Small-scale field evaluation of the efficacy and residual effect of Fludora® Fusion (mixture of clothianidin and deltamethrin) against susceptible and resistant Anopheles gambiae populations from Benin, West Africa.

BACKGROUND: In recognition of the threat of insecticide resistance in vectors of malaria, the WHO Global Malaria Programme recommends the development of an appropriate and comprehensive response to insecticide resistance. In principle, good resistance management practice requires the application of multiple insecticides of different modes of action, for example, in rotations and mixtures. Insecticides recommended by the World Health Organization for indoor residual spraying and long-lasting insecticide nets are limited. It is, therefore, judicious to prevent the rapid spread of insecticide resistance by evaluating new insecticides formulations with different modes of action and long residual effect. METHODS: Fludora® Fusion, a new neonicotinoid IRS formulation (a mixture of 500 g/kg clothianidin and 62.5 g/kg deltamethrin applied 200 mg ai/sqm + 25 mg ai/sqm, respectively) was tested. Small scale field evaluation of this product was conducted in the district of Dangbo in Benin, to compare its efficacy and residual effect on cement and mud walls against those of clothianidin 200 mg ai/sqm (WG 70) alone, and of deltamethrin 25 mg ai/sqm (WG 250) alone. WHO wall cone bioassays were conducted monthly with laboratory susceptible Anopheles "Kisumu" and wild Anopheles gambiae sensu stricto (s.s.) population from Dangbo. The induced mortality by each treatment per wall substrate for 24 h, 48 h, and 72 h post exposure were recorded every month and analysed. RESULTS: Fludora® Fusion and clothianidin WG 70 showed mortality rates over 80% WHO bio-efficacy threshold on cement walls either with susceptible or resistant An. gambiae s.s. over a period of 10 and 9 months, respectively. Treatment with Fludora® Fusion and clothianidin WG 70 on the mud walls showed residual effect for 6 months and 5 months respectively against both susceptible and resistant mosquitoes. During the whole evaluation period, deltamethrin WG 250 showed mortality rates below 80% against resistant Anopheles population. Furthermore, the knock down rates observed with the Fludora® Fusion combination were significantly higher (p < 5%) than those induced by Clothiandin WG 70. CONCLUSION: Both the Fludora® Fusion combination and clothianidin alone showed very good and lasting efficacy for IRS against resistant Anopheles with some residual benefit provided by the combination. The residual efficacy of the Fludora® Fusion combination evaluated at 10 months shows this product is a good candidate for IRS interventions.

[Distribution of Mycobacterium ulcerans (Buruli ulcer) in the district of Lalo in Benin]. / Distribution de l'infection a Mycobacterium ulcerans (Ulcere de Buruli dans la commune de Lalo au Benin.

This study aimed to determine the distribution of Buruli ulcer (BU) in Lalo, one of the endemic districts of the Couffo department in Bénin. A total of 752 BU patients were detected in this district with 160 active and 592 inactive cases. The overall prevalence of BU in this district is 86.6 per 10,000 inhabitants, varying from 0 to 249/10,000 between sub-districts. At village level the prevalence varies between 0 and 561 cases per 10,000 inhabitants. Our findings confirm the large variation of distribution of the disease at the village level in endemic area. Children under 15 years are frequently affected. We also found a significant association between age and location of Buruli lesions. Further epidemiological and environmental studies are needed to identify the reasons for the extraordinary variation in BU distribution between villages from the same sub-district, and to confirm if it is associated with temporal variations.

Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity.

During the 5-year period, 1997-2001, 1700 patients with a clinical diagnosis of Mycobacterium ulcerans disease [Buruli ulcer (BU)] were treated at the Centre Sanitaire et Nutritionnel Gbemoten, Zagnanado, Benin. The patients lived in the four regions of southern Benin: Atlantique, Mono, Oueme and Zou, with the largest number coming from the Zou Region where the centre is located. The median age of BU patients was 15 years (q1=7, q3=30). Lower limbs are involved 3.2 times more frequently than upper limbs in older patients and younger patients have the highest prevalence of multiple lesions. The latter are frequently associated with bone lesions. Specific detection rates for age and gender showed a distribution with maximum peaks in the 10-14 years group and among adults between 75 and 79 years. Over 59 years, males are more at risk of developing M. ulcerans disease than females. Children under 15 years represent the largest part of the BU disease burden and of the general population. The highest detection rates (per 100,000 population) were in the 75-79-year-old patients. The most likely explanation of this was reactivation of disease from a latent infection of M. ulcerans. Educational programmes should target especially these two groups of population at risk.

Mycobacterium bovis BCG vaccination as prophylaxis against Mycobacterium ulcerans osteomyelitis in Buruli ulcer disease.

Mycobacterium ulcerans disease, or Buruli ulcer (BU), causes significant morbidity in West Africa. Clinically, the disease presents in the skin as either nonulcerative or ulcerative forms and often invades bones either subjacent to the skin lesion (contiguous osteomyelitis) or remote from the skin lesion (metastatic osteomyelitis). Osteomyelitis represents a severe form of the disease that often requires numerous surgical interventions, even amputations. Surgery is accepted as the present definitive treatment for BU. In the absence of an effective drug treatment, the need for the development of preventive and control strategies becomes paramount. No specific vaccine, however, is presently available for BU. Of 372 consecutive patients in Benin presenting with BU (confirmed by microbiological and histopathological analyses) whose Mycobacterium bovis BCG scar statuses were known, 196 children (<15 years old) and 108 adults had neonatal BCG vaccination scars. Of 196 children with BCG scars, 17 (8.7%) had osteomyelitis, while 7 of 28 children without BCG scars (25.0%) had osteomyelitis. Of 108 adults with BCG scars, 17 (15.7%) had osteomyelitis, while 14 of 40 adults without BCG scars (35.0%) had osteomyelitis. Our results show that effective BCG vaccination at birth provides significant protection against the development of M. ulcerans osteomyelitis in children and adults. Therefore, health authorities should give attention to the enhancement of neonatal BCG vaccination coverage in all countries of Africa where BU is endemic. Protection against severe forms of BU and childhood tuberculosis would likewise be improved by this intervention.

Prophylactic effect of mycobacterium bovis BCG vaccination against osteomyelitis in children with Mycobacterium ulcerans disease (Buruli Ulcer).

Mycobacterium ulcerans disease, or Buruli ulcer (BU), causes significant morbidity in West Africa. In 233 consecutive, laboratory-confirmed samples from BU patients in Benin whose Mycobacterium bovis BCG scar status was known, 130 children (<15 years old) and 75 adults had a neonatal BCG vaccination scar. Of 130 children with BCG scars, 10 (7.7%) had osteomyelitis, while 3 of 9 children without BCG scars (33.3%) had osteomyelitis. Our observations support the conclusion that having a BCG vaccination scar provides significant protection against M. ulcerans osteomyelitis in children with BU disease.

Direct detection and identification of Mycobacterium ulcerans in clinical specimens by PCR and oligonucleotide-specific capture plate hybridization.

We compared various diagnostic tests for their abilities to detect Mycobacterium ulcerans infection in specimens from patients with clinically active disease. Specimens from 10 patients from the area of Zangnanado (Department of Zou, Benin) with advanced, ulcerated active M. ulcerans infections were studied by direct smear, histopathology, culture, PCR, and oligonucleotide-specific capture plate hybridization (OSCPH). A total of 27 specimens, including 12 swabs of exudate collected before debridement and 15 fragments of tissue obtained during debridement, were submitted to bacteriologic and histopathologic analysis. The histopathologic evaluation of tissues from all six patients so tested revealed changes typical of those caused by M. ulcerans infection. Five specimens were contaminated, and M. ulcerans was cultivated on Löwenstein-Jensen medium from 12 of the remaining 22 (54.5%) specimens. Detection of mycobacteria was performed by PCR, and M. ulcerans was detected by OSCPH with a new probe (5'-CACGGGATTCATGTCCTGT-3') reacting with M. ulcerans and Mycobacterium marinum. In 10 of 22 (45.5%) specimens, M. ulcerans was identified by PCR-OSCPH. There was no statistically significant difference between the detection of M. ulcerans by culture and by PCR-OSCPH (P > 0.05). This is the first demonstration of an amplification system (PCR-OSCPH) with a sensitivity similar to that of culture for the direct and rapid recognition of M. ulcerans in clinical specimens. This system is capable of identifying M. ulcerans, even in paucibacillary lesions. Our findings suggest that PCR-OSCPH should be used in the quest for the elusive environmental reservoir(s) of M. ulcerans.

[Buruli's ulcer, a pathology little known in Benin. Apropos of 227 cases]. / L'ulcère de Buruli, une pathologie peu connue au Bénin. A propos de 227 cas.

Cutaneous Mycobacterium infection is an endemic disease in Mono, Ouémé and Zou districts in the south of Benin, where it seems rarely known. The authors are reporting the results of a clinical, bacteriological, epidemiological and therapeutical study about 227 patients. Children are the principal targets of this disease. Ulceration are often seen in a critical step (3 or 4) and acid-fast bacilli have been found from 189 of 227 patients tested by bacilloscopy (smear microscopy). Medical treatments (antituberculosis and antileprosis drugs) are still disappointing. Also when necessary, surgery is done (broad excision, skin transplant afterwards) with promising results. However, complications like deformities and flexion contractors can persist after surgical treatment. In the south Benin, Buruli's ulcers are one of the major public health problems.