[Outbreak of meningitis in the province of Logone occidental (Chad): descriptive study using health ministry data from 1998 to 2001]. / Poussées epidémiques de méningites dans le département du Logone occidental (Tchad): etude descriptive a partir des données du ministère de la santé de 1998 a 2001.

UNLABELLED: Outbreaks of meningitis are a public health problem in sub-Saharan Africa where more than thousand cases are declared every year In Chad, the last outbreak happened between 1998 and 2001. The objective of this study is to describe epidemiologic profile of meningitis in the province of Logone Occidental from 1998 to 2001. METHODS: Study used epidemiologic data of surveillance's tools from years 1998 to 2001 in Chad. RESULTS: Data of the study indicated a two-yearly cycle with outbreaks in 1998 and 2000 occurring in endemic background during 1999 and 2001. The first cases began in January with an incidence rate close to 30 for 100.000/week. The epidemic peak occurred on the 11th week (1999-2001), on the 12th week (1998-2000) during dry season. Outbreak continued 9 weeks and stopped on the 16th week (April-May). The lethality average was 12% and reached 30% at the beginning of the outbreak. DISCUSSION: Despite vaccination campaigns during outbreaks, epidemiology did not change in Chad. Quality of epidemiological surveillance is not sufficient and political reaction is too slow. Moreover, human, material and financial deficiency add to these difficulties. Integrated vaccination against meningitis into the immunization preventive program was evocated but would not permit enough collective immunity. Biotope changes generated by human activity could contribute to perpetuating outbreaks. New outbreak of W135 meningitis in Burkina Faso (2002) may change the epidemiological profile of the meningitis in sub-Saharan Africa. CONCLUSION: Meningitis outbreaks control using vaccination after the first cases appears to be limited, however this strategy must be evaluated in Chad to know vaccination covering, target population and protection after vaccination.

Reduction of Wuchereria bancrofti adult worm circulating antigen after annual treatments of diethylcarbamazine combined with ivermectin in French Polynesia.

Circulating filarial antigen (CFA), determined with Og4C3 ELISA, is a marker of Wuchereria bancrofti adult worm infection. The reduction of CFA over 2 years was determined in 185 microfilaremic and 111 amicrofilaremic but CFA+ adults given an annual dose of either diethylcarbamazine (DEC) or ivermectin or the two combined. Reduction of CFA level was good with DEC but weak with ivermectin and followed the same pattern in amicrofilaremic and microfilaremic groups. Combinations and DEC alone had a similar impact on CFA level. CFA clearance was observed in amicrofilaremic but not in microfilaremic persons in all DEC-containing treatments. However, the highest clearance rate was observed in persons treated with DEC at 6 mg/kg combined with ivermectin. Continuous reduction of CFA level after repeated treatments shows that elimination of W. bancrofti infection, monitored by CFA clearance, might be achieved within a few years with annual treatments of DEC combined with ivermectin.

Control of bancroftian filariasis in an endemic area of Polynesia by ivermectin 400 micrograms/kg.

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.

A polymerase chain reaction assay for the detection of Wuchereria bancrofti in blood samples from French Polynesia.

A polymerase chain reaction (PCR) assay based on a highly repeated deoxyribonucleic acid (DNA) sequence found in Wuchereria bancrofti (the SspI repeat) has been developed to address the shortcomings of traditional diagnostic methods. In this field study in a W. bancrofti endemic region of French Polynesia, 373 human blood samples were collected and 100 microL of blood were screened by the SspI PCR assay and 1 microL by membrane filtration. The SspI PCR assay detected 99 of 113 blood samples in which microfilariae had been detected by filtration (sensitivity of 88%) with a specificity of 100%. All the samples missed by the SspI PCR assay had less than 8 microfilariae per mL of blood. To evaluate the efficacy of screening larger blood samples by PCR, both 100 microL and 500 microL samples from 50 patients with very low-level microfilaraemia were screened by the SspI PCR assay; the sensitivity increased from 60% to 84% when using the larger volume of blood. Finally, an enzyme-linked immunosorbent assay-based version of the SspI PCR assay was used to screen blood from 12 patients following treatment with diethylcarbamazine, ivermectin, or both. These results showed that the PCR assay closely paralleled the presence or absence of microfilariae in the blood and that no increase in the DNA level was seen immediately following drug treatment.

[Combinations of ivermectin and diethylcarbamazine for improved control of lymphatic filariasis]. / Associations de l'ivermectine et de la diéthylcarbamazine pour obtenir un meilleur contrôle de l'infection en filariose lymphatique.

Since 1993, a three arm double-blind controlled trial was implemented in French Polynesia to compare the efficacy of single doses of diethylcarbamazine (DEC) 6 mg/kg vs. ivermectin (IVR) 400 micrograms/kg vs. the combination IVR 400 + DEC 6 for treatment of Wuchereria bancrofti mf carriers. Of the 57 treated male patients, three groups of 19 were randomly selected and allocated to one of the three treatments. Twelve months after the first then the second treatment (M12 then M24) respectively, 3 (16%) then 10 (53%), 3 (16%) then 5 (26%), 7 (27%) then 10 (53%) of patients were mf negative in groups DEC 6, IVR 400 and IVR+DEC. Mf percent return was significantly lower in the group IVR+DEC (2% at M12 then M24) than for the groups DEC 6 (15% at M12 then 4% at M24) and IVR 400 (12% at M12 then 10% at M24). The combination IVR+DEC showed promising results for an annual strategy; to achieve the best results from a control program it is necessary to associate IVR+DEC.

[Control of hepatitis B in French Polynesia with a program of systematic vaccination of newborns with the Genhevac B vaccine]. / Lutte contre l'hépatite B en Polynésie française par un programme de vaccination systématique des nouveau-nés avec le vaccin Genhevac B.

In 1988, a 5-year vaccination program against hepatitis B was launched for all newborns in a pilot area, the Austral archipelago in French Polynesia. Genhevac B, a recombinant vaccine produced from mammalian cells was administered. Three different immunization schedules were used, none of them including additional specific immunoglobulin: i) four doses, one at each months (M) 0, 1, 2, and 12; ii) three doses one at each MO, M1 and M6; and iii) three doses one at each MO, M1 and M12. Each year during the 5 year period a serological survey was conducted. Of the 837 children who received at least one vaccine dose, 5 were HBsAg carriers. Seroprotection rates for anti-HBs and anti-PreS2 antibodies were 88% after one dose and 97% after two doses. After the third dose, seroprotection rates and geometric mean titers of anti-HBs antibodies were 95% and 217 mIU/ml for schedule (i) (three dose only); 92% and 389 mIU/ml for schedule (ii) and 93% and 344 mIU/ml for schedule (iii) respectively. After four doses (schedule i) the values were 100% and 1228 mIU/ml. Of the 18 newborns whose mothers were positive for both HBsAg and HBeAg, one was a HBsAg carrier. The estimated protective rate for prevention of perinatal transmission was 94%. This study suggests that in field conditions, systematic vaccination of newborns without using specific immunoglobulins can confer early protection. The schedule recommended for use in French Polynesia was three doses, at MO, M1 and M6-12 (between 6 and 12 months) with an additional booster dose at age 6 years, the last year of nursery school. Since April 1992, all children born in French Polynesia have been vaccinated according to this schedule. A catch-up program has been implemented for children aged 4 to 10 years old using a similar immunization schedule.

Advantages of an annual single dose of ivermectin 400 micrograms/kg plus diethylcarbamazine for community treatment of bancroftian filariasis.

In 1994 and 1995, 2 supervised single dose treatments for bancroftian filariasis were given to all inhabitants ( > 3500) aged > or = 3 years on a Polynesian island. This island is divided into 4 political zones. Each zone was treated with a different dosage of the combination ivermectin (IVR) and diethylcarbamazine (DEC) as follows: (1) IVR 400 micrograms/kg plus DEC 6mg/kg, (2) IVR 400 micrograms/kg alone, (3) DEC 6 mg/kg alone (4) IVR 400 micrograms/kg plus DEC 3 mg/kg. 1717 inhabitants (aged > or = 20 years) had venous blood sampled when treated. The reductions in microfilaraemia prevalence rates one year after treatment were, respectively, 32%, 11%, 14% and 32%. The reductions in microfilaraemia levels one year after treatment were, respectively, 96%, 80%, 82% and 95%. Stool specimens from 82 children aged 6 years were examined for intestinal nematodes just before and just after treatment. IVR 400 micrograms/kg significantly reduced the prevalence and intensity of trichiuriasis. The combination IVR + DEC is a powerful tool for the control of lymphatic filariasis. Further studies are required to determine the appropriate presentation of DEC (salt and/or tablets), the frequency of treatment, and the duration of the control programme necessary to eradicate this disease.

Alpha-thalassaemia and globin gene rearrangements in French Polynesia.

The prevalence of alpha-thalassaemia and various globin gene rearrangements was determined in 1992 individuals living on 11 islands in French Polynesia. The gene frequencies for alpha(+)-thalassaemia (almost exclusively the -alpha 3.7III deletion form) range from 5.3% to 19.2%. Haematological indices on 177 heterozygotes and 27 homozygotes for the -alpha 3.7III variant showed considerable overlap with indices of normal individuals; although there was a broad correlation of average indices with alpha-globin genotype, individual values were a poor indication of genotype. A non-deletion form of alpha(+)-thalassaemia (alpha alpha Th), triplicated alpha genes (alpha alpha alpha) and single zeta gene (-zeta) chromosomes were present at low frequencies (< 1%), whereas triplicated gamma gene (gamma gamma gamma) and triplicated zeta (zeta zeta zeta) arrangements were more common (1.1-16.3%). alpha 0-thalassaemia, probably introduced from Southeast Asia in the early part of this century, was observed in a number of individuals of Chinese and Chinese/Polynesian ancestry. Because of the high frequency of alpha(+)-Thalassaemia on some islands, it therefore seems likely that haemoglobin H disease (resulting from the interaction between alpha 0 and alpha(+)-thalassaemia) must occur in parts of French Polynesia.

Single doses of ivermectin 400 micrograms/kg-1: the most effective dosage in bancroftian filariasis.

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.

Combination ivermectin plus diethylcarbamazine, a new effective tool for control of lymphatic filariasis.

In 1993, a three arm double-blind controlled trial was implemented in French Polynesia, to compare the tolerance and efficacy of single doses of the combination ivermectin (IVR) 400 micrograms.kg-1 plus diethylcarbamazine (DEC) 6mg.kg-1 vs IVR 400 micrograms.kg-1 or DEC 6 mg.kg-1 alone, for treatment of Wuchereria bancrofti carriers. Of the 57 treated male patients in whom microfilaremia (mf) densities ranged from 22 to 4,709 mf/ml, three groups of 19 were randomly selected, and allocated to one of the three treatments. Twelve months after treatment 37%, 16% and 16% of patients were mf negative in groups DEC, IVR and IVR plus DEC respectively. Mf percent return to pretreatment level was significantly lower in the group IVR + DEC (1.9%) than for DEC 6 (14.7%) or IVR 400 (11.6%). Antigenemia percent return to pretreatment level was lower in the groups IVR + DEC or DEC 6 than for IVR 400. The combination IVR + DEC proved to be the most effective on macrofilariae and microfilariae (antigenemia and mf negative patients). The combination will be a very powerful tool for control of lymphatic filariasis. An annual filariasis day could be the most cost-effective strategy for administration of the drugs.

Wuchereria bancrofti filariasis in French Polynesia: age-specific patterns of microfilaremia, circulating antigen, and specific IgG and IgG4 responses according to transmission level.

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.

Low positive predictive value of anti-Brugia malayi IgG and IgG4 serology for the diagnosis of Wuchereria bancrofti.

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.

Double-blind controlled trial of a single dose of the combination ivermectin 400 micrograms/kg plus diethylcarbamazine 6 mg/kg for the treatment of bancroftian filariasis: results at six months.

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.

Efficacy of ivermectin for the treatment of head lice (Pediculosis capitis).

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.

Og4C3 circulating antigen, anti-Brugia malayi IgG and IgG4 titers in Wuchereria bancrofti infected patients, according to their parasitological status.

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 antigen: a marker of infection and adult worm burden in Wuchereria bancrofti filariasis.

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.

Advantages of ivermectin at a single dose of 400 micrograms/kg compared with 100 micrograms/kg for community treatment of lymphatic filariasis in Polynesia.

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.