Rachel Whelan & Jessie Liu
HumBio 153: Parasites & Pestilence
Identifying challenges for eliminating lymphatic filariasis in Lagos, Nigeria
Introduction. Lymphatic filariasis (LF) is a parasitic infection caused by three mosquito-borne species of nematode worms, Wucheria bancrofti (over 90% of cases), Brugia malayi, and Brugia timori. Worldwide, LF is endemic in 83 countries. An estimated 120 million people are infected with the parasite, and 1.3 billion more (over 20% of the population) are at risk, with most cases in Southeast Asia and sub-Saharan Africa. 9, 21, 22 Although mortality is low, the high morbidity associated with LF and the stigma against its disfiguring symptoms take a heavy economic, psychological, and physical toll18, amounting to 5.55 million DALYs and costing $1 billion/year in Africa13. An estimated 16 million people suffer from lymphoedema or elephantiasis, and 27 million men suffer from hydrocele.12
In response to his public health challenge, in 1997, the 50th session of the World Health Assembly passed a resolution (WHA50.29) to eliminate LF as a public health problem by 2020. Mass drug administration (MDA) of a two- or one- drug regimen over a period of at least 5 years has been shown to effectively interrupt transmission.21
Nigeria has the greatest number of people who are at risk of contracting LF in Africa, but mapping and MDA-based programs have not been implemented in all parts of the country (Figure 1). Lagos, its largest urban center, could potentially see an increase in LF prevalence because of rapid population growth, poor city planning leading to mosquito breeding grounds, lack of MDA-based programs. The WHO is still uncertain about the prevalence of LF in Lagos, because there are many challenges to mapping and LF elimination in urban settings.22 Identifying what challenges the LF elimination program may encounter in a rapidly growing urban center such as Lagos will be critical when designing interventions.
Figure 1. Completion of LF mapping in West Africa. 22
Specific Aims. This project aims to determine the effectiveness of prospective mass drug administration campaigns in Lagos, Nigeria. Specific aims include:
1) Assessing the need for LF mapping and MDA in Lagos
a. Conduct ICT tests and diagnose elephantiasis and hydrocele symptomatically in 6 LGAs in Lagos to determine disease burden
b. Access medical records in hospitals and clinics
2) Exposing the barriers and challenges faced by current MDA-based campaign efforts in Lagos
a. Survey households for burden of disease information, knowledge of the MDA program, and perception of LF
b. Interview / conduct small focus groups with healthcare workers and government officials to evaluate how the MDA program is progressing (e.g., plans on expanding infrastructure to accommodate growing population)
3) Probing expressed willingness to comply with an MDA-based program with or without educational intervention.
4) Making recommendations for assessment/distribution strategy; consider integrating MDA-based LF program with another campaign (e.g. onchocerciasis elimination or insecticide-treated bednet distribution)
Disease Profile. The life cycle of W. bancrofti is described below (Figure 2).
Figure 2. Life Cycle of Wuchereria bancrofti. Courtesy of CDC.
Clinical symptoms vary depending on the vector, host factors, parasitemia, and the periodicity of the parasite. Infected individuals may be asymptomatic for years, while others manifest acute symptoms right away. The acute phase of lymphatic filariasis is characterized by episodic fever and adenolymphangitis, the inflammation of inguinal lymph nodes, testis, spermatic cord, lymphedema, or some combination of these. Recurring lymphedema and inflammation results in permanent lymphatic damage, including chronic swelling, and elephantiasis of the legs, arms, scrotum, vulva, and breasts. In the chronic phase, the most common symptom in males is hydrocele. Acute infection is three times as prevalent as chronic infection.1
Until recently, most W. bancrofti infection diagnoses could only be made through microscope identification of microfilariae in blood samples taken at night. Microfilariae circulate at night (10 p.m. to 2 a.m.), when mosquitoes are more likely to bite, but spend the rest of the day in the microvessels of deep tissue, particularly the lungs, and microfilariae levels are near-undetectable in the blood. (Subperiodic LF is an exception; microfilaremia is detectable at all times). In addition to this limitation, low microfilarial loads may yield false negatives even under examination of thick films. A newer, more convenient and specific test is the immunochromatographic (ICT) card, a field-ready tool that detects the IgG4 antibody as a marker for microfilariae during the day.8 PCR-based detection of a 188-bp sequence of W. bancrofti DNA in mosquitoes can also be used to detect prevalence of parasitic infection of vectors.12 These newer methods allow for high-throughput analysis of human and vector samples that can be taken during the day.
Effective treatments are available for individuals with LF. Previously, it was thought that asymptomatic individuals did not need treatment, but treatment is now advised in all individuals exhibiting microfilaremia to prevent renal and lymphatic disease and as a method of prevention. Treatment options include ivermectin (targets microfilaria), albendazole (targets macrofilaria), and diethylcarbamazine (DEC; targets microfilaria and macrofilaria more slowly). Even a single treatment of a combination therapy that target both microfilaria and macrofilaria is highly effective, and adverse side effects are rare with risk as low as a 1: 4.5M.15
LF elimination and MDA-based programs. In 1997, the World Health Organization’s 50th World Health Assembly recognized the critical public health problems associated with LF, and launched the Global Programme to Eliminate Lymphatic Filariasis (GPELF). GPELF’s goals are to eliminate global LF by 2020 and to mitigate the hardships of individuals with disabilities caused by the disease. Under the auspices of this campaign in December 1997, GlaxoSmithKline agreed to donate enough albendazole free of charge until global LF elimination is achieved. Soon after, Merck offered to expand its ivermectin donation program to areas co-endemic for LF and onchocerciasis. These public-private partnerships, in collaboration with the World Bank and several non-governmental organizations, helped form the basis for the creation of the Global Alliance to Eliminate Lymphatic Filariasis (GAELF) in May 2000.9
It wasn’t until after the formation of GAELF that national governments in countries endemic for LF first began to put serious effort into LF elimination programs. The strategy to interrupt transmission of W. bancrofti has been mass drug administration (MDA) of anthelminthic drugs to entire at-risk populations with one of three WHO-approved oral drug regimens: 1) albendazole (donated by GSK) with ivermectin (Mectizan, donated by Merck & Co.), albendazole with diethylcarbamazine (DEC), or DEC-fortified salt (as in China).21,22 Albendazole with ivermectin is administered in areas where LF is co-endemic with oncocerciasis, because of severe adverse reactions of onchocerciasis patients treated with DEC. For this reason, especially in Africa where the geographic range of the two diseases overlap, the combination of ivermectin and albendazole is favored.21,22 The first two oral drug regimens will reduce the microfilarial load within a given population to below-endemicity levels after 5-10 years of once a year, two-drug treatment. In several countries, the LF elimination program is tacked on to one of several other elimination campaigns to control other diseases such as onchocerciasis, schistosomiasis, and/or malaria.10 Since becoming active in 2000, the LF elimination campaign has increased treatment more than ten-fold.6 In 2000, 25 million individuals were treated in 12 countries for LF worldwide. By the end of 2006, 44 countries were implementing MDA-based programs, targeting a total of 258 million individuals, and 63 had completed LF mapping in their countries.22
Factors that have contributed to the relative success of MDA-based programs include strong political will, strength of public-private partnerships, and biological factors of the parasite. W. bancrofti is an arthropod vector-borne parasite that has no non-human hosts, so decreasing parasitic load in the human population would be sufficient for regulating transmission and prevalence. Free, effective drugs are easy to administer via the oral route, and pharmaceutical companies have agreed to provide enough to achieve elimination. National governments and their ministries of health have cooperated by establishing mapping programs and distribution infrastructure like the community-directed distributors who go door-to-door handing out medications and, in joint programs, handing them out with other medications or bednets.6 However, a dearth of funding can preclude countries from continuing their MDA programs. Since microfilaria load of a population will not decrease below endemicity level unless MDA continues for 5-10 years with 65% coverage, halting the program undoes all the work that was accomplished.13
Individual non-compliance with consumption has been another identified challenge. The rate of MDA coverage in a region is directly dependent upon rate of consumption, which is the most crucial indicator of the success of MDA programs. One study in urban areas of southern India found that consumption rates decrease each successive year in a program, and reasons include adverse reactions to the drug, high mobility of urban populations, and lack of perceived benefits.14 Ramaiah, et al. 2006 found that even supervised consumption may not increase rates of compliance, unless a successful education campaign via media or door-to-door pre-distribution health worker visits is launched well enough in advance.16,17 Education campaigns have been found to be highly successful because people are skeptical of taking a treatment for a disease that they have no symptoms for and they believe they do not have/could not get. Studies have shown that there is a lack of basic knowledge about disease transmission, treatment, and prevention. In the Plateau and Nasarawa states of Central Nigeria, none of the interviewed individuals or focus group participants knew that LF was caused by parasites transmitted by mosquitoes; some cited adultery as the primary cause.10 In another study, half of the 749 individuals interviewed did not believe that elephantiasis is curable by modern medicines.4
Urban environments present additional challenges. Overpopulation, frequent migration, heterogeneous populations, less individual social capital, and poorly-planned city design, make MDA implementation and surveillance difficult.14,16 Rapid population growth often leads to poor city planning and poor sanitation, which result in the creation of mosquito breeding sites and a rise in mosquito vector levels. Greater socioeconomic stratification requires modification of the MDA implementation strategy; lower compliance is found in wealthier populations because wealthy individuals may believe that LF is not a significant health problem in the area and that they would never contract it.16 Also, as Nandha et al. 2007 found, it is more difficult to enter the premises of wealthier households. Urban migration proves to be one of the largest challenges because continuity within the program for more than 5 years is essential for success. For these and other reasons, urban environments report lower rates of coverage and compliance than corresponding rural regions. The focus of MDA campaigns has been in rural areas where disease burden has reportedly been highest, but chances of success are also higher. There have been few MDA programs in urban environments that have been fully evaluated to determine if it would be more efficacious to target subpopulations and communities with higher prevalence or the entire urban population. 18
LF in Lagos, Nigeria. Nigeria has third-largest number of people infected with LF in the world, preceded only by India and Indonesia. 18Nearly one in four Nigerians (25M) are infected with W. bancrofti, and in communities where LF is endemic, up to 10% of women may suffer from swollen limbs and 50% of men from hydrocele. 90 million people are at risk of developing the disease.10 Clinical data evidences that LF prevalence increases with tropical weather from north to south.10 As of 2006, only 16 of the 36 Nigerian states have been fully mapped. 22
Lagos, on the southern coast of Nigeria, remains largely unmapped. At 13.4M residents, it is the largest urban center in Africa and has the second-fastest growth rate in Africa. Lagos also ranks as the fourth densest city in the world, with 18,150 people/km2.7 Socioeconomically, city inhabitants range from very wealthy to very poor. City planning and sanitation have not kept up with population growth, and Lagos currently has no effective garbage collection nor sewage systems.19 Slums with open sewers and areas of standing water are particularly at risk for LF because they promote mosquito breeding.18
The mosquitoes responsible for transmitting W. bancrofti in Nigeria are primarily Anopholine and Culex spp., both of which are common in urban areas15, and A. gambiae populations are increasing in Lagos3,12. A. gambiae can be seen in the cooler, wet season (July-August) while A. arabiensis predominate in the hot, dry season (Nov-March). A. funestus also contributes to LF transmission but isn’t as capable of carrying developing larvae as A. gambiae or A. arabiensis. All mosquitoes become less prevalent in the dry season, but Cu.p. quinquefasciatus can breed in highly polluted water, particularly septic tanks, during the dry months when most surface water has evaporated.11 Mosquitoes positive for W. bancrofti can be found year-round, but transmission is highest during the peak of the rainy season.12
Since bed net use in Nigeria is currently only at 3%, insecticide-treated nets in conjunction with MDA-based programs are the primary prevention strategy in the country.6 In 2006, MDA-based programs in parts of Nigeria that had them targeted 4.5 million people, treated 3.3 million with ivermectin and albendazole, and had a coverage rate of 74%.22
Methods 2, 16, 23
This study will be conducted in four communities in Lagos, Nigeria, each representing different socioeconomic levels: high income, moderate income, low income, and very low income (adapted from Ramaiah et al. 2005). The study design consists of focus group/key informant discussions with community members, household surveys with ICT testing, semi-structured interviews with healthcare workers and government officials, and analysis of hospital records.
Five focus groups/key informant discussions will be conducted in each of four target communities. These discussions will probe:
- Local terminology for LF and LF-related manifestations,
- Community’s perceived needs, health needs, health-seeking behavior, perception of existing health services for LF, onchocerciasis, malaria, and polio
The household survey study population will consist of 600 households distributed evenly between the four communities. Surveys will be created using The Survey System, and they will be conducted by 20 local enumerators/health workers. They will be working in pairs, and each pair will be responsible for 60 houses, 15 in each community. Enumerators/health workers will be required to have had some health background and will be intensely trained for 2 weeks on how to conduct the ICT test and how to use handheld PDAs to conduct interviews. Two visits will be made to each household. The first visit to each HH will consist of:
- A baseline survey for
o individuals’ health concerns
o knowledge about LF (transmission, risk, prevention, and treatment)
o any past medical history with LF, onchocerciasis, malaria, polio
o willingness to comply with an MDA-based program and probe reasons for hesitance
o socioecomic status
- ICT tests and symptomatically look for cases of elephantiasis and hydrocele
Each of the four communities (with 150 HH each) will be divided into five cohorts, with 30 HH per cohort. In the second visit:
- Cohort #1 will receive their individual ICT test results.
- Cohort #2 will receive individual ICT test results as well as the compiled test results of the people tested in their community
- Cohort #3 will receive an educational pamphlet about LF transmission, prevention, and treatment
- Cohort #4 will receive an educational pamphlet AND their individual ICT results
- Cohort #5 will receive an educational pamphlet, their individual ICT results, and community results
During the second visit, all HH will be asked again their willingness to comply with an MDA-based program targeting LF. Survey results will be analyzed using SPSS. Hospital medical records on the number of patients who had LF-related symptoms will also be analyzed.
Interviews/focus group discussions will also be conducted with healthcare workers and government officials to assess current plans for MDA-based implementation of LF interventions in Lagos. Specifically, if there is a plan, we would ask questions regarding whether subpopulations at greater risk will be targeted first, if there are any plans for integration with the onchocerciasis elimination or bednet distribution campaign, and if there are any plans on how to accommodate a growing population and potentially greater disease burden.
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