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.

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.