The Effect of Plasmodium falciparum (Welch) (Haemospororida: Plasmodiidae) Infection on the Susceptibility of Anopheles gambiae s.l. and Anopheles funestus (Diptera: Culicidae) to Pyrethroid Insecticides in the North-Western and South-Eastern, Tanzania.

The rapid development of insecticide resistance in malaria vectors threatens insecticide-based interventions. It is hypothesized that infection of insecticide-resistant vectors with Plasmodium parasites increases their vulnerability to insecticides, thus assuring the effectiveness of insecticide-based strategies for malaria control. Nonetheless, there is limited field data to support this. We investigated the effect of the Plasmodium falciparum infection on the susceptibility of Anopheles gambiae s.l. and Anopheles funestus to pyrethroids in south-eastern (Kilombero) and north-western (Muleba), Tanzania. The wild-collected mosquitoes were tested against 0.05% deltamethrin and 0.75% permethrin, then assessed for sporozoite rate and resistant gene (kdr) mutations. All Anopheles gambiae s.l. from Kilombero were An. arabiensis (Patton, 1905) while those from Muleba were 87% An. gambiae s.s (Giles, 1902) and 13% An. Arabiensis. High levels of pyrethroid resistance were observed in both areas studied. The kdr mutation was only detected in An. gambiae s.s. at the frequency of 100% in survivors and 97% in dead mosquitoes. The P. falciparum sporozoite rates were slightly higher in susceptible than in resistant mosquitoes. In Muleba, sporozoite rates in An. gambiae s.l. were 8.1% and 6.4% in dead mosquitoes and survivors, respectively (SRR = 1.28, p = 0.19). The sporozoite rates in Kilombero were 1.3% and 0.7% in the dead and survived mosquitoes, respectively (sporozoite rate ratio (SRR) = 1.9, p = 0.33). In An. funestus group sporozoite rates were 6.2% and 4.4% in dead and survived mosquitoes, respectively (SRR = 1.4, p = 0.54). These findings indicate that insecticides might still be effective in malaria control despite the rapid development of insecticide resistance in malaria vectors.

Genetic Sequence Variation in the Plasmodium falciparum Histidine-Rich Protein 2 Gene from Field Isolates in Tanzania: Impact on Malaria Rapid Diagnosis.

Malaria rapid diagnosis test (RDT) is crucial for managing the disease, and the effectiveness of detection depends on parameters such as sensitivity and specificity of the RDT. Several factors can affect the performance of RDT. In this study, we focused on the pfhrp2 sequence variation and its impact on RDTs targeted by antigens encoded by Plasmodium falciparum histidine-rich protein 2 (pfhrp2). Field samples collected during cross-sectional surveys in Tanzania were sequenced to investigate the pfhrp2 sequence diversity and evaluate the impact on HRP2-based RDT performance. We observed significant mean differences in amino acid repeats between current and previous studies. Several new amino acid repeats were found to occur at different frequencies, including types AAY, AHHAHHAAN, and AHHAA. Based on the abundance of types 2 and 7 amino acid repeats, the binary predictive model was able to predict RDT insensitivity by about 69% in the study area. About 85% of the major epitopes targeted by monoclonal antibodies (MAbs) in RDT were identified. Our study suggested that the extensive sequence variation in pfhrp2 can contribute to reduced RDT sensitivity. The correlation between the different combinations of amino acid repeats and the performance of RDT in different malaria transmission settings should be investigated further.

Deletions of the Plasmodium falciparum histidine-rich protein 2/3 genes are common in field isolates from north-eastern Tanzania.

Plasmodium falciparum parasites lacking histidine-rich protein 2 and 3 (pfhrp2/3) genes have been reported in several parts of the world. These deletions are known to compromise the effectiveness of HRP2-based malaria rapid diagnostic tests (HRP2-RDT). The National Malaria Control Programme (NMCP) in Tanzania adopted HRP2-RDTs as a routine tool for malaria diagnosis in 2009 replacing microscopy in many Health facilities. We investigated pfhrp2/3 deletions in 122 samples from two areas with diverse malaria transmission intensities in Northeastern Tanzania. Pfhrp2 deletion was confirmed in 1.6% of samples while pfhrp3 deletion was confirmed in 50% of samples. We did not find parasites with both pfhrp2 and pfhrp3 deletions among our samples. Results from this study highlight the need for systematic surveillance of pfhrp2/3 deletions in Tanzania to understand their prevalence and determine their impact on the performance of mRDT.

Predictive markers of transmission in areas with different malaria endemicity in north-eastern Tanzania based on seroprevalence of antibodies against Plasmodium falciparum.

OBJECTIVE: A community-based cross-sectional study was done to assess Plasmodium falciparum exposure in areas with different malaria endemicity in north-eastern Tanzania using serological markers; PfAMA-1 and PfMSP-119. RESULTS: Bondo had a higher seroprevalence 36.6% (188) for PfAMA-1 as compared to Hai 13.8% (33), χ2 = 34.66, p < 0.01. Likewise, Bondo had a higher seroprevalence 201(36.6%) for PfMSP-1 as compared to Hai 41 (17.2%), χ2 = 29.62, p < 0.01. Anti-PfAMA-1 titters were higher in malaria positive individuals (n = 47) than in malaria negative individuals (n = 741) (p = 0.07). Anti-PfMSP-1 antibody concentrations were significantly higher in malaria-positive individuals (n = 47) than in malaria-negative individuals (n = 741) (p = 0.003). Antibody response against PfAMA-1 was significantly different between the three age groups; < 5 years, 5 to 15 years and > 15 years in both sites of Bondo and Hai. Likewise, antibody response against PfMSP-119 was significantly different between the three age groups in the two sites (p < 0.001). We also found significant differences in the anti-PfAMA-1and anti-PfMSP-119 antibody concentrations among the three age groups in the two sites (p = 0.004 and 0.005) respectively. Immunological indicators of P. falciparum exposure have proven to be useful in explaining long-term changes in the transmission dynamics, especially in low transmission settings.

Dynamics and monitoring of insecticide resistance in malaria vectors across mainland Tanzania from 1997 to 2017: a systematic review.

BACKGROUND: Malaria still claims substantial lives of individuals in Tanzania. Insecticide-treated nets (ITNs) and indoor residual spray (IRS) are used as major malaria vector control tools. These tools are facing great challenges from the rapid escalating insecticide resistance in malaria vector populations. This review presents the information on the dynamics and monitoring of insecticide resistance in malaria vectors in mainland Tanzania since 1997. The information is important to policy-makers and other vector control stakeholders to reflect and formulate new resistance management plans in the country. METHODS: Reviewed articles on susceptibility and mechanisms of resistance in malaria vectors to insecticides across mainland Tanzania were systematically searched from the following databases: PubMed, Google scholar, HINARI and AGORA. The inclusion criteria were articles published between 2000 and 2017, reporting susceptibility of malaria vectors to insecticides, mechanisms of resistance in the mainland Tanzania, involving field collected adult mosquitoes, and mosquitoes raised from the field collected larvae. Exclusion criteria were articles reporting insecticide resistance in larval bio-assays, laboratory strains, and unpublished data. Reviewed information include year of study, malaria vectors, insecticides, and study sites. This information was entered in the excel sheet and analysed. RESULTS: A total of 30 articles met the selection criteria. The rapid increase of insecticide resistance in the malaria vectors across the country was reported since year 2006 onwards. Insecticide resistance in Anopheles gambiae sensu lato (s.l.) was detected in at least one compound in each class of all recommended insecticide classes. However, the Anopheles funestus s.l. is highly resistant to pyrethroids and DDT. Knockdown resistance (kdr) mechanism in An. gambiae s.l. is widely studied in the country. Biochemical resistance by detoxification enzymes (P450s, NSE and GSTs) in An. gambiae s.l. was also recorded. Numerous P450s genes associated with metabolic resistance were over transcribed in An. gambiae s.l. collected from agricultural areas. However, no study has reported mechanisms of insecticide resistance in the An. funestus s.l. in the country. CONCLUSION: This review has shown the dynamics and monitoring of insecticide resistance in malaria vector populations across mainland Tanzanian. This highlights the need for devising improved control approaches of the malaria vectors in the country.