216 results on '"Kenangalem E"'
Search Results
2. Increased circulating myeloid-derived suppressor cells in vivax malaria and severe falciparum malaria
- Author
-
Leonardo, L, Kenangalem, E, Poespoprodjo, JR, Noviyanti, R, Price, RN, Anstey, NM, Minigo, G, and Kho, S
- Subjects
Infectious Diseases ,Indonesia ,Myeloid-Derived Suppressor Cells ,Plasmodium falciparum ,Malaria, Vivax ,Humans ,Parasitology ,Malaria, Falciparum ,Plasmodium vivax ,Malaria - Abstract
Background Circulating myeloid-derived-suppressor-cells (MDSC) with immunosuppressive function are increased in human experimental Plasmodium falciparum infection, but have not been studied in clinical malaria. Methods Using flow-cytometry, circulating polymorphonuclear-MDSC were evaluated in cryopreserved samples from patients with uncomplicated Plasmodium vivax (n = 8) and uncomplicated (n = 4) and severe (n = 16) falciparum malaria from Papua, Indonesia. Results The absolute number of circulating polymorphonuclear-MDSC were significantly elevated in severe falciparum malaria patients compared to controls (n = 10). Polymorphonuclear-MDSC levels in uncomplicated vivax malaria were also elevated to levels comparable to that seen in severe falciparum malaria. Conclusion Control of expansion of immunosuppressive MDSC may be important for development of effective immune responses in falciparum and vivax malaria.
- Published
- 2022
3. Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria
- Author
-
Studniberg, SI, Ioannidis, LJ, Utami, RAS, Trianty, L, Liao, Y, Abeysekera, W, Li-Wai-Suen, CSN, Pietrzak, HM, Healer, J, Puspitasari, AM, Apriyanti, D, Coutrier, F, Poespoprodjo, JR, Kenangalem, E, Andries, B, Prayoga, P, Sariyanti, N, Smyth, GK, Cowman, AF, Price, RN, Noviyanti, R, Shi, W, Garnham, AL, and Hansen, DS
- Subjects
Adult ,Immunosuppression Therapy ,General Immunology and Microbiology ,Applied Mathematics ,Plasmodium falciparum ,Parasitemia ,General Biochemistry, Genetics and Molecular Biology ,Computational Theory and Mathematics ,Humans ,CTLA-4 Antigen ,Malaria, Falciparum ,General Agricultural and Biological Sciences ,Asymptomatic Infections ,Information Systems - Abstract
Clinical immunity to P. falciparum malaria is non-sterilizing, with adults often experiencing asymptomatic infection. Historically, asymptomatic malaria has been viewed as beneficial and required to help maintain clinical immunity. Emerging views suggest that these infections are detrimental and constitute a parasite reservoir that perpetuates transmission. To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T-cell function, and CTLA-4 as a predicted regulator in these processes. As proof of concept, we demonstrated a role for CTLA-4 in the development of asymptomatic parasitemia in infection models. The results suggest that asymptomatic malaria is not innocuous and might not support the induction of immune processes to fully control parasitemia or efficiently respond to malaria vaccines.
- Published
- 2022
4. Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale.
- Author
-
Kho, S, Anstey, NM, Barber, BE, Piera, K, William, T, Kenangalem, E, McCarthy, JS, Jang, IK, Domingo, GJ, Britton, S, Grigg, MJ, Kho, S, Anstey, NM, Barber, BE, Piera, K, William, T, Kenangalem, E, McCarthy, JS, Jang, IK, Domingo, GJ, Britton, S, and Grigg, MJ
- Abstract
Commercial point-of-care tests remain insufficient for accurately detecting and differentiating low-level malaria infections in regions co-endemic with multiple non-falciparum species, including zoonotic Plasmodium knowlesi (Pk). A 5-plex chemiluminescent assay simultaneously measures pan-Plasmodium lactate dehydrogenase (pLDH), P. falciparum (Pf)-LDH, P. vivax (Pv)-LDH, Pf-histidine-rich protein-2 (HRP2), and C-reactive protein. We assessed its diagnostic performance on whole blood (WB) samples from 102 healthy controls and 306 PCR-confirmed clinical cases of Pf, Pv, Pk, P. malariae (Pm) and P. ovale (Po) mono-infections from Southeast-Asia. We confirm its excellent HRP2-based detection of Pf. Cross-reactivity of Pf-LDH with all non-falciparum species tested was observed (specificity 57.3%). Pv-LDH performance was suboptimal for Pv (93.9% sensitivity and 73.9% specificity). Poor specificity was driven by strong Pk cross-reactivity, with Pv-LDH detecting 93.9% of Pk infections. The pan-LDH-to-Pf-LDH ratio was capable of discerning Pv from Pk, and robustly differentiated Pf from Pm or Po infection, useful in regions with hrp2/3 deletions. We tested the platform's performance in plasma for the first time, with WB outperforming plasma for all analytes except Pv-LDH for Pk. The platform is a promising tool for WB malaria diagnosis, although further development is warranted to improve its utility in regions co-endemic for multiple non-falciparum species.
- Published
- 2022
5. Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children.
- Author
-
Oyong, DA, Loughland, JR, Soon, MSF, Chan, J-A, Andrew, D, Wines, BD, Hogarth, PM, Olver, SD, Collinge, AD, Varelias, A, Beeson, JG, Kenangalem, E, Price, RN, Anstey, NM, Minigo, G, Boyle, MJ, Oyong, DA, Loughland, JR, Soon, MSF, Chan, J-A, Andrew, D, Wines, BD, Hogarth, PM, Olver, SD, Collinge, AD, Varelias, A, Beeson, JG, Kenangalem, E, Price, RN, Anstey, NM, Minigo, G, and Boyle, MJ
- Abstract
BACKGROUND: Protective malarial antibodies are acquired more rapidly in adults than children, independently of cumulative exposure, however the cellular responses mediating these differences are unknown. CD4 T-follicular helper (Tfh) cells have key roles in inducing antibodies, with Th2-Tfh cell activation associated with antibody development in malaria. Whether Tfh cell activation in malaria is age dependent is unknown and no studies have compared Tfh cell activation in children and adults with malaria. METHODS: We undertook a comprehensive study of Tfh cells, along with B cells and antibody induction in children and adults with malaria. Activation and proliferation of circulating Tfh (cTfh) cell subsets was measured ex vivo and parasite-specific Tfh cell frequencies and functions studied with Activation Induced Marker (AIM) assays and intracellular cytokine staining. FINDINGS: During acute malaria, the magnitude of cTfh cell activation was higher in adults than in children and occurred across all cTfh cell subsets in adults but was restricted only to the Th1-cTfh subset in children. Further, adults had higher levels of parasite-specific cTfh cells, and cTfh cells which produced more Th2-Tfh associated cytokine IL-4. Consistent with a role of higher Tfh cell activation in rapid immune development in adults, adults had higher activation of B cells during infection and higher induction of antibodies 7 and 28 days after malaria compared to children. INTERPRETATION: Our data provide evidence that age impacts Tfh cell activation during malaria, and that these differences may influence antibody induction after treatment. Findings have important implications for vaccine development in children. FUNDING: This word was supported by the National Health and Medical Research Council of Australia, Wellcome Trust, Charles Darwin University Menzies School of Health Research, Channel 7 Children's Research Foundation, and National Health Institute.
- Published
- 2022
6. Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria
- Author
-
Studniberg, S, Ioannidis, LJ, Utami, RAS, Trianty, L, Liao, Y, Abeysekera, W, Li-Wai-Suen, CSN, Pietrzak, HM, Healer, J, Puspitasari, AM, Apriyanti, D, Coutrier, F, Poespoprodjo, JR, Kenangalem, E, Andries, B, Prayoga, P, Sariyanti, N, Smyth, GK, Cowman, AF, Price, RN, Noviyanti, R, Shi, W, Garnham, AL, Hansen, DS, Studniberg, S, Ioannidis, LJ, Utami, RAS, Trianty, L, Liao, Y, Abeysekera, W, Li-Wai-Suen, CSN, Pietrzak, HM, Healer, J, Puspitasari, AM, Apriyanti, D, Coutrier, F, Poespoprodjo, JR, Kenangalem, E, Andries, B, Prayoga, P, Sariyanti, N, Smyth, GK, Cowman, AF, Price, RN, Noviyanti, R, Shi, W, Garnham, AL, and Hansen, DS
- Abstract
Clinical immunity to P. falciparum malaria is non-sterilizing, with adults often experiencing asymptomatic infection. Historically, asymptomatic malaria has been viewed as beneficial and required to help maintain clinical immunity. Emerging views suggest that these infections are detrimental and constitute a parasite reservoir that perpetuates transmission. To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T-cell function, and CTLA-4 as a predicted regulator in these processes. As proof of concept, we demonstrated a role for CTLA-4 in the development of asymptomatic parasitemia in infection models. The results suggest that asymptomatic malaria is not innocuous and might not support the induction of immune processes to fully control parasitemia or efficiently respond to malaria vaccines.
- Published
- 2022
7. Supervised versus unsupervised primaquine radical cure for the treatment of falciparum and vivax malaria in Papua, Indonesia: a cluster-randomised, controlled, open-label superiority trial
- Author
-
Poespoprodjo, JR, Burdam, FH, Candrawati, F, Ley, B, Meagher, N, Kenangalem, E, Indrawanti, R, Trianty, L, Thriemer, K, Price, DJ, Simpson, JA, Price, RN, Poespoprodjo, JR, Burdam, FH, Candrawati, F, Ley, B, Meagher, N, Kenangalem, E, Indrawanti, R, Trianty, L, Thriemer, K, Price, DJ, Simpson, JA, and Price, RN
- Abstract
BACKGROUND: There is a high risk of Plasmodium vivax recurrence in patients treated for Plasmodium falciparum malaria in co-endemic areas. Primaquine radical cure has the potential to reduce P vivax recurrences in patients presenting with P falciparum as well as P vivax malaria but is undermined by poor adherence to the currently recommended 14-day regimen. We aimed to assess the efficacy and safety of supervised versus unsupervised primaquine radical cure in patients presenting with uncomplicated malaria. METHODS: We did a cluster-randomised, controlled, open-label superiority trial in Papua, Indonesia. 21 clusters of village health posts, matched by annual parasite index, were randomly assigned (1:1) to treat patients (age >12 months and body weight >5 kg) presenting with confirmed uncomplicated P falciparum or P vivax malaria with oral dihydroartemisinin-piperaquine plus either a supervised or unsupervised 14-day course of oral primaquine (0·5 mg/kg per day). Patients in the supervised group were supervised taking their primaquine dose on alternate days. Patients were followed-up for 6 months and those who presented again with malaria were retreated with the same drug regimen. Masking was not possible due to the nature of the study. The primary outcome was the incidence risk of P vivax malaria over 6 months, assessed in the modified intention-to-treat population (all patients who were assigned to a treatment group, excluding patients who were lost to follow-up after their first visit). This trial is now complete, and is registered with ClinicalTrials.gov, NCT02787070. FINDINGS: Between Sept 14, 2016, and July 31, 2018, 436 patients were screened for eligibility and 419 were enrolled; 223 (53%) patients in 11 clusters were assigned to supervised primaquine treatment and 196 (47%) in ten clusters to unsupervised primaquine treatment. 161 (72%) of 223 patients in the supervised group and 151 (77%) of 196 in the unsupervised group completed 6 months of follow-up. At
- Published
- 2022
8. Intermittent screening and treatment for malaria complementary to routine immunisation in the first year of life in Papua, Indonesia: a cluster randomised superiority trial
- Author
-
Poespoprodjo, JR, Hafiidhaturrahmah, Sariyanti, N, Indrawanti, R, McLean, ARD, Simpson, JA, Kenangalem, E, Burdam, FH, Noviyanti, R, Trianty, L, Fadhilah, C, Soenarto, Y, Price, RN, Poespoprodjo, JR, Hafiidhaturrahmah, Sariyanti, N, Indrawanti, R, McLean, ARD, Simpson, JA, Kenangalem, E, Burdam, FH, Noviyanti, R, Trianty, L, Fadhilah, C, Soenarto, Y, and Price, RN
- Abstract
BACKGROUND: In Papua (Indonesia), infants with P. falciparum and/or P. vivax malaria are at risk of severe anaemia and death. We hypothesized that in an area of high malaria transmission, intermittent screening and treatment of infants with malaria (ISTi) will reduce morbidity compared to passive case detection (PCDi). METHODS: We conducted a cluster randomised, open label, superiority trial. A total of 21 clusters of village health posts (VHP) were randomised 1:1 to either IST for infants coinciding with 4 routine immunisation visits or PCDi. Healthy term infants born to consenting mothers enrolled into a maternal malaria cluster randomised trial were included in the study and followed for 12 months. Point of care malaria rapid diagnostic tests were used to detect peripheral parasitaemia at 2, 3, 4 and 9 months old in all infants in ISTi clusters and when symptomatic in PCDi clusters. Infants with detected peripheral parasitaemia were treated with dihydroartemisinin-piperaquine. The co-primary outcomes were the incidence rate of clinical malaria in the first year of life and the prevalence of parasitaemia at age 12 months. The incidence rate ratio and prevalence ratio between ISTi and PCDi were estimated using mixed-effects Poisson and log-binomial regression modelling (accounting for clustering at VHP level). RESULTS: Between May 2014 and February 2017, 757 infants were enrolled into the study, 313 into 10 ISTi clusters, and 444 into 11 PCDi clusters. Overall, 132 episodes of parasitaemia were detected, of whom 17 (12.9%) were in symptomatic infants. Over 12 months, the incidence rate (IR) of clinical malaria was 24 [95% CI, 10-50] per 1000 children-years at risk in the ISTi arm and 19 [95% CI, 8,38] per 1000 children-years in the PCDi arm (adjusted incidence rate ratio [aIRR] 1.77 [95% CI, 0.62-5.01]; p = 0.280). The prevalence of parasitaemia at 12 months was 13% (33/254) in the IST clusters and 15% (57/379) in the PCD clusters (adjusted prevalence ratio (aPR) =
- Published
- 2022
9. Impacts of tuberculosis services strengthening and the COVID-19 pandemic on case detection and treatment outcomes in Mimika District, Papua, Indonesia: 2014-2021.
- Author
-
Eslava-Schmalbach, JH, Lestari, T, Kamaludin, Lowbridge, C, Kenangalem, E, Poespoprodjo, JR, Graham, SM, Ralph, AP, Eslava-Schmalbach, JH, Lestari, T, Kamaludin, Lowbridge, C, Kenangalem, E, Poespoprodjo, JR, Graham, SM, and Ralph, AP
- Abstract
Indonesia is a high-burden tuberculosis (TB) country with a wide case detection gap, exacerbated by the COVID-19 pandemic. We aimed to review the epidemiology of TB in a high-endemic setting of Indonesia before and during the implementation of health system strengthening activities for TB, including during the first two years of the COVID-19 pandemic. We analysed TB program data from Mimika District, Papua, Indonesia from 2014 to 2021. Health system strengthening activities to improve the programmatic management of TB were implemented from 2017 onwards. Activities included decentralization of TB services, training and mentoring of healthcare workers, improved screening for co-morbidities, and introduction and optimisation of Xpert testing in 2018. A total of 11,803 TB cases were notified to the Mimika District Health Office over eight years (2014-21). Between 2015 and 2019, there was a 67% increase in annual case notifications, an 89% increase in bacteriologically confirmed cases and the proportion of TB cases detected in primary care increased from 26% to 46%. In 2020, coinciding with the COVID-19 pandemic, investigation of people with presumptive TB fell by 38%, but the proportion of those tested with Xpert increased. TB case notifications decreased by 19% from 1,796 in 2019 to 1,461 in 2020, but then increased by 17% to 1,716 in 2021. Routine screening for co-morbidities (HIV, diabetes) among TB patients improved over time and was not affected by the pandemic. Treatment success overall was 71% and remained relatively unchanged. Loss to follow-up and death were 18% and 3.7% respectively. Improvements in TB case finding were observed over a period in which a range of health system strengthening activities were implemented. While COVID-19 had a negative impact on the TB program in Mimika District, there are encouraging signs of recovery. Further work is needed to improve TB treatment outcomes.
- Published
- 2022
10. Highly Effective Therapy for Maternal Malaria Associated With a Lower Risk of Vertical Transmission
- Author
-
Poespoprodjo, J. R., Fobia, W., Kenangalem, E., Hasanuddin, A., Sugiarto, P., Tjitra, E., Anstey, N. M., and Price, R. N.
- Published
- 2011
- Full Text
- View/download PDF
11. Multistate modelling to investigate the impact of recurrent malaria episodes on hospital admissions and mortality
- Author
-
Dini, S, Douglas, N, Poespoprodjo, JR, Kenangalem, E, Sugiarto, P, Plumb, I, Price, R, and Simpson, J
- Published
- 2021
12. Amplification of pvmdr1 Associated with Multidrug-Resistant Plasmodium vivax
- Author
-
Suwanarusk, R., Chavchich, M., Russell, B., Jaidee, A., Chalfein, F., Barends, M., Prasetyorini, B., Kenangalem, E., Piera, K. A., Lek-Uthai, U., Anstey, N. M., Tjitra, E., Nosten, F., Cheng, Q., and Price, R. N.
- Published
- 2008
- Full Text
- View/download PDF
13. Safety of primaquine in infants with Plasmodium vivax malaria in Papua, Indonesia
- Author
-
Setyadi, A, Arguni, E, Kenangalem, E, Hasanuddin, A, Lampah, DA, Thriemer, K, Anstey, NM, Sugiarto, P, Simpson, JA, Price, RN, Douglas, NM, and Poespoprodjo, JR
- Subjects
lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,parasitic diseases ,lcsh:RC109-216 ,Primaquine ,Safety ,Plasmodium vivax ,Evaluation ,Infants ,lcsh:Infectious and parasitic diseases - Abstract
Background: Primaquine (PQ) prevents relapses of vivax malaria but may induce severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Data on the safety of primaquine in infants are limited. Methods: A retrospective, hospital-based cohort study of infants aged 1–12 months with vivax malaria was carried out in Timika, Papua province, Indonesia. Risks of admission, death and severe haematological outcomes within 30 days of first presentation were compared between infants who did and did not receive primaquine. Infants were not tested routinely for G6PD deficiency as per local guidelines. Results: Between 2004 and 2013, 4078 infants presented to the hospital for the first time with vivax malaria, of whom 3681 (90.3%) had data available for analysis. In total 1228 (33.4%) infants were aged between 1 and 6 months and 2453 (66.6%) between 6 and 12 months of age. Thirty-three (0.9%) patients received low-dose primaquine (LDP), 174 (4.7%) received high-dose primaquine (HDP), 3432 (93.2%) received no primaquine (NPQ) and 42 patients received either a single dose or an unknown dose of primaquine. The risk of the Hb concentration falling by > 25% to less than 5 g/dL was similar in the LDP or HDP groups (4.3%, 1/23) versus the NPQ group (3.5%, 16/461). Three infants (1.4%) died following receipt of PQ, all of whom had major comorbidities. Seventeen patients (0.5%) died in the NPQ group. None of the infants had documented massive haemolysis or renal impairment. Conclusions: Severe clinical outcomes amongst infants treated with primaquine in Papua were rare. The risks of using primaquine in infancy must be weighed against the risks of recurrent vivax malaria in early life.
- Published
- 2019
14. Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia: a rising burden of Plasmodium vivax malaria
- Author
-
Poespoprodjo, JR, Kenangalem, E, Douglas, N, Burdam, L, Gdeumana, K, Chalfien, F, Prayoga, P, Thio, F, Devine, A, Marfurt, J, Waramori, G, Yeung, S, Noviyanti, R, Penttinen, P, Bangs, MJ, Sugiarto, P, Simpson, JA, Soenarto, Y, Anstey, NM, and Price, RN
- Published
- 2020
15. Adherence to radical cure for Plasmodium vivax malaria in Papua, Indonesia
- Author
-
Rahmalia, A, Poespoprodjo, JR, Landuwulang, CU, Ronse, M, Kenangalem, E, Burdam, FH, Ley, B, Price, RN, Thriemer, K, Grietens, KP, and Gryseels, C
- Published
- 2020
16. Dihydroartemisinin-piperaquine versus artesunate-amodiaquine: superior efficacy and posttreatment prophylaxis against multidrug-resistant plasmodium falciparum and plasmodium vivax malaria
- Author
-
Hasugian, A.R., Purba, H.L.E., Kenangalem, E., Wuwung, R.M., Ebsworth, E.P., Maristela, R., Penttinen, P.M.P., Laihad, F., Anstey, N.M., Tjitra, E., and Price, R.N.
- Subjects
Malaria -- Care and treatment ,Antimalarials -- Dosage and administration ,Antimalarials -- Research ,Drug therapy, Combination -- Research ,Health ,Health care industry - Published
- 2007
17. Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison
- Author
-
Ratcliff, A., Siswantoro, H., Kenangalem, E., Maristela, R., Wuwung, R.M., Laihad, F., Ebsworth, E.P., Anstey, N.M., Tjitra, E., and Price, R.N.
- Subjects
Artemisia -- Usage ,Artemisia -- Health aspects ,Malaria -- Care and treatment ,Drug resistance -- Care and treatment - Published
- 2007
18. The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia
- Author
-
Fuehrer, H-P, Thriemer, K, Poespoprodjo, J-R, Kenangalem, E, Douglas, NM, Sugiarto, P, Anstey, NM, Simpson, JA, Price, RN, Fuehrer, H-P, Thriemer, K, Poespoprodjo, J-R, Kenangalem, E, Douglas, NM, Sugiarto, P, Anstey, NM, Simpson, JA, and Price, RN
- Abstract
The widespread use of primaquine (PQ) radical cure for P. vivax, is constrained by concerns over its safety. We used routinely collected patient data to compare the overall morbidity and mortality in patients treated with and without PQ without prior testing of Glucose-6-Phosphate-Dehydrogenase (G6PD) deficiency in Papua, Indonesia, where there is a low prevalence of G6PD deficiency. Records were collated from patients older than 1 year, with P. vivax infection, who were treated with an artemisinin combination therapy (ACT). The risks of re-presentation, hospitalization, major fall in haemoglobin and death within 30 days were quantified and compared between patients treated with and without PQ using a Cox regression model. In total 26,216 patients with P. vivax malaria presented to the hospital with malaria during the study period. Overall 27.56% (95% Confidence Interval (95%CI): 26.96-28.16) of 21,344 patients treated with PQ re-presented with any illness within 30 days and 1.69% (1.51-1.88) required admission to hospital. The corresponding risks were higher in the 4,872 patients not treated with PQ; Adjusted Hazard Ratio (AHR) = 0.84 (0.79-0.91; p<0.001) and 0.54 (0.41-0.70; p<0.001) respectively. By day 30, 14.15% (12.45-16.05) of patients who had received PQ had a fall in haemoglobin (Hb) below 7g/dl compared to 20.43% (16.67-24.89) of patients treated without PQ; AHR = 0.66 (0.45-0.97; p = 0.033). A total of 75 (0.3%) patients died within 30 days of treatment with a mortality risk of 0.27% (0.21-0.35) in patients treated with PQ, compared to 0.38% (0.24-0.60) without PQ; AHR = 0.79 (0.43-1.45; p = 0.448). In Papua, Indonesia routine administration of PQ radical cure without prior G6PD testing, was associated with lower risk of all cause hospitalization and other serious adverse clinical outcomes. In areas where G6PD testing is not available or cannot be delivered reliably, the risks of drug induced haemolysis should be balanced against the potential benefits of
- Published
- 2020
19. The risk of morbidity and mortality following recurrent malaria in Papua, Indonesia: a retrospective cohort study
- Author
-
Dini, S, Douglas, NM, Poespoprodjo, JR, Kenangalem, E, Sugiarto, P, Plumb, ID, Price, RN, Simpson, JA, Dini, S, Douglas, NM, Poespoprodjo, JR, Kenangalem, E, Sugiarto, P, Plumb, ID, Price, RN, and Simpson, JA
- Abstract
BACKGROUND: An acute episode of malaria can be followed by multiple recurrent episodes either due to re-infection, recrudescence of a partially treated parasite or, in the case of Plasmodium vivax or P. ovale, relapse from the dormant liver stage of the parasite. The aim of this study was to quantify the impact of recurrent malaria episodes on morbidity and mortality in Papua, Indonesia. METHODS: We undertook a retrospective analysis of routinely collected data from malaria patients attending the primary referral hospital in Papua, Indonesia, between April 2004 and December 2013. Multi-state modelling was used to estimate the effect of recurring malaria episodes on re-presentation and admission to hospital and death. The risks of early (≤ 14 days) and late (15 to 365 days) hospital admission and death were estimated separately in our study to distinguish between the direct and indirect effects of malaria recurrence on adverse outcomes. RESULTS: A total of 68,361 patients were included in the analysis, of whom 37,168 (54.4%) presented initially with P. falciparum, 22,209 (32.5%) with P. vivax, and 8984 (13.1%) with other species. During 12 months of follow-up after each of the first four malaria episodes, 10,868 (15.9%) patients were admitted to hospital and 897 (1.3%) died. The risk of re-presenting to the hospital with malaria increased from 34.7% (95% CI 34.4%, 35.1%) at first episode to 58.6% (57.5%, 59.6%) following the third episode of malaria. After adjusting for co-factors, infection with P. vivax was a significant risk factor for re-presentation (hazard ratio (HR) = 1.48 (95% CI 1.44, 1.51)) and late admission to hospital (HR = 1.17 (1.11, 1.22)). Patients infected with P. falciparum had a greater overall rate of mortality within 14 days (HR = 1.54 (1.25, 1.92)), but after multiple episodes of malaria, there was a trend towards a higher rate of early death in patients infected with P. vivax compared to P. falciparum (HR = 1.91 (0.73, 4.97)). CONCLUSIONS: Com
- Published
- 2020
20. Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine–pyrimethamine in southern Papua, Indonesia
- Author
-
Ratcliff, A., Siswantoro, H., Kenangalem, E., Wuwung, M., Brockman, A., Edstein, M.D., Laihad, F., Ebsworth, E.P., Anstey, N.M., Tjitra, E., and Price, R.N.
- Published
- 2007
- Full Text
- View/download PDF
21. Bridging the knowledge-practice gap in tuberculosis contact management in a high-burden setting: a mixed-methods protocol for a multicenter health system strengthening study
- Author
-
Lestari, T, Graham, S, van den Boogard, C, Triasih, R, Poespoprodjo, JR, Ubra, RR, Kenangalem, E, Mahendradhata, Y, Anstey, NM, Bailie, RS, Ralph, AP, Lestari, T, Graham, S, van den Boogard, C, Triasih, R, Poespoprodjo, JR, Ubra, RR, Kenangalem, E, Mahendradhata, Y, Anstey, NM, Bailie, RS, and Ralph, AP
- Abstract
BACKGROUND: People in close contact with tuberculosis should have screening and appropriate management, as an opportunity for active case detection and prevention. However, implementation of tuberculosis contact screening and management is limited in high-burden settings. Behaviour change is needed across three levels of the healthcare system-policymakers, healthcare providers, and patients. To bridge the wide policy-practice gap, this study draws on the Consolidated Framework for Implementation Research, the Behaviour Change Wheel, and the RE-AIM model (Reach, Effectiveness, Adoption, Implementation, Maintenance) to respectively understand barriers, implement change, and evaluate process and outcome. METHODS: This methods paper describes a mixed-methods intervention study in Eastern Indonesia. Quantitative data will be collected during baseline, intervention, and sustainability periods and analyzed using time series analysis. The primary outcome is the number of individuals completing tuberculosis preventive therapy by the end of the two-year intervention phase. Of an estimated 10,000 contacts during this period, we anticipate that a minimum of 416 will be found to have active TB or will complete preventive therapy. Qualitative data (semi-structured interviews, focus group discussions, and observations) will be collected from consenting healthcare providers, patients, and contacts. Activities to promote policy implementation include healthcare provider training, quarterly continuous quality improvement workshops, a social media discussion forum, and promotional materials. The Consolidated Framework for Implementation Research will be used to identify reasons for limited policy implementation at baseline. The Behaviour Change Wheel will be used to ensure that a suitable range of activities are implemented to facilitate change. The RE-AIM model will be used as the evaluation framework. DISCUSSION: Use of theoretical frameworks in combination can ensure a comprehensiv
- Published
- 2019
22. Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia: A longitudinal surveillance study
- Author
-
von Seidlein, L, Kenangalem, E, Poespoprodjo, JR, Douglas, NM, Burdam, FH, Gdeumana, K, Chalfein, F, Prayoga, Thio, F, Devine, A, Marfurt, J, Waramori, G, Yeung, S, Noviyanti, R, Penttinen, P, Bangs, MJ, Sugiarto, P, Simpson, JA, Soenarto, Y, Anstey, NM, Price, RN, von Seidlein, L, Kenangalem, E, Poespoprodjo, JR, Douglas, NM, Burdam, FH, Gdeumana, K, Chalfein, F, Prayoga, Thio, F, Devine, A, Marfurt, J, Waramori, G, Yeung, S, Noviyanti, R, Penttinen, P, Bangs, MJ, Sugiarto, P, Simpson, JA, Soenarto, Y, Anstey, NM, and Price, RN
- Abstract
BACKGROUND: Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species. METHODS AND FINDINGS: A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre-policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of -12.9% (95% confidence interval [CI] -13.5% to -12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% [100/18,965] versus 0.32% [57/17,691]; difference = -0.21% [95% CI -0.34 to -0.07]) but not in patients with P. vivax malaria (0.28% [21/7,545] versus 0.23% [28/12,397]; difference = -0.05% [95% CI -0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR
- Published
- 2019
23. Early and late mortality after malaria in young children in Papua, Indonesia
- Author
-
Patriani, D, Arguni, E, Kenangalem, E, Dini, S, Sugiarto, P, Hasanuddin, A, Lampah, DA, Douglas, NM, Anstey, NM, Simpson, JA, Price, RN, Poespoprodjo, JR, Patriani, D, Arguni, E, Kenangalem, E, Dini, S, Sugiarto, P, Hasanuddin, A, Lampah, DA, Douglas, NM, Anstey, NM, Simpson, JA, Price, RN, and Poespoprodjo, JR
- Abstract
BACKGROUND: In southern Papua, Indonesia, malaria is highly prevalent in young children and is a significant cause of morbidity and early mortality. The association between malaria and delayed mortality is unknown. METHODS: Routinely-collected hospital surveillance data from southern Papua, Indonesia, were used to assess the risk of recurrent malaria and mortality within 12 months of an initial presentation with malaria in all children younger than 5 years old attending the local hospital. Analysis was primarily by Kaplan Meier and Cox regression methods. RESULTS: In total 15,716 children presenting with malaria between April 2004 and December 2013 were included in the analysis; 6184 (39.3%) with Plasmodium falciparum, 7499 (47.7%) with P. vivax, 203 (1.3%) with P. malariae, 3 with P. ovale and 1827 (11.6%) with mixed infections. Within 1 year, 48.4% (7620/15,716) of children represented a total of 16,957 times with malaria (range 1 to 11 episodes), with the incidence of malaria being greater in patients initially presenting with P. vivax infection (1334 [95%CI 1307-1361] per 1000 patient years) compared to those with P. falciparum infection (920 [896-944]). In total 266 (1.7%) children died within 1 year of their initial presentation, 129 (48.5%) within 30 days and 137 (51.5%) between 31 and 365 days. There was no significant difference in the mortality risk in patients infected with P. vivax versus P. falciparum either before 30 days (Hazard Ratio (HR) 1.02 [0.69,1.49]) or between 31 and 365 days (HR = 1.30 [0.90,1.88]). Children who died had a greater incidence of malaria, 2280 [95%CI 1946-2671] per 1000 patient years preceding their death, compared to 1141 [95%CI 1124-1158] per 1000 patient years in those surviving. CONCLUSIONS: Children under-5 years old with P. vivax malaria, are at significant risk of multiple representations with malaria and of dying within 1 year of their initial presentation. Preventing recurrent malaria must be a public health priority in
- Published
- 2019
24. Plasmodium falciparum Activates CD16(+) Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria
- Author
-
Loughland, JR, Woodberry, T, Boyle, MJ, Tipping, PE, Piera, KA, Amante, FH, Kenangalem, E, Price, RN, Engwerda, CR, Anstey, NM, McCarthy, JS, Minigo, G, Loughland, JR, Woodberry, T, Boyle, MJ, Tipping, PE, Piera, KA, Amante, FH, Kenangalem, E, Price, RN, Engwerda, CR, Anstey, NM, McCarthy, JS, and Minigo, G
- Abstract
BACKGROUND: The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs). METHODS: In this study, we show that Plasmodium falciparum skewed CD16+ DC cytokine responses towards interleukin (IL)-10 production in vitro, distinct to the cytokine profile induced by Toll-like receptor ligation. To determine CD16+ DC responsiveness in vivo, we assessed their function after induced P falciparum infection in malaria-naive volunteers. RESULTS: CD16+ DCs underwent distinctive activation, with increased expression of maturation markers human leukocyte antigen (HLA)-DR and CD86, enhanced tumor necrosis factor (TNF) production, and coproduction of TNF/IL-10. In vitro restimulation with P falciparum further increased IL-10 production. In contrast, during naturally acquired malaria episode, CD16+ DCs showed diminished maturation, suggesting increased parasite burden and previous exposure influence DC subset function. CONCLUSIONS: These findings identify CD16+ DCs as the only DC subset activated during primary blood-stage human Plasmodium infection. As dual cytokine producers, CD16+ DCs contribute to inflammatory as well as regulatory innate immune processes.
- Published
- 2019
25. High Risk of Plasmodium vivax Malaria Following Splenectomy in Papua, Indonesia
- Author
-
Kho, S, Andries, B, Poespoprodjo, JR, Commons, RJ, Shanti, PAI, Kenangalem, E, Douglas, NM, Simpson, JA, Sugiarto, P, Anstey, NM, Price, RN, Kho, S, Andries, B, Poespoprodjo, JR, Commons, RJ, Shanti, PAI, Kenangalem, E, Douglas, NM, Simpson, JA, Sugiarto, P, Anstey, NM, and Price, RN
- Abstract
BACKGROUND: Splenectomy increases the risk of severe and fatal infections; however, the risk of Plasmodium vivax malaria is unknown. We quantified the Plasmodium species-specific risks of malaria and other outcomes following splenectomy in patients attending a hospital in Papua, Indonesia. METHODS: Records of all patients attending Mitra-Masyarakat Hospital 2004-2013 were reviewed, identifying those who underwent splenectomy. Subsequent risks of specific clinical outcomes within 12 months for splenectomized patients were compared to nonsplenectomized patients from their first recorded hospital admission. In addition, patients splenectomized for trauma 2015-2016 were followed prospectively for 14 months. RESULTS: Of the 10774 patients hospitalized during 2004-2013, 67 underwent splenectomy. Compared to nonsplenectomized inpatients, patients undergoing splenectomy had a 5-fold higher rate of malaria presentation within 12 months (adjusted hazard ratio [AHR] = 5.0 [95% confidence interval (CI): 3.4-7.3], P < .001). The AHR was 7.8 (95% CI: 5.0-12.3) for P. vivax and 3.0 (95% CI: 1.7-5.4) for P. falciparum (both P < .001). Splenectomized patients had greater risk of being hospitalized for any cause (AHR = 1.8 [95% CI: 1.0-3.0], P = .037) and diarrheal (AHR = 3.5 [95% CI: 1.3-9.6], P = .016). In the 14-month prospective cohort, 12 episodes of P. vivax and 6 episodes of P. falciparum were observed in 11 splenectomised patients. CONCLUSIONS: Splenectomy is associated with a high risk of malaria, greater for P. vivax than P. falciparum. Eradication of P. vivax hypnozoites using primaquine (radical cure) and subsequent malaria prophylaxis is warranted following splenectomy in malaria-endemic areas.
- Published
- 2019
26. Plasmodium falciparum activates CD16+ dendritic cells to produce TNF and IL-10 in subpatent malaria
- Author
-
Loughland, JR, Woodberry, T, Boyle, MJ, Tipping, PE, Piera, KA, Amante, FH, Kenangalem, E, Price, RN, Engwerda, CR, Anstey, NM, McCarthy, JS, and Minigo, G
- Subjects
parasitic diseases ,hemic and immune systems ,chemical and pharmacologic phenomena - Abstract
The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs). Here, we show P. falciparum skewed CD16+ DC cytokine responses towards IL-10 production in vitro, distinct to the cytokine profile induced by toll-like receptor ligation. To determine CD16+ DC responsiveness in vivo, we assessed their function following induced P. falciparum infection in malaria-naive volunteers. CD16+ DCs underwent distinctive activation, with increased expression of maturation markers HLA-DR and CD86, enhanced TNF production and co-production of TNF/IL-10. In vitro re-stimulation with P. falciparum further increased IL-10 production. In contrast, during naturally acquired malaria episode CD16+ DCs showed diminished maturation, suggesting increased parasite burden and previous exposure influence DC subset function. These findings identify CD16+ DCs as the only DC subset activated during primary blood-stage human Plasmodium infection. As dual cytokine producers CD16+ DCs contribute to inflammatory as well as regulatory innate immune processes.
- Published
- 2018
27. Loss of complement regulatory proteins on uninfected erythrocytes in vivax and falciparum malaria anemia
- Author
-
Oyong, DA, Kenangalem, E, Poespoprodjo, JR, Beeson, JG, Anstey, NM, Price, RN, and Boyle, MJ
- Subjects
Adult ,Male ,Aging ,Infectious disease ,Erythrocytes ,Adolescent ,Plasmodium falciparum ,Immunology ,Complement ,Anemia ,CD47 Antigen ,Complement System Proteins ,Malaria ,Young Adult ,hemic and lymphatic diseases ,parasitic diseases ,Malaria, Vivax ,Humans ,Female ,Malaria, Falciparum ,Plasmodium vivax ,Complement Activation ,Research Article - Abstract
Anemia is a major complication of malaria, driven largely by loss of uninfected RBCs during infection. RBC clearance through loss of complement regulatory proteins (CRPs) is a significant contributor to anemia in Plasmodium falciparum infection, but its role in Plasmodium vivax infection is unknown. CRP loss increases RBC susceptibility to macrophage clearance, a process that is also regulated by CD47. We compared CRPs and CD47 expression on infected and uninfected RBCs in adult patients with vivax and falciparum malaria and different anemia severities from Papua, Indonesia. Complement activation and parasite-specific complement-fixing antibodies were measured by ELISA. Levels of CR1 and CD55 were reduced in severe anemia in both falciparum and vivax malaria. Loss of CRPs and CD47 was restricted to uninfected RBCs, with infected RBCs having higher expression. There was no association among complement-fixing antibodies, complement activation, and CRP loss. Our findings demonstrate that CRP loss is a pan-species, age-independent mechanism of malarial anemia. Higher levels of CRP and CD47 expression on infected RBCs suggest that parasites are protected from complement-mediated destruction and macrophage clearance. Lack of associations between protective antibodies and CRP loss highlight that complement pathogenic and protective pathways are distinct mechanisms during infection., Loss of complement regulatory proteins (CRPs) on uninfected RBCs is a pan-species and age-independent driver of malaria anemia.
- Published
- 2018
28. Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group
- Author
-
Thriemer, K, Bobogare, A, Ley, B, Gudo, CS, Alam, MS, Anstey, NM, Ashley, E, Baird, JK, Gryseels, C, Jambert, E, Lacerda, M, Laihad, F, Marfurt, J, Pasaribu, AP, Poespoprodjo, JR, Sutanto, I, Taylor, WR, van den Boogaard, C, Battle, KE, Dysoley, L, Ghimire, P, Hawley, B, Hwang, J, Khan, WA, Mudin, RNB, Sumiwi, ME, Ahmed, R, Aktaruzzaman, MM, Awasthi, KR, Bardaji, A, Bell, D, Boaz, L, Burdam, FH, Chandramohan, D, Cheng, Q, Chindawongsa, K, Culpepper, J, Das, S, Deray, R, Desai, M, Domingo, G, Duoquan, W, Duparc, S, Floranita, R, Gerth-Guyette, E, Howes, RE, Hugo, C, Jagoe, G, Sariwati, E, Jhora, ST, Jinwei, W, Karunajeewa, H, Kenangalem, E, Lal, BK, Landuwulang, C, Le Perru, E, Lee, S-E, Makita, LS, McCarthy, J, Mekuria, A, Mishra, N, Naket, E, Nambanya, S, Nausien, J, Duc, TN, Thi, TN, Noviyanti, R, Pfeffer, D, Qi, G, Rahmalia, A, Rogerson, S, Samad, I, Sattabongkot, J, Satyagraha, A, Shanks, D, Sharma, SN, Sibley, CH, Sungkar, A, Syafruddin, D, Talukdar, A, Tarning, J, Kuile, F, Thapa, S, Theodora, M, Huy, TT, Waramin, E, Waramori, G, Woyessa, A, Wongsrichanalai, C, Xa, NX, Yeom, JS, Hermawan, L, Devine, A, Nowak, S, Jaya, I, Supargiyono, S, Grietens, KP, and Price, RN
- Subjects
lcsh:Arctic medicine. Tropical medicine ,Efficacy ,Radical cure ,lcsh:RC955-962 ,Effectiveness ,Primaquine ,Meeting Report ,wc_750 ,lcsh:Infectious and parasitic diseases ,qv_258 ,Adherence ,qx_135 ,Vivax malaria ,APMEN ,lcsh:RC109-216 ,Plasmodium vivax - Abstract
The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness.
- Published
- 2018
29. High Risk of Plasmodium vivax Malaria Following Splenectomy in Papua, Indonesia
- Author
-
Kho, S, Andries, B, Poespoprodjo, JR, Commons, RJ, Shanti, PAI, Kenangalem, E, Douglas, NM, Simpson, JA, Sugiarto, P, Anstey, NM, and Price, RN
- Subjects
Adult ,Male ,Adolescent ,malaria ,Middle Aged ,Risk Assessment ,splenectomy ,vivax ,Young Adult ,falciparum ,Indonesia ,parasitic diseases ,Malaria, Vivax ,Animals ,Humans ,Female ,Prospective Studies ,Child ,Articles and Commentaries - Abstract
In Papua, splenectomized individuals have greater risk of malaria in the 12 months following splenectomy but not of mortality. Malaria risk was higher for Plasmodium vivax than P. falciparum. Early radical cure and prophylaxis are warranted in malaria endemic areas., Background Splenectomy increases the risk of severe and fatal infections; however, the risk of Plasmodium vivax malaria is unknown. We quantified the Plasmodium species-specific risks of malaria and other outcomes following splenectomy in patients attending a hospital in Papua, Indonesia. Methods Records of all patients attending Mitra-Masyarakat Hospital 2004–2013 were reviewed, identifying those who underwent splenectomy. Subsequent risks of specific clinical outcomes within 12 months for splenectomized patients were compared to nonsplenectomized patients from their first recorded hospital admission. In addition, patients splenectomized for trauma 2015–2016 were followed prospectively for 14 months. Results Of the 10774 patients hospitalized during 2004–2013, 67 underwent splenectomy. Compared to nonsplenectomized inpatients, patients undergoing splenectomy had a 5-fold higher rate of malaria presentation within 12 months (adjusted hazard ratio [AHR] = 5.0 [95% confidence interval (CI): 3.4–7.3], P < .001). The AHR was 7.8 (95% CI: 5.0–12.3) for P. vivax and 3.0 (95% CI: 1.7–5.4) for P. falciparum (both P < .001). Splenectomized patients had greater risk of being hospitalized for any cause (AHR = 1.8 [95% CI: 1.0–3.0], P = .037) and diarrheal (AHR = 3.5 [95% CI: 1.3–9.6], P = .016). In the 14-month prospective cohort, 12 episodes of P. vivax and 6 episodes of P. falciparum were observed in 11 splenectomised patients. Conclusions Splenectomy is associated with a high risk of malaria, greater for P. vivax than P. falciparum. Eradication of P. vivax hypnozoites using primaquine (radical cure) and subsequent malaria prophylaxis is warranted following splenectomy in malaria-endemic areas.
- Published
- 2018
30. Treatment-Seeking Behavior after the Implementation of a Unified Policy of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Malaria in Papua, Indonesia
- Author
-
Devine, A, Kenangalem, E, Burdam, FH, Anstey, NM, Poespoprodjo, JR, Price, RN, Yeung, S, Devine, A, Kenangalem, E, Burdam, FH, Anstey, NM, Poespoprodjo, JR, Price, RN, and Yeung, S
- Abstract
Artemisinin combination therapy is recommended for the treatment of multidrug resistant Plasmodium falciparum and Plasmodium vivax. In March 2006, antimalarial policy in Indonesia was changed to a unified treatment with dihydroartemisinin-piperaquine for all species of malaria because of the low efficacy of previous drug treatments. In 2013, a randomized cross-sectional household survey in Papua was used to collect data on demographics, parasite positivity, treatment-seeking behavior, diagnosis and treatment of malaria, and household costs. Results were compared with a similar survey undertaken in 2005. A total of 800 households with 4,010 individuals were included in the 2013 survey. The prevalence of malaria parasitemia was 12% (348/2,795). Of the individuals who sought treatment of fever, 67% (66/98) reported attending a public provider at least once compared with 46% (349/764) before policy change (P < 0.001). During the 100 visits to healthcare providers, 95% (95) included a blood test for malaria and 74% (64/86) resulted in the recommended antimalarial for the diagnosed species, the corresponding figures before policy change were 48% (433/894) and 23% (78/336). The proportion of individuals seeking treatment more than once fell from 14% (107/764) before policy change to 2% (2/98) after policy change (P = 0.005). The mean indirect cost per fever episode requiring treatment seeking decreased from US$44.2 in 2005 to US$33.8 in 2013 (P = 0.006). The implementation of a highly effective antimalarial treatment was associated with better adherence of healthcare providers in both the public and private sectors and a reduction in clinical malaria and household costs.
- Published
- 2018
31. Passively versus actively detected malaria: similar genetic diversity but different complexity of infection
- Author
-
Pava, Z, Handayuni, I, Trianty, L, Utami, RAS, Tirta, YK, Puspitasari, AM, Burdam, F, Kenangalem, E, Wirjanata, G, Kho, S, Trimarsanto, H, Anstey, N, Poespoprodjo, JR, Noviyanti, R, Price, RN, Marfurt, J, and Auburn, S
- Subjects
Male ,Adolescent ,Genotyping Techniques ,Plasmodium falciparum ,Genetic Variation ,Articles ,DNA, Protozoan ,Linkage Disequilibrium ,Sympatry ,Cross-Sectional Studies ,Indonesia ,Child, Preschool ,parasitic diseases ,Malaria, Vivax ,Humans ,Female ,Malaria, Falciparum ,Child ,Plasmodium vivax ,Asymptomatic Infections ,Microsatellite Repeats - Abstract
The surveillance of malaria is generally undertaken on the assumption that samples passively collected at health facilities are comparable to or representative of the broader Plasmodium reservoir circulating in the community. Further characterization and comparability of the hidden asymptomatic parasite reservoir are needed to inform on the potential impact of sampling bias. This study explores the impact of sampling strategy on molecular surveillance by comparing the genetic make-up of Plasmodium falciparum and Plasmodium vivax isolates collected by passive versus active case detection. Sympatric isolates of P. falciparum and P. vivax were collected from a large community survey and ongoing clinical surveillance studies undertaken in the hypomesoendemic setting of Mimika District (Papua, Indonesia). Plasmodium falciparum isolates were genotyped at nine microsatellite loci and P. vivax at eight loci. Measures of diversity and differentiation were used to compare different patient and parasitological sample groups. The results demonstrated that passively detected cases (symptomatic) had comparable population diversity to those circulating in the community (asymptomatic) in both species. In addition, asymptomatic patent infections were as diverse as subpatent infections. However, a significant difference in multiplicity of infection (MOI) and percentage of polyclonal infections was observed between actively and passively detected P. vivax cases (mean MOI: 1.7 ± 0.7 versus 1.4 ± 1.4, respectively; P = 0.001). The study findings infer that, in hypomesoendemic settings, passive sampling is appropriate for molecular parasite surveillance strategies using the predominant clone in any given infection; however, the findings suggest caution when analyzing complexity of infection. Further evaluation is required in other endemic settings.
- Published
- 2017
32. Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study
- Author
-
Douglas, NM, Poespoprodjo, JR, Patriani, D, Malloy, MJ, Kenangalem, E, Sugiarto, P, Simpson, JA, Soenarto, Y, Anstey, NM, Price, RN, and Garner, P
- Subjects
parasitic diseases - Abstract
Background: Primaquine is the only licensed drug for eradicating Plasmodium vivax hypnozoites and, therefore, preventing relapses of vivax malaria. It is a vital component of global malaria elimination efforts. Primaquine is efficacious when supervised in clinical trials, but its effectiveness in real-world settings is unknown. We aimed to determine whether unsupervised primaquine was effective for preventing re-presentation to hospital with vivax malaria in southern Papua, Indonesia. Methods and findings: Routinely-collected hospital surveillance data were used to undertake a pragmatic comparison of the risk of re-presentation to hospital with vivax malaria in patients prescribed dihydroartemisinin-piperaquine (DHP) combined with primaquine versus those patients prescribed DHP alone. The omission of primaquine was predominantly due to 3 stock outages. Individual clinical, pharmacy, and laboratory data were merged using individual hospital identification numbers and the date of presentation to hospital. Between April 2004 and December 2013, there were 86,797 documented episodes of vivax malaria, of which 62,492 (72.0%) were included in the analysis. The risk of re-presentation with vivax malaria within 1 year was 33.8% (95% confidence Interval [CI] 33.1%–34.5%) after initial monoinfection with P. vivax and 29.2% (95% CI 28.1%–30.4%) after mixed-species infection. The risk of re-presentation with P. vivax malaria was higher in children 1 to < 5 years of age (49.6% [95% CI 48.4%–50.9%]) compared to patients 15 years of age or older (24.2% [95% CI 23.4–24.9%]); Adjusted Hazard Ratio (AHR) = 2.23 (95% CI 2.15–2.31), p < 0.001. Overall, the risk of re-presentation was 37.2% (95% CI 35.6%–38.8%) in patients who were prescribed no primaquine compared to 31.6% (95% CI 30.9%–32.3%) in those prescribed either a low (≥1.5 mg/kg and
- Published
- 2017
33. Plasmodium falciparum and P. vivax demonstrate contrasting chloroquine resistance reversal phenotypes
- Author
-
Wirjanata, G, Handayuni, I, Prayoga, P, Leonardo, L, Apriyanti, D, Trianty, L, Wandosa, R, Gobay, B, Kenangalem, E, Poespoprodjo, JR, Noviyanti, R, Kyle, DE, Cheng, Q, Price, R, and Marfurt, J
- Subjects
parasitic diseases - Abstract
High-grade chloroquine (CQ) resistance has emerged in both P. falciparum and P. vivax The aim of the present study was to investigate phenotypic differences of CQ resistance in both of these species and the ability of known CQ resistance reversal agents (CQRRAs) to alter CQ susceptibility.Between April 2015 and April 2016, the potential of verapamil (VP), mibefradil (MF), L703,606 (L7), and primaquine (PQ) to reverse CQ resistance was assessed in 46 P. falciparum and 34 P. vivax clinical isolates in Papua, Indonesia, where CQ resistance is present in both species, using a modified schizont maturation assay.In P. falciparum, CQ IC50s were reduced when CQ was combined with VP (1.4-fold), MF (1.2-fold), L7 (4.2 fold), or PQ (1.8 fold). The degree of CQ resistance reversal in P. falciparum was highly correlated with CQ susceptibility for all CQRRAs: VP (R(2)=0.951), (R(2)=0.852), L7 (R(2)=0.962), and PQ (R(2)=0.901), in line with observations in P. falciparum laboratory strains. In contrast, no reduction in CQ IC50s was observed with any of the CQRRAs in P. vivax, even in those isolates with high chloroquine IC50s.The differential effect of CQRRAs in P. falciparum and P. vivax suggests significant differences in CQ kinetics and potentially the likely mechanism of CQ resistance between these two species.
- Published
- 2017
34. Challenges for achieving safe and effective radical cure of P. vivax – a round table discussion of the APMEN Vivax Working Group
- Author
-
Thriemer, K, Ley, B, Bobogare, A, Dysoley, L, Alam, M, Pasaribu, A, Sattabongkot, J, Jambert, E, Domingo, G, Commons, R, Auburn, S, Marfurt, J, Devine, A, Akturazzaman, M, Sohel, N, Namgay, R, Drukpa, T, Sharma, S, Sarawati, E, Samad, I, Theodora, M, Nambanya, S, Ounekham, S, Mudin, R, Da Thakur, G, Makita, L, Deray, R, Lee, S, Boaz, L, Danansuriya, M, Mudiyanselage, S, Chinanonwait, N, Kitchakarn, S, Nausien, J, Naket, E, Duc, T, Manh, H, Hong, Y, Cheng, Q, Richards, J, Kusriastuti, R, Satyagraha, A, Noviyanti, R, Ding, X, Khan, W, Swe, C, Guoding, Z, Qi, G, Kaneko, A, Miotto, O, Nguitragool, W, Roobsoong, W, Battle, K, Howes, R, Roca-Feltrer, A, Duparc, S, Bhowmick, I, Kenangalem, E, Bibit, J, Berry, A, Sintasath, D, Abeyasinghe, R, Sibley, C, McCarthy, J, von Seidlein, L, Baird, K, and Price, R
- Subjects
parasitic diseases - Abstract
The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia-Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network (APMEN) Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this review the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should highlight the caveats as well as the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.
- Published
- 2017
35. Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group
- Author
-
Thriemer, K., Ley, B., Bobogare, A., Dysoley, L., Alam, M.S., Pasaribu, A.P., Sattabongkot, J., Jambert, E., Domingo, G.J., Commons, R., Auburn, S., Marfurt, J., Devine, A., Aktaruzzaman, M.M., Sohel, N., Namgay, R., Drukpa, T., Sharma, S.N., Sarawati, E., Samad, I., Theodora, M., Nambanya, S., Ounekham, S., Mudin, R.N.B., Da Thakur, G., Makita, L.S., Deray, R., Lee, S.E., Boaz, L., Danansuriya, M.N., Mudiyanselage, S.D., Chinanonwait, N., Kitchakarn, S., Nausien, J., Naket, E., Duc, T.N., Do Manh, H., Hong, Y.S., Cheng, Q., Richards, J.S., Kusriastuti, R., Satyagraha, A., Noviyanti, R., Ding, X.C., Khan, W.A., Swe Phru, C., Guoding, Z., Qi, G., Kaneko, A., Miotto, O., Nguitragool, W., Roobsoong, W., Battle, K., Howes, R.E., Roca-Feltrer, A., Duparc, S., Bhowmick, I.P., Kenangalem, E., Bibit, J.A., Barry, Alyssa, Sintasath, D., Abeyasinghe, R., Sibley, C.H., McCarthy, J., Von Seidlein, L., Baird, J.K., Price, R.N., Thriemer, K., Ley, B., Bobogare, A., Dysoley, L., Alam, M.S., Pasaribu, A.P., Sattabongkot, J., Jambert, E., Domingo, G.J., Commons, R., Auburn, S., Marfurt, J., Devine, A., Aktaruzzaman, M.M., Sohel, N., Namgay, R., Drukpa, T., Sharma, S.N., Sarawati, E., Samad, I., Theodora, M., Nambanya, S., Ounekham, S., Mudin, R.N.B., Da Thakur, G., Makita, L.S., Deray, R., Lee, S.E., Boaz, L., Danansuriya, M.N., Mudiyanselage, S.D., Chinanonwait, N., Kitchakarn, S., Nausien, J., Naket, E., Duc, T.N., Do Manh, H., Hong, Y.S., Cheng, Q., Richards, J.S., Kusriastuti, R., Satyagraha, A., Noviyanti, R., Ding, X.C., Khan, W.A., Swe Phru, C., Guoding, Z., Qi, G., Kaneko, A., Miotto, O., Nguitragool, W., Roobsoong, W., Battle, K., Howes, R.E., Roca-Feltrer, A., Duparc, S., Bhowmick, I.P., Kenangalem, E., Bibit, J.A., Barry, Alyssa, Sintasath, D., Abeyasinghe, R., Sibley, C.H., McCarthy, J., Von Seidlein, L., Baird, J.K., and Price, R.N.
- Published
- 2017
36. Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study
- Author
-
Garner, P, Douglas, NM, Poespoprodjo, JR, Patriani, D, Malloy, MJ, Kenangalem, E, Sugiarto, P, Simpson, JA, Soenarto, Y, Anstey, NM, Price, RN, Garner, P, Douglas, NM, Poespoprodjo, JR, Patriani, D, Malloy, MJ, Kenangalem, E, Sugiarto, P, Simpson, JA, Soenarto, Y, Anstey, NM, and Price, RN
- Abstract
BACKGROUND: Primaquine is the only licensed drug for eradicating Plasmodium vivax hypnozoites and, therefore, preventing relapses of vivax malaria. It is a vital component of global malaria elimination efforts. Primaquine is efficacious when supervised in clinical trials, but its effectiveness in real-world settings is unknown. We aimed to determine whether unsupervised primaquine was effective for preventing re-presentation to hospital with vivax malaria in southern Papua, Indonesia. METHODS AND FINDINGS: Routinely-collected hospital surveillance data were used to undertake a pragmatic comparison of the risk of re-presentation to hospital with vivax malaria in patients prescribed dihydroartemisinin-piperaquine (DHP) combined with primaquine versus those patients prescribed DHP alone. The omission of primaquine was predominantly due to 3 stock outages. Individual clinical, pharmacy, and laboratory data were merged using individual hospital identification numbers and the date of presentation to hospital. Between April 2004 and December 2013, there were 86,797 documented episodes of vivax malaria, of which 62,492 (72.0%) were included in the analysis. The risk of re-presentation with vivax malaria within 1 year was 33.8% (95% confidence Interval [CI] 33.1%-34.5%) after initial monoinfection with P. vivax and 29.2% (95% CI 28.1%-30.4%) after mixed-species infection. The risk of re-presentation with P. vivax malaria was higher in children 1 to <5 years of age (49.6% [95% CI 48.4%-50.9%]) compared to patients 15 years of age or older (24.2% [95% CI 23.4-24.9%]); Adjusted Hazard Ratio (AHR) = 2.23 (95% CI 2.15-2.31), p < 0.001. Overall, the risk of re-presentation was 37.2% (95% CI 35.6%-38.8%) in patients who were prescribed no primaquine compared to 31.6% (95% CI 30.9%-32.3%) in those prescribed either a low (≥1.5 mg/kg and <5 mg/kg) or high (≥5 mg/kg) dose of primaquine (AHR = 0.90 [95% CI 0.86-0.95, p < 0.001]). Limiting the comparison to high dose versus no primaquin
- Published
- 2017
37. Plasmodium vivax infection: A major determinant of severe anaemia in Papua, Indonesia
- Author
-
Price, RN, Tjitra, E, Karyana, M, Warikar, NM, Kenangalem, E, Lampah, DA, Sugiarto, P, and Anstey, NM
- Published
- 2016
38. Haemolysis, impaired nitric oxide bioavailability and L-arginine-reversible endothelial dysfunction in adults with falciparum malaria
- Author
-
Yeo, TW, Lampah, DA, Gitawati, R, Tjitra, E, Kenangalem, E, McNeill, YR, Darcy, CJ, Granger, DL, Weinberg, JB, Lopansri, BK, Price, RN, Duffull, SB, Celermajer, DS, and Anstey, NM
- Published
- 2016
39. Impaired endothelial function in adults with severe falciparum malaria in Papua, Indonesia
- Author
-
Yeo, TW, Lampah, DA, Kenangalem, E, Gitawati, R, Waramori, G, McNeil, Y, Duffull, S, Tjitra, E, Price, RN, Celermajer, D, and Anstey, NM
- Published
- 2016
40. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial
- Author
-
Faiz, MA, Bin Yunus, E, Rahman, MR, Islam, F, Hoque, MG, Hasan, MU, Samad, R, Aung, S, Thein, S, Than, M, Thwe, Y, Ohn, KM, Hla, S, Lwin, S, Htut, Y, Lin, K, Kyaw, MP, Win, N, Aung, WN, Win, M, Oo, AZ, Aung, Z, Shein, OM, Kyi, MM, Myint, WW, Pyar, KP, Nyein, K, Win, KK, Mishra, SK, Mohanty, S, Pattnaik, RB, Acharya, SK, Mohanty, A, Mohapatra, D, Tijtra, E, Anstey, N, Price, R, Handoyo, T, Gampamola, D, Kenangalem, E, Takaendengan, D, Lampat, A, Harijanto, P, Dondorp, AE, Nosten, F, Day, N, Stepniewska, K, Tipmanee, P, Douthwaite, S, Silamut, K, Proux, S, Pongsawat, K, White, N, and Grp, SEAQUAMAT
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,030231 tropical medicine ,Artesunate ,Loading dose ,law.invention ,Antimalarials ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Bolus (medicine) ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,Malaria, Falciparum ,Quinine ,Intention-to-treat analysis ,business.industry ,General Medicine ,medicine.disease ,Artemisinins ,3. Good health ,Survival Rate ,chemistry ,Child, Preschool ,Female ,business ,Sesquiterpenes ,Malaria ,medicine.drug - Abstract
BACKGROUND: In the treatment of severe malaria, intravenous artesunate is more rapidly acting than intravenous quinine in terms of parasite clearance, is safer, and is simpler to administer, but whether it can reduce mortality is uncertain. METHODS: We did an open-label randomised controlled trial in patients admitted to hospital with severe falciparum malaria in Bangladesh, India, Indonesia, and Myanmar. We assigned individuals intravenous artesunate 2.4 mg/kg bodyweight given as a bolus (n=730) at 0, 12, and 24 h, and then daily, or intravenous quinine (20 mg salt per kg loading dose infused over 4 h then 10 mg/kg infused over 2-8 h three times a day; n=731). Oral medication was substituted when possible to complete treatment. Our primary endpoint was death from severe malaria, and analysis was by intention to treat. FINDINGS: We assessed all patients randomised for the primary endpoint. Mortality in artesunate recipients was 15% (107 of 730) compared with 22% (164 of 731) in quinine recipients; an absolute reduction of 34.7% (95% CI 18.5-47.6%; p=0.0002). Treatment with artesunate was well tolerated, whereas quinine was associated with hypoglycaemia (relative risk 3.2, 1.3-7.8; p=0.009). INTERPRETATION: Artesunate should become the treatment of choice for severe falciparum malaria in adults.
- Published
- 2016
41. Severe disease associated with both Plasmodium falciparum and P-vivax infection in Papua, Indonesia
- Author
-
Tjitra, E, Anstey, NM, Warrikar, NM, Kenangalem, E, Lampah, DA, Karyana, M, Sugiarto, P, and Price, RN
- Published
- 2016
42. Study of molecular mechanism of pregnancy-associated malaria in Indonesia: characterization of Plasmodium falciparum var gene of peripheral and placental isolates
- Author
-
Noviyanti, R, Trianty, L, Poespoprodjo, J, Dadlani, H, Nursamsy, N, Trimarsanto, H, Lampah, D, Kenangalem, E, Tjitra, E, Price, R, Brown, G, Duffy, M, Anstey, N, and Rogerson, S
- Published
- 2016
43. Plasmodium vivax infection: a major determinant of severe anaemia in infancy
- Author
-
Kenangalem, E, Karyana, M, Burdarm, L, Yeung, S, Simpson, JA, Tjitra, E, Anstey, NM, Poespoprodjo, JR, Price, RN, Douglas, NM, Kenangalem, E, Karyana, M, Burdarm, L, Yeung, S, Simpson, JA, Tjitra, E, Anstey, NM, Poespoprodjo, JR, Price, RN, and Douglas, NM
- Abstract
BACKGROUND: Most malarious countries outside of Africa are co-endemic for Plasmodium falciparum and Plasmodium vivax. The comparative burden of anaemia in the community caused by these two species is incompletely characterized. METHODS: A three-stage, cross-sectional, community survey was used to determine the proportion of moderate or severe anaemia (haemoglobin <7 g/dL) attributable to patent P. vivax, P. falciparum and mixed parasitaemia in Papua, Indonesia. Adjusted population-attributable fractions were calculated from multivariable logistic regression models. Eight hundred and twenty-five households were surveyed with a total of 5255 occupants, 3890 (74 %) of whom were present and provided a blood sample. Plasmodium falciparum parasitaemia was present in 8.1 % (n = 315) of participants, P. vivax in 6.4 % (n = 250) and mixed infections in 1.9 % (n = 72). Overall, P. falciparum was associated with a mean reduction in haemoglobin of 1.16 g/dL compared to those without patent parasitaemia [95 % confidence interval (95 % CI) 0.91, 1.41 g/dL]. The corresponding values for P. vivax and mixed infections were 0.66 g/dL (95 % CI 0.35, 0.96) and 1.25 g/dL (0.71, 1.80), respectively. Overall, 16.7 % (95 % CI 8.52, 24.2 %) of haemoglobin concentrations <7 g/dL in the community were estimated to be attributable to patent parasitaemia. The fractions for infants and 1-5 years old were 34.4 % (95 % CI -3.30, 58.3 %) and 23.2 % (95 % CI 3.34, 39.0 %), respectively. Plasmodium vivax was associated with a greater than threefold higher attributable fraction of anaemia in infants compared with P. falciparum [27.6 % (95 % CI -3.20, 49.2 %) versus 7.94 % (-5.87, 20.0 %)]. CONCLUSION: Despite comparatively low-level endemicity, malaria is associated with a significant proportion of all cases of community anaemia in southern Papua. Contrary to its benign reputation, P. vivax is an important and preventable risk factor for anaemia during infancy-a probable consequence of relapsing disea
- Published
- 2016
44. Treatment-seeking behaviour and associated costs for malaria in Papua, Indonesia
- Author
-
Karyana, M, Devine, A, Kenangalem, E, Burdarm, L, Poespoprodjo, JR, Vemuri, R, Anstey, NM, Tjitra, E, Price, RN, Yeung, S, Karyana, M, Devine, A, Kenangalem, E, Burdarm, L, Poespoprodjo, JR, Vemuri, R, Anstey, NM, Tjitra, E, Price, RN, and Yeung, S
- Abstract
BACKGROUND: Malaria remains a significant public health issue in Eastern Indonesia, where multidrug resistant Plasmodium falciparum and Plasmodium vivax are highly prevalent. The objective of this study was to describe treatment-seeking behaviour and household costs prior to a change to a unified treatment policy of dihydroartemisinin-piperaquine in Mimika district, Papua province in 2006. METHODS: In 2005 a randomized cross-sectional household survey was conducted to collect data on demographics, socio-economic status (SES), treatment-seeking, case management, and household costs. Information on the cost of illness was also collected from patients exiting health facilities, in order to compare the cost of episodes diagnosed as P. vivax compared with those diagnosed as P. falciparum. RESULTS: 825 households were included in the survey. Of the 764 individuals who sought treatment for fever outside the home in the last month, 46% (349/764) went to a public health facility. Of the 894 reported visits to healthcare providers, 48% (433) resulted in a blood test, of which 78% (337) were reportedly positive. Only 10% (17/177) of individuals who reported testing positive for P. falciparum or mixed infection received the first-line treatment of chloroquine with SP, and 38% (61/159) of those with a diagnosis of P. vivax reportedly received the first-line treatment of chloroquine and primaquine. Overall, public facilities were more likely to prescribe the correct prevailing first-line drug combinations than private providers (OR = 3.77 [95% CI 2.31-6.14], p < 0.001). The mean cost to the household of an episode of P. vivax was similar to the cost of P. falciparum [US$44.50 (SD: 46.23) vs US$48.58 (SD: 64.65)]. CONCLUSIONS: Private providers were a popular source of treatment for malaria, but adherence to the national guidelines was low and the economic burden of malaria for both P. falciparum and P. vivax infections was substantial. Engagement with the private sector is needed
- Published
- 2016
45. Analysis of ex vivo drug response data of Plasmodium clinical isolates: the pros and cons of different computer programs and online platforms
- Author
-
Wirjanata, G, Handayuni, I, Zaloumis, SG, Chalfein, F, Prayoga, P, Kenangalem, E, Poespoprodjo, JR, Noviyanti, R, Simpson, JA, Price, RN, Marfurt, J, Wirjanata, G, Handayuni, I, Zaloumis, SG, Chalfein, F, Prayoga, P, Kenangalem, E, Poespoprodjo, JR, Noviyanti, R, Simpson, JA, Price, RN, and Marfurt, J
- Abstract
BACKGROUND: In vitro drug susceptibility testing of malaria parasites remains an important component of surveillance for anti-malarial drug resistance. The half-maximal inhibition of growth (IC50) is the most commonly reported parameter expressing drug susceptibility, derived by a variety of statistical approaches, each with its own advantages and disadvantages. METHODS: In this study, licensed computer programs WinNonlin and GraphPad Prism 6.0, and the open access programs HN-NonLin, Antimalarial ICEstimator (ICE), and In Vitro Analysis and Reporting Tool (IVART) were tested for their ease of use and ability to estimate reliable IC50 values from raw drug response data from 31 Plasmodium falciparum and 29 P. vivax clinical isolates tested with five anti-malarial agents: chloroquine, amodiaquine, piperaquine, mefloquine, and artesunate. RESULTS: The IC50 and slope estimates were similar across all statistical packages for all drugs tested in both species. There was good correlation of results derived from alternative statistical programs and non-linear mixed-effects modelling (NONMEM) which models all isolate data simultaneously. The user-friendliness varied between packages. While HN-NonLin and IVART allow users to enter the data in 96-well format, IVART and GraphPad Prism 6.0 are capable to analyse multiple isolates and drugs in parallel. WinNonlin, GraphPad Prism 6.0, IVART, and ICE provide alerts for non-fitting data and incorrect data entry, facilitating data interpretation. Data analysis using WinNonlin or ICE took the longest computationally, whilst the offline ability of GraphPad Prism 6.0 to analyse multiple isolates and drugs simultaneously made it the fastest among the programs tested. CONCLUSION: IC50 estimates obtained from the programs tested were comparable. In view of processing time and ease of analysis, GraphPad Prism 6.0 or IVART are best suited for routine and large-scale drug susceptibility testing.
- Published
- 2016
46. Submicroscopic and Asymptomatic Plas-modium Parasitaemia Associated with Significant Risk of Anaemia in Papua, Indonesia
- Author
-
Tsuboi, T, Pava, Z, Burdam, FH, Handayuni, I, Trianty, L, Utami, RAS, Tirta, YK, Kenangalem, E, Lampah, D, Kusuma, A, Wirjanata, G, Kho, S, Simpson, JA, Auburn, S, Douglas, NM, Noviyanti, R, Anstey, NM, Poespoprodjo, JR, Marfurt, J, Price, RN, Tsuboi, T, Pava, Z, Burdam, FH, Handayuni, I, Trianty, L, Utami, RAS, Tirta, YK, Kenangalem, E, Lampah, D, Kusuma, A, Wirjanata, G, Kho, S, Simpson, JA, Auburn, S, Douglas, NM, Noviyanti, R, Anstey, NM, Poespoprodjo, JR, Marfurt, J, and Price, RN
- Abstract
Submicroscopic Plasmodium infections are an important parasite reservoir, but their clinical relevance is poorly defined. A cross-sectional household survey was conducted in southern Papua, Indonesia, using cluster random sampling. Data were recorded using a standardized questionnaire. Blood samples were collected for haemoglobin measurement. Plasmodium parasitaemia was determined by blood film microscopy and PCR. Between April and July 2013, 800 households and 2,830 individuals were surveyed. Peripheral parasitaemia was detected in 37.7% (968/2,567) of individuals, 36.8% (357) of whom were identified by blood film examination. Overall the prevalence of P. falciparum parasitaemia was 15.4% (396/2567) and that of P. vivax 18.3% (471/2567). In parasitaemic individuals, submicroscopic infection was significantly more likely in adults (adjusted odds ratio (AOR): 3.82 [95%CI: 2.49-5.86], p<0.001) compared to children, females (AOR = 1.41 [1.07-1.86], p = 0.013), individuals not sleeping under a bednet (AOR = 1.4 [1.0-1.8], p = 0.035), and being afebrile (AOR = 3.2 [1.49-6.93], p = 0.003). The risk of anaemia (according to WHO guidelines) was 32.8% and significantly increased in those with asymptomatic parasitaemia (AOR 2.9 [95% 2.1-4.0], p = 0.007), and submicroscopic P. falciparum infections (AOR 2.5 [95% 1.7-3.6], p = 0.002). Asymptomatic and submicroscopic infections in this area co-endemic for P. falciparum and P. vivax constitute two thirds of detectable parasitaemia and are associated with a high risk of anaemia. Novel public health strategies are needed to detect and eliminate these parasite reservoirs, for the benefit both of the patient and the community.
- Published
- 2016
47. Plasmodium malariae Infection Associated with a High Burden of Anemia: A Hospital-Based Surveillance Study
- Author
-
Sinnis, P, Langford, S, Douglas, NM, Lampah, DA, Simpson, JA, Kenangalem, E, Sugiarto, P, Anstey, NM, Poespoprodjo, JR, Price, RN, Sinnis, P, Langford, S, Douglas, NM, Lampah, DA, Simpson, JA, Kenangalem, E, Sugiarto, P, Anstey, NM, Poespoprodjo, JR, and Price, RN
- Abstract
BACKGROUND: Plasmodium malariae is a slow-growing parasite with a wide geographic distribution. Although generally regarded as a benign cause of malaria, it has been associated with nephrotic syndrome, particularly in young children, and can persist in the host for years. Morbidity associated with P. malariae infection has received relatively little attention, and the risk of P. malariae-associated nephrotic syndrome is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used data from a very large hospital-based surveillance system incorporating information on clinical diagnoses, blood cell parameters and treatment to describe the demographic distribution, morbidity and mortality associated with P. malariae infection in southern Papua, Indonesia. Between April 2004 and December 2013 there were 1,054,674 patient presentations to Mitra Masyarakat Hospital of which 196,380 (18.6%) were associated with malaria and 5,097 were with P. malariae infection (constituting 2.6% of all malaria cases). The proportion of malaria cases attributable to P. malariae increased with age from 0.9% for patients under one year old to 3.1% for patients older than 15 years. Overall, 8.5% of patients with P. malariae infection required admission to hospital and the median length of stay for these patients was 2.5 days (Interquartile Range: 2.0-4.0 days). Patients with P. malariae infection had a lower mean hemoglobin concentration (9.0 g/dL) than patients with P. falciparum (9.5 g/dL), P. vivax (9.6g/dL) and mixed species infections (9.3g/dL). There were four cases of nephrotic syndrome recorded in patients with P. malariae infection, three of which were in children younger than 5 years old, giving a risk in this age group of 0.47% (95% Confidence Interval; 0.10% to 1.4%). Overall, 2.4% (n = 16) of patients hospitalized with P. malariae infection subsequently died in hospital, similar to the proportions for the other endemic Plasmodium species (range: 0% for P. ovale to 1.6% for P. falciparum). CONC
- Published
- 2015
48. Severe Malarial Thrombocytopenia: A Risk Factor for Mortality in Papua, Indonesia
- Author
-
Lampah, DA, Yeo, TW, Malloy, M, Kenangalem, E, Douglas, NM, Ronaldo, D, Sugiarto, P, Simpson, JA, Poespoprodjo, JR, Anstey, NM, Price, RN, Lampah, DA, Yeo, TW, Malloy, M, Kenangalem, E, Douglas, NM, Ronaldo, D, Sugiarto, P, Simpson, JA, Poespoprodjo, JR, Anstey, NM, and Price, RN
- Abstract
BACKGROUND: The significance of thrombocytopenia to the morbidity and mortality of malaria is poorly defined. We compared the platelet counts and clinical correlates of patients with and those without malaria in southern Papua, Indonesia. METHODS: Data were collated on patients presenting to a referral hospital between April 2004 and December 2012. RESULTS: Platelet measurements were available in 215 479 patients (23.4%), 66 421 (30.8%) of whom had clinical malaria. Patients with Plasmodium falciparum monoinfection had the lowest platelet counts and greatest risk of severe thrombocytopenia (platelet count, <50,000 platelets/µL), compared with those without malaria (adjusted odds ratio [OR], 6.03; 95% confidence interval [CI], 5.77-6.30]). The corresponding risks were 5.4 (95% CI, 5.02-5.80) for mixed infections, 3.73 (95% CI, 3.51-3.97) for Plasmodium vivax infection, and 2.16 (95% CI, 1.78-2.63) for Plasmodium malariae infection (P<.001). In total, 1.3% of patients (2701 of 215 479) died. Patients with severe malarial anemia alone (hemoglobin level, <5 g/dL) had an adjusted OR for death of 4.93 (95% CI, 3.79-6.42), those with severe malarial thrombocytopenia alone had an adjusted OR of 2.77 (95% CI, 2.20-3.48), and those with both risk factors had an adjusted OR of 13.76 (95% CI, 10.22-18.54; P<.001). CONCLUSIONS: Severe thrombocytopenia identifies both children and adults at increased risk of death from falciparum or vivax malaria, particularly in those with concurrent severe anemia.
- Published
- 2015
49. MULTIDRUG RESISTANT VIVAX MALARIA: A MAJOR CAUSE OF MORBIDITY IN EARLY LIFE
- Author
-
Poespoprodjo, JR, Fobia, W, Kenangalem, E, Lampah, D, Hasanuddin, A, Warikar, N, Sugiarto, P, Tjitra, E, Anstey, N, and Price, R
- Published
- 2008
50. ANGIOPOIETIN-2, AN AUTOCRINE MEDIATOR OF ENDOTHELIAL ACTIVATION IS ASSOCIATED WITH PARASITE BIOMASS, ENDOTHELIAL DYSFUNCTION AND MORTALITY IN SEVERE FALCIPARUM MALARIA
- Author
-
Yeo, T, Lampah, D, Tjitra, E, Gitawati, R, Kenangalem, E, Piera, K, Price, R, Duffull, S, Celermajer, D, and Anstey, N
- Published
- 2008
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.