile disability prevention team (health education, medical care and shoe workshop). Every two months a visit of the patients, at their home town, was organized, with the purpose to assess whether they could actually put into practice the foot and hand as having been trained for. At the same time, further advice and encouragement were given to the patients. Adapted footwear was brought to the patient, at reduced fee, the foot prints and special moulds having been taken during the previous visit. The local health worker were responsible for light surgical cares. Among the 242 followed-up patients: of 107 without CPU at beginning, 90 (84%) remained so, of 135 with CPU at beginning, 57 (42%) were cured, of 135 with CPU at beginning, 74 (55%) remained stable (no worsening), the last 21, of whom 17 showed severe foot deformities but without CPU, worsened (all presented one or more CPU at the last control). Of the 242 patients, 221 (91%) remained stable or showed substantial improvement. Therefore, it must be emphasized that careful follow-up of patients is essential to insure the improvement or care of CPU as well as to prevent the onset, worsening or reappearance of CPU. Such follow-up must consist of cares, health education and special shoe wearing.

Peripheral blood mononuclear cells from 27 healthy leprosy contacts were analyzed for lymphoproliferation and TH-1 cytokine secretion (interleukin-2 and gamma interferon) in response to heat shock proteins with molecular masses of 65, 18, and 10 kDa from Mycobacterium leprae and the 30-32-kDa antigen 85 (Ag 85) from Mycobacterium bovis BCG. Cells from 18 and 19 of 19 lepromin-positive contacts proliferated or produced TH-1 cytokines in response to the M. leprae 10-kDa protein and to Ag 85, respectively. Limiting-dilution analysis for two lepromin-positive contacts indicated that about one-third of M. leprae-reactive T cells displayed specificity to the M. leprae 10-kDa protein and Ag 85. The M. leprae 65- and 18-kDa proteins were less potent TH-1 response inducers: gamma interferon and interleukin-2 could be measured in 14 and 19 lepromin-positive contacts, respectively. In contrast, very low or undetectable proliferative and cytokine responses were found for 8 lepromin-negative contacts. Our data demonstrate that the fibronectin-binding Ag 85 and the 10-kDa GroES homolog are powerful mycobacterial TH-1 response inducers in the vast majority of lepromin-positive contacts and suggest that they might be valuable candidates for a future subunit vaccine.

Enzyme-linked immunosorbent assays (ELISAs) for anti-Brugia malayi immunoglobulin (Ig) G and IgG4 were evaluated on sera from 1561 subjects in French Polynesia for the serodiagnosis of Wuchereria bancrofti filariasis, compared with the test for Onchocerca gibsoni circulating antigen (Og4C3) as a 'gold standard'. The sensitivity of the ELISA-IgG and ELISA-IgG4 assays was 90.8% and 94.5%, and the specificity was 45.9% and 50.7%. The positive predictive values were 41% and 45% respectively for an antigen prevalence rate of 30%. Thus antibody prevalences exceeded by two-fold the antigen prevalence, which itself exceeded by two-fold the prevalence of microfilaraemia.

In 1993, a three-arm double-blind controlled trial was implemented in French Polynesia to compare the tolerance and efficacy of a single dose of the combination ivermectin (IVR) 400 micrograms/kg plus diethylcarbamazine (DEC) 6 mg/kg vs. IVR 400 micrograms/kg alone vs. DEC 6 mg/kg alone, for treatment of Wuchereria bancrofti carriers. Of the 57 treated male patients in whom microfilaria (mf) densities ranged from 22 to 4709 mg/mL, 3 groups of 19 were randomly selected and allocated to one of the 3 treatments. Side effects were experienced by 34 patients (60%), but none suffered a severe reaction. Grade of reaction did not differ between treatment group, but was significantly correlated with the pretreatment mf density. Six months after treatment, 26%, 32% and 53% of patients were amicrofilaraemic in the DEC, IVR and IVR+DEC groups, respectively. Mf levels were 6.3%, and 3.1% and 1.0% of the pretreatment level, respectively, significantly lower in the IVR+DEC group than in both the IVR and DEC comparison groups. The combination IVR+DEC showed promise in term of sustained mf decrease, and could be an effective alternative for lymphatic filariasis control programmes.

Lymphoproliferation and gamma interferon (IFN-gamma) secretion in response to 28 overlapping 20-mer synthetic peptides covering the complete sequence of the mature (295-amino-acid) 85A component of the major secreted, fibronectin-binding antigen 85 complex from Mycobacterium tuberculosis and Mycobacterium bovis BCG (MTAg85A) was examined by using peripheral blood mononuclear cell (PBMC) cultures from healthy tuberculin- and lepromin-positive volunteers and from patients with tuberculosis and leprosy. Peptide recognition was largely promiscuous, with a variety of human leukocyte antigen haplotypes reacting to the same peptides. PBMC from all tuberculin-positive subjects reacted to Ag85, and the majority proliferated in response to peptide 6 (amino acids 51 to 70), peptides 13, 14, and 15 (amino acids 121 to 160), or peptides 20 and 21 (amino acids 191 to 220). PBMC from tuberculosis patients demonstrated a variable reactivity to Ag85 and its peptides, and the strongest proliferation was observed against peptide 7 (amino acids 61 to 80). MTAg85A peptides were also recognized by PBMC from healthy lepromin-positive volunteers and paucibacillary leprosy patients (again in a promiscuous manner), but despite a 90% homology between the 85A proteins of M. leprae and M. tuberculosis, the peptides recognized were different. PBMC from lepromin-positive healthy contacts reacted against peptide 2 (amino acids 11 to 30), peptide 5 (amino acids 41 to 60), and peptides 25 and 26 (amino acids 241 to 270). PBMC from paucibacillary patients reacted preferentially against peptide 1 (amino acids 1 to 20) and peptide 5. Multibacillary patients were not reactive to Ag85 or the MT85A peptides. IFN-gamma production was generally detected simultaneously with positive lymphoproliferative responses, although peptide 1 mostly stimulated proliferation and peptides 27 and 28 mostly elicited an IFN-gamma response. In conclusion, regions 41 to 80 and 241 to 295 demonstrated powerful and promiscuous T-cell-stimulatory properties, resulting in proliferative responses and IFN-gamma secretion, respectively, in the majority of reactive subjects tested in this study. These results could be of value in the development of a subunit vaccine for tuberculosis and leprosy.

Twenty six male and female patients aged 5 to 17 years who had head lice infestation confirmed by eggs presence and received treatments with a single 200 mu/kg oral dose of ivermectin in open fashion. At day 14 after treatment, 20 responded to the treatment (77%), and 6 patients (23%) presented with a complete disappearance of eggs and all clinical symptoms. At day 28, 7 patients were healed (27%), but 4 patients of the 6 healed at day 14 presented with signs of reinfestation. This study suggests that ivermectin is a promising treatment of head lice, and a second dose at day 10 should be appropriate for a further comparative trial.

This study involved 221 microfilaremic (Mf+), 302 amicrofilaremic (Mf-) antigen positive (AG+) and 1454 Mf-antigen negative (AG-) individuals living in endemic villages. Whatever the group considered, antigen and antibody titers were widely distributed. Og4C3 antigen, detected both in Mf- and Mf+ patients, was significantly higher in Mf+ patients. The Mf parasitological status did not significantly influence the antifilarial antibodies levels in the infected AG+ individuals, although IgG4 was more discriminant. In the supposedly uninfected individuals (Mf-AG-), anti-filarial IgG and IgG4 could be detected in a large proportion of the group. Og4C3 circulating antigen test was confirmed to be a good marker of active Wuchereria bancrofti infection.

Og4C3 circulating filarial antigen was detected in the sera of 94.5% (259/274) of microfilaremic patients, 32% (239/751) of persons with presumption of filariasis, and 23% (11/48) of chronic filariasis patients. The antigen level was correlated with the microfilariae (Mf) density and patient age (P < .01). It remained stable in patients treated with microfilaricidal drugs. Og4C3 antigen, undetectable in Mf culture media, was demonstrated to be a rare somatic Mf antigen. It appears to be an excreted or secreted antigen from adult filaria. It could be used as a marker of infection and an indicator of adult worm burden.

In April and October in 1991-1993, 5 supervised single doses of ivermectin were given to inhabitants aged > or = 3 years in a Polynesian district: the first 3 treatments were with 100 micrograms/kg and the 2 latter with 400 micrograms/kg. At each treatment, about 97% of the eligible population (899) were treated and blood samples were collected just before treatment from 96% of the 613 inhabitants aged > or = 15 years. Following the 5 successive treatments, adverse reactions were observed in, respectively, 23.8, 13, 6.2, 13.6 and 7.9% of the microfilariae (mf) carriers, and in less than 1% of amicrofilaraemic subjects. Neither the frequency nor the intensity of adverse reactions was significantly different between single doses of 100 micrograms/kg and 400 micrograms/kg. Although the geometric mean microfilaraemia (GMM) was reduced, the mf carrier prevalence remained unchanged before and after 3 mass treatments with 100 micrograms/kg (21.4 and 20.7% respectively), and the mf recurrence rate 6 months after each dose of 100 micrograms/kg was roughly stable (respectively, 34.3%, 21.6% and 31.2% of the initial GMM). In contrast, after one dose round of 400 micrograms/kg, the mf carrier prevalence decreased significantly to 14.9% (P < 10(-6)), and the mf recurrence rate dropped to 9.9% (P < 10(-3)) of the initial GMM. These results confirm the safety and the effectiveness of 400 micrograms/kg of ivermectin for lymphatic filariasis control.

When multidrug therapy was implemented in Senegal, 406 multibacillary (MB) patients who had been treated for more than 10 years by dapsone alone, and who had become clinically inactive and skin-smear negative, were released from treatment. Of these 406 patients, 298 were given a supervised single dose of 1500 mg of rifampin. Subsequently, 302 of them (229 who had been given rifampin and 73 who had not) were followed up by means of annual clinical and bacteriological examinations. Of the former 229 followed up for a mean period of 4.9 years, 34 patients relapsed (22 males and 12 females), giving a crude relapse rate of 15% and an overall risk of relapse of 3.1 per 100 patient-years. Of the latter 73 followed up for a mean period of 2.4 years, 5 relapsed (4 males and 1 female), giving a crude relapse rate of 6.8% and an overall risk of relapse of 2.9 per 100 patient-years. Such results, which are in agreement with those of a similar study conducted recently in Mali, indicate that the intake of a single dose of 1500 mg of rifampin by MB patients when they are released from long-course dapsone monotherapy does not result in a decrease of the relapse rate. Therefore, MB patients who have been treated with dapsone alone, even for long periods, should be put under multidrug therapy prior to their release from control.

T cell proliferation and interferon-gamma (IFN-gamma) production of peripheral blood mononuclear cells (PBMC) from 20 household contacts were tested against the 18- and 65-kD heat shock proteins from Mycobacterium leprae (ML18 and ML65 respectively) and antigen 85 from Myco. bovis bacille Calmette-Guérin (BCG) (Ag 85) during a 12-months follow-up study. Among the eight contacts that became positive, eight showed positive reactivity against Ag 85, 5/8 against ML65 and 4/8 against ML18 at the end of the study. Of the 16 contacts who were lepromin-positive either at first or second testing, all responded to Ag 85, 11 to ML 65, but only eight reacted to ML18 antigen. Contacts who were lepromin-positive at first testing developed responses to ML18 only at second testing. In contrast, among the four contacts that remained lepromin-negative during the follow up, three proliferated to Ag 85 either at first or second testing, but only one produced IFN-gamma against Ag 85 at the end of the study. These results demonstrated that T cell reactivity and particularly IFN-gamma secretion against Ag 85, but not against ML18 and ML65, might be a predominant mechanism in the early stages of acquired protective immunity against Myco. leprae.

The effects of ivermectin, diethylcarbamazine (DEC), and the combination of both drugs on levels of microfilaremia (mf) were studied in 30 male Polynesian Wuchereria bancrofti carriers. Microfilarial densities were measured 30 min (H1/2), 1 hr (H1), and 2, 4, 8, 24, and 96 hr (H2, H4, H8, H24, and H96) after supervised single doses of ivermectin plus DEC (400 micrograms/kg plus 1 mg/kg, respectively, 400 micrograms/kg plus 3 mg/kg, respectively, and 400 micrograms/kg plus 6 mg/kg, respectively), DEC (6 mg/kg) alone, and ivermectin (400 micrograms/kg and 100 micrograms/kg, respectively) alone given to six groups of five patients each. The results showed that 1) DEC alone or combined with ivermectin induced a rapid clearance of mf after drug intake; at H1/2, the number of circulating microfilariae was reduced to 16%, 8%, 28%, and 31%, respectively, of pretreatment values in the groups receiving ivermectin plus DEC (400 micrograms/kg plus 1 mg/kg, 400 micrograms/kg plus 3 mg/kg, and 400 micrograms/kg plus 6 mg/kg) and DEC (6 mg/kg) alone; 2) ivermectin alone induced a rapid increase of mf densities during the first 2 hr, followed by a sharp decrease from H4 to H96; and 3) between H8 and H96, mf clearance was almost complete with the combination of ivermectin and DEC. A comparison among groups did not show any synergistic interaction between ivermectin and DEC on the clearance of microfilaria, with the effect of each drug being additive to each another.

Between 1988 and 1992, 21 biopsies for pathological examination were taken from 20 Senegalese leprosy patients suffering from chronic plantar ulcers (CPU) suspected of malignant transformation. The diagnosis of squamous cell carcinoma was effectively made in 13 cases and that of pseudoepitheliomatous hyperplasia in the remaining 8 cases. The mean period of time between the onset of CPU and that of malignant transformation was 10 years (range: 1 to 15 years); the mean annual frequency of the malignant transformation was 2 per 1,000 CPU. In countries where pathological examination is not available, below knee amputation could be considered whenever main clinical signs of malignant transformation are present. In countries where pathological examination is available, the therapeutic decision may differ according to the diagnosis: below knee amputation supplemented with block dissection of inguinal lymph nodes whenever possible in cases of carcinoma; below knee amputation depending on the function status of the foot and on the volume of tumor in case of pseudo-epitheliomatous hyperplasia.

Forty-three Wuchereria bancrofti carriers were given 4 successive semi-annual single doses of ivermectin 100 micrograms/kg (IVER 100). The geometric mean microfilaremia (mf) recurrence percentages, compared to the pre-initial treatment mf level, were 35%, 21%, 17% and 17% at 6, 12, 18 and 24 months respectively. However, the recurrence of mf 6 months after the fourth treatment remained high in 15 individuals, considered as 'bad responders'. At month 24, the subjects were randomly allocated into 2 groups: the first group was treated with a fifth dose of IVER 100 and the second with a first, single dose of 400 micrograms/kg of ivermectin (IVER 400). At month 30, the mf recurrence percentage was significantly higher in patients treated with IVER 100 than in those receiving IVER 400 (61% vs. 8%, P < 0.05). In the IVER 100 group, 6 of the 8 'bad responders' remained 'bad responders', whereas only 2 of 7 did so in the IVER 400 group. Only 3 additional patients in the IVER 100 group became consistently amicrofilaraemic, whereas 9 did so in the IVER 400 group. Two 'good responders' in the IVER 100 group became 'bad responders'. A single dose of 400 micrograms/kg of ivermectin has been demonstrated to be efficient for the treatment of carriers refractory to repeated doses of 100 micrograms/kg and to result in better long-term mf suppression. These results suggest a possible effect of 400 micrograms/kg of ivermectin on macrofilaria.

A randomized investigator-blinded trial of oral ivermectin 100 micrograms/kg single dose vs. benzyl benzoate 10% application in the treatment of scabies, was conducted in 1992 in French Polynesia. In total, 44 patients aged 5-56 years were included in the study: 23 in the group ivermectin (IVER) and 21 in the group benzyl benzoate (BB). At day 30 after treatment, the cumulative recovery rates were 70% (16/23) in the group IVER, and 48% (10/21) in the group BB, 95% confidence intervals 51-87% and 29-70% respectively. The rates of recovery were greater in the group IVER at day 7, 14 and 30, but the difference was not statistically significant. Our results show that oral ivermectin is a valuable alternative to benzyl benzoate local treatment.

In April 1992, a safety trial was performed with a single dose of ivermectin 400 micrograms.kg-1 (IVER 400). In 37 bancroftian filariasis carriers, 6 and 12 months after IVER 400 treatment, the microfilaremia recurrences were 3.2% and 13.5%, respectively. As compared to results from other studies with diethylcarbamazine and IVER at different dosages and periodicities, the dosage of IVER 400 seems the most effective; but a yearly intake might not be sufficient.

In 1983, a cohort study to follow up the family contacts of leprosy cases was implemented in French Polynesia to assess the usefulness and applicability of phenolic glycolipid-I (PGL-I) serology in a leprosy control program. A total of 1201 contacts (666 females, 535 males) have been included in the study. The IgM anti-PGL-I seroprevalence determined on the initial sera was 17%. It was significantly higher among females than males (20% vs 15%, p = 0.02). From 1983 to 1992, 4 out of 204 (2%) anti-PGL-I seropositive contacts developed the disease (1 indeterminate, 1 BT, 1 BL, 1 LL) compared with 10 out of 997 (1%) seronegative contacts (4 indeterminate, 3 BT, 1 BB, 2 TT). Of these 10 patients, only 3 (2 indeterminate, 1 BT) converted to seropositivity when leprosy was diagnosed. The risk of developing leprosy was not significantly higher among seropositive than among seronegative groups (2% vs 1%, p = 0.2). A PGL-I circulating antigen test performed on 216 selected sera at entry into the trial showed a higher antigen prevalence when the antibody level was higher. PGL-I antigen was detectable in 5 of 12 patients tested prior to diagnosis (1 LL, 1 BL, 3 indeterminate). The median time to externalize the disease was not significantly different among antibody-positive and -negative contacts (17 vs 25 months, p = 0.3). The relative risk of developing leprosy for contact individuals was 30.8 times that of noncontacts, and 15% of the total new cases detected between 1983 and 1992 emerged from the study population.(ABSTRACT TRUNCATED AT 250 WORDS)

Forty-six Polynesian carriers of Wuchereria bancrofti were treated with 3 successive single doses of ivermectin, 100 micrograms/kg, given every 6 months. Immediate microfilaricidal activity of ivermectin was excellent in all carriers, since residual mean microfilaraemia levels, 2 d after each of the 3 treatments, were less than 1% of pretreatment levels. Before initial treatment, geometric mean microfilaraemia was 500 microfilaria (mf)/ml for the whole group (range 21-6398 mf/ml); 6 months after each successive treatment it was 197, 108 and 87 mg/ml, respectively, 39.4, 21.6 and 17.4% of the pre-initial treatment level. By considering the mean percentage recurrent level at 6 months after the 3rd treatment (36.8%) as a threshold, it was possible to classify the carriers into 2 groups: 17 in whom the percentage recurrent level was > 36.8% and who were considered as 'fast repopulating' individuals, and the remaining 29 who were considered as 'slow repopulating' individuals. In the latter group, 6 months after each of the 3 treatments, the recurrent microfilaremia levels were 22.7%, 8.0% and 4.9% of the pre-initial treatment level, respectively, while they were 95.1%, > 100% and > 100% in the former. The constant recurrence of mf suggests that ivermectin, at a dosage of 100 micrograms/kg, had no effect on adult worms in 'fast repopulating' individuals, whereas the progressive lessening in recurrence of mf suggests some activity (sterilizing or killing) of ivermectin on W. bancrofti macrofilariae in 'slow repopulating' individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

In 1992, a study on microfilaremia periodicity was carried out on 12 Wuchereria bancrofti carriers in the Marquesas islands. Blood samples were collected simultaneously every 4 hours during a 48 hour period by finger-prick and venipuncture for determination of microfilaremia by both blood film and membrane filtration technique methods, and for determination of antigenemia. The membrane filtration results showed no significant nycthemeral variations between the microfilaria densities at hours 16:00, 20:00, 24:00, 04:00, 08:00 and 12:00. Conversely, the blood film method showed a significant difference between the microfilaria densities: the microfilaremia was higher during the day (12:00-20:00 hours) than during the night (24:00-08:00 hours). As for antigenemia, using Og 4 C3 monoclonal antibody, there was no significant fluctuation during 48 hours. These results confirm that W. bancrofti var. pacifica is subperiodic and diurnal in French Polynesia. In particular, they substantiate the validity of examining venous blood by the membrane filtration technique as the judgment criterion of choice in therapeutic trials and of examining capillary blood during peak hours by the blood film method for evaluating the endemic level in a population.

From 1902 onward, notification and follow up of leprosy patients has been systematic in French Polynesia. Since 1960, a tuberculosis control program and a register has also been implemented. From 1902 to 1959, 673 cases of leprosy were detected [346 multibacillary (MB), 138 paucibacillary (PB), and 179 unclassified due to the loss of medical files by the time of classification which was done during the 1980s]. Of these 673 cases, 89 (13.2%) died from tuberculosis, giving a mean annual death rate of tuberculosis in leprosy patients of 232 per 100,000. Mortality from tuberculosis in leprosy patients detected between 1901 and 1930 was 20.7%, and decreased to 8.04% in patients detected from 1931 to 1959. In total, it was estimated that 26.4% of the leprosy cases had developed tuberculosis. From 1960 to 1991, 350 new cases of leprosy were detected (141 MB, 209 PB). Of them, 12 (3.4%) developed tuberculosis (7 before detection of leprosy, 5 after detection of leprosy). The dramatic decrease of the proportion of leprosy patients who developed tuberculosis between the periods 1902-1959 (26.4%) and 1960-1991 (3.4%) might be related to the important decline of the tuberculosis situation since 1960. From 1902 to 1959, mortality from tuberculosis occurred significantly more frequently in MB patients (13%) than in PB patients [4%, relative risk (RR) = 3.21, p = 0.003]. From 1960 to 1991, the incidence of tuberculosis seemed more frequent in MB patients (RR = 2.96, p = 0.07) whatever the sequence of detection of the two diseases. Our study suggests that lepromatous patients could share factors of susceptibility to mycobacterial diseases with patients developing tuberculosis.

A supervised safety trial of the treatment with a combination of ivermectin 400 micrograms.kg-1 (IVER 400) plus increasing doses of diethylcarbamazine (DEC), given simultaneously in single dose, was performed on five groups of Polynesian Wuchereria bancrofti carriers, 49 males aged 25 to 73 years, in whom microfilaremia ranged from 1 to 6,137 mf/ml. The trial was hospital-based, open, dose-escalating (1 group per week). Safety of an unchanging dose of IVER 400 and ascending doses of DEC were studied in the 5 following groups: group 1- IVER 400 plus DEC 1 mg.kg-1, 12 patients; group 2- IVER 400 plus DEC 3 mg.kg-1, 17 patients; group 3- IVER 400 plus DEC 6 mg.kg-1, 10 patients. Two control groups were included in the study, group 4- DEC 6 mg.kg-1 alone, 5 patients; group 5-: IVER 400 alone, 5 patients. Carriers were examined and questioned regarding their experience of adverse reactions, which were graded 0 to 3 according to severity, at 6, 12 and 24 hours and at 4 days after treatment. Biological examination was performed 4 days before and 4 days after treatment and included determination of microfilaremia, complete blood count, liver function tests and assessment of creatinine and urea levels. Adverse reactions were observed in 51% of 49 carriers (15 of grade 1, 8 of grade 2, 2 of grade 3). None was considered serious and they all disappeared in 2 days. The main symptoms were fever > or = 37.5 degrees C, myalgia, arthralgia, headache, asthenia, anorexia, vertigo and chills. Adverse reactions of patients were not significantly different between the five groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Different population groups of French Polynesia, Cook Islands and Fiji were screened for Human T-Lymphotropic Virus type I (HTLV-I) antibodies. Among 1487 individuals sampled in French Polynesia, twelve were considered Western Blot (WB) indeterminate and one was considered WB-positive for HTLV-I infection. This positive subject originated from France and was a blood donor. Out of 196 Polynesians of the Cook Islands, one was WB-indeterminate. Among populations sampled in Fiji, one of 222 Melanesians was found WB-indeterminate and one of 211 Indians was WB-indeterminate.

IgG antibodies against antigens 85A and 85B from Mycobacterium bovis BCG, IgM antibodies against phenolic glycolipid-I (PGL-I) and circulating PGL-I antigen were measured in the serum of 11 patients with lepromatous leprosy receiving multidrug therapy (MDT). Before treatment, 6 patients were reactive to antigen 85A, 10 patients to antigen 85B, and 11 patients to PGL-I; circulating PGL-I was detected in the sera of all of them. After 2 years of MDT PGL-I antigen could no longer be detected in all of the patients, except for two who were not compliant with treatment. IgG antibodies directed against the 85A and 85B antigens and IgM antibodies against the PGL-I antigen also decreased significantly during treatment but more slowly. The determination of circulating PGL-I antigen remains the most appropriate tool for monitoring lepromatous leprosy under MDT.

Two groups of Polynesian Wuchereria bancrofti carriers, 17 females aged 21 to 84 years and 20 males aged 26 to 57 years, in whom microfilaraemia ranged from 1 to 10,121 mf/ml and from 1 to 6,484 mf/ml, respectively, were given a supervised singledose treatment with 400 mcg/kg of ivermectin. Carriers were examined and questioned regarding their experience of adverse reactions, which were graded 0 to 3 according to severity, at 6, 12 and 24 hours and at 4 days after treatment. Biological examinations which included determination of microfilaraemia, complete blood count, liver function tests and assessment of creatinine and urea levels were performed at 4 days before and 4 days after treatment. Adverse reactions were observed in 65% of female and in 70% of male carriers; they were of grade > or = 2 in 35% of carriers in both groups. None as considered serious; they all disappeared in 24-48 hours. The main symptoms were headache, fever > or = 37.5 degrees C and myalgia in females. One male vomited 3 hours after treatment; as a result the drug was not ingested and no decrease of microfilaraemia was noted. Twelve days afterwards, he was given a second 400 mcg/kg dose, he experienced again a grade 1 reaction and his microfilaraemia fell to zero. The 37 carriers in the present study were matched with 37 other Polynesian carriers treated with a 100 mcg/kg single dose of ivermectin in previous trials for pretreatment mf density and sex: no significant difference could be found in adverse reactions between the 2 treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The analysis of computerized data (OMSLEP system) on patients from French Polynesia followed since 1940 has shown a decrease in the mean annual detection rates for leprosy, all forms combined, from 24.73 per 100,000 inhabitants in 1946 to 8.1 per 100,000 in 1987 (y = -0.49 x + 45.83; p < 0.05). In fact, the decrease was significant (y = -1.18 x + 83.54; p < 0.05) during the first half of the study period (1946-66), but not during the second half (1967-87). Similarly, a significant decrease in all of the specific mean annual detection rates (according to the form of leprosy and to the sex and age of patients), in the proportion of multibacillary patients among the total of newly detected cases, and in the proportion of all patients with disabilities at the onset of leprosy was observed only during the first half of the study period (1946-66). Nevertheless, when comparing age-specific cumulative detection rates, calculated by 10-year age groups over the period 1946-66, to those of the period 1967-87, an ageing of the leprosy population was noted. Finally, the decrease of mean annual detection rates was greater in the smaller populations of remote islands than in the population of Tahiti, the main island, where 70% of the total population were living during the study period. This decline was shown to correspond to an effective improvement of the leprosy situation which could be attributed, among other factors (such as economic development and systematic BCG vaccination), to the implementation of a control programme for leprosy in 1950. The introduction in 1982 of multidrug therapy for all patients suffering active leprosy has raised the hope of a subsequent decline of leprosy in French Polynesia in the near future.

In January-February 1988, a program of chemoprophylaxis for leprosy, using a single 25 mg/kg dose of rifampin, was conducted among 2786 (98.7%) inhabitants of the Southern Marquesas and 3144 South Marquesan "emigrants" and their families. Among the treated population, during the 4 years which followed the implementation of the program, two leprosy patients were detected, one of whom can be considered as a failure of chemoprophylaxis because she was not known by the leprosy control unit. During the same period (1988-1991), a decrease in detection rates for leprosy in the entire French Polynesian population has been observed, an event which makes the interpretation of these findings very difficult. Nevertheless, according to presently available data, the effectiveness of chemoprophylaxis with a single dose of 25 mg/kg rifampin is estimated to be about 40% to 50%. When considering not only the results of the present study but also the financial and logistic constraints raised by such a program, one is led to the conclusion that chemoprophylaxis, even with a single dose of rifampin, is not likely to become an effective component of leprosy control programs.

The evaluation of microfilaremia (mf) was performed in 96% of the population aged 15 years or more in a village of Moorea, one of the Society Islands in French Polynesia. Finger-prick and venous blood samples were collected simultaneously from 782 individuals in order to compare the results obtained by the standard blood film method and the membrane filtration technique. Of the 782 blood-sampled inhabitants 69 (8.8%) were found mf positive. 39 (5%) were mf positive by both methods and 30 were mf positive by the membrane filtration technique only. In these latter 30 carriers the geometric mean mf count was 19.7 mf/ml, significantly lower than that of 651.1 mf/ml in the 39 carriers positive by both techniques. Using the membrane filtration technique, the mf carrier prevalence rate increased from 1.9% in the youngest age group (15-19 years) to 16.9% in the oldest (< or = 60 years) while using the blood film method, it increased from 1.3% to 12.7%. Roughly, when using the membrane filtration technique, the mf carrier prevalence rate was 1.77 higher than that found using the blood film method, considering either the whole population or successive age-groups. Moreover, when using the blood film method in the 40 years and more age group, the mf carrier prevalence rate was 10%, a proportion similar to the 8.8% prevalence rate determined by the membrane filtration technique in the whole population. Further studies are planned to assess whether the last finding may be confirmed in other Polynesian populations.(ABSTRACT TRUNCATED AT 250 WORDS)

In April 1991 supervised mass prophylaxis of lymphatic filariasis with a single dose of ivermectin, 100 micrograms/kg, was carried out in a Polynesian village with a high infection rate of Wuchereria bancrofti in humans and active transmission by the vector mosquito, Aedes polynesiensis. Of 876 inhabitants aged 3 years or more (pregnant women excluded), 864 (98.6%) were treated. Simultaneously, venous blood samples were collected from 577 (97.5%) of the 595 inhabitants aged 15 years or more, of whom 122 (21.4%) were found to be microfilaria (mf) carriers (86 males and 36 females). The geometric mean microfilariae (GMM) count was 358.7 mf/ml for the whole group, 387 mf/ml for males (range 1-8160 mf/ml) and 280 mf/ml for females (range 1-7769 mf/ml). Following treatment, 33 (3.8%) of the 864 persons treated experienced some adverse reactions (21 with grade 1 and 12 with grade 2). Of the 33 with reactions, 29 were among the 122 (23.8%) mf carriers and 4 among the 831 (0.5%) non-microfilaraemic persons. Six months later, 123 (21.1%) of 584 inhabitants sampled were microfilaraemic: the GMM count for the whole group was 106 mf/ml (1-8177), with 29 mf/ml (1-3740) in 35 female and 177 mf/ml (1-8177) in 88 male carriers. Of these 123, 15 (whose GMM count was 4.5 mf/ml; range 1-204) were amicrofilaraemic 6 months before, and 19 had a microfilaraemia level higher than that 6 months earlier, before treatment. 117 of the 122 carriers identified in April were resampled: comparison of their GMM counts before and 6 months after mass treatment indicated that treatment with a single dose of 100 micrograms/kg ivermectin resulted in a reduction of microfilaraemia by 69%.