Impact of seven rounds of mass administration of diethylcarbamazine and ivermectin on prevalence of chronic lymphatic filariasis in south India

Objective To evaluate the impact of seven rounds of mass administration of diethylcarbamazine (DEC) and ivermectin on the prevalence of chronic lymphatic filariasis and to compare it with that observed in a placebo arm in a community‐level trial. Methods Cross‐sectional clinical surveys were carried out before and after seven rounds of mass drug administration (MDA). About 54–75% of the target population were treated at each round of MDA. Results After seven rounds, the hydrocele prevalence had declined from the pre‐intervention level of 20.5–5.1% (P < 0.05) in the DEC arm, from 23.9% to 10.4% (P < 0.05) in the ivermectin arm and from 20.4% to 10.9% (P < 0.05) in the placebo arm, equivalent to reductions of 75.3%, 56.6% and 46.6%, respectively. The lymphoedema/elephantiasis prevalence declined only marginally and without statistical significance from 3.7% to 3.2%, 4.6% to 3.9% and 2.9% to 2.3% in the DEC, ivermectin and placebo arm. After the seventh MDA, none of the sampled people in the 0–20 age group was found with hydrocele and there was a statistically significant decline in hydrocele prevalence in all other age groups in the communities treated with DEC, the drug known to have macrofilaricidal effect. The impact was relatively less in ivermectin arm. Conclusion Repeated DEC administration has the potential to prevent incidence of new hydrocele cases and may resolve the manifestation at least in a proportion of affected people. Apart from reducing the microfilaraemia prevalence and transmission of infection, MDA also results in significant public health benefits by reducing the burden of hydrocele in treated communities.     

Inadvertent exposure of pregnant women to ivermectin and albendazole during mass drug administration for lymphatic filariasis

The current strategy for the interruption of transmission of lymphatic filariasis in areas where the disease is co-endemic with onchocerciasis is repeated annual mass treatment of endemic communities with ivermectin and albendazole. These drugs are not recommended for use in pregnancy. Pregnant women are excluded on the basis of their last menses. This exclusion criterion based on recall carries some inherent errors, leading sometimes to inadvertent exposure of foetuses to these drugs. This study set out to document the extent of inadvertent exposure of pregnant women to albendazole and ivermectin and assess the relative risk of congenital malformations because of inadvertent treatment with these drugs in early pregnancy. The study was conducted in the Ahanta West District of Ghana. Local pregnancy revelation norms were studied, followed by a household survey of women aged 15-45 years to assess drug administration coverage. All infants born within 42 weeks of the mass drug treatment were examined to document any congenital malformations. Mothers who had lost any such infants responded to a verbal autopsy to ascertain the probable cause of death. Health facilities and local Traditional Birth Attendants were also visited to review maternity records. Of 2985 women of childbearing age (15-49 years) who were interviewed, 343 were pregnant during the mass drug administration. The sensitivity of the last menstrual period in detecting pregnancy and thus being excluded from treatment was 0.854 (293 of 343). Some pregnant women 50 of 343 (14.6%) had thus been inadvertently treated. This represents 1.7% of women in fertile age group (15-49 years). Of the six children found with some congenital malformations in these communities, one had been exposed to the drugs in-utero. The relative risk for congenital malformation after exposure was 1.05 (P=1.0). Two of nine reported spontaneous abortions had been exposed to the drugs (P=0.62). We conclude that the local mode of excluding pregnancy in the current programme, while not perfect, is sufficiently effective and reliable for such a public health intervention; and importantly, that there is no evidence of a higher risk of congenital malformation or abortions in those who are inadvertently exposed.     

Long-term population migration: an important aspect to be considered during mass drug administration for elimination of lymphatic filariasis

Annual 2-drug, single-dose mass drug administration (MDA) to 80-90% of the eligible population for 4-6 years are pre-requisites for the successful elimination of lymphatic filariasis (LF) from endemic communities by interruption of transmission and eventual elimination of new infections. In an experimental intervention project on the control of LF in Villupuram district of Tamil Nadu state, India, migration patterns of the villagers were investigated to determine the appropriate timing to implement MDA in order to attain high coverage in a village-level study. Between January and December 1997, 16 observations took place at 3-week intervals, following MDA with two drugs viz., diethylcarbamazine and ivermectin, in July-August 1996. The migrants from the village constituted 17-27% at different points of time and both short-term and long-term migrating patterns were observed. More villagers were available during the agricultural season (September-January), peaking around mid-January [83%; significantly higher (P < 0.05)] than during most of the remaining months, including a substantial portion of the migrant population. There is an urgent need to reschedule the yearly MDA in this area to take place in January and to plan mopping up operations by involving local self-help groups to include migrants (both short-term and long-term) in the LF elimination efforts.     

Albendazole for the control and elimination of lymphatic filariasis: systematic review

OBJECTIVES: The Global Programme to Eliminate Lymphatic Filariasis recommends albendazole in combination with other antifilarial drugs. This systematic review examines albendazole in treatment and control of lymphatic filariasis. DATASOURCES: The Cochrane Controlled Trials Register, MEDLINE and EMBASE to April 2005; contacting experts, international organisations and drug manufacturers. METHODS: Randomised or quasi-randomised controlled trials included; two reviewers independently assessed eligibility, quality, and extracted data. We calculated the relative risk of microfilaraemia (mf) prevalence using fixed effect, or random effects model in case of heterogeneity. RESULTS: Six trials met inclusion criteria. Three trials compared albendazole with placebo: no effect was demonstrated on mf prevalence, but density was lower in one of the three studies at 6 months. Three trials added albendazole to ivermectin, with no demonstrable effect; prevalence tended to be lower at 4--6 months but not at 12 months (4--6 months; RR 0.49, 95% CI 0.18 to 1.39, n=255, 2 trials; 12 months: RR 1.00, 95% CI 0.88 to 1.13, n=348, 2 trials). Mf density was significantly lower in two of the three trials; one of two trials measuring density at 12 months showed a difference. Three trials added albendazole to diethylcarbamazine; two were small trials with no difference demonstrated; the third study tended to favour combination at 6 months (RR=0.62, 95% CI 0.32 to 1.21, n=491), with a significant difference for density. CONCLUSIONS: The effect of albendazole against adult and larval filarial parasites, alone and in combination with other antifilarial drugs, deserves further rigorous research.     

Coverage, compliance and some operational issues of mass drug administration during the programme to eliminate lymphatic filariasis in Orissa, India

This paper reports the coverage, compliance and other operational issues of mass drug administration (MDA) of diethylcarbamazine and albendazole under a programme to eliminate lymphatic filariasis (LF) in Orissa state of India. Both quantitative and qualitative methods were used to collect data from 90 villages and nine urban areas of four districts of Orissa, India. In Orissa, 67% of people older than 2 years had received the drugs during MDA and 42% had consumed them. About 25% of people had not taken the tablets although they received them. Urban areas recorded lower rates than rural areas. The paper discusses some policy/health system-, community- and drug-related issues that influenced coverage and compliance of MDA. It is essential to improve compliance in future rounds of MDA to achieve targets of control and eventual elimination of LF in a reasonable time frame.     

Optimizing the malaria data recording system through a study of case detection and treatment in Sri Lanka

The potential of using malaria incidence data routinely collected from endemic regions for disease control and research has increased with the availability of advanced computer-based technologies, but will depend on the quality of the data itself. We report here an investigation into the relevance of malaria statistics provided by the routine data collection system in Moneragala, a rural malaria-endemic region in Sri Lanka. All patients (n = 321) treated for malaria in 2 clusters of health care centres (HCCs) of both the private and the public sector in the administrative regions of Moneragala and Buttala Divisional Secretariat (D.S.). Divisions were studied in December 1995/January 1996. The catchment area of these HCCs included a population resident in 53 Grama Niladhari (GN) areas, the smallest administrative units of the country. Almost equal numbers of malaria patients were detected and treated at Government and private health care institutions, and in 70% of them treatment was based on a diagnosis confirmed by microscopy. The routine data recording system, however, included only statistics from the Government sector, and only of patients whose diagnosis was microscopically confirmed. In compiling data, the origin of a case of malaria is attributed to the D.S. Division in which the institution (at which the patient was treated) was located, rather than the area in which the patient was resident, which was inaccurate because 90% of malaria patients sought health care at institutions located closest to their residence, thus crossing administrative boundaries. It also led to a loss of resolution of spatial data because patients' addresses recorded at the Government HCCs to the village-level are replaced in the statistics by the D.S. Division, which is a coarse spatial unit. Modifications to the system for malaria case recording needed to correct these anomalies are defined here. If implemented, these could result in major improvements to the quality of data, a valuable resource for the future of malaria control. The paper reiterates the call for the use of a standard spatial unit within a country to facilitate exchange of data among health and other sectors for the control of tropical diseases.     

Using knowledge, attitudes and practice (KAP) surveys on lymphatic filariasis to prepare a health promotion campaign for mass drug administration in Alor District, Indonesia

We report the results of two surveys of people's knowledge, attitudes and practices (KAP) regarding lymphatic filariasis (LF) in Alor District, eastern Indonesia. The results of the surveys were used to prepare and evaluate the social mobilization component of a pilot mass drug administration (MDA) in five villages. In the study area, the filarial parasites Brugia timori and Wuchereria bancrofti are highly endemic. Frequent and severe adverse reactions after MDA may occur especially in areas endemic for B. timori and therefore, a special communication strategy was designed to inform and to educate communities about LF and its control. The first KAP survey was conducted as a baseline pre-MDA with diethylcarbamazine and albendazole and the second as a post-intervention evaluation in order to obtain information on the impact of the communication campaign. Before the information campaign and the subsequent MDA, 54% of the study population had heard of one of the three main terms for LF, whereas after health education and MDA, 89% had heard of at least one of the three terms. Similarly, pre-MDA, 21% reported having had previously taken the treatment for filariasis, while post-MDA, 88% reported having taken the treatment during the pilot treatment period. The historical fears and traumatic experiences associated with past LF treatment campaigns in Indonesia were averted since both the communication campaign and the MDA were designed appropriately for and together with the community. As a result, compliance was sufficient in the first round to successfully begin the elimination process.     

The effect of six rounds of single dose mass treatment with diethylcarbamazine or ivermectin on Wuchereria bancrofti infection and its implications for lymphatic filariasis elimination

Annual mass treatment with single-dose diethylcarbamazine (DEC) or ivermectin (IVM) in combination with albendazole (ALB) for 4-6 years is the principal tool of lymphatic filariasis (LF) elimination strategy. This placebo-controlled study examined the potential of six rounds of mass treatment with DEC or IVM to eliminate Wuchereria bancrofti infection in humans in rural areas in south India. A percentage of 54-75 of the eligible population (> or =15 kg body weight) received treatment during different rounds of treatment - 27.4% in the DEC arm and 30.7% in the IVM arm received all six treatments, 4.8% and 5.6% received none, and the remainder received one to five treatments. After six cycles of treatment, the microfilaria (Mf) prevalence in treated communities dropped by 86% in the DEC arm (P < 0.01) (n = 5 villages) and by 72% in the IVM arm (P < 0.01) (n = 5 villages), compared with 37% in the placebo arm (P < 0.05) (n = 5 villages). The geometric mean intensity of Mf fell by 91% (t = 8.11, P < 0.05), 84% (t = 6.91, P < 0.05) and 46% (t = 2.98, P < 0.05) in the DEC, IVM and placebo arms, respectively. The proportion of high-count Mf (>50 Mf per 60 mm(3) of blood) carriers was reduced by 94% (P < 0.01) in the DEC arm and by 90% (P < 0.01) in the IVM arm. Among those who received all six treatments, 1.4% in the DEC arm and 2.4% in the IVM arm remained positive for Mf. Two of five villages in the DEC arm and one of five in the IVM arm showed zero Mf prevalence, but continued to have low levels of transmission of infection. The results also indicate that DEC is as effective as or slightly better than IVM against microfilaraemia. Results from this and other recent operational studies proved that single-dose treatment with antifilarials is very effective at community level, feasible, logistically easier and cheap and hence a highly appropriate strategy to control or eliminate LF. Higher treatment coverage than that observed in this study and a few more than six cycles of treatment and more effective treatment tools/strategies may be necessary to reduce microfilaraemia to zero level in all communities, which may lead to elimination of LF.     

Prevalence and projections of diabetes and pre‐diabetes in adults in Sri Lanka—Sri Lanka Diabetes,Cardiovascular Study (SLDCS)

Aims To determine the prevalence of diabetes mellitus and pre‐diabetes (impaired fasting glucose and impaired glucose tolerance) in adults in Sri Lanka. Projections for the year 2030 and factors associated with diabetes and pre‐diabetes are also presented. Methods This cross‐sectional study was conducted between 2005 and 2006. A nationally representative sample of 5000 adults aged ≥ 18 years was selected by a multi‐stage random cluster sampling technique. Fasting plasma glucose was tested in all participants and a 75‐g oral glucose tolerance test was performed in non‐diabetic subjects. Prevalence was estimated for those > 20 years of age. Results Response rate was 91% (n = 4532), males 40%, age 46.1 ± 15.1 years (mean ± standard deviation). The age–sex standardized prevalence (95% confidence interval) of diabetes for Sri Lankans aged ≥ 20 years was 10.3% (9.4–11.2%) [males 9.8% (8.4–11.2%), females 10.9% (9.7–12.1%), P = 0.129). Thirty‐six per cent (31.9–40.1%) of all diabetic subjects were previously undiagnosed. Diabetes prevalence was higher in the urban population compared with rural [16.4% (13.8–19.0%) vs. 8.7% (7.8–9.6%); P < 0.001]. The prevalence of overall, urban and rural pre‐diabetes was 11.5% (10.5–12.5%), 13.6% (11.2–16.0%) and 11.0% (10.0–12.0%), respectively. Overall, 21.8% (20.5–23.1%) had some form of dysglycaemia. The projected diabetes prevalence for the year 2030 is 13.9%. Those with diabetes and pre‐diabetes compared with normal glucose tolerance were older, physically inactive, frequently lived in urban areas and had a family history of diabetes. They had higher body mass index, waist circumference, waist–hip ratio, systolic/diastolic blood pressure, low‐density lipoprotein cholesterol and triglycerides. Insulin was prescribed to 4.4% (2.7–6.1%) of all diabetic subjects. Conclusions One in five adults in Sri Lanka has either diabetes or pre‐diabetes and one‐third of those with diabetes are undiagnosed.     

Effectiveness of two annual, single-dose mass drug administrations of diethylcarbamazine alone or in combination with albendazole on soil-transmitted helminthiasis in filariasis elimination programme

A longitudinal community-trial on the control of soil-transmitted helminths (STHs), as part of a lymphatic filariasis elimination campaign, was taken up in two revenue blocks of southern India in the years 2001 and 2002 to assess the impact of two annual single-dose mass drug administration (MDA) of diethylcarbamazine (DEC) + albendazole (ALB) with that of DEC alone. The prevalences and intensities of STHs were studied among cross-sectional samples of school children aged 9-10 years by using the Kato-Katz technique at baseline and 11 months after each MDA. The combined drug mass treatment produced a higher reduction in the prevalence (RIP) (51-77%) and the egg reduction rate (ERR) (92-98%) compared with 12-15% RIP and 58-62% ERR of DEC alone mass treatment. The effect of two-drug therapy after two annual treatments was relatively long lasting as shown by RIP and ERR indicating that the reinfection rates were relatively lower in this approach than single-drug therapy. This study demonstrates that mass drug co-administration of DEC + ALB in Global Programme for Elimination of Lymphatic Filariasis (GPELF) targeted at the community had a synergistic and sustainable effect against soil-transmitted helminthiasis and provided considerable 'beyond filariasis' benefits. The additional advantages accrued to the community underscore the importance of scaling-up GPELF to cover the entire population at risk.     

Efficacy of albendazole and its combinations with ivermectin or diethylcarbamazine (DEC) in the treatment of Trichuris trichiura infections in Sri Lanka

The efficacy of the drugs currently available for treatment of infection with Trichuris trichiura is low compared with that of the drugs used against roundworm and hookworm. Single-dose combinations of albendazole with ivermectin or of albendazole with diethylcarbamazine (DEC) have recently been seen to produce raid and sustained reductions in Wuchereria bancrofti microfilaraemia. This observation prompted the present study, on the efficacy of these combinations against trichuriasis. The drug regimens tested were albendazole (400 mg) alone, albendazole (400 mg) with ivermectin (200 micrograms/kg), and albendazole (400 mg) with DEC (6 mg/kg). Most (155) of the 176 children (4-14 years of age) who each provided a single, pre-treatment, stool sample were found positive for Trichuris ova. These 155 were each randomly allocated to one of the three treatment groups and checked for infection 3 weeks post-treatment, again by a single stool examination. Single-dose therapy with albendazole plus ivermectin produced a 'cure rate' (79.3%) and an egg-reduction rate (93.8%) which were significantly higher than the corresponding rates produced by albendazole alone or albendazole plus DEC (P < 0.01 for each). The efficacies of albendazole with DEC and of albendazole alone were statistically equivalent. Single-dose treatment with the albendazole-ivermectin combination appears to be highly effective against trichuriasis and could prove valuable for routine use.     

Frequency,severity, and costs of adverse reactions following mass treatment for lymphatic filariasis using diethylcarbamazine and albendazole in Leogane,Haiti, 2000

In October 2000, 71,187 persons were treated for lymphatic filariasis using albendazole and diethylcarbamazine (DEC) or DEC alone in Leogane, Haiti. We documented the frequency of adverse reactions, severity and cost of treatment. Adverse reactions were classified as minor, moderate, or severe. Overall, 24% (17,421) of the treated persons reported one or more adverse reactions. There were 15,916 (91%) minor and 1502 (9%) moderate adverse reaction reports. Men outnumbered women 2:1 in reporting moderate problems. Three patients, representing roughly one in 25,000 persons treated, were hospitalized with severe adverse reactions judged to be treatment-associated by physician review. The cost per person treated for adverse reactions was more than twice the cost per person treated for lymphatic filariasis (dollar 1.60 versus dollar 0.71). Severe adverse reactions to lymphatic filariasis treatment using DEC with or without albendazole are uncommon. Minor and moderate reactions are more commonly reported and their management represents a challenge to lymphatic filariasis elimination programs.     

Predictors of compliance with a mass drug administration programme for lymphatic filariasis in Orissa State,India 2008

Objectives To assess the performance of an educational campaign to increase adherence to a mass‐administered DEC regimen against lymphatic filariasis (LF) in Orissa, and to identify factors that could enhance future campaigns. Method Randomized cluster survey, comparing areas that did and did not receive the educational campaign, using a household coverage survey and knowledge, attitudes and practices (KAP) survey. Results LF MDA coverage for the entire population (n = 3449) was 56% (95% CI: 50.0–61.9). There was no statistical difference between the areas that did and did not receive the educational campaign. The most common barriers to adherence were fear of medication side effects (47.4%) and lack of recognition of one’s risk for LF (15.8%). Modifiable, statistically significant, multivariable predictors of adherence were knowing that DEC prevents LF (aOR = 2.6, 95% CI: 1.4–5.1), knowing that mosquitoes transmit LF (aOR = 1.9, 95% CI: 1.1–3.2), and knowing both about the mass drug administration (MDA) in advance and that mosquitoes transmit LF (aOR = 5.4, 95% CI: 2.8–10.4). Conclusions India needs to increase compliance with MDA programmes to reach its goal of interrupting LF transmission. Promoting a simple public health message before MDA distribution, which takes into account barriers to and predictors of adherence, could raise compliance with the LF MDA programme.     

Characteristics and sputum conversion of tuberculosis (TB) patients in Kalutara,Sri Lanka

Background

Tuberculosis (TB) is an infectious bacterial disease; remains as one of the important public health problem affecting every part of the world. Substantial number of TB cases are reported from Sri Lanka every year irrespective of its strong preventive health system. The aim of this analysis is to describe the characteristics of TB patients and to assess the factors associated with sputum conversion. This analysis was based on the data from the District Chest Clinic of Kalutara district, Sri Lanka.

Operational feasibility of lot quality assurance sampling (LQAS) as a tool in routine process monitoring of filariasis control programmes

Lot quality assurance sampling (LQAS) with two-stage sampling plan was applied for rapid monitoring of coverage after every round of mass drug administration (MDA). A Primary Health Centre (PHC) consisting of 29 villages in Thiruvannamalai district, Tamil Nadu was selected as the study area. Two threshold levels of coverage were used: threshold A (maximum: 60%; minimum: 40%) and threshold B (maximum: 80%; minimum: 60%). Based on these thresholds, one sampling plan each for A and B was derived with the necessary sample size and the number of allowable defectives (i.e. defectives mean those who have not received the drug). Using data generated through simple random sampling (SRSI) of 1,750 individuals in the study area, LQAS was validated with the above two sampling plans for its diagnostic and field applicability. Simultaneously, a household survey (SRSH) was conducted for validation and cost-effectiveness analysis. Based on SRSH survey, the estimated coverage was 93.5% (CI: 91.7-95.3%). LQAS with threshold A revealed that by sampling a maximum of 14 individuals and by allowing four defectives, the coverage was >or=60% in >90% of villages at the first stage. Similarly, with threshold B by sampling a maximum of nine individuals and by allowing four defectives, the coverage was >or=80% in >90% of villages at the first stage. These analyses suggest that the sampling plan (14,4,52,25) of threshold A may be adopted in MDA to assess if a minimum coverage of 60% has been achieved. However, to achieve the goal of elimination, the sampling plan (9, 4, 42, 29) of threshold B can identify villages in which the coverage is <80% so that remedial measures can be taken. Cost-effectiveness analysis showed that both options of LQAS are more cost-effective than SRSH to detect a village with a given level of coverage. The cost per village was US dollars 76.18 under SRSH. The cost of LQAS was US dollars 65.81 and 55.63 per village for thresholds A and B respectively. The total financial cost of classifying a village correctly with the given threshold level of LQAS could be reduced by 14% and 26% of the cost of conventional SRSH method.     

Need for a differential criteria to stop mass drug administration,based on an epidemiological perspective of lymphatic filariasis in Thiruvananthapuram,Kerala, India

ObjectiveTo determine the prevalence of any of the clinical manifestations of lymphatic filariasis, parasitological and entomological indices in Thiruvananthapuram district, Kerala, India, prior to launching mass drug administration (MDA) in the district in 2005.MethodsA cross sectional survey was conducted in 7 endemic wards of the district, in a sample of 2 472 individuals above the age of one year. The study consisted of data collection using questionnaire, night blood smear examination and mosquito collection followed by identification and dissection.ResultsThe prevalence of any of the clinical manifestations of filariasis in this endemic area was 3% (73/2 472) (95% CI between 2.3% to 3.7%). The microfilaria rate was found to be 0.38%. Culex quinquefasciatus formed the predominant mosquito species. The vector infection rate was 1.4% and infectivity rate was 0.47%. Half of the population had satisfactory knowledge regarding the disease. In almost an equal number, the knowledge was poor and only about 10% had good knowledge. Most of the people had not heard about the MDA program.ConclusionsThe prevalence of filariasis even in an area considered to be endemic in Kerala, was low. Microfilaraemia was much lower than the clinical manifestations. However, the potential risk of transmission of disease continues. For such areas which had a pre-MDA mf rate less than 1%, there needs to be more stringent criteria for evaluating the effectiveness of the programme, doing transmission assessment surveys and stopping MDA.     

Glycemic and cardiometabolic effects of exercise in South Asian Sri Lankans with type 2 diabetes mellitus: A randomized controlled trial Sri Lanka diabetes aerobic and resistance training study (SL-DARTS)

Background and aimsTo examine the effects of aerobic training (AT) and resistance training (RT) compared to standard care on glycemic control in South Asian Sri Lankan adults with Type 2 Diabetes Mellitus (T2DM).MethodsRandomized controlled trial (RCT) with parallel-group design recruited 86 sedentary Sri Lankans (aged 35–65 years) with T2DM into aerobic training (AT, n = 28), resistance training (RT, n = 28) and control (CN, n = 30) groups. Supervised progressive exercise training consisting of 75 min per session, 2 days per week for 12 weeks was conducted. The primary outcome was pre- and post-intervention absolute change in hemoglobin A1c (HBA1c). Secondary outcomes were serum lipids, liver enzymes, chronic inflammatory status, anthropometry, body composition and blood pressure.ResultsThe absolute change in HbA1c of RT vs. CN was ?0.08% (95% CI, 0.8% to ?0.7%, p = 0.8) and AT vs. CN was ?0.22% (95% CI, 0.95% to ?0.5%). Subgroup analysis (n = 49) with a high baseline HbA1c (>7.5%), absolute reduction in HbA1c in exercise groups were statistically significant (RT vs. CN was ?0.37%; 95% CI 1.3% to ?0.6%, p = 0.04 and AT vs. CN was ?0.57%; 95% CI 1.7% to ?0.6%, p = 0.03). The effect sizes (total and subgroup HbA1c >7.5%) ranged from 0.7 to 1.0 in AT, 0.4 to 1.1 in RT compared to 0.35 to 0.6 for the CN. Secondary outcomes did not significantly differ among groups.ConclusionsExercise training 2 days/week improved glycemic control in Sri Lankan adults with T2DM and the effects were significant in high baseline HbA1c (>7.5%) groups (RT > AT).     

The impact of six rounds of single-dose mass administration of diethylcarbamazine or ivermectin on the transmission of Wuchereria bancrofti by Culex quinquefasciatus and its implications for lymphatic filariasis elimination programmes

Lymphatic filariasis (LF) is targeted for global elimination. Transmission interruption through repeated annual single-dose mass administration of anti-filarial drugs is the mainstay of the LF elimination strategy. This study examined the ability of six rounds of mass administration of diethylcarbamazine (DEC) or ivermectin (IVM) to interrupt transmission of Wuchereria bancrofti by Culex quinquefasciatus, the predominant parasite and vector species, respectively. After six rounds of mass drug administration (MDA), received by 54-75% of the eligible population (> or =15 kg body weight), the resting vector infection and infectivity rates fell by 83% and 79% in the DEC arm, 85% and 84% in the IVM arm and 31% and 45% in the placebo arm, respectively. The landing vector infection and infectivity rates fell by 83% and 94% in the DEC arm, 63% and 75% in the IVM arm and 1% each in the placebo arm, respectively. The filarial larval load per resting mosquito declined by 92% and 93% and per landing mosquito by 83% and 69% in the DEC and IVM arms, respectively. The annual infective biting rate (AIBR) fell from 735 to 93 (87%) in the DEC arm, 422 to 102 (76%) in the IVM arm and 472 to 398 (16%) in the placebo arm. The annual transmission potential (ATP) declined from 2514 to 125 (95%), 1212 to 241 (80%) and 1547 to 1402 (9%) in the DEC, IVM and placebo arms, respectively. However, mosquitoes with infection [microfilaria/larva 1/larva 2 (Mf/L1/L2)] were found in all study villages. Three of five villages in the IVM arm and two of five in the DEC arm recorded no resting mosquitoes with infective-stage (L3) larva. Although the ATP, after six rounds of MDA, fell substantially and remained at 125 and 241 in the DEC and IVM arms, respectively, the cumulative exposure to infective stage larvae (ATP) during the treatment period of 6 years was as high as 2995 in the DEC arm and 1522 in the IVM arm, because of considerable level of transmission during the initial (1-3) rounds of MDA. We conclude that (i) six rounds of MDA, even with 54-75% treatment coverage, can reduce LF transmission very appreciably; (ii) better treatment coverage and a few more rounds of MDA may achieve total interruption of transmission; (iii) high vector densities may partly nullify the reductions achieved in vector infection and infectivity rates by MDA and (iv) achievement of 'true zero' Mf prevalence in communities and 0% infection rate (mosquitoes with Mf/L1/L2) in mosquitoes may be necessary to totally interrupt Culex-transmitted LF.     

The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji

Diethylcarbamazine (DEC), first introduced in 1947, was shown to have strong efficacy and safety for treatment of human lymphatic filariasis, which is caused mostly by a species Wuchereria bancrofti. Many studies to optimize the dosage and treatment schedule of DEC followed, and, based on the results, control programs with various regimens were implemented in different endemic areas/countries. By the mid 1970s, with endorsement by the WHO Expert Committee on Filariasis (3rd report, 1974), the standard DEC regimen for W. bancrofti infection in mass treatment had been established in principle: a total dose of 72 mg/kg of body weight given in 12 divided doses, once weekly or monthly, at 6 mg/kg each. Not long after the committee report, the efficacy of annual single-dose treatment at 6 mg/kg, which is only one twelfth of the WHO-recommended dose in a year, was reported effective in French Polynesia (study period: 1973-78), and later in Samoa (study period: 1979-81). These results were published between 1978 and 1985 in the Bulletin of WHO but received little attention. In the mid 1980s, the efficacy of ivermectin, the first-choice drug for onchocerciasis, against lymphatic filariae came to light. Since the effect at a single dose was remarkable, and often better than DEC, it was predicted that the newly introduced drug would replace DEC. Treatment experiments with ivermectin increased quickly in number. Meanwhile, annual single-dose mass drug administration (MDA) with DEC at 6 mg/kg was under scrutiny in Samoa and Fiji. In the early 1990s, the Samoan study, which covered the entire population of 160,000 with 3 annual MDAs, reported a significant reduction in microfilaria (mf) prevalence and mean mf density, while in Fiji, the efficacy of 5 rounds of annual MDA (total dose, 30 mg/kg) was shown to be as effective as 28 multi-dose MDA spread over 2 years (6 weekly plus 22 monthly treatments at 5 mg/kg; total dose, 140 mg/kg). Several additional studies carried out in Samoa in relation to the annual single-dose MDAs revealed that low density mf carriers, who have a very low mf count of 1-20/ml of venous blood, could not play a significant role in filariasis transmission.From around 1990, studies on spaced low-dose DEC treatments and various types of combination chemotherapy with DEC and ivermectin increased. Albendazole, a well-known anti-intestinal helminths agent, was later added to the combination. The main findings of these studies with W. bancrofti are: (i) a single dose of DEC at 6 mg/kg reduced mean mf density by ca. 90% 1 year after treatment; (ii) the same dose could damage/kill adult worms; (iii) a single dose of ivermectin at ca. 400 μg/kg was more effective than DEC in reducing mf density during the first year and was similarly or less effective in the second year; (iv) ivermectin probably could not kill adult worms; (v) a single combined dose of albendazole (400 mg) and DEC (6 mg/kg) was effective to reduce mf density by 85 to nearly 100% 12-24 months after treatment; and (vi) ivermectin or albendazole included in the combination chemotherapy produced "beyond-filariasis" benefits: clearance/reduction of intestinal helminths, and, additionally, in the case of ivermectin, skin-dwelling ectoparasites.The Global Programme to Eliminate Lymphatic Filariasis (GPELF) started its worldwide activities in 2000, with the target of elimination by 2020. The basic strategy is to conduct annual single-dose MDAs for 4-6 years. In 2000-2007, a minimum of 570 million individuals were treated in 48 of 83 endemic countries. The drugs used are DEC 6 mg/kg plus albendazole 400 mg in most countries, or ivermectin 200-400 μg/kg plus albendazole 400 mg particularly in onchocerciasis endemic countries in Africa. (MDAs with DEC alone had been used in India.)The GPELF achieved impressive results in terms of parasitological cure/improvement, clinical benefits, social and economic impacts, etc. However, the most impressive result of all was the programme's success in mobilizing hundreds of millions of local people, who not only took drugs but many of them actively supported MDAs as drug distributors and volunteers. Beyond filariasis, the role people can play in supplementing rural health services is now a topic of discussion and a source of hope for a new sustainable system.