Jpn. J. Infect. Dis., 54, 2001

Laboratory and Epidemiology Communications

Further Simulation on Survival of Mutants under Non‑Selective Condition
Yoshimitsu Yanaka, Ken‑Ichi Hanaki, Hiroshi Yoshikura and Kenji Yamamoto*Department of Medical Ecology and Informatics, International Medical Center of Japan,
Toyama 1‑21‑1, Shinjuku‑ku, Too,0 162‑8655
Communicated by Hiroshi Yoshikura(Accepted May 21, 2001)
where wr(t) and mr(t) indicate number of bacteria removed

The fate of mutants introduced into a population is anduring tlme t tO t+1.

interestlng question in relation to the introduction of geneti‑

cally modified organisms in environment. When a bacterial

The simulation was performed by uslng a Sun Ultra5

mutant is introduced into the gut nora, what could be ancomputer (Micro Sun Ltd., Palo Alto, Calif., USA) and C

outcome? Unless there is any selective pressure, such as bylanguage. For each case ofm(0)/C ‑ 0･01, 0･02, and Ol10, theantibiotic intake, mutants will be removed at random. In themean number of divisions required f♭r elimination of thehuman gut, the total population remains constant･ Therefore,mutants (I) was estimated for varying flora sizes (C). For

One bacteria in two will be removed at random at each cellobtainlng each polnt, 100 simulations were per允)‑ed･ Withdivision. We previously computer‑simulated the outcome whenincreasing C value, I increased (Fig. 1), and between T and

one mutant was introduced into bacterialflora ofvarioussizes.

C, the fbllowlng relation was observed, i.e.,

lnflora ranging ln Size from 10 to 10,000, the mutants disap‑

T ‑kC‑‑･【5].

In Figure lA, we noticed, in addition, that the k value

peared within a finite length of time, and, counter‑intuitively,

became larger as the mutant/flora ratio increased.

the time required fb∫ complete elimination was proportionalln Figure 2, the k value was plotted against m(0)/CJn theto the flora size (1).

We extended the work and examined outcomes obtainedwith variousmutant/flora ratios at various flora sizes. We usedrange studied, there was a linear relation ofk ‑ 12.9【m(0)/C】+0.12‑‑･ [6】.

the same program as in the previous report･Therefore, 7 ‑ 12.9 m(0) + 0.12C (0 ≦C ≦4,000; 0.01

W(t)+m(t)‑W(0)+m(0)‑C ‑ [11,≦m(0)/C ≦0.1) ‑‑･ [7].

C the total number of bacteria in the gut. As halfthe popula‑

Figure lB shows the relation between T, number of cell
divisions required for elimination of the mutants, and C･ A
similar relation as between T and C was observed, but, thetion of bacteria are eliminated at random,plots of the two c0‑0rdinates deviated relatively widely丘om

where w(t) and m(t) respectively indicate the number offlora
and mutant bacteria at tlme (number of cell divisions) t, andW(t+1) ‑ 2W(tトwr(t)‑‑･ [2],m(t+1) ‑ 2m(t) ‑ mr(t)･･･････ [3],wr(I)+mr(t)‑C･‑‑

straight lines.

The observation that the elimination of mutants requlreS alonger duration as the size oftheflora increases is slgnificant

[4],

1AlB

(suo!S!^!p)i(suo!S!^!p)1

仰 仙40｡｡ 30｡｡ 州000

0

1 000

2000

3000

4000

05000

1000

2000

3000

4000

CCFig. 1. Relation between T and C (Fig. lA) orrelation between Tan° C (Fig. 1B) at m(0)/C ‑ 1% (▲), 2% (●), 5% (○),

7%(■)andlO%(ロ).

*Co汀eSpOnding author: Fax: +8 1‑3‑38 16‑4802, E‑mail: backen@ri.imcj.go.jp
84

5000

HPEVI was orlglnally isolated in 1956 during an epidemic

Neutralizing antibody titers and the antibody‑positive rateof sumヮer diarrhea (2)･ Previ?us studies reported that theof age groups agalnSt HPEVl are shownin Fig･ I ･ Significant

predomlnant Clinical manifestatlOnS Caused by HPEV 1 werelevels orantibody agalnSt HPEVI were fわund in almost all

infantile diarrhea and respiratory illness (317), but more

the sera tested (178/195; 91%), with the titers rang.iTg fromserioussymptoms such as myocarditis and encephalitis have

1 :4 to 1 :5 12 or more. The number of antibody‑posltlVe Sera

also been reported (3). Reports on infections and the epide‑

began to increase from 6 months of age, and then rapidly

miology of this virus, however, have been few, probably

increased further. Almost all the children aged between I andbecause infection with this virus is rare compared with other15 years old had antibody against HPEVl (ト5 years old:enteroviruses such as echoviruS 30 (8). In this study, we investi‑78%, 6110: 100%, 1 1‑15: 89%, respectively)･ Additionally,

gated the antibody prevalence of HPEV 1 in order to elucidate
the extent of its infection in Hiroshima Prefecture.

the geometric mean of neutralizing tlterS in these age groups

was higher than in other age groups (Fig.1). Similar

A total of 195 sera, collected in October 2000丘om residentsseroepidemiologlCal findings on HPEV 1 have been reported

living in Hiroshima Prefecture aged between 5 months andby others. ln a study in Finland, 72 of 79 individuals aged

79 years old, Were measured fわr neutralizing antibody titerover 1 year (9 1 %) had neutralizing antibodies against HPEV 1

Pgainst HPEVl I A recent isolate ofHPEVl (HAO0‑243 strain:lS｡lated in Hiroshima Prefecture in July 2000) (9) was used(5), and studies ca汀ied out in the 1960s in Japan showed thatas an antlgen, and the method used was the standard micro‑

HPEVl (6, 10). These results indicate that the seroconversion
for HPEVl antibodies occur in almost all children shortly

almost all the children aged over 1 year had antibody agalnSt

neutralizing technique for enteroviruses with some modifica‑

a洗er 1 year of age. Furthermore, HPEVI was most commonly*Corresponding author: Fax: +81‑82‑25411908, E‑mail: takao

found in children aged under 1 year: according to the WHOdata from 1967 to 1974, 61% ofHPEVl infections reported@urban.ne.jp85