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Impact Of Mass Drug Administration On Anopheles-Transmitted Filariasis In Africa: Emerging Data From Ghana And Mali

21 Jan 2008

Source: WHO/TDR

JO Gyapong ¹ , DA Boakye ² , SF Traore ³

¹Health Research Unit, Ghana Health Service, Accra, Ghana
²Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana
³Faculty of Medicine, Pharmacy and Dentistry of Bamako Malaria Research & Training Centre, Bamako, Mali

Working paper for the Scientific Working Group meeting on Lymphatic Filariasis Research, convened by the Special Programme for Research and Training in Tropical Diseases, Geneva, 10–12 May 2005

Full text source: Scientific Working Group, Report on Lymphatic Filariasis, 10–12 May 2005, Geneva, Swizterland, Copyright © World Health Organization on behalf of the Special Programme for Research and Training in Tropical Diseases, 2005, http://www.who.int/tdr/publications/publications/swg_lymph_fil.htm

Introduction

Recent evidence suggests that anopheline transmitted lymphatic filariasis can be eliminated worldwide because of the phenomenon of facilitation. This hypothesis indicates that, at low microfilaria densities, Anopheles vectors of filariasis are less efficient in transmitting Wuchereria bancrofti. This has been borne out by observations in Papua New Guinea where the vector is Anopheles punctulatus [6]. However, it may not be practical to generalize this observation worldwide since the threshold levels of microfilaraemia needed for elimination of anopheline transmitted W. bancrofti lymphatic filariasis (LF) might differ from species to species [16–18]. For example, results from earlier studies in sub-Saharan Africa, on the quantitative relationship between transmission intensity and microfilarial reservoir, indicated variation among members of the An. gambiae complex and An. funestus [3,4,14].

In Ghana, several sympatric Anopheles species are vectors of Wuchereria bancrofti [10]; these species are likely to differ in their vectorial role and capacity to transmit low density microfilaraemia. For example, Appawu et al. [1] observed that no An. arabiensis (a member of the An. gambiae complex) was positive for W. bancrofti although this species formed 9%–14% of An. gambiae s.l. Furthermore, analysis of pooled data for Anopheles mosquitoes from a recent study by Boakye et al. [2] indicated presence of the ‘limitation’ process, although larger samples need to be investigated to determine whether this process occurs only in An. gambiae s.l. or An. funestus or in both of these taxa.

Although the impact of treatment on transmission of LF has not been studied in Ghana, there have been some transmission studies and investigations on the efficacy of different treatment regimes [1,9]. Concerning treatment efficiency, Dunyo and Simonsen [9] observed that re-treatment of Wuchereria bancrofti microfilaraemia with a combination of ivermectin and albendazole resulted one year later in an overall mean reduction in microfilarial intensity of 76.2%. The efficacy of the combination treatment thus appeared to be largely independent of the type of primary treatment given and was multiplicative when used repeatedly. Gyapong [11] evaluated the impact of a single dose of ivermectin in six communities in Ghana after two years (due to unavailability of the drug for re-treatment in the second year); this showed the community microfilaraemia prevalence and intensity to be reduced, respectively, by only 25.5% and 39.5% of pre-treatment levels.

Although LF has been known in Mali since 1912 [19], only a few studies have been aimed at determining disease burden and transmission patterns [13,20]. The data show, however, that the LF infection rate increases from the northern to the southern part of the country, and they confirm the nocturnal periodicity of W. bancrofti. Entomological data have identified the gambiae and funestus complexes as the main vectors of LF in Mali. Recently Coulibaly [7] reported a survey carried out 20 years after a previously reported study in the same endemic area (savannah area). The data show a significant decrease of infection rate in both human and vector in the absence of any control measures. Data from Keita [13] however, on the prevalence of elephantiasis in the country, show that LF is a major public heath problem in Mali.

The Ministry of Health (MOH) coordinating group undertook mapping of LF in eight regions of the country in 2002, and in Bamako, the capital city, in 2004 (supported by WHO). In the eight regions, the infection rate by the immunochromatographic card test (ICT) ranged from 1% in Timbuktu (northern part) to 18.6% in Sikasso (southern part) with a mean infection rate of 7.07% (n = 100 per community). In the capital city (six communes), the average infection rate was 1.5% (n = 5990); four communes were found positive using ICT.

The Lymphatic Filariasis Elimination Programme of the Ghana Health Service and the Malian MOH are undertaking elimination of LF using mass drug administration (MDA) with ivermectin and albendazole. The elimination programmes have been set up in both countries as part of the Global Programme to Eliminate Lymphatic Filariasis using the following strategies:

• Information, education and communication (IEC).

• Mass drug administration to the populations at risk.

• Prevention of disabilities.

• Integration into other programmes at operational, intermediate and central levels.

This provides the opportunity to investigate the impact of MDA on transmission by members of the An. gambiae complex and An. funestus group.

Current state of knowledge and available evidence on impact of MDA on transmission

These studies were organized as multicountry studies with the aim of evaluating the effect of community-based mass chemotherapy on the transmission of LF. The specific objectives were to:

• Determine the infection rates in mosquitoes after two rounds of community-based mass treatment.

• Determine the prevalence of W. bancrofti infection and associated clinical signs after one round of community-based mass treatment.

• Identify and determine the prevalence of adverse events (side effects) associated with mass treatment with albendazole-ivermectin.

• Determine the trend of major entomological and parasitological parameters after two rounds of treatment.

In Ghana, the study sites included eight villages in a district with a record of filariasis endemicity where there had not been any community-wide treatment but which had been earmarked for treatment with ivermectin and albendazole. A census was carried out in all eight villages: all houses were enumerated and demographic data of the inhabitants recorded, including the use of bednets. In Mali, similar baseline data were collected using a common protocol.

Entomological studies (assessing transmission)

Mosquito collection

Each village was divided into four sections and one house per section selected randomly for overnight mosquito collection using the man-landing catch method. Four houses were sampled in each village per night (from July to December, from 2001 to 2004); the mosquitoes were later dissected in the laboratory.

Parasitological studies

Inhabitants surveyed for W. bancrofti infection were randomly selected by computer. The first prevalence survey was conducted during February 2002 before mass treatment of the inhabitants (in March 2002). Subsequent surveys were done in 2003, 2004 and 2005. Each time, the surveys preceded MDA in the communities.

Results

Ghana

The average coverage by MDA in the three years for the eight villages was around 66% (table 1). The lowest coverage was 13.9% in the village of Fawomanye in 2002; this situation improved to 62% and 65% in subsequent years (2003 and 2004, respectively). At the time of writing, treatment had been completed at all sites for 2005 and data were being collected.

Parasitological examination of blood smears has shown a decrease in proportion of positive individuals in the population. In 2002, the proportion was 4.6%; in the most recent survey, in January 2005, this had declined to 0.9% (fig. 1 and table 2).

Figure 1

Table 2

Final analysis of the entomological data for 2005 is being compiled. Data for the first three years showed an overall decreasing trend in the annual transmission potential (ATP) (from 356.2 in 2001, through 296.6 in 2002, to 229.4 in 2003) (fig. 2). However, when this was broken down to the contributions made by different Anopheles species, it was realized that, while the ATP of An. funestus had significantly decreased, that for An. gambiae had not. A critical examination of the data indicated that the ATP is being influenced by collections from one site (Mampong); the current analysis will take this into account. The ATP is mirrored in the annual infective biting rate (fig. 3).

Figure 2

Figure 3

Mali

The treatment coverage based on total study population was 67% with 0.6% having side effects in 2002, and 69.4% with 0.4% having side effects in 2003.

Parasitological and clinical studies

• 2001 sample size: 1141 people, with 29.7 % loss to follow-up in 2004.

• Average infection rate: 9.3% reduction between 2002 and 2004 (fig 4).

  Figure 4

  

  Parasitological data variation before and after treatment (Mali)

• Geometric mean parasitaemia: 19.5% between 2001 and 2004.

• Side effects: 0.6 % in 2002 and 0.4% in 2003.

Entomological studies

• Main vectors: An. gambiae s.l. (>86%) and An. funestus (table 3).

  Table 3

  Species composition (Mali)

  Mali:	An. funestus	An. gambiae s.l	Total no. of mosquitoes examined
  2001	9.9%	90.1%	23 265
  2002	14%	86.0%	12 986
  2003	3.1%	96.9%	18 394
  2004	9.2%	90.8%	13 021

• Infection rate: 73.8% reduction between 2001 and 2004 (after two MDAs) (fig 5).

  Figure 5

  

  Vector infection and infectivity rates, 2001–2004 (Mali)

• Infectivity rate: 94.8% reduction between 2001 and 2004 (after two MDAs) (fig 5).

• Man-biting rate: not affected by the treatment (after two MDAs) (fig 6).

  Figure 6

  

  Vector man-biting rates (MBR) and entomological inoculation rates (EIR), 2001–2004 (Mali)

• Annual transmission potential: 97.25% reduction between 2001 and 2004 (fig 7).

  Figure 7

  

  Vector annual transmission potential, 2001–2004, expressed in number of infective bites per man per year

Summary of the major remaining uncertainties and research questions, and suggestions for specific studies

The observation that Anopheles-transmitted W. bancrofti in the Bongo area of Ghana shows the process of limitation [2] indicates that the situation needs clarification in terms of the species involved in transmission. A similar study to look at specific Anopheles species is necessary.

The study on trends in transmission after MDA in the eight communities in Ghana indicates that some of the vectors (An. gambiae s.s.) are able to pick up the infection and transmit infective larvae at very low levels of microfilaraemia in humans. Although the 2004 entomological analysis is yet to be completed, it may be necessary to consider continuing the study for longer than the five years of MDA planned by the national programme. As now planned, the study will end after four years of MDA, but this may not be enough to arrive at a definite conclusion.

Pichon [15] postulated that low level prevalence and intensity of microfilaraemia may increase the mean lifespan of some of the local Anopheles species and may worsen the problem posed by malaria. How this increase in mean lifespan affects the transmission of W. bancrofti has not, however, been examined.

Issues to be addressed to increase the chances of eliminating lymphatic filariasis by mass drug administration

• Treatment coverage required to have maximum impact and reduce the duration of intervention.

• Untreated people (persistent refusals, migration) as a source of vector infection.

• IEC for better involvement of the population.

• Vector control as an adjunct to MDA.

Suggestions for specific studies

• Impact of insecticide-treated nets on LF transmission: effect of intense use during MDA in high, middle and low transmission areas.

• Finding a good macrofilaricidal drug: other drugs (e.g. if combined with antibiotics) with effects on adult worm (as deduced by sonographic assessment).

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