Jo Lines

Experimental hut trials of permethrin‐impregnated mosquito nets and eave curtains against malaria vectors in Tanzania

ABSTRACT. Permethrin impregnated netting was tested against Tanza‐nian populations of Anopheles arabiensis Patton, An.gambiae Giles and An.funestus Giles in experimental huts fitted with traps to catch samples of the mosquitoes exiting during the night. Treated bednets killed some mosquitoes and increased the tendency of survivors to exit during the night. Treated cotton did not perform so well as treated nylon bednets. An impregnated bednet in which holes had been cut, to simulate a torn net, reduced the number of mosquitoes which fed and survived approximately as well as an intact untreated net. Treated curtains around the eaves of experimental huts did not perform so well as bednets but caused considerable reductions in the number of mosquitoes which fed and survived. However, there was no such effect when treated netting was placed around the eaves of a dwelling house. When one child slept under a treated net and another slept outside the net in the same hut, the number of bites on the latter child was less than if neither child had been under a net. Various aspects of the applicability of permethrin impregnated nets on a community basis are discussed.

Trial of pyrethroid impregnated bednets in an area of Tanzania holoendemic for malaria. Part 2. Effects on the malaria vector population.

The malaria vector population consisted mainly of Anopheles gambiae s.s. with a small contribution from An. funestus and An. rivulorum. The mosquitoes coming to bite in bedrooms were monitored with light traps set beside untreated bednets. When impregnated bednets were provided for all the other beds in a village the Anopheles populations declined but the Culex quinquefasciatus populations were unaffected. The survival of An. gambiae (as measured by the mean number of ovarian dilatations) and the sporozoite rate declined following introduction of the nets and the estimated sporozoite inoculation rates into people not under their nets declined by more than 90%. The net introductions caused sharp declines in the number of mosquitoes resting indoors, but the evidence was inconclusive regarding diversion to outdoor resting, animal biting, earlier biting or outdoor biting. DDT spraying greatly reduced the Anopheles populations.

A Research Agenda for Malaria Eradication: Vector Control

Different challenges are presented by the variety of malaria transmission environments present in the world today. In each setting, improved control for reduction of morbidity is a necessary first step towards the long-range goal of malaria eradication and a priority for regions where the disease burden is high. For many geographic areas where transmission rates are low to moderate, sustained and well-managed application of currently available tools may be sufficient to achieve local elimination. The research needs for these areas will be to sustain and perhaps improve the effectiveness of currently available tools. For other low-to-moderate transmission regions, notably areas where the vectors exhibit behaviours such as outdoor feeding and resting that are not well targeted by current strategies, new interventions that target predictable features of the biology/ecologies of the local vectors will be required. To achieve elimination in areas where high levels of transmission are sustained by very efficient vector species, radically new interventions that significantly reduce the vectorial capacity of wild populations will be needed. Ideally, such interventions should be implemented with a one-time application with a long-lasting impact, such as genetic modification of the vectorial capacity of the wild vector population.

MONITORING HUMAN BITING MOSQUITOES (DIPTERA: CULICIDAE) IN TANZANIA WITH LIGHT TRAPS HUNG BESIDE MOSQUITO NETS

Mosquitoes were caught in bedrooms in Tanzanian villages by human-biting catches and in light-traps set close to occupied untreated bed nets. Catches by each method were carried out on pairs of nights in the same week at different seasons and in different villages. The pairs of adjacent catches by the different methods showed a strong correlation. Analysis of the ratio between the catches by the two methods on pairs of nights in the same week indicated that on average three light-traps caught about the same number of mosquitoes as a team of two human catchers. The ratio did not differ significantly between Anopheles gambiae Giles ( sensu lato ), A. funestus Giles, and Culex quinquefasciatus Say, nor between the villages, or between times when mosquito populations were high or low. The distribution of numbers of ovarian dilatations differed significantly between catches in different villages and seasons but not between pairs of catches by the two methods. Similarly, the parity and sporozoite rates agreed between pairs of light-trap and house-resting catches, but differed markedly between villages and seasons. Thus it is concluded that light-traps used in conjunction with bed nets catch a representative sample of the vectors which would have bitten humans in bedrooms in this area.

Seasonal intermittent preventive treatment with artesunate and sulfadoxine-pyrimethamine for prevention of malaria in Senegalese children: a randomised placebo-controlled double-blind trial.

BACKGROUND In the Sahel and sub-Sahelian regions of Africa, malaria transmission is highly seasonal. During a short period of high malaria transmission, mortality and morbidity are high in children under age 5 years. We assessed the efficacy of seasonal intermittent preventive treatment-a full dose of antimalarial treatment given at defined times without previous testing for malaria infection. METHODS We did a randomised, placebo-controlled, double-blind trial of the effect of intermittent preventive treatment on morbidity from malaria in three health-care centres in Niakhar, a rural area of Senegal. 1136 children aged 2-59 months received either one dose of artesunate plus one dose of sulfadoxine-pyrimethamine or two placebos on three occasions during the malaria transmission season. The primary outcome was a first or single episode of clinical malaria detected through active or passive case detection. Primary analysis was by intention-to-treat. This study is registered with , number NCT00132561. FINDINGS During 13 weeks of follow-up, the intervention led to an 86% (95% CI 80-90) reduction in the occurrence of clinical episodes of malaria. With passive case detection, protective efficacy against malaria was 86% (77-92), and when detected actively was 86% (78-91). The incidence of malaria in children on active drugs was 308 episodes per 1000 person-years at risk, whereas in those on placebo it was 2250 episodes per 1000 person-years at risk. 13 children were not included in the intention-to-treat analysis, which was restricted to children who received a first dose of antimalarial or placebo. There was an increase in vomiting in children who received the active drugs, but generally the intervention was well tolerated. INTERPRETATION Intermittent preventive treatment could be highly effective for prevention of malaria in children under 5 years of age living in areas of seasonal malaria infection.

An estimation of the entomological inoculation rate for Ifakara: a semi-urban area in a region of intense malaria transmission in Tanzania.

Summary An entomological study on vectors of malaria and their relative contribution to Plasmodium falciparum transmission in the semi‐urban area of Ifakara, south‐eastern Tanzania, was conducted. A total of 32 houses were randomly sampled from the area and light trap catches (LTC) performed in one room in each house every 2 weeks for 1 year. A total of 147 448 mosquitoes were caught from 789 LTC; 26 134 Anopheles gambiae s.l., 615 A. funestus, 718 other anophelines and 119 981 culicines. More than 60% of the total A. gambiae s.l. were found in five (0.6%) LTCs, with a maximum of 5889 caught in a single trap. Of 505 A. gambiae s.l. speciated by polymerase chain reaction, 91.5% were found to be A. arabiensis. Plasmodium falciparum sporozoite enzyme‐linked immunosorbent assay tests were performed on 10 108 anopheles mosquitoes and 39 (0.38%) were positive. Entomological inoculation rate (EIR) estimates were generated using a standard method and an alternative method that allows the calculation of confidence intervals based on a negative binomial distribution of sporozoite positive mosquitoes. Overall EIR estimates were similar; 31 vs. 29 [95% confidence interval (CI): 19, 44] infectious bites per annum, respectively. The EIR ranged from 4 (95% CI: 1, 17) in the cool season to 108 (95% CI: 69, 170) in the wet season and from 54 (95% CI: 30, 97) in the east of the town to 15 (95% CI: 8, 30) in the town centre. These estimates show large variations over short distances in time and space. They are all markedly lower than those reported from nearby rural areas and for other parts of Tanzania.

Multi‐country field trials comparing wash‐resistance of PermaNet™ and conventional insecticide‐treated nets against anopheline and culicine mosquitoes

Abstract.  Insecticide‐treated bednets (ITNs) are commonly used as a means of personal protection from malaria transmission by anopheline mosquitoes (Diptera: Culicidae). Long‐lasting insecticidal nets (LLINs) have special treatments intended to remain effective after many washes. The present trials assessed the efficacy and wash‐resistance of several production batches of PermaNet™ (polyester net coated with polymer resin containing pyrethroid insecticide deltamethrin 55 mg ai/m2) against malaria vectors in Pakistan, Iran and Tanzania compared to ITNs conventionally treated with alphacypermethrin 15 or 20 mg ai/m2, or deltamethrin 25 or 50 mg ai/m2. Insecticidal efficacy of the nets before and after repeated washing (using W.H.O. recommended and traditional local washing procedures) was monitored through contact bioassays with Anopheles and by experimental hut and outdoor platform tests. Local washing regimes gradually reduced the insecticidal efficacy of conventionally treated nets, but they were not exhausted, even after 21 washes. Using a more rigorous laboratory washing method, insecticide was more readily stripped from conventionally treated nets. PermaNet retained high efficacy after 21 washes, giving more than 97% mortality of Anopheles in contact bioassays with 3‐min exposure. Using the more sensitive bioassay criterion of ‘median time to knockdown’, PermaNet showed no loss of insecticidal activity against Anopheles after washing repeatedly in 2 out of 6 trials; whereas in a further three trials knockdown activity of PermaNet and conventional ITNs declined at comparable rates. Higher mortality levels of Anopheles in contact bioassays did not always translate to superiority in experimental hut or enclosed platform trials. In only one of four comparative field trials did PermaNet out‐perform conventional ITNs after washing: this was in the trial of PermaNet 2.0 – the product with improved quality assurance. Because PermaNet and conventionally treated nets were both quite tolerant of local washing procedures, it is important in field trials to compare LLINs with conventional ITNs washed an equivalent number of times. Our comparison of PermaNet 2.0 against conventionally treated deltamethrin nets (CTDN) in Pakistan demonstrated superior performance of the LLIN after 20 washes in phase I and phase II bioassays, and this was corroborated by chemical assays of residual deltamethrin. Although PermaNet 2.0 has received WHOPES interim recommendation for malaria control purposes, its performance should be monitored in everyday use throughout its lifespan in various cultural settings to assess its durability and long‐term effectiveness for malaria prevention and control. As many millions of conventionally treated nets are already in routine use, and these will require regular re‐treatment, programme strategies should be careful to preserve the effectiveness of ITNS before and after establishing the reliability of LLINs in long‐term use.

Insecticide-treated nets

Insecticide-treated nets (ITNs) are the most powerful malaria control tool to be developed since the advent of indoor residual spraying (IRS) and chloroquine in the 1940s, and as such they have been an important component of global and national malaria control policies since the mid-1990s. Yet a decade later, coverage is still unacceptably low: only 3% of African children are currently sleeping under an ITN, and only about 20% are sleeping under any kind of net. This review charts the scientific, policy and programmatic progress of ITNs over the last 10 years. Available evidence for the range of programmatic delivery mechanisms used at country level is presented alongside the key policy debates that together have contributed to the evolution of ITN delivery strategies over the past decade. There is now global consensus around a strategic framework for scaling up ITN usage in Africa, which recognizes a role for both the public sector (targeting vulnerable groups to promote equity) and the private sector (sustainable supply). So, while progress with increasing coverage to date has been slow, there is now global support for the rapid scale-up of ITNs among vulnerable groups by integrating ITN delivery with maternal and child health programmes (and immunization in particular), at the same time working with the private sector in a complementary and supportive manner to ensure that coverage can be maintained for future generations of African children.

Mosquito nets and insecticides for net treatment: a discussion of existing and potential distribution systems in Africa

Mosquito nets treated with pyrethroid insecticides can provide African children with a remarkable degree of protection against malaria, and more generally against death before the age of five. In a series of field trials just completed, the introduction of treated nets has been associated with reductions in all-cause child mortality of 17% in Ghana, 33% in Kenya, and 63% and 25% in two separate trials in The Gambia (Binka et al. 1996; Nevi11 et al. 1996; Alonso et al. 1993b; D’Alessandro et al. 1 9 9 5 4 . I t is not yet clear that in the intense transmission conditions of Africa, the long-term benefits will be quite so great. A decline in exposure may lead to a decline in immunity; this is not likely to leave overall levels of disease higher than before, but may cause the burden of disease to be shifted to older age-groups (Lines & Armstrong 1992; Snow & Marsh 1995). Such doubts have recently been reinforced by observations in Senegal (Trape & Rogier 1996). Thus, despite the impressive shortterm results, the evidence i s not yet strong enough to stop asking questions about efficacy. It is, however, enough to start asking what can be done to promote wider access to this technology (Lengeler et al. 1996a). This article was written primarily for those involved in public health who are planning, in one way or another, to further this goal, and it i s intended as an introduction to the issues that must be considered. It i s one point of view; other useful suggestions, and more technical details, may be found in the recent and useful reviews by Carnevale and Coosemans (1996), Coosemans and Carnevale ( r996) , and in those edited by Lengeler et al. ( I 9 9 6 b ) .

A trial of the efficacy, safety and impact on drug resistance of four drug regimens for seasonal intermittent preventive treatment for malaria in Senegalese children.

Summary In the Sahel, most malaria deaths occur among children 1–4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives. Methods 2102 children aged 6–59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP. Findings The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76–1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30–0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group. Conclusions Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria. Trial Registration Clinicaltrials.gov NCT00132548