Secondary Malaria Vectors of Sub-Saharan Africa: Threat to Malaria Elimination on the Continent?

Secondary vectors of malaria include those anopheline species that are known to play minor part in malaria transmission. Primary vectors of malaria in Africa are Anopheles gambiae s.s, Anopheles coluzzii, Anopheles arabiensis, Anopheles funestus, Anopheles moucheti and Anopheles nili, while Anopheles rivolorum, Anopheles pharoensis, Anopheles ziemanni, among others are secondary vectors. They are recognized for their importance in malaria transmission, as they may help to augment or extend the malaria transmission period and potentially sustain malaria transmission after the main indoor resting and indoor biting vectors have been reduced by vector control measures such as indoor residual spraying or Long-lasting insecticidal nets (LLINs). Thus, the terminology “secondary” versus “primary” vector is fluid and forged by ecological conditions and malaria control strategies. Most secondary vectors are outdoor resting and outdoor biting are thus, not taken care of in the current control methods. High use of insecticides for vector control in Africa, climate change, unprecedented land use changes in Africa are some of the factors that could influence the conversion of secondary vectors to become main vectors in Africa. This chapter examines the role of secondary vectors in malaria transmission and the possibility of them becoming main vectors in future

Insecticide resistance status of Aedes aegypti in Southern and Northern Ghana

Background: Outbreaks of Aedes-borne arboviral diseases are becoming rampant in Africa. In Ghana, there is no organized arboviral control programme with interventions restricted to mitigate outbreaks. Insecticide application is a crucial part of outbreak responses and future preventative control measures. Thus, knowledge of the resistance status and underlying mechanisms of Aedes populations is required to ensure optimal insecticide choices. The present study assessed the insecticide resistance status of Aedes aegypti populations from southern Ghana (Accra, Tema and Ada Foah) and northern Ghana (Navrongo) respectively. Methods: Phenotypic resistance was determined with WHO susceptibility tests using Ae. aegypti collected as larvae and reared into adults. Knockdown resistance (kdr) mutations were detected using allele-specific PCR. Synergist assays were performed with piperonyl butoxide (PBO) to investigate the possible involvement of metabolic mechanisms in resistance phenotypes. Results: Resistance to DDT was moderate to high across sites (11.3% to 75.8%) and for the pyrethroids, deltamethrin and permethrin, moderate resistance was detected (62.5% to 88.8%). The 1534C kdr and 1016I kdr alleles were common in all sites (0.65 to 1) and may be on a trajectory toward fixation. In addition, a third kdr mutant, V410L, was detected at lower frequencies (0.03 to 0.31). Pre-exposure to PBO significantly increased the susceptibility of Ae. aegypti to deltamethrin and permethrin (P<0.001). This indicates that in addition to kdr mutants, metabolic enzymes (monooxygenases) may be involved in the resistance phenotypes observed in the Ae. aegypti populations in these sites. Conclusion: Insecticide resistance underpinned by multiple mechanisms in Ae. aegypti indicates the need for surveillance to assist in developing appropriate vector control strategies for arboviral disease control in Ghana. Keywords: insecticide resistance, target-site mutations, Aedes aegypti, Piperonyl butoxide Synergist, knockdown resistance, Ghana

High-throughput barcoding method for the genetic surveillance of insecticide resistance and species identification in Anopheles gambiae complex malaria vectors.

Surveillance of malaria vector species and the monitoring of insecticide resistance are essential to inform malaria control strategies and support the reduction of infections and disease. Genetic barcoding of mosquitoes is a useful tool to assist the high-throughput surveillance of insecticide resistance, discriminate between sibling species and to detect the presence of Plasmodium infections. In this study, we combined multiplex PCR, custom designed dual indexing, and Illumina next generation sequencing for high throughput single nucleotide polymorphism (SNP)-profiling of four species from the Anopheles (An.) gambiae complex (An. gambiae sensu stricto, An. coluzzii, An. arabiensis and An. melas). By amplifying and sequencing only 14 genetic fragments (500 bp each), we were able to simultaneously detect Plasmodium infection; insecticide resistance-conferring SNPs in ace1, gste2, vgsc and rdl genes; the partial sequences of nuclear ribosomal internal transcribed spacers (ITS1 and ITS2) and intergenic spacers (IGS), Short INterspersed Elements (SINE), as well as mitochondrial genes (cox1 and nd4) for species identification and genetic diversity. Using this amplicon sequencing approach with the four selected An. gambiae complex species, we identified a total of 15 non-synonymous mutations in the insecticide target genes, including previously described mutations associated with resistance and two new mutations (F1525L in vgsc and D148E in gste2). Overall, we present a reliable and cost-effective high-throughput panel for surveillance of An. gambiae complex mosquitoes in malaria endemic regions

Marked variation in MSP-119 antibody responses to malaria in western Kenyan highlands

<p>Abstract</p> <p>Background</p> <p>Assessment of malaria endemicity at different altitudes and transmission intensities, in the era of dwindling vector densities in the highlands, will provide valuable information for malaria control and surveillance. Measurement of serum anti-malarial antibodies is a useful marker of malaria exposure that indicates long-term transmission potential. We studied the serologic evidence of malaria endemicity at two highland sites along a transmission intensity cline. An improved understanding of the micro-geographic variation in malaria exposure in the highland ecosystems will be relevant in planning effective malaria control.</p> <p>Methods</p> <p>Total IgG levels to <it>Plasmodium falciparum </it>MSP-1₁₉were measured in an age-stratified cohort (< 5, 5-14 and ≥ 15 years) in 795 participants from an uphill and valley bottom residents during low and high malaria transmission seasons. Antibody prevalence and level was compared between different localities. Regression analysis was performed to examine the association between antibody prevalence and parasite prevalence. Age-specific MSP-1₁₉seroprevalence data was fitted to a simple reversible catalytic model to investigate the relationship between parasite exposure and age.</p> <p>Results</p> <p>Higher MSP-1₁₉seroprevalence and density were observed in the valley residents than in the uphill dwellers. Adults (> 15 years) recorded high and stable immune response in spite of changing seasons. Lower responses were observed in children (≤ 15 years), which, fluctuated with changing seasons particularly in the valley residents. In the uphill population, annual seroconversion rate (SCR) was 8.3% and reversion rate was 3.0%, with seroprevalence reaching a plateau of 73.3% by age of 20. Contrary, in the valley bottom population, the annual SCR was 35.8% and the annual seroreversion rate was 3.5%, and seroprevalence in the population had reached 91.2% by age 10.</p> <p>Conclusion</p> <p>The study reveals the micro-geographic variation in malaria endemicity in the highland eco-system; this validates the usefulness of sero-epidemiological tools in assessing malaria endemicity in the era of decreasing sensitivity of conventional tools.</p

Effectiveness of artemether–lumefantrine for treating uncomplicated malaria in low- and high-transmission areas of Ghana

Abstract Background Artemisinin-based combination therapy (ACT) has been effective in the supervised treatment of uncomplicated malaria in Ghana. Since ACT usage is primarily unsupervised, this study aimed to determine the effectiveness of artemether–lumefantrine (AL) for treating malaria patients in two transmission settings in Ghana. Methods Eighty-four individuals with uncomplicated Plasmodium falciparum malaria were recruited from Lekma Hospital (LH) in Accra (low-transmission area; N = 28), southern Ghana, and King’s Medical Centre (KMC) in Kumbungu (high-transmission area; N = 56), northern Ghana. Participants were followed up for 28 days after unsupervised treatment with AL. The presence of asexual parasites was determined by microscopic examination of Giemsa-stained blood smears. Plasmodium species identification was confirmed using species-specific primers targeting the 18S rRNA gene. Parasite recrudescence or reinfection was determined by genotyping the Pfmsp 1 and Pfmsp 2 genes. Results After AL treatment, 3.6% (2/56) of the patients from KMC were parasitaemic on day 3 compared to none from the LH patients. One patient from KMC with delayed parasite clearance on day 3 remained parasite-positive by microscopy on day 7 but was parasite-free by day 14. While none of the patients from LH experienced parasite recurrence during the 28-day follow-up, three and two patients from KMC had recurrent parasitaemia on days 21 and 28, respectively. Percentage reduction in parasite densities from day 1, 2, and 3 for participants from the KMC was 63.2%, 89.5%, and 84.5%. Parasite densities for participants from the LH reduced from 98.2%, 99.8% on day 1, and 2 to 100% on day 3. The 28-day cumulative incidence rate of treatment failure for KMC was 12.8% (95% confidence interval: 1.9–23.7%), while the per-protocol effectiveness of AL in KMC was 89.47%. All recurrent cases were assigned to recrudescence after parasite genotyping by Pfmsp 1 and Pfmsp 2. Conclusion While AL is efficacious in treating uncomplicated malaria in Ghana, when taken under unsupervised conditions, it showed an 89.4% PCR-corrected cure rate in northern Ghana, which is slightly below the WHO-defined threshold

Insecticide resistance status of Aedes aegypti in southern and northern Ghana

Abstract Background Outbreaks of Aedes-borne arboviral diseases are becoming rampant in Africa. In Ghana, there is no organized arboviral control programme with interventions restricted to mitigate outbreaks. Insecticide application is a crucial part of outbreak responses and future preventative control measures. Thus, knowledge of the resistance status and underlying mechanisms of Aedes populations is required to ensure optimal insecticide choices. The present study assessed the insecticide resistance status of Aedes aegypti populations from southern Ghana (Accra, Tema and Ada Foah) and northern Ghana (Navrongo) respectively. Methods Phenotypic resistance was determined with WHO susceptibility tests using Ae. aegypti collected as larvae and reared into adults. Knockdown resistance (kdr) mutations were detected using allele-specific PCR. Synergist assays were performed with piperonyl butoxide (PBO) to investigate the possible involvement of metabolic mechanisms in resistance phenotypes. Results Resistance to DDT was moderate to high across sites (11.3 to 75.8%) and, for the pyrethroids deltamethrin and permethrin, moderate resistance was detected (62.5 to 88.8%). The 1534C kdr and 1016I kdr alleles were common in all sites (0.65 to 1) and may be on a trajectory toward fixation. In addition, a third kdr mutant, V410L, was detected at lower frequencies (0.03 to 0.31). Pre-exposure to PBO significantly increased the susceptibility of Ae. aegypti to deltamethrin and permethrin (P < 0.001). This indicates that in addition to kdr mutants, metabolic enzymes (monooxygenases) may be involved in the resistance phenotypes observed in the Ae. aegypti populations in these sites. Conclusion Insecticide resistance underpinned by multiple mechanisms in Ae. aegypti indicates the need for surveillance to assist in developing appropriate vector control strategies for arboviral disease control in Ghana. Graphical Abstrac

Coverage of preventive measures and surveillance for neglected tropical diseases in hard-to-reach communities in Ghana

Abstract Background Neglected tropical diseases (NTDs) are a major public health burden which mainly affects poor populations living in tropical environments and hard-to-reach areas. The study sought to examine coverage of preventive efforts, and case surveillance for NTDs in hard-to-reach communities in Ghana. Methods The study investigated treatment efforts for lymphatic filariasis (LF), and onchocerciasis and schistosomiasis/soil transmitted helminths (SCH/STH) at household level, in difficult-to-access communities in Ghana. A total of 621 households were sampled from 6 communities in the Western, Oti and Greater Accra regions. Results Over 95% of the households surveyed were covered under mass drug administration (MDA) campaigns for lymphatic filariasis (LF) and onchocerciasis. More than 80% of households had received at least two visits by community drug distributors under the MDA campaigns in the last two years preceding the study. In addition, over 90% of households in the LF and onchocerciasis endemic communities had at least one member using anthelminthic medications under the MDA campaigns in the 12 months preceding the study. However, households where no member had taken anthelminthic medications in 12 months preceding the study were over 6 times likely to have someone in the household with LF. Conclusions This study determined that SCH/STH, LF and onchocerciasis are of serious public health concern in some communities in Ghana. There is an urgent need for holistic practical disease control plan involving both financial and community support to ensure total control of NTDs in difficult-to-access communities is achieved

Additional file 1 of Coverage of preventive measures and surveillance for neglected tropical diseases in hard-to-reach communities in Ghana

Additional file 1: S1. File Household Questionnaire-2