Prevention of mother-to-child transmission of HIV at the second immunization visit: a cross-sectional study, Burkina Faso.

Objective: To evaluate the performance of the cascade of activities for prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) at the second immunization visit in Burkina Faso. Methods: In a cross-sectional study, we recruited mothers attending the second immunization visit for their infant in 20 health centres of Bobo-Dioulasso city, Burkina Faso over 12 months (2019-2020). We administered a short questionnaire to 14 176 mothers and performed HIV serological tests on mothers who had not been tested in the last 3 months. All mothers were asked about their attendance for antenatal care and HIV rapid testing. HIV-infected mothers were also asked about the timing of their HIV diagnosis, antiretroviral therapy, pre-exposure prophylaxis initiation at birth and infant diagnosis of HIV. Findings: Of 14 136 respondents, 13 738 (97.2%) had at least one HIV serological test in their lifetime. Of 13 078 mothers who were never tested or were HIV-negative, 12 454 (95.2%) were tested during or after their last pregnancy. Among HIV-infected mothers already aware of their status, 110/111 (99.1%) women were on antiretroviral therapy. Among HIV-exposed infants, 84/101 (83.2%) babies received 6 weeks of antiretroviral prophylaxis at birth and 58/110 (52.7%) had a blood sample collected for early infant diagnosis. Only two mothers received their child's test results at the time of the second immunization visit. Four mothers were newly diagnosed as HIV-positive during the study. Conclusion: Collecting data at the second immunization visit, a visit rarely missed by mothers, could be useful for identifying gaps in the PMTCT cascade in settings where mothers are difficult to reach, such as in low-income countries with intermediate or low HIV prevalence.

Eliminating postnatal HIV transmission in high incidence areas: need for complementary biomedical interventions.

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies.

Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso.

Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6-8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm). Trial registration number (www.clinicaltrials.gov): NCT03869944. Submission category: Study Design, Statistical Design, Study Protocols.

Targeted application of an organophosphate-based paint applied on windows and doors against Anopheles coluzzii resistant to pyrethroids under real life conditions in Vallée du Kou, Burkina Faso (West Africa).

BACKGROUND: A novel strategy applying an organophosphate-based insecticide paint on doors and windows in combination with long-lasting insecticide-treated nets (LLINs) was tested for the control of pyrethroid-resistant malaria vectors in a village setting in Vallée du Kou, a rice-growing area west of Burkina Faso. METHODS: Insecticide Paint Inesfly 5A IGR™, comprised of two organophosphates and an insect growth regulator, was applied to doors and windows and tested in combination with pyrethroid-treated LLINs. The killing effect was monitored for 5 months by early morning collections of anophelines and other culicids. The residual efficacy was evaluated monthly by WHO bioassays using Anopheles gambiae 'Kisumu' and local populations of Anopheles coluzzii resistant to pyrethroids. The spatial mortality efficacy (SME) at distances of 1 m was also assessed against pyrethroid-susceptible and -resistant malaria vectors. The frequency of L1014F kdr and Ace-1 R G119S mutations was, respectively, reported throughout the study. The Insecticide Paint Inesfly 5A IGR had been tested in past studies yielding a long-term mortality rate of 80% over 12 months against An. coluzzii, the local pyrethroid-resistant malaria vector. The purpose of the present study is to test if treating smaller, targeted surfaces (e.g. doors and windows) was also efficient in killing malaria vectors. RESULTS: Treating windows and doors alone yielded a killing efficacy of 100% for 1 month against An. coluzzii resistant to pyrethroids, but efficacy reduced quickly afterwards. Likewise, WHO cone bioassays yielded mortalities of 80-100% for 2 months but declined to 90 and 40% 2 and 3 months after treatment, respectively. Mosquitoes exposed to insecticide paint-treated surfaces at distances of 1 m, yielded mortality rates of about 90-80% against local pyrethroids-resistant An. coluzzii during the first 2 months, but decreased to 30% afterwards. Anopheles coluzzii was reported to be exclusively the local malaria vector and resistant to pyrethroids with high L1014 kdr frequency. CONCLUSION: The combination of insecticide paint on doors and windows with LLINs yielded high mortality rates in the short term against wild pyrethroid-resistant malaria vector populations. A high SME was observed against laboratory strains of pyrethroid-resistant malaria vectors placed for 30 min at 1 m from the treated/control walls. The application of the insecticide paint on doors and windows led to high but short-lasting mortality rates. The strategy may be an option in a context where low cost, rapid responses need to be implemented in areas where malaria vectors are resistant to pyrethroids.

Pilot study on the combination of an organophosphate-based insecticide paint and pyrethroid-treated long lasting nets against pyrethroid resistant malaria vectors in Burkina Faso.

A pilot study to test the efficacy of combining an organophosphate-based insecticide paint and pyrethroid-treated Long Lasting Insecticide Treated Nets (LLINs) against pyrethroid-resistant malaria vector mosquitoes was performed in a real village setting in Burkina Faso. Paint Inesfly 5A IGR™, comprised of two organophosphates (OPs) and an Insect Growth Regulator (IGR), was tested in combination with pyrethroid-treated LLINs. Efficacy was assessed in terms of mortality for 12 months using Early Morning Collections of malaria vectors and 30-minute WHO bioassays. Resistance to pyrethroids and OPs was assessed by detecting the frequency of L1014F and L1014S kdr mutations and Ace-1(R)G119S mutation, respectively. Blood meal origin was identified using a direct enzyme-linked immunosorbent assay (ELISA). The combination of Inesfly 5A IGR™ and LLINs was effective in killing 99.9-100% of malaria vector populations for 6 months regardless of the dose and volume treated. After 12 months, mortality rates decreased to 69.5-82.2%. The highest mortality rates observed in houses treated with 2 layers of insecticide paint and a larger volume. WHO bioassays supported these results: mortalities were 98.8-100% for 6 months and decreased after 12 months to 81.7-97.0%. Mortality rates in control houses with LLINs were low. Collected malaria vectors consisted exclusively of Anopheles coluzzii and were resistant to pyrethroids, with a L1014 kdr mutation frequency ranging from 60 to 98% through the study. About 58% of An. coluzzii collected inside houses had bloodfed on non-human animals. Combining Inesfly 5A IGR™ and LLINs yielded a one year killing efficacy against An. coluzzii highly resistant to pyrethroids but susceptible to OPs that exhibited an anthropo-zoophilic behaviour in the study area. The results obtained in a real setting supported previous work performed in experimental huts and underscore the need to study the impact that this novel strategy may have on clinical malaria and malaria exposure in children in a similar area of high pyrethroid resistance in South-Western Burkina Faso.

Proposed use of spatial mortality assessments as part of the pesticide evaluation scheme for vector control.

BACKGROUND: The WHO Pesticide Evaluation Scheme to evaluate the efficacy of insecticides does not include the testing of a lethal effect at a distance. A tool was developed to evaluate the spatial mortality of an insecticide product against adult mosquitoes at a distance under laboratory and field conditions. Operational implications are discussed. METHODS: Insecticide paint, Inesfly 5A IGR™, containing two organophosphates (OPs): chlorpyrifos and diazinon, and one insect growth regulator (IGR): pyriproxyfen, was the product tested. Laboratory tests were performed using "distance boxes" with surfaces treated with one layer of control or insecticide paint at a dose of 1 kg/6 sq m. Field tests were conducted up to 12 months in six experimental huts randomly allocated to control or one or two layers of insecticide paint at 1 kg/6 sq m. All distance tests were performed using reference-susceptible strains of Anopheles gambiae and Culex quinquefasciatus left overnight at a distance of 1 m from control or treated surfaces. RESULTS: After an overnight exposition at distances of 1 m, field and laboratory evaluations at 0 months after treatment (T0) yielded 100% mortality rates on surfaces treated with one layer at 1 kg/6 sq m against susceptible strains of An. gambiae and Cx. quinquefasciatus. Testing for long-term efficacy in the field gave mortality rates of 96-100% after an overnight exposition at a distance of 1 m for up to 12 months in huts where a larger volume was treated (walls and ceilings) with one or two layers of insecticide paint. CONCLUSION: A comprehensive evaluation of the full profile of insecticide products, both upon contact and spatially, may help rationalize vector control efforts more efficiently. Treating a large enough volume may extend a product's mortality efficacy in the long-term, which contact tests would fail to assess. It is hereby proposed to explore the development of cost effective methods to assess spatial mortality and to include them as one additional measurement of insecticide efficacy against mosquitoes and other arthropod vectors in WHOPES Phase I and Phase II studies.

Efficacy of an insecticide paint against insecticide-susceptible and resistant mosquitoes - part 1: laboratory evaluation.

BACKGROUND: The main malaria vector Anopheles gambiae and the urban pest nuisance Culex quinquefasciatus are increasingly resistant to pyrethroids in many African countries. There is a need for new products and strategies. Insecticide paint Inesfly 5A IGR™, containing two organophosphates (OPs), chlorpyrifos and diazinon, and insect growth regulator (IGR), pyriproxyfen, was tested under laboratory conditions for 12 months following WHOPES Phase I procedures. METHODS: Mosquitoes used were laboratory strains of Cx. quinquefasciatus susceptible and resistant to OPs. The paint was applied at two different doses (1 kg/6 m2 and 1 kg/12 m2) on different commonly used surfaces: porous (cement and stucco) and non-porous (softwood and hard plastic). Insecticide efficacy was studied in terms of delayed mortality using 30-minute WHO bioassay cones. IGR efficacy on fecundity, fertility and larval development was studied on OP-resistant females exposed for 30 minutes to cement treated and control surfaces. RESULTS: After treatment, delayed mortality was high (87-100%) even against OP-resistant females on all surfaces except cement treated at 1 kg/12 m2. Remarkably, one year after treatment delayed mortality was 93-100% against OP-resistant females on non-porous surfaces at both doses. On cement, death rates were low 12 months after treatment regardless of the dose and the resistance status. Fecundity, fertility and adult emergence were reduced after treatment even at the lower dose (p < 10(-3)). A reduction in fecundity was still observed nine months after treatment at both doses (p < 10(-3)) and adult emergence was reduced at the higher dose (p < 10(-3)). CONCLUSIONS: High mortality rates were observed against laboratory strains of the pest mosquito Cx. quinquefasciatus susceptible and resistant to insecticides. Long-term killing remained equally important on non-porous surfaces regardless the resistance status for over 12 months. The paint's effect on fecundity, fertility and adult emergence may continue to provide an additional angle of attack in reducing overall population densities when the lethal effect of OPs diminishes over time. Some options on how to deal with porous materials are given. Implications in vector control are discussed.

Efficacy of an insecticide paint against malaria vectors and nuisance in West Africa--part 2: field evaluation.

BACKGROUND: Widespread resistance of the main malaria vector Anopheles gambiae to pyrethroids reported in many African countries and operational drawbacks to current IRS methods suggest the convenience of exploring new products and approaches for vector control. Insecticide paint Inesfly 5A IGR™, containing two organophosphates (OPs), chlorpyrifos and diazinon, and one insect growth regulator (IGR), pyriproxyfen, was tested in Benin, West Africa, for 12 months. METHODS: Field trials were conducted in six experimental huts that were randomly allocated to one or two layers of insecticide at 1 Kg/6 m2 or control. Evaluations included: (i) early mosquito collection, (ii) mosquito release experiments, (iii) residual efficacy tests and (iv) distance tests. Early mosquito collections were performed on local populations of pyrethroid-resistant An. gambiae and Culex quinquefasciatus. As per WHOPES phase II procedures, four entomological criteria were evaluated: deterrence, excito-repellence, blood-feeding inhibition and mortality. Mosquito release experiments were done using local malaria-free An. gambiae females reared at the CREC insectarium. Residual efficacy tests and distance tests were performed using reference susceptible strains of An. gambiae and Cx. quinquefasciatus. RESULTS: Six months after treatment, mortality rates were still 90-100% against pyrethroid-resistant mosquito populations in experimental huts. At nine months, mortality rates in huts treated with two layers was still about 90-93% against An. gambiae and 55% against Cx. quinquefasciatus. Malaria-free local mosquito release experiments yielded a 90% blood-feeding inhibition in the absence of a physical barrier. A long-term residual efficacy of 12 months was observed by WHO-bioassays in huts treated with two layers (60-80%). Mortality after an overnight exposition at distances of 1 meter was 96-100% for up to 12 months. CONCLUSION: The encouraging results obtained on the insecticide paint Inesfly 5A IGR™ in terms of mortality, be it in direct contact or at a distance, and its new operational approach could constitute an additional option in malaria control efforts in areas of pyrethroid resistance. Phase III studies will be performed to assess the product's epidemiological impact and sociological acceptance.