Keynote Speech

2nd Live Love Animals International Conference on Animal Care in Kobe 2012

13

基調講演
Keynote Speech
長崎大学 学長／医学博士・片峰 茂

Shigeru KATAMINE, MD, PhD, President of Nagasaki University

感染症はいかに制御できるのか
感染症は 21 世紀人類が直面する最大の課題の一つでATL は 1977 年その存在が明らかにされ、続いて 81

す。世界で年間 2,000 万人以上のヒトが感染症で死んで年原因ウイルス HTLV-I が初のヒト・レトロウイルスとしいると推定され、そのほとんどが、サハラ以南のアフリて分離されました。そして、長崎県が世界最大の HTLV-I

カを中心にした熱帯・亜熱帯地域に集中しています。最流行地域の一つであり、県民全死亡原因の１％弱（年間

貧国の多い途上国には、現代医学の恩恵がもたらされて約 100 名）が ATL であることが判明しました。私たちいないのです。そして、いま、人類は新たな感染症の脅は HTLV-I の感染経路解明と感染予防に関する研究を開威に直面しています。新しい感染症（新興感染症）の出始しました。まず、疫学調査と動物実験により HTLV-I

現です。この 30 年で、エボラ出血熱、エイズ、SARS なの主要感染経路が母乳による母親から児への感染である

ど多くの感染症が新たに出現し、私たちを恐怖に陥れてらしいことをつきとめました。しかし、その最終証明にいます。その多くは動物の世界の病原体が、ヒトの世界

は感染母親から児への母乳を止めることで感染率が実際に侵入してきたものです。森林開発など様々の人為的要に低下することを示す必要がありました。1987 年長崎

因で人間と動物の出会いの頻度が飛躍的に増大したこと県の支援のもと長崎大学と産婦人科医協会を中心に介入が原因となっています。そして、交通手段の発達により、事業を開始しました。事業は (1) 全妊婦の HTLV-I 抗体検

ヒトやモノが国境をこえて超高速で往来する中、世界の査 (2) 感染妊婦への母乳遮断の勧奨 (3) 出生児の追跡調

何処かに出現した感染症が瞬時に世界中に伝播してしま

査の 3 本柱から成ります。その後事業は 24 年間継続さうのです。

れ今日に至っています。これまでに妊婦 255,340 名もの感染症はいまや重要な危機管理の対象の一つです。人抗体検査を行い 8,500 名（3.3%）の感染者を見出しまし

類には、さまざまな感染症の流行をコントロール（制御）た。その約 9 割は完全断乳に同意したと推定しています。

し予防するための知恵と努力が必要とされています。講

母乳栄養児の感染率約 26% が完全断乳により 1/10 に低演では、或るがん（癌）の原因ウイルス流行克服のために、下し、母乳が主要感染経路であることが最終的に証明さ長崎県という一つの地域が 24 年間にわたって取り組んれました。感染率や ATL 発症率を勘案すると、本事業はできた事業の成果を紹介させていただき、皆さんと感染

約 2,000 件の母子感染を防止し、100 例以上の ATL 発症症の制御について考えてみたいと思います。

を予防したと推定できます。当初 5％を上回っていた県

肝がん、子宮頸がん、成人 T 細胞白血病（ATL）など、内の感染妊婦比率は、事業始後に出生した女児が妊婦集

日本人のがんの 1/4 程度にウイルス感染が関っています。

団の主体となる 5 年後には、1％を大幅に下回ると予想

原因ウイルスの感染者の一部にのみ、長い潜伏期の後にされ、次世代には年間 ATL 発症ゼロを展望できるところがんが発生しますが、一方がん患者のほとんどはウイルまできました。このまま推移すれば地域内ウイルス感染

スに感染しています。即ち、これらのがんの発生にはウの予防による癌（ATL）征圧という世界にも類例のない

イルス感染は必要条件であり、理論的にはもし原因ウイ成果となるはずです。

ルスの感染を完璧に予防することができればがん発生をゼロにすることができるのです。

14

りぶ・らぶ・あにまるず 神戸アニマルケア国際会議 2012

How we can Control Infectious Diseases: Intervention in the mother-to-child transmission of HTLV-I
in Nagasaki, Japan, for 24 years.

Reducing the risk of infectious diseases is a major global
issue in the 21st century. More than 20 million people
annually die due to infectious diseases. Most of them
are in tropical and subtropical regions including the subSaharan Africa, and they die from curable diseases such as
diarrhea, pneumonia, malaria, measles, and so on. People
from developing countries within these regions have
hardly received any benefit from modern medical science.
Additionally, mankind has been facing the global-wide riskof several newly emerged infectious diseases, which include
Ebola, AIDS, SARS, and pandemic Flu. More than half ofthese have emerged through invasion of animal pathogens
into human communities. The reclamation of woodlands,
for example, has increased the chance of malign contact
between human and animals, and the efficiencies of moderntransportation systems have helped the emerged pathogens
propagate more easily all around the world.
In my lecture, which will introduce an intervention program
deployed to reduce the prevalence of HTLV-I, a causative
virus of adult T-cell leukemia (ATL), in Nagasaki Prefecturesince 1987, I shall discuss how we can control infectious
diseases.
Approximately 25% of cancers in Japanese people are
etiologically related with the infection of viruses. Almost
all the cases of hepatic cancer, cervical cancer, and ATL arecaused by hepatitis B/C viruses, human papilloma virus,
and HTLV-I, respectively. Therefore, successful prophylaxis
against the viruses theoretically will lead to a dramatic
decrease in the number of patients with these cancers.

HTLV-I. The annual incidence of ATL in the Prefecture
was about 100 which equated to 1% of total deaths.
This prompted us to conduct a study to elucidate themajor transmission route of HTLV-I in order to develop
prophylactic measures. Intensive epidemiological studies
and animal experiments strongly suggested that ‘mother-tochild transmission via breast feeding’ was a major pathway.
In order to test the idea, and to reduce the prevalence of
HTLV-I, an intervention program named “ATL Prevention
Program, Nagasaki”, was started in 1987 through thecollaboration of Nagasaki University, the Obstetrician
Association, and the Prefectural Government. The program
consisted of, (1) the serological HTLV-I screening of all
pregnant women, (2) advising infected pregnant women torefrain from breast feeding, and (3) serological follow-up ofchildren born to infected mothers. This has been continued
up until the present for the past 24 years. So far we havetested 255,300 pregnant women including 8,500 infected
women. More than 90% of them agreed to refrain frombreast feeding.
Our results have shown that breast feeding transmits
HTLV-I to about 26% of children, whereas if women refrainfrom breast feeding, this rate reduces substantially down
to 2.7%. Therefore it is estimated that the intervention
program has prevented more than 2,000 cases of mother-tochild transmission and more than 100 ATL cases. Moreover,
we readily expect that the rate of infected pregnant women,born after the start of the program, will be dramaticallyreduced and that the annual incidence of ATL in Nagasaki
Prefecture will be less than 1% within the next generation.

ATL, a highly malignant and incurable leukemia, wasidentified as a new clinical entity in 1977. Some uniqueepidemiological features of ATL strongly suggested the
involvement of infectious agents, and successively thecausative virus, HTLV-I, was isolated in 1981, then soonafter, Nagasaki was found to be heavily endemic for

2nd Live Love Animals International Conference on Animal Care in Kobe 201215

Keynote Speech
Record16

りぶ・らぶ・あにまるず 神戸アニマルケア国際会議 2012

基調講演
Keynote Speech
長崎大学 学長／医学博士・片峰 茂

Shigeru KATAMINE, MD, PhD, President of Nagasaki University

That was a very kind introduction, good morning

As the chairman mentioned, my talk will be a very

everybody. I am Shigeru Katamine from Nagasaki

unique and extraordinary. I will talk in English but the

University and it is my great pleasure and honor to beslides I will show will be mainly written in Japanese.

here to give a lecture on the occasion of the opening ofHere is one such slide and I hope it will help you

The Second International Conference on Animal Careunderstanding my Japanese English. I also hope thatin Kobe 2012. I would like to state my appreciation to

my talk today will somehow help to strengthen yourthe conference organizers for inviting me to this very

understanding of infectious diseases and provide ideas

meaningful and exciting meeting. In particular I am

on how we can control them.

very grateful to the Secretary General and to today’s chair, Ms. Kayoko TOMINAGA. She has strongly andSo, let me start with the global issues. You can see here

continuously approached and encouraged me to mountthat infectious diseases are the most prominent cause

this platform. Thank you.

of death around the world. We can estimate the total
number of deaths in the world to be 50 million and, ofCurrently, I am involved in administrative work at thethese, 40% or about 20 million people are dying due

headquarters of Nagasaki University, but I am basicallyto infectious diseases. For example diarrhea caused

a scientist. My field of research is virology, studying

by various viruses (such as noroviruses, rotaviruses

the viruses that cause various diseases in mankind. Soor enterobacteria) is killing about 5 million people

the topic I will be talking about this morning concerns

every year. Most of them are children, including new

infectious diseases caused by viruses. As you knowborn babies. A similar number of people are killed

reducing the risk of infectious diseases is one of theby pneumonia, followed by AIDS (2 million people),major global issues in the 21st century. Many people

tuberculosis (2 million) and measles and malaria (1.5

are dying due to infectious diseases and, in recent

million each).

years, so many new pathogens have emerged withinhuman communities and have propagated all around

The most important point is that these diseases are

the world.

common in the world. In the developed countries,
including United States, the EU and Japan, these

My talk will consist of two stories.

diseases are curable by post-hospitalization, by drug
treatment and also preventable by inoculating vaccines.

First I will talk about and briefly summarize theEven with AIDS, while a significant number of AIDS

global issue of infectious diseases. Then I will movepatients are dying even in the developed countries,

to my second story about intervention on mother torecent advances in anti-HIV therapy can greatly prolong

child transmission of HTLV-1, the virus causing Adultthe incubation periods of the HIV-infected individual.

T-cell Leukemia, ATL. It is a very nice example of the(The incubation period refers to the time interval

battle leading to the successful control of a particularbetween HIV infection and the onset of the disease).

infectious disease.

So this means that most of these 20 million people
killed by infectious diseases are residing in developing

2nd Live Love Animals International Conference on Animal Care in Kobe 201217

have been neglected by global societies.
Additionally, over the last 30 years, mankind has begun
to face a global risk from newly emerging infectious
diseases, such as Ebola, SARS, AIDS and pandemic
flu, which have all been breaking out within humansocieties in recent years. In some cases pathogens
persistent in restricted small geographical areas havespread into new geographic areas. For example, in the
1980s, AIDS which had been present in some small
countries - in the tropic and sub-tropic areas in theisolated rural areas of Western Africa, spread to urban

world, including sub-Sahara Africa.

areas and then rapidly propagated all over the world.
Many other cases broke out through an invasion of

The situation in developing countries in the tropicalanimal pathogens into human communities. The Ebola

areas is very bad. They have very bad nutrition, veryvirus came from monkeys, the Nipavirus from fruit

bad sanitary systems. Therefore various infectious

bats, BSE and mad cow disease from cattle, SARS from

diseases easily propagate in human communities.

a kind of domestic cat, and influenza viruses from fowl

Moreover there are few hospitals and no public careand pigs. Changes in the genomes of pathogens are alsosystem to distribute vaccines and drugs. And the

involved in the emergence of new strains of influenza

people have no money to be hospitalized or to buy

viruses and also drug resistant bacteria.

drugs and vaccine. People in developing countries, inthese regions, have barely received any of the benefits

Many things are responsible for their emergence, suchof modern medical science. As a consequence, there is

as socio-economic factors, changes of environmentsa very high prevalence and high mortality by infectious

and changes in human behavior. For example, thediseases in developing countries. This really reflects thereclaiming of woodland has increased the chances

social, political and economic inequality between theto link between humans and animals. Mo dernnorth and south of the world.

transportation systems have made the emergence of
pathogens and their rapid propagation around theIn addition to the common diseases, there are soworld far easier.

many other infectious diseases specifically present in
the tropical areas. We call them “Neglected Tropical

So far, I have briefly summarized the global issues

Diseases” (NTD) and these include sleeping diseases,

relating to infectious diseases. The most important

scistosomiasis and Changes diseases by parasites,

point is that the main focus of this global issue exists

Dengue fever and Japanese encephalitis caused byin tropical and sub-tropical regions. People in thoseviruses, and cholera and diphtheria caused by bacteria.

regions need the help of the world.

The important point is that these diseases are restricted

Now I will move to the second story. The story is about

to the tropical and sub-tropically areas. There are no

Nagasaki prefecture-wide intervention in the mother todiseases like these in developed countries. For thischild transmission of HTLV-1, a causative virus of adultreason researchers and pharmaceutical companies haveT-cell leukemia, ATL. I myself have been involved in thisnot given any attention to these kinds of diseases, theproject for a very long time, more than 20 years.

NTDs. As a consequence the pathogenic mechanisms

18

remain to be elucidated, and the therapeutic or

As you know, cancer is the most important cause of

preventive measures to combat them still remain to bedeath in Japanese people. About one third of Japanesedeveloped. So far, these particular infectious diseases

people die with cancer. Of these, about 25% of cancer

りぶ・らぶ・あにまるず 神戸アニマルケア国際会議 2012

cases are closely related to infection by viruses.

prefectures. And if they were not, the patients’ parents

Most hepatic cancers, cervical cancers and those ofor grandparents appear to have been born in thoseadult T-cell leukemia, ATL are closely associated withareas. There are also so many reports of familial cases,

infection by hepatitis B / C viruses, human papillomathat is, more than two patients in the same family.

viruses and HTLV-1, respectively. And the Burkitt

These finding strongly suggested a prevalence in

Lymphoma (prevalent on the Africa continent) andsouthwestern Japan, and the involvement of infectious

the Nasopharyngeal Carcinoma (in China) are closely

pathogens in the development of ATL. As you can see

associated with the infection by the Epstein-Barr virus,[in the slide] the blue colors referring to Nagasaki,

EB virus. Theoretically, by successful prophylaxis - byKumamoto, Kagoshima and Okinawa prefectures show

successfully preventing infections by these viruses - thea very high incidence of adult T-cell leukemia.

human community can overcome these cancers.
In 1981, four years after the discovery of ATL,
What you are seeing here are some cells of adult T-cell

Professor Yorio Hinuma of Kyoto University identified

leukemia surrounded by many small red blood cells.

the virus that causes ATL, namely the Human

You can see very characteristic, irregular shaped nuclei

T-lymphotropic virus Type I, in short HTLV-1. HTLV-

in cells. Sometimes cells look as if they have two nuclei.

1 are found to be the first human retroviruses and isThis is a very unique, morphological feature of adultcapable of immortalizing human T-lymphocyte in vitro.

T-cell leukemia cells. This can be distinguished fromAnd also importantly, worldwide survey showed thatany other leukemia.

there is a prevalence of HTLV-1 infections in someparticular areas of the world including southwestern

ATL, adult T-cell leukemia was first described by

Japan, the Caribbean basin and African continent.

Professor Uchiyama and Takatsuki in Kyoto University

Importantly those prevalent areas completely matchin 1977. In addition to their very unique morphologicaland overlap with areas having a high incidence of ATL.

appearance, they are distinguishable from otherleukemia by the presence of the frequent skin lesions

Also later clinical studies show that about 5% of HTLV-1

and also high levels of blood calcium. ATL cells are also

infected individuals develop Adult T-cell Leukemia, ATL,

very resistant to any chemotherapeutic agent.

and that every ATL patient was infected with HTLV-1.
And also HTLV-1 is later shown to be associated with

Therefore the prognosis of a patient with ATL issome other diseases including a kind of myelopathy,

extremely poor and most will die within two years after

rheumatoid arthritis and other autoimmune diseases.

diagnosis. A very important finding is that most of thepatients themselves appear to have resided or wereAs I mentioned, HTLV-1 belongs to the retroviruses.

born in a particular area of Japan, namely southwestern

Retroviruses have a unique life cycle by the presence ofJapan including Nagasaki, Kagoshima and Okinawa

a unique enzyme, reverse transcriptase. Once infected,
this kind of virus genome integrates into the genome ofthe host cells and persists into the cells. Once infected,
you cannot remove the virus from the infected host,and after infection, the individual stays healthy fora long time, usually for their whole lifetime, with no
disease.
However, some infected individuals develop the disease
after a long incubation period during which the infectedindividual releases the viruses and behaves as a sourceof further infection. This is the problem. We know of

2nd Live Love Animals International Conference on Animal Care in Kobe 201219

two kinds of virus in human retroviruses. One is thesource with hosts. These three factors are essential for

HTLV-1 and the other is HIV. Both of these two kinds

the infection. In other words, without one of the three,of virus infect the human T-cell T-lymphocytes but theinfection will no longer be established. So if you thinkdisease outcomes are completely different. HTLV-1

about prophylactic measures for a particular infectious

immortalizes the infected T-cells leading to leukemia

disease, you can focus on one of them, one of the three.

and T-cell leukemia. In contrast, HIV destructs theinfected T-cell finally leading to the immunodeficiency

Vaccination giving a host resistance against a particularsyndrome AIDS.

pathogen is the trendy measure of the prophylaxis.
But, in the case of HTLV-1, effective vaccines are not

This slide shows the relationship between the HTLV-

available so far, which is also the case in HIV. How

1 infection and the outcome of the disease. In the caseabout the source of the pathogens? As I mentioned,of rheumatoid arthritis, some patients appear to beonce infected you cannot remove HTLV-I from theinfected with HTLV-1 but most of other patients are nothost. The virus persists in the infected individual for

infected. In contrast, in the case of ATL only a small

an entire lifetime and most of the infected people stayproportion, about 5% of infected individuals, develop

healthy. You cannot separate them from the general

ATL but conversely every ATL patient is infected withpopulation due to human rights, so the remaining focus

HTLV-1. So we can conclude that if we can successfully

should be to address the third factor, the root of thecontrol the HTLV-1 infection, we can overcome ATL,

infections. This prompted us to look for the major root

the highly malignant and fatal cancer.

of HTLV-1 transmissions. A very important finding
was that ATL patients clustered within a family. In theThis slide shows the situation of Nagasaki Prefecture insame way many members in a family were infected

the late 1980s. As you see, the total population is about

with HTLV-1, which suggested that the route might

1.5 million. Within this population 4% were infected

be very close contact between family members, suchwith HTLV-1 which is a very high rate of infection.

as a mother to child, or husband to wife, and so on.

In people above 50-years of age, the infection rate

This was important data in our early studies and firstwas 10% - very high indeed. And, more importantly,

provided evidence for the presence of mother to childin the areas of remote islands including Goto Island,transmission of HTLV-1. When children born to 78

Hirado, Iki and the Tsushima there was an extremely

infected mothers were tested, 17 children appearedhigh prevalence of HTLV-1 infection. There, more

to be infected, an infection rate of 22%. This isthan 20%, 30% and sometimes 40% of people weresignificantly higher than the control of age-matched

infected with HTLV-1. The annual incidence of ATL inchildren, 2.6%. Conversely if the mothers of infected

Nagasaki Prefecture was about 100. This corresponded

children are tested, 12 out of 13 appear to be infected,

to roughly 1% of total deaths in the prefecture. So the

92% in comparison with the age-matched female, 5.5%.

control of HTLV-1 infection is a very important public

There is a highly significant difference. Similarly whenhealth issue in the prefecture.

12 mothers of infected pregnant women were tested,

Let’s think about prophylactic measures for HTLV-1.
When you consider prophylactic methods (meaning,the method for preventions), there is a very importantconcept - three essential factors behind infections.
One of the factors is the host, usually this host is anindividual yet to be infected. A second factor is thesource of the infection and in the case of HTLV-1 thesource of the infection is an infected individual. A third
factor is the route of the infection that connects the20

りぶ・らぶ・あにまるず 神戸アニマルケア国際会議 2012

10 appeared to be infected, or 83%. This is, again,

three months after birth. This results clearly showedsignificantly higher than age-matched control of 6.4%.

that the breast milk of infected mother has an infection

So these epidemiological studies clearly show thepotential when drunk by babies. So we can speculatepresence of a mother to child transmission as a routethat mother to child transmission by breast feeding isfor HTLV-1.

the major route of HTLV-1 infections.

From mother to child, the virus can transmit by three

Clinical studies at that time gave us very importantpossible pathways. One is perinatal, that is, the virus

information.

transmits to the babies in the uterus. We call this,transmission, HTLV-1 can also transmit horizontally

intrauterine infection. Secondly, the infection can occurby blood or sexual contact. But clinical data showedduring delivery, perinatal infection. Thirdly, postnatalno ATL cases developed from this population infectedtransmission – the virus infects from mother to childwith HLTV-1 at adult age. All the ATL cases without

mainly via breast milk, breast feedings.

exceptions had developed in the population infected

O t h e r t h a n t h e m o t h e r- t o - c h i l dvery early in life. So we knew that to overcome ATL in
To look for the route of mother to child transmission

the community we had to control this mother-to-childof HTLV-1 we followed the children born to infected

infection route.

mothers, and found that the infection of the children
can be diagnosed very late after birth, later than one

In 1987 we started a prefecture wide project namely

year after birth. We thought that the postnatal pathway

the “ATL Prevention Program – Nagasaki” (APP

is the most probable cause of mother to child HTLV-1

Nagasaki), 25 years ago. One purpose of this projecttransmission so we decided to examine the breast milk

was to finally confirm the idea that breast milk was theof infected mothers. We asked infected mothers to give

major route of ATL transmission from mother to child.

us their breast milk and we tested it. First we foundIf the mother could refrain from breast feeding, thethat there are many cells in the breast milk and in

infection rate could dramatically decline. If it would

these cells we could find many HTLV-I-infected cells. So

be the case, the idea could be confirmed. Secondly,

breast milk can be a source of infection for everyone.

by having the infected mothers refrain from breast
feeding, we could overcome ATL in the communities.

Next we inoculated the breast milk into experimental
animals. We used the common marmoset as the

So the first step of the program consisted of screening

experiment animal. We inoculated the cells from theall the pregnant women in Nagasaki Prefecture whether

breast milk of the infected mothers via the oral cavity

or not they were infected with HTLV-1. In the secondof the marmoset, and inoculated about 6.8 x 108 cells

step of the program, when an infected mother wasin the oral cavity. That included about 7 x 105 infected

identified, we explained the risk of breast feeding to her,cells.

asking her to refrain from breast feeding. Thirdly, we
followed up on the children born to infected mothers.

This slide shows the time course of the experiment.

This program was conducted through a very close

We followed the inoculated marmoset, 1 month, 2

collaboration between the prefectural government, themonths, 3 months, 4 months, 5 months, 6 months, evendoctors association, (pediatricians, obstetricians) and7 months after the inoculation and tested the presence

also Nagasaki University and it has continued to dateand levels of the antibody against HTLV-1 in thefor more than 25 years.

blood. The presence of serum antibody is evidence for
infection with HTLV-1.

This slide shows the details of the program. Once awoman becomes pregnant she consults with the office

As you see, two months after the inoculation, theof obstetricians where she is asked to have a test for

antibody titer begins to elevate and reach the peak level

the antibody against HTLV-1. The cost for the antibody

2nd Live Love Animals International Conference on Animal Care in Kobe 201221

test is supported by the prefectural government. If thethat the risk of transmission with HTLV-1 also depends

results are positive, the pregnant woman is informed onon the length of breast feeding.

her next visit to the office. If infected with HTLV-1 therisks associated with breast feeding are explained so

The third important finding was that, in spite ofshe can select another nursing method. She can refrain

refraining from breast feeding, there was still afrom breast feeding and change to bottle feeding

significant number of mothers who unwittingly

and her secretion of breast milk is stopped by drugtransmitted the virus to their children, albeit a very

treatment. However some mothers do still select breast

low rate of 2.7%. This indicates the presence of an

feeding and we ask them the length of their breast

unidentified route other than the breast milk fromfeeding period afterwards, for six months or less, or for

mother to child.

more than six months. The children born to infected

So the project can conclude that breast milk is a major

mothers received follow up 6 months, 12 months, 18

source of the mother to child of HTLV-1 transmission,months, 24 months, and 36 months after birth in aand that the risk of infection depends on the length

pediatrician’s registered office.

of the breast feeding, and that there may also be
an unknown route of mother-to-child transmission.

This is the project summary. So far, for over 23 years,

Ultimately, the project can conclude that refraining

from 1987 to 2009 we have tested 255,340 pregnant

from breast feeding is the most effective measure to

women. This corresponds to far more than 80% of theprevent mother to child transmission of HTLV-1.

total pregnant women in the prefecture. We foundabout 8,500 infected pregnant women. So the infection

The figures shown on this slide are estimations. So far

rate of the pregnant women in Nagasaki prefectures

we have tested 255,000 pregnant women including

was computed to be 3.3%. These infected mothers

8,500 infected mothers. More than 90% of the infected

selected by themselves how to nurse their children.

mothers agreed to refrain from breast feeding while

Most of them, more than 90%, decided to refrain fromthe risk of infection from long-term breast feedingbreast feeding and nursed their children with bottle

was 26% compared to the 2.7% risk of infection frommilk.

bottle feeding. So we can calculate that this program
has so far prevented 1,770 cases of mother to childThis slide shows the representative results and theirtransmission. As 5% of them would develop ATL in theinterpretation. We can see three important findings.

future, this project can be said to have so far prevented

The first is that when infected mothers refrained

88 future ATL cases.

completely from breast feeding and the children were
nursed by bottle instead, the infection rate was 2.7%.

Another estimation is that if the current population of

In contrast, for those children fed with breast milk the

Nagasaki has a 3.2% infection rate, then in the annual

infection rate appears to be 17.6%. This is a highly

age population (meaning the population of each age

significant difference and clearly confirms that breast

fixed as 25,000), there are 800 infected people of eachmilk is a major source of mother-to-child transmission

age in Nagasaki Prefecture. From this 800, in the futurewith HTLV-1.

40 of them will develop ATL. Then for next generation
after that, if the mothers in that population feed their

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The second important finding is that if you look at thechildren by breast feeding, and the infection rate islength of the breast feeding periods, in those children

26%, we can calculate that the affliction rate will bewhose mothers gave them breast milk for less than

0.8%. If the mothers in this population also refrain fromsix months the infection rate was 6.7%. In contrast, inbreast feeding, then we can expect that the infection

those children fed breast milk for a very long time, forrate over the next generation to be only 0.1%. Now,

more than six months, the infection rate appeared as

this corresponds to 200 and 25 infected people in each

26%. This is a highly significant difference. It meansage. Among them 10 and 1 ATL cases will develop. As

りぶ・らぶ・あにまるず 神戸アニマルケア国際会議 2012

I mentioned, this is only our estimation, so this value

a national level. The prevalence of HTLV-1 in othermay be much lower.

areas of Japan is very low - less than 0.1% - but the
total number of infected individuals nationwide is still

Nagasaki Prefecture readily expects the rate of infected

estimated to be 1 million people. This means that, inpregnant women – those born after the start of theorder to overcome ATL, the Nagasaki system has to be

program - will be dramatically declined and the annual

popularized and expanded to a national level.

incidence of ATL will be less than one person. The
annual incidence means that the annual number of

In December 2010, the Ministry of Health, Labor andpatients with ATL will be less than one in the next

Welfare in Japan concluded a general counter plan

generation or at least by the next-next generation. So

for HTLV-1. Under this plan the Ministry decided toNagasaki Prefecture will overcome this fatal and highly

support the cost of conducting the HTLV-1 antibody

malignant cancer in the future.

test on every pregnant woman all over Japan. So this isa giant step towards “ATL Zero” in Japan.

However, some issues remain to be challenged. The
first one, as I mentioned, is that the program indicatedI am confident that the success of APP in Nagasaki

the presence of an unidentified mother to childhas strongly pushed the Ministry’s decision. Today, intransmission route. We are very sorry that there weremy lecture, I have given you an introduction to APP

even a few but a significant number of mothers who

Nagasaki, a long-term prefecture-wide intervention andunwittingly transmitted the virus to their children inshown you that the success of the program has beenspite of refraining from breast feeding. So firstly wea consequence of the dedicated collaboration of many

have a duty to identify the unidentified transmission

people in Nagasaki. This of course includes the manyroute.

mothers and their children, as well as all those officials
and healthcare workers in the prefectural government,

Secondly, we are also responsible to the more thanand the many pediatricians and obstetricians as well as

8000 mother who were informed that they weremany young researchers.

infected. We can easily presume that from these
8000 mothers, 5% of them (equivalent to about 400

I would like to close my talk by expressing my heartfelt

people) will develop ATL. But unfortunately we havegratitude to all the people involved in this program.

no measures to prevent the development of ATL in

Thank you very much for your attention.

the infected individuals. That is the second issue to bechallenged.
The third issue is complicated. This concerns thebalance between the advantages and disadvantages ofinfected mothers refraining from breast feeding. As
you well know, breast milk has a huge great benefit forchildren. It provides the children with nutrition, and ofcourse, antibodies and natural immunity against various
pathogens. But the skin-ship interaction between
mother and baby also seems to be very important forthe child’s future development. So this is a complicatedproblem to be challenged.
Finally I would like to point out the need for an
extension and popularization of the APP success to

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