Abel Eigege

Epidemiological and Entomological Evaluations after Six Years or More of Mass Drug Administration for Lymphatic Filariasis Elimination in Nigeria

The current strategy for interrupting transmission of lymphatic filariasis (LF) is annual mass drug administration (MDA), at good coverage, for 6 or more years. We describe our programmatic experience delivering the MDA combination of ivermectin and albendazole in Plateau and Nasarawa states in central Nigeria, where LF is caused by anopheline transmitted Wuchereria bancrofti. Baseline LF mapping using rapid blood antigen detection tests showed mean local government area (LGA) prevalence of 23% (range 4–62%). MDA was launched in 2000 and by 2003 had been scaled up to full geographic coverage in all 30 LGAs in the two states; over 26 million cumulative directly observed treatments were provided by community drug distributors over the intervention period. Reported treatment coverage for each round was ≥85% of the treatment eligible population of 3.7 million, although a population-based coverage survey in 2003 showed lower coverage (72.2%; 95% CI 65.5–79.0%). To determine impact on transmission, we monitored three LF infection parameters (microfilaremia, antigenemia, and mosquito infection) in 10 sentinel villages (SVs) serially. The last monitoring was done in 2009, when SVs had been treated for 7–10 years. Microfilaremia in 2009 decreased by 83% from baseline (from 4.9% to 0.8%); antigenemia by 67% (from 21.6% to 7.2%); mosquito infection rate (all larval stages) by 86% (from 3.1% to 0.4%); and mosquito infectivity rate (L3 stages) by 76% (from 1.3% to 0.3%). All changes were statistically significant. Results suggest that LF transmission has been interrupted in 5 of the 10 SVs, based on 2009 finding of microfilaremia ≥1% and/or L3 stages in mosquitoes. Four of the five SVs where transmission persists had baseline antigenemia prevalence of >25%. Longer or additional interventions (e.g., more frequent MDA treatments, insecticidal bed nets) should be considered for ‘hot spots’ where transmission is ongoing.

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

Abstract 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

Long-Lasting Insecticidal Nets Are Synergistic with Mass Drug Administration for Interruption of Lymphatic Filariasis Transmission in Nigeria

123, 624 to

Contributions of different mosquito species to the transmission of lymphatic filariasis in central Nigeria: implications for monitoring infection by PCR in mosquito pools.

72, 870. Cost savings were limited in larger populations due to economies of scale. TDA is recommended for mature MDA.

Status of Onchocerciasis Transmission after More Than a Decade of Mass Drug Administration for Onchocerciasis and Lymphatic Filariasis Elimination in Central Nigeria: Challenges in Coordinating the Stop MDA Decision

In central Nigeria Anopheles mosquitoes transmit malaria and lymphatic filariasis (LF). The strategy used for interrupting LF transmission in this area is annual mass drug administration (MDA) with albendazole and ivermectin, but after 8 years of MDA, entomological evaluations in sentinel villages showed continued low-grade mosquito infection rates of 0.32%. After long-lasting insecticidal net (LLIN) distribution by the national malaria program in late 2010, however, we were no longer able to detect infected vectors over a 24-month period. This is evidence that LLINs are synergistic with MDA in interrupting LF transmission.

Triple drug administration (TDA), with praziquantel, ivermectin and albendazole, for the prevention of three neglected tropical diseases in Nigeria.

Background Members of the Anopheles gambiae complex are important vectors of lymphatic filariasis (LF) in sub-Saharan Africa, but little is known about the relative contributions of all mosquitoes to lymphatic filariasis transmission in this area. Methods Over a 28 month period, mosquitoes were collected from 13 villages in Plateau and Nasarawa states in central Nigeria and dissected to determine W. bancrofti infection status. Wings and legs from a subset of the mosquitoes visually identified as A. gambiae s.l. were identified by PCR as either A. gambiae s.s. or A. arabiensis. Results A. gambiae s.s peaked in abundance during the rainy season while A. arabiensis predominated during drier parts of the year. Both species were found equally likely to be infected with the developing stages (L1-L3) of W. bancrofti (9.2% and 11.1%, respectively). Fewer A. funestus (1.1%, p < 0.001) were infected than A. gambiae s.l. Conclusion Understanding the relative contributions of morphologically indistinguishable species to LF transmission is essential if PCR is to be performed on mosquito pools. In the study area, the use of mosquito pools composed of A. gambiae sibling species would not be problematic, as both A. gambiae s.s. and A. arabiensis contribute equally to LF transmission.

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

Background This study was undertaken in five onchocerciasis/lymphatic filariasis (LF) co-endemic local government areas (LGAs) in Plateau and Nasarawa, Nigeria. Annual MDA with ivermectin had been given for 17 years, 8 of which were in combination with albendazole. In 2008, assessments indicated that LF transmission was interrupted, but that the MDA had to continue due to the uncertain status of onchocerciasis transmission. Accordingly, assessments to determine if ivermectin MDA for onchocerciasis could be stopped were conducted in 2009. Methods We evaluated nodule, microfilarial (mf) skin snip, and antibody (IgG4 response to OV16) prevalence in adults and children in six sentinel sites where baseline data from the 1990s were available. We applied the 2001 WHO criteria for elimination of onchocerciasis that defined transmission interruption as an infection rate of <0.1% in children (using both skin snip and OV16 antibody) and a rate of infective (L3) blackflies of <0.05%. Results Among adult residents in sentinel sites, mean mf prevalence decreased by 99.37% from the 1991–1993 baseline of 42.95% (64/149) to 0.27% (2/739) in 2009 (p<0.001). The OV16 seropositivity of 3.52% (26/739) among this same group was over ten times the mf rate. No mf or nodules were detected in 4,451 children in sentinel sites and ‘spot check’ villages, allowing the exclusion of 0.1% infection rate with 95% confidence. Seven OV16 seropositives were detected, yielding a seroprevalence of 0.16% (0.32% upper 95%CI). No infections were detected in PCR testing of 1,568 Simulium damnosum s.l. flies obtained from capture sites around the six sentinel sites. Conclusion Interruption of transmission of onchocerciasis in these five LGAs is highly likely, although the number of flies caught was insufficient to exclude 0.05% with 95% confidence (upper CI 0.23%). We suggest that ivermectin MDA could be stopped in these LGAs if similar results are seen in neighboring districts.

Assessing the WHO 50% Prevalence Threshold in School- Aged Children as Indication for Treatment of Urogenital Schistosomiasis in Adults in Central Nigeria

Schistosomiasis, onchocerciasis and lymphatic filariasis (LF) are co-endemic ‘neglected tropical diseases’ in the Plateau and Nasarawa states of central Nigeria, with each infection reaching levels of endemicity that justify a preventive strategy of annual mass drug administrations (Hopkins et al., 2002; Richards et al., 2006; WHO, 2006). In these areas, community-based distributors (CBD), working with the support of the national Ministry of Health and staff from The Carter Center in Nigeria, have safely provided over 900,000 praziquantel treatments for schistosomiasis, and over 15,000,000 ivermectin–albendazole treatments for LF and onchocerciasis since 1999. Although there have been no serious adverse events associated with any of these activities, there have been concerns about interactions between the praziquantel and the ivermectin–albendazole combination, and these have led to each praziquantel distribution being temporally separated from the mass drug administrations against LF and onchocerciasis, by at least 1 week. If safe, a triple drug administration, with praziquantel, ivermectin and albendazole given concurrently, could save money and reduce the workloads of the distributors and programme staff. In a recent study, NaBangchang et al. (2006) found no evidence of any clinically relevant pharmacokinetic interactions in uninfected volunteers given ivermectin, praziquantel and albendazole concurrently, and the adverse reactions observed were no more common or more severe than those observed when each drug was given individually. These encouraging results paved the way to the implementation of ‘triple drug administrations’ (TDA) in co-endemic areas and the further integration of preventive chemotherapy. A ‘roll-out’ monitoring of such a TDA strategy in central Nigeria was encouraged in early 2006, by the Nigerian Minister of Health and the World Health Organization’s Regional Office for Africa, in consultation with the World Health Organization in Geneva, Merck and Co., Inc. (the donators of ivermectin) and GlaxoSmithKline (the donators of albendazole). The protocol for the pilot study described below received national ethical clearance from the Federal Ministry of Health of Nigeria, and was approved by the Plateau State Ministry of Health. One aim of the study was to provide each eligible individual living in five villages in the Mikang local government area of Plateau state with albendazole (400 mg), ivermectin (150 mg/kg) and praziquantel (40 mg/kg) at the same time. The praziquantel tablets used (DistocideH; Shin Poong, Seoul) each contained 600 mg of the drug and were triple-scored. The albendazole tablets were fruit-flavoured, to assist with compliance. To be eligible for treatment, a person had to be resident in an endemic area, not seriously ill, not pregnant or nursing a child under 1 week of age, and to be at least 94 cm tall (WHO, 2006). Each of the study villages had received two annual rounds of ivermectin–albendazole (in 2004 and 2005) and one of praziquantel (in 2005). Since the risk of adverse events is usually greatest after the first round of mass drug Annals of Tropical Medicine & Parasitology, Vol. 102, No. 2, 177–179 (2008)

Evidence for Stopping Mass Drug Administration for Lymphatic Filariasis in Some, But Not All Local Government Areas of Plateau and Nasarawa States, Nigeria

Abstract 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.

Criteria to Stop Mass Drug Administration for Lymphatic Filariasis Have Been Achieved Throughout Plateau and Nasarawa States, Nigeria

Preventive chemotherapy with praziquantel is recommended in adults by the World Health Organization when prevalence of schistosomiasis in school-aged children (SAC) is ≥ 50%. This study ascertained the value of this threshold in predicting prevalence and intensity of Schistosoma hematobium (SH) infection in adults in central Nigeria. We evaluated urogenital schistosomiasis prevalence in 1,164 adults: 659 adults in 12 communities where mean hematuria among SAC in 2008 was 26.6% and 505 adults in 7 communities where the mean hematuria among SAC in 2008 was 70.4%. No statistically significant differences were found between the two groups of adults in prevalence of hematuria, prevalence of SH eggs, or intensity of infections. We conclude that, in this setting, the SAC threshold is not useful for treatment decisions in adults. Given the increased risk of subtle morbidity or urogenital schistosomiasis as a risk factor for human immunodeficiency virus (HIV), more liberal treatment of adults with praziquantel is warranted.