Epilation for Minor Trachomatous Trichiasis: Four-Year Results of a Randomised Controlled Trial

BackgroundTrachomatous trichiasis (TT) needs to be managed to reduce the risk of vision loss. The long-term impact of epilation (a common traditional practice of repeated plucking of lashes touching the eye) in preventing visual impairment and corneal opacity from TT is unknown. We conducted a randomized controlled trial of epilation versus surgery for the management of minor TT (fewer than six lashes touching the eye) in Ethiopia. Here we report the four-year outcome and the effect on vision and corneal opacity.

Methodology/ Principal Findings

1300 individuals with minor TT were recruited and randomly assigned to quality trichiasis surgery or repeated epilation using high quality epilation forceps by a trained person with good near vision. Participants were examined six-monthly for two-years, and then at four-years after randomisation. At two-years all epilation arm participants were offered free surgery. At four-years 1151 (88.5%) were re-examined: 572 (88%) and 579 (89%) from epilation and surgery arms, respectively. At that time, 21.1% of the surgery arm participants had recurrent TT; 189/572 (33%) of the epilation arm had received surgery, while 383 (67%) declined surgery and had continued epilating (“epilation-only”). Among the epilation-only group, 207 (54.1%) fully controlled their TT, 166 (43.3%) had minor TT and 10 (2.6%) had major TT (>5 lashes). There were no differences between participants in the epilation-only, epilation-to-surgery and surgery arm participants in changes in visual acuity and corneal opacity between baseline and four-years.

Conclusions/ Significance

Most minor TT participants randomised to the epilation arm continued epilating and controlled their TT. Change in vision and corneal opacity was comparable between surgery and epilation-only participants. This suggests that good quality epilation with regular follow-up is a reasonable second-line alternative to surgery for minor TT for individuals who either decline surgery or do not have immediate access to surgical treatment.     

Use of Pentamidine As Secondary Prophylaxis to Prevent Visceral Leishmaniasis Relapse in HIV Infected Patients,the First Twelve Months of a Prospective Cohort Study

Background

Visceral leishmaniasis (VL) has become an important opportunistic infection in persons with HIV-infection in VL-endemic areas. The co-infection leads to profound immunosuppression and high rate of annual VL recurrence. This study assessed the effectiveness, safety and feasibility of monthly pentamidine infusions to prevent recurrence of VL in HIV co-infected patients.

Methods

A single-arm, open-label trial was conducted at two leishmaniasis treatment centers in northwest Ethiopia. HIV-infected patients with a VL episode were included after parasitological cure. Monthly infusions of 4mg/kg pentamidine-isethionate diluted in normal-saline were started for 12months. All received antiretroviral therapy (ART). Time-to-relapse or death was the primary end point.

Results

Seventy-four patients were included. The probability of relapse-free survival at 6months and at 12 months was 79% and 71% respectively. Renal failure, a possible drug-related serious adverse event, occurred in two patients with severe pneumonia. Forty-one patients completed the regimen taking at least 11 of the 12 doses. Main reasons to discontinue were: 15 relapsed, five died and seven became lost to follow-up. More patients failed among those with a CD4+cell count ≤ 50cells/μl, 5/7 (71.4%) than those with counts above 200 cells/μl, 2/12 (16.7%), (p = 0.005).

Conclusion

Pentamidine secondary prophylaxis led to a 29% failure rate within one year, much lower than reported in historical controls (50%-100%). Patients with low CD4+cell counts are at increased risk of relapse despite effective initial VL treatment, ART and secondary prophylaxis. VL should be detected and treated early enough in patients with HIV infection before profound immune deficiency installs.     

Altered thymidine metabolism due to defects of thymidine phosphorylase.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive human disease due to mutations in the thymidine phosphorylase (TP) gene. TP enzyme catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxy-D-ribose 1-phosphate. We present evidence that thymidine metabolism is altered in MNGIE. TP activities in buffy coats were reduced drastically in all 27 MNGIE patients compared with 19 controls. All MNGIE patients had much higher plasma levels of thymidine than normal individuals and asymptomatic TP mutation carriers. In two patients, the renal clearance of thymidine was approximately 20% that of creatinine, and because hemodialysis demonstrated that thymidine is ultrafiltratable, most of the filtered thymidine is likely to be reabsorbed by the kidney. In vitro, fibroblasts from controls catabolized thymidine in medium; by contrast, MNGIE fibroblasts released thymidine. In MNGIE, severe impairment of TP enzyme activity leads to increased plasma thymidine. In patients who are suspected of having MNGIE, determination of TP activity in buffy coats and thymidine levels in plasma are diagnostic. We hypothesize that excess thymidine alters mitochondrial nucleoside and nucleotide pools leading to impaired mitochondrial DNA replication, repair, or both. Therapies to reduce thymidine levels may be beneficial to MNGIE patients.     

QTL mapping identifies a major locus for resistance in wheat to Sunn pest (<Emphasis Type="Italic">Eurygaster</Emphasis><Emphasis Type="Italic">integriceps</Emphasis>) feeding at the vegetative growth stage

Key message

This research provides the first report of a major locus controlling wheat resistance to Sunn pest. It developed and validated SNP markers that will be useful for marker-assisted selection.

Abstract

Sunn pest (Eurygaster integriceps Puton) is the most destructive insect pest of bread wheat and durum wheat in West and Central Asia and East Europe. Breeding for resistance at the vegetative stage of growth is vital in reducing the damage caused by overwintered adult populations that feed on shoot and leaves of seedlings, and in reducing the next generation of pest populations (nymphs and adults), which can cause damage to grain quality by feeding on spikes. In the present study, two doubled haploid (DH) populations involving resistant landraces from Afghanistan were genotyped with the 90k SNP iSelect assay and candidate gene-based KASP markers. The DH lines and parents were phenotyped for resistance to Sunn pest feeding, using artificial infestation cages at Terbol station, in Lebanon, over three years. Quantitative trait locus (QTL) analysis identified a single major locus on chromosome 4BS in the two populations, with the resistance allele derived from the landrace accessions, IG139431 and IG139883. The QTL explained a maximum of 42 % of the phenotypic variation in the Cham6 × IG139431 and 56 % in the Cham6 × IG139883 populations. SNP markers closest to the QTL showed high similarity to rice genes that putatively encode proteins for defense response to herbivory and wounding. The markers were validated in a large, unrelated population of parental wheat genotypes. All wheat lines carrying the ‘C–G’ haplotype at the identified SNPs were resistant, suggesting that selection based on a haplotype of favourable alleles would be effective in predicting resistance status of unknown genotypes.

     

A Venue-Based Survey of Malaria,Anemia and Mobility Patterns among Migrant Farm Workers in Amhara Region,Ethiopia

Background

Mobile populations present unique challenges to malaria control and elimination efforts. Each year, a large number of individuals travel to northwest Amhara Region, Ethiopia to seek seasonal employment on large-scale farms. Agricultural areas typically report the heaviest malaria burden within Amhara thereby placing migrants at high risk of infection. Yet little is known about these seasonal migrants and their malaria-related risk factors.

Methods and Findings

In July 2013, a venue-based survey of 605 migrant laborers 18 years or older was conducted in two districts of North Gondar zone, Amhara. The study population was predominantly male (97.7%) and young (mean age 22.8 years). Plasmodium prevalence by rapid diagnostic test (RDT) was 12.0%; One quarter (28.3%) of individuals were anemic (hemoglobin <13 g/dl). Nearly all participants (95.6%) originated from within Amhara Region, with half (51.6%) coming from within North Gondar zone. Around half (51.2%) slept in temporary shelters, while 20.5% regularly slept outside. Only 11.9% of participants had access to a long lasting insecticidal net (LLIN). Reported net use the previous night was 8.8% overall but 74.6% among those with LLIN access. Nearly one-third (30.1%) reported having fever within the past two weeks, of whom 31.3% sought care. Cost and distance were the main reported barriers to seeking care. LLIN access (odds ratio [OR] = 0.30, P = 0.04) and malaria knowledge (OR = 0.50, P = 0.02) were significantly associated with reduced Plasmodium infection among migrants, with a similar but non-significant trend observed for reported net use the previous night (OR = 0.16, P = 0.14).

Conclusions

High prevalence of malaria and anemia were observed among a young population that originated from relatively proximate areas. Low access to care and low IRS and LLIN coverage likely place migrant workers at significant risk of malaria in this area and their return home may facilitate parasite transport to other areas. Strategies specifically tailored to migrant farm workers are needed to support malaria control and elimination activities in Ethiopia.     

Maternal Mortality in Rural South Ethiopia: Outcomes of Community-Based Birth Registration by Health Extension Workers

Introduction

Rural communities in low-income countries lack vital registrations to track birth outcomes. We aimed to examine the feasibility of community-based birth registration and measure maternal mortality ratio (MMR) in rural south Ethiopia.

Methods

In 2010, health extension workers (HEWs) registered births and maternal deaths among 421,639 people in three districts (Derashe, Bonke, and Arba Minch Zuria). One nurse-supervisor per district provided administrative and technical support to HEWs. The primary outcomes were the feasibility of registration of a high proportion of births and measuring MMR. The secondary outcome was the proportion of skilled birth attendance. We validated the completeness of the registry and the MMR by conducting a house-to-house survey in 15 randomly selected villages in Bonke.

Results

We registered 10,987 births (81·4% of expected 13,492 births) with annual crude birth rate of 32 per 1,000 population. The validation study showed that, of 2,401 births occurred in the surveyed households within eight months of the initiation of the registry, 71·6% (1,718) were registered with similar MMRs (474 vs. 439) between the registered and unregistered births. Overall, we recorded 53 maternal deaths; MMR was 489 per 100,000 live births and 83% (44 of 53 maternal deaths) occurred at home. Ninety percent (9,863 births) were at home, 4% (430) at health posts, 2·5% (282) at health centres, and 3·5% (412) in hospitals. MMR increased if: the male partners were illiterate (609 vs. 346; p= 0·051) and the villages had no road access (946 vs. 410; p= 0·039). The validation helped to increase the registration coverage by 10% through feedback discussions.

Conclusion

It is possible to obtain a high-coverage birth registration and measure MMR in rural communities where a functional system of community health workers exists. The MMR was high in rural south Ethiopia and most births and maternal deaths occurred at home.     

CoQ10 supplementation rescues nephrotic syndrome through normalization of H2S oxidation pathway

Nephrotic syndrome (NS), a frequent chronic kidney disease in children and young adults, is the most common phenotype associated with primary coenzyme Q₁₀ (CoQ₁₀) deficiency and is very responsive to CoQ₁₀ supplementation, although the pathomechanism is not clear. Here, using a mouse model of CoQ deficiency-associated NS, we show that long-term oral CoQ₁₀ supplementation prevents kidney failure by rescuing defects of sulfides oxidation and ameliorating oxidative stress, despite only incomplete normalization of kidney CoQ levels and lack of rescue of CoQ-dependent respiratory enzymes activities. Liver and kidney lipidomics, and urine metabolomics analyses, did not show CoQ metabolites. To further demonstrate that sulfides metabolism defects cause oxidative stress in CoQ deficiency, we show that silencing of sulfide quinone oxido-reductase (SQOR) in wild-type HeLa cells leads to similar increases of reactive oxygen species (ROS) observed in HeLa cells depleted of the CoQ biosynthesis regulatory protein COQ8A. While CoQ₁₀ supplementation of COQ8A depleted cells decreases ROS and increases SQOR protein levels, knock-down of SQOR prevents CoQ₁₀ antioxidant effects. We conclude that kidney failure in CoQ deficiency-associated NS is caused by oxidative stress mediated by impaired sulfides oxidation and propose that CoQ supplementation does not significantly increase the kidney pool of CoQ bound to the respiratory supercomplexes, but rather enhances the free pool of CoQ, which stabilizes SQOR protein levels rescuing oxidative stress.     

Response of corn to combinations of atrazine, propyl gallate and ozone

Growth chamber experiments were conducted to determine the influence of the air pollutant ozone (O₃) [0.2 and 0.3 ppm (v/v)] on the growth of corn (Zea mays L.) treated with the herbicide atrazine (2.5 and 3.5 kg/ha) and the antioxidant propyl gallate (5 and 8 kg/ha). At both concentrations O₃ at 0.3 ppm alone reduced dry weights of corn and chlorophyll. Chlorophyll a was more affected than chlorophyll b by O₃ at 0.3 ppm alone and in combination with atrazine. Propyl gallate at both rates protected corn against O₃ injury. The interaction between atrazine and O₃ at 0.2 ppm was additive whereas at 0.3 ppm it was antagonistic. But combinations of atrazine and propyl gallate did not protect corn from O₃ injury.     

‘If an Eye Is Washed Properly,It Means It Would See Clearly’: A Mixed Methods Study of Face Washing Knowledge,Attitudes, and Behaviors in Rural Ethiopia

BackgroundFace cleanliness is a core component of the SAFE (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements) strategy for trachoma control. Understanding knowledge, attitudes, and behaviors related to face washing may be helpful for designing effective interventions for improving facial cleanliness.MethodsIn April 2014, a mixed methods study including focus groups and a quantitative cross-sectional study was conducted in the East Gojjam zone of the Amhara region of Ethiopia. Participants were asked about face washing practices, motivations for face washing, use of soap (which may reduce bacterial load), and fly control strategies.ResultsOverall, both knowledge and reported practice of face washing was high. Participants reported they knew that washing their own face and their children’s faces daily was important for hygiene and infection control. Although participants reported high knowledge of the importance of soap for face washing, quantitative data revealed strong variations by community in the use of soap for face washing, ranging from 4.4% to 82.2% of households reporting using soap for face washing. Cost and forgetfulness were cited as barriers to the use of soap for face washing. Keeping flies from landing on children was a commonly cited motivator for regular face washing, as was trachoma prevention.ConclusionsInterventions aiming to improve facial cleanliness for trachoma prevention should focus on habit formation (to address forgetfulness) and address barriers to the use of soap, such as reducing cost. Interventions that focus solely on improving knowledge may not be effective for changing face-washing behaviors.