METHODS: The study utilized a cross-sectional study design, using a structured and pre-tested questionnaire to obtain information from 380 respondents. Respondents were classified as ITN users if they slept under an ITN for at least 3 days in a week, while those who did not at all, or slept under it less frequently were classified as ITN non-users. Chi squared test was performed to test the bivariate association between ITN use and each of the items of the questionnaire. A further multivariate logistic regression was performed to determine the predictors of ITN use.
RESULTS: The respondents' ages ranged from 15 to 45 years, with median (interquartile range) age of 25 (8) years. Eighty percent of them were aware of ITN, but 50.5% believed ITNs could be dangerous. Only 5.5% and 0.8% respectively felt that sleeping under and ITN was either just bad or very bad for their health. Thirty-five percent of the respondents were ITN users. Not having a previous miscarriage (OR = 2.38; 95% CI 1.41-4.03, p = 0.001), knowledge that ITNs were not to be washed after every 1 month (OR = 3.60; 95% CI 1.18-11.06), significant others thinking they should sleep under an ITN (OR = 3.06; 95% CI 1.35-6.96), ability to effectively persuade others to sleep under an ITN (OR = 2.37; 95% CI 1.14-4.94) were significantly associated with ITN use.
CONCLUSIONS: A large proportion of pregnant women in this study were not sleeping under ITNs. The development of health promotion interventions aimed at boosting their self-efficacies for ITN use, and improving social support from their spouses are, therefore, recommended. Health education on ITN use should also be incorporated into post-abortal management.
METHODS: The study was a randomized controlled parallel-group study, where 372 randomly selected antenatal care attendees were randomly assigned to one of either two groups after collecting baseline data. The intervention group then received a four-hour health education intervention in Hausa language, which was developed based on the IMB model, while the control group received a similarly designed health education on breastfeeding. Follow up data were then collected from the participants at a first (2 months post-intervention) and second (4 months post-intervention) follow up, and at the end of their pregnancies.
RESULTS: For both groups, reported ITN use had increased from baseline (Intervention: Often-14.0%, Almost always-9.1; Control: Often-12.4%; Almost always 16.1%) to the time of second follow up (Intervention: Often -28.10%, Almost always-24.5; Control: Often-17.2%; Almost always 19.5%). Reported IPTp uptake at second follow up was also higher for the intervention group (Intervention: Two doses-59.0%, Three doses 22.3%; Control group: Two doses-48.4%, Three doses-7.0%). The drop in the haematocrit levels was greater for the control group (32.42% to 30.63%) compared to the intervention group (33.09% to 31.93%). The Generalized Linear Mixed Models (GLMM) analysis revealed that the intervention had significantly improved reported ITN use, reported IPTp uptake, and haematocrit levels, but had no significant effect on the incidence of reported malaria diagnosis or babies' birth weights.
CONCLUSIONS: The intervention was effective in improving ITN use, IPTp uptake, and haematocrit levels. It is, therefore, recommended for the modules to be adopted and incorporated into the routine antenatal care programmes in health centres with predominantly Hausa speaking clients.
TRIAL REGISTRATION: Pan African Clinical Trial Registry, PACTR201610001823405. Registered 26 October 2016, www.pactr.org .
MAIN TEXT: Plasmodium knowlesi is the most common cause of malaria in Malaysia, and cases have also been reported in nearly all countries of Southeast Asia. Outside of Malaysia, P. knowlesi is frequently misdiagnosed by microscopy as Plasmodium falciparum or Plasmodium vivax. Thus, P. knowlesi may be underdiagnosed in affected regions and its true incidence underestimated. Acknowledgement in the World Malaria Report of the regional importance of P. knowlesi will facilitate efforts to improve surveillance of this emerging parasite. Furthermore, increased recognition will likely lead to improved delivery of effective treatment for this potentially fatal infection, as has occurred in Malaysia where P. knowlesi case-fatality rates have fallen despite rising incidence. In a number of knowlesi-endemic countries, substantial progress has been made towards the elimination of P. vivax and P. falciparum. However, efforts to eliminate these human-only species should not preclude efforts to reduce human malaria from P. knowlesi. The regional importance of knowlesi malaria was recognized by the WHO with its recent Evidence Review Group meeting on knowlesi malaria to address strategies for prevention and mitigation.
CONCLUSION: The WHO World Malaria Report has an appropriate focus on falciparum and vivax malaria, the major causes of global mortality and morbidity. However, the authors hope that in future years this important publication will also incorporate data on the progress and challenges in reducing knowlesi malaria in regions where transmission occurs.
CASE PRESENTATION: A 61 years old asplenic man was admitted to a tertiary referral hospital in Sabah, Malaysia, with severe knowlesi malaria characterized by hyperparasitaemia (7.9 %), jaundice, respiratory distress, metabolic acidosis, and acute kidney injury. He was commenced on intravenous artesunate, but1 day later developed haemoglobinuria, associated with a 22 % reduction in admission haemoglobin. Additional investigations, including a cell-free haemoglobin of 10.2 × 10(5) ng/mL and an undetectable haptoglobin, confirmed intravascular haemolysis. The patient continued on intravenous artesunate for a total of 48 h prior to substitution with artemether-lumefantrine, and made a good recovery with resolution of his haemoglobinuria and improvement of his kidney function by day 3.
CONCLUSIONS: An asplenic patient with hyperparasitaemic severe knowlesi malaria developed haemoglobinuria after treatment with intravenous artesunate. There are plausible mechanisms for increased haemolysis with hyperparasitaemia, and following both splenectomy and artesunate. Although in this case the patient made a rapid recovery, knowlesi malaria patients with this unusual complication should be closely monitored for potential deterioration.
METHODS: Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and disease progression was evaluated.
RESULTS: Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice.
CONCLUSION: These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection.
CASE PRESENTATION: A 23-year old splenectomized patient with beta thalassaemia major presented with fever 11 days after receiving a blood transfusion from a pre-symptomatic donor who presented with knowlesi malaria 12 days following blood donation. The infection resulted in severe disease in the recipient, with a parasite count of 84,000/µL and associated metabolic acidosis and multi-organ failure. She was treated with intravenous artesunate and made a good recovery. Sequencing of a highly diverse 649-base pair fragment of the P. knowlesi bifunctional dihydrofolate reductase-thymidylate synthase gene (pkdhfr) revealed that the recipient and donor shared the same haplotype.
CONCLUSIONS: This case demonstrates that acquisition of P. knowlesi from blood transfusion can occur, and that clinical consequences can be severe. Furthermore, this case raises the possibility that thalassaemic patients, particularly those who are splenectomized, may represent a high-risk group for TTM and severe malaria. With rising P. knowlesi incidence, further studies in Sabah are required to determine the risk of TTM in order to guide screening strategies for blood transfusion services.
METHODS: The prevalence of G6PD deficiency among 408 Thai participants diagnosed with malaria by microscopy (71), and malaria-negative controls (337), was assessed using a phenotypic test based on water-soluble tetrazolium salts. High-resolution melting (HRM) curve analysis was developed from a previous study to enable the detection of 15 common missense, synonymous and intronic G6PD mutations in Asian populations. The identified mutations were subjected to biochemical and structural characterisation to understand the molecular mechanisms underlying enzyme deficiency.
RESULTS: Based on phenotypic testing, the prevalence of G6PD deficiency (T) and intronic (c.1365-13T>C and c.486-34delT) mutations was detected with intermediate to normal enzyme activity. The double missense mutations were less catalytically active than their corresponding single missense mutations, resulting in severe enzyme deficiency. While the mutations had a minor effect on binding affinity, structural instability was a key contributor to the enzyme deficiency observed in G6PD-deficient individuals.
CONCLUSIONS: With varying degrees of enzyme deficiency, G6PD genotyping can be used as a complement to phenotypic screening to identify those who are eligible for 8-aminoquinolines. The information gained from this study could be useful for management and treatment of malaria, as well as for the prevention of unanticipated reactions to certain medications and foods in the studied population.
METHODS: Mosquito collections were carried out using human landing catches at ground and canopy levels in the Tawau Division of Sabah. Collections were conducted along an anthropogenic disturbance gradient (primary forest, lightly logged virgin jungle reserve and salvage logged forest) between 18:00 and 22:00 h.
RESULTS: Anopheles balabacensis, a vector of P. knowlesi, was the predominant species in all collection areas, accounting for 70 % of the total catch, with a peak landing time of 18:30-20:00 h. Anopheles balabacensis had a preference for landing on humans at ground level compared to the canopy (p
CASE PRESENTATION: A 46-year-old man presented with fever and acute surgical abdomen with concomitant P. knowlesi malaria infection at Kapit Hospital. He was in compensated shock upon arrival to the hospital. He had generalized abdominal tenderness, maximal at the epigastric region. Bedside focused abdominal ultrasonography revealed free fluid in the abdomen. He underwent emergency exploratory laparotomy in view of haemodynamic instability and worsening peritonism. Intraoperatively, haemoperitoneum and bleeding from the spleen was noted. Splenectomy was performed. Histopathological examination findings were suggestive of splenic rupture and presence of malarial pigment. Analysis of his blood sample by nested PCR assays confirmed P. knowlesi infection. The patient completed a course of anti-malarial treatment and recovered well post-operation.
CONCLUSIONS: Spontaneous splenic rupture is a rare complication of malaria. This is the first reported case of splenic rupture in P. knowlesi malaria infection. Detection of such a complication requires high index of clinical suspicion and is extremely challenging in hospitals with limited resources.
METHODS: A total of 46 csp genes were subjected to polymerase chain reaction amplification. The genes were obtained from P. knowlesi isolates collected from different divisions of Sabah, Malaysian Borneo, and Peninsular Malaysia. The targeted gene fragments were cloned into a commercial vector and sequenced, and a phylogenetic tree was constructed while incorporating 168 csp sequences retrieved from the GenBank database. The genetic diversity and natural evolution of the csp sequences were analysed using MEGA6 and DnaSP ver. 5.10.01. A genealogical network of the csp haplotypes was generated using NETWORK ver. 4.6.1.3.
RESULTS: The phylogenetic analysis revealed indistinguishable clusters of P. knowlesi isolates across different geographic regions, including Malaysian Borneo and Peninsular Malaysia. Nucleotide analysis showed that the csp non-repeat regions of zoonotic P. knowlesi isolates obtained in this study underwent purifying selection with population expansion, which was supported by extensive haplotype sharing observed between humans and macaques. Novel variations were observed in the C-terminal non-repeat region of csp.
CONCLUSIONS: The csp non-repeat regions are relatively conserved and there is no distinct cluster of P. knowlesi isolates from Malaysian Borneo and Peninsular Malaysia. Distinctive variation data obtained in the C-terminal non-repeat region of csp could be beneficial for the design and development of vaccines to treat P. knowlesi.
CASE PRESENTATION: A 59-year old man staying near the Belum-Temengor rainforest at the Malaysia-Thailand border was admitted with fever for 6 days, with respiratory distress. His non-structural protein 1 antigen and Anti-DENV Immunoglobulin M tests were positive. He was treated for severe dengue with compensated shock. Treating the dengue had so distracted the clinicians that a blood film for the malaria parasite was not done. Despite aggressive supportive treatment in the intensive care unit (ICU), the patient had unresolved acidosis as well as multi-organ failure involving respiratory, renal, liver, and haematological systems. It was due to the presentation of shivering in the ICU, that a blood film was done on the second day that revealed the presence of P. knowlesi with a parasite count of 520,000/μL. The patient was subsequently treated with artesunate-doxycycline and made a good recovery after nine days in ICU.
CONCLUSIONS: This case contributes to the body of literature on co-infection between DENV and P. knowlesi and highlights the clinical consequences, which can be severe. Awareness should be raised among health-care workers on the possibility of dengue-malaria co-infection in this region. Further research is required to determine the real incidence and risk of co-infection in order to improve the management of acute febrile illness.