In Côte d'Ivoire, there is a high intensity of pyrethroid resistance in malaria vectors which may threaten successful vector control. Molecular studies of the target site mutation in the voltage-gated sodium channel (VGSC) 1014F show that the gene frequencies of these mutations are high, widely spread across Côte d'Ivoire, and even fixed in some areas. To further characterize insecticide resistance in Côte d'Ivoire beyond target site mutations, the metabolic resistance mechanism was explored. Overexpression of the metabolic enzyme cytochrome CYP6M2, CYP6P3, CYP6P4, and CYP6P5 was investigated in Anopheles gambiae (s.s.) and An. coluzzii collected from 30 insecticide resistance monitoring sites across the country in 2021 and 2022. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was carried out using RNA-later preserved 60 surviving mosquitoes from each site after phenotypic susceptibility tests. Additionally, a subsample of about 100 mosquitoes from each site was identified to species by PCR, and the frequency of the VGSC 1014F and 1014S was determined. All four CYPs were found to be overexpressed in Côte d'Ivoire with at least one CYP statistically significantly overexpressed in 27 of the 30 sites investigated compared to the susceptible An. gambiae (s.s.) Kisumu (P < 0.005). CYP6M2 was overexpressed in 89% of sites and was the sole overexpressed gene in 10 sites, while the overexpression of CYP6P3 was found in only 10 sites. CYP6P4 and CYP6P5 were overexpressed in 16 and 13 sites, respectively. Furthermore, seven sites (Adzopé, Bongouanou, Daloa, Gagnoa, Guiglo Jacqueville, and Sassandra) had overexpression of all four CYPs. Overall, An. coluzzii showed higher overexpression of CYPs than An. gambiae (s.s.). This study highlights the involvement of selected CYPs in insecticide resistance where target site mutation genes are already present, suggesting that insecticide resistance is complex and multifaceted at a molecular level. Where feasible, it may be helpful to include metabolic resistance surveillance to further characterize insecticide resistance. © 2024 The Authors

BACKGROUND: A low-level risk of intussusception following rotavirus vaccination has been observed in some settings and may vary by vaccine type. We examined the association between RotaTeq vaccination and intussusception in low-income settings in a pooled analysis from 5 African countries that introduced RotaTeq into their national immunization program. METHODS: Active surveillance was conducted at 20 hospitals to identify intussusception cases. A standard case report form was completed for each enrolled child, and vaccination status was determined by review of the child's vaccination card. The pseudo-likelihood adaptation of self-controlled case-series method was used to assess the association between RotaTeq administration and intussusception in the 1-7, 8-21, and 1-21 day periods after each vaccine dose in infants aged 28-245 days. RESULTS: Data from 318 infants with confirmed rotavirus vaccination status were analyzed. No clustering of cases occurred in any of the risk windows after any of the vaccine doses. Compared with the background risk of naturally occurring intussusception, no increased risk was observed after dose 1 in the 1-7 day (relative incidence = 2.71; 95% confidence interval [CI] = 0.47-8.03) or the 8-21 day window (relative incidence = 0.77; 95%CI = 0.0-2.69). Similarly, no increased risk of intussusception was observed in any risk window after dose 2 or 3. CONCLUSIONS: RotaTeq vaccination was not associated with increased risk of intussusception in this analysis from 5 African countries. This finding mirrors results from similar analyses with other rotavirus vaccines in low-income settings and highlights the need for vaccine-specific and setting-specific risk monitoring.

BACKGROUND: Entomological surveillance provides critical information on vectors for appropriate malaria vector control and strategic decision-making. The widely documented insecticide resistance of malaria vectors in Côte d'Ivoire requires that any vector control intervention deployment be driven by entomological data to optimize its effectiveness and appropriate resource allocations. To achieve this goal, this study documents the results of monthly vector surveillance and insecticide susceptibility tests conducted in 2019 and a review of all previous entomological monitoring data used to guide vector control decision making. Furthermore, susceptibility to pirimiphos-methyl and clothianidin was assessed in addition to chlorfenapyr and pyrethroids (intensity and piperonyl butoxide (PBO) synergism) tests previously reported. Vector bionomic data were conducted monthly in four sites (Sakassou, Béoumi, Dabakala and Nassian) that were selected based on their reported high malaria incidence. Adult mosquitoes were collected using human landing catches (HLCs), pyrethrum spray catches (PSCs), and human-baited CDC light traps to assess vector density, behaviour, species composition and sporozoite infectivity. RESULTS: Pirimiphos-methyl and clothianidin susceptibility was observed in 8 and 10 sites, respectively, while previous data reported chlorfenapyr (200 µg/bottle) susceptibility in 13 of the sites, high pyrethroid resistance intensity and increased mortality with PBO pre-exposure at all 17 tested sites. Anopheles gambiae sensu lato was the predominant malaria vector collected in all four bionomic sites. Vector density was relatively higher in Sakassou throughout the year with mean biting rates of 278.2 bites per person per night (b/p/n) compared to Béoumi, Dabakala and Nassian (mean of 48.5, 81.4 and 26.6 b/p/n, respectively). The mean entomological inoculation rate (EIR) was 4.44 infective bites per person per night (ib/p/n) in Sakassou, 0.34 ib/p/n in Beoumi, 1.17 ib/p/n in Dabakala and 1.02 ib/p/n in Nassian. The highest EIRs were recorded in October in Béoumi (1.71 ib/p/n) and Nassian (3.22 ib/p/n), in July in Dabakala (4.46 ib/p/n) and in May in Sakassou (15.6 ib/p/n). CONCLUSION: Based on all results and data review, the National Malaria Control Programme developed and implemented a stratified insecticide-treated net (ITN) mass distribution in 2021 considering new generation ITNs. These results also supported the selection of clothianidin-based products and an optimal spraying time for the first indoor residual spraying (IRS) campaign in Sakassou and Nassian in 2020.

BACKGROUND: With limited SARS-CoV-2 testing capacity in the US at the start of the epidemic (January - March), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. METHODS: All of Us study participants in all 50 US states provided blood specimens during study visits from January 2 to March 18, 2020. A participant was considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. Sensitivity and specificity of the Abbott and EUROIMMUNE ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated with 95% confidence intervals. RESULTS: The estimated sensitivity of Abbott and EUROIMMUN was 100% (107/107 [96.6%, 100%]) and 90.7% (97/107 [83.5%, 95.4%]), respectively. The estimated specificity of Abbott and EUROIMMUN was 99.5% (995/1,000 [98.8%, 99.8%]) and 99.7% (997/1,000 [99.1%, 99.9%), respectively. The net sensitivity and specificity of our sequential testing algorithm was 90.7% (97/107 [83.5%, 95.4%]) and 100.0% (1,000/1,000 [99.6%, 100%]), respectively. Of the 24,079 study participants with blood specimens from January 2 to March 18, 2020, 9 were seropositive, 7 of whom were seropositive prior to the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. CONCLUSIONS: Our findings indicate SARS-CoV-2 infections weeks prior to the first recognized cases in 5 US states.

In Côte d'Ivoire, the Family Approach to Counseling and Testing (FACT) program began in 2015 and provides facility-based HIV testing to the sexual partners, children and other household family members of HIV-positive index cases. We evaluated whether the FACT program is an effective approach to HIV case finding. We reviewed 1762 index patient charts to evaluate outcomes of the FACT program, held across 36 facilities in Abidjan. Index cases enumerated a total of 644 partners, 2301 children and 508 other family members including parents and siblings. Among the partners tested for HIV, the positivity rate was 21%; for children the positivity rate was 5% and for all other family members the positivity rate was 11%. Offering HIV testing services to the family members of HIV positive index cases is an effective approach to case finding in Côte d'Ivoire. Particularly, offering HIV testing to the partners of positive women index cases can be key to identifying previously undiagnosed men and linking them to treatment.

Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged <15 years were estimated to be living with HIV (including 170,000 infants born in 2015), with the vast majority living in sub-Saharan Africa. In 2014, 150,000 children died from HIV-related causes worldwide. Access to timely HIV diagnosis and treatment for HIV-infected infants reduces HIV-associated mortality, which is approximately 50% by age 2 years without treatment. Since 2011, the annual number of HIV-infected children has declined by 50%. Despite this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test for HIV, and in 2015, only 51% of children living with HIV received antiretroviral therapy (1). Access to services for early infant diagnosis of HIV (which includes access to testing for HIV-exposed infants and clinical diagnosis of HIV-infected infants) is critical for reducing HIV-associated mortality in children aged <15 years. Using data collected from seven countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the provision of HIV testing services for early infant diagnosis was assessed. During 2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as recommended by the World Health Organization (WHO) increased in all seven countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi, South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV positivity among those tested declined in all seven countries, with three countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda) reporting >50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection.

BACKGROUND: Correct treatment of potentially life-threatening illnesses (PLTIs) in children under 5 years, such as malaria, pneumonia, and diarrhea, can substantially reduce mortality. The Integrated Management of Childhood Illness (IMCI) strategy has been shown to improve treatment of child illnesses, but multiple studies have shown that gaps in health worker performance remain after training. To better understand factors related to health worker performance, we analyzed 9,330 patient consultations in Benin from 2001-2002, after training one of the first cohorts of 32 health workers in IMCI. METHODS: With data abstracted from patient registers specially designed for IMCI-trained health workers, we examined associations between health facility-, health worker-, and patient-level factors and 10 case-management outcomes for PLTIs. RESULTS: Altogether, 63.6 % of children received treatment for all their PLTIs in accordance with IMCI guidelines, and 77.8 % received life-saving treatment (i.e., clinically effective treatment, even if not exactly in accordance with IMCI guidelines). Performance of individual health workers varied greatly, from 15-88 % of patients treated correctly, on average. Multivariate regression analyses identified several factors that might have influenced case-management quality, many outside a manager's direct control. Younger health workers significantly outperformed older ones, and infants received better care than older children. Children with danger signs, those with more complex illnesses, and those with anemia received worse care. Health worker supervision was associated with improved performance for some outcomes. CONCLUSIONS: A variety of factors, some outside the direct control of program managers, can influence health worker practices. An understanding of these influences can help inform the development of strategies to improve performance.

OBJECTIVE: Training health workers to use Integrated Management of Childhood Illness (IMCI) guidelines can improve care for ill children in outpatient settings in developing countries. However, even after IMCI training, important performance gaps exist. One potential reason is that the effect of training can rapidly wane. Our aim was to determine if the performance of IMCI-trained health workers deteriorated over 3 years. METHODS: We studied two departments in Benin. First, we performed a record review of 32 IMCI-trained health workers during the first year of IMCI implementation (2001-2002). Second, we analysed data from cross-sectional health facility surveys from 2001 to 2004 that represented the entire study area. Primary outcomes were the proportion of children under 5 years old with potentially life-threatening illnesses who received either recommended or adequate treatment, and among all children, an index of overall guideline adherence. Secondary outcomes reflected the treatment of individual diseases. Outcomes were calculated monthly, and time trends were evaluated with regression modelling. RESULTS: The record review included 9393 consultations, and the surveys included 411 consultations performed by 105 health workers. For both data sources, performance trends were essentially flat for nearly all outcomes. Absolute levels of performance revealed substantial performance gaps. CONCLUSIONS: We found no evidence that performance declined over 3 years after IMCI training. However, important performance gaps found immediately after IMCI training persisted and should be addressed. (2012 Blackwell Publishing Ltd.)