Browsing by Author "Mulamba, Charles"

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Evaluation Of The Malaria Transmission-Reducing Activity Of Pfs25-Imx313/Matrix-M Vaccine And Naturally Acquired Antibodies In Tanzanian Volunteers
(NM-AIST, 2025-07) Mulamba, Charles
Malaria is still a public health challenge in Tanzania, control relies on the use of artemisinin-based combination therapies and insecticide-treated materials. The effectiveness of these interventions is threatened by drug and insecticide resistance in parasites and vectors respectively. Transmission-blocking interventions are therefore needed to supplement the current interventions. This study evaluated the ability of vaccine-induced Pfs25 antibodies, to block malaria parasite development in mosquitoes, following a Phase1 vaccine trial in Bagamoyo, Tanzania, between 2021 and 2023. The transmission reducing activity (TRA) was evaluated via Standard Membrane Feeding Assays (SMFAs), where laboratory mosquitoes were fed with a mixture of test or control antibodies and cultured Plasmodium falciparum gametocytes. The TRA was determined as the reduction in the number of oocysts by test antibodies compared to a negative control lacking blocking antibodies. In addition, a survey was conducted to determine the seroprevalence of natural antibodies to malaria antigens; Pfs25, Pfs230D1M, and Pfs48/45, as well as the malaria prevalence in 467 participants from five villages in Bagamoyo district. The malaria and natural antibody survey were conducted as a baseline for phase1 evaluation of Pfs25-IMX313/Matrix-M vaccine candidate. Trial results indicated that the Pfs25-IMX313/Matrix-M vaccine induced long-lasting antibodies, which promoted significant TRA in 18 of the 20 vaccinated participants. Survey findings showed that 23.5% (110/467) of the participants tested positive for malaria, and 24% of the malaria-positive participants had the sexual form of malaria (gametocytes) responsible for transmission. Regression analysis showed that gametocytes were more likely to be present among male participants than female participants [ORa: 2.79 (95% CI: 1.19 – 6.59) p=0.019]. The survey results further indicated that the seroprevalence of Pfs230D1M IgG was 56% (157/281), whereas that of Pfs48/45 IgG was 49% (141/291). Seroprevalence for anti-Pfs230 and anti-Pfs48/45 IgG increased significantly with participants’ age, with adults more likely to have antibodies than children; for Pfs230 [adjusted OR 3.18, (95% CI: 1.85 - 5.57), p=<0.0001], and Pfs45/48 [OR 3.11, (95% CI: 1.83 - 5.29), p = <0.0001]. When Pfs48/45 and Pfs230 seropositive serum was tested in the SMFAs, only two (2) of the 10 participants demonstrated significant TRA. We conclude that a transmission-blocking vaccine will be a great addition to the current malaria interventions, and children as well as adults should be targeted, if malaria elimination to be achieved. The Pfs25-IMX313/Matrix-M vaccine in this study should be further developed in combination with another transmission-blocking target such as Pfs230D1M or Pfs48/45.
Plasmodium falciparum gametocyte burden in a Tanzanian heterogeneous transmission setting
(BMC, 2025-02-21) Mulamba, Charles; Odufuwa, Olukayode; Kweyamba, Prisca; Lazaro, Linda; Chabo, Muhamed; Kamage, Janeth; Kreppel, Katharina; Olotu, Ally; Williams, Chris
Background Malaria transmission depends on the presence of gametocytes in the peripheral blood of infected human hosts. Understanding malaria infectious reservoirs enables transmission-blocking interventions to target the most important hosts for the disease. This study characterized the distribution of gametocyte carriage as a baseline for the clinical evaluation of a Pfs25-based transmission-blocking vaccine candidate in Bagamoyo, Tanzania. Methods A malaria survey was conducted in five locations from May to August 2022. A total of 467 participants—192 children (5–12 years), 65 adolescents (13–17 years) and 210 adults (18–45 years)—were enrolled. Malaria was detected using three methods: rapid diagnostic tests, light microscopy and quantitative polymerase chain reaction. The geometric mean of the gametocyte density, and weighted arithmetic mean of the gametocytes sex ratio were estimated. Results Overall, 23.5% (110/467) of the participants tested positive for malaria parasites, with the majority of positives (> 92%) being Plasmodium falciparum. The overall gametocytaemia was 5.6%, with a percent positivity of 6.8% (13/192), 6.2% (4/65) and 4.3% (9/210), in children, adolescents, and adults, respectively. The geometric mean gametocyte density (gametocytes/μL) was greater in adults (124.6) than in children (71.7) and adolescents (50.5). Regression analysis revealed that gametocytes were more likely to be present among male participants than among female participants [ORa: 2.79 (95% CI: 1.19 – 6.59) p = 0.019]. The gametocyte sex ratio in children and adult gametocyte carriers was similar but greater than that in adolescents. Conclusion The observed gametocyte densities and distribution across age groups suggest the need for malaria transmission-blocking interventions to target all populations in heterogeneous transmission settings. The implication of targeting only children may leave residual malaria transmission and reinfection from the left-out groups.
Plasmodium falciparum gametocyte burden in a Tanzanian heterogeneous transmission setting
(Springer Nature, 2025-02-21) Mulamba, Charles; Odufuwa, Olukayode; Kweyamba, Prisca; Lazaro, Linda; Chabo, Muhamed; Kamage, Janeth; Kreppel, Katharina; Olotu, Ally; Williams, Chris
Background Malaria transmission depends on the presence of gametocytes in the peripheral blood of infected human hosts. Understanding malaria infectious reservoirs enables transmission-blocking interventions to target the most important hosts for the disease. This study characterized the distribution of gametocyte carriage as a base- line for the clinical evaluation of a Pfs25-based transmission-blocking vaccine candidate in Bagamoyo, Tanzania. Methods A malaria survey was conducted in five locations from May to August 2022. A total of 467 partici- pants—192 children (5–12 years), 65 adolescents (13–17 years) and 210 adults (18–45 years)—were enrolled. Malaria was detected using three methods: rapid diagnostic tests, light microscopy and quantitative polymerase chain reac- tion. The geometric mean of the gametocyte density, and weighted arithmetic mean of the gametocytes sex ratio were estimated. Results Overall, 23.5% (110/467) of the participants tested positive for malaria parasites, with the majority of posi- tives (> 92%) being Plasmodium falciparum. The overall gametocytaemia was 5.6%, with a percent positivity of 6.8% (13/192), 6.2% (4/65) and 4.3% (9/210), in children, adolescents, and adults, respectively. The geometric mean gameto- cyte density (gametocytes/μL) was greater in adults (124.6) than in children (71.7) and adolescents (50.5). Regression analysis revealed that gametocytes were more likely to be present among male participants than among female par- ticipants [ORa: 2.79 (95% CI: 1.19 – 6.59) p = 0.019]. The gametocyte sex ratio in children and adult gametocyte carriers was similar but greater than that in adolescents. Conclusion The observed gametocyte densities and distribution across age groups suggest the need for malaria transmission-blocking interventions to target all populations in heterogeneous transmission settings. The implication of targeting only children may leave residual malaria transmission and reinfection from the left-out groups