BACKGROUND: Primary malaria prevention on a large scale depends on two vector control interventions: indoor residual spraying (IRS) and insecticide-treated mosquito nets (ITNs). Historically, IRS has reduced malaria transmission in many settings in the world, but the health effects of IRS have never been properly quantified. This is important, and will help compare IRS with other vector control interventions. OBJECTIVES: To quantify the impact of IRS alone, and to compare the relative impacts of IRS and ITNs, on key malariological parameters. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (September 2009), CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to September 2009), EMBASE (1974 to September 2009), LILACS (1982 to September 2009), mRCT (September 2009), reference lists, and conference abstracts. We also contacted researchers in the field, organizations, and manufacturers of insecticides (June 2007). SELECTION CRITERIA: Cluster randomized controlled trials (RCTs), controlled before-and-after studies (CBA) and interrupted time series (ITS) of IRS compared to no IRS or ITNs. Studies examining the impact of IRS on special groups not representative of the general population, or using insecticides and dosages not recommended by the World Health Organization (WHO) were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed trials for inclusion. Two authors extracted data, assessed risk of bias and analysed the data. Where possible, we adjusted confidence intervals (CIs) for clustering. Studies were grouped into those comparing IRS with no IRS, and IRS compared with ITNs, and then stratified by malaria endemicity. MAIN RESULTS: IRS versus no IRSStable malaria (entomological inoculation rate (EIR) 1): Two studies; for incidence and prevalence, the malaria rates were higher in the IRS group compared to the ITN group in one study. Malaria incidence was higher in the IRS arm in India (risk ratio IRS:ITN = 1.48) and in South Africa (risk ratio 1.34 but the cluster unadjusted CIs included 1). For malaria prevalence, ITNs appeared to give better protection against any infection compared to IRS in India (risk ratio IRS:ITN = 1.70) and also for both P. falciparum (risk ratio IRS:ITN = 1.78) and P. vivax (risk ratio IRS:ITN = 1.37). AUTHORS' CONCLUSIONS: Historical and programme documentation has clearly established the impact of IRS. However, the number of high-quality trials are too few to quantify the size of effect in different transmission settings. The evidence from randomized comparisons of IRS versus no IRS confirms that IRS reduces malaria incidence in unstable malaria settings, but randomized trial data from stable malaria settings is very limited. Some limited data suggest that ITN give better protection than IRS in unstable areas, but more trials are needed to compare the effects of ITNs with IRS, as well as to quantify their combined effects

Indoor residual spraying for preventing malaria

The precise function of eosinophils in parasitic infection in vivo remains poorly understood despite eosinophils having been shown to be potent effectors in killing parasites in vitro. Although it has long been held that the primary function of the eosinophil is protection against helminth parasites, there are little data to prove this unequivocally. Moreover, eosinophils are responsible for a considerable amount of inflammatory pathology accompanying helminth infections. This article will provide an overview of our current knowledge about eosinophils and their role, both protective and pathogenetic, in parasitic helminth infections.

The role of eosinophils in host defense against helminth parasites

Mass drug administration (MDA) was a component of many malaria programs during the eradication era, but later was seldomly deployed due to concerns regarding efficacy and feasibility and fear of accelerating drug resistance. Recently, however, there has been renewed interest in the role of MDA as an elimination tool. Following a 2013 Cochrane Review that focused on the quantitative effects of malaria MDA, we have conducted a systematic, qualitative review of published, unpublished, and gray literature documenting past MDA experiences. We have also consulted with field experts, using their historical experience to provide an informed, contextual perspective on the role of MDA in malaria elimination. Substantial knowledge gaps remain and more research is necessary, particularly on optimal target population size, methods to improve coverage, and primaquine safety. Despite these gaps, MDA has been used successfully to control and eliminate Plasmodium falciparum and P. vivax malaria in the past, and should be considered as part of a comprehensive malaria elimination strategy in specific settings.

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Review of Mass Drug Administration for Malaria and Its Operational Challenges

Diethylcarbamazine (DEC) is an effective microfilaricidal drug against Wuchereria bancrofti, Brugia malayi, and Brugia timori--the three lymphatic-dwelling filariae infecting humans. However, effectiveness in killing the adult stage of these parasites has been more difficult to establish. The present review of available evidence from the literature suggests that: (1) in addition to being a microfilaricidal agent, DEC in conventional dosages effectively kills adult worms of these three parasites in many patients; (2) relatively high total dosages of DEC (including dosages considerably in excess of those currently recommended) generally give better long-term therapeutic results than lower dosages; (3) spaced doses of DEC (weekly or monthly) are more effective than the same total dosage given in consecutive daily doses; (4) chronic administration of low-dose DEC, as in medicated salt, can effectively control filariasis caused by W. bancrofti or B. malayi; and (5) rational determination of the DEC regimen ideal for the killing of adult filarial parasites awaits the development of assays capable of sensitively detecting the presence of living adult parasites.

Efficacy of diethylcarbamazine in eradicating infection with lymphatic-dwelling filariae in humans.

Background Studies evaluating mass drug administration (MDA) in malarious areas have shown reductions in malaria immediately following the intervention. However, these effects vary by endemicity and are not sustained. Since the 2013 version of this Cochrane Review on this topic, additional studies have been published. Objectives Primary objectives To assess the sustained effect of MDA with antimalarial drugs on: - the reduction in malaria transmission in moderate- to high-transmission settings; - the interruption of transmission in very low- to low-transmission settings. Secondary objective To summarize the risk of drug-associated adverse effects following MDA. Search methods We searched several trial registries, citation databases, conference proceedings, and reference lists for relevant articles up to 11 February 2021. We also communicated with researchers to identify additional published and unpublished studies. Selection criteria Randomized controlled trials (RCTs) and non-randomized studies comparing MDA to no MDA with balanced co-interventions across study arms and at least two geographically distinct sites per study arm. Data collection and analysis Two review authors independently assessed trials for eligibility and extracted data. We calculated relative risk (RR) and rate ratios with corresponding 95% confidence intervals (CIs) to compare prevalence and incidence, respectively, in MDA compared to no-MDA groups. We stratified analyses by malaria transmission and by malaria species. For cluster-randomized controlled trials (cRCTs), we adjusted standard errors using the intracluster correlation coefficient. We assessed the certainty of the evidence using the GRADE approach. For non-randomized controlled before-and-after (CBA) studies, we summarized the data using difference-in-differences (DiD) analyses. Main results Thirteen studies met our criteria for inclusion. Ten were cRCTs and three were CBAs. Cluster-randomized controlled trials Moderate- to high-endemicity areas (prevalence ≥ 10%) We included data from two studies conducted in The Gambia and Zambia. At one to three months after MDA, the Plasmodium falciparum (hereafter, P falciparum) parasitaemia prevalence estimates may be higher compared to control but the CIs included no effect (RR 1.76, 95% CI 0.58 to 5.36; Zambia study; low-certainty evidence); parasitaemia incidence was probably lower (RR 0.61, 95% CI 0.40 to 0.92; The Gambia study; moderate-certainty evidence); and confirmed malaria illness incidence may be substantially lower, but the CIs included no effect (rate ratio 0.41, 95% CI 0.04 to 4.42; Zambia study; low-certainty evidence). At four to six months after MDA, MDA showed little or no effect on P falciparum parasitaemia prevalence (RR 1.18, 95% CI 0.89 to 1.56; The Gambia study; moderate-certainty evidence) and, no persisting effect was demonstrated with parasitaemia incidence (rate ratio 0.91, 95% CI 0.55 to 1.50; The Gambia study). Very low- to low-endemicity areas (prevalence

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Mass drug administration for malaria

Studies on filariasis in Malaya: the vertebrate hosts of Brugia malayi and B. pahangi.

1. 1) An attempt was made to transmit back to man a strain of Brugia malayi originally obtained from man and transmitted through a macaque monkey and thence to a cat. Two volunteers were inoculated with infective larvae of this strain which had developed in Mansonia longipalpis. Neither of these volunteers subsequently developed microfilariae. 2. 2) An attempt was also made to transmit to man a strain of B. pahangi, a species hitherto only known as an infection of animals. Two volunteers were inoculated with infective larvae from Armigeres obturbans which had fed on a cat carrying a strain of B. pahangi originally obtained from a naturally infected civet cat. 3. 3) One of the volunteers inoculated with B. pahangi developed microfilariae 84 days later, and these persisted in small numbers for a further 56 days. The microfilariae resembled B. pahangi morphologically, and the identification was confirmed by mosquito-feeding experiments and by experimental transmission to a cat from which an adult male B. pahangi was later recovered. The other volunteer did not develop microfilariae. 4. 4) All four volunteers suffered from episodes of lymphangitis, lymphadenitis, and oedema in the inoculated limb, starting in each instance about one month after the inoculation. 5. 5) Although there was no true leucocytosis, all four volunteers developed a relative increase in eosinophils with maxima ranging from 18 to 32 per cent. occurring 12 to 13 weeks after the inoculation. 6. 6) All volunteers showed positive complement-fixation tests and skin tests (to Dirofilaria antigen) about 12 weeks after the inoculation. 7. 7) One volunteer from each pair developed subcutaneous nodules in the inoculated arm about 4 months afterwards. 8. 8) The significance of these findings is discussed. B. pahangi must now be regarded as potentially infective to man. The clinical episodes are considered to be reactions to the immature developing worms, whereas the eosinophilia is more probably a response to some product of the adult worms. Subcutaneous nodules do not seem to have been described previously in association with filarial infection.

Experimental transmission of Brugia Malayi and B. Pahangi to man

1. 1) Brugia pahangi occurs naturally in the domestic cat and dog and in several species of forest animals in areas where B. malayi is endemic. 2. 2) Attempts were made to transmit B. pahangi by the direct inoculation of infective larvae to domestic cats, slow loris, macaque monkeys, civet cats, squirrels, tree-shrews and guinea-pigs. Cats, slow loris and civet cats were successfully infected, but no monkeys became infected. 3. 3) The prepatent period in cats varied from 59–83 days. Microfilaria counts rose to high levels and have been maintained for more than 2 1 2 years. 4. 4) The rate of development in the vertebrate host was followed. 5. 5) Feeding experiments with a wide range of mosquitoes showed that Armigeres obturbans is a very efficient host. Mansonia annulatus is also a good host but M. uniformis is less efficient and M. longipalpis is a comparatively poor laboratory host. M. (C.) crassipes, Anopheles barbirostris, A. umbrosus and small numbers of Aedes aegypti and Culex fatigans also supported development to the infective stage. 6. 6) M. longipalpis and M. annulatus were proved to be vectors in nature.

J. F. B. Edeson

Papers

Studies on filariasis in Malaya: the vertebrate hosts of Brugia malayi and B. pahangi.

Experimental transmission of Brugia Malayi and B. Pahangi to man

A preliminary account of the transmission, maintenance and laboratory vectors of Brugia pahangi.

The Experimental Transmission of Wuchereria malayi from Man to Various Animals in Malaya.

The occurrence of two forms of Wuchereria malayi in man