Global progress toward the elimination of active trachoma: an analysis of 38 countries.

BACKGROUND: Global elimination of trachoma as a public health problem was targeted for 2020. We reviewed progress towards the elimination of active trachoma by country and geographical group. METHODS: In this retrospective analysis of national survey and implementation data, all countries ever known to be endemic for trachoma that had either implemented at least one trachoma impact survey shown in the publicly available Trachoma Atlas, or are in Africa were invited to participate in this study. Scale-up was described according to the number of known endemic implementation units and mass drug administration implementation over time. The prevalence of active trachoma-follicular among children aged 1-9 years (TF1-9) from baseline, impact, and surveillance surveys was categorised and used to show programme progress towards reaching the elimination threshold (TF1-9 <5%) using dot maps, spaghetti plots, and boxplots. FINDINGS: We included data until Nov 10, 2021, for 38 countries, representing 2097 ever-endemic implementation units. Of these, 1923 (91·7%) have had mass drug administration. Of 1731 implementation units with a trachoma impact survey, the prevalence of TF1-9 had reduced by at least 50% in 1465 (84·6%) implementation units and 1182 (56·4%) of 2097 ever-endemic implementation units had reached the elimination threshold. 2 years after reaching a TF1-9 prevalence below 5%, most implementation units sustained this target; however, 58 (56·3%) of 103 implementation units in Ethiopia showed recrudescence. INTERPRETATION: Global elimination of trachoma as a public health problem by 2020 was not possible, but this finding masks the great progress achieved. Implementation units in high baseline categories and recrudescent TF1-9 might prolong the attainment of elimination of active trachoma. Elimination is delayed but, with an understanding of the patterns and timelines to reaching elimination targets and a commitment toward meeting future targets, global elimination can still be achieved by 2030. FUNDING: None.

A strong effect of individual compliance with mass drug administration for lymphatic filariasis on sustained clearance of soil-transmitted helminth infections.

BACKGROUND: The impact of semiannual mass drug administration (MDA) with albendazole (ALB; 400 mg) alone on lymphatic filariasis (LF) and soil-transmitted helminth (STH) infections was assessed during two trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of Congo. The collected data were analyzed to evaluate the effect of compliance with ALB treatment on STH infections. METHODS: STH infections were diagnosed with duplicate Kato-Katz thick smears and the results are reported as eggs per gram of stool. All subjects with at least two STH infection assessments were included in the analyses. We used parametric survival models to assess the influence of compliance with ALB treatment on the probability of (i) achieving sustained clearance of an STH infection, and (ii) acquiring an STH infection during the follow-up. RESULTS: Out of 2658 subjects included in the trials, data on 202 participants (701 person-years; PY) with hookworm infection, 211 (651 PY) with Ascaris lumbricoides infection and 270 (1013 PY) with Trichuris trichiura infection were available to calculate the probability of achieving sustained clearance of infection. The effect of ALB was dose related for all three STH. For hookworm, the time required for sustained clearance was longer (4.3 years, P < 0.001) for participants who took zero doses per year and shorter (3.4 years, P = 0.112) for participants who took two doses per year compared to those who took one dose per year (3.7 years). For Ascaris, the time required to obtain sustained clearance followed the same pattern: 6.1 years (P < 0.001) and 3.2 years (P = 0.004) vs 3.6 years for, zero, two and one dose per year, respectively. For Trichuris, less time was required for sustained clearance (4.2 years, P < 0.001) for fully compliant participants, i.e. those who took two doses per year, than for those who only took one dose per year (5.0 years). ALB was more effective in achieving sustained clearance of STH infection in subjects with light baseline infection intensities compared to those with higher egg counts. CONCLUSION: Our results illustrate the importance of MDA compliance at the level of the individual with respect to the STH benefit provided by semiannual ALB MDA, which is used for the elimination of LF in Central Africa.

Effect of Lymphatic Filariasis and Hookworm Infection on Pregnancy Course and Outcome in Women Living in the Democratic Republic of the Congo.

Little is known about the effect of helminth infections on the natural gynecological and pregnancy course. Our goal was to assess the relationship between Wuchereria bancrofti and hookworm (HW) infections with pregnancy course and outcome in a group of 82 women living in a rural area of the Democratic Republic of the Congo. Demographics and information on gynecological and obstetrical histories were collected retrospectively with standardized questionnaires. Wuchereria bancrofti and HW infections were diagnosed using a filarial antigen-detection test and the Kato-Katz method, respectively. Analyses consisted of multivariable logistic regressions adjusting for age, number of deliveries, and history of anthelmintic treatment (HAHT). The median age of study participants was 35 (interquartile range [IQR]: 30-44) years, and the median number of deliveries was five (IQR: 3-7). Wuchereria bancrofti and HW infection rates were 44.5% and 43.3%, respectively. Filarial antigenemia and HW infection were not significantly associated with the number of deliveries. The proportions of women with a history of pregnancy resulting in neonatal death, miscarriage, premature birth, and postpartum hemorrhage were 56%, 44%, 23%, and 36%, respectively. History of pregnancy associated with neonatal death was less frequent in women with HAHT, tended to be more frequent in women with filarial antigenemia, and was not associated with HW infection. None of the three other pregnancy events studied (miscarriage, premature birth, and postpartum hemorrhage) were associated with filarial antigenemia or HW infection. The positive association found between HAHT and lower risk of neonatal death warrants investigation in larger groups of women.

Results From 2 Cohort Studies in Central Africa Show That Clearance of Wuchereria bancrofti Infection After Repeated Rounds of Mass Drug Administration With Albendazole Alone Is Closely Linked to Individual Adherence.

BACKGROUND: Two community trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of the Congo demonstrated the efficacy of semiannual mass drug administration (MDA) with albendazole (ALB) alone on lymphatic filariasis (LF). However, a high interindividual heterogeneity in the clearance of infection was observed. METHODS: We analyzed trial data to assess the effect of individual adherence to ALB MDA on clearance of circulating filarial antigenemia (CFA) and microfilaremia. Community residents were offered a single dose of ALB every 6 months and tested for LF with a rapid test for CFA at baseline and then annually. CFA test results were scored on a semiquantitative scale. At each round, microfilaremia was assessed in CFA-positive individuals. All CFA-positive individuals for whom at least 1 follow-up measure was available were included in the analyses. Parametric survival models were used to assess the influence of treatment adherence on LF infection indicators. RESULTS: Of 2658 individuals enrolled in the trials, 394 and 129 were eligible for analysis of CFA and microfilaremia clearance, respectively. After adjusting for age, sex, and initial CFA score, the predicted mean time for clearing CFA was shorter in persons who had taken 2 doses of ALB per year (3.9 years) than in persons who had taken 1 or 0 dose (4.4 and 5.3 years; P < .001 for both). A similar pattern was observed for microfilaremia clearance. CONCLUSIONS: These results demonstrate a clear dose-response relationship for the effect of ALB on clearance of CFA and microfilaremia.

The impact of four years of semiannual treatments with albendazole alone on lymphatic filariasis and soil-transmitted helminth infections: A community-based study in the Democratic Republic of the Congo.

BACKGROUND: The World Health Organization now recommends semiannual mass drug administration (MDA) of albendazole with integrated vector management as an option for eliminating lymphatic filariasis (LF) in areas of loiasis-endemic countries where it may not be safe to use diethylcarbamazine or ivermectin in MDA programs. However, the published evidence base to support this policy is thin, and uptake by national programs has been slow. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community trial to assess the impact of semiannual MDA on lymphatic filariasis and soil-transmitted helminth infections (STH) in two villages in the Bandundu province of the Democratic Republic of the Congo with moderately high prevalences for LF and hookworm infections. MDA with albendazole was provided every six months from June 2014 to December 2017 with treatment coverages of the eligible population (all ≥ 2 year of age) that ranged between 56% and 88%. No adverse effects were reported during the trial. Evaluation at 48 months, (i.e. 6 months after the 8th round of MDA), showed that W. bancrofti microfilaremia (Mf) prevalence in the study communities had decreased between 2014 to 2018 from 12% to 0.9% (p<0.001). The prevalence of W. bancrofti antigenemia was also significantly reduced from 31.6% to 8.5% (p<0.001). MDA with albendazole also reduced hookworm, Ascaris lumbricoides and Trichuris trichiura infection prevalences in the community from 58.6% to 21.2% (p<0.001), from 14.0% to 1.6% and 4.1% to 2.9%, respectively. Hookworm and Ascaris infection intensities were reduced by 93% (p = 0.02) and 57% (p = 0.03), respectively. In contrast, Trichuris infection intensity was not significantly reduced by MDA (p = 0.61) over this time period. CONCLUSION/SIGNIFICANCE: These results provide strong evidence that semiannual MDA with albendazole alone is a safe and effective strategy for LF elimination in Central Africa. Community MDA also had a major impact on STH infections.

Risk factors for lymphatic filariasis in two villages of the Democratic Republic of the Congo.

BACKGROUND: Little is known regarding risk factors for lymphatic filariasis (LF) in Central Africa. To expand on what is known, we studied the epidemiology of LF in two endemic villages in the Democratic Republic of the Congo. METHODS: Dependent variables were Wuchereria bancrofti antigenaemia detected with filarial test strips (FTS) and microfilaraemia detected by night blood smears. The following factors were investigated: sex, age, the use of bednets, the use of latrines, hunting, fishing and agricultural activities, history of treatment with anthelmintic drugs, overnight stays in the bush, population density, the number of household members, and distance to rivers. Mixed multivariate logistic regression models were used. RESULTS: Two hundred and fifty nine out of 820 (31.6%) of subjects aged ≥ 5 years had W. bancrofti antigenaemia and 11.8% (97/820) had microfilaraemia. Multivariable analysis of risk factors for antigenaemia demonstrated increased risk for males (aOR = 1.75, 95% CI: 1.20-2.53, P = 0.003), for older individuals (aOR = 9.12 in those aged > 35 years, 95% CI: 4.47-18.61, P < 0.001), for people not using bednets (aOR = 1.57, 95% CI: 1.06-2.33, P = 0.023), for farmers (aOR = 2.21, 95% CI: 1.25-3.90, P = 0.006), and for those who live close to a river (aOR = 2.78, 95% CI: 1.14-6.74, P = 0.024). Significant risk factors for microfilaraemia included age, male gender, overnight stay in the bush, and residence close to a river (aOR = 1.86, 2.01, 2.73; P = 0.011, 0.010, 0.041; for the three latter variables, respectively). People who reported having taken levamisole (n = 117) during the prior year had a significantly decreased risk of having filarial antigenaemia (aOR = 0.40, 95% CI: 0.21-0.76, P = 0.005). CONCLUSIONS: Age, sex, not using bednets, and occupation-dependent exposure to mosquitoes were important risk factors for infection with W. bancrofti in this study. The association with levamisole use suggests that the drug may have prevented filarial infections. Other results suggest that transmission often occurs outside of the village. This study provides interesting clues regarding the epidemiology of LF in Central Africa.

Albendazole Treatment Improves Work Capacity in Women Smallholder Farmers Infected with Hookworm: A Double-Blind Randomized Control Trial.

An estimated 4.7 billion people live in regions exposed to soil-transmitted helminths, intestinal parasites that have significant impacts on the health of women smallholder farmers. The goal of this trial was to determine whether treatment with albendazole impacts the work capacity of these farmers. This is a prospective double-blind, randomized effectiveness trial. Participants (N = 250) were randomly selected from safe motherhood groups in the Democratic Republic of Congo. Prevalence/intensity of hookworm infection, hemoglobin, and demographics was obtained. At study (Time = 0), participants were randomized into treatment (albendazole 400 mg) and placebo (similar placebo tablet) groups. A step test was administered as a proxy metric for work capacity. Work capacity was defined as ∆heart rate before and after 3 minutes of step testing, in beats per minute. At study (time = 7 months), the step test was repeated and work capacity remeasured. The ∆work capacity (time = 0 minus time = 7 months) was the primary outcome. Investigators/field assistants were blinded to who was enrolled in groups, hookworm status, and step test results. Regression showed highly significant interactive effects of hookworm status and treatment group relative to ∆work capacity after controlling for resting pulse rate and age (P < 0.002). Estimated marginal means for work capacity (WC) for each of four groups (hookworm positive plus placebo, hookworm positive plus treatment, hookworm negative plus placebo, and hookworm negative plus treatment) showed women who were hookworm positive and received treatment decreased heart rate by 9.744 (95% confidence interval [CI]: 6.42, 13.07) beats per minute (increased WC), whereas women who were hookworm positive and received placebo saw a nonsignificant decrease of 0.034 (95% CI: -3.16, 3.84) beats per minute. Treatment with albendazole was associated with improved aerobic work capacity posttreatment. Given modest costs of drug distributions, risk benefits of periodic deworming warrants further study in larger controlled trials.

A multi-center field study of two point-of-care tests for circulating Wuchereria bancrofti antigenemia in Africa.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis uses point-of-care tests for circulating filarial antigenemia (CFA) to map endemic areas and for monitoring and evaluating the success of mass drug administration (MDA) programs. We compared the performance of the reference BinaxNOW Filariasis card test (ICT, introduced in 1997) with the Alere Filariasis Test Strip (FTS, introduced in 2013) in 5 endemic study sites in Africa. METHODOLOGY: The tests were compared prior to MDA in two study sites (Congo and Côte d'Ivoire) and in three sites that had received MDA (DRC and 2 sites in Liberia). Data were analyzed with regard to % positivity, % agreement, and heterogeneity. Models evaluated potential effects of age, gender, and blood microfilaria (Mf) counts in individuals and effects of endemicity and history of MDA at the village level as potential factors linked to higher sensitivity of the FTS. Lastly, we assessed relationships between CFA scores and Mf in pre- and post-MDA settings. PRINCIPAL FINDINGS: Paired test results were available for 3,682 individuals. Antigenemia rates were 8% and 22% higher by FTS than by ICT in pre-MDA and in post-MDA sites, respectively. FTS/ICT ratios were higher in areas with low infection rates. The probability of having microfilaremia was much higher in persons with CFA scores >1 in untreated areas. However, this was not true in post-MDA settings. CONCLUSIONS/SIGNIFICANCE: This study has provided extensive new information on the performance of the FTS compared to ICT in Africa and it has confirmed the increased sensitivity of FTS reported in prior studies. Variability in FTS/ICT was related in part to endemicity level, history of MDA, and perhaps to the medications used for MDA. These results suggest that FTS should be superior to ICT for mapping, for transmission assessment surveys, and for post-MDA surveillance.

Measurement of Circulating Filarial Antigen Levels in Human Blood with a Point-of-Care Test Strip and a Portable Spectrodensitometer.

The Alere Filariasis Test Strip (FTS) is a qualitative, point-of-care diagnostic tool that detects Wuchereria bancrofti circulating filarial antigen (CFA) in human blood, serum, or plasma. The Global Program to Eliminate Lymphatic Filariasis employs the FTS for mapping filariasis-endemic areas and assessing the success of elimination efforts. The objective of this study was to explore the relationship between the intensity of positive test lines obtained by FTS with CFA levels as determined by enzyme-linked immunosorbent assay (ELISA) with blood and plasma samples from 188 individuals who live in a filariasis-endemic area. The intensity of the FTS test line was assessed visually to provide a semiquantitative score (visual Filariasis Test Strip [vFTS]), and line intensity was measured with a portable spectrodensitometer (quantitative Filariasis Test Strip [qFTS]). These results were compared with antigen levels measured by ELISA in plasma from the same subjects. qFTS measurements were highly correlated with vFTS scores (ρ = 0.94; P < 0.001) and with plasma CFA levels (ρ = 0.91; P < 0.001). Thus, qFTS assessment is a convenient method for quantifying W. bancrofti CFA levels in human blood, which are correlated with adult worm burdens. This tool may be useful for assessing the impact of treatment on adult filarial worms in individuals and communities.