The n e w e ng l a n d j o u r na l of m e dic i n e

original article

Insecticidal Bed Nets and Filariasis

Transmission in Papua New Guinea
Lisa J. Reimer, Ph.D., Edward K. Thomsen, M.Sc., Daniel J. Tisch, Ph.D.,
Cara N. Henry-Halldin, Ph.D., Peter A. Zimmerman, Ph.D., Manasseh E. Baea,
Henry Dagoro,* Melinda Susapu, B.A., Manuel W. Hetzel, Ph.D.,
Moses J. Bockarie, Ph.D., Edwin Michael, Ph.D., Peter M. Siba, Ph.D.,
and James W. Kazura, M.D.

A bs t r ac t

Background
Global efforts to eliminate lymphatic filariasis are based on the annual mass ad- From the Papua New Guinea Institute of
ministration of antifilarial drugs to reduce the microfilaria reservoir available to Medical Research, Goroka and Madang
(L.J.R., E.K.T., M.E.B., H.D., M.W.H.,
the mosquito vector. Insecticide-treated bed nets are being widely used in areas in P.M.S.), and the Papua New Guinea De-
which filariasis and malaria are coendemic. partment of Health, Port Moresby (M.S.)
— all in Papua New Guinea; Case West-
ern Reserve University, Cleveland (L.J.R.,
Methods E.K.T., D.J.T, C.N.H.-H., P.A.Z., J.W.K.);
We studied five villages in which five annual mass administrations of antifilarial Liverpool School of Tropical Medicine,
drugs, which were completed in 1998, reduced the transmission of Wuchereria ban- Liverpool, United Kingdom (L.J.R., E.K.T.,
M.S., M.J.B.); University of Queensland,
crofti, one of the nematodes that cause lymphatic filariasis. A total of 21,899 anoph- School of Population Health, Herston,
eles mosquitoes were collected for 26 months before and 11 to 36 months after bed Australia (M.W.H.); and the University of
nets treated with long-lasting insecticide were distributed in 2009. We evaluated the Notre Dame, South Bend, IN (E.M.). Ad-
dress reprint requests to Dr. Kazura at
status of filarial infection and the presence of W. bancrofti DNA in anopheline mos- the Center for Global Health and Dis­
quitoes before and after the introduction of insecticide-treated bed nets. We then eases, Case Western Reserve University,
used a model of population dynamics to estimate the probabilities of transmission School of Medicine, 2109 Adelbert Rd.,
Suite 431, Cleveland, OH 44106-4983, or
cessation. at [email protected].

Results Dr. Reimer and Mr. Thomsen contributed

equally to this article.
Village-specific rates of bites from anopheline mosquitoes ranged from 6.4 to 61.3
bites per person per day before the bed-net distribution and from 1.1 to 9.4 bites for *Deceased.
11 months after distribution (P<0.001). During the same period, the rate of detec- N Engl J Med 2013;369:745-53.
tion of W. bancrofti in anopheline mosquitoes decreased from 1.8% to 0.4% DOI: 10.1056/NEJMoa1207594
(P = 0.005), and the rate of detection of filarial DNA decreased from 19.4% to 14.9% Copyright © 2013 Massachusetts Medical Society.

(P = 0.13). The annual transmission potential was 5 to 325 infective larvae inoculated
per person per year before the bed-net distribution and 0 after the distribution.
Among all five villages with a prevalence of microfilariae of 2 to 38%, the probabil-
ity of transmission cessation increased from less than 1.0% before the bed-net dis-
tribution to a range of 4.9 to 95% in the 11 months after distribution.

Conclusions
Vector control with insecticide-treated bed nets is a valuable tool for W. bancrofti
elimination in areas in which anopheline mosquitoes transmit the parasite. (Funded
by the U.S. Public Health Service and the National Institutes of Health.)

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 The n e w e ng l a n d j o u r na l of m e dic i n e

L
ymphatic filariasis is a parasitic- ervoir diminishes, whereas the converse occurs
worm infection caused by Wuchereria ban- in lymphatic filariasis transmitted by culicine
crofti, Brugia malayi, and B. timori that affects mosquitoes.13 In both systems, a decrease in the
approximately 120 million people in Africa, Asia, rate of mosquito bites will increase the worm
the Pacific, and the Americas.1 Adult filarial breakpoint (i.e., the threshold below which the
worms live in the lymphatic system, causing lymph- prevalence of microfilariae spontaneously moves
edema of the limbs, elephantiasis, and hydrocele. to zero).10 Therefore, the elimination of lymphatic
Fecund adult female worms release micro­f ilariae, filariasis becomes more attainable if vector con-
which ultimately enter the bloodstream, where trol accompanies mass drug-administration cam-
they are ingested by anthropophilic mosquitoes paigns. Elimination end points may also be af-
of various genera. Microfilariae develop through fected by differences in local endemicity, infection
several stages in mosquito vectors until they be- aggregation, and the magnitude of acquired im-
come infective larvae (L3), which continue trans- munity.10 For example, the worm breakpoint has
mission by establishing infection in humans been estimated to differ among neighboring vil-
through the bite site created during blood feed- lages in Papua New Guinea, where Anopheles punctu-
ing. Safe, single-dose, inexpensive drug regimens latus is the primary vector.11 These difficulties
have been developed that significantly reduce suggest that a uniform global strategy for perma-
blood loads of microfilariae in humans for more nent cessation of transmission of lymphatic fila-
than a year. For this reason, lymphatic filariasis riasis may not be resilient and that a lack of vector
has been targeted for global elimination by the control may hinder progress toward this goal.14
year 2020 on the basis of annual mass adminis- The possibility of including vector control as
tration of single-dose albendazole combined with part of programs to eliminate lymphatic filariasis
either ivermectin or diethylcarbamazine for 5 or has received increased attention.15,16 In sub-Saha-
more years, the estimated reproductive life span ran Africa and Papua New Guinea, where anoph-
of adult worms, which is anticipated to break the eles species transmit both W. bancrofti and malaria,
transmission of lymphatic filariasis from hu- there is the opportunity to integrate the elimina-
mans to mosquitoes.2,3 tion of lymphatic filariasis with national malaria-
Although this effort has had successes, in- control programs in which vector interventions
cluding the distribution of drugs to 570 million are an essential component.17 Observations made
people in 48 countries,4 it is faced with several during malaria-eradication efforts in the Solomon
challenges.5 Annual treatment of at least 80% of Islands from 1974 through 1977 support the effi-
eligible persons is key to elimination, but this level cacy of vector control, since indoor residual spray-
of population coverage has proved to be difficult to ing with insecticides decreased the prevalence of
achieve in some areas because of health-system microfilariae from 22% to 0% without the use of
constraints6 and human migration.7 Financial and antifilarial drugs.18 Currently, the most widely
political limitations constrain the sustainability implemented vector intervention used by malaria-
of control programs for lymphatic filariasis,8 and control programs is universal coverage with insec-
there is the possibility of drug resistance develop- ticide-treated bed nets. However, only one study in
ing in the parasite population.9 Finally, elimination Kenya has examined the effect of conventional
thresholds are site-specific and unknown in most permethrin-impregnated nets on W. bancrofti trans-
areas.10-12 Therefore, program managers in coun- mission by anophelines,19 and there are no data
tries in which lymphatic filariasis is endemic may that quantify how the use of bed nets treated
lack the evidence necessary to make informed deci- with long-lasting insecticide will complement the
sions regarding whether to conclude, continue, or mass administration of anti­f ilarial drugs in re-
reinstitute mass drug-administration campaigns. ducing transmission of lymphatic filariasis and
Heterogeneities in elimination thresholds for the probability of cessation of transmission.
lymphatic filariasis are due largely to differences We measured the transmission of lymphatic
in vector–parasite relationships. In anopheline filariasis in five villages in the East Sepik Prov-
mosquitoes, the proportion of microfilariae that ince of Papua New Guinea before and after a
develop to become infective larvae decreases as nationwide bed-net distribution effort in 2009.
the number that are ingested decreases, making Communities in this area had received the last
this vector less efficient as the microfilaria res- of five annual treatments with antifilarial drugs

746 n engl j med 369;8  nejm.org  august 22, 2013

 Insecticidal Bed Nets and Filariasis Tr ansmission

more than 10 years earlier (1998) with no subse- Study Participants

quent interventions until 2009. Since entomologic Mosquito collectors and village residents who par-
and human-infection data from this earlier time ticipated in surveys of the prevalence of microfi-
were available,20 we were able to compare mass lariae and bed nets provided written informed
drug administration alone and the distribution of consent after protocols were approved by the in-
insecticide-treated bed nets alone with respect to stitutional review boards at University Hospitals
the effect on the rate of transmission of lymphatic Case Medical Center in Cleveland, the Institute of
filariasis in the same region. Medical Research, and the Medical Research Ad-
visory Committee in Papua New Guinea.
Me thods
Prevalence of Microfilariae
Study Area We measured the prevalence of microfilariae in
Lymphatic filariasis is highly endemic in Papua 2008, before the distribution of insecticide-treat-
New Guinea, where it is estimated that 4.4 million ed bed nets, by counting the number of microfi-
of the country’s 6.3 million residents live in areas lariae in a 1-ml sample of nocturnally collected
that qualify for disease elimination.21 We selected venous blood after passing it through a 5-μm poly-
five villages in the Ambunti-Dreikikir District of carbonate filter.
East Sepik Province for entomologic surveys and
quantification of the prevalence of microfilariae Mosquito Collection and Analysis
(Fig. 1). Transmission of lymphatic filariasis in Mosquitoes were collected monthly after landing
these villages has been well characterized.20,22-24 on human adult collectors from July 2007 through
We present our findings in the context of his- July 2010. The collectors sat outdoors within sev-
torical endemicity levels on the basis of annual eral meters of the household entrance from 6 p.m.
transmission potentials (the number of infective to 6 a.m. with their lower legs and feet exposed.
larvae that were inoculated per person per year), Collectors worked in teams, with one member
which were measured before a trial of mass ad- collecting from 6 p.m. to midnight and the other
ministration of antifilarial drugs conducted from from midnight to 6 a.m. Mosquitoes landing in
1993 through 1998.22 search of a blood meal were captured with an

High Moderate
Endemicity Endemicity
INDONESIA

Peneng

PAPUA NEW GUINEA Albulum

Nanaha Dreikikir
Yauatong

Ngahmbule

142.70° 142.75°
142.75

VANUATU

FIJI
AUSTRALIA

Figure 1. Location of Study Villages in East Sepik Province, Papua New Guinea.

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 The n e w e ng l a n d j o u r na l of m e dic i n e

aspirator and stored according to the hour they children if they had slept under a bed net the
were collected. Each village was divided into four previous night.
hamlets, with monthly collections in each ham-
let. The total effort each month varied from 40 to Statistical Analysis
48 collection nights. Mosquitoes were morpho- We estimated the daily mosquito-biting rates on
logically identified as A. punctulatus, A. koliensis, or the basis of the mean number of host-seeking
A. farauti sensu lato, according to criteria established anopheline mosquitoes that were collected in a
previously,25 and were stored according to species, 12-hour period. We calculated annual transmission
location, and hour collected. Half the mosquitoes potentials by multiplying the mean daily biting
were stored in 70% ethanol for later dissection rate in the community by 365, which was then
and the other half on silica gel for DNA diagnostic multiplied by the proportion of bites that were
evaluation, as described below. A total of 10,578 infective and by the mean number of L3 larvae per
mosquitoes were stained individually with Mayer’s infective bite. We used the Mann–Whitney U test
hemalum,26 separated into body sections on a glass to compare biting rates before and after bed-net
slide, and dissected with forceps and needles un- distribution and Fisher’s exact test to compare
der a microscope. Dissected specimens were ex- rates of mosquito infection and infectivity before
amined for W. bancrofti in the infective larval and after bed-net distribution. All statistical analy-
stage and other developing larval stages (L1 and ses were performed with the use of PASW Statis-
L2) with the use of standard criteria.27 tics, version 17.0.3 (IBM).
Genomic DNA was extracted from unfed dried We used a numerical-modeling and Bayesian
mosquitoes singly or in pools of two (Qiagen). analysis method that was based on the mosqui-
Identification of the species of 2867 mosquitoes to-biting rate and the prevalence of microfilari-
was confirmed with the use of polymerase-chain- ae, stratified according to the age of residents in
reaction (PCR) amplification of the internal tran- the 2008 survey, to estimate the likelihood of
scribed spacer 2 region of mosquito ribosomal transmission cessation before and after bed-net
DNA and either digested with MSP1 enzyme28 or distribution.10,11 (Details are provided in the Sup-
used in a ligase detection reaction–fluorescent plementary Appendix, available with the full text
microsphere assay.29 A total of 1009 samples were of this article at NEJM.org.)
also screened for W. bancrofti DNA by PCR ampli-
fication of the long DNA repeat region to be used R e sult s
as a xenomonitoring tool.30
At the close of the study, one village with a Prevalence of Human Infection
moderate transmission level (Nanaha) and one Descriptive characteristics of the study popula-
with a high transmission level (Yauatong) were se- tion20 are summarized in Table 1. In 2008, the
lected for long-term assessment of rates of mos- prevalence of microfilariae in the three study vil-
quito biting. Mosquito collections were conducted lages in the high-transmission zone ranged from
quarterly in the second and third year after the 23.7% to 38.6%. These values were significantly
bed-net distribution. higher than in 1998, when the values ranged
from 3.7 to 10.8% (P<0.001 by Fisher’s exact test),
Insecticide-Treated Bed Nets 1 year after the fourth annual mass administra-
PermaNet 2.0, an insecticide-treated bed net im- tion of antifilarial drugs and immediately before
pregnated with 55 mg of deltamethrin per square the fifth and final mass treatment. In contrast,
meter (Vestergaard Frandsen), was distributed to the prevalence of microfilariae in the two villag-
study communities by the East Sepik Province es in the moderate-transmission zone, Nanaha
Division of Health in August 2009. At that time, and Ngahmbule, remained low and did not change
the national target for bed-net coverage was 80% significantly during the 10-year period, with prev-
of household ownership and 80% use for chil- alences of 3.4% or less in both villages in 2008
dren under the age of 5 years and for pregnant (P = 0.78 and P = 0.39, respectively, for comparisons
women. Surveys regarding bed-net use were con- with 1998 values). Notably, the prevalence of mi-
ducted in November 2008 and again in Septem- crofilariae in 2008 did not increase in any of the
ber through December 2009 by asking adults villages to the level in 1994, before mass drug
(≥18 years of age) and parents or guardians of administration (Table 1).

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 Insecticidal Bed Nets and Filariasis Tr ansmission

Table 1. Status of Lymphatic Filariasis and Use of Insecticide-Treated Bed Nets in the Study Villages.*

Level of Village Population Bed-Net Use before Bed Nets Bed-Net Use after
Transmission Name Microfilariae Prevalence of Village Distribution in 2009 Distributed Distribution

1994 1998 2008

% no. % no. %
High Yauatong 79.5 10.8 38.6 408 12.4 190 84.3
High Albulum 78.3 7.4 38.4 526 NA 234 81.7
High Peneng 61.5 3.7 23.7 233 3.8 142 75.0
Moderate Nanaha 48.3 2.4 2.0 507 NA 222 84.1
Moderate Ngahmbule 36.2 1.7 3.4 256 NA 109 90.6

* Transmission levels are based on annual transmission potentials determined in 1993 and 1994. Five annual mass antifilarial treatments
consisting of diethylcarbamazine alone or diethylcarbamazine plus ivermectin were administered from 1994 through 1998. (This regimen
differed from the standard treatment in the global program to eliminate lymphatic filariasis.) Insecticide-treated bed nets were distributed in
August 2009, with a target coverage of at least 80% of households per village. NA denotes not available.

Use of Insecticide-Treated Bed Nets were similar during each of the 2 years preced-
Immediately before bed-net distribution, 3.8% ing bed-net distribution, that number dropped
and 12.4% of households of the two study vil- to zero for the year after bed-net distribution
lages surveyed used bed nets of any type. Four to (Fig. 3). The proportion of anopheline mosquitoes
5 months after distribution, self-reported house- that tested positive for W. bancrofti DNA, an indi-
hold use of bed nets in the five study villages cator of the reservoir of microfilariae, was 19.4%
ranged from 75.0 to 90.6% (Table 1). (761 mosquitoes) before bed-net distribution and
14.9% (248 mosquitoes) after bed-net distribu-
Mosquito Vectors tion (P = 0.13 by Fisher’s exact test).
A total of 20,345 anopheline mosquitoes were
collected in the 26 months before bed-net distri- Mosquito-Biting Rates
bution and 1554 in the 11 months after distribu- The daily biting rates for anopheline mosquitoes
tion. The subgroups of mosquitoes in which the decreased significantly after bed-net distribution,
species was confirmed included 78% of A. punctu- with a mean (±SE) of 61.3±4.9 bites per person
latus and 21% of A. koliensis; the remaining 1% was per day before bed-net distribution versus 9.4±1.9
a mix of A. hinesorum, A. farauti 4, and A. farauti sensu after bed-net distribution in Yauatong, 22.6±2.5
stricto. Among A. koliensis mosquitoes, 94% were versus 7.3±2.0 in Albulum, 6.4±0.8 versus 1.5±0.4
caught in Nanaha and Ngahmbule; molecular in Peneng, 21.5±1.3 versus 1.1±0.2 in Nanaha,
confirmation of the morphologic identification of and 8.9±0.8 versus 1.5±0.3 in Ngahmbule (P<0.001
A. punctulatus resulted in 95% concordance. Only for all comparisons by the Mann–Whitney U test).
mosquitoes that were identified as A. punctulatus The rates remained consistently low for an addi-
on morphologic analysis harbored W. bancrofti in- tional 2 years in Yauatong and Nanaha (Fig. 4).
fective larvae. Subsequent data are therefore The probability of the transmission cessation
based on morphologically identified A. punctulatus. was less than 1.0% in all five villages before
The proportion of A. punctulatus mosquitoes bed-net distribution. After bed-net distribution,
that were infected with any stage of larvae de- the probabilities increased to 4.9%, 7.7%, 90.5%,
creased from 1.8% to 0.4% after bed-net distri- 95.8%, and 61.5% in Yauatong, Albulum, Peneng,
bution (P = 0.005 by Fisher’s exact test) (Fig. 2). Nanaha, and Ngahmbule, respectively. Further
None of the mosquitoes that were collected in reductions in biting rates by years 2 and 3 after
Peneng, Nanaha, or Ngahmbule after bed-net dis- bed-net distribution increased the probabilities
tribution contained larvae of any stage. Notably, to 36.8% and more than 99% in Yauatong and
no mosquitoes harboring infective larvae were Nanaha, respectively. These high probabilities pro-
identified in any of the villages after bed-net vide support for the empirical finding that an-
distribution (P = 0.07 by Fisher’s exact test). There- nual transmission potentials were reduced to
fore, although annual transmission potentials zero after bed-net distribution (Fig. 2).

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 The n e w e ng l a n d j o u r na l of m e dic i n e

ing developing larvae, no mosquitoes containing

4.0
Yauatong infective larvae, and no children under the age of
10 years who tested positive for filarial antigen.24
Percent of Mosquitoes Infected

3.5 Albulum
3.0 Peneng However, it is clear from observations in 2008
Nanaha and 2009 that transmission was still occurring,
2.5
or Infective

Ngahmbule
since annual transmission potentials among the
2.0 Infective
study villages ranged from 5 to 325 infective lar-
1.5
vae that were inoculated per person per year, and
1.0 the prevalence of microfilariae had significantly
0.5 rebounded in three villages. Human migration
0.0 may have contributed to continuing transmission
Before Bed-Net Distribution After Bed-Net Distribution and increased prevalence of microfilariae after
the cessation of mass treatment.31 The fact that
Figure 2. Proportion of Anopheles punctulatus Mosquitoes Carrying
­Nematodes Causing Lymphatic Filariasis, before and after the Distribution worm breakpoints that were necessary for the ces-
of Insecticide-Treated Bed Nets in Five Villages in Papua New Guinea. sation of transmission were not attained is prob-
Shown are the percentage of mosquitoes that were found to be infected ably of greater importance. In 1997, after four
(solid colors) and the percentage that were found to be infective (hatched annual mass drug administrations, the prevalence
areas) on dissection before bed-net distribution (8181 mosquitoes) and af- of microfilariae in moderate- and high-transmis-
ter bed-net distribution (678 mosquitoes). The T bars indicate 95% confi-
sion zones was 1% and 5%, respectively.20 How-
dence intervals.
ever, worm breakpoints for anopheline systems
are estimated to be 0.75%.11
The introduction of insecticide-treated bed nets
350 profoundly affected the vector population and
Yauatong
(no. of infective larvae/person/yr)

therefore the transmission of lymphatic filariasis.

Annual Transmission Potential

300 Albulum
Peneng A similar proportion of mosquitoes tested posi-
250
Nanaha tive for W. bancrofti DNA before and after bed-net
200 Ngahmbule distribution. However, significantly fewer mos-
150
quitoes contained developing worms after bed-
net distribution. These findings indicate that
100
mosquitoes were imbibing microfilaremic blood,
50
No detectable
but larval development was interrupted. The use
0
transmission of bed nets may reduce the transmission of vec-
2007–2008 2008–2009 2009–2010 torborne diseases by shortening the life span of
mosquitoes,32 and W. bancrofti microfilariae re-
Figure 3. Annual Transmission Potential for Lymphatic Filariasis in the Five
Study Villages during the 26 Months before and 11 Months after Bed-Net
quire at least 13 days to develop into infective
Distribution. larvae in A. punctulatus.33 Therefore, a slight re-
Shown are the estimated numbers of infective larvae that were inoculated duction in average life span could have a major
per person per year during the periods of July 2007 through August 2008, effect on the number of infective larvae. In addi-
September 2008 through August 2009, and September 2009 through July tion, after the introduction of bed nets, most
2010. Insecticide-treated bed nets were distributed in the villages in August mosquitoes that fed successfully probably were
2009.
feeding before residents went to bed. We saw
that a greater proportion of the mosquito popu-
Discussion lation was biting at earlier hours after bed nets
were introduced. Because of the nocturnal peri-
Residents of villages in our study participated in odicity of microfilaremia in Papua New Guinea,
a 5-year program of mass administration of anti- earlier biters will ingest fewer microfilariae than
filarial drugs, with 77 to 86% of eligible residents those biting during the time of peak blood den-
receiving such drugs annually from 1994 through sity of microfilariae (around 1:30 a.m.) (Fig. S1
1998.20 The prospect of the elimination of lym- in the Supplementary Appendix).
phatic filariasis was promising at the end of the Previous studies have shown how vector con-
campaign and seemed even more likely after a trol alone can be used to reduce the prevalence
2003 survey showed very few mosquitoes contain- of microfilariae34 and to accelerate this decrease

750 n engl j med 369;8  nejm.org  august 22, 2013

 Insecticidal Bed Nets and Filariasis Tr ansmission

A Probability of Extinction B Yauatong C Albulum

1.0 9 9

8 8
0.8

Mosquito-Biting Rate (loge)

Mosquito-Biting Rate (loge)

7 7
Probability of Extinction

0.6 6 6
5% 5%
5 5
0.4 50%
50%
4 4
95% 95%
0.2 3 3

2 2
0.0
3.5 4.0 4.5 5.0 Estimate Before 1 2 3 Estimate Before 1 Yr after
Bed Nets Yr after Bed Nets Bed Nets
Mosquito-Biting Rate (loge)
Bed Nets

D Peneng E Nanaha F Ngahmbule

7 7 7
Mosquito-Biting Rate (loge)

Mosquito-Biting Rate (loge)

Mosquito-Biting Rate (loge)

6 6 6

5%
5 5% 5 5
50% 5%
50%
4 4 4 50%
95% 95% 95%
3 3 3

2 2 2

Estimate Before 1 Yr after Estimate Before 1 2 3 Estimate Before 1 Yr after

Bed Nets Bed Nets Bed Nets Yr after Bed Nets Bed Nets
Bed Nets

Figure 4. Probabilities of the Cessation of Transmission of Lymphatic Filariasis before and after Bed-Net Distribution on the Basis
of Village-Specific Goodness of Fit with the Anopheline Transmission Model.
Panel A shows the probability of the cessation of transmission of lymphatic filariasis in the village of Peneng, according to mosquito-biting
rates, which are expressed as the natural logarithm (loge) on the x axis. The horizontal dashed lines show the biting thresholds associated
with cessation probabilities of 50%, 75% and 95%. The bars at the bottom of the panel indicate the frequency distribution of the model-
estimated biting thresholds for Peneng. Panels B through F show changes in the mosquito-biting rate and probabilities of cessation in
the five study villages before the distribution of insecticide-treated bed nets and 1 or more years after bed-net distribution. (Mosquito-
biting rates were available for Yauatong and Nanaha for years 2 and 3 after the distribution.) Shown are estimates (open circles) of the
most likely 500 biting thresholds calculated by goodness of fit of the model with 2008 data regarding the prevalence of microfilariae,
stratified according to the age of residents in the five villages in the study. The shaded bands between dashed lines denote the range
and biting threshold values associated with 5%, 50%, and 95% probabilities of transmission cessation. The diamonds indicate mea-
sured biting rates, and the I bars 95% confidence intervals.

when combined with mass administration of an- Saharan Africa. Thus, our study highlights the
tifilarial drugs.35,36 However, our study quanti- importance of integrating vectorborne disease
fies the effect of the most widely implemented interventions. However, in order for the use of
vector-control measure, the use of insecticide- bed nets to be a sustainable strategy to eliminate
treated bed nets. Although vector control is not lymphatic filariasis, biting rates must remain be-
currently a part of the global strategy to eliminate low the threshold until lymphatic-dwelling adult
lymphatic filariasis, universal bed-net distribution worms in the population die. The likelihood of
is now used widely for malaria control-and-elim- transmission cessation that we observed is a
ination efforts in Papua New Guinea and sub- snapshot of a temporally dynamic transmission

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 The n e w e ng l a n d j o u r na l of m e dic i n e

system. A small increase in biting rate with no calculated for Peneng, where the prevalence of
change in human prevalence of microfilariae microfilariae in 2008 was 23.7%, but the mos-
could quickly lead to a reestablishment of stable quito-biting rate was similar to rates in the moder-
transmission. ate-transmission villages after bed-net distribution.
Program managers wanting to determine trans- If the use of bed nets remains high and vector
mission end points during elimination campaigns populations continue to be susceptible, the use
are met with the challenge of detecting human of bed nets may eliminate lymphatic filariasis in
infection at progressively lower levels.37 In our areas where the reservoir of microfilariae has
study, we used data on the prevalence of micro- first been reduced by mass drug administration,
filariae before the intervention and a model of as in the populations included in this study, or
the transmission of lymphatic filariasis to quan- where preintervention endemicity is already low,
tify the probability of transmission cessation on such as in the Solomon Islands.18 In high-trans-
the basis of mosquito-biting rates alone. Annual mission areas, the use of bed nets could work
transmission potentials dropped to zero after bed- synergistically with mass drug administration by
net distribution in all villages on the basis of an increasing the worm breakpoint to a more easily
absence of infective larvae in blood-seeking mos- attainable level. Given the challenges of reaching
quitoes, though detection of infective mosquitoes 80% compliance with mass drug administration
was constrained by very low vector densities. The for at least 5 years,38,39 efforts to eliminate lym-
probability of transmission cessation was more phatic filariasis would greatly benefit from inte-
than 50% in the two moderate-transmission vil- grated vector management.40
lages, where the prevalence of microfilariae was Funded by the U.S. Public Health Service and a grant (U19
AI065717) from the National Institutes of Health.
3.4% or less before bed-net distribution. A simi- Disclosure forms provided by the authors are available with
lar likelihood of transmission cessation was the full text of this article at NEJM.org.

References

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