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.

Mapping trachoma in Nasarawa and Plateau States, central Nigeria.

OBJECTIVES: The World Health Organization has called upon member states to eliminate blinding trachoma by 2020 using the SAFE strategy. We aimed to determine the prevalence of trachoma and quantify intervention needs for each aspect of the SAFE (surgery, mass administration of antibiotics, promotion of facial cleanliness and environmental improvements) strategy in Nasarawa and Plateau States, Nigeria. METHODS: District-based, household cluster surveys were conducted in all 30 local government areas (LGAs) within the states. RESULTS: A total of 46 960 persons were examined from 7883 selected households. Prevalence estimates of trachomatous inflammation follicular among children 1-9 years of age ranged from 1.7 to 15.8% by LGA. Trichiasis prevalence among adults varied by LGA from 0 to 2.1% and was more common among women (OR = 1.99, 95% CI 1.3 to 3.1). Access to water within a 30 min round trip was reported by 82.3% of households. CONCLUSION: LGA-wide trachoma control interventions are warranted in seven LGAs targeting: 5409 persons for surgery to correct trichiasis, 778 698 persons to receive at least three rounds of mass antibiotic distribution, 855 villages in which to promote face-washing and sanitation, and 102 751 households for latrine construction. These mapping surveys demonstrate an example of evidence-based programme planning necessary for measuring progress towards achieving the GET 2020 objective and can be replicated in other areas yet to be mapped for trachoma.

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.

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).

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.

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.

Unexpected autoantibody production in membrane Ig-mu-deficient/lpr mice.

In the B lymphocyte lineage, Fas-mediated cell death is important in controlling activated mature cells, but little is known about possible functions at earlier developmental stages. In this study we found that in mice lacking the IgM transmembrane tail exons (muMT mice), in which B cell development is blocked at the pro-B stage, the absence of Fas or Fas ligand allows significant B cell development and maturation, resulting in high serum Ig levels. These B cells demonstrate Ig heavy chain isotype switching and autoimmune reactivity, suggesting that lack of functional Fas allows maturation of defective and/or self-reactive B cells in muMT/lpr mice. Possible mechanisms that may allow maturation of these B cells are discussed.

Problems and perspectives of managing an onchocerciasis control programme: a case study from Plateau state, Nigeria.

The onchocerciasis control programme in Plateau state (now Plateau and Nasarawa states), Nigeria, was one of the pioneering Mectizan-distribution projects in Nigeria. Although initiated under the River Blindness Foundation (RBF) in 1991, in collaboration with the Ministry of Health, it was absorbed into the Carter Center's Global 2000 River Blindness Programme (GRBP) in 1996. The objectives of the programme were to support the delivery of Mectizan (ivermectin, MSD) to at least 80% of those living in communities where onchocerciasis was highly endemic, within the first 3 years of the project's inception, and to maintain this coverage for a period of 10-15 years. The programme has so far been successful, and much of this success is attributed to problem identification and problem-solving through continuous review and evaluation of programme activities, and implementation of strategies, when required, to ensure those programme objectives are met. The implementation steps of the programme, and some of the managerial problems identified during the course of the effort, are reviewed. The challenge now is to learn how to transform this functional, programme-designed and programme-directed effort into the new community-directed treatment being promoted by the African Programme for Onchocerciasis Control. The new challenges of the transition require middle-level managers and implementors with effective, efficient and indeed state-of-the-art management skills.

Community-based ivermectin distributors: onchocerciasis control at the village level in Plateau State, Nigeria.

The use of community residents as agents for distributing mass ivermectin therapy for onchocerciasis provides a component of community participation absent from mobile team delivery methods. Community-based distribution, however, presupposes preexisting human resources in the endemic villages capable of fulfilling the essential functions of an ivermectin distribution process: mobilizing and educating the population, dispensing the drug, maintaining records, and monitoring and treating adverse reactions. Even when such human resources exist, the community workers must continue to receive tangible support from both external (government and donor agencies) and internal (community) sources. Donor and government agencies must accept that their data collection demands will be limited by the literacy standards of the communities being served. Community leaders must agree to set and use their own local standards of payment (including food stuffs or exchange in kind) to compensate the distributors for their time and efforts. The use of locally available human and remunerative resources is a prerequisite for true community ownership of a program.

Association of pregnancy-induced hypertension with duration of sexual cohabitation before conception.

Pregnancy-induced hypertension affects at least 10% of all pregnancies. An association with first pregnancy or a change in paternity for subsequent pregnancies has been suggested. We studied the duration of sexual cohabitation with the father prior to conception and the incidence of pregnancy-induced hypertension. During a five-month period, 1011 consecutive women who delivered in an obstetric unit were interviewed about paternity and duration of sexual cohabitation before conception. Obstetric charts were abstracted to identify three groups: those with pregnancy-induced hypertension, chronic hypertension, and normal blood pressure. The incidence of pregnancy-induced hypertension was 11.9% among primigravidae, 4.7% among same-paternity multigravidae, and 24.0% among new-paternity multigravidae. For both primigravidae and multigravidae, length of sexual cohabitation before conception was inversely related to the incidence of pregnancy-induced hypertension (p < 0.0001). Similar results were observed after control for race, education, maternal age, marital status, and number of pregnancies. Pregnancy-induced hypertension may be a problem of primipaternity rather than primigravidity. Furthermore, an extended duration of sexual cohabitation before conception may protect against pregnancy-induced hypertension.