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1.
Charles S. Wondji Michael Coleman Immo Kleinschmidt Themba Mzilahowa Helen Irving Miranda Ndula Andrea Rehman John Morgan Kayla G. Barnes Janet Hemingway 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(47):19063-19070
The impact of insecticide resistance on insect-borne disease programs is difficult to quantify. The possibility of eliminating malaria in high-transmission settings is heavily dependent on effective vector control reducing disease transmission rates. Pyrethroids are the dominant insecticides used for malaria control, with few options for their replacement. Their failure will adversely affect our ability to control malaria. Pyrethroid resistance has been selected in Malawi over the last 3 y in the two major malaria vectors Anopheles gambiae and Anopheles funestus, with a higher frequency of resistance in the latter. The resistance in An. funestus is metabolically based and involves the up-regulation of two duplicated P450s. The same genes confer resistance in Mozambican An. funestus, although the levels of up-regulation differ. The selection of resistance over 3 y has not increased malaria transmission, as judged by annual point prevalence surveys in 1- to 4-y-old children. This is true in areas with long-lasting insecticide-treated nets (LLINs) alone or LLINs plus pyrethroid-based insecticide residual spraying (IRS). However, in districts where IRS was scaled up, it did not produce the expected decrease in malaria prevalence. As resistance increases in frequency from this low initial level, there is the potential for vector population numbers to increase with a concomitant negative impact on control efficacy. This should be monitored carefully as part of the operational activities in country.The push for malaria elimination and eventual eradication will be heavily dependent on our ability to reduce disease transmission. A recent editorial suggests that we have the tools to take on this challenge in African malaria heartlands (1). This is predicated on ensuring that vector control prevention and drug treatment tools are fully deployed, reaching every person at risk. There will need to be improved delivery of these tools and better clinical management of malaria cases. In highly endemic areas our ability to reduce malaria transmission will be dependent on vector control, before the focus can shift to killing the parasite in infected people. Two forms of vector control, indoor residual spraying (IRS) and the distribution of long-lasting insecticide-treated nets (LLINs) have been demonstrated to reduce transmission when properly deployed against insecticide susceptible mosquito populations. The use of both interventions has dramatically increased since 2000 in many malaria endemic countries, with increased donor funding to attain the Roll Back Malaria targets and support the malaria elimination agenda (2).IRS and LLINs function by reducing the female mosquito daily survival rate and human biting frequency. Pyrethroids are the only insecticides recommended for use on LLINs, and only four chemical classes of insecticides that attack two target sites are available for IRS, and again pyrethroids dominate the IRS market. Resistance to pyrethroids has been selected in Anopheles gambiae and Anopheles funestus, the major African malaria vectors, although the frequency and level (fold) resistance conferred can vary dramatically. The impact of this resistance on the ability of either control intervention to reduce disease transmission is poorly understood, and current monitoring and evaluation practices are not sufficiently robust to assess this unless catastrophic failures occur. The perceived threat of pyrethroid resistance is now sufficiently high for the World Health Organization (WHO) to convene an international multidonor effort to counteract this.Operationally significant pyrethroid resistance has the potential to limit effective malaria control, owing to the small number of alternative public health insecticides. Pyrethroid resistance in malaria vectors has increased dramatically over the last decade (3, 4), particularly in Africa, where the bulk of malaria-related mortality occurs. Typically resistance is monitored by bioassays, for which the WHO has defined a diagnostic dosage for each insecticide that kills susceptible anopheline mosquitoes (5). Mosquitoes surviving the diagnostic dosage are an indication that resistance has been selected and that an operational problem may be developing, but bioassays alone do not signify control failure.Little operational monitoring of the underlying mechanisms of resistance occurs. Two mechanisms are predominantly responsible for insecticide resistance: changes in the insecticide target site, reducing binding of the insecticide, and increases in the rate at which the insecticide is metabolized (6). Information on the resistance mechanisms is more predictive than bioassays, providing information on the level of resistance and potential cross-resistance between insecticides. For example, two common mutations in the sodium channel convey low-level resistance to pyrethroids and higher-level resistance to dichlorodiphenyltrichloroethane (DDT) in An. gambiae (7, 8), whereas a cytochrome P450-based metabolic regulatory mechanism conveys very high-level pyrethroid and low-level carbamate resistance in An. funestus (9).Vector control interventions are being rapidly scaled up in Malawi, where malaria is highly endemic. Malaria accounts for 34% of all outpatient hospital visits and is the main cause of hospital admissions in children aged <5 y (10). Before 2007 sporadic WHO bioassays were undertaken, which indicated that the two major malaria vectors, An. gambiae and An. funestus, remained fully susceptible to pyrethroids. In 2007 pyrethroid-impregnated LLINs were distributed through antenatal and under-5 clinics at district and central hospitals countrywide. The numbers distributed were sufficient to achieve the Roll Back Malaria targets of 80% of pregnant women and children aged <5 y sleeping under a treated net. In 2008, a pilot study of IRS with the pyrethroid lambda cyhalothrin (ICON, Syngenta) was initiated in Nkhota Khota District, supported by the President’s Malaria Initiative (PMI). The initial program targeted 26,950 houses, and was expanded to 74,772 houses in 2009. Approximately 4 million LLINs were procured and ∼2 million distributed during this time. In 2010 the PMI-supported IRS was expanded to cover the whole of Nkohta Khota district, and the Malawian Ministry of Health supported IRS in a further six districts.A series of sentinel sites were established during this period to track the effect of this rapid increase in insecticide selection pressure on the local vectors and assess any impact on malaria transmission. This was particularly pertinent owing to the high levels of pyrethroid resistance reported in the southern part of neighboring Mozambique in An. funestus, which had prompted a switch from pyrethroids to carbamates or DDT for IRS in the Lubombo Spatial Development Initiative area of Mozambique (11, 12). 相似文献
2.
Vasileia Balabanidou Anastasia Kampouraki Marina MacLean Gary J. Blomquist Claus Tittiger M. Patricia Juárez Sergio J. Mijailovsky George Chalepakis Amalia Anthousi Amy Lynd Sanou Antoine Janet Hemingway Hilary Ranson Gareth J. Lycett John Vontas 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(33):9268-9273
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Katrijn Verhaeghen Wim Van Bortel Patricia Roelants Paul Edward Okello Ambrose Talisuna Marc Coosemans 《The American journal of tropical medicine and hygiene》2010,82(4):566-573
The planned upscaling of vector control strategies requires insight into the epidemiological consequences of vector resistance. Therefore, the pyrethroid and DDT resistance status of Anopheles gambiae s.l. was assessed in Uganda from 2004 to 2006, and spatial and seasonal variations in knockdown resistance (kdr) frequencies were analyzed in terms of epidemiological significance. Anopheles gambiae s.l. was DDT and pyrethroid resistant in central and eastern Uganda. The L1014S kdr allele frequencies varied from 3% to 48% in An. gambiae s.s. Although the homozygous resistant genotype was the most prevalent genotype among survivors, the genotypes could not entirely explain the bioassay results. In the dry season, the kdr frequency was significantly higher in Plasmodium falciparum-infected mosquitoes, indicating that mosquitoes bearing a kdr mutation have a better adult survival, hence a higher likelihood of becoming infectious. This study showed that kdr might have an epidemiological impact that could jeopardize the vector control strategies. 相似文献
5.
Claire Sangbakembi-Ngounou Carlo Costantini Neil Michel Longo-Pendy Carine Ngoagouni Ousman Akone-Ella Nil Rahola Sylvie Cornelie Pierre Kengne Emmanuel Rivalyn Nakoun Narcisse Patrice Komas Diego Ayala 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(21)
Malaria control interventions target nocturnal feeding of the Anopheles vectors indoors to reduce parasite transmission. Mass deployment of insecticidal bed nets and indoor residual spraying with insecticides, however, may induce mosquitoes to blood-feed at places and at times when humans are not protected. These changes can set a ceiling to the efficacy of these control interventions, resulting in residual malaria transmission. Despite its relevance for disease transmission, the daily rhythmicity of Anopheles biting behavior is poorly documented, most investigations focusing on crepuscular hours and nighttime. By performing mosquito collections 48-h around the clock, both indoors and outdoors, and by modeling biting events using circular statistics, we evaluated the full daily rhythmicity of biting in urban Bangui, Central African Republic. While the bulk of biting by Anopheles gambiae, Anopheles coluzzii, Anopheles funestus, and Anopheles pharoensis occurred from sunset to sunrise outdoors, unexpectedly ∼20 to 30% of indoor biting occurred during daytime. As biting events did not fully conform to any family of circular distributions, we fitted mixtures of von Mises distributions and found that observations were consistent with three compartments, corresponding indoors to populations of early-night, late-night, and daytime-biting events. It is not known whether these populations of biting events correspond to spatiotemporal heterogeneities or also to distinct mosquito genotypes/phenotypes belonging consistently to each compartment. Prevalence of Plasmodium falciparum in nighttime- and daytime-biting mosquitoes was the same. As >50% of biting occurs in Bangui when people are unprotected, malaria control interventions outside the domiciliary environment should be envisaged.Transmission of parasites of the genus Plasmodium that are the causative agents of human malaria is considered to occur mainly from sunset to sunrise, when their vectors, mosquitoes of the genus Anopheles, feed on human hosts that are at rest or asleep (1, 2). This principle is so firmly established that sampling protocols to measure the strength of transmission usually disregard diurnal Anopheles feeding (3). This has not always been so: sampling routines implemented in the early 20th century by medical entomologists generally covered the whole 24-h biting cycle of different mosquito species (4). It is generally assumed that nighttime blood-feeding evolved because hosts are less active at this time, so that mosquitoes incur a lower risk of being swatted or chased away, enabling higher feeding success (2). Human hosts, however, most often rest indoors; many human-biting anophelines, therefore, penetrate inside households in order to have access to and feed on humans. Current mainstay vector control tactics exploit these behaviors in order to reduce transmission by means of two interventions: protecting humans under long-lasting insecticidal bed nets (LLINs), and spraying houses with residual insecticides (i.e., indoor residual spraying, IRS) (5). Additional benefits of IRS come from the habit of some malaria vectors to rest inside dwellings, using them as refugia either before or after blood-feeding (1).Despite the incontestable success of these control interventions in reducing the burden of malaria (6), a plateau in the incidence rate of malaria cases has been observed in Africa during the last years (7). This could be at least in part explained by the intensive selection pressure put up by insecticides (8). Indeed, mutations conferring insecticide resistance have rapidly emerged (9), and resistance to different classes of insecticides is presently widespread in most malaria vector populations (10, 11). Moreover, there is evidence that some vector populations are changing their behavior in response to control interventions by feeding progressively more at places and at times when humans are less likely to be protected (12, 13). So far, behavioral modifications have resulted in more biting during the evening and early morning and out-of-doors (14–21). Recent studies reporting significant amounts of daytime biting, however, remain somewhat anecdotal, with few exceptions. Overall, these modifications increase the window of opportunity for human–vector contact, producing what is called residual malaria transmission (22, 23): this expression implies that transmission will persist even if LLINs and IRS are fully effective. It is feared, therefore, that the malaria elimination target set upon current control interventions may be compromised in the long term by residual malaria transmission (24). Countering this phenomenon should be based on better knowledge of the biology and behavior of the vectors, with the aim to develop more suitable interventions (12, 23, 25).In the Central African Republic, malaria remains a major public health problem and the main cause of deaths among children <5 y old (26). In 2006, the National Malaria Control Program implemented the first phase of the Global Fund Program for Malaria based on free distribution of LLINs to pregnant women and children <5 y old, with moderate results (26, 27). A new campaign of mass LLIN distribution was deployed in 2015. Yet, malaria incidence was not significantly reduced (28). Several studies reported the presence in the country of populations of the major malaria vectors Anopheles gambiae, Anopheles coluzzii, and Anopheles funestus that are resistant to pyrethroids, the class of insecticides used for impregnation of bed nets (29–31). It is not known, however, the degree to which insecticide resistance is responsible for such moderate reductions in malaria incidence in this country, above and beyond what can be accounted for by a national health system weakened by years of civil war and unrest.In order to appreciate the potential of residual malaria transmission in this epidemiological context, we investigated the biting behavior of the malaria vectors occurring in urban settings of Bangui, Central African Republic. We implemented two significant modifications to the sampling protocol and analytical procedures that are usually applied in this kind of investigation. First, the sampling plan consisted of monthly sessions of 48-h around-the-clock collections of mosquitoes coming to feed on human hosts both indoors and outdoors. Second, the daily rhythmicity of the observed biting events was analyzed quantitatively using a circular statistics framework that models these events on a circumference rather than along the usual linear representation (32–34). Unexpectedly, we found that 20 to 30% of malaria vector biting occurred at full daytime indoors. These results suggest that current vector control interventions may not be enough to achieve sufficient reductions in malaria transmission in Bangui. Perhaps even more significant, these observations suggest that Anopheles mosquitoes may have the potential to achieve fundamental modifications in the temporal organization and circadian control of their feeding behavior, with major impacts on malaria control strategies in Africa. We elaborate these results as follows. 相似文献
6.
Michael Coleman Geraldine M. Foster Rinki Deb Rudra Pratap Singh Hanafy M. Ismail Pushkar Shivam Ayan Kumar Ghosh Sophie Dunkley Vijay Kumar Marlize Coleman Janet Hemingway Mark J. I. Paine Pradeep Das 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(28):8573-8578
Indoor residual spraying (IRS) is used to control visceral leishmaniasis (VL) in India, but it is poorly quality assured. Quality assurance was performed in eight VL endemic districts in Bihar State, India, in 2014. Residual dichlorodiphenyltrichloroethane (DDT) was sampled from walls using Bostik tape discs, and DDT concentrations [grams of active ingredient per square meter (g ai/m2)] were determined using HPLC. Pre-IRS surveys were performed in three districts, and post-IRS surveys were performed in eight districts. A 20% threshold above and below the target spray of 1.0 g ai/m2 was defined as “in range.” The entomological assessments were made in four districts in IRS and non-IRS villages. Vector densities were measured: pre-IRS and 1 and 3 mo post-IRS. Insecticide susceptibility to 4% DDT and 0.05% deltamethrin WHO-impregnated papers was determined with wild-caught sand flies. The majority (329 of 360, 91.3%) of pre-IRS samples had residual DDT concentrations of <0.1 g ai/m2. The mean residual concentration of DDT post-IRS was 0.37 g ai/m2; 84.9% of walls were undersprayed, 7.4% were sprayed in range, and 7.6% were oversprayed. The abundance of sand flies in IRS and non-IRS villages was significantly different at 1 mo post-IRS only. Sand flies were highly resistant to DDT but susceptible to deltamethrin. The Stockholm Convention, ratified by India in 2006, calls for the complete phasing out of DDT as soon as practical, with limited use in the interim where no viable IRS alternatives exist. Given the poor quality of the DDT-based IRS, ready availability of pyrethroids, and susceptibility profile of Indian sand flies, the continued use of DDT in this IRS program is questionable.Leishmaniases are diseases caused by protozoan parasites that are transmitted to humans through the bites of infected female sand flies. The visceral form of leishmaniasis (VL) is endemic on the Indian subcontinent and in East Africa and Brazil, and 90% of the estimated 200–400,000 annual cases come from people living in these countries (1).An estimated 200 million people are at risk for VL, of whom 65 million live in India (2). The majority of Indian VL cases occur in the northeastern states, predominantly in Bihar (3, 4). The numbers of VL cases reported in India are based on passive case reporting, and therefore may be an underestimation (2, 5); however, regardless, advances in VL diagnostic tests and improved treatment modalities have ensured that the number of deaths due to VL in India has gradually decreased over the past 5 y (6).VL in India is caused by Leishmania donovani and is only transmitted by the female sand fly, Phlebotomus argentipes; no animal reservoir exists (2, 7). During the period of 1953–1962, indoor residual spraying (IRS) undertaken by the Indian national malaria program using dichlorodiphenyltrichloroethane (DDT) at 1 grams of active ingredient per square meter (g ai/m2) for malaria control had the beneficial side effect of significantly reducing the number of VL cases in India. A similar effect on VL due to IRS for malaria control was also seen in Bangladesh from 1961–1970 (8). In India, VL did not reappear in areas such as Assam until the late 1970s (9). This inadvertent control of VL led to the adoption of IRS by the Indian VL elimination program as the main focus for P. argentipes control, and two periods of IRS using DDT at 1 g ai/m2 during 1977–1979 and 1992–1995 both saw sharp decreases in the number of VL cases reported (6).In India, IRS is performed by spraying houses and animal shelters to control the endophilic and exophagic vector P. argentipes (10). Although the effect of IRS on P. argentipes is based on limited data (11–13), a cluster randomized trial performed in India, Bangladesh, and Nepal demonstrated that IRS using DDT reduced the indoor abundance of P. argentipes by 72.4% in intervention clusters compared with controls; this effect was greater than the effect of environmental modification or the use of long-lasting insecticide-treated nets (42.0% and 43.7%, respectively) (14). Older models also predict that IRS is capable of achieving VL elimination, provided that sand fly densities are reduced by 67% (15). Given that effective prevention through vector control and rapid diagnosis and treatment methodologies exist (7, 16), elimination of VL in this region should therefore be technically feasible. However, in order for the predicted outcomes of IRS to become a reality, the IRS itself must be of sufficient quality to achieve an impact (17, 18).Strong regional political support for VL elimination was established through a tripartite agreement between Bangladesh, India, and Nepal that was signed in 2005 with the aim of reducing the annual incidence of VL and post–kala-azar dermal leishmaniasis (PKDL) to less than one case per 10,000 population at the subdistrict level by 2015 (19). This program was a four-phase process to interrupt transmission, enhance early diagnosis and treatment, and improve health education (20). The tripartite agreement also aimed to standardize IRS in the region, as recommended by the regional technical advisory group (RTAG) (21) (Years Phase 2005–2007 Preparatory phase: Establish IRS and build capacity 2008–2013 Attack phase: Intensify IRS, increase vector surveillance, improve early diagnosis and treatment, and introduce case surveillance 2014–2016 Consolidation phase: Limited IRS and case surveillance 2016 onward Maintenance phase: Surveillance and rapid response to prevent reintroduction