Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
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Correction: Testing and treatment for malaria elimination: a systematic review
Newby G , Cotter C , Roh ME , Harvard K , Bennett A , Hwang J , Chitnis N , Fine S , Stresman G , Chen I , Gosling R , Hsiang MS . Malar J 2024 23 (1) 63 |
Mass drug administration: Contextual factor considerations
Schneider ZD , Busbee AL , Boily MC , Shah MP , Hwang J , Lindblade KA , Gutman JR . Am J Trop Med Hyg 2024 In designing mass drug administration (MDA) campaigns, it is imperative to consider contextual factors that affect uptake of the intervention, including acceptability, cost, feasibility, and health system considerations, to ensure optimal coverage. We reviewed the literature on contextual factors influencing MDA delivery to provide programs with information to design a successful campaign. From 1,044 articles screened, 37 included contextual factors relevant to participants' values and preferences, drivers of MDA acceptability, health equity concerns, financial and economic aspects, and feasibility barriers; 13 included relevant modeling data. Key findings were abstracted by two reviewers and summarized. No studies directly assessed values or direct health equity concerns with respect to MDA, which represents an evidence gap as unequal distributions of effects and factors that impact participant acceptability and program feasibility must be considered to ensure equitable access. Participant acceptability was the most widely surveyed factor, appearing in 28 of 37 studies; perceived adverse events were a frequently noted cause of nonparticipation, mentioned in 15 studies. Feasibility considerations included when, where, and how drugs will be delivered and how to address pregnant women, as these can all have substantial implications for participation. Mass drug administration costs (∼$1.04 to $19.40 per person per round) are driven primarily by drug prices, but the delivery mechanism can have varying costs as well, and integration with other interventions may provide cost savings. Both programmatic goals and sociopolitical and economic contexts must be carefully considered before embarking on an MDA program to ensure programmatic success. |
Understanding psychosocial determinants of malaria behaviours in low-transmission settings: a scoping review
Casella A , Monroe A , Toso M , Hunter G , Underwood C , Pillai R , Hughes J , Van Lith LM , Cash S , Hwang J , Babalola S . Malar J 2024 23 (1) 15 BACKGROUND: Recent estimates show progress toward malaria elimination is slowing in many settings, underscoring the need for tailored approaches to fight the disease. In addition to essential structural changes, human behaviour plays an important role in elimination. Engagement in malaria behaviours depends in part on psychosocial determinants such as knowledge, perceived risk, and community norms. Understanding the state of research on psychosocial determinants in low malaria transmission settings is important to augment social and behaviour change practice. This review synthesizes research on psychosocial factors and malaria behaviours in low-transmission settings. METHODS: A systematic search of peer-reviewed literature and supplemental manual search of grey literature was conducted using key terms and eligibility criteria defined a priori. Publications from 2000-2020 in the English language were identified, screened, and analysed using inductive methods to determine the relationship between the measured psychosocial factors and malaria behaviours. RESULTS: Screening of 961 publications yielded 96 for inclusion. Nineteen articles collected data among subpopulations that are at increased risk of malaria exposure in low-transmission settings. Purposive and cluster randomized sampling were common sampling approaches. Quantitative, qualitative, and mixed-methods study designs were used. Knowledge, attitudes, and perceived risk were commonly measured psychosocial factors. Perceived response-efficacy, perceived self-efficacy, and community norms were rarely measured. Results indicate positive associations between malaria knowledge and attitudes, and preventive and care-seeking behaviour. Studies generally report high rates of correct knowledge, although it is comparatively lower among studies of high-risk groups. There does not appear to be sufficient extant evidence to determine the relationship between other psychosocial variables and behaviour. CONCLUSIONS: The review highlights the need to deploy more consistent, comprehensive measures of psychosocial factors and the importance of reaching subpopulations at higher risk of transmission in low transmission contexts. Malaria-related knowledge is generally high, even in settings of low transmission. Programmes and research should work to better understand the psychosocial factors that have been positively associated with prevention and care-seeking behaviours, such as norms, perceived response efficacy, perceived self-efficacy, and interpersonal communication. These factors are not necessarily distinct from that which research has shown are important in settings of high malaria transmission. However, the importance of each factor and application to malaria behaviour change programming in low-transmission settings is an area in need of further research. Existing instruments and approaches are available to support more systematic collection of psychosocial determinants and improved sampling approaches and should be applied more widely. Finally, while human behaviour is critical, health systems strengthening, and structural interventions are essential to achieve malaria elimination goals. |
Mass drug administration to reduce malaria transmission: A systematic review and meta-analysis
Schneider ZD , Shah MP , Boily MC , Busbee AL , Hwang J , Lindblade KA , Gutman JR . Am J Trop Med Hyg 2023 Malaria remains a significant cause of morbidity and mortality, even in low-transmission settings. With the advent of longer acting, more effective, and well-tolerated antimalarials, there is renewed interest in the efficacy of mass drug administration (MDA) to accelerate to elimination. We conducted a systematic review and meta-analysis to assess the efficacy of MDA to reduce the incidence and prevalence of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) infection. From 1,044 articles screened, 14 articles, including 10 randomized controlled trials (RCTs), were identified. Five included data on Pf only; five included Pf and Pv. Two of the Pf studies were conducted in areas of high-moderate transmission, the remainder were in areas of low-very low transmission. In higher transmission areas, MDA reduced incidence of Pf parasitemia (rate ratio = 0.61, 95% CI: 0.40-0.92; moderate certainty) 1 to 3 months after drug administration; no significant effect of MDA on Pf parasitemia prevalence was detected 1 to 3 months post-MDA (risk ratio [RR] = 1.76, 95% CI: 0.58-5.36; low certainty). In lower transmission settings, both incidence and prevalence of Pf parasitemia were reduced 1 to 3 months post-MDA (rate ratio = 0.37, 95% CI: 0.21-0.66; RR = 0.25, 95% CI: 0.15-0.41, respectively). Pv prevalence was reduced 1 to 3 months post-MDA (RR = 0.15, 95% CI: 0.10-0.24); there were no RCTs providing data on incidence of Pv. There was no significant effect of MDA at later time points. MDA may have short-term benefits; however, there was no evidence for longer term impact, although none of the trials assessed prolonged interventions. |
Mass relapse prevention to reduce transmission of plasmodium vivax-a systematic review
Shah MP , Westercamp N , Lindblade KA , Hwang J . Am J Trop Med Hyg 2023 Several temperate countries have used mass chemoprevention interventions with medicines of the 8-aminoquinoline class that prevent relapses from Plasmodium vivax before peak transmission to reduce transmission of malaria. The WHO commissioned a systematic review of the literature and evidence synthesis to inform development of recommendations regarding this intervention referred to as "mass relapse prevention" (MRP). Electronic databases were searched, 866 articles screened, and 25 assessed for eligibility after a full-text review. Two nonrandomized studies were included, one from the Democratic People's Republic of Korea (391,357 participants) and the second from the Azerbaijan Soviet Socialist Republic (∼30,000 participants). The two studies administered a single round of primaquine over 14 days (0.25 mg/kg per day). From 1 to 3 months after the treatment round, the incidence of P. vivax infections was significantly lower in areas that received MRP than those that did not (pooled rate ratio [RR] 0.08, 95% CI 0.07-0.08). At 4 to 12 months after the treatment round, the prevalence of P. vivax infection was significantly lower in MRP villages than non-MRP villages (odds ratio 0.12, 95% CI 0.03-0.52). No severe adverse events were found. The certainty of evidence for all outcomes was very low and no conclusions as to the effectiveness or safety of MRP could be drawn. However, it is not likely that this intervention will be needed in the future as most temperate countries where P. vivax is transmitted are nearing or have already eliminated malaria. |
Contextual factors to improve implementation of malaria chemoprevention in children: A systematic review
Gatiba P , Laury J , Steinhardt L , Hwang J , Thwing JI , Zulliger R , Emerson C , Gutman JR . Am J Trop Med Hyg 2023 110 (1) 69-78 Malaria remains a leading cause of childhood morbidity and mortality in sub-Saharan Africa, particularly among children under 5 years of age. To help address this challenge, the WHO recommends chemoprevention for certain populations. For children and infants, the WHO recommends seasonal malaria chemoprevention (SMC), perennial malaria chemoprevention (PMC; formerly intermittent preventive treatment in infants [IPTi]), and, more recently, intermittent preventive treatment in school children (IPTsc). This review describes the contextual factors, including feasibility, acceptability, health equity, financial considerations, and values and preferences, that impact implementation of these strategies. A systematic search was conducted on July 5, 2022, and repeated April 13, 2023, to identify relevant literature. Two reviewers independently screened titles for eligibility, extracted data from eligible articles, and identified and summarized themes. Of 6,295 unique titles identified, 65 were included. The most frequently evaluated strategy was SMC (n = 40), followed by IPTi (n = 18) and then IPTsc (n = 6). Overall, these strategies were highly acceptable, although with IPTsc, there were community concerns with providing drugs to girls of reproductive age and the use of nonmedical staff for drug distribution. For SMC, door-to-door delivery resulted in higher coverage, improved caregiver acceptance, and reduced cost. Lower adherence was noted when caregivers were charged with giving doses 2 and 3 unsupervised. For SMC and IPTi, travel distances and inclement weather limited accessibility. Sensitization and caregiver education efforts, retention of high-quality drug distributors, and improved transportation were key to improving coverage. Additional research is needed to understand the role of community values and preferences in chemoprevention implementation. |
Low utilization of confirmatory testing for tinea capitis by pediatricians at an academic center in New York, United States, 2005-2021
Hwang JK , Gold JAW , Paller AS , Lipner SR . Front Pediatr 2023 11 1297339 We retrospectively reviewed physician diagnostic and treatment practices for pediatric tinea capitis at an academic institution over 16 years, in assessing adherence with published guidelines. We demonstrate the need to increase utilization of confirmatory testing and systemic therapy, and call for directed pediatrician education towards these goals. |
Evidence for a role of Anopheles stephensi in the spread of drug and diagnosis-resistant malaria in Africa
Emiru T , Getachew D , Murphy M , Sedda L , Ejigu LA , Bulto MG , Byrne I , Demisse M , Abdo M , Chali W , Elliott A , Vickers EN , Aranda-Díaz A , Alemayehu L , Behaksera SW , Jebessa G , Dinka H , Tsegaye T , Teka H , Chibsa S , Mumba P , Girma S , Hwang J , Yoshimizu M , Sutcliffe A , Taffese HS , Bayissa GA , Zohdy S , Tongren JE , Drakeley C , Greenhouse B , Bousema T , Tadesse FG . Nat Med 2023 29 (12) 3203-3211 Anopheles stephensi, an Asian malaria vector, continues to expand across Africa. The vector is now firmly established in urban settings in the Horn of Africa. Its presence in areas where malaria resurged suggested a possible role in causing malaria outbreaks. Using a prospective case control design, we investigated the role of An. stephensi in transmission following a malaria outbreak in Dire Dawa, Ethiopia in April-July 2022. Screening contacts of malaria patients and febrile controls revealed spatial clustering of P. falciparum infections around malaria patients in strong association with An. stephensi presence in the household vicinity. Plasmodium sporozoites were detected in these mosquitoes. This outbreak involved clonal propagation of parasites with molecular signatures of artemisinin and diagnostic resistance. This study provides the strongest evidence to date for a role of An. stephensi in driving an urban malaria outbreak in Africa, highlighting the major public health threat this fast-spreading mosquito poses. |
Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis
Commons RJ , Rajasekhar M , Edler P , Abreha T , Awab GR , Baird JK , Barber BE , Chu CS , Cui L , Daher A , Gonzalez-Ceron L , Grigg MJ , Hwang J , Karunajeewa H , Lacerda MVG , Ladeia-Andrade S , Lidia K , Llanos-Cuentas A , Longley RJ , Pereira DB , Pasaribu AP , Pukrittayakamee S , Rijal KR , Sutanto I , Taylor WRJ , Thanh PV , Thriemer K , Vieira JLF , Watson JA , Zuluaga-Idarraga LM , White NJ , Guerin PJ , Simpson JA , Price RN . Lancet Infect Dis 2023 BACKGROUND: Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient data meta-analysis to investigate the efficacy and tolerability of different primaquine dosing regimens to prevent P vivax recurrence. METHODS: For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, and if they included a treatment group with daily primaquine given over multiple days, where primaquine was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. We assessed the effects of total dose and duration of primaquine regimens on the rate of first P vivax recurrence between day 7 and day 180 by Cox's proportional hazards regression (efficacy analysis). The effect of primaquine daily dose on gastrointestinal symptoms on days 5-7 was assessed by modified Poisson regression (tolerability analysis). The study was registered with PROSPERO, CRD42019154470. FINDINGS: Of 226 identified studies, 23 studies with patient-level data from 6879 patients from 16 countries were included in the efficacy analysis. At day 180, the risk of recurrence was 51·0% (95% CI 48·2-53·9) in 1470 patients treated without primaquine, 19·3% (16·9-21·9) in 2569 patients treated with a low total dose of primaquine (approximately 3·5 mg/kg), and 8·1% (7·0-9·4) in 2811 patients treated with a high total dose of primaquine (approximately 7 mg/kg), regardless of primaquine treatment duration. Compared with treatment without primaquine, the rate of P vivax recurrence was lower after treatment with low-dose primaquine (adjusted hazard ratio 0·21, 95% CI 0·17-0·27; p<0·0001) and high-dose primaquine (0·10, 0·08-0·12; p<0·0001). High-dose primaquine had greater efficacy than low-dose primaquine in regions with high and low relapse periodicity (ie, the time from initial infection to vivax relapse). 16 studies with patient-level data from 5609 patients from ten countries were included in the tolerability analysis. Gastrointestinal symptoms on days 5-7 were reported by 4·0% (95% CI 0·0-8·7) of 893 patients treated without primaquine, 6·2% (0·5-12·0) of 737 patients treated with a low daily dose of primaquine (approximately 0·25 mg/kg per day), 5·9% (1·8-10·1) of 1123 patients treated with an intermediate daily dose (approximately 0·5 mg/kg per day) and 10·9% (5·7-16·1) of 1178 patients treated with a high daily dose (approximately 1 mg/kg per day). 20 of 23 studies included in the efficacy analysis and 15 of 16 in the tolerability analysis had a low or unclear risk of bias. INTERPRETATION: Increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg can reduce P vivax recurrences by more than 50% in most endemic regions, with a small associated increase in gastrointestinal symptoms. FUNDING: Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture. |
Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis
Mehdipour P , Rajasekhar M , Dini S , Zaloumis S , Abreha T , Adam I , Awab GR , Baird JK , Brasil LW , Chu CS , Cui L , Daher A , do Socorro MGomes M , Gonzalez-Ceron L , Hwang J , Karunajeewa H , Lacerda MVG , Ladeia-Andrade S , Leslie T , Ley B , Lidia K , Llanos-Cuentas A , Longley RJ , Monteiro WM , Pereira DB , Rijal KR , Saravu K , Sutanto I , Taylor WRJ , Thanh PV , Thriemer K , Vieira JLF , White NJ , Zuluaga-Idarraga LM , Guerin PJ , Price RN , Simpson JA , Commons RJ . Malar J 2023 22 (1) 306 BACKGROUND: Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence. METHODS: Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis. RESULTS: Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1-16.1] in patients with poor adherence compared to 5.8% [5.0-6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8-2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3-15.2] in patients with poor adherence and 4.9% [4.1-5.8] in patients with full adherence; p < 0.001. CONCLUSION: Reduced adherence, including less supervision, increases the risk of vivax recurrence. |
Primaquine dose and the risk of haemolysis in patients with uncomplicated Plasmodium vivax malaria: a systematic review and individual patient data meta-analysis
Rajasekhar M , Simpson JA , Ley B , Edler P , Chu CS , Abreha T , Awab GR , Baird JK , Bancone G , Barber BE , Grigg MJ , Hwang J , Karunajeewa H , Lacerda MVG , Ladeia-Andrade S , Llanos-Cuentas A , Pukrittayakamee S , Rijal KR , Saravu K , Sutanto I , Taylor WRJ , Thriemer K , Watson JA , Guerin PJ , White NJ , Price RN , Commons RJ . Lancet Infect Dis 2023 BACKGROUND: Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We undertook a systematic review and individual patient data meta-analysis to investigate the haematological safety of different primaquine regimens for P vivax radical cure. METHODS: For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, if they included a treatment group with daily primaquine given over multiple days where primaquine was commenced within 3 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine), and if they recorded haemoglobin or haematocrit concentrations on day 0. We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. The main outcome was haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL by day 14. Haemoglobin concentration changes between day 0 and days 2-3 and between day 0 and days 5-7 were assessed by mixed-effects linear regression for patients with glucose-6-phosphate dehydrogenase (G6PD) activity of (1) 30% or higher and (2) between 30% and less than 70%. The study was registered with PROSPERO, CRD42019154470 and CRD42022303680. FINDINGS: Of 226 identified studies, 18 studies with patient-level data from 5462 patients from 15 countries were included in the analysis. A haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL occurred in one (0·1%) of 1208 patients treated without primaquine, none of 893 patients treated with a low daily dose of primaquine (<0·375 mg/kg per day), five (0·3%) of 1464 patients treated with an intermediate daily dose (0·375 mg/kg per day to <0·75 mg/kg per day), and six (0·5%) of 1269 patients treated with a high daily dose (≥0·75 mg/kg per day). The covariate-adjusted mean estimated haemoglobin changes at days 2-3 were -0·6 g/dL (95% CI -0·7 to -0·5), -0·7 g/dL (-0·8 to -0·5), -0·6 g/dL (-0·7 to -0·4), and -0·5 g/dL (-0·7 to -0·4), respectively. In 51 patients with G6PD activity between 30% and less than 70%, the adjusted mean haemoglobin concentration on days 2-3 decreased as G6PD activity decreased; two patients in this group who were treated with a high daily dose of primaquine had a reduction of more than 25% to a concentration of less than 7 g/dL. 17 of 18 included studies had a low or unclear risk of bias. INTERPRETATION: Treatment of patients with G6PD activity of 30% or higher with 0·25-0·5 mg/kg per day primaquine regimens and patients with G6PD activity of 70% or higher with 0·25-1 mg/kg per day regimens were associated with similar risks of haemolysis to those in patients treated without primaquine, supporting the safe use of primaquine radical cure at these doses. FUNDING: Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture. |
Testing and treatment for malaria elimination: A systematic review
Newby G , Cotter C , Roh ME , Harvard K , Bennett A , Hwang J , Chitnis N , Fine S , Stresman G , Chen I , Gosling R , Hsiang MS . Malar J 2023 22 (1) 254 BACKGROUND: Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies. METHODS: A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission. RESULTS: A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively. CONCLUSION: Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting. |
Isolation of terbinafine-resistant trichophyton rubrum from onychomycosis patients who failed treatment at an academic center in New York, United States
Hwang JK , Bakotic WL , Gold JAW , Magro CM , Lipner SR . J Fungi (Basel) 2023 9 (7) Onychomycosis is a common nail infection. Terbinafine-resistant dermatophyte infections pose an emerging global public health concern, but few cases have been described in the United States. We retrospectively reviewed and characterized clinical, histopathological, and mycological features of patients with mycologically confirmed onychomycosis who failed oral terbinafine treatment for onychomycosis at a U.S. academic nail referral center and ascertained for terbinafine-resistant isolates. During 1 June 2022-31 January 2023 at Weill Cornell Medicine in New York City, USA, 96 patients with mycologically confirmed onychomycosis were treated with oral terbinafine. Among 64 patients with adequate follow-up, 36 had clinical or complete cure. Of 28 patients who failed treatment, 17 underwent terbinafine resistance testing. Trichophyton rubrum with terbinafine resistance-conferring mutations was isolated from two patients. Overall, terbinafine failures for onychomycosis were relatively common, with some cases associated with terbinafine-resistant T. rubrum infections. These findings underscore the need for a clinical awareness of this emerging problem and public health efforts to monitor and prevent spread. We highlight the importance of diagnostic testing and species identification for onychomycosis patients and the increasingly important role of fungal identification and susceptibility testing to guide therapy. |
Defining operational research priorities to improve malaria control and elimination in sub-Saharan Africa: Results from a country-driven research prioritization setting process
Tine R , Herrera S , Badji MA , Daniels K , Ndiaye P , Smith Gueye C , Tairou F , Slutsker L , Hwang J , Ansah E , Littrell M . Malar J 2023 22 (1) 219 BACKGROUND: In order to reignite gains and accelerate progress toward improved malaria control and elimination, policy, strategy, and operational decisions should be derived from high-quality evidence. The U.S. President's Malaria Initiative (PMI) Insights project together with the Université Cheikh Anta Diop of Dakar, Senegal, conducted a broad stakeholder consultation process to identify pressing evidence gaps in malaria control and elimination across sub-Saharan Africa (SSA), and developed a priority list of country-driven malaria operational research (OR) and programme evaluation (PE) topics to address these gaps. METHODS: Five key stakeholder groups were engaged in the process: national malaria programmes (NMPs), research institutions in SSA, World Health Organization (WHO) representatives in SSA, international funding agencies, and global technical partners who support malaria programme implementation and research. Stakeholders were engaged through individual or small group interviews and an online survey, and asked about key operational challenges faced by NMPs, pressing evidence gaps in current strategy and implementation guidance, and priority OR and PE questions to address the challenges and gaps. RESULTS: Altogether, 47 interviews were conducted with 82 individuals, and through the online survey, input was provided by 46 global technical partners. A total of 33 emergent OR and PE topics were identified through the consultation process and were subsequently evaluated and prioritized by an external evaluation committee of experts from NMPs, research institutions, and the WHO. The resulting prioritized OR and PE topics predominantly focused on generating evidence needed to close gaps in intervention coverage, address persistent challenges faced by NMPs in the implementation of core strategic interventions, and inform the effective deployment of new tools. CONCLUSION: The prioritized research list is intended to serve as a key resource for informing OR and PE investments, thereby ensuring future investments focus on generating the evidence needed to strengthen national strategies and programme implementation and facilitating a more coordinated and impactful approach to malaria operational research. |
Study protocol for a cluster-randomized split-plot design trial to assess the effectiveness of targeted active malaria case detection among high-risk populations in Southern Lao PDR (the AcME-Lao study)
Lover AA , Dantzer E , Hocini S , Estera R , Rerolle F , Smith JL , Hwang J , Gosling R , Yukich J , Greenhouse B , Jacobson J , Phetsouvanh R , Hongvanthong B , Bennett A . Gates Open Res 2019 3 1730 Introduction: Novel interventions are needed to accelerate malaria elimination, especially in areas where asymptomatic parasitemia is common, and where transmission generally occurs outside of village-based settings. Testing of community members linked to a person with clinical illness (reactive case detection, RACD) has not shown effectiveness in prior studies due to the limited sensitivity of current point-of-care tests. This study aims to assess the effectiveness of active case finding in village-based and forested-based settings using novel high-sensitivity rapid diagnostic tests in Lao People's Democratic Republic (Lao PDR). Methods and analysis: This study is a cluster-randomized split-plot design trial. The interventions include village-based mass test and treat (MTAT), focal test and treat in high-risk populations (FTAT), and the combination of these approaches, using high-sensitivity rapid diagnostic tests (HS-RDTs) to asses P. falciparum infection status. Within four districts in Champasak province, Lao PDR fourteen health center-catchment areas will be randomized to either FTAT or control; and within these HCCAs, 56 villages will be randomized to either MTAT or control. In intervention areas, FTAT will be conducted by community-based peer navigators on a routine basis, and three separate rounds of MTAT are planned. The primary study outcome will be PCR-based Plasmodium falciparum prevalence after one year of implementation. Secondary outcomes include malaria incidence; interventional coverage; operational feasibility and acceptability; and cost and cost- effectiveness. Ethics and dissemination: Findings will be reported on clinicaltrials.gov, in peer-reviewed publications and through stakeholder meetings with Ministry of Health and community leaders in Lao PDR and throughout the Greater Mekong Subregion. Trial registration: clinicaltrials.gov NCT03783299 (21/12/2018). |
Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
WorldWide Antimalarial Resistance Network Falciparum Haematology Study Group , Hwang J , Plucinski M , Thwing JI . BMC Med 2022 20 (1) 85 BACKGROUND: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. METHODS: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. RESULTS: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001). CONCLUSIONS: In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery. |
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis
WorldWide Antimalarial Resistance Network Methodology Study Group , Desai M , Hwang J , Plucinski MM , Udhayakumar V . Malar J 2022 21 (1) 106 BACKGROUND: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria. METHODS: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up. RESULTS: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with ≤ 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution. CONCLUSIONS: Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance. |
Therapeutic efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and chloroquine and dihydroartemisinin-piperaquine for uncomplicated Plasmodium vivax infection in Ethiopia
Assefa A , Mohammed H , Anand A , Abera A , Sime H , Minta AA , Tadesse M , Tadesse Y , Girma S , Bekele W , Etana K , Alemayehu BH , Teka H , Dilu D , Haile M , Solomon H , Moriarty LF , Zhou Z , Svigel SS , Ezema B , Tasew G , Woyessa A , Hwang J , Murphy M . Malar J 2022 21 (1) 359 BACKGROUND: Routine monitoring of anti-malarial drugs is recommended for early detection of drug resistance and to inform national malaria treatment guidelines. In Ethiopia, the national treatment guidelines employ a species-specific approach. Artemether-lumefantrine (AL) and chloroquine (CQ) are the first-line schizonticidal treatments for Plasmodium falciparum and Plasmodium vivax, respectively. The National Malaria Control and Elimination Programme in Ethiopia is considering dihydroartemisinin-piperaquine (DHA/PPQ) as an alternative regimen for P. falciparum and P. vivax. METHODS: The study assessed the clinical and parasitological efficacy of AL, CQ, and DHA/PPQ in four arms. Patients over 6 months and less than 18 years of age with uncomplicated malaria mono-infection were recruited and allocated to AL against P. falciparum and CQ against P. vivax. Patients 18 years or older with uncomplicated malaria mono-infection were recruited and randomized to AL or dihydroartemisinin-piperaquine (DHA/PPQ) against P. falciparum and CQ or DHA/PPQ for P. vivax. Patients were followed up for 28 (for CQ and AL) or 42 days (for DHA/PPQ) according to the WHO recommendations. Polymerase chain reaction (PCR)-corrected and uncorrected estimates were analysed by Kaplan Meier survival analysis and per protocol methods. RESULTS: A total of 379 patients were enroled in four arms (n = 106, AL-P. falciparum; n = 75, DHA/PPQ- P. falciparum; n = 142, CQ-P. vivax; n = 56, DHA/PPQ-P. vivax). High PCR-corrected adequate clinical and parasitological response (ACPR) rates were observed at the primary end points of 28 days for AL and CQ and 42 days for DHA/PPQ. ACPR rates were 100% in AL-Pf (95% CI: 96-100), 98% in CQ-P. vivax (95% CI: 95-100) at 28 days, and 100% in the DHA/PPQ arms for both P. falciparum and P. vivax at 42 days. For secondary endpoints, by day three 99% of AL-P. falciparum patients (n = 101) cleared parasites and 100% were afebrile. For all other arms, 100% of patients cleared parasites and were afebrile by day three. No serious adverse events were reported. CONCLUSION: This study demonstrated high therapeutic efficacy for the anti-malarial drugs currently used by the malaria control programme in Ethiopia and provides information on the efficacy of DHA/PPQ for the treatment of P. falciparum and P. vivax as an alternative option. |
Assessing urinary phenol and paraben mixtures in pregnant women with and without gestational diabetes mellitus: A case-control study
Chen WJ , Robledo C , Davis EM , Goodman JR , Xu C , Hwang J , Janitz AE , Garwe T , Calafat AM , Peck JD . Environ Res 2022 214 113897 Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable logistic regression was used to evaluate the associations between individual chemical biomarkers and GDM while controlling for confounding. We used probit implementation of BKMR with hierarchical variable selection to estimate the mean difference in GDM probability for each component of the phenol and paraben mixtures while controlling for the correlation among the chemical biomarkers. When analyzing individual chemicals using logistic regression, benzophenone-3 was positively associated with GDM [adjusted odds ratio (aOR) per interquartile range (IQR)=1.54, 95% confidence interval (CI) 1.15, 2.08], while BPA was negatively associated with GDM (aOR 0.61, 95% CI 0.37, 0.99). In probit-BKMR analysis, an increase in z-score transformed log urinary concentrations of benzophenone-3 from the 10th to 90th percentile was associated with an increase in the estimated difference in the probability of GDM (0.67, 95% Credible Interval 0.04, 1.30), holding other chemicals fixed at their medians. No associations were identified between other chemical biomarkers and GDM in the BKMR analyses. We observed that the association of BPA and GDM was attenuated when accounting for correlated phenols and parabens, suggesting the importance of addressing chemical mixtures in perinatal environmental exposure studies. Additional prospective investigations will increase the understanding of the relationship between benzophenone-3 exposure and GDM development. |
Missed plasmodium ovale infections among symptomatic persons in Angola, Mozambique, and Ethiopia
Leonard CM , Hwang J , Assefa A , Zulliger R , Candrinho B , Dimbu PR , Saifodine A , Plucinski M , Rogier E . Open Forum Infect Dis 2022 9 (7) ofac261 The majority of symptomatic malaria in sub-Saharan Africa is caused by Plasmodium falciparum. Infection with Plasmodium ovale is often not recorded and not considered clinically relevant. Here, we describe 8 cases of P ovale infection from 3 African countries-all of which were misdiagnosed at the presenting health facility. |
Involvement of a putative ATP-Binding Cassette (ABC) Involved in manganese transport in virulence of Listeria monocytogenes.
Liu Y , Yoo BB , Hwang CA , Martinez MR , Datta AR , Fratamico PM . PLoS One 2022 17 (5) e0268924 Listeria monocytogenes is a foodborne pathogen and the causative agent of listeriosis, a disease associated with high fatality (20-30%) and hospitalization rates (>95%). ATP-Binding Cassette (ABC) transporters have been demonstrated to be involved in the general stress response. In previous studies, in-frame deletion mutants of the ABC transporter genes, LMOf2365_1875 and LMOf2365_1877, were constructed and analyzed; however, additional work is needed to investigate the virulence potential of these deletion mutants. In this study, two in vitro methods and one in vivo model were used to investigate the virulence potential of in-frame deletion mutants of ABC transporter genes. First, the invasion efficiency in host cells was measured using the HT-29 human cell line. Second, cell-to-cell spread activity was measured using a plaque forming assay. Lastly, virulence potential of the mutants was tested in the Galleria mellonella wax moth model. Our results demonstrated that the deletion mutant, ⊿LMOf2365_1875, displayed decreased invasion and cell-to-cell spread efficiency in comparison to the wild-type, LMOf2365, indicating that LMOf2365_1875 may be required for virulence. Furthermore, the reduced virulence of these mutants was confirmed using the Galleria mellonella wax moth model. In addition, the expression levels of 15 virulence and stress-related genes were analyzed by RT-PCR assays using stationary phase cells. Our results showed that virulence-related gene expression levels from the deletion mutants were elevated (15/15 genes from ⊿LMOf2365_1877 and 7/15 genes from ⊿LMOf2365_1875) compared to the wild type LMOf2365, suggesting that ABC transporters may negatively regulate virulence gene expression under specific conditions. The expression level of the stress-related gene, clpE, also was increased in both deletion mutants, indicating the involvement of ABC transporters in the stress response. Taken together, our findings suggest that ABC transporters may be used as potential targets to develop new therapeutic strategies to control L. monocytogenes. |
The use of a chimeric antigen for Plasmodium falciparum and P. vivax seroprevalence estimates from community surveys in Ethiopia and Costa Rica.
McCaffery JN , Singh B , Nace D , Assefa A , Hwang J , Plucinski M , Calvo N , Moreno A , Udhayakumar V , Rogier E . PLoS One 2022 17 (5) e0263485 BACKGROUND: In low-transmission settings, accurate estimates of malaria transmission are needed to inform elimination targets. Detection of antimalarial antibodies provides exposure history, but previous studies have mainly relied on species-specific antigens. The use of chimeric antigens that include epitopes from multiple species of malaria parasites in population-based serological surveys could provide data for exposure to multiple Plasmodium species circulating in an area. Here, the utility of P. vivax/P. falciparum chimeric antigen for assessing serological responses was evaluated in Ethiopia, an endemic country for all four human malarias, and Costa Rica, where P. falciparum has been eliminated with reports of sporadic P. vivax cases. METHODS: A multiplex bead-based assay was used to determine the seroprevalence of IgG antibodies against a chimeric malaria antigen (PvRMC-MSP1) from blood samples collected from household surveys in Ethiopia in 2015 (n = 7,077) and Costa Rica in 2015 (n = 851). Targets specific for P. falciparum (PfMSP1) and P. vivax (PvMSP1) were also included in the serological panel. Seroprevalence in the population and seroconversion rates were compared among the three IgG targets. RESULTS: Seroprevalence in Costa Rica was 3.6% for PfMSP1, 41.5% for PvMSP1 and 46.7% for PvRMC-MSP1. In Ethiopia, seroprevalence was 27.6% for PfMSP1, 21.4% for PvMSP1, and 32.6% for PvRMC-MSP1. IgG levels in seropositive individuals were consistently higher for PvRMC-MSP1 when compared to PvMSP1 in both studies. Seroconversion rates were 0.023 for PvMSP1 and 0.03 for PvRMC-MSP1 in Costa Rica. In Ethiopia, seroconversion rates were 0.050 for PfMSP1, 0.044 for PvMSP1 and 0.106 for PvRMC-MSP1. CONCLUSIONS: Our data indicate that chimeric antigen PvRMC-MSP1 is able to capture antibodies to multiple epitopes from both prior P. falciparum and P. vivax infections, and suitable chimeric antigens can be considered for use in serosurveys with appropriate validation. |
Evaluation of the effect of targeted mass drug administration and reactive case detection on malaria transmission and elimination in Eastern Hararghe zone, Oromia, Ethiopia: A cluster randomized control trial
Abdelmenan S , Teka H , Hwang J , Girma S , Chibsa S , Tongren E , Murphy M , Haile M , Dillu D , Kassim J , Behaksra S , Tadesse FG , Yukich J , Berhane Y , Worku A , Keating J , Zewde A , Gadisa E . Trials 2022 23 (1) 267 BACKGROUND: Reactive and proactive case detection measures are widely implemented by national malaria elimination programs globally. Ethiopia decided to include Reactive Case Detection (RCD) and targeted Mass Drug Administration (tMDA) approaches as part of their elimination strategy along with rigorous evaluation. The purpose of this study is to compare the impact of RCD and tMDA on malaria elimination over the 2-year study period, by looking at the annual parasite incidence before and after the intervention. METHODS: The study will be conducted in the East Hararghe zone of Ethiopia. Malaria transmission in the area is low to moderate. This study will deploy a community-based, three-arm, cluster-randomized control trial implemented over 2 years. Forty-eight clusters (16 clusters per arm) will be selected based on the annual number of confirmed malaria cases seen in the cluster. All clusters will receive the current standard of care in terms of malaria elimination interventions provided by the national malaria control program. In addition, following the identification of malaria parasite infection, individuals who reside within a 100-m radius of the index case will receive a diagnosis for malaria and treatment if positive in the RCD arm or presumptive treatment in the tMDA arm. The primary effectiveness endpoint will be measured at baseline and endline for each intervention arm and compared to the control arm using a difference in difference approach. DISCUSSION: This randomized controlled trial will provide evidence of the impact of the proposed intervention approaches for malaria elimination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04241705 . Registration date: January 27, 2020. |
Investigation of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions and performance of a rapid diagnostic test for identifying asymptomatic malaria infection in northern Ethiopia, 2015.
Leonard CM , Assefa A , McCaffery JN , Herman C , Plucinski M , Sime H , Mohammed H , Kebede A , Solomon H , Haile M , Murphy M , Hwang J , Rogier E . Malar J 2022 21 (1) 70 BACKGROUND: Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis of both symptomatic and asymptomatic infections. Although RDTs are a reliable and practical diagnostic tool, the sensitivity of histidine-rich protein 2 (HRP2)-based RDTs can be reduced if pfhrp2 or pfhrp3 (pfhrp2/3) gene deletions exist in the Plasmodium falciparum parasite population. This study evaluated dried blood spot (DBS) samples collected from a national household survey to investigate the presence of pfhrp2/3 deletions and the performance of the RDT used in the cross-sectional survey in a low transmission setting. METHODS: The 2015 Ethiopia Malaria Indicator Survey tested household members by RDT and collected DBS samples. DBS (n = 2648) from three regions in northern Ethiopia were tested by multiplex bead-based antigen detection assay after completion of the survey. The multiplex assay detected pan-Plasmodium lactate dehydrogenase (LDH), pAldolase, and HRP2 antigens in samples. Samples suspected for pfhrp2/3 gene deletions (pLDH and/or pAldolase positive but low or absent HRP2) were further investigated by molecular assays for gene deletions. Antigen results were also compared to each individual's RDT results. Dose-response logistic regression models were fit to estimate RDT level of detection (LOD) antigen concentrations at which 50, 75, 90, and 95% of the RDTs returned a positive result during this survey. RESULTS: Out of 2,648 samples assayed, 29 were positive for pLDH or pAldolase antigens but low or absent for HRP2 signal, and 15 of these samples (51.7%) were successfully genotyped for pfhrp2/3. Of these 15 P. falciparum infections, eight showed single deletions in pfhrp3, one showed a single pfhrp2 deletion, and six were pfhrp2/3 double-deletions. Six pfhrp2 deletions were observed in Tigray and one in Amhara. Twenty-five were positive for HRP2 by the survey RDT while the more sensitive bead assay detected 30 HRP2-positive samples. A lower concentration of HRP2 antigen generated a positive test result by RDT compared to pLDH (95% LOD: 16.9 ng/mL vs. 319.2 ng/mL, respectively). CONCLUSIONS: There is evidence of dual pfhrp2/3 gene deletions in the Tigray and Amhara regions of Ethiopia in 2015. As the prevalence of malaria was very low (< 2%), it is difficult to make strong conclusions on RDT performance, but these results challenge the utility of biomarkers in household surveys in very low transmission settings. |
Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions from persons with symptomatic malaria infection in Ethiopia, Kenya, Madagascar, and Rwanda
Rogier E , McCaffery JN , Nace D , Svigel SS , Assefa A , Hwang J , Kariuki S , Samuels AM , Westercamp N , Ratsimbasoa A , Randrianarivelojosia M , Uwimana A , Udhayakumar V , Halsey ES . Emerg Infect Dis 2022 28 (3) 608-616 Histidine-rich protein 2 (HRP2)-based rapid diagnostic tests detect Plasmodium falciparum malaria and are used throughout sub-Saharan Africa. However, deletions in the pfhrp2 and related pfhrp3 (pfhrp2/3) genes threaten use of these tests. Therapeutic efficacy studies (TESs) enroll persons with symptomatic P. falciparum infection. We screened TES samples collected during 2016-2018 in Ethiopia, Kenya, Rwanda, and Madagascar for HRP2/3, pan-Plasmodium lactate dehydrogenase, and pan-Plasmodium aldolase antigen levels and selected samples with low levels of HRP2/3 for pfhrp2/3 genotyping. We observed deletion of pfhrp3 in samples from all countries except Kenya. Single-gene deletions in pfhrp2 were observed in 1.4% (95% CI 0.2%-4.8%) of Ethiopia samples and in 0.6% (95% CI 0.2%-1.6%) of Madagascar samples, and dual pfhrp2/3 deletions were noted in 2.0% (95% CI 0.4%-5.9%) of Ethiopia samples. Although this study was not powered for precise prevalence estimates, evaluating TES samples revealed a low prevalence of pfhrp2/3 deletions in most sites. |
Child nutritional status as screening tool for identifying undernourished mothers: an observational study of mother-child dyads in Mogadishu, Somalia, from November 2019 to March 2020
Zacks R , Ververs M , Hwang C , Mahdi A , Leidman E . BMJ Nutr Prev Health 2021 4 (2) 501-509 BACKGROUND: Active screening of only pregnant and lactating mothers (PLMs) excludes other mothers of reproductive age susceptible to undernutrition. Our analysis evaluated if mothers presenting with wasted children were more likely to be undernourished themselves. METHODS: The observational study enrolled mother and child dyads presenting to an outpatient facility in Mogadishu, Somalia, between November 2019 and March 2020. Trained nurses recorded lower extremity oedema for children aged 6-59 months, parity and gestational status for women aged 19-50 years and age, access to care, height/length, mid-upper arm circumference (MUAC) and weight for both. Weight-for-height z-score (WHZ) for children and body mass index (BMI) for mothers were calculated using standard procedures. Wasting was defined as WHZ <-2, MUAC <12.5 cm and/or presence of oedema for children. Undernutrition was defined as MUAC <23 cm for PLMs and BMI <18.5 kg/m(2) for neither pregnant nor lactating mothers (non-PLMs). Four multivariable linear regression models were fit to evaluate maternal anthropometric indicators (BMI or MUAC) given child anthropometric indicators (MUAC or WHZ), adjusting for maternal age, parity and gestational status. RESULTS: A total of 93.6% (2142/2288) of enrolled dyads met inclusion criteria. Wasting was observed among 57.5% of children; 20.2% of pregnant mothers, 20.0% of lactating mothers and 7.95% of non-PLMs were undernourished. Models suggest significant, positive associations between child and maternal anthropometrics; a one-unit increase in WHZ and a 1 cm increase in child MUAC were associated with 0.22 kg/m(2) (95% CI 0.22 to 0.24) and 0.19 kg/m(2) (95% CI 0.16 to 0.21) increases in maternal BMI, respectively, and 0.20 cm (95% CI 0.18 to 0.22) and 0.24 cm (95% CI 0.23 to 0.25) increases in maternal MUAC, respectively. Adjusted R(2) values were low (range 0.06-0.10). CONCLUSIONS: Undernutrition among non-PLMs illustrates the importance of expanding screening. However, while significant, the strength of association between mother and child anthropometrics does not support child nutritional status as a screening tool for identifying at-risk mothers. |
Biomonitoring of exposure to Great Lakes contaminants among licensed anglers and Burmese refugees in Western New York: Toxic metals and persistent organic pollutants, 2010-2015
Hsu WH , Zheng Y , Savadatti SS , Liu M , Lewis-Michl EL , Aldous KM , Parsons PJ , Kannan K , Rej R , Wang W , Palmer CD , Wattigney WA , Irvin-Barnwell E , Hwang SA . Int J Hyg Environ Health 2022 240 113918 Between 2010 and 2015, the New York State Department of Health (NYSDOH) conducted a biomonitoring program to gather exposure data on Great Lakes contaminants among licensed anglers and Burmese refugees living in western New York who ate locally caught fish. Four hundred and nine adult licensed anglers and 206 adult Burmese refugees participated in this program. Participants provided blood and urine samples and completed a detailed questionnaire. Herein, we present blood metal levels (cadmium, lead, and total mercury) and serum persistent organic pollutant concentrations [polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dichlorodiphenyldichloroethylene (DDE), and trans-nonachlor]. Multiple linear regression was applied to investigate the associations between analyte concentrations and indicators of fish consumption (locally caught fish meals, store-bought fish meals, and consuming fish/shellfish in the past week). Licensed anglers consumed a median of 16 locally caught fish meals and 22 store-bought fish meals while Burmese refugees consumed a median of 106 locally caught fish meals and 104 store-bought fish/shellfish meals in the past year. Compared to the general U.S. adult population, licensed anglers had higher blood lead and mercury levels; and Burmese refuges had higher blood cadmium, lead, and mercury, and higher serum DDE levels. Eating more locally caught fish was associated with higher blood lead, blood mercury, and serum PCBs concentrations among licensed anglers. Licensed anglers and Burmese refugees who reported fish/shellfish consumption in the past week had elevated blood mercury levels compared with those who reported no consumption. Among licensed anglers, eating more store-bought fish meals was also associated with higher blood mercury levels. As part of the program, NYSDOH staff provided fish advisory outreach and education to all participants on ways to reduce their exposures, make healthier choices of fish to eat, and waters to fish from. Overall, our findings on exposure levels and fish consumption provide information to support the development and implementation of exposure reduction public health actions. |
Assessing exposures to per- and polyfluoroalkyl substances in two populations of Great Lakes Basin fish consumers in Western New York State
Liu M , Nordstrom M , Forand S , Lewis-Michl E , Wattigney WA , Kannan K , Wang W , Irvin-Barnwell E , Hwang SA . Int J Hyg Environ Health 2021 240 113902 BACKGROUND: Fish and other seafood are an important dietary source of per- and polyfluoroalkyl substances (PFAS) exposure in many areas of the world, and PFAS were found to be pervasive in fish from the Great Lakes area. Few studies, however, have examined the associations between Great Lakes Basin fish consumption and PFAS exposure. Many licensed anglers and Burmese refugees and immigrants residing in western New York State consume fish caught from the Great Lakes and surrounding waters, raising their risk of exposure to environmental contaminants including PFAS. The aims of this study were to: 1) present the PFAS exposure profile of the licensed anglers and Burmese refugees and 2) examine the associations between serum PFAS levels and local fish consumption. METHODS: Licensed anglers (n = 397) and Burmese participants (n = 199) provided blood samples and completed a detailed questionnaire in 2013. We measured 12 PFAS in serum. Multiple linear regression was used to assess associations between serum PFAS concentrations and self-reported consumption of fish from Great Lakes waters. RESULTS: Licensed anglers and Burmese participants reported consuming a median of 16 (IQR: 6-36) and 88 (IQR: 44-132) meals of locally caught fish in the year before sample collection, respectively (data for Burmese group restricted to 10 months of the year). Five PFAS were detected in almost all study participants (PFOS, PFOA, PFHxS, PFNA and PFDA; 97.5-100%). PFOS had the highest median serum concentration in licensed anglers (11.6 ng/mL) and the Burmese (35.6 ng/mL), approximately two and six times that of the U.S. general population, respectively. Serum levels of other PFAS in both groups were generally low and comparable to those in the general U.S. POPULATION: Among licensed anglers, Great Lakes Basin fish meals over the past year were positively associated with serum PFOS (P < 0.0001), PFDA (P < 0.0001), PFHxS (P = 0.01), and PFNA (P = 0.02) and the number of years consuming locally caught fish was positively associated with serum PFOS (P = 0.01) and PFDA (P = 0.01) levels. In the Burmese group, consuming Great Lakes Basin fish more than three times a week in the past summer was positively associated with serum PFOS (P = 0.004) and PFDA (P = 0.02) among the Burmese of non-Karen ethnicity, but not among those of Karen ethnicity, suggesting potential ethnic differences in PFAS exposure. CONCLUSIONS: Great Lakes Basin fish consumption was associated with an increase in blood concentrations of some PFAS, and especially of PFOS, among licensed anglers and Burmese refugees and immigrants in western New York State. In the Burmese population, there may be other important PFAS exposure routes related to residential history and ethnicity. Continued outreach efforts to increase fish advisory awareness and reduce exposure to contaminants are needed among these populations. |
Missed Plasmodium falciparum and Plasmodium vivax Mixed Infections in Ethiopia Threaten Malaria Elimination.
Leonard CM , Mohammed H , Tadesse M , McCaffery JN , Nace D , Halsey ES , Girma S , Assefa A , Hwang J , Rogier E . Am J Trop Med Hyg 2021 106 (2) 667-670 Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia. This study investigated whether mixed infections were missed by microscopy from a 2017 therapeutic efficacy study at two health facilities in Ethiopia. All patients (N = 304) were initially classified as having single-species P. falciparum (n = 148 samples) or P. vivax infections (n = 156). Dried blood spots were tested for Plasmodium antigens by bead-based multiplex assay for pan-Plasmodium aldolase, pan-Plasmodium lactate dehydrogenase, P. vivax lactate dehydrogenase, and histidine-rich protein 2. Of 304 blood samples, 13 (4.3%) contained both P. falciparum and P. vivax antigens and were analyzed by polymerase chain reaction for species-specific DNA. Of these 13 samples, five were confirmed by polymerase chain reaction for P. falciparum/P. vivax co-infection. One sample, initially classified as P. vivax by microscopy, was found to only have Plasmodium ovale DNA. Plasmodium falciparum/P. vivax mixed infections can be missed by microscopy even in the context of a therapeutic efficacy study with multiple trained readers. |
Biomonitoring of per- and polyfluoroalkyl substances in minority angler communities in central New York State
Wattigney WA , Savadatti SS , Liu M , Pavuk M , Lewis-Michl E , Kannan K , Wang W , Spliethoff H , Marquez-Bravo L , Hwang SA . Environ Res 2021 204 112309 Onondaga Lake in central New York State was listed as a Superfund site in 1994 due to industrial disposal of pollutants. A biomonitoring program was conducted to assess exposure to over 70 legacy contaminants and contaminants of emerging concern in populations disproportionately at risk for exposure residing near Onondaga Lake and to educate these communities on how to reduce exposures. The populations of focus were refugees from Burma and Bhutan and low-income, primarily African American, anglers (urban anglers). These communities consume locally caught fish for economic as well as cultural reasons and therefore may be at higher risk of exposure. This study focuses on assessment of exposure to per- and polyfluoroalkyl substances (PFAS) and associations with local fish consumption. Using respondent driven sampling, 311 refugees and 89 urban anglers were enrolled in the study. Following informed consent, study participants provided blood and urine specimens and completed a questionnaire. Percentiles of locally caught fish meals in the past 12 months by race/ethnicity groups showed that the Burmese participants of Karen ethnicity were the highest consumers, with a median of 135 meals compared to 103 meals for the other Burmese participants, 70 meals for the urban anglers, and 44 meals for the Bhutanese participants. Compared to the National Health and Nutrition Examination Survey (NHANES) 2015-16 sample of the general U.S. population, the Karen participants had markedly elevated perfluorooctane sulfonic acid (PFOS) and perfluorodecanoic acid (PFDA) levels with median serum concentrations 9.5 times greater (41.6 ng/mL vs. 4.4 ng/mL) and 26.9 times greater (2.69 ng/mL vs. 0.10 ng/mL), respectively; the other Burmese participants had moderately elevated levels of PFOS and PFDA with median serum concentrations 3.0 times greater (13.3 ng/mL vs. 4.4 ng/mL) and 7.3 greater times greater (0.73 ng/mL vs. 0.10 ng/mL), respectively; and, PFAS levels were not elevated in the Bhutanese or urban angler cohorts. Male gender was consistently the strongest predictor of PFAS exposure among all study cohorts. A positive association between local fish consumption was indicated only for PFOS among urban anglers. An association between local fish consumption and PFAS was not statistically significant among the refugee cohorts, perhaps due to the lack of 'lower-end' exposure or exposure variability. Community events were held by the program staff to present the biomonitoring results and distribute community outreach materials with visual aids specific for the study populations to promote safe fish eating. |
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