Biochemical studies on malathion resistance in Anopheles arabiensis from Sudan

The change from larval to adult mosquito control in the Gezira area of Sudan resulted in a decrease in the prevalence of malaria in this region. House spraying with malathion began in 1975 and resistance to this compound was first detected in 1978. Laboratory tests showed that adult Anopheles arabiensis Patton were resistant to malathion and phenthoate but susceptible to all other organophosphates tested. The larvae of this strain were susceptible to malathion. The malathion resistance in the adults was synergized by triphenyl phosphate, but not by piperonyl butoxide. This suggests that a carboxylesterase enzyme may be the basis of malathion resistance in this strain. Analysis of general esterase levels to alpha- and beta-naphthyl acetate showed that there was no quantitative change in the amount of carboxylesterase enzyme present in the resistant strain as compared to the susceptible. The absence of larval resistance suggests that house spraying rather than agricultural spraying is the major source of selection pressure. The presence of a high level of adult malathion resistance in A. arabiensis may decrease the efficacy of malathion for malaria control in Sudan. The lack of cross-resistance to organophosphates which do not contain a carboxylester bond means that insecticides such as fenitrothion are still practical alternatives.     

La lutte contre le paludisme en Afrique tropicale.

Although spraying with insecticides has caused a spectacular regression in malaria in many parts of Africa, it cannot be said that the transmission of the disease has been definitely interrupted in any large area on the mainland. There is therefore some uneasiness regarding the methods so far adopted and doubts as to whether the very considerable expenditure involved is justified. There is, moreover, acute anxiety about the possible development of resistance to insecticides by the vector anopheles. Fortunately, so far there does not appear to be any in Africa, and the author considers that logical aim should be complete eradication of malaria before resistance does appear to the powerful insecticides now available. Control measures must inevitably be continued indefinitely, but if the aim of eradication is achieved, operations could cease and it would be possible for anopheles to co-exist with man without transmitting malaria. The author points out that before any continent-wide campaign can be begun, there are, in addition to the problem of funds, a number of other problems which must be carefully studied. Among these are the lack of trained specialized staff at all levels, transport difficulties, shortage of water over vast areas in the dry season and floods during the rains, the differing habits of the various African populations, and the biology of the vector mosquitos. Despite these problems, however, the time for concerted action to achieve eradication in Africa draws nearer with each succeeding day.     

Malaria resurgence in India: a critical study

In 1953, the Indian National Malaria Control Programme (NMCP) was started. Encouraged by the results, and the fact that insecticide resistance in vector species may evolve and become an obstacle, in 1958 a control programme was converted to the National Malaria Eradication Programme (NMEP). By 1964, malaria was eradicated from 88% of the area and it was in the advanced stage of spraying in the remaining parts. At that time, focal outbreaks that occurred in 1965 and increased in later years, could not be contained due to the shortages of DDT. As a result, large areas in consolidation and maintenance phases were reverted to the attack phase. Besides, the infrastructure in general health services was not adequate and mature enough to take up surveillance and vigilance. This produced a large number of secondary cases due to the re-introduction and relapse of malaria. Added to this was the problem of urban malaria, the control of which was the responsibility of local bodies. Malaria cases increased in towns, and started diffusing to the rural areas, due to inadequate staff and the shortages of malarial larvicidal oil (MLO). Later, it turned out, that while it was technically feasible to eradicate malaria from 91% of the population, the strategy of indoor spraying of DDT to interrupt transmission did not succeed in 9.0% of the population, despite more than 12-14 years of regular spraying. During the years of resurgence, there was no research support to the programme, so that technical problems were not properly appreciated, understood and tackled. The reservoir of parasites that were present throughout the country started multiplying and spreading to newer areas due to the presence of vectors in high densities. Thus malaria resurged and re-established itself even in areas that were at one time freed from the disease. The analysis of the pattern of malaria resurgence revealed that malaria outbreaks preceded the true problem of insecticide resistance. It is noteworthy to mention that malaria resurgence occurred in towns where the control measures were non-insecticidal and in regions which were not under the influence of insecticide-resistant vectors. The study also revealed that resurgence occurred before the introduction of high-yielding varieties programme in the country, and had no relationship to either the cotton or rice growing or intensive agriculture.     

DDT, global strategies, and a malaria control crisis in South America.

Malaria is reemerging in endemic-disease countries of South America. We examined the rate of real growth in annual parasite indexes (API) by adjusting APIs for all years to the annual blood examination rate of 1965 for each country. The standardized APIs calculated for Brazil, Peru, Guyana, and for 18 other malaria-endemic countries of the Americas presented a consistent pattern of low rates up through the late 1970s, followed by geometric growth in malaria incidence in subsequent years. True growth in malaria incidence corresponds temporally with changes in global strategies for malaria control. Underlying the concordance of these events is a causal link between decreased spraying of homes with DDT and increased malaria; two regression models defining this link showed statistically significant negative relationships between APIs and house-spray rates. Separate analyses of data from 1993 to 1995 showed that countries that have recently discontinued their spray programs are reporting large increases in malaria incidence. Ecuador, which has increased use of DDT since 1993, is the only country reporting a large reduction (61%) in malaria rates since 1993. DDT use for malaria control and application of the Global Malaria Control Strategy to the Americas should be subjects of urgent national and international debate. We discuss the recent actions to ban DDT, the health costs of such a ban, perspectives on DDT use in agriculture versus malaria control, and costs versus benefits of DDT and alternative insecticides.     

Knowledge, practices, and perceptions about malaria in rural communities of Zimbabwe: relevance to malaria control.

A survey of 411 household heads was undertaken in Gokwe district, Zimbabwe, to assess villagers'' knowledge, practices and perceptions about malaria and their implications for malaria control. Our results show that although the government has sustained an annual indoor insecticide spraying programme for over four decades, about 50% of respondents did not adequately understand its purpose, with 26% believing that the programme was intended to kill domestic pests, not including mosquitos. During the 1991-92 spraying cycle, 72% of the villagers had their homes sprayed. However, 21% of such villagers refused to have some rooms in their homes sprayed. Householders'' understanding of the function of the spraying programme was significantly related to their compliance with it (P < 0.05). A total of 82% of respondents reported not taking any measures to protect themselves from malaria. Taking preventive measures was significantly related to knowledge of the causes of malaria (P < 0.05). The study shows the importance of involving communities in a control programme intended to be to their benefit and of informing them about available options for protection against malaria.     

Possible Interruption of Malaria Transmission, Highland Kenya, 2007�C2008

Highland areas where malaria transmission is unstable are targets for malaria elimination because transmission decreases to low levels during the dry season. In highland areas of Kipsamoite and Kapsisiywa, Kenya (population ≈7,400 persons), annual household indoor residual spraying with a synthetic pyrethroid was performed starting in 2005, and artemether/lumefantrine was implemented as first-line malaria treatment in October 2006. During April 2007–March 2008, no microscopy-confirmed cases of malaria occurred at the sites. In 4 assessments of asymptomatic persons during May 2007–April 2008, a total of <0.3% of persons were positive for asexual Plasmodium falciparum by microscopy or PCR at any time, and none were positive by PCR at the last 2 sample collections. Our findings show that in such areas, interruption and eventual elimination of malaria transmission may be achievable with widespread annual indoor residual spraying of households and artemisinin combination therapy.     

A field test for the estimation of chloroquine in urine

The use of antimalarial drugs is indissolubly linked with the use of insecticides in malaria eradication campaigns and is, indeed, of quite particular importance in areas in which insecticides have for various reasons—such as acquired resistance by anophelines—proved to be of limited value or in which residual spraying has ceased and potential foci of infection must be suppressed.     

Fluctuating asymmetry and exposure to pyrethroid insecticides in Triatoma infestans populations in northeastern Argentina

Fluctuating asymmetry (FA), a phenotypic marker used as indicator of developmental stress or instability, is sometimes associated with insecticide application and resistance. Here we investigated the occurrence and amount of wing size and wing shape FA in Triatoma infestans females and males collected before and 4 months after a community-wide pyrethroid spraying campaign in a well-defined rural area of Pampa del Indio, Argentina. Moderate levels of pyrethroid resistance were previously confirmed for this area, and postspraying house infestation was mainly attributed to this condition. In the absence of insecticide-based selective pressures over the previous 12 years, we hypothesized that 1- if postspraying triatomines were mostly survivors to insecticide spraying (pyrethroid resistant), they would have higher levels of FA than prespraying triatomines. 2- if postspraying triatomines have a selective advantage, they would have lower FA levels than their prespraying counterparts, whereas if postspraying infestation was positively associated with immigrants not exposed to the insecticide, prespraying and postspraying triatomines would display similar FA levels. For 243 adult T. infestans collected at identified sites before insecticide spraying and 112 collected 4 months postspraying, wing size and wing shape asymmetry was estimated from landmark configurations of left and right sides of each individual. At population level, wing size and shape FA significantly decreased in both females and males after spraying. Males displayed greater wing size and shape FA than females. However, at a single peridomestic site that was persistently infested after spraying, FA declined similarly in females whereas the reverse pattern occurred in males. Our results suggest differential survival of adults with more symmetric wings. This pattern may be related to a selective advantage of survivors to insecticide spraying, which may be mediated or not by their pyrethroid-resistant status or to lower triatomine densities after insecticide spraying and the concomitant increase in feeding success.     

Spatiotemporal distribution of insecticide resistance in Anopheles culicifacies and Anopheles subpictus in Sri Lanka

The malaria situation in Sri Lanka worsened during the 1990s with the emergence and spread of resistance to the drugs and insecticides used for control. Chloroquine resistance has increased rapidly over this period, but adverse changes in malaria transmission are more closely associated with insecticide use rather than drug resistance. Insecticide susceptibility tests were routinely carried out in key anopheline vectors across the country for more than a decade. These sentinel data were combined with data collected by other research programmes and used to map the spatial and temporal trends of insecticide resistance in the main vectors, Anopheles culicifacies and A. subpictus, and to examine the relationship between insecticide resistance, changes in national spraying regimens and malaria prevalence. Both species had widespread resistance to malathion, the insecticide of choice in the early 1990s. Both species were initially susceptible to the organophosphate and pyrethroid insecticides used operationally from 1993, but some resistance has now been selected. The levels of malathion and fenitrothion resistance in A. subpictus were higher in some ecological regions than others, which may be related to the distribution of sibling species, agricultural pesticide exposure and/or environmental factors. The study highlights that the emergence and spread of insecticide resistance is a constant threat and that active surveillance systems are vital in identifying key vectors and evidence of resistance.     

Malaria in the highlands of Madagascar after five years of indoor house spraying of DDT

The central region of Madagascar is a vast area of highlands (altitude 700-2000 m). Malaria transmission has re-established itself here since the last epidemic of 1985-90 and has caused the deaths of 40,000 persons according to the Minister of Health. To combat the main malaria vector in the region, Anopheles funestus, annual programmes of indoor house spraying of DDT were carried out between December 1993 and January 1998 in most rural areas at altitude 1000-1500 m. A parasitological and serological study was then conducted in the highland schools to evaluate the impact of the programme and set up a database on the region. Using a cluster-sampling method 2 independent selections were conducted (one of 130 sites, the other of 40 sites). During the study, 13,462 schoolchildren were examined, 71% living in sprayed villages. Parasite prevalence among schoolchildren declined as altitude increases, from 11% at 700-900 m to 0.4% at > 1500 m. Below 1500 m, the impact of the spraying on the prevalence of the parasite was very clear (an average decrease of from 20% to 2.7% below 1000 m and of from 4.5% without spraying to 0.8% at 1000-1500 m). Geographical analysis of the data showed that the marginal regions remained the most affected by malaria (especially outside spraying zones), and persistence of 'pockets of transmission' at 1000-1500 m, essentially in areas where spraying has never been used. In 9 schools, anti-Plasmodium antibodies were sought by indirect immunofluorescence on thick smears of parasitized red blood cells. The seroprevalence ranged from 22% to 63%, which suggests that the parasite is still circulating in the region. Even though our data show that vector control continues to be very successful in the Madagascan highlands, rapid reinfection could occur and must be monitored following spraying. To this end, the Minister for Health, with the support of the Italian Co-operation, has placed the region under epidemiological surveillance since 1997. An alert system for the timely detection of the sources of epidemics and the targeting of the antivectoral campaign is also in operation. Our study suggests that this strategy should be reinforced by the spraying of DDT in the marginal zones in order to consolidate the results obtained at higher altitudes.     

Ineffectiveness of DDT residual spraying in stopping malaria transmission in the Jordan Valley

The malaria-control campaign in the Jordan Valley-undertaken by the United Nations Relief and Works Agency for Palestine Refugees in the Near East in 1949-has been based solely on DDT residual spraying in the northeastern areas, but in certain southern districts some larvicidal and drainage work has been done.Observations made in the north-east showed that active malaria transmission had occurred in 4 of the 12 villages surveyed in 1951, and in 8 of the 9 villages surveyed in 1952. That the insecticide was effective was demonstrated by the fact that sprayed structures were almost entirely free from anophelines four months after the last spraying, but entomological surveys showed that Anopheles sergenti and A. superpictus (the main malaria vectors) were successfully evading contact with sprayed surfaces by using caves and fissures in hills as daytime resting-places.The author discusses the bearing that the topography of the area and the habits of the population have on the transmission of the disease, and stresses the importance of surveys. He recommends the resumption of antilarval measures in the Jordan Valley.     

Experience with mass drug administration as a supplementary attack measure in areas of vivax malaria

Mass drug administration was introduced in Syria to supplement DDT spraying after the main malaria vector Anopheles sacharovi had developed considerable resistance to the insecticide. Mass administration of weekly doses of chloroquine and pyrimethamine was carried out in the Ghab area from August to October, the coverage obtained being over 80% for most of the time. The number of cases with positive blood films declined rapidly from August onwards. Entomological observations showed that the house-resting density decreased shortly after the second round of DDT spraying but soon regained its previous level. Some relapsing cases were detected in 1969 but none were found in 1970, and it is considered that the possibility of relapses should not deter authorities from using mass drug administration in emergency situations.     

Distribution of insecticide-treated bednets during a polio immunization campaign--Niger, 2005

The West African country of Niger (2005 population: approximately 14 million) is among the poorest in the world. In 2005, malaria was reported in approximately 760,000 persons and caused 2,000 deaths; however, surveillance has been inadequate, and the true numbers likely were even higher. In 2004, the overall mortality rate in Niger among children aged <5 years was 259 per 1,000 live births. At least 8% of these deaths likely were caused by malaria, and the actual proportion might be as high as 50%. In addition, Niger was one of only 10 countries with poliomyelitis during the first 3 months of 2006, and the risk for polio importation from neighboring Nigeria is high. Routine polio vaccination coverage remains low in Niger; in 2003, coverage with 3 doses of oral poliovirus vaccine (OPV) was 54%. To reduce the prevalence of malaria and bolster polio eradication measures, Niger's Ministry of Health, with support from international partners, launched a nationwide integrated health campaign in 2005. In coordination with a supplemental immunization activity (SIA) distributing OPV, long-lasting insecticide-treated bednets (ITNs) for malaria prevention were provided free of charge to mothers of children aged <5 years. In sub-Saharan Africa, ITNs have reduced all-cause mortality in children aged 1-59 months by 17%. This was the second such national campaign worldwide; the first was conducted in Togo in December 2004. This report describes findings from a survey of Niger's integrated health campaign and highlights differences with the campaign in Togo.     

Evaluation of fenitrothion for the control of malaria.

Fenitrothion was evaluated for residual spraying in antimalaria programmes in a large-scale field trial near Kisumu, Kenya from 1972 to 1976. The insecticide was applied in a hyper/holoendemic malarious area of 200 km² inhabited by about 50 000 people. All houses and animal shelters were sprayed at a target dosage rate of 2 g/m² at 3-month intervals for a total of 8 consecutive spray rounds in 2 years. The malaria vectors Anopheles gambiae species A and B and A. funestus were reduced to negligible densities indoors and outdoors immediately after initiation of spraying and for 10 months after the last spray round. However, A. gambiae reappeared during the main wet season at densities high enough to reestablish low-level transmission for short periods. Spraying produced a marked and rapid decrease in both the incidence and prevalence of malaria. The daily probability of acquiring malaria infection was reduced from 0.009 before spraying to 0.0003 under spray protection, a reduction of 96%. Data collected on a longitudinal basis indicated that sustained spray protection would reduce malaria prevalence to an asymptotic limit of 6.9% under the assumption that the inoculation and recovery rates remain stable. However, to attain malaria eradication in this type of epidemiological situation, complementary measures such as mass drug administration appear to be necessary.     

A malaria-control experiment in the interior of Borneo

A first experiment on malaria control in the interior of Borneo by spraying with residual insecticides is described. The work was carried out in the isolated, sparsely populated valleys of the Baram River and its tributary, the Tinjar, in northern Sarawak. The experimental area was divided into three parts: a DDT test area, where a 75% suspension of wettable powder was applied at the rate of 2 g of DDT per m(2) of surface; a BHC test area, where a 50% suspension of wettable powder was applied at the rate of 0.10 g of gamma isomer per m(2); and a check area.Entomological investigations made before the spraying operations were started showed that Anopheles leucosphyrus D?nitz, 1901 was the main malaria vector in both the test and the check areas. Out of a total of 7568 A. leucosphyrus dissected, 30 gland infections were detected-a sporozoite-rate of 0.40%. A. barbirostris was found to be a secondary vector throughout the experimental area.THE RESULTS OF INSECTICIDE SPRAYING WERE SATISFACTORY: in the DDT test area, the spleen-rate fell from 51.8% to 25.1%, and the parasite-rate from 35.6% to 1.6%, in 21 months, and a similar reduction in the rates was observed in the BHC test area. In the check area, the spleen- and parasite-rates rose during the period of observations. It is considered that if such a degree of control can be obtained in 21 months, complete eradication can be expected in the near future.Although BHC spraying proved effective, the fact that it has to be repeated every three months makes it impracticable in the interior of Sarawak, where communications are very poor and difficulties of transport very great. DDT spraying, which need only be done twice a year, is therefore to be preferred. The cost of the DDT operations-US$ 0.45 per person protected per year-is comparatively high, owing to the difficulty of communications and to the necessity for spraying not only the village "longhouses", but also the temporary shelters which the semi-nomadic people in the interior of Sarawak build each year in the rice-fields.     

Parachuting cats and crushed eggs the controversy over the use of DDT to control malaria

The use of DDT to control malaria has been a contentious practice for decades. This controversy centers on concerns over the ecological harm caused by DDT relative to the gains in public health from its use to prevent malaria. Given the World Health Organization's recent policy decisions concerning the use of DDT to control malaria, it is worth reviewing the historical context of DDT use. Ecological concerns focused on evidence that DDT ingestion by predatory birds resulted in eggs with shells so thin they were crushed by adult birds. In addition, DDT spraying to control malaria allegedly resulted in cats being poisoned in some areas, which led to increased rodent populations and, in turn, the parachuting of cats into the highlands of the island of Borneo to kill the rodents, a story that influenced the decision to ban DDT spraying. I focus on this story with the intention of grounding the current debate on lessons from the past.     

Malaria control in Iran--present and future

The malaria eradication campaign in Iran, which started in 1958, has not been able to achieve its final goals. The technical, administrative, socio-economic and financial obstacles involved in this unfinished task are mentioned and the present status of malaria in the country is discussed. It is urged that eradication policy, presently used, be substituted by malaria control program, as defined by The World Health Organization. This would serve as a prerequisite for eventual eradication of malaria, from the country, in the future. Within such agreement, the improvement of basic health services and search for better technical means of controlling the transmission of the infection are emphasized as vital to achieve this goal. Intensive training of experienced staff, in Iran, for stimulation and promotion of relevant research and training activities in malaria control is highly recommended.     

Water-related vector-borne diseases

Land planning and engineering before construction can do much to control the water-related, vector-borne diseases schistosomiasis, malaria and filariasis. An example of control through land planning is buffer strips between habitations and water sources. Engineering controls involve regulation of water drainage and flow. The best way to control schistosomiasis, which is transmitted by human feces and urine released into freshwater, is to provide sanitation. In addition, it is helpful to speed the flow rate of streams, and to clear aquatic vegetation from irrigation canals. Engineering to control malaria means draining or filling areas that tend to collect water, especially if wastewater collects there. This will aid the usual malaria control techniques such as spraying houses, using bed nets taking prophylactic medication, and clearing refuse that can retain standing water. Filariasis, also spread by mosquitos, can be controlled by eliminating standing or slow-moving streams of contaminated water, speeding its flow rate, and providing sanitation to keep water clean, and latrines that do not flood. The health implications of development must be addressed before construction, not by more expensive vector control afterward.     

Genetic structure of Plasmodium falciparum and elimination of malaria, Comoros archipelago

The efficacy of malaria control and elimination on islands may depend on the intensity of new parasite inflow. On the Comoros archipelago, where falciparum malaria remains a major public health problem because of spread of drug resistance and insufficient malaria control, recent interventions for malaria elimination were planned on Moheli, 1 of 4 islands in the Comoros archipelago. To assess the relevance of such a local strategy, we performed a population genetics analysis by using multilocus microsatellite and resistance genotyping of Plasmodium falciparum sampled from each island of the archipelago. We found a contrasted population genetic structure explained by geographic isolation, human migration, malaria transmission, and drug selective pressure. Our findings suggest that malaria elimination interventions should be implemented simultaneously on the entire archipelago rather than restricted to 1 island and demonstrate the necessity for specific chemoresistance surveillance on each of the 4 Comorian islands.     

Effects of suspended residual spraying and of imported malaria on malaria control in the USA

The activities of the National Malaria Eradication Programme, a co-operative campaign inaugurated in July 1947 by the United States Public Health Service and certain State and local health agencies, are outlined. Control operations reached their maximal level in 1948, when 1,364,950 dwellings in 13 "malarious" States were sprayed with residual DDT, and the percentage of mosquito control achieved was 83.2.In 1950, only 2,227 cases of malaria were reported, as compared with 16,203 in 1947 and 9,797 in 1948. But the return of infected servicemen from Korea caused a temporary increase in the incidence in 1951 and 1952, when the totals were 5,600 and 7,023, respectively. In 1953, however, only 559 civilian cases were reported; of the cases appraised, 28 were of local origin, and, of these, at least 24 are known to have been infected in 1952.The Public Health Service ceased active participation in the Programme in 1951, but continued to give technical advice. At the same time, State authorities received Federal support in activating malaria surveillance-and-prevention programmes. More-selective anti-anopheline activities have replaced residual insecticide spraying, which is now carried out in only a few isolated areas. It is believed that these measures have prevented imported malaria from increasing the diminishing incidence of primary indigenous cases in the USA.