Lymphatic filariasis elimination efforts in Rufiji, southeastern Tanzania: decline in circulating filarial antigen prevalence in young school children after twelve rounds of mass drug administration and utilization of long-lasting insecticide-treated nets.

BACKGROUND: Lymphatic filariasis (LF) is a parasitic infection transmitted by mosquito vectors, and in Sub-Saharan Africa it is caused by the nematode Wuchereria bancrofti. The disease has been targeted for global elimination with the annual mass drug administration (MDA) strategy. Vector control is known to play an important complementary role to MDA in reducing the transmission of LF. The effects of an MDA and insecticide-treated net intervention implemented in an endemic area of southeastern Tanzania are reported here.
METHODS: A cross-sectional study assessing W. bancrofti circulating filarial antigen (CFA) was conducted in five primary schools in five different villages. Standard one pupils aged 6-9 years were screened for CFA using immunochromatographic test cards (ICT), with a total of 413 screened in 2012 and 659 in 2015. Just after CFA testing, the children were interviewed on their participation in the MDA campaign. Moreover, 246 heads of households in 2012 and 868 in 2015 were interviewed on their participation in MDA and utilization of long-lasting insecticide-treated nets (LLINs).
RESULTS: The prevalence of CFA for the 413 children tested in 2012 was 14.3%, while it was 0.0% for the 659 children tested in 2015. The Tanzanian National Lymphatic Filariasis Elimination Programme reported annual treatment coverage for Rufiji District ranging from 54.3% to 94.0% during the years 2002-2014. The surveyed treatment was 51.6% in 2011 and 57.4% in 2014. With regard to LLINs, possession and utilization increased from 63.4% and 59.2%, respectively, in 2012, to 92.5% and 75.4%, respectively, in 2015.
CONCLUSIONS: The findings suggest that 12 rounds of MDA complemented with vector control through the use of insecticide-treated nets resulted in a marked reduction in W. bancrofti CFA in young school children.

Introduction

Lymphatic filariasis (LF) is a disease of major public health significance, affecting people in the tropical areas of Africa, India, and South and Central America (Michael et al., 1996). It is caused by the filarial nematode Wuchereria bancrofti and is transmitted by a variety of genera of mosquitoes, including Culex, Anopheles, Aedes, and Mansonia (Bockarie Moses et al., 2009). In Sub-Saharan Africa, the most important species of mosquito vector are Anopheles and Culex (Bockarie Moses et al., 2009). Members of the Anopheles gambiae complex Anopheles funestus group and Culex quinquefasciatus have been identified as important filarial vectors in Tanzania (Rwegoshora et al., 2005, Simonsen et al., 2010). Globally, it is estimated that 120 million people are infected with the parasite and approximately one billion are at risk of infection (WHO, 2005). Manifestations of the disease include chronic lymphoedema, elephantiasis involving the limbs and sometimes the genital area, chyluria, and attacks of acute adenolymphangitis (Gasarasi et al., 2000). LF has been ranked as the leading cause of permanent disability in the world (Zeldenryk et al., 2011).

The World Health Organization (WHO) launched a global programme for the elimination of LF (GPELF) in 2000, with the goal of eliminating the disease globally by 2020 (WHO, 2002). The main strategy proposed to achieve LF elimination is the provision of repeated mass drug administration (MDA) with a combination of albendazole and either diethylcarbamazine or ivermectin to people living in endemic areas who are at risk of the disease (Gyapong et al., 2005, Tisch et al., 2005). These drug combinations are mainly microfilaricidal, aimed at reducing the transmission of the parasite. It is assumed that once the community has been treated long enough, levels of microfilariae will be reduced below the required threshold to sustain transmission (Ottesen, 2000). The period required to achieve this goal has been estimated at 4 to 6 years, which corresponds to the reproductive lifespan of the adult W. bancrofti worm (Ottesen, 2012).

It has been suggested that the interruption of transmission of this infection depends on the proportion of the population receiving antifilarial drugs every year. Furthermore, it was estimated that four to six annual rounds of MDA, with a minimum effective coverage of 60–70% of the target population, would be sufficient to interrupt transmission (Michael et al., 2004). However 5 years after the launch of the GPELF, it was concluded that more than four to six annual rounds of MDA may be required to interrupt transmission in many endemic areas (Swaminathan et al., 2012).

Tanzania initiated the implementation of LF control with the launch of the Tanzanian National Lymphatic Filariasis Elimination Programme (NLFEP) in 1997 (Malecela Mwele et al., 2009). The control strategy adopted by NLFEP was to apply annual MDA with a combination of ivermectin (150–200 mg/kg) and albendazole (400 mg) to all individuals aged 5 years and above living in selected endemic areas. In the year 2000, the Tanzanian NLFEP launched its first MDA campaign in Mafia District, in which 45 000 people were treated (Malecela Mwele et al., 2009). The programme has expanded to cover more than 13 million people treated at least once, and the goal is to expand the programme to the entire at-risk population of around 39 million people (Kisoka et al., 2014).

Rufiji District in southeastern Tanzania started implementing MDA in 2002, with a baseline W. bancrofti circulating filarial antigen (CFA) prevalence ranging from 49% to 64% among the community members aged 5 years and above (Ministry of Health and Social Welfare (MoHSW) 2012, unpublished). From 2012, the MDA programme coincided with the universal distribution of long-lasting insecticide-treated nets (LLINs) by the malaria control programme in Tanzania, which aimed to cover 80% of the general population (West et al., 2012). The use of insecticide-treated nets (ITNs) for malaria control has shown a significant effect in lowering filarial rates (Odermatt et al., 2008, Ashton et al., 2011, Njenga et al., 2011).

Monitoring the effect of MDA on the transmission of lymphatic filariasis is crucial for measuring progress towards the elimination goal and also forms the basis for establishing treatment endpoints. Studies have indicated that the monitoring of circulating filarial antigen in young children who are born during the intervention period is a good indicator for assessing the impact of MDA in a community (Simonsen et al., 2010). In endemic regions, children are most susceptible to acquiring the infection because of their lack of immunity and high exposure to infective larvae; infections established in childhood may act as the reservoir for future disease later in life (Lammie et al., 1994).

The use of new sensitive and highly specific diagnostic tools for the detection of CFA released by adult W. bancrofti parasites has shown that many children acquire the infection earlier than was previously thought and that often a considerable proportion of young children are CFA-positive. As reduced transmission will lead to reduced acquisition of infection, it has been suggested that young children be screened to assess the effectiveness of transmission interventions during the LF elimination programme. Children born after the initiation of MDA are of particular interest, as they provide an evaluation sample on the interruption of transmission. The current study monitored the impact of 12 rounds of MDA and the deployment of a universal LLIN coverage intervention on the prevalence of CFA in standard one school children in Rufiji.

Materials and methods

Study site and population

All study sites are located in Rufiji District in southeastern Tanzania (7°57′ S and 38°43′ E), which had a population of 217 274 people in 2012 (National Census 2012, National Bureau of Statistics, Tanzania). The district was purposively selected for this study due to its history of high LF transmission, with a baseline prevalence of W. bancrofti CFA reported at 49% before the start of control activities (MoHSW 2012, unpublished). The study sampled participants from the community (heads of households) and primary schools (standard one children) in the villages of Nyamisati, Mchukwi, Nyanjati, Bungu, and Nyambili in Rufiji. The villages were purposively selected to represent the diverse geographical features of the district. Nyamisati village lies in the coastal belt of the Indian Ocean, while Mchukwi, Nyanjati, Nyambili, and Bungu are inland villages. Each village has only one primary school and all standard one pupils in each school were recruited for the study.

A list of heads of households was obtained from the village officials in the enrolled villages. A simple random sampling technique was applied to obtain participants from each village. The selected participants were identified and recruited into the study. The enrolled heads of households were interviewed to gather information on MDA coverage and ITN use.

The NLFEP in Rufiji District was implemented in 2002. By 2014, the programme had administered 12 rounds of annual MDA, with an interruption in 2005 due to logistical issues. The current study was conducted from April to May in 2012 and was repeated at the same time in 2015, coinciding with the 9th and 12th rounds of MDA, respectively.

Detection of CFA and MDA participation

On the survey dates, all standard one children were invited to participate in the blood screening using the class registers containing the names and sexes of the pupils. They were examined for CFA using immunochromatographic test cards (ICT) (BinaxNOW Filariasis; Inverness Medical Innovations Inc.); the manufacturer’s instructions were followed. Prior to the field survey, two cards from the lot were tested in the laboratory using a positive control obtained from the National Institute for Medical Research, Tanzania. The results for both cards were positive.

In brief, a finger prick was conducted using a sterile disposable lancet after cleaning the finger with an alcohol swab. One hundred microlitres of finger-prick blood was collected using a sterile disposable capillary tube and applied to the test card. The results were read after exactly 10 min as positive, negative, or undetermined. Just after the blood test, the children were interviewed on their age and participation in the previous MDA rounds. To guide the pupils, the drugs used in the MDA were displayed to them and they were then asked if they had swallowed the drugs or not.

Assessment of community participation in MDA and utilization of ITNs

The treatment coverage was obtained using two different methods. The first method involved obtaining the official programme coverage for all administrative wards from the Rufiji District neglected tropical disease (NTD) coordination office. The second method involved interviews with the heads of households within the study villages to determine their participation in the MDA campaign and utilization of ITNs. Participants were asked whether they had participated in previous MDAs and whether household members slept under ITNs. The investigators asked if they could examine the respondents’ bedrooms for the presence of ITNs in each household. Moreover, demographic information for the respondents and their reasons for not taking drugs during MDA rounds were also recorded.

Data analysis

Data were entered into Excel and subsequently analyzed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, NY, USA). For the data analysis, respondents were categorized into three age groups: 15–29 years, 30–49 years, and ≥50 years. Educational status was categorized into four groups: those with no formal education, primary education, secondary education, and post-secondary education. The duration of stay in the village was categorized into four groups: since birth, less than 1 year, 1–5 years, and more than 5 years. The different categories were compared with the Chi-square test. p-Values of ≤0.05 were considered statistically significant.

Ethics

This study was reviewed and approved by the Muhimbili University of Health and Allied Sciences Research Ethics Review Board, as well as the WHO Ethics Review Committee. Permission to conduct the study was obtained from the Executive Director of Rufiji District. The parents/guardians and community were informed of the purpose of the survey through the village meetings. Children were recruited at their respective schools and given consent forms (in Kiswahili) to give to their parents/guardians for consenting. Parents/guardians or school pupils who refused to participate in the surveys were excluded. Verbal consent to participate in the community component of the study was sought from the heads of households prior to the interviews.

Results

CFA prevalence and treatment coverage in pupils

In 2012, 413 children aged between 6 and 9 years were screened for CFA in five selected primary schools. Of those screened, 236 (57.1%) were female and 177 (42.9%) were male. A total of 59 (14.3%) screened pupils were positive for W. bancrofti CFA (Table 1). The prevalence of CFA increased significantly with increasing age of the pupils (Chi-square test of trends, p = 0.016; Table 1). Just a third (33.7%) of the children screened in 2012 reported having swallowed the drugs in the 2011 MDA round. The prevalence of CFA was not significantly different among those who participated (12.2%) and those who did not participate (15.3%) in the 2011 MDA (Chi-square test, p = 0.4).

Table 1

CFA status among standard one school children aged 6 to 9 years in five different primary schools in Rufiji District.

Name of school	2012 Survey				2015 Survey
	No. tested	Sex ratioa	Mean age (years)	CFA positive (%)	No. tested	Sex ratioa	Mean age (years)	CFA positive (%)
Nyanjati	76	0.6	6.9	7 (9.2)	173	0.7	6.87	0.0
Nyamisati	81	0.7	7.6	15 (18.5)	132	1.8	7.86	0.0
Mchukwi	79	0.9	7.5	12 (15.1)	130	1.2	7.68	0.0
Bungu	97	0.7	7.8	16 (16.5)	122	1.1	7.66	0.0
Nyambili	80	0.9	7.4	9 (11.3)	102	1.6	7.73	0.0
Total	413	0.8	7.4	59 (14.3)	659	1.1	7.51	0.0

CFA, circulating filarial antigen.

Ratio of males to females.

In 2015, a total of 659 standard one children aged between 6 and 9 years (mean 7.5 years) were tested for W. bancrofti CFA in the five selected schools. Of the tested pupils, 346 (52.5%) were male and 313 (47.5%) were female. None of the pupils examined tested positive for W. bancrofti CFA (Table 1). With respect to participation in MDA, 54.3% (n = 358) of the tested pupils reported that they had always swallowed the drugs when given out in each MDA round. The same proportion of pupils (54.3%) reported having swallowed the drugs during the last MDA that took place in October 2014 (12th round). Statistical analysis revealed that participation in the MDA was not significantly different with regard to sex (Chi-square test, p = 0.012) or age (Chi-square test, p = 0.15) of the pupils.

Reported and surveyed community treatment coverage

MDA treatment coverage was assessed using two methods: the official NLFEP-reported coverage from the district NTD office and interviews conducted in the study villages (Table 2, Table 3). The NLFEP reported annual treatment coverage for Rufiji District ranging from 54.3% to 94.0% during the years 2002–2014. MDA was not administered in 2005 (Table 2).

Table 2

Official NLFEP treatment coverage for Rufiji District where the five study schools are located.

Year	Target population	No. treated	% treated
2014	226 939	154 319	68.7
2013	217 274	168 930	77.7
2012	203 835	124 747	61.2
2011	170 606	150 133	88
2010	166 682	113 677	68.2
2009	162 848	130 279	80
2008	159 103	115 350	72.5
2007	155 443	116 583	75
2006	151 868	85 046	56
2005	–	–	–
2004	144 962	136 267	94
2003	141 628	123 216	87
2002	138 370	75 135	54.3

NLFEP, Tanzanian National Lymphatic Filariasis Elimination Programme.

Source: Tanzania Neglected Tropical Disease Control Programme.

Table 3

Drug uptake and ownership and use of insecticide-treated nets in relation to population characteristics among interviewed adults in Rufiji District, southeastern Tanzania.

2012 survey				2015 survey
Population characteristics	No. of people (% per category)	Drug uptake (%)	p-Value	Population characteristics	No. of people (% per category)	Drug uptake (%)	p-Value
Gender (n = 246)				Gender (n = 868)
Female	159 (64.6)	72 (45.2)	0.007	Female	471 (54.2)	277 (58.2)	0.254
Male	87 (35.4)	55 (63.2)		Male	397 (45.8)	218 (54.9
Age group (years) (n = 246)				Age groups (years) (n = 868)
15–29	94 (38.2)	43 (45.7)	0.001	15–29	345 (39.7)	182 (52.7)	0.000
30–49	115 (46.7)	65 (56.5)		30–49	357 (41.1)	228 (63.7)
≥50	37 (15.1)	19 (51.3)		≥50	166 (19.1)	85 (73.2)
Education (n = 246)				Education (n = 868)
Not gone to school	40 (25.8)	16 (40)	0.001	No education	224 (25.8)	119 (53.6)	0.001
Primary education	88 (35.8)	45 (51.1)		Primary education	487 (56.2)	286 (58.7)
Secondary education	86 (35.0)	44 (51.1)		Secondary education	139 (16.0)	80 (57.6)
Post-secondary education	32 (13.0)	20 (62.5)		Post-secondary education	18 (2.1)	10 (55.6)
Stay in the village (n = 246)				Stay in the village (n = 868)
Since birth	116 (47.2)	64 (55.2)	0.7	Since birth	413 (47.6)	206 (49.9)	0.004
Less than 1 year	70 (28.5)	33 (47.1)		Less than 1 year	48 (5.5)	23 (47.9)
1–5 years	39 (15.9)	20 (51.3)		1–5 years	103 (11.9)	69 (66.9)
More than 5 years	21 (8.5)	10 (41.7)		More than 5 years	279 (32.2)	172 (61.3)
No answer	0	0		No answer	25 (2.8)	25 (100)
Participated in the last MDA (n = 246)				Participated in the last MDA (n = 868)
Swallowed drugs	127 (51.6)		0	Swallowed drugs	495 (57.0)		0.000
Did not swallow drugs	119 (48.4)			Did not swallow drugs	341 (39.3)
				Don’t remember	32 (3.6)
Possess LLINs (n = 246)				Possess LLINs (n = 868)
Own LLINs	156 (63.4)	79 (50.6)	0.684	Own LLINs	803 (92.5)	440 (54.7)	0.000
Do not possess LLINs	90 (36.6)	48 (53.5)		Do not possess LLINs	65 (7.5)	55 (84.6)
Used LLINs last night (n = 246)				Used LLINs last night (n = 764)
Used	146 (59.2)	74 (50.7)	0.721	Used	576 (75.4)	321 (5.8)	0.004
Not used	100 (40.7)	53 (53)		Not used	188 (24.6)	153 (81.4)

MDA, mass drug administration; LLINs, long-lasting insecticide-treated nets.

Surveyed treatment coverage was assessed by interviews conducted in 2012 and 2015. Demographic information of the respondents in both surveys is presented in Table 3. In the 2012 survey, in which 246 heads of households were interviewed, it was found that the drug uptake in the 2011 MDA campaign was 51.6%. Moreover, participation in more than four previous rounds of MDA was reported to be 33.0%. Analysis by gender, age group, and education level revealed that individuals above 30 years of age were significantly more compliant with the MDA (Table 3).

In the 2015 survey, a total of 868 heads of households were interviewed, of whom 54.2% were female and 45.8% were male. Of these respondents, more than half (57.0%) reported having swallowed the drugs in the 2014 MDA campaign. Only 22.1% reported having swallowed the drugs more than four times in the previous MDA rounds. Analysis by age group revealed that individuals above 30 years of age were significantly more compliant with the MDA (Chi-square test, p = 0.000; Table 3). Being absent during drug distribution was cited as the major reason for not participating in MDA rounds, as presented in Figure 1.

Figure 1

Reasons given for not taking drugs in the last round of mass drug administration (MDA); results are expressed as the percentage of the respondents who did not take drugs in the last MDA in 2015 (n = 370).

Community utilization of LLINs

Heads of households were interviewed on their possession and utilization of LLINs, and if allowed, the interviewer verified the availability of the LLINs. In the 2012 survey, 63.4% of the 246 heads of households interviewed possessed LLINs and 59.2% reported having slept under LLINs the previous night (Table 3). In contrast, in the 2015 survey of 868 heads of households, possession was reported to be 92.5% and sleeping under LLINs the previous night was reported to be 75.4% (Table 3).

Discussion

Since the launch of the GPELF in 2000, countries in endemic areas have initiated LF transmission control activities based on MDA, and progress towards the elimination goal has been reported elsewhere (Ottesen et al., 2008). Moreover, studies have indicated that ITNs lower the prevalence and transmission of LF (Odermatt et al., 2008, Ashton et al., 2011, Njenga et al., 2011). As a reduction in transmission will lead to a simultaneous decrease in acquisition of infection, it has been suggested that young children be screened to assess the effectiveness of transmission control interventions during LF elimination programmes (Witt and Ottesen, 2001). The current study monitored the effect of MDA on LF infection in school children living in the endemic district of Rufiji in southeastern Tanzania. Compliance with MDA and the utilization of ITNs were assessed in the study areas.

Before the onset of LF control activities in Rufiji District, the baseline W. bancrofti CFA in adults was reported to range from 49% to 64% (MoHSW 2012, unpublished). In the current study, surveys conducted in 2012 and 2015, which coincided with the 9th and 12th rounds of MDA, reported W. bancrofti CFA prevalence of 14.3% and 0.0%, respectively. The findings of the 2015 survey indicate a remarkable reduction in W. bancrofti CFA prevalence in young children after 12 rounds of MDA. Based on other studies that have reported a reduction in CFA as a result of MDA (Simonsen et al., 2011, Simonsen et al., 2014), the findings suggest a decrease in acquisition of new infections by young school children as a result of MDA.

Treatment coverage and community compliance are important factors for successful LF elimination through the MDA strategy. It has been shown that in areas with high pre-MDA levels of infection, maintaining high drug intake during MDA is crucial in order to reach the elimination goal within a reasonable time frame (Michael et al., 2004, Michael et al., 2006). In the current study, the overall surveyed drug uptake for 2011 (surveyed in 2012) was 51.6% and for 2014 (surveyed in 2015) was 57.4%. The official reported treatment coverage for the respective years was 88.0% and 68.7%. This suggests that reported MDA coverage was relatively higher than surveyed coverage, as has also been reported elsewhere (Simonsen et al., 2013). The surveyed percentages of drug uptake in the current study were lower than the minimum of 65% required to attain the interruption of LF transmission, and this observation has been documented in other places implementing the programme (World Health Organization, 2011). Lower than optimal drug uptake is a challenge to the success of MDA campaigns in some areas of Tanzania (Kisoka et al., 2014, Simonsen et al., 2014). In the current study, being absent during drug distribution was cited as the major reason for not taking the drugs. This was also noted in studies conducted previously in other parts of Tanzania (Kisoka et al., 2014, Simonsen et al., 2014).

Despite the lower than optimal treatment coverage observed in this study, the survey for CFA in school pupils in 2015 indicated a marked reduction in transmission when compared to 2012 infection levels. These contrasting findings may be due to an increase in ownership and utilization of ITNs, found to be 92.5% and 75.4%, respectively, in the 2015 survey. Of particular relevance, it has been shown that the use ITNs for malaria control has had an effect in reducing filarial rates (Odermatt et al., 2008, Ashton et al., 2011, Kelly-Hope et al., 2013). Moreover, a study conducted in the Coast Region of Kenya reported a sustained reduction in LF transmission despite missed rounds of MDA, due to the impact of the ITN intervention (Njenga et al., 2011). It is thus suggested that the lower drug uptake in this study was complemented by high ITN coverage, which sustained the CFA reductions observed. Although this study recorded a marked reduction in acquisition of new infection by young school pupils in the study areas, a formal transmission assessment survey (TAS) is recommended to establish whether the transmission of LF has been interrupted in Rufiji District.

In conclusion, the findings of this study suggest that 12 rounds of MDA complemented with vector control through the use of ITNs resulted in a marked reduction in W. bancrofti CFA in young school children. It is recommended that a formal TAS is conducted to establish whether the transmission of LF has been interrupted in Rufiji District.

Funding

The study received financial support from TDR, Special Programme for Research and Training in Tropical Diseases, co-sponsored by UNICEF, UNDP, the World Bank, and the WHO (project number HQTDR1409931). The sponsor did not take part in the writing or submission of the manuscript.

Conflict of interest

The authors declare that they have no competing interests.