Cost-effectiveness of triple drug administration (TDA) with praziquantel, ivermectin and albendazole for the prevention of neglected tropical diseases in Nigeria.

Onchocerciasis, lymphatic filariasis (LF), schistosomiasis and soil transmitted, helminthiasis (STH) are all co-endemic in Nigeria. Annual mass drug administration (MDA) with ivermectin (for onchocerciasis), albendazole (for STH and with ivermectin for LF) and praziquantel (for schistosomiasis) is the WHO-recommended treatment strategy for preventive chemotherapy. Separate delivery rounds for distribution of these drugs have been the usual approach to MDA. All three drugs, however, have now been shown to be clinically and programmatically safe for co-administration with what has come to be known as triple drug administration (TDA). We examined the cost savings of converting from separate delivery rounds to TDA in two states in Nigeria. In 2008, eight local government areas received a single round of ivermectin with albendazole followed at least 1 week later by a single round of praziquantel to school-aged children. The following year, a single round was administered with TDA. The number of treated individuals was essentially unchanged during both years (1,301,864 in 2008 and 1,297,509 in 2009) and no change in adverse events was reported. The total programmatic costs for the MDA, not including drug and overhead costs, reduced by 41% from $123,624 to $72,870. Cost savings were limited in larger populations due to economies of scale. TDA is recommended for mature MDA.

The presumptive treatment of all school-aged children is the least costly strategy for schistosomiasis control in Plateau and Nasarawa states, Nigeria.

The results of previous studies in Nigeria indicate that 81% of the villages in Plateau and Nasarawa states probably qualify for the mass administration of praziquantel (PZQ) because of Schistosoma haematobium (SH) and/or S. mansoni (SM) infection. To determine the best strategy, relative costs were modelled for four different programmatic approaches to mass drug administration (MDA) at village level. The approaches considered were (1) village-by-village screening for SH (using dipsticks to test for haematuria), with MDA confined to those villages where at least 20% of school-aged children were found infected; (2) screening for both SM (using Kato-Katz smears) and SH, with MDA confined to those villages where at least 20% of school-aged children were found infected with SH or at least 10% of such children were found SM-positive; (3) the presumptive annual treatment of all school-aged children with PZQ (without village-by-village screening); and (4) the presumptive annual treatment of all eligible adults and children with PZQ. In the MDA in models 1 and 2, treatment is only given to children unless the prevalence of schistosome infection is >or=50%, when adults are also treated. As first-year 'assessment' costs were particularly high for the models that included screening, costs were projected over 5 years for all four models. The total 5-year costs, to cover a population of 30,000, were U.S.$18,673 for the model with screening only for SH, U.S.$36,816 for the model with screening for both SH and SM, U.S. $15,510 for the treatment of all school-aged children, and U.S.$68,610 for the treatment of the entire population. Although the presumptive treatment of school-aged children appeared to be the cheapest approach, it would exclude the community-wide treatment of highly endemic communities, the importance of which needs further study.

Missed treatment opportunities for schistosomiasis mansoni, in an active programme for the treatment of urinary schistosomiasis in Plateau and Nasarawa states, Nigeria.

Both Schistosoma haematobium and S. mansoni are endemic in Nigeria. Since 1999 the ministries of health of Plateau and Nasarawa states, assisted by The Carter Center, have provided mass drug administrations with praziquantel to villages where >20% of the school-aged children tested with urine dipsticks have been found to have haematuria (presumed to be caused by S. haematobium). The current extent of S. mansoni in Nigeria remains relatively unknown because the tests needed to detect human infection with this parasite are difficult to perform in many endemic areas. In a cross-sectional survey involving 924 children, the prevalence of S. mansoni was determined in 30 villages (in four local government areas) that had been excluded from mass praziquantel administrations because the prevalence of haematuria in their school-aged children had been found to be <20%. Seventeen (57%) of the surveyed villages had sufficient S. mansoni (i.e. prevalences of at least 10%) to warrant treatment. The results indicated that, if both S. haematobium and S. mansoni are taken into account, 81% of the villages in the four local government areas studied require treatment, compared with 50% if only S. haematobium is considered. At the moment, the costs of the village-by-village diagnosis of S. haematobium and S. mansoni would be greater than those of the presumptive treatment of the school-aged children in all villages. Until improved and cheaper rapid diagnostic methods for S. mansoni become available, the cheapest approach to the overall problem of schistosomiasis in this part of Nigeria would therefore be wide-spread mass drug distributions, without screening for at-risk populations.

Factors affecting the attrition of community-directed distributors of ivermectin, in an onchocerciasis-control programme in the Imo and Abia states of south-eastern Nigeria.

In areas of Nigeria where onchocerciasis is endemic, community-directed distributors (CDD) distribute ivermectin annually, as part of the effort to control the disease. Unfortunately, it has been reported that at least 35% of the distributors who have been trained in Nigeria are unwilling to participate further as CDD. The selection and training of new CDD, to replace those unwilling to continue, leads to annual expense that the national onchocerciasis-programme is finding difficult to meet, given other programme priorities and the limited resources. If the reported levels of attrition are true, they seriously threaten the sustainability of community-directed treatment with ivermectin (CDTI) in Nigeria. In 2002, interviews were held with 101 people who had been trained as CDD, including those who had stopped serving their communities, from 12 communities in south-eastern Nigeria that had high rates of CDD attrition. The results showed that, although the overall reported CDD attrition was 40.6%, the actual rate was only 10.9%. The CDD who had ceased participating in the annual rounds of ivermectin blamed a lack of incentives (65.9%), the demands of other employment (14.6%), the long distances involved in the house-to-house distribution (12.2%) or marital duties (7.3%). Analysis of the data obtained from all the interviewed CDD showed that inadequate supplies of ivermectin (P<0.01), lack of supervision (P<0.05) and a lack of monetary incentives (P<0.001) led to significant increases in attrition. Conversely, CDD retention was significantly enhanced when the distributors were selected by their community members (P<0.001), supervised (P<0.001), supplied with adequate ivermectin tablets (P<0.05), involved in educating their community members (P<0.05), and/or involved in other health programmes (P<0.001). Although CDD who were involved in other health programmes were relatively unlikely to cease participating in the distributions, they were more likely to take longer than 14 days to complete ivermectin distribution than other CDD, who only distributed ivermectin. Data obtained in interviews with present and past CDD appear vital for informing, directing, protecting and enhancing the performance of CDTI programmes, in Nigeria and elsewhere.

Health care at the end of the road: opportunities from 20 years of partnership in onchocerciasis control.

The unprecedented decision of Merck & Co., Inc., to donate ivermectin through the Mectizan(R) Donation Program, has catalysed an exemplary partnership, to distribute the drug to the communities at risk of onchocerciasis, and empower them to take charge of the drug distribution themselves. Integration with other activities has always been part of the plan, but has been accelerated in recent years because of the need to strengthen primary health care, and to meet the challenges of integrating the rapid impact of Neglected Tropical Disease programmes. Activities that have been integrated include provision of vitamin A capsules, elimination of lymphatic filariasis, the distribution of insecticide-treated nets, and comprehensive eye health. Although these integrated activities show promising results for all programmes involved, challenges still remain. The risk of overburdening communities with multiple activities, and the problem of remuneration at the community level, are the major concerns, as is the need for effective coordination. The expanded onchocerciasis control partnership is a model of translating the eighth Millennium Development Goal (MDG), namely 'develop a global partnership for development', into action and also addresses other key MDGs. In 2006, the partnership provided more than 62 million treatments for onchocerciasis control, and offers a firm foundation from which to deliver other needed health interventions while safeguarding the achievements of onchocerciasis control thus far.

Urban lymphatic filariasis in central Nigeria.

Wuchereria bancrofti and the other mosquito-borne parasites that cause human lymphatic filariasis (LF) infect over 120 million people world-wide. Global efforts are underway to stop transmission of the parasites, using annual, single-dose mass drug administrations (MDA) to all at-risk populations. Although most MDA to date have been in rural settings, they are also recommended in urban areas of transmission. It remains unclear whether there is significant urban transmission in West Africa, however, and the need for urban MDA in this region therefore remains a matter of debate.Clinic-based surveillance, for the clinical manifestations of LF, has now been used to identify areas of urban transmission of W. bancrofti in Jos, the major urban population centre of Plateau state, Nigeria. The eight clinics investigated were all located in slum areas, close to vector breeding sites, and were therefore considered to serve at-risk populations. Over a 1-month period, selected providers in these clinics sought hydrocele, lymphoedema, elephantiasis, or acute adenolymphangitis among the patients seeking treatment. The consenting patients who were suspected clinical cases of LF, and a cohort of patients suspected to be cases of onchocerciasis, were tested for W. bancrofti antigenaemia. All the patients were asked a series of questions in an attempt to determine if those found antigenaemic could only have been infected in an urban area. During the study, 30 suspected clinical cases of LF were detected and 18 of these (including two patients who were found to be antigenaemic) lived in urban areas. Of the 98 patients with exclusively urban exposure who were tested for filarial antigenaemia, six (6.1%) were found antigenaemic. Clinic-based surveillance appears to be a useful tool for determining if there is W. bancrofti transmission in an urban setting.

Mass ivermectin treatment for onchocerciasis: lack of evidence for collateral impact on transmission of Wuchereria bancrofti in areas of co-endemicity.

There has long been interest in determining if mass ivermectin administration for onchocerciasis has 'unknowingly' interrupted lymphatic filariasis (LF) transmission where the endemicity of the two diseases' overlaps. We studied 11 communities in central Nigeria entomologically for LF by performing mosquito dissections on Anopheline LF vectors. Six of the communities studied were located within an onchocerciasis treatment zone, and five were located outside of that zone. Communities inside the treatment zone had been offered ivermectin treatment for two-five years, with a mean coverage of 81% of the eligible population (range 58-95%). We found 4.9% of mosquitoes were infected with any larval stage of W. bancrofti in the head or thorax in 362 dissections in the untreated villages compared to 4.7% infected in 549 dissections in the ivermectin treated villages (Mantel-Haenszel ChiSquare 0.02, P = 0.9). We concluded that ivermectin annual therapy for onchocerciasis has not interrupted transmission of Wuchereria bancrofti (the causative agent of LF in Nigeria).

Community-directed interventions strategy enhances efficient and effective integration of health care delivery and development activities in rural disadvantaged communities of Uganda.

The community-directed interventions (CDI) strategy achieved a desired coverage of the ultimate treatment goal (UTG) of at least 90% with ivermectin distribution for onchocerciasis control, and filled the gap between the health care services and the communities. However, it was not clear how its primary actors--the community-directed health workers (CDHW) and community-directed health supervisors (CDHS)--would perform if they were given more responsibilities for other health and development activities within their communities. A total of 429 of 636 (67.5%) of the CDHWs who were involved in other health and development activities performed better than those who were involved only in ivermectin distribution, with a drop-out rate of 2.3%. A total of 467 of 864 (54.1%) of CDHSs who were involved in other health and development activities also maintained the desired level of performance. They facilitated updating of household registers (P<0.05), trained and supervised CDHWs, and educated community members about onchocerciasis control (P<0.001). Their drop-out rate was 2.6%. The study showed that the majority of those who dropped out had not been selected by their community members. Therefore, CDI strategy promoted integration of health and development activities with a high potential for sustainability.

Significant decrease in the prevalence of Wuchereria bancrofti infection in anopheline mosquitoes following the addition of albendazole to annual, ivermectin-based, mass treatments in Nigeria.

A prospective entomological survey was conducted in four sentinel villages in central Nigeria from 1999-2002, to assess the impact of annual, single-dose, mass drug administrations (MDA), with a combination of ivermectin and albendazole, on the transmission of Wuchereria bancrofti. As they were also endemic for human onchocerciasis, the four villages had received annual MDA based on ivermectin alone for 7 years prior to the addition of albendazole. Resting Anophelines gambiae s. l., An. funestus and Culex species were collected from 92 sequentially sampled households and dissected. Mosquitoes harbouring any larval stage of W. bancrofti were classified as 'infected', and those containing the third-stage larvae of the parasite were classified as 'infective'. Over the 41-month observation period, 4407 mosquitoes were captured and dissected, of which 64% were An. gambiae s. l., 34% An. funestus, and 1% Culex species. The baseline data, from dissections performed before the addition of albendazole to the MDA, showed high prevalences of mosquito infection (8.9%) and infectivity (2.9%), despite apparently good treatment coverages during the years of annual ivermectin monotherapy. Only the anopheline mosquitoes were found to harbour W. bancrofti larvae. After the third round of MDA with the ivermectin-albendazole combination, statistically significant decreases in the prevalences of mosquito infection (down to 0.6%) and infectivity (down to 0.4%) were observed (P<0.0001 for each). The combination of albendazole and ivermectin appears to be superior to ivermectin alone for reducing the frequency of W. bancrofti infection in mosquitoes.

Missed treatment opportunities, for pregnant and breast-feeding women, in onchocerciasis mass-treatment programmes in south-eastern Nigeria.

During annual rounds of mass treatment against onchocerciasis, women who are pregnant or nursing neonates should not to be offered ivermectin. The aim of the present study was to determine how many women were not treated, as a result of this policy, in four villages in south-eastern Nigeria. Of the 1714 women of reproductive age present during the 2000 round of mass treatment, 599 (35%) were excluded because they were pregnant or nursing babies aged < 1 month. Most (56%) of the 599 excluded women were, however, treated individually later in the year. Of the 264 excluded women who did not receive a dose of ivermectin at all in 2000, 123 (47%) said they would have actively sought ivermectin treatment had they been made aware of the short duration of exclusion for nursing. If they had all known of the short duration of the exclusion and when and how to locate and receive treatment in their villages after the round of mass treatment, 91% of the women excluded from the round of mass treatment would probably have been treated later in the year. Better treatment systems, follow-up and health education, targeted at pregnant and lactating women, would improve treatment coverage of this group after parturition and early nursing.

Implementing community-directed treatment with ivermectin for the control of onchocerciasis in Uganda (1997-2000): an evaluation.

Over the period 1997-2000, an evaluation was made, in 10 districts of Uganda, of the onchocerciasis-control programme based on community-directed treatment with ivermectin (CDTI). This programme is supported by the Ministry of Health, the African Progamme for Onchocerciasis Control (APOC) and The Carter Center Global 2000 River Blindness Programme. The data analysed came from: (1) monthly and annual reports; (2) annual interviews, in randomly-selected communities in selected districts, with heads of household, community leaders and ivermectin distributors; (3) participatory evaluation meetings (PEM); (4) participant observation studies; and (5) key informants. The percentage of treated communities in the 10 study districts achieving satisfactory treatment coverage [i.e. > or = 90% of the annual treatment objective (ATO)] rose from 46.0 in 1997 to 86.8 in 2000. This improvement was largely attributable to the adoption of collective CDTI decision-making by community members, avoidance of paving monetary incentives to the ivermectin distributors, and the satisfaction with the programme of those who had been treated. Coverage improved as the numbers of community members who were involved in choosing the method of distribution and in selecting their own community-directed health workers (CDHW) increased. Health education was also critical in improving individual members' involvement in decision-making, and in mobilizing other community members to take part in CDTI. Involvement of kinship groups, as well as educated community members as supervisors of CDHW, also helped to increase coverage. In a regression model, satisfaction with the programme was revealed as a significant predictor of the achievement of the target coverage (P<0.001). Cost per person, as an indicator for sustainability, varied with the size of the population under treatment, from at least U.S. $0.40 when the district ATO was <15,000 people, to U.S. $0.26 with an ATO of 15,000-40,000 and less than U.S. $0.10 when the district ATO exceeded 40,000 people. These results cast doubt on the validity of the current APOC indicator for sustainability, of a cost of no more than U.S. $0.20/person for all CDTI projects, whatever the size of the population to be treated. Although some women were involved in decision-making, their current involvement as supervisors or CDHW was minimal. Most of the present data were obtained through monitoring and operational-research activities that have been carried out, in an integrated fashion, within the Ugandan CDTI programme since its launch. It is recommended that assessment, monitoring and evaluation be widely used within all CDTI efforts. Operational research should remain focused and appropriate and directly involve the personnel who are executing the programme.

The Carter Center's assistance to river blindness control programs: establishing treatment objectives and goals for monitoring ivermectin delivery systems on two continents.

Periodic mass treatment with ivermectin in endemic communities prevents eye and dermal disease due to onchocerciasis. As part of an international global partnership to control onchocerciasis, The Carter Center's Global 2000 River Blindness Program (GRBP) assists the ministries of health in ten countries to distribute ivermectin (Mectizan, donated by Merck & Co.). The GRBP priorities are to maximize ivermectin treatment coverage and related health education and training efforts, and to monitor progress through regular reporting of ivermectin treatments measured against annual treatment objectives and ultimate treatment goals (e.g., full coverage, which is defined as reaching all persons residing in at risk villages who are eligible for treatment). Since the GRBP began in 1996, more than 21.2 million ivermectin treatment encounters have been reported by assisted programs. In 1999, more than 6.6 million eligible persons at risk for onchocerciasis received treatment, which represented 96% of the 1999 annual treatment objective of 6.9 million, and 78% of the ultimate treatment goal in assisted areas.

Community-directed health (CDH) workers enhance the performance and sustainability of CDH programmes: experience from ivermectin distribution in Uganda.

The performance and 'drop-out' rates of ivermectin (Mectizan) distributors in the Ugandan programme for community-directed treatment with ivermectin (CDTI) were investigated and related to the manner in which the distributors were recruited. Distributors, from randomly selected communities endemic for onchocerciasis in seven of the 10 affected districts, were interviewed. Questionnaires were initially completed for 296 communities (in which ivermectin had been distributed in 1998 but not in 1999) and then extended to another 310 communities (in which ivermectin had been distributed in both study years). Discussions were also held with some other community members, in participatory evaluation meetings (PEM) in 14 communities from four districts. Despite the CDTI being labelled as 'community-directed', the first round of interviews and questionnaires revealed that there were in fact three categories of distributors: 322 (69.4%) of those questioned had been selected by community members and were therefore truly community-directed health workers (CDHW) but 101 (22%) were community-based health workers appointed by the leaders of the local council (CBHW-LC) and 41 (9%) were self-appointed volunteers (CBHW-SA). During 1999, only the CDHW received good community support; they still helped to mobilise and educate their community members and advocate CDTI, and 98% of them agreed that they would distribute ivermectin during the following year. In contrast, many of the CBHW-LC were neither supported nor appreciated by the community members. Presumably in consequence, many of the CBHW-LC did not help to mobilise or educate their community members in 1999, nor did they advocate CDTI. Almost all (95%) of the CBHW-LC said that they would not be available to distribute in the following year, and were therefore regarded as total 'drop-outs' from the CDTI. The CBHW-SA were better supported by community members than were the CBHW-LC, they did more to advocate the CDTI, and 93% reported that they would distribute ivermectin during the following year. The 'drop-out' rates for 1999 were < 2% for the CDHW, 7% for the CBHW-SA, and 95% for the CBHW-LC. The results also indicated that the CBHW-SA were not as reliable as the CDHW. Similar results were obtained from the second round of questionnaires, in which 224 (73%) of the interviewees were CDHW, 57 (18%) were CBHW-LC and 28 (9%) were CBHW-SA. The results of the PEM showed that the CDHW, who mainly came from the same kinship groups as the people who selected them, were likely to achieve higher ivermectin coverage within a week than the other categories of distributors. It is clear that, for the optimum performance and sustainability of the CDTI, the distributors used should be CDHW selected by their own community members.

In rural Ugandan communities the traditional kinship/clan system is vital to the success and sustainment of the African Programme for Onchocerciasis Control.

In rural Ugandan communities where onchocerciasis is meso- or hyper-endemic, control of the disease is now being carried out using a strategy of community-directed programmes for the annual distribution of ivermectin to all persons eligible to take the drug. For these programmes to achieve their annual target coverage of at least 90% of the population eligible to take ivermectin, and to continue to sustain themselves for 10-15 years or more, even after external donor funding ceases, it has been found essential to replace the initial community-based strategy, imposed from outside, by a community-directed strategy developed by the community members themselves. Furthermore, it is essential for success that full use be made of the traditional social system, which is very strong in all rural communities in Uganda. This system is based on patrilineal kinships and clans, governed by traditional law, and in it women pay an important role. If this system is ignored or by-passed by government health personnel or by the sponsors and promoters of the programme, the communities are likely to fail to reach their targets. When rural communities increase in size and complexity, following development and the arrival of migrant families, they become semi-urbanized. The kinship/clan system is then weakened, community-directed drug distribution is much more difficult to organize, and coverage targets are not often achieved. This effect is of minor importance in a rural disease, such as onchocerciasis, but is likely to be of greater significance in the control of diseases, such as tuberculosis and lymphatic filariasis, which thrive in urban environments.

Controlling onchocerciasis by community-directed, ivermectin-treatment programmes in Uganda: why do some communities succeed and others fail?

In Uganda, human onchocerciasis is controlled by annual, mass, community-directed, ivermectin-treatment programmes (CDITP) in all endemic communities where the prevalence of the disease is > or = 30%. This is a practical, long-term and cost-effective strategy. In some communities, this system succeeds in providing treatment at the desired level of coverage (i.e. 90% of the annual treatment objective, which is itself equivalent to all those individuals eligible to take ivermectin). Other communities, however, fail to reach this target. The aim of the present study was to determine the factors that were significantly associated with success or failure in achieving this target. The data analysed were answers to a questionnaire completed by 10 household heads randomly selected from each of 64 randomly selected endemic communities (of which 36 succeeded and 28 failed to reach their coverage target) in the four districts of Kabale, Moyo, Nebbi and Rukungiri. Among the programme-related factors investigated, success was associated, at a statistical level of significance (P < or = 0.05), with involvement of community members in: (1) decisions about the execution of the programme; (2) attendance at health-education sessions; (3) selection of the community-based distributors (CDB); and (4) rewarding CBD in kind. In general, the involvement of community members in the planning and execution of a CDITP (and the resultant sense of pride in community ownership) was more likely to produce successful results than when external health workers or even community leaders or local councils took responsibility.

Rural Ugandan communities: the traditional kinship

In rural Ugandan communities where onchocerciasis is meso- or hyper-endemic; control of the diseases is now being carried out using a strategy of community-directed programmes for the annual distribution of ivermectin to all persons eligible to take the drug. For these programmes to achieve their annual target coverage of at least 90of the population eligible to take ivermectin; and to continue to sustain themselves for 10-15 years or more; even after external donor funding ceases; it has beenfound essential to replace the initial community-based strategy; imposed from outside; by a community-directed strategy developed by the community members themselves. Furthermore; it is essential for success that full use be made of the traditional social system; which is very strong in all rural communities in Uganda. This system is based on patrilineal kinships and clans; governed by traditional law; and in it women pay an important role. If this system is ignored or by-passed by government health personnel or by the sponsors and promoters of the programme; the communities are likely to fail to reach their targets. When rural communities semi-urbanized. The kinship/ clan system is then weakened; community-directed drug distribution is much more difficult to organize; and coverage targets are not often achieved. This effect is of minor importance in a rural disease; such as onchocerciasis; but is likely to be of greater significance in the control of diseases; such as tuberculosis and lymphatic filariasis; which thrive in urban environments