Kelly Callahan

Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: two cohort studies.

Background Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors. Methodology/Principal Findings We recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31–10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60–12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1. Conclusions/Significance Scarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level.

The Contributions of Onchocerciasis Control and Elimination Programs toward the Achievement of the Millennium Development Goals

In 2000, 189 member states of the United Nations (UN) developed a plan for peace and development, which resulted in eight actionable goals known as the Millennium Development Goals (MDGs). Since their inception, the MDGs have been considered the international standard for measuring development progress and have provided a blueprint for global health policy and programming. However, emphasis upon the achievement of priority benchmarks around the “big three” diseases—namely HIV, tuberculosis (TB), and malaria—has influenced global health entities to disproportionately allocate resources. Meanwhile, several tropical diseases that almost exclusively impact the poorest of the poor continue to be neglected, despite the existence of cost-effective and feasible methods of control or elimination. One such Neglected Tropical Disease (NTD), onchocerciasis, more commonly known as river blindness, is a debilitating and stigmatizing disease primarily affecting individuals living in remote and impoverished areas. Onchocerciasis control is considered to be one of the most successful and cost-effective public health campaigns ever launched. In addition to improving the health and well-being of millions of individuals, these programs also lead to improvements in education, agricultural production, and economic development in affected communities. Perhaps most pertinent to the global health community, though, is the demonstrated effectiveness of facilitating community engagement by allowing communities considerable ownership with regard to drug delivery. This paper reviews the contributions that such concentrated efforts to control and eliminate onchocerciasis make to achieving select MDGs. The authors hope to draw the attention of public policymakers and global health funders to the importance of the struggle against onchocerciasis as a model for community-directed interventions to advance health and development, and to advocate for NTDs inclusion in the post 2015 agenda.

Posterior lamellar versus bilamellar tarsal rotation surgery for trachomatous trichiasis in Ethiopia: a randomised controlled trial

Summary Background Eyelid surgery is done to correct trachomatous trichiasis to prevent blindness. However, recurrent trichiasis is frequent. Two procedures are recommended by WHO and are in routine practice: bilamellar tarsal rotation (BLTR) and posterior lamellar tarsal rotation (PLTR). This study was done to identify which procedure gives the better results. Methods A randomised, controlled, single masked clinical trial was done in Ethiopia. Participants had upper lid trachomatous trichiasis with one or more eyelashes touching the eye or evidence of epilation, in association with tarsal conjunctival scarring. Exclusion criteria were age less than 18 years, recurrent trichiasis after previous surgery, hypertension, and pregnancy. Participants were randomly assigned (1:1) to either BLTR or PLTR surgery, stratified by surgeon. The sequences were computer-generated by an independent statistician. Surgery was done in a community setting following WHO guidelines. Participants were examined at 6 months and 12 months by assessors masked to allocation. The primary outcome was the cumulative proportion of individuals who developed recurrent trichiasis by 12 months. Primary analyses were by modified intention to treat. The intervention effect was estimated by logistic regression, controlled for surgeon as a fixed effect in the model. The trial is registered with the Pan African Clinical Trials Registry (number PACTR201401000743135). Findings 1000 participants with trichiasis were recruited, randomly assigned, and treated (501 in the BLTR group and 499 in the PLTR group) between Feb 13, 2014, and May 31, 2014. Eight participants were not seen at either 6 month or 12 month follow-up visits and were excluded from the analysis: three from the PLTR group and five from the BLTR group. The follow-up rate at 12 months was 98%. Cumulative recurrent trichiasis by 12 months was more frequent in the BLTR group than in the PLTR group (110/496 [22%] vs 63/496 [13%]; adjusted odds ratio [OR] 1·96 [95% CI 1·40–2·75]; p=0·0001), with a risk difference of 9·50% (95% CI 4·79–14·16). Interpretation PLTR surgery was superior to BLTR surgery for management of trachomatous trichiasis, and could be the preferred procedure for the programmatic management of trachomatous trichiasis. Funding The Wellcome Trust.

Contributions of the Guinea Worm Disease Eradication Campaign toward Achievement of the Millennium Development Goals

Infectious diseases have influenced the biological, historical, and political development of the human species more than any other factor: from the outcome of wars to the success of empires, from the pace of technological advance to the structure of society [1]. Dracunculiasis (Guinea worm disease) was considered a mild affliction not warranting a widespread public health campaign. However, examination of the benefits of eradicating Guinea worm disease (GWD) reveals the effort is contributing to development, including contributions to certain Millennium Development Goals (MDGs) [2]. Given the use of the MDGs in the development of global health agendas, it is timely to consider the contributions of neglected tropical disease (NTD) programs, such as the Guinea Worm Eradication Program (GWEP), toward the achievement of the MDGs. The prevention of NTDs, and their cost-effective interventions, fuels long-term economic growth and development, and human advancement [3]. The effort to eradicate GWD is considered one of the most cost-effective health interventions available [2,4,5]. The authors provide evidence that concentrated efforts on eradication, elimination, and control of some NTDs can yield far-reaching results, and given these results, stimulate increased efforts toward NTD eradication, elimination, and control among public health advocates, global health entities, and donors. GWD is a disease of the poor, debilitating many in the most remote and disadvantaged communities in parts of sub-Saharan Africa, where potable water is limited and health care and education are lacking [6]. Endemic GWD transmission is an indicator of extreme poverty [6,7]. GWD is a preventable, painful, and incapacitating waterborne helminthic disease, which harms health, agriculture, school attendance, and overall quality of life for individuals and communities [7–9]. GWD is transmitted when humans drink water, usually from stagnant water sources, containing tiny copepods that have ingested larvae of the parasite. Once consumed, the digestive juices in the human stomach kill the copepods, allowing the larvae to be released and move to the intestinal wall where they migrate to connective tissues of the thorax. Male and female larvae mature and mate 60–90 days after infection. Symptoms appear 10–14 months later when the gravid adult female(s), measuring up to 70–100 cm long, emerges from the skin, causing a painful lesion [10]. When the emerging worm is exposed to water, she ejects hundreds of thousands of larvae into the water to continue the cycle. During emergence, an infected person can be incapacitated for an average of 8.5 weeks [10,11]. Although rarely fatal, GWD inflicts devastating pain and infection resulting in immobility [8,12]. The pain is so long-lasting that infected individuals may be incapacitated for up to three months during and after the Guinea worm (GW) emerges [11,13–15]. Other symptoms include nausea, vomiting, diarrhea, and dizziness; secondary bacterial infections can also occur and can lead to arthritis, tetanus, and permanent crippling [8]. There is no cure, vaccine, or immunity after infection [11]. Since there is no evidence that animals are reservoir hosts, the disease is deemed a good candidate for eradication [8]. The global eradication campaign began at the United States Centers for Disease Control and Prevention (CDC) in 1980 and was then adopted as a subgoal of the United Nations International Drinking-Water Supply and Sanitation Decade (1981–1990). In that same year, the decision-making body of the World Health Organization (WHO) adopted a resolution (WHA 34.25) recognizing the decade could be an opportunity to eliminate GWD. Since 1986, The Carter Center (TCC) has led the effort, with the help of the CDC, WHO, United Nations Children’s Fund (UNICEF), and many other donors and nongovernmental organizations, to assist national eradication efforts by governments of the countries where GWD is endemic [11]. The GWEP assists ministries of health (MOH) in each endemic country to provide GWD interventions. The GWEP is an eradication effort that relies heavily on behavioral change via health education and interventions. The GWEP has demonstrated that when people are given the proper tools and health education, cases decrease dramatically [16]. The most effective and cost-efficient way to prevent GWD is the promotion of its health campaign coupled with proper and consistent use of filters to remove the copepods from drinking water, case containment, and the application of ABATE, a safe chemical larvicide, to control the copepods [4,17–19]. GWD is an infectious disease categorized as a neglected tropical disease (NTD) [20]. NTDs are among the most common infectious diseases of the world’s poorest people [21,22]. An estimated 1.2 billion people are infected with one or more NTDs [23]. These individuals are among the billion people living on less than

Risk factors for trachomatous trichiasis in children: cross-sectional household surveys in Southern Sudan

1 per day, a population identified as the ‘‘bottom billion’’ [23]. NTDs are a group of parasitic, bacterial, and viral diseases that cause

Trachoma and Relative Poverty: A Case-Control Study

We have previously documented blinding trachoma to be a serious public health problem in Southern Sudan, with an unusually high prevalence of trachomatous trichiasis (TT) among children. We aimed to investigate risk factors for TT in children in Southern Sudan. Cross-sectional surveys were undertaken in 11 districts between 2001 and 2006, and eligible participants were examined for trachoma signs. Risk factors were assessed through interviews and observations. Using logistic regression, associations between TT in children and potential risk factors were investigated. In total, 11155 children aged 1-14 years from 3950 households were included in the analysis. Overall prevalence of TT was 1.5% (95% CI 1.1-2.1). Factors independently associated with increased odds of TT in children aged 1-14 years were: increasing age (P(trend)<0.001); female gender (odds ratio=1.5; 95% CI 1.1-2.1); increasing proportion of children in the household with trachomatous inflammation-intense (TI) (P(trend)=0.002); and increasing number of adults in the household with TT (P(trend)<0.001). Our study revealed risk factors for TT in children consistent with those previously reported for TT in adults. While the associations of TT in children with TI in siblings and TT in adult relatives merit further investigation, there is an urgent need for trachoma prevention interventions and trichiasis surgery services that are tailored to cater for young children in Southern Sudan.

Impact of Trichiasis Surgery on Quality of Life: A Longitudinal Study in Ethiopia.

Background Trachoma is widely considered a disease of poverty. Although there are many epidemiological studies linking trachoma to factors normally associated with poverty, formal quantitative data linking trachoma to household economic poverty within endemic communities is very limited. Methodology/Principal Findings Two hundred people with trachomatous trichiasis were recruited through community-based screening in Amhara Region, Ethiopia. These were individually matched by age and gender to 200 controls without trichiasis, selected randomly from the same sub-village as the case. Household economic poverty was measured through (a) A broad set of asset-based wealth indicators and relative household economic poverty determined by principal component analysis (PCA, (b) Self-rated wealth, and (c) Peer-rated wealth. Activity participation data were collected using a modified ‘Stylised Activity List’ developed for the World Bank’s Living Standards Measurement Survey. Trichiasis cases were more likely to belong to poorer households by all measures: asset-based analysis (OR = 2.79; 95%CI: 2.06–3.78; p<0.0001), self-rated wealth (OR, 4.41, 95%CI, 2.75–7.07; p<0.0001) and peer-rated wealth (OR, 8.22, 95% CI, 4.59–14.72; p<0.0001). Cases had less access to latrines (57% v 76.5%, p = <0.0001) and higher person-to-room density (4.0 v 3.31; P = 0.0204) than the controls. Compared to controls, cases were significantly less likely to participate in economically productive activities regardless of visual impairment and other health problems, more likely to report difficulty in performing activities and more likely to receive assistance in performing productive activities. Conclusions/Significance This study demonstrated a strong association between trachomatous trichiasis and relative poverty, suggesting a bidirectional causative relationship possibly may exist between poverty and trachoma. Implementation of the full SAFE strategy in the context of general improvements might lead to a virtuous cycle of improving health and wealth. Trachoma is a good proxy of inequality within communities and it could be used to target and evaluate interventions for health and poverty alleviation.

The Impact of Trachomatous Trichiasis on Quality of Life: A Case Control Study.

Background Trachomatous trichiasis significantly reduces vision and health related quality of life (QoL). Although trichiasis surgery is widely performed to treat trichiasis, there is little data on the effect of surgery on QoL. We measured the impact of trichiasis surgery on vision and health related QoL in a longitudinal study from Amhara Region, Ethiopia. Methodology/Principal Findings We recruited 1000 adult participants with trichiasis (cases) and 200 comparison participants, matched to every fifth trichiasis case on age (+/- two years), sex and location. Vision-related quality of life (VRQoL) and health-related quality of life (HRQoL) were measured using the WHO/PBD-VF20 and WHOQOL-BREF questionnaires respectively, at enrolment and 12 months after enrolment. All trichiasis cases received free standard trichiasis surgery immediately after enrolment. The mean difference in QoL scores between enrolment and follow-up for cases and comparison participants, and the difference-in-differences by baseline trichiasis status was analysed using random effects linear regression, the later adjusted for age, sex and socioeconomic status. At 12-months follow-up, data was collected from 980 (98%) and 198 (98%) trichiasis cases and comparison participants respectively. At this follow-up visit, VRQoL and HRQoL scores of trichiasis cases improved substantially in all subscales and domains by 19.1–42.0 points (p<0.0001) and 4.7–17.2 points (p<0.0001), respectively. In contrast, among the comparison participants, there was no evidence of improvement in VRQoL and HRQoL domain scores during follow-up. The improvement in VRQoL and HRQoL in cases was independent of the presence of visual acuity improvement at 12 months. Conclusions/Significance Trichiasis surgery substantially improves both VRQoL and HRQoL regardless of visual acuity change. Unprecedented effort is needed to scale-up trichiasis surgical programmes not only to prevent the risk of sight loss but also to improve overall wellbeing and health perception of affected individuals.

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

Background Trachomatous trichiasis is thought to have a profound effect on quality of life (QoL), however, there is little research in this area. We measured vision and health-related QoL in a case-control study in Amhara Region, Ethiopia. Methodology/Principal Findings We recruited 1000 adult trichiasis cases and 200 trichiasis-free controls, matched to every fifth trichiasis case on age (+/- two years), sex and location. Vision-related quality of life (VRQoL) and health-related quality of life (HRQoL) were measured using the WHO/PBD-VF20 and WHOQOL-BREF questionnaires. Comparisons were made using linear regression adjusted for age, sex and socioeconomic status. Trichiasis cases had substantially lower VRQoL than controls on all subscales (overall eyesight, visual symptom, general functioning and psychosocial, p<0.0001), even in the sub-group with normal vision (p<0.0001). Lower VRQoL scores in cases were associated with longer trichiasis duration, central corneal opacity, visual impairment and poor contrast sensitivity. Trichiasis cases had lower HRQoL in all domains (Physical-health, Psychological, Social, Environment, p<0.0001), lower overall QoL (mean, 34.5 v 64.6; p<0.0001) and overall health satisfaction (mean, 38.2 v 71.7; p<0.0001). This association persisted in a sub-group analysis of cases and controls with normal vision. Not having a marriage partner (p<0.0001), visual impairment (p = 0.0068), daily labouring (p<0.0001), presence of other health problems (p = 0.0018) and low self-rated wealth (p<0.0001) were independently associated with lower overall QoL scores in cases. Among cases, trichiasis caused 596 (59%) to feel embarrassed, 913 (91.3%) to worry they may lose their remaining eyesight and 681 (68.1%) to have sleep disturbance. Conclusions/Significance Trachomatous trichiasis substantially reduces vision and health related QoL and is disabling, even without visual impairment. Prompt trichiasis intervention is needed both to prevent vision loss and to alleviate physical and psychological suffering, social exclusion and improve overall well-being. Implementation of the full SAFE strategy is needed to prevent the development of trachomatous trichiasis.

Is Using a Latrine “a Strange Thing To Do”? A Mixed-Methods Study of Sanitation Preference and Behaviors in Rural Ethiopia

Background Trachomatous 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.