The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on haemoglobin levels in Ethiopia: a longitudinal cohort study.

BACKGROUND: To interrupt residual malaria transmission and achieve successful elimination of Plasmodium falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT), without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of haemolysis in patients with G6PD deficiency (G6PDd), PQ use is uncommon. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency. METHODS: An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and haemoglobin (Hb) concentrations. G6PD levels were measured by a quantiative CareSTART™ POCT S1 biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone. RESULTS: A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 28-15) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to - 0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PDd ACT + SLD-PQ group (- 0.60 g/dL) than in the G6PDd ACT alone group (- 0.48 g/dL); however, there was no statistically significant difference (P = 0.465). Overall, D14 losses were 0.10 g/dl (95% CI = - 0.00 to 0.20) and 0.05 g/dl (95% CI = - 0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412). CONCLUSIONS: This study's findings indicate that using SLD-PQ in combination with ACT is safe for uncomplicated P. falciparum malaria regardless of the patient's G6PD status in Ethiopian settings. Caution should be taken in extrapolating this finding in other settings with diverse G6DP phenotypes.

The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on hemoglobin levels in Ethiopia: a longitudinal cohort study.

Background: To interrupt residual malaria transmission and achieve successful elimination of P. falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of hemolysis in patients with G6PD deficiency (G6PDd), PQ use is not as common. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency. Methods: An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and hemoglobin (Hb) concentrations. G6PD levels were masured by a quantiative biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone. Results: A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 14) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to -0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PD deficiency group (-0.56 g/dL) than in the G6PD normal group (-0.39 g/dL); however, there was no statistically significant difference (P = 0.359). Overall, D14 losses were 0.10 g/dl (95% CI = -0.00 to 0.20) and 0.05 g/dl (95% CI = -0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412). Conclusions: Our findings showed that single low-dose primaquine (SLD-PQ) treatment for uncomplicated P. falciparum malaria is safe and does not increase the risk of hemolysis in G6PDd patients. This evidence suggests that the wider deployment of SLD-PQ for P. falciparum is part of a global strategy for eliminating P. falciparum malaria.

First report of Anopheles stephensi from southern Ethiopia.

BACKGROUND: Anopheles stephensi is an emerging exotic invasive urban malaria vector in East Africa. The World Health Organization recently announced an initiative to take concerted actions to limit this vector's expansion by strengthening surveillance and control in invaded and potentially receptive territories in Africa. This study sought to determine the invasion of An. stephensi in southern Ethiopia. METHODS: A targeted entomological survey, both larvae and adult, was conducted in Hawassa City, southern Ethiopia between November 2022 and February 2023. Anopheles larvae were reared to adults for species identification. CDC light traps and BG Pro traps were used indoors and outdoors overnight at selected houses to collect adult mosquitoes in the study area. Prokopack aspirator was employed to sample indoor resting mosquitoes in the morning. Adults of An. stephensi was identified using morphological keys and then confirmed by PCR. RESULTS: Larvae of An. stephensi were found in 28 (16.6%) of the 169 potential mosquito breeding sites surveyed. Out of 548 adult female Anopheles mosquitoes reared from larvae, 234 (42.7%) were identified as An. stephensi morphologically. A total of 449 female anophelines were caught, of which 53 (12.0%) were An. stephensi. Other anopheline species collected in the study area included Anopheles gambiae sensu lato (s.l.), Anopheles pharoensis, Anopheles coustani, and Anopheles demeilloni. CONCLUSION: This study confirmed the presence of An. stephensi in southern Ethiopia. The presence of both larval and adult stages of this mosquito attests that this species established sympatric colonization with native vector species such as An. gambiae (s.l.) in southern Ethiopia. The findings warrant further investigation on the ecology, behaviour, population genetics, and role of An. stephensi in malaria transmission in Ethiopia.

First report of Anopheles stephensi in Southern Ethiopia.

Background: Anopheles stephensi is an emerging exotic invasive urban vector of malaria in East Africa. The World Health Organization recently announced an initiative to take concerted actions to limit this vector's expansion by strengthening surveillance and control in invaded and potentially receptive territories in Africa. This study sought to determine the geographic distribution of An. stephensi in southern Ethiopia. Methods: A targeted entomological survey, both larvae and adult, was conducted in Hawassa city, Southern Ethiopia between November 2022 and February 2023. Anopheles Larvae were reared to adults for species identification. CDC light traps and BG Pro traps were used overnight both indoor and outdoor at selected houses to collect adult mosquitoes in the study area. Prokopack Aspirator was employed to sample indoor resting mosquitoes in the morning. Adults of An. stephensi was identified using morphological keys, and then confirmed by PCR. Results: Larvae of An. stephensi were found in 28 (16.6%) of the 169 potential mosquito breeding sites surveyed. Out of 548 adult female Anopheles mosquitoes reared from larvae, 234 (42.7%) were identified to be An. stephensi morphologically. A total of 449 female anophelines were caught, of which 53 (12.0%) were An. stephensi. Other anopheline species collected in the study area included An. gambiae (s.l.), An. pharoensis, An. coustani, and An. demeilloni. Conclusion: The study, for the first time, confirmed the presence of An. stephensi in southern Ethiopia. The presence of both larval and adult stages of this mosquito attest that this species established a sympatric colonization with native vector species such as An. gambiae (s.l.) in Southern Ethiopia. The findings warrant further investigation on the ecology, behavior, population genetics, and role of An. stephensi in malaria transmission in Ethiopia.

Increased malaria incidence following irrigation practices in the Endorheic Rift Valley Basin of Sidama Region, Ethiopia.

BACKGROUND: Water resource development practice such as irrigation is key to ensuring economic growth and food security in developing countries. However, unintended public health problems such as malaria linked to such development projects have been a concern. This study aimed to determine the impact of irrigation on malaria incidence and vector mosquito abundance in southern Ethiopia. METHODS: Eight years' malaria morbidity data were extracted from the medical registers of health facilities in both irrigated and non-irrigated settings. Additionally, adult and larval malaria vector surveys were carried out in both irrigated and non-irrigated villages. The trend of malaria incidence, case distribution across age and sex, seasonality, parasite species proportion, and mosquito density were analyzed and compared between irrigated and non-irrigated villages. RESULTS: The result showed that annual mean malaria incidence was 6.3 higher in the irrigated (95% CI: 0.7-33.6) than in the non-irrigated villages (95% CI: 1.2-20.6). Although a remarkable declining trend in malaria incidence was observed for four successive years (2013-2017), a significant resurgence between 2018 and 2020 was noted following the introduction of irrigation schemes. The densities of adult Anopheles mosquitoes were 15-fold higher in the irrigated compared to non-irrigated villages. Of the total potential mosquito-breeding habitats surveyed, the majority (93%) were from irrigated villages. CONCLUSION: Higher malaria incidence, adult Anopheles density, and mosquito-breeding habitat were recorded in the irrigated villages compared to non-irrigated villages. These observations have important implications for the effectiveness of existing malaria interventions. Environmental management could help reduce the breeding of malaria vector mosquitoes around irrigation schemes.

Evidence of pyrethroid resistance in Anopheles amharicus and Anopheles arabiensis from Arjo-Didessa irrigation scheme, Ethiopia.

BACKGROUND: Indoor residual spraying and insecticide-treated nets are among the key malaria control intervention tools. However, their efficacy is declining due to the development and spread of insecticide resistant vectors. In Ethiopia, several studies reported resistance of An. arabiensis to multiple insecticide classes. However, such data is scarce in irrigated areas of the country where insecticides, pesticides and herbicides are intensively used. Susceptibility of An. gambiae s.l. to existing and new insecticides and resistance mechanisms were assessed in Arjo-Didessa sugarcane plantation area, southwestern Ethiopia. METHODS: Adult An. gambiae s.l. reared from larval/pupal collections of Arjo-Didessa sugarcane irrigation area and its surrounding were tested for their susceptibility to selected insecticides. Randomly selected An. gambiae s.l. (dead and survived) samples were identified to species using species-specific polymerase chain reaction (PCR) and were further analyzed for the presence of knockdown resistance (kdr) alleles using allele-specific PCR. RESULTS: Among the 214 An. gambiae s.l. samples analyzed by PCR, 89% (n = 190) were An. amharicus and 9% (n = 20) were An. arabiensis. Mortality rates of the An. gambiae s.l. exposed to deltamethrin and alphacypermethrin were 85% and 86.8%, respectively. On the other hand, mortalities against pirmiphos-methyl, bendiocarb, propoxur and clothianidin were 100%, 99%, 100% and 100%, respectively. Of those sub-samples (An. amharicus and An. arabiensis) examined for presence of kdr gene, none of them were found to carry the L1014F (West African) allelic mutation. CONCLUSION: Anopheles amharicus and An. arabiensis from Arjo-Didessa sugarcane irrigation area were resistant to pyrethroids which might be synergized by extensive use of agricultural chemicals. Occurrence of pyrethroid resistant malaria vectors could challenge the ongoing malaria control and elimination program in the area unless resistance management strategies are implemented. Given the resistance of An. amharicus to pyrethroids, its behavior and vectorial capacity should be further investigated.

The impact of large and small dams on malaria transmission in four basins in Africa.

Expansion of various types of water infrastructure is critical to water security in Africa. To date, analysis of adverse disease impacts has focused mainly on large dams. The aim of this study was to examine the effect of both small and large dams on malaria in four river basins in sub-Saharan Africa (i.e., the Limpopo, Omo-Turkana, Volta and Zambezi river basins). The European Commission's Joint Research Center (JRC) Yearly Water Classification History v1.0 data set was used to identify water bodies in each of the basins. Annual malaria incidence data were obtained from the Malaria Atlas Project (MAP) database for the years 2000, 2005, 2010 and 2015. A total of 4907 small dams and 258 large dams in the four basins, with 14.7million people living close (< 5 km) to their reservoirs in 2015, were analysed. The annual number of malaria cases attributable to dams of either size across the four basins was 0.9-1.7 million depending on the year, of which between 77 and 85% was due to small dams. The majority of these cases occur in areas of stable transmission. Malaria incidence per kilometre of reservoir shoreline varied between years but for small dams was typically 2-7 times greater than that for large dams in the same basin. Between 2000 and 2015, the annual malaria incidence showed a broadly declining trend for both large and small dam reservoirs in areas of stable transmission in all four basins. In conclusion, the malaria impact of dams is far greater than previously recognized. Small and large dams represent hotspots of malaria transmission and, as such, should be a critical focus of future disease control efforts.

Predicting distribution of malaria vector larval habitats in Ethiopia by integrating distributed hydrologic modeling with remotely sensed data.

Larval source management has gained renewed interest as a malaria control strategy in Africa but the widespread and transient nature of larval breeding sites poses a challenge to its implementation. To address this problem, we propose combining an integrated high resolution (50 m) distributed hydrological model and remotely sensed data to simulate potential malaria vector aquatic habitats. The novelty of our approach lies in its consideration of irrigation practices and its ability to resolve complex ponding processes that contribute to potential larval habitats. The simulation was performed for the year of 2018 using ParFlow-Common Land Model (CLM) in a sugarcane plantation in the Oromia region, Ethiopia to examine the effects of rainfall and irrigation. The model was calibrated using field observations of larval habitats to successfully predict ponding at all surveyed locations from the validation dataset. Results show that without irrigation, at least half of the area inside the farms had a 40% probability of potential larval habitat occurrence. With irrigation, the probability increased to 56%. Irrigation dampened the seasonality of the potential larval habitats such that the peak larval habitat occurrence window during the rainy season was extended into the dry season. Furthermore, the stability of the habitats was prolonged, with a significant shift from semi-permanent to permanent habitats. Our study provides a hydrological perspective on the impact of environmental modification on malaria vector ecology, which can potentially inform malaria control strategies through better water management.

Survivorship of Anopheles gambiae sensu lato in irrigated sugarcane plantation scheme in Ethiopia.

BACKGROUND: To ensure food security, sub-Saharan Africa has initiated massive water resource development projects, such as irrigated agriculture, in recent years. However, such environmental modifications affect the survivorship and development of mosquitoes, which are vectors of different diseases. This study aimed at determining the effects of irrigation practices on development and survivorship of Anopheles gambiae s.l. in Ethiopia. METHODS: A life table experiment was conducted to examine the effect of environmental modification on survivorship of both immature and adult An. gambiae s.l. in irrigated and non-irrigated areas. The pupation rate and development time of the immatures and adult longevity and fecundity were compared between the two settings. RESULTS: The estimated mean survival time of female An. gambiae s.l. in the irrigated and non-irrigated areas was 37.9 and 31.3 days, respectively. A survival analysis showed that adult females of An. gambiae s.l. placed in an irrigated area lived significantly longer than those in a non-irrigated area (χ2 = 18.3, df = 1, P <0.001), and An. gambiae s.l. females lived significantly longer than males in both areas (P < 0.001). CONCLUSIONS: Adult An. gambiae s.l. survivorship was found to be enhanced in the irrigated area compared to non-irrigated area. Longer survival of adult mosquitoes in irrigated areas could have important implications for vectorial capacity and hence malaria transmission.