An estimated 13 million people in the Oriental Region have brugian filariasis. The filarial parasites that cause this disease exist in periodic and sub-periodic forms and are transmitted by four genera of mosquito: Anopheles, Mansonia and, less frequently, Coquillettidia and Ochlerotatus. In most endemic countries, control of the disease has been entirely based on chemotherapy, although house-spraying and use of insecticide-treated bednets can be quite effective against the vectors of nocturnally periodic Brugia malayi and B. timori. The vector-control methods that may be applied against the Mansonia mosquitoes that transmit the parasites causing sub-periodic brugian filariasis are reviewed here. Most of the conventional methods for controlling the immature, aquatic stages of mosquitoes have proved unsatisfactory against Mansonia. The reason is that, unlike the those of other genera, the larvae and pupae of Mansonia spp. are relatively immobile and obtain air not at the water surface but from the underwater roots, stems and leaves of floating plants to which the larvae and pupae attach. Removal of host plants can be very effective in reducing Mansonia productivity, whereas large-scale use of herbicides is restricted by the potential adverse effects on the ecosystem. Environmental management in water-development projects remains the best option.
A field trial of the use of expanded polystyrene beads (EPSB) to control the breeding of mosquito larvae in household septic tanks was conducted in Sarawak. One week after treatment, the breeding of Culex quinquefasciatus and Aedes albopictus was reduced by 100% and 68.7% respectively. For both species combined, a 57.25% reduction in the adult emergence rate was achieved. No adult was caught in the emergence trap one month after treatment. A reduction in mosquito biting rates was reported by 87.3% of respondents. All households regarded the EPSB treatment as effective. This study has reduced the relatively high infestation rate of A. albopictus in the septic tanks to 16-20%. The EPSB treatment is feasible and practical. Post-treatment assessment using adult emergence traps and the implications for the vector control programme of the local authority are discussed.
Studies on larval population densities and adult emergence rates of the Brugian filariasis vectors Mansonia bonneae Edwards and Ma. dives Schiner were conducted in freshwater swamp forest bordering the Sadong River, Serian District, Sarawak, East Malaysia, during 1984-85. Three species of aquatic host-plants in the Family Araceae were identified as supporting immature stages of the Ma. bonneae/dives complex. Proportions of positive plants were 4.7%, 6.5% and 3.4% with 6.4 +/- 2.6, 7.3 +/- 2.8 and 10.1 +/- 1.1 larvae per positive plant, respectively, for the plant species Homalomena cordata Schott, H. rostrata Griffiths and Hydrostemma motleyi (Hook. f.) Mabberley. These data indicate no significant preferences between the three types of host-plant. Detailed monitoring of the host-plant H. cordata revealed no significant monthly fluctuations in larval density per plant nor the proportion of positive plants. 11.6% of larvae were Ma. dives and 88.4% were Ma. bonneae. Mean daily yields of Ma. bonneae/dives adults per square metre of H. cordata vegetated water surface were 0.45 males plus 0.57 females during the wet season (December-February) compared with 0.2 males plus 0.31 females during the dry season (June-August). Thus output of adults per plant was approximately halved, and suitable breeding areas were further reduced, during the dry season. By extrapolation from these rates, a crude mean estimate for productivity of Ma. bonneae/dives females is 1.6 million per hectare per annum in swamp forest habitats vegetated with any of the host-plants studied.
Surveys were conducted of adult and immature mosquitoes in an area undergoing oil palm development in north Sarawak. Point prevalence data from 2 sites were collected annually, coinciding with annual phases of forest clearing, burning/cultivation, and maintenance. Major habitat perturbation during the forest/clearing transition shifted the major mosquito faunal equilibrium in terms of species composition, relative density and occurrence. Analyses of variance showed that the mean numbers of 4 species of Anopheles decreased significantly after forest clearing. Relative densities of immature stages decreased after forest clearing, but A. letifer and Culex tritaeniorhynchus remained relatively unchanged after the second year. Comparisons with the pre-development forest stage showed that the reductions in person-biting rates, adult survival and combined entomological inoculation rates (EIR) of A. donaldi and A. letifer decreased the risk of malaria transmission by 90% over the 4 years period. Concomitant reductions in EIR and annual malaria incidence were also correlated. This study highlighted the 'law of unintended consequences', since 2 contrasting effects were observed: reduction of malaria vectors but concomitant increase of dengue vectors.
Entomological investigations on malaria and bancroftian filariasis transmission were carried out in the endemic area of Baram District, Sarawak. The Anopheles composition, survival and infection rates of malaria and filariasis were compared in the village and 0.5 km from the village ecotype, in forested areas. Anopheles leucosphyrus, An. barbirostris and An. donaldi are the vectors for malaria and bancroftian filariasis in both ecotypes. Biting and infection rates vary, but An. leucosphyrus differed with a peak around midnight in the forested area and soon after dusk in the village setting. The parous rate of An. leucosphyrus was significantly higher in the forest ecotype (P < 0.0001); however, the proportion of 3-parous and older was not overall higher in the forest ecotype (P = 0.68). The entomological inoculation of malaria parasites by An. leucosphyrus was comparatively higher in the forested areas (P > 0.5). The implications of malaria and filariasis transmission in the forested areas in Baram District are discussed.
Two field trials in the control of subperiodic brugian filariasis vectors, mainly Mansonia bonneae and Mansonia dives were carried out in Sarawak, East Malaysia. In the first trial, malathion ultra-low volume (ULV) spray was used to control the Mansonia mosquitos in two filariasis endemic villages. Six spray rounds were applied at biweekly intervals at Kampung Rasau and two spray rounds were applied at monthly intervals in Kampung Triboh. ULV malathion spray reduced biting Ma. bonneae population for 3 days after spraying. The biting density decreased to 50% of the pre-treatment level by the 12th - 13th day and reached the pre-treatment level by the 24th - 25th day. Contact bioassay tests on caged Mansonia mosquitos revealed considerable penetration of the malathion aerosol indoors and relatively adequate coverage outdoors. The estimated number of bites per case per day was 1.09 to 4 times less in the sprayed kampung than in an unsprayed control kampung. The parous and daily survival rates of Mansonia mosquitos were not significantly affected by the spraying. In a second trial, chemotherapy with diethylcarbamazine citrate (DEC) was combined with vector control through indoor residual spraying in Kampung Ampungan. The results were compared with the use of only DEC mass treatment in Kampung Sebangkoi and Kampung Sebamban. The combined control measures in Kampung Ampungan reduced the MfD-50 to 44% of the pre-treatment level over a period of 4 years. In the other two kampungs where only mass DEC therapy was applied, the microfilarial rate and MfD-50 declined significantly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. The total insecticidal impact for Ma. bonneae was 3.9 to 1 indoors and 2.7 to 1 outdoors. These results indicated that quarterly pirimiphos-methyl indoor spraying used in integrated control could reduce indoor transmission by 3.9 times. The infective rate from the Ma. bonneae dissected in all three kampungs after the interventions, irrespective of DEC treatment alone or in combination with pirimiphos-methyl residual spraying were reduced by two fold. However the infection rate of brugian filarial larvae in Kampung Ampungan was significantly reduced after the use of DEC and insecticide. Annual Transmission Potential (ATP) showed a high significant reduction in Kampung Ampungan (p > 0.001) compared with Kampungs Sebangkoi and Schambam. In Ampungan, the ATP was reduced by 8.5 times indoors after the MDA and insecticidal application and 3 times outdoors. The reduction rate for Sebangkoi and Sebamban both indoors and outdoors were less than 2 fold.(ABSTRACT TRUNCATED AT 400 WORDS)
A control programme against subperiodic brugian filariasis was implemented in three villages, (Kg. Ampungan, Kg. Sebangkoi and Kg. Sebamban) in Sarawak, Malaysia. In Kampong Ampungan, the mass administration of diethylcarbamazine (DEC-citrate) combined with residual house spraying of pirimiphos-methyl reduced microfilarial rate to 8% of the pre-treatment level and microfilarial density (MfD50) to 44% of the pre-treatment level over a period of four years. In Kampong Sebangkoi and Kampong Sebamban, where only mass DEC therapy was applied, the microfilarial rate and MfD50 declined distinctly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. In Kg, Ampungan, we observed a significant reduction of infective biting rate (88.3%), infection rate (62.5%) and transmission potential (88.1%) of Mansonia bonneae at the fourth spray round. The corresponding reduction rates in Kg. Sebangkoi and Kg. Sebamban were 35.3%, 26.7%, 42.2% and 24%, 30.8% and 15.4% respectively. The biting density of the vector was reduced by 79.8% indoors and 31.8% outdoors at the sprayed village, while only a slight decrease in densities (17.9% indoors and 12.4% outdoors) was observed at the unsprayed village. Bioassay tests revealed that pirimiphos-methyl had a substantial fumigant effect on the vector. The integrated control measure in controlling subperiodic brugian filariasis is discussed.
The measurement of the ultimate effects of the microbial insecticides on mosquito density is best obtained by assessment of adult populations. The main aims of this study are: (1) to assess the effect of Bacillus thuringiensis israelensis (Bti) FC Skeetal and Bactimos briquettes on the emergence rate of Mansonia bonneae developed from the introduced first-instar stage larvae and (2) to measure the effect of these two formulations of insecticides on Mansonia adult populations emerging from the natural breeding plots. Bti Skeetal and Bactimos briquettes at the lower applied dosages of 2.3 kg/ha and 1 briquette case/20 m2 respectively achieved 39-40% pupation rates and 31.5-34.2% adult emergence rates. At these low applied dosages, there was little or no direct effect on pupation from the surviving larvae and thereafter on the emergence of adults from the pupae. A two-fold increase in dosage, however, produced a drastic decline in the pupation rate and adult emergence rate. The rates dropped to 6.5% (pupation) and 4.3% (adult emergence) of the total larvae for Bactimos briquettes and to merely 1.5% (pupation) and 1.3% (adult emergence) of the total larvae for Skeetal. In studying the effect of Bti on the field populations of Mansonia mosquitos, two plots each were treated with Bactimos at 1 briquette case/10 m2 and Skeetal at 4.6 kg/ha. A wooden pyramid-shaped screened cage was placed on a cluster of host plants for a period of 2 weeks to trap the emerging adult mosquitoes. There were a total of 24 clusters of host plants in each plot.(ABSTRACT TRUNCATED AT 250 WORDS)
School children from 3 primary and 2 secondary schools in Sarawak were examined for the presence of gastrointestinal helminths. One primary school and 1 secondary school were located in a town (Serian), the other primary and secondary schools were in the countryside outside Serian. The intestinal helminths detected were Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis and hookworm. Children from the rural schools had higher numbers of eggs in their faeces than those from the Serian schools. Children from the rural primary schools had higher number of eggs than those from the rural secondary school. The prevalence of Ascaris, Trichuris and hookworms in male and female and in primary and secondary school children was recorded.
A total of 82 persons have been found to be positive for microfilaria a sub-periodic Brugia malayi out of 1,613 examined in seven villages in Serian District. This represents an average microfilaria infection rate of 5.1% with a range of zero to 10.7%. It is found that males are more predominantly affected than females with a ratio of 3:1. It is also confirmed that Mansonia dives and M. bonneae are possible vectors for the transmission of the disease although Anopheles species cannot be ruled out owing to the small number of specimens examined. The study is confined to areas where indoor DDT spraying has been done since 1960 and only in two of the areas it has been terminated in 1966. Yet to be published data shows higher filaria infection rate than any of these villages.
Two separate observations from recent electrophoretic studies of the systematics and population genetics of laboratory-reared populations which had a long history of colonization in various laboratories, were found to be inconsistent with the present study which used wild-caught populations from East Malaysia. Reanalysis of the two data sets generally indicated a low amount of genetic variation in laboratory colonies. The latter is characterized by higher frequency of monomorphic loci, low average heterozygosity values and, in one extreme case, no variability at two loci. However, natural populations of An. balabacensis and An. leucosphyrus showed more protein variability by the use of polyacrylamide gel electrophoresis. Since laboratory-maintained mosquitoes are genetically and phenotypically different from those in the field, results of laboratory studies on the systematics and population genetics of Anopheles species complexes may be biased.
Chemotherapy was conventionally applied to kill cancer cells, but regrettably, they also induce damage to normal cells with high-proliferative capacity resulting in cardiotoxicity, nephrotoxicity, peripheral nerve toxicity, and ovarian toxicity. Of these, chemotherapy-induced ovarian damages mainly include but are not limited to decreased ovarian reserve, infertility, and ovarian atrophy. Therefore, exploring the underlying mechanism of chemotherapeutic drug-induced ovarian damage will pave the way to develop fertility-protective adjuvants for female patients during conventional cancer treatment. Herein, we firstly confirmed the abnormal gonadal hormone levels in patients who received chemotherapy and further found that conventional chemotherapeutic drugs (cyclophosphamide, CTX; paclitaxel, Tax; doxorubicin, Dox and cisplatin, Cis) treatment significantly decreased both the ovarian volume of mice and the number of primordial and antral follicles and accompanied with the ovarian fibrosis and reduced ovarian reserve in animal models. Subsequently, Tax, Dox, and Cis treatment can induce the apoptosis of ovarian granulosa cells (GCs), likely resulting from excessive reactive oxygen species (ROS) production-induced oxidative damage and impaired cellular anti-oxidative capacity. Thirdly, the following experiments demonstrated that Cis treatment could induce mitochondrial dysfunction through overproducing superoxide in GCs and trigger lipid peroxidation leading to ferroptosis, first reported in chemotherapy-induced ovarian damage. In addition, N-acetylcysteine (NAC) treatment could alleviate the Cis-induced toxicity in GCs by downregulating cellular ROS levels and enhancing the anti-oxidative capacity (promoting the expression of glutathione peroxidase, GPX4; nuclear factor erythroid 2-related factor 2, Nrf2 and heme oxygenase-1, HO-1). Our study confirmed the chemotherapy-induced chaotic hormonal state and ovarian damage in preclinical and clinical examination and indicated that chemotherapeutic drugs initiated ferroptosis in ovarian cells through excessive ROS-induced lipid peroxidation and mitochondrial dysfunction, leading to ovarian cell death. Consequently, developing fertility protectants from the chemotherapy-induced oxidative stress and ferroptosis perspective will ameliorate ovarian damage and further improve the life quality of cancer patients.
BACKGROUND: Topical immunotherapy has recently been found useful in the treatment of chronic and extensive Alopecia Areata (AA).
OBJECTIVE: To evaluate the efficacy and safety of diphenylcyclopropenone (DPCP) use among Chinese patients with steroid resistant and extensive AA in our institute.
METHODS: The medical records of 31 Chinese patients treated with DPCP were analysed retrospectively. The efficacy, adverse effects, and relapse rate of DPCP treatment were reviewed.
RESULTS: Thirty-one (16 male, 15 female) Chinese patients with extensive, steroid resistant Alopecia Areata and a mean age of 28.9 years (SE 10.4) were treated. The mean age of onset was 17.8 years (SE 8.8) with an average disease duration of 11.2 years (SE 7.7). Ten patients had a history of atopy and 4 had a history of thyroid disease. Nail changes were found in 14 patients and a family history of AA was found in 2 patients. Thirteen patients (41.9%) had experienced total hair loss. Two patients abandoned the treatment due to severe side effects. Of the remaining 29 patients, 4 (13.8%), 7 (24.1%), 5 (17.2%), and 13 (44.8%) achieved >90% complete response, >50-90% partial response, >10-50% minimal response, and <10% no response hair regrowth, respectively. Adverse effects included pruritus, erythema, vesiculation, scaling, cervical lymphadenopathy, dyspigmentation and urticarial reactions. Relapse occurred (>25% hair loss) in 69.23% of patients after 18 months of follow up.
CONCLUSIONS: DPCP is an effective and tolerable treatment for Chinese patients with extensive, steroid resistant AA.