Evidence supporting deployment of next generation insecticide treated nets in Burkina Faso: bioassays with either chlorfenapyr or piperonyl butoxide increase mortality of pyrethroid-resistant Anopheles gambiae.

BACKGROUND: Pyrethroid resistance poses a major threat to the efficacy of insecticide-treated nets (ITNs) in Burkina Faso and throughout sub-Saharan Africa, particularly where resistance is present at high intensity. For such areas, there are alternative ITNs available, including the synergist piperonyl butoxide (PBO)-based ITNs and dual active ingredient ITNs such as Interceptor G2 (treated with chlorfenapyr and alpha-cypermethrin). Before deploying alternative ITNs on a large scale it is crucial to characterize the resistance profiles of primary malaria vector species for evidence-based decision making. METHODS: Larvae from the predominant vector, Anopheles gambiae sensu lato (s.l.) were collected from 15 sites located throughout Burkina Faso and reared to adults for bioassays to assess insecticide resistance status. Resistance intensity assays were conducted using WHO tube tests to determine the level of resistance to pyrethroids commonly used on ITNs at 1×, 5 × and 10 × times the diagnostic dose. WHO tube tests were also used for PBO synergist bioassays with deltamethrin and permethrin. Bottle bioassays were conducted to determine susceptibility to chlorfenapyr at a dose of 100 µg/bottle. RESULTS: WHO tube tests revealed high intensity resistance in An. gambiae s.l. to deltamethrin and alpha-cypermethrin in all sites tested. Resistance intensity to permethrin was either moderate or high in 13 sites. PBO pre-exposure followed by deltamethrin restored full susceptibility in one site and partially restored susceptibility in all but one of the remaining sites (often reaching mortality greater than 80%). PBO pre-exposure followed by permethrin partially restored susceptibility in 12 sites. There was no significant increase in permethrin mortality after PBO pre-exposure in Kampti, Karangasso-Vigué or Mangodara; while in Seguenega, Orodara and Bobo-Dioulasso there was a significant increase in mortality, but rates remained below 50%. Susceptibility to chlorfenapyr was confirmed in 14 sites. CONCLUSION: High pyrethroid resistance intensity in An. gambiae s.l. is widespread across Burkina Faso and may be a predictor of reduced pyrethroid ITN effectiveness. PBO + deltamethrin ITNs would likely provide greater control than pyrethroid nets. However, since susceptibility in bioassays was not restored in most sites following pre-exposure to PBO, Interceptor G2 may be a better long-term solution as susceptibility was recorded to chlorfenapyr in nearly all sites. This study provides evidence supporting the introduction of both Interceptor G2 nets and PBO nets, which were distributed in Burkina Faso in 2019 as part of a mass campaign.

Safety monitoring of artemisinin combination therapy through a national pharmacovigilance system in an endemic malaria setting.

BACKGROUND: The National Malaria Control Programme in Senegal, introduced since 2006, artemisinin-based combination therapy (ACT administration) for the treatment of uncomplicated malaria cases. In this framework, an anti-malarial pharmacovigilance plan was developed and implemented in all public health services. This study investigated the occurrence of Adverse Drug Events (ADEs) after ACT. METHODS: The study was conducted between January 2007 and December 2009. It was based on spontaneous reports of ADEs in public health facilities. Data on patient demographic characteristics, dispensing facility, adverse signs and symptoms and causality were collected from a total of 123 patients. RESULTS: The age range of these patients was six months to 93 years with a mean of 25.9 years. Of the reported symptoms, 46.7% were related to the abdomen and the digestive system. Symptoms related to the nervous system, skin and subcutaneous tissue, circulatory and respiratory systems and general symptoms and signs were 7%, 9.7%, 3.5% and 31.3%, respectively. Causality results linked 14.3% of symptoms to Falcimon® (Artesunate-Amodiaquine) with certainty. Effects were classified as mild and severe in 69.1% and 7.3% of cases respectively while 23.6% were serious. All patients with serious ADEs were hospitalized. One death was reported in a patient who had taken 24 pills at once. CONCLUSION: These results confirm the need to develop and implement pharmacovigilance systems in malaria endemic countries in order to monitor the safety of anti-malarial treatments.

Scale-up of home-based management of malaria based on rapid diagnostic tests and artemisinin-based combination therapy in a resource-poor country: results in Senegal.

BACKGROUND: Effective case management of malaria requires prompt diagnosis and treatment within 24 hours. Home-based management of malaria (HMM) improves access to treatment for populations with limited access to health facilities. In Senegal, an HMM pilot study in 2008 demonstrated the feasibility of integrated use of RDTs and ACT in remote villages by volunteer Home Care Providers (HCP). Scale-up of the strategy began in 2009, reaching 408 villages in 2009 and 861 villages in 2010. This paper reports the results of the scale-up in the targeted communities and the impact of the strategy on malaria in the formal health sector. METHODS: Data reported by the HCPs were used to assess their performance in 2009 and 2010, while routine malaria morbidity and mortality data were used to assess the impact of the HMM programme. Two high transmission regions where HMM was not implemented until 2010 were used as a comparison. RESULTS AND DISCUSSION: From July 2009 through May 2010, 12582 suspected cases were managed by HCPs, 93% (11672) of whom were tested with an RDT. Among those tested, 37% (4270) had a positive RDT, 97% (4126) of whom were reported treated and cured. Home care providers referred 6871 patients to health posts for management: 6486 with a negative RDT, 119 infants < 2 months, 105 pregnant women, and 161 severe cases. There were no deaths among these patients. In 2009 compared to 2008, incidence of suspected and confirmed malaria cases, all hospitalizations and malaria-related hospitalizations decreased in both intervention and comparison regions. Incidence of in-hospital deaths due to malaria decreased by 62.5% (95% CI 43.8-81.2) in the intervention regions, while the decrease in comparison regions was smaller and not statistically significant. CONCLUSION: Home-based management of malaria including diagnosis with RDT and treatment based on test results is a promising strategy to improve the access of remote populations to prompt and effective management of uncomplicated malaria and to decrease mortality due to malaria. When scaled-up to serve remote village communities in the regions of Senegal with the highest malaria prevalence, home care providers demonstrated excellent adherence to guidelines, potentially contributing to a decrease in hospital deaths attributed to malaria.

Characteristics and presenting complaints of outpatients with undiagnosed HIV infection: potential utility in selecting subjects for HIV testing.

HIV testing of individuals presenting to outpatient medical clinics has generally been based upon a selection system, with testing limited to those having signs or symptoms previously found associated with HIV-1 infection among hospitalized patients. However, little is known about the efficacy of this approach, particularly in Africa. Among patients presenting to a large outpatient infectious disease clinic in Dakar, Senegal, the utility of using specific demographic and behavioral characteristics and individual presenting complaints to identify individuals with previously undiagnosed HIV-1 or HIV-2 infection was examined. Using a simple statistical approach, a composite screening rule was estimated to identify subjects with the highest probability of testing HIV positive, ie, patients who would most benefit from HIV testing. Using the presenting complaint allows identification of 83% of HIV-infected women by testing only 35% of women presenting to the clinic. Similarly, using the presenting complaint and various demographic and behavioral characteristics, it was possible to identify 84% of HIV-infected men by screening 40% of men presenting to the clinic. This study suggests that this method might provide a cost-effective approach that permits limited screening resources to be spent in a way that maximizes individual and societal benefit.

Increased risk of high-grade cervical squamous intraepithelial lesions and invasive cervical cancer among African women with human immunodeficiency virus type 1 and 2 infections.

To assess the risk of prevalent high-grade cervical squamous intraepithelial lesions (HSILs) or invasive cervical cancer (ICC) associated with human immunodeficiency virus (HIV) type 1, HIV-2, and human papillomavirus (HPV) infections, HIV load, and CD4 cell count, we studied 4119 women attending an outpatient clinic in Senegal. HIV infection was associated with increased rates of cervical infection with high-risk HPVs. Among women infected with high-risk HPVs, those with HIV-1 (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0-4.8), HIV-2 (OR, 6.0; 95% CI, 2.1-17.1), or dual HIV infection (OR, 8.0; 95% CI, 2.0-31.5) were more likely to have HSILs or ICC diagnosed than were HIV-negative women; this association was not observed among women not infected with high-risk HPVs. Among women with HIV, higher HIV plasma RNA loads and lower CD4 cell counts were associated with high-risk HPV infection and degree of cervical abnormality. Furthermore, HIV-2-positive women were more likely to have HSILs (OR, 3.3; 95% CI, 0.9-12.4) or ICC (OR, 7.9; 95% CI, 1.1-57) than were HIV-1-positive women.