Primaquine alternative dosing schedules for preventing malaria relapse in people with Plasmodium vivax.

BACKGROUND: Plasmodium vivax liver stages (hypnozoites) may cause relapses, prolonging morbidity, and impeding malaria control and elimination. The World Health Organization (WHO) recommends three schedules for primaquine: 0.25 mg/kg/day (standard), or 0.5 mg/kg/day (high standard) for 14 days, or 0.75 mg/kg once weekly for eight weeks, all of which can be difficult to complete. Since primaquine can cause haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, clinicians may be reluctant to prescribe primaquine without G6PD testing, and recommendations when G6PD status is unknown must be based on an assessment of the risks and benefits of prescribing primaquine. Alternative safe and efficacious regimens are needed. OBJECTIVES: To assess the efficacy and safety of alternative primaquine regimens for radical cure of P vivax malaria compared to the standard or high-standard 14-day courses. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); LILACS (BIREME); WHO International Clinical Trials Registry Platform and ClinicalTrials.gov up to 2 September 2019, and checked the reference lists of all identified studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) of adults and children with P vivax malaria using either chloroquine or artemisinin-based combination therapy plus primaquine at a total adult dose of at least 210 mg, compared with the WHO-recommended regimens of 0.25 or 0.5 mg/kg/day for 14 days. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality, and extracted data. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data. We grouped efficacy data according to length of follow-up, partner drug, and trial location. We analysed safety data where included. MAIN RESULTS: 0.5 mg/kg/day for seven days versus standard 0.25 mg/kg/day for 14 days There may be little or no difference in P vivax recurrences at six to seven months when using the same total dose (210 mg adult dose) over seven days compared to 14 days (RR 0.96, 95% CI 0.66 to 1.39; 4 RCTs, 1211 participants; low-certainty evidence). No serious adverse events were reported. We do not know if there is any difference in the number of adverse events resulting in discontinuation of primaquine (RR 1.04, 95% CI 0.15 to 7.38; 5 RCTs, 1427 participants) or in the frequency of anaemia (RR 3.00, 95% CI 0.12 to 72.91, 1 RCT, 240 participants) between the shorter and longer regimens (very low-certainty evidence). Three trials excluded people with G6PD deficiency; two did not provide this information. Pregnant and lactating women were either excluded or no details were provided. High-standard 0.5 mg/kg/day for 14 days versus standard 0.25 mg/kg/day for 14 days There may be little or no difference in P vivax recurrences at six months with 0.5 mg/kg/day primaquine for 14 days compared to 0.25 mg/kg/day for 14 days (RR 0.84 (95% CI 0.49 to 1.43; 2 RCTs, 677 participants, low-certainty evidence). No serious adverse events were reported. We do not know whether there is a difference in adverse events resulting in discontinuation of treatment with the high-standard dosage (RR 4.19, 95% CI 0.90 to 19.60; 1 RCT, 778 participants, very low-certainty evidence). People with G6PD deficiency and pregnant or lactating women were excluded. 0.75 mg/kg/week for eight weeks versus high-standard 0.5 mg/kg/day for 14 days We do not know whether weekly primaquine increases or decreases recurrences of P vivax compared to high-standard 0.5 mg/kg/day for 14 days, at 11 months' follow-up (RR 3.18, 95% CI 0.37 to 27.60; 1 RCT, 122 participants; very low-certainty evidence). No serious adverse events and no episodes of anaemia were reported. G6PD-deficient patients were not randomized but included in the weekly primaquine group (only one patient detected). 1 mg/kg/day for seven days versus high standard 0.5 mg/kg/day for 14 days There is probably little or no difference in P vivax recurrences at 12 months between 1.0 mg/kg/day primaquine for seven days and the high-standard 0.5 mg/kg/day for 14 days (RR 1.03, 95% CI 0.82 to 1.30; 2 RCTs, 2526 participants; moderate-certainty evidence). There may be moderate to large increase in serious adverse events in the 1.0 mg/kg/day primaquine for seven days compared with the high-standard 0.5 mg/kg/day for 14 days, during 42 days follow-up (RR 12.03, 95% CI 1.57 to 92.30; 1 RCT, 1872 participants, low-certainty evidence). We do not know if there is a difference between 1.0 mg/kg/day primaquine for seven days and high-standard 0.5 mg/kg/day for 14 days in adverse events that resulted in discontinuation of treatment (RR 2.50, 95% CI 0.49 to 12.87; 1 RCT, 2526 participants, very low-certainty evidence), nor if there is difference in frequency of anaemia by 42 days (RR 0.93, 95% CI 0.62 to 1.41; 2 RCTs, 2440 participants, very low-certainty evidence). People with G6PD deficiency were excluded. Other regimens Two RCTs evaluated other rarely-used doses of primaquine, one of which had very high loss to follow-up. Adverse events were not reported. People with G6PD deficiency and pregnant or lactating women were excluded. AUTHORS' CONCLUSIONS: Trials available to date do not detect a difference in recurrence between the following regimens: 1) 0.5 mg/kg/day for seven days versus standard 0.25 mg/kg/day for 14 days; 2) high-standard 0.5 mg/kg/day for 14 days versus standard 0.25 mg/kg/day for 14 days; 3) 0.75 mg/kg/week for eight weeks versus high-standard 0.5 mg/kg/day for 14 days; 4) 1 mg/kg/day for seven days versus high-standard 0.5 mg/kg/day for 14 days. There were no differences detected in adverse events for Comparisons 1, 2 or 3, but there may be more serious adverse events with the high seven-day course in Comparison 4. The shorter regimen of 0.5 mg/kg/day for seven days versus standard 0.25 mg/kg/day for 14 days may suit G6PD-normal patients. Further research will help increase the certainty of the findings and applicability in different settings.

Preventive chemotherapy reverses covert, lymphatic-associated tissue change in young people with lymphatic filariasis in Myanmar.

OBJECTIVES: This longitudinal comparative study investigated the effect of preventive chemotherapy (PC) on covert tissue changes associated with lymphatic filariasis (LF) among young people living in an LF-endemic area in Myanmar. METHODS: Tissue compressibility and extracellular free fluid in the lower limbs of people aged 10-21 years were measured using indurometry and bioimpedance spectroscopy (BIS). Baseline measures were taken in October 2014, annual mass drug administration (MDA) of PC was delivered in December, and in March 2015 further PC was offered to LF-positive cases who had missed MDA. Follow-up measures were taken in February and June 2015. RESULTS: A total of 50 antigen-positive cases and 46 antigen-negative controls were included. Self-reported PC consumption was 60.1% during 2014 MDA and 66.2% overall. At second follow-up, 24 of 34 cases and 27 of 43 controls had consumed PC. Significant and clinically relevant between-group differences at baseline were not found post-PC. Bayesian linear mixed models showed a significant change in indurometer scores at both calves for antigen-positive cases who consumed any PC (dominant calf: -0.30 [95% CI -0.52, -0.07], P < 0.05 and non-dominant calf: -0.35 [95% CI -0.58, -0.12], P < 0.01). Changes in antigen-negative participants or those not consuming PC were not significant. CONCLUSION: This study is the first attempt to use simple field-friendly tools to track fluid and tissue changes after treatment of asymptomatic people infected with LF. Results suggested that PC alone is sufficient to reverse covert lymphatic disturbance. Longer follow-up of larger cohorts is required to confirm these improvements and whether they persist over time. These findings should prompt increased efforts to overcome low PC coverage, which misses many infected young people, particularly males, who are unaware of their infection status, unmotivated to take PC and at risk of developing lymphoedema. Indurometry and BIS should be considered in assessment of lymphatic filariasis-related lymphedema.

OBJECTIFS: Cette étude comparative longitudinale a investigué l'effet de la chimiothérapie préventive (CP) sur les modifications tissulaires cachées associées à la filariose lymphatique (FL) chez les jeunes vivant dans une zone d'endémie pour la FL au Myanmar. MÉTHODES: La compressibilité des tissus et le liquide libre extracellulaire dans les membres inférieurs des personnes âgées de 10 à 21 ans ont été mesurés par indurométrie et spectroscopie de bioimpédance (BIS). Les mesures de base ont été prises en octobre 2014, la distribution en masse de médicament (DMM) annuelle a été administrée en décembre et en mars 2015, et une CP additionnelle a été offerte aux cas positifs pour la FL qui avaient manqué la DMM. Des mesures de suivi ont été prises en février et juin 2015. RÉSULTATS: 50 cas positifs pour l'antigène et 46 témoins négatifs ont été inclus. L'administration de CP auto-déclarée était de 60,1% durant la DMM de 2014 et de 66,2% au total. Au deuxième suivi, 24 des 34 cas et 27 des 43 témoins avaient pris la CP. Des différences significatives et cliniquement pertinentes entre les groupes au départ n'ont pas été trouvées après la CP. Les modèles mixtes linéaires bayésiens ont montré un changement significatif des scores d'indurometrie aux deux mollets pour les cas positifs pour l'antigène qui prenaient une CP (mollet dominant: -0,30 [IC95%: -0,52, -0,07], p <0,05, mollet non dominant: - 0,35 [IC95%: -0,58, -0,12], p <0,01). Les changements chez les participants négatifs pour l'antigène ou ceux qui ne prenaient pas de CP n'étaient pas significatifs. CONCLUSION: Cette étude est la première tentative d'utilisation d'outils simples, conviviaux sur le terrain, pour suivre les modifications du tissu conjonctif après le traitement de personnes asymptomatiques infectées par la FL. Les résultats suggèrent que la CP seule est suffisante pour inverser les modifications lymphatiques cachées. Un suivi plus long de plus grandes cohortes est nécessaire pour confirmer ces améliorations et déterminer si elles persistent ou non. Ces résultats devraient inciter à redoubler d'efforts pour surmonter la faible couverture en CP, qui rate beaucoup de jeunes infectés, en particulier les hommes, qui ne sont pas au courant de leur statut d'infection, qui ne sont pas motivés pour prendre une CP et risquent de développer un lymphœdème. L'indurométrie et la BIS devraient être considérées dans l'évaluation du lymphoedème associé à la filariose lymphatique.

Impact of Race and Socioeconomic Status on Psychologic Outcomes in Childhood Cancer Patients and Caregivers.

Complex relationships between race and socioeconomic status have a poorly understood influence on psychologic outcomes in pediatric oncology. The Family Symptom Inventory was used to assess symptoms of depression and anxiety in pediatric patients with cancer and their caregivers. Separate hierarchical linear regression models examined the relationship between demographic variables, cancer characteristics, socioeconomic status, and access to care and patient or caregiver depression/anxiety. Participants included 196 pediatric patients with cancer (mean age, 11.21 y; 49% African American) and their caregivers. On average, caregivers reported low levels of depression/anxiety. Symptoms of depression and anxiety in patients were correlated with poorer mental health in caregivers (r=0.62; P<0.01). Self-reported financial difficulty (ß=0.49; P<0.001) and brain cancer diagnosis for their child (ß=0.42; P=0.008) were significantly associated with depression and anxiety in caregivers. Analysis did not reveal significant associations between race, household income, or access to care and patient or caregiver depression/anxiety. Perception of financial hardship can adversely impact mental health in caregivers of children with cancer. Psychosocial assessment and interventions may be especially important for caregivers of patients with brain tumors and caregivers who report feeling financial difficulty.

Primaquine at alternative dosing schedules for preventing relapse in people with Plasmodium vivax malaria.

BACKGROUND: Malaria caused by Plasmodium vivax requires treatment of the blood-stage infection and treatment of the hypnozoites that develop in the liver. This is a challenge to effective case management of P vivax malaria, as well as being a more general substantial impediment to malaria control. The World Health Organization (WHO) recommends a 14-day drug course with primaquine, an 8-aminoquinoline, at 0.25 mg/kg/day in most of the world (standard course), or 0.5 mg/kg/day in East Asia and Oceania (high-standard course). This long treatment course can be difficult to complete, and primaquine can cause dangerous haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, meaning that physicians may be reluctant to prescribe in areas where G6PD testing is not available. This Cochrane Review evaluated whether more patient-friendly alternative regimens are as efficacious as the standard regimen for radical cure ofP vivax malaria. OBJECTIVES: To assess the efficacy and safety of alternative primaquine regimens for radical cure of P vivax malaria compared to the standard or high-standard 14 days of primaquine (0.25 or 0.5 mg/kg/day), as well as comparison of these two WHO-recommended regimens. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); and LILACS (BIREME) up to 17 December 2018. We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov, and checked the reference lists of all studies identified by the above methods. SELECTION CRITERIA: Randomized controlled trials (RCTs) of adults and children with P vivax malaria using any regimen of either chloroquine or an artemisinin-based combination therapy (ACT) plus primaquine with either higher daily doses for 14 days, shorter regimens with the same total dose, or using weekly dosing regimens; compared with the usual standard regimens recommended by the WHO (0.25 or 0.5 mg/kg/day for 14 days), or a comparison of these two WHO-recommended regimens. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality, and extracted data. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data. We grouped efficacy data according to length of follow-up. We analysed safety data where this information was included. MAIN RESULTS: High-standard 14-day course versus standard 14-day courseTwo RCTs compared the high-standard 14-day regimen with the standard 14-day regimen. People with G6PD deficiency and pregnant or lactating women were excluded. We do not know if there is any difference in P vivax recurrences at 6 months with 0.5 mg/kg/day primaquine therapy for 14 days compared to 0.25 mg/kg/day primaquine therapy for 14 days (with chloroquine: RR 0.82, 95% CI 0.47 to 1.43, 639 participants, very low-certainty evidence; with chloroquine or an ACT: RR 1.11, 95% CI 0.17 to 7.09, 38 participants, very low-certainty evidence). No serious adverse events were reported. We do not know whether there is a difference in adverse events with the higher dosage (very low-certainty evidence).0.5 mg/kg/day primaquine for 7 days versus standard 14-day courseFive RCTs compared 0.5 mg/kg/day primaquine for 7 days with the standard 14-day course. There may be little or no difference in P vivax recurrences at 6 to 7 months when using the same total dose (0.5 mg/kg/day to 210 mg) over 7 days as compared to 14 days (RR 0.96, 95% CI 0.66 to 1.39; 1211 participants; low-certainty evidence). No serious adverse events were reported. There may be little or no difference in the number of adverse events known to occur with primaquine between the primaquine shorter regimen as compared to the longer regimen (RR 1.06, 95% CI 0.64 to 1.76; 1154 participants; low-certainty evidence). We do not know whether there is any difference in the frequency of anaemia or discontinuation of treatment between groups (very low-certainty evidence). Three trials excluded people with G6PD deficiency, and two did not provide this information. Pregnant and lactating women were either excluded or no details were provided regarding their inclusion or exclusion.0.75 mg/kg primaquine/week for 8 weeks versus high-standard course One RCT compared weekly primaquine with the high-standard 14-day course. G6PD-deficient patients were not randomized but were included in the weekly primaquine group. Only one G6PD-deficient participant was detected during the trial. We do not know whether weekly primaquine increases or decreases recurrences of P vivax compared to the 14-day regimen at 11 months' follow-up (RR 3.18, 95% CI 0.37 to 27.6; 122 participants; very low-certainty evidence). No serious adverse events and no episodes of anaemia were reported.Three other RCTs evaluated different alternative regimens and doses of primaquine, but one of these RCTs did not have results available, and two used regimens that have not been widely used and the evidence was of very low certainty. AUTHORS' CONCLUSIONS: Although limited data were available, the analysis did not detect a difference in recurrence between the 7-day regimen and the standard 14-day regimen of 0.5 mg/kg/day primaquine, and no serious adverse events were reported in G6PD-normal participants taking 0.5 mg/kg/day of primaquine. This shorter regimen may be useful in G6PD-normal patients if there are treatment adherence concerns. Further large high-quality RCTs are needed, such as the IMPROV trial, with more standardised comparison regimens and longer follow-up to help resolve uncertainties.

The epidemiology of tuberculosis in the rural Balimo region of Papua New Guinea.

OBJECTIVE: Papua New Guinea (PNG) has an emerging tuberculosis (TB) epidemic which has become a national public health priority. In Western Province, there are few data about TB outside Daru and the South Fly District. This study describes the epidemiology of TB diagnosed at Balimo District Hospital (BDH) in the Middle Fly District of Western Province, PNG. METHODS: All patients (n = 1614) diagnosed with TB at BDH from April 2013 to February 2017 were recorded. Incidence of reported new cases was calculated for the combined Balimo Urban and Gogodala Rural local level government areas. Analyses investigated patient demographic and clinical information, differences between pulmonary and extrapulmonary TB patients, and predictors of treatment failure. RESULTS: The average case notification rate (2014-2016) was 727 TB cases per 100 000 people per year. One-quarter of TB cases were in children, and 77.1% of all cases had an extrapulmonary TB diagnosis. There was a 1:1.1 ratio of female to male TB cases. When comparing pulmonary and extrapulmonary TB patients, extrapulmonary TB was more likely in those aged up to 14 years and over 54 years. Extrapulmonary TB was more likely in new patients, and pulmonary TB more likely in previously treated patients. Residence in rural regions was associated with treatment failure. CONCLUSION: There is a high burden of TB in the Balimo region, including a very high proportion of extrapulmonary TB. These factors emphasise the importance of BDH as the primary hospital for TB cases in the Balimo region and the Middle Fly District, and the need for resources and staff to manage both drug-susceptible and drug-resistant TB cases.

Primaquine or other 8-aminoquinolines for reducing Plasmodium falciparum transmission.

BACKGROUND: The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance. This replaced the previous recommendation of 0.75 mg/kg, aiming to reduce haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malarious areas. Whether this approach, and at this dose, is effective in reducing transmission is not clear. OBJECTIVES: To assess the effects of single dose or short-course PQ (or an alternative 8AQ) alongside treatment for people with P. falciparum malaria. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; and the WHO International Clinical Trials Registry Platform (ICRTP) portal using 'malaria*', 'falciparum', 'primaquine', '8-aminoquinoline', and eight 8AQ drug names as search terms. We checked reference lists of included trials, and contacted researchers and organizations. Date of last search: 21 July 2017. SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs in children or adults, adding PQ (or alternative 8AQ) as a single dose or short course alongside treatment for P. falciparum malaria. DATA COLLECTION AND ANALYSIS: Two authors screened abstracts, applied inclusion criteria, and extracted data. We sought evidence on transmission (community incidence), infectiousness (people infectious and mosquitoes infected), and potential infectiousness (gametocyte measures assessed by microscopy or polymerase chain reaction [PCR]). We grouped trials into artemisinin and non-artemisinin treatments, and stratified by PQ dose (low, 0.2 to 0.25 mg/kg; moderate, 0.4 to 0.5 mg/kg; high, 0.75 mg/kg). We used GRADE, and absolute effects of infectiousness using trial control groups. MAIN RESULTS: We included 24 RCTs and one quasi-RCT, comprising 43 arms. Fourteen trials evaluated artemisinin treatments (23 arms), nine trials evaluated non-artemisinin treatments (13 arms), and two trials included both artemisinin and non-artemisinin arms (three and two arms, respectively). Two trial arms used bulaquine. Seven PQ arms used low dose (six with artemisinin), 11 arms used moderate dose (seven with artemisinin), and the remaining arms used high dose. Fifteen trials tested for G6PD status: 11 excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and three included all, irrespective of status. The remaining 10 trials either did not test or did not report on testing.No cluster trials evaluating community effects on malaria transmission met the inclusion criteria.With artemisinin treatmentLow dose PQInfectiousness (participants infectious to mosquitoes) was reduced (day 3 or 4: RR 0.12, 95% CI 0.02 to 0.88, 3 trials, 105 participants; day 8: RR 0.34, 95% CI 0.07 to 1.58, 4 trials, 243 participants; low certainty evidence). This translates to a reduction in percentage of people infectious on day 3 or 4 from 14% to 2%, and, for day 8, from 4% to 1%; the waning infectiousness in the control group by day 8 making the absolute effect smaller by day 8. For gametocytes detected by PCR, there was little or no effect of PQ at day 3 or 4 (RR 1.02, 95% CI 0.87 to 1.21; 3 trials, 414 participants; moderate certainty evidence); with reduction at day 8 (RR 0.52, 95% CI 0.41 to 0.65; 4 trials, 532 participants; high certainty evidence). Severe haemolysis was infrequent, with or without PQ, in these groups with few G6PD-deficient individuals (RR 0.98, 95% CI 0.69 to 1.39; 4 trials, 752 participants, moderate certainty evidence).Moderate dose PQInfectiousness was reduced (day 3 or 4: RR 0.13, 95% CI 0.02 to 0.94; 3 trials, 109 participants; day 8 RR 0.33, 95% CI 0.07 to 1.57; 4 trials, 246 participants; low certainty evidence). Illustrative risk estimates for moderate dose were the same as low dose. The pattern and level of certainty of evidence with gametocytes detected by PCR was the same as low dose, and severe haemolysis was infrequent in both groups.High dose PQInfectiousness was reduced (day 4: RR 0.2, 95% CI 0.02 to 1.68, 1 trial, 101 participants; day 8: RR 0.18, 95% CI 0.02 to 1.41, 2 trials, 181 participants, low certainty evidence). The effects on gametocyte prevalence showed a similar pattern to moderate and low dose PQ. Trials did not systematically report evidence of haemolysis.With non-artemisinin treatmentTrials with non-artemisinin treatment have been conducted only for moderate and high dose PQ. With high dose, infectiousness appeared markedly reduced on day 5 (RR 0.09, 95% CI 0.01 to 0.62; 30 participants, very low certainty evidence), with similar reductions at day 8. For both moderate dose (two trials with 221 people) and high dose (two trials with 30 people), reduction in gametocytes (detected by microscopy) showed similar patterns as for artemisinin treatments, with little or no effect at day 4 or 5, and larger effects by day 8. No trials with non-artemisinin partner drugs systematically sought evidence of severe haemolysis.Two trials comparing bulaquine with PQ suggest bulaquine may have larger effects on gametocytes by microscopy on day 8 (RR 0.41, 95% CI 0.26 to 0.66; 2 trials, 112 participants). AUTHORS' CONCLUSIONS: A single low dose of PQ (0.25 mg/kg) added to artemisinin-based combination therapy for malaria reduces infectiousness of people to mosquitoes at day 3-4 and day 8, and appears as effective as higher doses. The absolute effect is greater at day 3 or 4, and smaller at day 8, in part because of the lower infectiousness in the control group. There was no evidence of increased haemolysis at 0.25 mg/kg, but few G6PD-deficient individuals were included in the trials. The effect on infectiousness precedes the effect of PQ on gametocyte prevalence. We do not know whether single dose PQ could reduce malaria transmission at community level.

Safety of primaquine given to people with G6PD deficiency: systematic review of prospective studies.

BACKGROUND: Haemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people. METHODS: Major electronic databases (to August 2016) were searched for single or short course 8-aminoquinolines (8-AQ) in (1) randomized comparisons against placebo in G6PD deficient people; and (2) observational comparisons in G6PD deficient compared to replete people. Two authors independently assessed eligibility, risk-of-bias, and extracted data. RESULTS: Five randomized controlled trials and four controlled observational cohorts were included. In G6PD deficient individuals, high-dose (0.75 mg/kg) PQ resulted in lower average haemoglobin levels at 7 days (mean difference [MD] -1.45 g/dl, 95% CI -2.17 to -0.74, 2 trials) and larger percentage fall from baseline to day 7 (MD -10.31%, 95% CI -17.69 to -2.92, 3 trials) compared to placebo. In G6PD deficient compared to replete people, average haemoglobin was lower at 7 days (MD -1.19 g/dl, 95% CI -1.94 to -0.44, 2 trials) and haemoglobin change from baseline to day 7 was greater (MD -9.10%, 95% CI -12.55 to -5.65, 5 trials). One small trial evaluated mid-range PQ dose (0.4-0.5 mg/kg) in G6PD deficient people, with no difference detected in average haemoglobin at day 7 compared to placebo. In one cohort comparing G6PD deficient and replete people there was a greater fall with G6PD deficiency (MD -4.99%, 95% CI -9.96 to -0.02). For low-dose PQ (0.1-0.25 mg/kg) in G6PD deficient people, haemoglobin change from baseline was similar to the placebo group (MD 1.72%, 95% CI -1.89 to 5.34, 2 trials). Comparing low dose PQ in G6PD deficient with replete people, the average haemoglobin was lower in the G6PD deficient group at 7 days (-0.57 g (95% CI -0.97 to -0.17, 1 trial)); although change from baseline was similar (MD -1.45%, 95% CI -5.69 to 2.78, 3 trials). CONCLUSIONS: Falls in average haemoglobin are less marked with the 0.1 to 0.25 mg/kg PQ than with the 0.75 mg/kg dose, and severe haemolytic events are not common. However, data were limited and the evidence GRADE was low or very low certainty.

Surgical Treatment of Genital Manifestations of Lymphatic Filariasis: A Systematic Review.

Genital manifestations of lymphatic filariasis (genital LF) are a significant cause of disfigurement and disability in the developing world. Surgery is the standard treatment; however, definitive publications are lacking and best practice remains unclear. An exhaustive search strategy using keyword and subject headings was applied to Medline, EMBASE, Web of Science, CINAHL, and Scopus. Additionally citation lists, Google and Google Scholar, archives of relevant journals and websites were searched systematically. Studies with data on one or more human patient(s) who underwent surgery for genital LF were included. Articles were screened and data extracted by the first author with data verification by the second author. Fifty-seven studies were included: 18 series of ablative surgery, four series of non-ablative surgery and 35 case reports. Poor study quality, heterogeneous case definitions, lack of severity grading and limited follow-up precluded meta-analysis. Two series of simple hydrocelectomies performed in resource-limited settings reported early complication rates of 3.0-3.5 % using eversion and 5-7 % using excision, with recurrence of 7 % and 3-5 %, respectively. Complications were minimal for single-surgeon series and greater (12-18 %) when scrotal reconstruction was performed. There is little useful evidence for lymphatic bypass procedures in genital LF. Under-recognition of atypical manifestation of genital LF leads to potentially unnecessary surgeries. Surgery for genital LF is safe in resource-limited settings; however, more well-designed studies with better follow-up are needed. Research priorities include validation of case definitions and severity grading systems, and solutions to improve post-operative follow-up in resource-limited settings.

Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission.

BACKGROUND: Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to 8-aminoquinolines (8AQ), and consequently these drugs could prevent parasite transmission from infected people to mosquitoes and reduce the incidence of malaria. However, when used in this way, these drugs will not directly benefit the individual.In 2010, the World Health Organization (WHO) recommended a single dose of primaquine (PQ) at 0.75 mg/kg alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013, the WHO revised this to 0.25 mg/kg to reduce risk of harms in people with G6PD deficiency. OBJECTIVES: To assess the effects of PQ (or an alternative 8AQ) given alongside treatment for P. falciparum malaria on malaria transmission and on the occurrence of adverse events. SEARCH METHODS: We searched the following databases up to 5 January 2015: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (Issue 1, 2015); MEDLINE (1966 to 5 January 2015); EMBASE (1980 to 5 January 2015); LILACS (1982 to 5 January 2015); metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', 'primaquine', 8-aminoquinoline and eight individual 8AQ drug names as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs in children or adults, comparing PQ (or alternative 8AQ) as a single dose or short course alongside treatment for P. falciparum malaria, with the same malaria treatment given without PQ/8AQ. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all abstracts, applied inclusion criteria and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, asexual parasite clearance time and recrudescence. We stratified the analysis by artemisinin and non-artemisinin treatments; and by PQ dose (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg). We used the GRADE approach to assess evidence quality. MAIN RESULTS: We included 17 RCTs and one quasi-RCT. Eight trials tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining 10 trials either did not report on whether they tested (eight trials), or reported that they did not test (two trials).Nine trials included study arms with artemisinin-based treatments and eleven included study arms with non-artemisinin-based treatments.Only one trial evaluated PQ given as a single dose of less than 0.4 mg/kg. PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence or entomological inoculation rate) and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two-thirds with the high dose PQ category (RR 0.29, 95% confidence interval (CI) 0.22 to 0.37; seven trials, 1380 participants, high quality evidence) and the medium dose PQ category (RR 0.30, 95% CI 0.16 to 0.56; one trial, 219 participants, moderate quality evidence). For the low dose category, the effect size was smaller and the 95% CIs include the possibility of no effect (dose: 0.1 mg/kg: RR 0.67, 95% CI 0.44 to 1.02; one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory in China evaluated infectiousness to mosquitoes, and reported that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by three-fifths with high dose PQ category (RR 0.39, 95% CI 0.25 to 0.62; four trials, 186 participants, high quality evidence), and by around two-fifths with medium dose category (RR 0.60, 95% CI 0.49 to 0.75; one trial, 216 participants, high quality evidence), with no trial in the low dose PQ category reporting this outcome. Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis.Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (N = 112) preclude a definite conclusion. AUTHORS' CONCLUSIONS: In individual patients, PQ added to malaria treatments reduces gametocyte prevalence, but this is based on trials using doses of more than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission.For the currently recommended low dose regimen, there is currently little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved, or that it is safe in people with G6PD deficiency.

Brief neurocognitive screening in youth with brain tumours: A preliminary investigation of the Lebby-Asbell Neurocognitive Screening Examination (LANSE).

PRIMARY OBJECTIVE: It is well-documented that survivors of paediatric brain tumour are at risk for neurocognitive deficits resulting in an increased interest in neurocognitive assessment for these youth. Given the scarcity of well-validated brief assessments for this purpose, this study examines the reliability and validity of a brief neurocognitive screening measure. RESEARCH DESIGN: Cross-sectional data on youth (aged 6-17.9) administered a brief neurocognitive screening device and broader neurocognitive batteries was collected via chart review to evaluate the reliability and validity of a brief neurocognitive screening device. METHODS AND PROCEDURES: Fifty-one youth with brain tumours and 26 youth with traumatic brain injury (TBI) were administered The Lebby-Asbell Neurocognitive Screening Examination (LANSE) during clinic visits. A sub-set of children were administered a more comprehensive neurocognitive evaluation and scores from the LANSE and these evaluations were compared to assess preliminary validity. MAIN OUTCOME AND RESULTS: Most LANSE sub-scales demonstrated adequate reliability and preliminary validity with some exceptions. Comparison of youth with brain tumours to those with a TBI revealed a similar pattern of potential neurocognitive impairment across several cognitive domains. CONCLUSIONS: This study demonstrates the preliminary reliability and validity of a brief neurocognitive screening examination for youth with brain tumours.

Sickle cell pain: a critical reappraisal.

Sickle cell pain includes 3 types: acute recurrent painful crises, chronic pain syndromes, and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the emergency department. It evolves through 4 phases: prodromal, initial, established, and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage, such as acute chest syndrome, multiorgan failure, and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation, and nociception. Aborting the acute painful episode at the prodromal phase could potentially prevent or minimize tissue damage. Our hypothesis is that managing these events with hydration, anti-inflammatory drugs, aggressive analgesia, and possibly vasodilators could abort the crisis and prevent or minimize further damage. Chronic pain syndromes are associated with or accompany avascular necrosis and leg ulcers. Neuropathic pain is not well studied in patients with sickle cell disease but has been modeled in the transgenic sickle mouse. Management of sickle cell pain should be based on its own pathophysiologic mechanisms rather than borrowing guidelines from other nonsickle pain syndromes.

Estimation of insecticide persistence, biological activity and mosquito resistance to PermaNet® 2 long-lasting insecticidal nets over three to 32 months of use in Ethiopia.

BACKGROUND: Information is needed on the expected durability of insecticidal nets under operational conditions. The persistence of insecticidal efficacy is important to estimate the median serviceable life of nets under field conditions and to plan for net replacement. METHODS: Deltamethrin residue levels were evaluated by the proxy method of X-ray fluorescence spectrometry on 189 nets used for three to six months from nine sites, 220 nets used for 14-20 months from 11 sites, and 200 nets used for 26-32 months from ten sites in Ethiopia. A random sample of 16.5-20% of nets from each time period (total 112 of 609 nets) were tested by bioassay with susceptible mosquitoes, and nets used for 14-20 months and 26-32 months were also tested with wild caught mosquitoes. RESULTS: Mean insecticide levels estimated by X-ray fluorescence declined by 25.9% from baseline of 66.2 (SD 14.6) mg/m2 at three to six months to 44.1 (SD 21.2) mg/m2 at 14-20 months and by 30.8% to 41.1 (SD 18.9) mg/m2 at 26-32 months. More than 95% of nets retained greater than 10 mg/m2 of deltamethrin and over 79% had at least 25 mg/m2 at all time periods. By bioassay with susceptible Anopheles, mortality averaged 89.0% on 28 nets tested at three to six months, 93.3% on 44 nets at 14-20 months and 94.1% on 40 nets at 26-32 months. With wild caught mosquitoes, mortality averaged 85.4% (range 79.1 to 91.7%) at 14-20 months but had dropped significantly to 47.2% (39.8 to 54.7%) at 26-32 months. CONCLUSIONS: Insecticide residue level, as estimated by X-ray fluorescence, declined by about one third between three and six months and 14-20 months, but remained relatively stable and above minimum requirements thereafter up to 26-32 months. The insecticidal activity of PermaNet® 2.0 long-lasting insecticidal nets in the specified study area may be considered effective to susceptible mosquitoes at least for the duration indicated in this study (32 months). However, results indicated that resistance in the wild population is already rendering nets with optimum insecticide concentrations less effective in practice.

Malaria prevalence, anemia and baseline intervention coverage prior to mass net distributions in Abia and Plateau States, Nigeria.

BACKGROUND: Nigeria suffers the world's largest malaria burden, with approximately 51 million cases and 207,000 deaths annually. As part of the country's aim to reduce by 50% malaria-related morbidity and mortality by 2013, it embarked on mass distribution of free long-lasting insecticidal nets (LLINs). METHODS: Prior to net distribution campaigns in Abia and Plateau States, Nigeria, a modified malaria indicator survey was conducted in September 2010 to determine baseline state-level estimates of Plasmodium prevalence, childhood anemia, indoor residual spraying (IRS) coverage and bednet ownership and utilization. RESULTS: Overall age-adjusted prevalence of Plasmodium infection by microscopy was similar between Abia (36.1%, 95% CI: 32.3%-40.1%; n = 2,936) and Plateau (36.6%, 95% CI: 31.3%-42.3%; n = 4,209), with prevalence highest among children 5-9 years. P. malariae accounted for 32.0% of infections in Abia, but only 1.4% of infections in Plateau. More than half of children ≤10 years were anemic, with anemia significantly higher in Abia (76.9%, 95% CI: 72.1%-81.0%) versus Plateau (57.1%, 95% CI: 50.6%-63.4%). Less than 1% of households in Abia (n = 1,305) or Plateau (n = 1,335) received IRS in the 12 months prior to survey. Household ownership of at least one bednet of any type was 10.1% (95% CI: 7.5%-13.4%) in Abia and 35.1% (95% CI: 29.2%-41.5%) in Plateau. Ownership of two or more bednets was 2.1% (95% CI: 1.2%-3.7%) in Abia and 14.5% (95% CI: 10.2%-20.3%) in Plateau. Overall reported net use the night before the survey among all individuals, children <5 years, and pregnant women was 3.4%, 6.0% and 5.7%, respectively in Abia and 14.7%, 19.1% and 21.0%, respectively in Plateau. Among households owning nets, 34.4% of children <5 years and 31.6% of pregnant women in Abia used a net, compared to 52.6% of children and 62.7% of pregnant women in Plateau. CONCLUSIONS: These results reveal high Plasmodium prevalence and childhood anemia in both states, low baseline coverage of IRS and LLINs, and sub-optimal net use-especially among age groups with highest observed malaria burden.

Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission.

BACKGROUND: Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ) and other 8-aminoquinolines (8AQ); these drugs could prevent parasite transmission from infected people to mosquitoes, and consequently reduce the incidence of malaria. However, PQ will not directly benefit the individual, and could be harmful to those with glucose-6-phosphate dehydrogenase (G6PD) deficiency.In 2010, The World Health Organization (WHO) recommended a single dose of PQ at 0.75 mg/kg, alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013 the WHO revised this to 0.25 mg/kg due to concerns about safety. OBJECTIVES: To assess whether giving PQ or an alternative 8AQ alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events when PQ is given for this purpose. SEARCH METHODS: We searched the following databases up to 10 Feb 2014 for trials: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs comparing PQ (or alternative 8AQ) given as a single dose or short course alongside treatment for P. falciparum malaria with malaria treatment given without PQ/8AQ in adults or children. DATA COLLECTION AND ANALYSIS: Two authors independently screened all abstracts, applied inclusion criteria, and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, as well as secondary outcomes of asexual clearance time and recrudescence. We stratified by whether the malaria treatment regimen included an artemisinin derivative or not; by PQ dose category (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg); and by PQ schedules. We used the GRADE approach to assess evidence quality. MAIN RESULTS: We included 17 RCTs and one quasi-RCT. Eight studies tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining ten trials either did not report on whether they tested (8), or reported that they did not test (2). Nine trials included study arms with artemisinin-based malaria treatment regimens, and eleven included study arms with non-artemisinin-based treatments.Only two trials evaluated PQ given at low doses (0.25 mg/kg in one and 0.1 mg/kg in the other). PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence, or entomological inoculation rate), and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two thirds with high dose PQ category (RR 0.29, 95% CI 0.22 to 0.37, seven trials, 1380 participants, high quality evidence), and with medium dose PQ category (RR 0.34, 95% CI 0.19 to 0.59, two trials, 269 participants, high quality evidence), but the trial evaluating low dose PQ category (0.1 mg/kg) did not demonstrate an effect (RR 0.67, 95% CI 0.44 to 1.02, one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline, and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory evaluated infectiousness to mosquitoes, and report that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by around half with high dose PQ category (RR 0.44, 95% CI 0.27 to 0.70, three trials, 206 participants, high quality evidence), and by around a third with medium dose category (RR 0.62, 0.50 to 0.76, two trials, 283 participants, high quality evidence), but the single trial using low dose PQ category did not demonstrate a difference between groups (one trial, 59 participants, very low quality evidence). Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis.Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (n = 112) preclude a definite conclusion. AUTHORS' CONCLUSIONS: In individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic settings approaching elimination, or in highly-endemic settings where many people are infected but have no symptoms and are unlikely to be treated.For the currently recommended low dose regimen, there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved.Most trials excluded people with G6PD deficiency, and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course.

Hemodynamic predictors of mortality in adults with sickle cell disease.

BACKGROUND: Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality, but no prior studies have evaluated quantitative relationships of mortality to physiological measures of pre- and postcapillary PH. OBJECTIVES: To identify risk factors associated with mortality and to estimate the expected survival in a cohort of patients with SCD with PH documented by right heart catheterization. METHODS: Nine-year follow-up data (median, 4.7 yr) from the National Institutes of Health SCD PH screening study are reported. A total of 529 adults with SCD were screened by echocardiography between 2001 and 2010 with no exclusion criteria. Hemodynamic data were collected from 84 patients. PH was defined as mean pulmonary artery pressure (PAP) ≥ 25 mm Hg. Survival rates were estimated by the Kaplan-Meier method, and mortality risk factors were analyzed by the Cox proportional hazards regression. MEASUREMENTS AND MAIN RESULTS: Specific hemodynamic variables were independently related to mortality: mean PAP (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.05-2.45 per 10 mm Hg increase; P = 0.027), diastolic PAP (HR, 1.83; 95% CI, 1.09-3.08 per 10 mm Hg increase; P = 0.022), diastolic PAP - pulmonary capillary wedge pressure (HR, 2.19; 95% CI, 1.23-3.89 per 10 mm Hg increase; P = 0.008), transpulmonary gradient (HR, 1.78; 95% CI, 1.14-2.79 per 10 mm Hg increase; P = 0.011), and pulmonary vascular resistance (HR, 1.44; 95% CI, 1.09-1.89 per Wood unit increase; P = 0.009) as risk factors for mortality. CONCLUSIONS: Mortality in adults with SCD and PH is proportional to the physiological severity of precapillary PH, demonstrating its prognostic and clinical relevance despite anemia-induced high cardiac output and less severely elevated pulmonary vascular resistance.

A preliminary investigation of serological tools for the detection of Onchocerca lupi infection in dogs.

Onchocerca lupi is a neglected filarioid causing nodular lesions associated with acute or chronic ocular disease in dogs. Despite the recent appraisal of its zoonotic potential, human cases are increasingly reported in the Old and New Worlds. Therefore, the development of accurate tools for the rapid diagnosis of O. lupi infections in dogs is becoming a priority. In this study, we conducted a preliminary investigation aimed at evaluating the usefulness of a commercially available ELISA test for the detection of O. lupi antigens in canine sera. The potential use of this tool for larger epidemiological studies of canine onchocerciasis is discussed.

Ongoing transmission of lymphatic filariasis in Samoa 4.5 years after one round of triple-drug mass drug administration.

BACKGROUND: Lymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds of mass drug administration (MDA). In certain scenarios, including when elimination targets have not been met with two-drug MDA, triple-drug MDA (using ivermectin, diethylcarbamazine and albendazole) is recommended. In this study, we report on antigen (Ag) and microfilaria (Mf) prevalence in eight primary sampling units (PSUs) in Samoa 4.5 years after one round of triple-drug MDA. METHODOLOGY: In 2023, community surveys were conducted in eight PSUs that had been surveyed previously in 2018 (between 1.5 and 3.5 months post triple-drug MDA) and 2019 (six to eight-months post triple-drug MDA). Fifteen houses were randomly selected in each PSU with household members aged ≥ 5 years invited to participate. Blood samples were tested for Ag and Mf. PRINCIPAL FINDINGS: Ag-positive participants were observed in six of the eight PSUs, and Ag prevalence was significantly above the 1% threshold in four PSUs. The presence of Mf-positive participants in five PSUs confirms the presence of residual active infections. CONCLUSIONS/SIGNIFICANCE: This study provides evidence of persistent LF transmission in Samoa 4.5 years after one round of triple-drug MDA, confirming that one round was insufficient for interruption of transmission in this setting. Our findings highlight the negative impact of delaying MDA rounds, for example, due to public health emergencies.

Field laboratory comparison of STANDARD Q Filariasis Antigen Test (QFAT) with Bioline Filariasis Test Strip (FTS) for the detection of Lymphatic Filariasis in Samoa, 2023.

BACKGROUND: To monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions. METHODOLOGY/PRINCIPAL FINDINGS: During an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability. CONCLUSION/SIGNIFICANCE: QFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions.

Physical durability of PermaNet 2.0 long-lasting insecticidal nets over three to 32 months of use in Ethiopia.

BACKGROUND: Ethiopia scaled up net distribution markedly starting in 2006. Information on expected net life under field conditions (physical durability and persistence of insecticidal activity) is needed to improve planning for net replacement. Standardization of physical durability assessment methods is lacking. METHODS: Permanet®2.0 long-lasting insecticidal bed nets (LLINs), available for distribution in early 2007, were collected from households at three time intervals. The number, size and location of holes were recorded for 189 nets used for three to six months from nine sites (2007) and 220 nets used for 14 to 20 months from 11 sites (2008). In 2009, a "finger/fist" sizing method classified holes in 200 nets used for 26 to 32 months from ten sites into small (<2 cm), medium (> = 2 to < =10 cm) and large (>10 cm) sizes. A proportionate hole index based on both hole number and area was derived from these size classifications. RESULTS: After three to six months, 54.5% (95% CI 47.1-61.7%) of 189 LLINs had at least one hole 0.5 cm (in the longest axis) or larger; mean holes per net was 4.4 (SD 8.4), median was 1.0 (Inter Quartile Range [IQR] 0-5) and median size was 1 cm (IQR 1-2). At 14 to 20 months, 85.5% (95% CI 80.1-89.8%) of 220 nets had at least one hole with mean 29.1 (SD 50.1) and median 12 (IQR 3-36.5) holes per net, and median size of 1 cm (IQR 1-2). At 26 to 32 months, 92.5% of 200 nets had at least one hole with a mean of 62.2 (SD 205.4) and median of 23 (IQR 6-55.5) holes per net. The mean hole index was 24.3, 169.1 and 352.8 at the three time periods respectively. Repairs were rarely observed. The majority of holes were in the lower half of the net walls. The proportion of nets in 'poor' condition (hole index >300) increased from 0% at three to six months to 30% at 26 to 32 months. CONCLUSIONS: Net damage began quickly: more than half the nets had holes by three to six months of use, with 40% of holes being larger than 2 cm. Holes continued to accumulate until 92.5% of nets had holes by 26 to 32 months of use. An almost complete lack of repairs shows the need for promoting proper use of nets and repairs, to increase LLIN longevity. Using the hole index, almost one third of the nets were classed as unusable and ineffective after two and a half years of potential use.

Phenocopy of warfarin syndrome in an infant born to a mother with sickle cell anemia and severe transfusional iron overload.

Neonatal chondrodysplasia punctata (CDP) is characterized by epiphyseal stippling and midfacial hypoplasia. CDP is usually inherited, but can be acquired because of maternal vitamin K deficiency. We describe an infant with CDP born to a teenager with sickle cell anemia and transfusional iron overload. The mother had severe liver fibrosis, elevated liver iron concentration (34 mg Fe/g), and coagulopathy, but no gestational use of warfarin. Fetal abnormalities were attributed to vitamin K deficiency secondary to liver dysfunction from iron toxicity. Treatment of iron overload among women with sickle cell anemia of childbearing potential is important to avoid possible CDP in newborns.