BackgroundPublic health strategies that target mosquito vectors, particularly pyrethroid long‐lasting insecticidal nets (LLINs), have been largely responsible for the substantial reduction in the number of people in Africa developing malaria. The spread of insecticide resistance in Anopheles mosquitoes threatens these impacts. One way to control insecticide‐resistant populations is by using insecticide synergists. Piperonyl butoxide (PBO) is a synergist that inhibits specific metabolic enzymes within mosquitoes and has been incorporated into pyrethroid‐LLINs to form pyrethroid‐PBO nets. Pyrethroid‐PBO nets are currently produced by four LLIN manufacturers and, following a recommendation from the World Health Organization (WHO) in 2017, are being included in distribution campaigns in countries. This review examines epidemiological and entomological evidence on whether the addition of PBO to LLINs improves their efficacy.Objectives1. Evaluate whether adding PBO to pyrethroid LLINs increases the epidemiological and entomological effectiveness of the nets.2. Compare the effects of pyrethroid‐PBO nets currently in commercial development or on the market with their non‐PBO equivalent in relation to:a. malaria infection (prevalence or incidence); b. entomological outcomes.Search methodsWe searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register; CENTRAL, MEDLINE, Embase, Web of Science, CAB Abstracts, and two clinical trial registers (ClinicalTrials.gov and WHO International Clinical Trials Registry Platform) up to 24 August 2018. We contacted organizations for unpublished data. We checked the reference lists of trials identified by the above methods.Selection criteriaWe included laboratory trials, experimental hut trials, village trials, and randomized clinical trials with mosquitoes from the Anopheles gambiae complex or Anopheles funestus group.Data collection and analysisTwo review authors assessed each trial for eligibility, extracted data, and determined the risk of bias for included trials. We resolved disagreements through discussion with a third review author. We analysed the data using Review Manager 5 and assessed the certainty of the evidence using the GRADE approach.Main resultsFifteen trials met the inclusion criteria: two laboratory trials, eight experimental hut trials, and five cluster‐randomized controlled village trials.One village trial examined the effect of pyrethroid‐PBO nets on malaria infection prevalence in an area with highly pyrethroid‐resistant mosquitoes. The latest endpoint at 21 months post‐intervention showed that malaria prevalence probably decreased in the intervention arm (OR 0.40, 95% CI 0.20 to 0.80; 1 trial, 1 comparison, moderate‐certainty evidence).In highly pyrethroid‐resistant areas (< 30% mosquito mortality), in comparisons of unwashed pyrethroid‐PBO nets to unwashed standard‐LLINs, PBO nets resulted in higher mosquito mortality (risk ratio (RR) 1.84, 95% CI 1.60 to 2.11; 14,620 mosquitoes, 5 trials, 9 comparisons, high‐certainty evidence) and lower blood feed...

Background Mass drug administration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission. Objectives To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA‐associated adverse events. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings. Selection criteria Cluster‐randomized trials and non‐randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before‐and‐after studies comparing post‐MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub‐populations (for example, pregnant women, children or infants) were excluded. Data collection and analysis Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co‐administration of 8‐aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach. Main results Two cluster‐randomized trials, eight non‐randomized controlled studies and 22 uncontrolled before‐and‐after studies are included in this review. Twenty‐two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were conducted in areas of low endemicity (≤5%), 12 in areas of moderate endemicity (6‐39%) and 15 in areas of high endemicity (≥ 40%). Ten studies evaluated MDA plus other vector control measures. The studies used a wide variety of MDA regimens incorporating different drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now more than 30 years old. Areas of low endemicity ( ≤5 %) Within the first month post‐MDA, a single uncontrolled before‐and‐after study conducted in 1955 on a small Taiwanese island reported a much lower prevalence of parasitaemia following a single course of chloroquine compared to baseline (1 study, very low quality evidence ). This lower parasite prevalence was still present after more than 12 months (one study, very low quality evidence ...

Metronomic chemotherapy in this patient population is feasible and shows encouraging preliminary results, especially in patients with metastatic disease who have not received craniospinal radiation. Further investigation of this strategy in newly diagnosed patients with CNS tumors is warranted.

Background The 8‐aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low‐transmission areas or those with artemisinin resistance. This replaced the previous recommendation of 0.75 mg/kg, aiming to reduce haemolysis risk in people with glucose‐6‐phosphate dehydrogenase deficiency, common in people living in malarious areas. Whether this approach, and at this dose, is effective in reducing transmission is not clear. Objectives To assess the effects of single dose or short‐course PQ (or an alternative 8AQ) alongside treatment for people with P. falciparum malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; and the WHO International Clinical Trials Registry Platform (ICRTP) portal using ‘malaria*', ‘falciparum', ‘primaquine', ‘8‐aminoquinoline', and eight 8AQ drug names as search terms. We checked reference lists of included trials, and contacted researchers and organizations. Date of last search: 21 July 2017. Selection criteria Randomized controlled trials (RCTs) or quasi‐RCTs in children or adults, adding PQ (or alternative 8AQ) as a single dose or short course alongside treatment for P. falciparum malaria. Data collection and analysis Two authors screened abstracts, applied inclusion criteria, and extracted data. We sought evidence on transmission (community incidence), infectiousness (people infectious and mosquitoes infected), and potential infectiousness (gametocyte measures assessed by microscopy or polymerase chain reaction [PCR]). We grouped trials into artemisinin and non‐artemisinin treatments, and stratified by PQ dose (low, 0.2 to 0.25 mg/kg; moderate, 0.4 to 0.5 mg/kg; high, 0.75 mg/kg). We used GRADE, and absolute effects of infectiousness using trial control groups. Main results We included 24 RCTs and one quasi‐RCT, comprising 43 arms. Fourteen trials evaluated artemisinin treatments (23 arms), nine trials evaluated non‐artemisinin treatments (13 arms), and two trials included both artemisinin and non‐artemisinin arms (three and two arms, respectively). Two trial arms used bulaquine. Seven PQ arms used low dose (six with artemisinin), 11 arms used moderate dose (seven with artemisinin), and the remaining arms used high dose. Fifteen trials tested for G6PD status: 11 excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and three included all, irrespective of status. The remaining 10 trials either did not test or did not report on testing. No cluster trials ev...

BackgroundInsecticide‐treated nets (ITNs) and indoor residual spraying (IRS) are used to control malaria vectors. Both strategies use insecticides to kill mosquitoes that bite and rest indoors. For ITNs, the World Health Organization (WHO) only recommended pyrethroids until 2018, but mosquito vectors are becoming resistant to this insecticide. For IRS, a range of insecticides are recommended. Adding IRS to ITNs may improve control, simply because two interventions may be better than one; it may improve malaria control where ITNs are failing due to pyrethroid resistance; and it may slow the emergence and spread of pyrethroid resistance.ObjectivesTo summarize the effect on malaria of additionally implementing IRS, using non‐pyrethroid‐like or pyrethroid‐like insecticides, in communities currently using ITNs.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; LILACS; the WHO International Clinical Trials Registry Platform; ClinicalTrials.gov; and the ISRCTN registry up to 18 March 2019.Selection criteriaCluster‐randomized controlled trials (cRCTs), interrupted time series (ITS), or controlled before‐and‐after studies (CBAs) comparing IRS plus ITNs with ITNs alone.Data collection and analysisTwo review authors independently assessed trials for eligibility, analyzed risk of bias, and extracted data. We used risk ratio (RR) and 95% confidence intervals (CI). We stratified by type of insecticide, ‘pyrethroid‐like’ and ‘non‐pyrethroid‐like’; the latter could improve malaria control better than adding IRS insecticides that have the same way of working as the insecticide on ITNs (‘pyrethroid‐like'). We used subgroup analysis of ITN usage in the trials to explore heterogeneity. We assessed the certainty of evidence using the GRADE approach.Main resultsSix cRCTs (eight comparisons) met our inclusion criteria conducted since 2008 in sub‐Saharan Africa. Malaria transmission in all sites was from mosquitoes belonging to the Anopheles gambiae s.l. complex species; two trials in Benin and Tanzania also reported the vector Anopheles funestus. Three trials used insecticide with targets different to pyrethroids (two used bendiocarb and one used pirimiphos‐methyl); two trials used dichloro‐diphenyl‐trichlorethane (DDT), an insecticide with the same target as pyrethroids; and one trial used both types of insecticide (pyrethroid deltamethrin in the first year, switching to bendiocarb for the second‐year). ITN usage was greater than 50% in three trials, and less than 50% in the remainder.Indoor residual spraying using ‘non‐pyrethroid‐like' insecticidesAdding IRS with a non‐pyrethroid‐like insecticide had mixed results. Overall, we do not know if the addition of IRS impacted on malaria incidence (rate ratio 0.93, 95% CI 0.46 to 1.86; 2 cRCTs, 566 child‐years; very low‐certainty evidence); it may have reduced malaria parasite prevalence (0.67, 95% CI 0.35 to 1.28; 5 comparisons from 4 cRCTs, 10,440 participants; low‐certainty e...