Piperonyl butoxide (PBO) combined with pyrethroids in long‐lasting insecticidal nets (LLINs) to prevent malaria in Africa
Referencias
Additional references
| WHOPES Phase | Definition |
| WHOPES Phase I. Laboratory bioassays | Cone bioassays: these are studies that are conducted in the laboratory setting and use standard WHO protocols (WHOPES 2013, Section 2.2.1), where mosquitoes are exposed to a suitable LLIN (treated intervention or untreated control) for three minutes using a standard plastic WHO cone. Following net exposure, mosquitoes are transferred to a holding container and maintained on a sugar solution diet while entomological outcomes (mosquitoes knocked down one hour post‐exposure, and mosquito mortality 24 hours post‐exposure) are measured. Tunnel tests: these are studies conducted in the laboratory setting that use standard WHO protocols (WHOPES 2013, Section 2.2.2). Mosquitoes are released into a glass tunnel covered at each end with untreated netting. The intervention or control LLIN net sample is placed one‐third down the length of the tunnel and the net contains nine holes that enable mosquitoes to pass through. A suitable bait is immobilized in the shorter section of the tunnel where it is available for mosquito biting. Mosquitoes are released into the opposite end of the tunnel and must make contact with the net and locate holes before being able to feed on the bait. After 12 to 15 hours, mosquitoes are removed from both sections of the tunnel and entomological outcomes (the number of mosquitoes in each section, mortality, and blood‐feeding inhibition at the end of the assay and 24 hours post‐exposure) are recorded. Wire‐ball bioassays: these are studies conducted in the laboratory setting where mosquitoes are introduced into a wire‐ball frame that has been covered with either the intervention or control LLIN. Mosquitoes are exposed for three minutes, after which they are transferred to a holding container and entomological outcomes (mosquitoes knocked down one hour post‐exposure, and mosquito mortality 24 hours post‐exposure) are measured. |
| WHOPES Phase II. Experimental hut trials | WHOPES Phase II experimental hut trials are field trial studies conducted in Africa where wild mosquito populations or local colonized populations are evaluated. Volunteers or livestock sleep in experimental huts under a purposefully holed LLIN, with one person or animal per hut. Huts are designed to resemble local housing based on a West or East African design (WHOPES 2013; Section 3.3.1‐2). However they have identical design features, such as eave gaps or entry slits to allow mosquitoes to enter, and exit traps to capture exiting mosquitoes. LLINs and volunteers are randomly allocated to huts and rotated in a Latin square to avoid bias, with huts cleaned between rotations to avoid contamination. Several nets, including an untreated control net, can be tested at the same time. Dead and alive mosquitoes are collected each morning from inside the net, inside the hut, and inside the exit traps. They are then scored as either blood‐fed or non‐blood‐fed, and either alive or dead, and live mosquitoes are maintained for a further 24 hours to assess delayed mosquito mortality. |
| WHOPES Phase III. Village trials | WHOPES Phase III village trials are village trials conducted in Africa where wild mosquito populations are evaluated. Villages chosen to be included in the study are similar in terms of size, housing structure, location, and the data available on the insecticide resistance status of the local malaria vectors. Households are assigned either conventional LLINs or PBO‐LLINs. Randomization can be at the household or village level. Adult mosquitoes are collected from the study houses and mosquito density is measured. An indication of malaria transmission is measured in the study sites either by recording infections in mosquitoes, malaria prevalence, or malaria incidence. |
| Product name | Product type | Status of WHO recommendation |
| DawaPlus 2.0 | Deltamethrin coated on polyester | Interim |
| DawaPlus 3.0 | Combination of deltamethrin coated onto polyester (side panels), and deltamethrin and PBO incorporated into polyester (roof) | Interim |
| DawaPlus 4.0 | Deltamethrin and PBO incorporated into polyester | Interim |
| Duranet | Alpha‐cypermethrin incorporated into polyethylene | Full |
| Interceptor | Alpha‐cypermethrin coated on polyester | Full |
| LifeNet | Deltamethrin incorporated into polypropylene | Interim |
| MAGNet | Alpha‐cypermethrin incorporated into polyethylene | Full |
| MiraNet | Alpha‐cypermethrin incorporated into polyethylene | Interim |
| Olyset Net | Permethrin incorporated into polyethylene | Full |
| Olyset Plus | Permethrin and PBO incorporated into polyethylene | Interim |
| Panda Net 2.0 | Deltamethrin incorporated into polyethylene | Interim |
| PermaNet 2.0 | Deltamethrin coated on polyester | Full |
| PermaNet 3.0 | Combination of deltamethrin coated on polyester with strengthened border (side panels), and deltamethrin and PBO incorporated into polyethylene (roof) | Interim |
| Royal Sentry | Alpha‐cypermethrin incorporated into polyethylene | Full |
| SafeNet | Alpha‐cypermethrin coated on polyester | Full |
| Veeralin | Alpha‐cypermethrin and PBO incorporated into polyethylene | Interim |
| Yahe | Deltamethrin coated on polyester | Interim |
| Yorkool | Deltamethrin coated on polyester | Full |
| Abbreviations: LLIN: long‐lasting insecticidal net; WHO: World Health Organization. | ||
| Insecticide | Formulation1 | Dosage2 |
| Alpha‐cypermethrin | SC 10% | 20 to 40 |
| Cyfluthrin | EW 5% | 50 |
| Deltamethrin | SC 1% | 15 to 25 |
| Etofenprox | EW 10% | 200 |
| Lambda‐cyhalothrin | CS 2.5% | 10 to 15 |
| Permethrin | EC 10% | 200 to 500 |
| 1Abbreviations: EC: emulsifiable concentrate; EW: emulsion, oil in water; CS: capsule suspension; SC: suspension concentrate; WT: water dispersible tablet. | ||
| Outcome | Confirmed resistance | Suspected resistance | Susceptible | Unclassified |
| WHO mosquito mortality | < 90% | 90% to 97 % | 98% to 100% | Unknown |
| CDC knock‐down | < 90% | 80% to 97% | 98% to 100% | Unknown |
| Abbreviations: CDC: Centers for Disease Control and Prevention; WHO: World Health Organization. Definition of resistance level based on mosquito mortality (%) after exposure to insecticide in a WHO diagnostic dose assay (WHO mosquito mortality), or a CDC bottle bioassay (CDC knock‐down) using the methodology, diagnostic doses, and diagnostic times recommended by each test respectively. | ||||
| Outcome | Low | Moderate | High | Unclassified |
| Mosquito mortality1 | 61% to 90% | 31% to 60% | < 30% | Unknown |
| 124‐hour post‐exposure mortality (%). | ||||
| Criteria | Assessment | Comments | ||
| Yes | No | Unclear | ||
| Mosquito population | ||||
| Did the study test Anopheles gambiae complex or Anopheles funestus group mosquitoes? | ↓ | — | ↓ | State mosquito species |
| Were a minimum of 50 mosquitoes tested per study arm? | ↓ | — | ↓ | |
| Intervention | ||||
| Did the study include an long‐lasting insecticidal net (LLIN) or insecticide treated net (ITN)? | ↓ | — | ↓ | State net LLIN or ITN |
| Was the intervention net either of the following?
| ↓ | — | ↓ | State net type |
| Was the control net either of the following?
| ↓ | — | ↓ | State which objective study meets |
| Study design | ||||
| Was the study one of the following?
| ↓ | — | ↓ | State study type |
| For laboratory bioassay. Did the study use standard‐WHO protocol? | ↓ | — | ↓ | |
| For experimental hut study and village trial. Was the study conducted in Africa? | ↓ | — | ↓ | State country |
| Outcome | ||||
| Did the study include at least one of the following outcome measures?
| ↓ | — | ↓ | |
| Decision | ||||
| Is the study eligible for inclusion? | — | — | ↓ | State reason(s) for exclusion |
| Discuss with authors | ||||
