Distribution of a Knockdown Resistance Mutation (L1014S) in Anopheles gambiae s.s. and Anopheles arabiensis in Western and Southern Kenya

In Kenya, insecticide-treated mosquito nets (ITNs) distributed to pregnant women and children under 5 years old through various programs have resulted in a significant reduction in malaria deaths. All of the World Health Organization-recommended insecticides for mosquito nets are pyrethroids, and vector mosquito resistance to these insecticides is one of the major obstacles to an effective malaria control program. Anopheles gambiae s.s. and Anopheles arabiensis are major malaria vectors that are widely distributed in Kenya. Two point mutations in the voltage-gated sodium channel (L1014F and L1014S) are associated with knockdown resistance (kdr) to DDT and pyrethroids in An. gambiae s.s. While the same point mutations have been reported to be rare in An. arabiensis, some evidence of metabolic resistance has been reported in this species. In order to determine the distribution of the point mutation L1014S in An. gambiae s.s. and An. arabiensis in southern and western Kenya, we collected larvae and screened for the mutation by DNA sequencing. We found high allelic and homozygous frequencies of the L1014S mutation in An. gambiae s.s. The L1014S mutation was also widely distributed in An. arabiensis, although the allelic frequency was lower than in An. gambiae s.s. The same intron sequence (length: 57 base) found in both species indicated that the mutation was introgressed by hybridization. The allelic frequency of L1014S was higher in both species in western regions, demonstrating the strong selection pressure imposed by long-lasting insecticide-treated nets (LLITN)/ITN on the An. gambiae s.s. and An. arabiensis populations in those areas. The present contribution of the L1014S mutation to pyrethroid resistance in An. arabiensis may be negligible. However, the homozygous frequency could increase with continuing selection pressure due to expanded LLITN coverage in the future

Multimodal pyrethroid resistance in malaria vectors, Anopheles gambiae s.s., Anopheles arabiensis, and Anopheles funestus s.s. in western Kenya.

Anopheles gambiae s.s., Anopheles arabiensis, and Anopheles funestus s.s. are the most important species for malaria transmission. Pyrethroid resistance of these vector mosquitoes is one of the main obstacles against effective vector control. The objective of the present study was to monitor the pyrethroid susceptibility in the 3 major malaria vectors in a highly malaria endemic area in western Kenya and to elucidate the mechanisms of pyrethroid resistance in these species. Gembe East and West, Mbita Division, and 4 main western islands in the Suba district of the Nyanza province in western Kenya were used as the study area. Larval and adult collection and bioassay were conducted, as well as the detection of point mutation in the voltage-gated sodium channel (1014L) by using direct DNA sequencing. A high level of pyrethroid resistance caused by the high frequency of point mutations (L1014S) was detected in An. gambiae s.s. In contrast, P450-related pyrethroid resistance seemed to be widespread in both An. arabiensis and An. funestus s.s. Not a single L1014S mutation was detected in these 2 species. A lack of cross-resistance between DDT and permethrin was also found in An. arabiensis and An. funestus s.s., while An. gambiae s.s. was resistant to both insecticides. It is noteworthy that the above species in the same area are found to be resistant to pyrethroids by their unique resistance mechanisms. Furthermore, it is interesting that 2 different resistance mechanisms have developed in the 2 sibling species in the same area individually. The cross resistance between permethrin and DDT in An. gambiae s.s. may be attributed to the high frequency of kdr mutation, which might be selected by the frequent exposure to ITNs. Similarly, the metabolic pyrethroid resistance in An. arabiensis and An. funestus s.s. is thought to develop without strong selection by DDT

Scoliosis and spine involvement in fibrous dysplasia of bone

Few studies focused on the prevalence of scoliosis and involvement of the spine in patients with fibrous dysplasia (FD) of bone. We examined for FD involvement of the spine and scoliosis in 56 patients affected by FD of bone. Fifty patients were part of a cohort reported in a multicentric study on FD promoted by European Pediatric Orthopedic Society (EPOS) in 1999, and six were new patients. There were 30 females and 26 males (mean age 12.5 years; range 1–42 years). Twenty-three had monostotic FD, 9 polyostotic FD, and 24 McCune-Albright Syndrome (MAS). Scoliosis was observed in 11 cases of polyostotic FD and MAS (33.3%). In seven of the patients with scoliosis (63.3%) spine was involved by FD lesional tissue. FD lesions involved the thoracic or lumbar spine in all patients but one, where cervical spine was also affected. A correlation between scoliosis and either spinal (p < 0.01) or pelvic lesions (p < 0.05) and pelvic obliquity (p < 0.01) was observed. Three of the 11 patients showed familiarity for scoliosis but in 2 of them spine was involved by FD. Scoliosis and spine involvement were never detected in monostotic FD. This study indicates that in FD patients with polyostotic disease (1) the prevalences of FD involvement of the spine and scoliosis are high enough to include spine in the clinico-radiographic survey of these patients, and (2) the involvement of the spine and pelvis by FD lesions and pelvic obliquity are important determinants in the occurrence of scoliosis