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TIMESTEPv7.r
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TIMESTEPv7.r
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########## TB XPERT DIAGNOSTIC MODEL 2012 ##########
########## TIMESTEP FILE ##########
## NOTES
# a. This is the workhorse function, calculating each new month of the model.
# b. This is a single function, taking as its arguments (i) a state vector and (ii) a subset of variables (all the time varying ones), and (iii) a partially filled model matrix.
# c. New entrants are added to state vector, deaths removed
# d. Variables are retransformed and dynamic functions calculated (TB force of infection)
# e. Static model matrix is updated with time-varying values, diagonal elements calculated so that rowsums = 1
# f. Matrix multiplication to update state vector
# g. Results calculated
# h. State vector and results vector outputed
# NOTE: The difference between v6 and v5 is that the former does not have a local RateMat inside the timestep function, instead modifying the global RateMatStat.
# NOTE: The difference between v7 and v6 is that the former does not have a loop over z inside the timestep function, instead using explicit linear combinations.
######## EXTRA INDICES ##########
i1 <- j1 <- rep(0,0); for(j in 0:6) { for (i in Vtemp1[1:10+j*10]+2) { i1[i]<-i; j1[i]<-j } }
i1 <- as.numeric(na.omit(i1)); j1 <- as.numeric(na.omit(j1))+1
a1 <- cbind(i1,i1+1); a2 <- cbind(i1,i1+2); a3 <- cbind(i1+1,i1+2)
a4 <- cbind(i1+1,i1); a5 <- cbind(i1+2,i1); a6 <- cbind(1:72+72,1:72+216)
a7 <- cbind(1:72+216,1:72+360); a8 <- cbind(73:504,rep(505,432))
i2 <- rep(Vtemp4[1:35],8)+rep(c(5:8,5:8+36),each=35)
a9 <- cbind(i2,rep(Vtemp4[1:35],8)+2+36)
a10 <- cbind(1,i2); a11 <- cbind(2,i2)
a12 <- cbind(i2,rep(Vtemp4[1:35],8)+rep(c(5:8+36,5:8+36),each=35))
a13 <- cbind(i2,rep(Vtemp4[1:35],8)+rep(c(3,3,4,4,3,3,4,4)+36,each=35))
a14 <- matrix(NA,7*6*8*5,7)
i3 <- Vtemp4[rep(rep(1:5,7*6),each=8)+rep(rep(rep(0:6*5,each=5),6),each=8)]+rep(c(5:8,5:8+36),5*6*7)
a14[,1] <- Vtemp4[rep(rep(1:5,7*6),each=8)+rep(rep(rep(0:6*5,each=5),6),each=8)]+rep(c(5:8,5:8+36),5*6*7)
a14[,2] <- Vtemp4[2+rep(rep(rep(0:6*5,each=5),6),each=8)]+rep(c(3,3,4,4,3,3,4,4)+36,5*6*7)
a14[,3] <- Vtemp4[3+rep(rep(rep(0:6*5,each=5),6),each=8)]+rep(c(3,3,4,4,3,3,4,4)+36,5*6*7)
a14[,4] <- Vtemp4[4+rep(rep(rep(0:6*5,each=5),6),each=8)]+rep(c(3,3,4,4,3,3,4,4)+36,5*6*7)
a14[,5] <- Vtemp4[4+rep(rep(rep(0:6*5,each=5),6),each=8)]+rep(c(3,3,4,4,3,3,4,4)+36,5*6*7)
a14[,6] <- Vtemp4[4+rep(rep(rep(0:6*5,each=5),6),each=8)]+rep(c(3,3,4,4,3,3,4,4)+36,5*6*7)
a14[,7] <- Vtemp4[5+rep(rep(rep(0:6*5,each=5),6),each=8)]+rep(c(3,3,4,4,3,3,4,4)+36,5*6*7)
i4 <- rep(0:6,each=10)+1; i5 <- rep(0:6,each=2*5*5)+1
a15 <- cbind(rep(rep(c(1,37),each=5),7)+(i4-1)*72,rep(rep(c(1,37),each=5),7)+(i4-1)*72+1+rep(0:4,14)*7)
a16 <- cbind(rep(rep(c(1,37),each=5),7)+(i4-1)*72,rep(rep(c(1,37),each=5),7)+(i4-1)*72+2+rep(0:4,14)*7)
a17 <- cbind(rep(rep(c(1,37),each=5),7)+(i4-1)*72,rep(rep(c(1,37),each=5),7)+(i4-1)*72+3+rep(0:4,14)*7)
a18 <- cbind(rep(rep(c(2,38),each=5*5),7)+(i5-1)*72+rep(0:4*7,7*2*5),rep(rep(c(2,38),each=5*5),7)+(i5-1)*72+0+rep(rep(0:4,each=5),7*2)*7)
a19 <- cbind(rep(rep(c(2,38),each=5*5),7)+(i5-1)*72+rep(0:4*7,7*2*5),rep(rep(c(2,38),each=5*5),7)+(i5-1)*72+1+rep(rep(0:4,each=5),7*2)*7)
a20 <- cbind(rep(rep(c(2,38),each=5*5),7)+(i5-1)*72+rep(0:4*7,7*2*5),rep(rep(c(2,38),each=5*5),7)+(i5-1)*72+2+rep(rep(0:4,each=5),7*2)*7)
a21 <- cbind(Vtemp1[1:70]+3,Vtemp1[1:70]+5); a22 <- cbind(Vtemp1[1:70]+3,Vtemp1[1:70]+6)
a23 <- cbind(Vtemp1[1:70]+4,Vtemp1[1:70]+7); a24 <- cbind(Vtemp1[1:70]+4,Vtemp1[1:70]+8)
a25 <- cbind(1:72,1:72+72); a26 <- cbind(1:72+360,1:72+432); a27 <- cbind(1:72+216,1:72+288)
i6 <- rep(0:13*36,each=35)+1; a28 <- cbind(rep(0:13*36,each=35)+1,rep(0:13*36,each=35)+rep(2:36,14))
i7 <- rep(0:13*36,each=30*6)+rep(rep(c(1,2,9,16,23,30),each=30),14); a29 <- cbind(rep(0:13*36,each=30*6)+rep(rep(c(1,2,9,16,23,30),each=30),14),rep(Vtemp7[1:30],6*14)+rep(0:13*36,each=30*6))
i8 <- rep(0:1*36,each=30)+1; a30 <- cbind(rep(0:1*36,each=30)+1,rep(Vtemp7[1:30],2)+rep(0:1*36,each=30))
i9 <- rep(2:13*36,each=30)+1; a31 <- cbind(rep(2:13*36,each=30)+1,rep(Vtemp7[1:30],12)+rep(2:13*36,each=30))
i10 <- rep(0:1*36,each=30*5)+rep(rep(c(2,9,16,23,30),each=30),2); a32 <- cbind(rep(0:1*36,each=30*5)+rep(rep(c(2,9,16,23,30),each=30),2),rep(Vtemp7[1:30],2*5)+rep(0:1*36,each=30*5))
i11 <- rep(2:13*36,each=30*5)+rep(rep(c(2,9,16,23,30),each=30),12); a33 <- cbind(rep(2:13*36,each=30*5)+rep(rep(c(2,9,16,23,30),each=30),12),rep(Vtemp7[1:30],12*5)+rep(2:13*36,each=30*5))
i12 <- rep(0:13*36,each=11*5)+rep(rep(c(1,2,3,9,10,16,17,23,24,30,31),each=5),14); a34 <- cbind(rep(0:13*36,each=11*5)+rep(rep(c(1,2,3,9,10,16,17,23,24,30,31),each=5),14),rep(c(4,11,18,25,32),11*14)+rep(0:13*36,each=11*5))
i13 <- rep(2:13*36,each=11*5)+rep(rep(c(1,2,3,9,10,16,17,23,24,30,31),each=5),12); a35 <- cbind(rep(2:13*36,each=11*5)+rep(rep(c(1,2,3,9,10,16,17,23,24,30,31),each=5),12),rep(c(4,11,18,25,32),11*12)+rep(2:13*36,each=11*5))
i14 <- rep(0:13*36,each=5)+rep(c(4,11,18,25,32),14); a36 <- cbind(rep(0:13*36,each=5)+rep(c(4,11,18,25,32),14),rep(0:13*36,each=5)+rep(c(4,11,18,25,32),14)+3)
i15 <- rep(0:13*36,each=5)+rep(c(3,10,17,24,31),14); a37 <- cbind(rep(0:13*36,each=5)+rep(c(3,10,17,24,31),14),rep(0:13*36,each=5)+rep(c(3,10,17,24,31),14)+2)
i16 <- rep(0:13*36,each=5)+rep(c(4,11,18,25,32),14); a38 <- cbind(rep(0:13*36,each=5)+rep(c(4,11,18,25,32),14),rep(0:13*36,each=5)+rep(c(4,11,18,25,32),14)+4)
i17 <- rep(0:13*36,each=5)+rep(c(3,10,17,24,31),14); a39 <- cbind(rep(0:13*36,each=5)+rep(c(3,10,17,24,31),14),rep(0:13*36,each=5)+rep(c(3,10,17,24,31),14)+3)
i18 <- rep(0:6*72,each=8*16)+rep(rep(c(10:11,17:18,24:25,31:32),each=16),7); a40 <- cbind(rep(0:6*72,each=8*16)+rep(rep(c(10:11,17:18,24:25,31:32),each=16),7),rep(c(12:15,19:22,26:29,33:36),8*7)+rep(0:6*72,each=8*16))
i19 <- rep(0:6*72,each=4*8)+rep(rep(c(24:25,31:32),each=8),7); a41 <- cbind(rep(0:6*72,each=4*8)+rep(rep(c(24:25,31:32),each=8),7),rep(c(26:29,33:36),4*7)+rep(0:6*72,each=4*8))
i20 <- rep(0:6*72,each=2*4)+rep(rep(31:32,each=4),7); a42 <- cbind(rep(0:6*72,each=2*4)+rep(rep(31:32,each=4),7),rep(33:36,2*7)+rep(0:6*72,each=2*4))
i21 <- rep(0:6*72+36,each=8*16)+rep(rep(c(10:11,17:18,24:25,31:32),each=16),7); a43 <- cbind(rep(0:6*72+36,each=8*16)+rep(rep(c(10:11,17:18,24:25,31:32),each=16),7),rep(c(12:15,19:22,26:29,33:36),8*7)+rep(0:6*72+36,each=8*16))
i22 <- rep(0:6*72+36,each=4*8)+rep(rep(c(24:25,31:32),each=8),7); a44 <- cbind(rep(0:6*72+36,each=4*8)+rep(rep(c(24:25,31:32),each=8),7),rep(c(26:29,33:36),4*7)+rep(0:6*72+36,each=4*8))
i23 <- rep(0:6*72+36,each=2*4)+rep(rep(31:32,each=4),7); a45 <- cbind(rep(0:6*72+36,each=2*4)+rep(rep(31:32,each=4),7),rep(33:36,2*7)+rep(0:6*72+36,each=2*4))
a46 <- cbind(1:505,1:505)
########################################################
########################################################
### B. SETTING UP STATIC PARTS OF RATE MATRIX (FOR SPEED OF TIMESTEP FUNCTION)
RateMatStat<- matrix(0,nrow=505,ncol=505); rownames(RateMatStat) <- StatNam; colnames(RateMatStat) <- StatNam
### B1. BREAKDOWN TO ACTIVE DISEASE (Stay in HIV / Resistance / Treatment subdivisions)
RateMatStat[a1] <- VrBreakD[j1]*(1-VpToIp[j1]); RateMatStat[a2] <- VrBreakD[j1]*VpToIp[j1]
### B2. SMEAR NEG CONVERT TO SMEAR POS (Stay in HIV / Resistance / Treatment subdivisions)
RateMatStat[a3] <- rNtoP
### B3. SPONTANEOUS CURE (Stay in HIV / Resistance / Treatment subdivisions)
RateMatStat[a4] <- VrIToLs[j1]; RateMatStat[a5] <- VrIToLs[j1]
### B4. HIV Progression
RateMatStat[a6] <- H1toH2; RateMatStat[a7] <- H2toH3
### B5. POPULATE MORTALITY RATES
RateMatStat[a8] <- rep(VmuHIV,each=72) # HIV mortality
RateMatStat[Vtemp1+3,505] <- RateMatStat[Vtemp1+3,505] + muIn # Untreated Smear-neg TB mortality
RateMatStat[Vtemp1+4,505] <- RateMatStat[Vtemp1+4,505] + muIp # Untreated Smear-pos TB mortality
VTrStatz <- rep(0,504) # Creates a vector for contact rates
VTrStatz[Vtemp1+3] <- rep(TrIn*RelFit,14) # Contact rates for smear neg
VTrStatz[Vtemp1+4] <- rep(RelFit,14) # Contact rates for smear pos
#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%
#%#%
timestep <- function(Vcurrent,t,ArtNdCov11,DIAG,OutMat1) { # Start of function!
#%#%
#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%
### C1. ADD NEW ENTRANTS TO STATE VECTOR
Vnext <- Vcurrent # Initializes new vector
Vnext[505] <- 0 # Clears out deaths
Vnext[1] <- Vnext[1] + NewEntt[t]*1000000 # Adds new entrants to NU0Su based on birth rate
### Compute the relative weights of each diacgnostic
coeff1 = (1 - PhaseIn1[t]) * (1 - PhaseIn2[t])
coeff2 = PhaseIn1[t] * (1 - PhaseIn2[t])
coeff3 = 0
if (DIAG == 1) {
coeff1 = coeff1 + PhaseIn2[t]
}
else if (DIAG == 2) {
coeff2 = coeff2 + PhaseIn2[t]
}
else { # DIAG = 3
coeff3 = coeff3 + PhaseIn2[t]
}
### TREATMENT TRANSITIONS, BY ALGORITHM
### B5. POPULATE MORTALITY RATES
RateMatStat[Vtemp6,505] <- RateMatStat[Vtemp6,505] + (coeff1/TxMatAlg1[1,Vtemp6] + coeff2/TxMatAlg2[1,Vtemp6] + coeff3/TxMatAlg3[1,Vtemp6]) *2*rep(c(muIn,muIn,muIp,muIp),70)*TunTxMort # Treatment TB mortality
RateMatStat[Vtemp9[101:120],505] <- muTBH # TB-HIV mortality for CD4 350
# Vector of current contact rates...
VTrStatz[Vtemp6] = (1 - (coeff1 * TxMatAlg1[2,Vtemp6] + coeff2 * TxMatAlg2[2,Vtemp6] + coeff3 * TxMatAlg3[2,Vtemp6]) * TxEft[t]) * rep(rep(c(TrIn, TrIn, 1, 1), 5) * rep(RelFit, each=4), 14)
# Contact rates for individuals on treatment
### B5. TREATMENT OUTCOMES (Stay in HIV / Resistance subdivisions)
RateMatStat[a9] <- RateMatStat[a9] + (coeff1*TxMatAlg1[a11]/TxMatAlg1[a10] + coeff2*TxMatAlg2[a11]/TxMatAlg2[a10] + coeff3*TxMatAlg3[a11]/TxMatAlg3[a10])*(12*TxEft[t]) # Cures back to Ls state, treatment experienced subdivision
RateMatStat[a12] <- RateMatStat[a12] + (coeff1*(1-TxEft[t]*TxMatAlg1[a11])/TxMatAlg1[a10] +coeff2*(1-TxEft[t]*TxMatAlg2[a11])/TxMatAlg2[a10] + coeff3*(1-TxEft[t]*TxMatAlg3[a11]) / TxMatAlg3[a10]) * (12*pReTx) # Failures identified and reinitiated on treatment, treatment experienced subdivision
vec1 = apply(cbind(0, 12 / TxMatAlg1[a10] * (rep(rep(c(pDeft[t], pDefND), each=35), 4) + (1 - TxEft[t] * TxMatAlg1[a11]) * (1-pReTx)) - colSums(TxMatAlg1[3:8, i2])), 1, max)
vec2 = apply(cbind(0, 12 / TxMatAlg2[a10] * (rep(rep(c(pDeft[t], pDefND), each=35), 4) + (1 - TxEft[t] * TxMatAlg2[a11]) * (1-pReTx)) - colSums(TxMatAlg2[3:8, i2])), 1, max)
vec3 = apply(cbind(0, 12 / TxMatAlg3[a10] * (rep(rep(c(pDeft[t], pDefND), each=35), 4) + (1 - TxEft[t] * TxMatAlg3[a11]) * (1-pReTx)) - colSums(TxMatAlg3[3:8, i2])), 1, max)
RateMatStat[a13] <- RateMatStat[a13] + (coeff1 * vec1 + coeff2 * vec2 + coeff3 * vec3) # Defaulters and failures to active disease
for(k in 1:6) {
RateMatStat[a14[,c(1,k+1)]] <- RateMatStat[a14[,c(1,k+1)]] + coeff1 * TxMatAlg1[k+2,i3] + coeff2 * TxMatAlg2[k+2,i3] + coeff3 * TxMatAlg3[k+2,i3]
} # Defaulters and failures to active disease with Acquired Resistance
### C3. UPDATE MORTALITY RATES WITH BACKGROUND MORTALITY
RateMatStat[-505,505] <- RateMatStat[-505,505]+mubt[t]
### C4. TB INCIDENCE (Can change strain subdivision, stay in HIV / treatment subd.)
VInf <- Vnext[1:504]/sum(Vnext[1:504])*VTrStatz*CRt[t] # P(meet carrier)*CR|carrier, homogeneous mixing
m <- c(sum(VInf[Vtemp2+0*7]),sum(VInf[Vtemp2+1*7]),sum(VInf[Vtemp2+2*7]),sum(VInf[Vtemp2+3*7]),sum(VInf[Vtemp2+4*7])); m <- rep(m,14)
RateMatStat[a15] <- RateMatStat[a15]+m*(1-Vpfast[i4])
RateMatStat[a16] <- RateMatStat[a16]+m*Vpfast[i4]*(1-VpToIp[i4])
RateMatStat[a17] <- RateMatStat[a17]+m*Vpfast[i4]*VpToIp[i4]
### C5. SUPERINFECTION (Can change strain subdivision, stay in HIV / treatment subd.)
VSupInf <- VInf*(1-rep(VPartIm,each=72)) # As above, with partial immunity, homogeneous mixing
v <- c(sum(VSupInf[Vtemp2+0*7]),sum(VSupInf[Vtemp2+1*7]),sum(VSupInf[Vtemp2+2*7]),sum(VSupInf[Vtemp2+3*7]),sum(VSupInf[Vtemp2+4*7])); v <- v[rep(rep(1:5,each=5),7*2)]
RateMatStat[a18] <- RateMatStat[a18]+v*(1-Vpfast[i5])
RateMatStat[a19] <- RateMatStat[a19]+v*Vpfast[i5]*(1-VpToIp[i5])
RateMatStat[a20] <- RateMatStat[a20]+v*Vpfast[i5]*VpToIp[i5]
### C6. DIAGNOSIS AND TREATMENT STRATEGY (Stay in HIV / Resistance / Treatment subdivisions)
# C6a. Specifying diagnosis and treatment as a result of algorithm
TxMat = coeff1 * TxMatAlg1 + coeff2 * TxMatAlg2 + coeff3 * TxMatAlg3
TruPosD = coeff1 * TruPosDAlg1 + coeff2 * TruPosDAlg2 + coeff3 * TruPosDAlg3
FalsPosD = coeff1 * FalsPosDAlg1 + coeff2 * FalsPosDAlg2 + coeff3 * FalsPosDAlg3
TruPosDB = coeff1 * TruPosDAlgB1 + coeff2 * TruPosDAlgB2 + coeff3 * TruPosDAlgB3
FalsPosDB = coeff1 * FalsPosDAlgB1 + coeff2 * FalsPosDAlgB2 + coeff3 * FalsPosDAlgB3
VTestCostD= coeff1 * VTestCostD1 + coeff2 * VTestCostD2 + coeff3 * VTestCostD3
VTxCost = coeff1 * VTxCost1 + coeff2 * VTxCost2 + coeff3 * VTxCost3
GetXpt = coeff1 * GetXpt1 + coeff2 * GetXpt2 + coeff3 * GetXpt3
# C6b. Diagnosis and tx initiation
RateMatStat[a21] <- DTestt[t]*TruPosD[1:70*2-1]*rTstIn # From In to Tn1
RateMatStat[a22] <- NDTestt[t]*TruPosND[1:70*2-1]*rTstIn # From In to Tn2
RateMatStat[a23] <- DTestt[t]*TruPosD[1:70*2] # From Ip to Tp1
RateMatStat[a24] <- NDTestt[t]*TruPosND[1:70*2] # From Ip to Tp2
### C8. HIV INCIDENCE and ART ENROLLMENT
# HIV incidence
RateMatStat[a25] <- rHIVt[t]
RMtemp <- RateMatStat; diag(RMtemp) <- 0
RMrowsum <- rowSums(RMtemp[c(217:288,361:432),])
OnTx <- sum(Vnext[c(145:216,289:360,433:504)])-sum(Vnext[c(145:216,289:360,433:504)]%*%(RateMatStat[c(145:216,289:360,433:504),-c(145:216,289:360,433:504)]/12))
TxNeed200 <- sum(Vnext[361:432])-sum(Vnext[361:432]%*%(RMtemp[361:432,]/12))
TxNeed350 <- sum(Vnext[217:288])-sum(Vnext[217:288]%*%(RMtemp[217:288,]/12))
##### ART Enrollment up to end 2011
if(t<(12*61+1)) {
# Below assumes preferential uptake from CD4<200
VH3toT3A <- max(0,min(1,(ArtHistt[t]-OnTx)/(TxNeed200+10^-6)))*(12-RMrowsum[73:144])
VH2toT2A <- max(0,min(1,(ArtHistt[t]-OnTx-TxNeed200)/(TxNeed350+10^-6)))*(12-RMrowsum[1:72])
# Below assumes equal probability of uptake from CD4<200 and 200-350
VH3toT3B <- max(0,min(1,(ArtHistt[t]-OnTx)/(TxNeed200+TxNeed350+10^-6)))*(12-RMrowsum[73:144])
VH2toT2B <- max(0,min(1,(ArtHistt[t]-OnTx)/(TxNeed200+TxNeed350+10^-6)))*(12-RMrowsum[1:72]) } else {
##### ART Enrollment post 2011
# ART enrollment under demand constraint
if(ARTConstr==1) {
# Below assumes preferential uptake from CD4<200
VH3toT3A <- max(0,min(1,(ARTVolt[t-732]-OnTx)/(TxNeed200+10^-6)))*(12-RMrowsum[73:144])
VH2toT2A <- max(0,min(1,(ARTVolt[t-732]-OnTx-TxNeed200)/(TxNeed350+10^-6)))*(12-RMrowsum[1:72])
# Below assumes equal probability of uptake from CD4<200 and 200-350
VH3toT3B <- max(0,min(1,(ARTVolt[t-732]-OnTx)/(TxNeed200+TxNeed350+10^-6)))*(12-RMrowsum[73:144])
VH2toT2B <- max(0,min(1,(ARTVolt[t-732]-OnTx)/(TxNeed200+TxNeed350+10^-6)))*(12-RMrowsum[1:72]) }
##### ART enrollment without demand constraint
if(ARTConstr==0|(ARTConstr==2&DIAG==2)) {
PctCov <- c(seq(ArtNdCov11,ArtFutCov,length.out=10*12),rep(ArtFutCov,21*12))[t-732]
VH3toT3A <- max(0,min(1,(PctCov*sum(Vnext[217:504])-OnTx)/(TxNeed200+10^-6)))*(12-RMrowsum[73:144])
VH2toT2A <- max(0,min(1,(PctCov*sum(Vnext[217:504])-OnTx-TxNeed200)/(TxNeed350+10^-6)))*(12-RMrowsum[1:72])
# Below assumes equal probability of uptake from CD4<200 and 200-350
VH3toT3B <- max(0,min(1,(PctCov*sum(Vnext[217:504])-OnTx)/(TxNeed200+TxNeed350+10^-6)))*(12-RMrowsum[73:144])
VH2toT2B <- max(0,min(1,(PctCov*sum(Vnext[217:504])-OnTx)/(TxNeed200+TxNeed350+10^-6)))*(12-RMrowsum[1:72]) }
##### ART enrollment with constraint formed by Status Quo
if(ARTConstr==2&DIAG==3) {
xxx <- OutMat1[,"NArt"]
VH3toT3A <- max(0,min(1,(xxx[t]-OnTx)/(TxNeed200+10^-6)))*(12-RMrowsum[73:144])
VH2toT2A <- max(0,min(1,(xxx[t]-OnTx-TxNeed200)/(TxNeed350+10^-6)))*(12-RMrowsum[1:72])
# Below assumes equal probability of uptake from CD4<200 and 200-350
VH3toT3B <- max(0,min(1,(xxx[t]-OnTx)/(TxNeed200+TxNeed350+10^-6)))*(12-RMrowsum[73:144])
VH2toT2B <- max(0,min(1,(xxx[t]-OnTx)/(TxNeed200+TxNeed350+10^-6)))*(12-RMrowsum[1:72]) } }
RateMatStat[a26] <- VH3toT3A*PriCD4200t[t] + VH3toT3B*(1-PriCD4200t[t])
RateMatStat[a27] <- VH2toT2A*PriCD4200t[t] + VH2toT2B*(1-PriCD4200t[t])
# C9. CONSTRUCT TRANSITION MATRIX
TransMat <- RateMatStat/12 # uses the rates to approximate the probabilities (means that probabilities are independent)
TransMat[a46] <- 1-(rowSums(TransMat)-TransMat[a46])
# C10. Calculate costs etc
CostTxD <- sum(Vnext[Vtemp1+5]*VTxCost[Vtemp1+5]+Vnext[Vtemp1+7]*VTxCost[Vtemp1+7])
CostTxND <- sum(Vnext[Vtemp1+6]*VTxCost[Vtemp1+6]+Vnext[Vtemp1+8]*VTxCost[Vtemp1+8])
CostRegD <- sum(Vnext[Vtemp1+5]*TxMat[9,Vtemp1+5]+Vnext[Vtemp1+7]*TxMat[9,Vtemp1+7])
CostRegND <- sum(Vnext[Vtemp1+6]*TxMat[9,Vtemp1+6]+Vnext[Vtemp1+8]*TxMat[9,Vtemp1+8])
CostFalsTxD <- sum(Vnext[Vtemp8]*rTstSL*DTestt[t]/12*FalsPosD*VTxCost[5]*1/(2+pDeft[t])*12)
CostFalsRegD <- sum(Vnext[Vtemp8]*rTstSL*DTestt[t]/12*FalsPosD*TxMat[9,5]*1/(2+pDeft[t])*12)
CostFalsTxND <- sum(Vnext[Vtemp8]*rTstSL*NDTestt[t]/12*FalsPosND*VTxCost[6]*1/(2+pDefND)*12)
CostFalsRegND <- sum(Vnext[Vtemp8]*rTstSL*NDTestt[t]/12*FalsPosND*TxMat[9,6]*1/(2+pDefND)*12)
CostART <- sum(Vnext[c(145:216,289:360,433:504)])*CArt
CostTestD <- sum(Vnext[-505]*Vtestfreq*DTestt[t]/12*VTestCostD)
CostTestND <- sum(Vnext[-505]*Vtestfreq*NDTestt[t]/12*VTestCostND)
# C10. MATRIX MULTIPLY TO UPDATE STATE VECTOR
Vnext <- Vnext%*%TransMat
# C11. OUTPUTS
# State Membership
Vout["NAll"] <- sum(Vnext[-505]) # Total N
Vout["Ndaly"] <- Vnext[-505]%*%(1-VDwt) # Total N, adjusted for YLD from HIV and TB
Vout["NAnyTb"] <- sum(Vnext[-505])- sum(Vnext[1+0:13*36]) # Any TB, incl latent infection and on treatment
Vout["NActDis"] <- sum(Vnext[Vtemp7]) # Active TB, incl those on treatment
Vout["NUnTx"] <- sum(Vnext[Vtemp9]) # Active TB, excl those on treatment
Vout["NUnTxH"] <- sum(Vnext[Vtemp9[21:140]]) # Active TB with HIV, excl those on treatment
Vout["NSmP"] <- sum(Vnext[Vtemp1+4])+sum(Vnext[Vtemp1+7])+sum(Vnext[Vtemp1+8]) # Smear positive, incl those on treatment
Vout["NStr1n"] <- sum(Vnext[rep(3:4,7)+rep(0:6*72,each=2)]) # Active TB not on tx, Pansensitive strain, tx naive
Vout["NStr2n"] <- sum(Vnext[rep(3:4,7)+rep(0:6*72,each=2)+7]) # Active TB not on tx, INH monores strain, tx naive
Vout["NStr3n"] <- sum(Vnext[rep(3:4,7)+rep(0:6*72,each=2)+14]) # Active TB not on tx, RIF monores strain, tx naive
Vout["NStr4n"] <- sum(Vnext[rep(3:4,7)+rep(0:6*72,each=2)+21]) # Active TB not on tx, MDR-TB strain, tx naive
Vout["NStr5n"] <- sum(Vnext[rep(3:4,7)+rep(0:6*72,each=2)+28]) # Active TB not on tx, MDR+ / XDR-TB strain, tx naive
Vout["NStr1e"] <- sum(Vnext[rep(39:40,7)+rep(0:6*72,each=2)]) # Active TB not on tx, Pansensitive strain, tx experienced
Vout["NStr2e"] <- sum(Vnext[rep(39:40,7)+rep(0:6*72,each=2)+7]) # Active TB not on tx, INH monores strain, tx experienced
Vout["NStr3e"] <- sum(Vnext[rep(39:40,7)+rep(0:6*72,each=2)+14]) # Active TB not on tx, RIF monores strain, tx experienced
Vout["NStr4e"] <- sum(Vnext[rep(39:40,7)+rep(0:6*72,each=2)+21]) # Active TB not on tx, MDR-TB strain, tx experienced
Vout["NStr5e"] <- sum(Vnext[rep(39:40,7)+rep(0:6*72,each=2)+28]) # Active TB not on tx, MDR+ / XDR-TB strain, tx experienced
Vout["NTxD"] <- sum(Vnext[Vtemp1+5])+sum(Vnext[Vtemp1+7]) # DOTS Treatment
Vout["NTxND"] <- sum(Vnext[Vtemp1+6])+sum(Vnext[Vtemp1+8]) # Non-DOTS Treatment
Vout["NHiv"] <- sum(Vnext[73:504]) # HIV
Vout["NHiv350"] <- sum(Vnext[217:504]) # HIV CD4 <350
Vout["NArt"] <- sum(Vnext[c(145:216,289:360,433:504)]) # On HAART
Vout["NTbH"] <- sum(Vnext[Vtemp7[-(1:60)]]) # TB-HIV (HIV) incl those on treatment
Vout["NTxSp"] <- sum(Vnext[Vtemp1+7])+sum(Vnext[Vtemp1+8]) # Smear Positive on Treatment
Vout["NMDR"] <- sum(Vnext[rep(c(24,25,31,32),7)+rep(0:13*36,each=4)]) # MDR, Active disease, not on treatment
# State Transitions
Vout["NMort"] <- Vnext[505] # All cause mortality
Vout["NHivMort"] <- as.vector(Vnext[73:504]%*%TransMat[73:504,505]) # Mortality in HIV +ve
Vout["NTbMort"] <- as.vector(Vnext[Vtemp7]%*%TransMat[Vtemp7,505]) # Mortality in Active TB / on treatment
Vout["NSmPMort"] <- as.vector(Vnext[c(Vtemp1+4,Vtemp1+7,Vtemp1+8)]%*%TransMat[c(Vtemp1+4,Vtemp1+7,Vtemp1+8),505])
# Mortality in Sm Pos Active TB / on treatment
Vout["NTbHMort"] <- as.vector(Vnext[Vtemp7[61:420]]%*%TransMat[Vtemp7[61:420],505]) # Mortality in TB-HIV
Vout["NInf"] <- sum(Vnext[i6]*TransMat[a28])
# New infections (ignores superinfection)
Vout["NCase"] <- sum(Vnext[i7]*TransMat[a29]) # New TB Cases (active disease)
Vout["NCaseNF"] <- sum(Vnext[i8]*TransMat[a30]) # New TB Cases, HIV-Neg, Fast (active disease)
Vout["NCaseHF"] <- sum(Vnext[i9]*TransMat[a31]) # New TB Cases, HIV-Pos, Fast (active disease)
Vout["NCaseNS"] <- sum(Vnext[i10]*TransMat[a32]) # New TB Cases, HIV-Neg, Slow (active disease)
Vout["NCaseHS"] <- sum(Vnext[i11]*TransMat[a33]) # New TB Cases, HIV-Pos, Slow (active disease)
Vout["NCaseIp"] <- sum(Vnext[i12]*TransMat[a34]) # New Smear-positive TB Cases (from Su,Ls and In)
Vout["NCaseIpHiv"] <- sum(Vnext[i13]*TransMat[a35]) # New Smear-positive TB Cases in HIV CD4<500 (from Su,Ls and In)
Vout["SuspctD"] <- sum(Vnext[-505]*Vtestfreq*DTestt[t]/12) # No suspects, DOTS programs
Vout["SuspctDTB"] <- sum((Vnext[-505]*Vtestfreq*DTestt[t]/12)[Vtemp9]) # No suspects, DOTS programs
Vout["SuspctND"] <- sum(Vnext[-505]*Vtestfreq*NDTestt[t]/12) # No suspects, Non-DOTS programs
Vout["NCdIpD"] <- sum(Vnext[i14]*TransMat[a36]) # TB Case detections, Smear Pos, DOTS,(minus losses before tx init)
Vout["NCdInD"] <- sum(Vnext[i15]*TransMat[a37]) # TB Case detections, Smear Neg, DOTS,(minus losses before tx init)
Vout["NCdIpND"] <- sum(Vnext[i16]*TransMat[a38]) # TB Case detections, Smear Pos, NonDOTS,(minus losses before tx init)
Vout["NCdInND"] <- sum(Vnext[i17]*TransMat[a39]) # TB Case detections, Smear Neg, NonDOTS,(minus losses before tx init)
Vout["NCdFalsD"] <- sum(Vnext[Vtemp8]*rTstSL*DTestt[t]/12*FalsPosD) # False-positive diagnoses, DOTS ,(minus losses before tx init)
Vout["NCdFalsND"] <- sum(Vnext[Vtemp8]*rTstSL*NDTestt[t]/12*FalsPosND) # False-positive diagnoses, Non-DOTS ,(minus losses before tx init)
Vout["NTxResU"] <- sum(Vnext[i18]*TransMat[a40]) # Any resistance starting treatment (tx naive)
Vout["NTxMdrU"] <- sum(Vnext[i19]*TransMat[a41]) # MDR starting treatment (incl XDR) (tx naive)
Vout["NTxXdrU"] <- sum(Vnext[i20]*TransMat[a42]) # MDR+/XDR starting treatment (tx naive)
Vout["NTxResR"] <- sum(Vnext[i21]*TransMat[a43]) # Any resistance starting treatment (tx experienced)
Vout["NTxMdrR"] <- sum(Vnext[i22]*TransMat[a44]) # MDR starting treatment (incl XDR) (tx experienced)
Vout["NTxXdrR"] <- sum(Vnext[i23]*TransMat[a45]) # MDR+/XDR starting treatment (tx experienced)
# Costs
Vout["CostTxD"] <- CostTxD # Non-drug cost for treatment in DOTS programs
Vout["CostTxND"] <- CostTxND # Non-drug cost for treatment in Non-DOTS programs
Vout["CostRegD"] <- CostRegD # Drug cost for treatment in DOTS programs
Vout["CostRegND"] <- CostRegND # Drug cost for treatment in Non-DOTS programs
Vout["CostFalsTxD"] <- CostFalsTxD # Non-drug cost for treatment in DOTS programs
Vout["CostFalsTxND"] <- CostFalsTxND # Non-drug cost for treatment in Non-DOTS programs
Vout["CostFalsRegD"] <- CostFalsRegD # Drug cost for treatment in DOTS programs
Vout["CostFalsRegND"] <- CostFalsRegND # Drug cost for treatment in Non-DOTS programs
Vout["CostART"] <- CostART # HAART costs
Vout["CostTestD"] <- CostTestD # Diagnosis costs in DOTS programs
Vout["CostTestND"]<- CostTestND # Diagnosis costs in Non-DOTS programs
Vout["TC"] <- CostTxD+CostTxND+CostRegD+CostRegND+CostFalsTxD+CostFalsTxND+CostFalsRegD+CostFalsRegND+CostART+CostTestD+CostTestND
# Total Costs
# Additional outcomes
Vout["Check1"] <- min(TransMat[a46]) # Check to see p(stay in state) doesnt become negative
Vout["PfailDtx"]<- sum(Vnext[Vtemp6[1:140*2-1]]*(12/TxMat[1,Vtemp6[1:140*2-1]]*(1-TxEft[t]*TxMat[2,Vtemp6[1:140*2-1]])))/
(sum(Vnext[Vtemp6[1:140*2-1]]*(12/TxMat[1,Vtemp6[1:140*2-1]]+12/TxMat[1,Vtemp6[1:140*2-1]]*pDeft[t]+RateMatStat[Vtemp6[1:140*2-1],505]))+10^-6)
# Average failure probability in DOTS programs
Vout["PcureDtx"] <- sum(Vnext[Vtemp6[1:140*2-1]]*(12/TxMat[1,Vtemp6[1:140*2-1]]*TxEft[t]*TxMat[2,Vtemp6[1:140*2-1]]))/
(sum(Vnext[Vtemp6[1:140*2-1]]*(12/TxMat[1,Vtemp6[1:140*2-1]]+12/TxMat[1,Vtemp6[1:140*2-1]]*pDeft[t]+RateMatStat[Vtemp6[1:140*2-1],505]))+10^-6)
# Average cure probability in DOTS programs
Vout["PdfltDtx"] <- sum(Vnext[Vtemp6[1:140*2-1]]* 12/TxMat[1,Vtemp6[1:140*2-1]]*pDeft[t])/
(sum(Vnext[Vtemp6[1:140*2-1]]*(12/TxMat[1,Vtemp6[1:140*2-1]]+ 12/TxMat[1,Vtemp6[1:140*2-1]]*pDeft[t]+RateMatStat[Vtemp6[1:140*2-1],505]))+10^-6)
# Average default probability in DOTS programs
Vout["PmortDtx"] <- sum(Vnext[Vtemp6[1:140*2-1]]*RateMatStat[Vtemp6[1:140*2-1],505])/
(sum(Vnext[Vtemp6[1:140*2-1]]*(12/TxMat[1,Vtemp6[1:140*2-1]]+ 12/TxMat[1,Vtemp6[1:140*2-1]]*pDeft[t]+RateMatStat[Vtemp6[1:140*2-1],505]))+10^-6)
# Average mortality probability in DOTS programs
Vout["DurInfSn"] <- 1/((sum(Vnext[Vtemp1+3]*apply(TransMat[Vtemp1+3,c(Vtemp1+2,Vtemp6,505)],1,sum))+10^-6)/(sum(Vnext[Vtemp1+3])+10^-6))/12
# Duration of infectiousness smear negative
Vout["DurInfSp"] <-1/((sum(Vnext[Vtemp1+4]*apply(TransMat[Vtemp1+4,c(Vtemp1+2,Vtemp6,505)],1,sum))+10^-6)/(sum(Vnext[Vtemp1+4])+10^-6))/12
# Duration of infectiousness smear positive
Vout["DurInfAll"] <-1/((sum(Vnext[c(Vtemp1+3,Vtemp1+4)]*apply(TransMat[c(Vtemp1+3,Vtemp1+4),c(Vtemp1+2,Vtemp6,505)],1,sum))+10^-6)/(sum(Vnext[c(Vtemp1+3,Vtemp1+4)])+10^-6))/12
# Duration of infectiousness, all
Vout["EffContRate"] <- sum(Vnext[c(Vtemp1+3,Vtemp1+4)]*VTrStatz[c(Vtemp1+3,Vtemp1+4)])/(sum(Vnext[c(Vtemp1+3,Vtemp1+4)])+10^-6)*CRt[t]
# Effective contact rate, untreated active disease
Vout["ExTbC"] <- sum(Vnext[Vtemp9[1:20]]*apply(TransMat[Vtemp9[1:20],Vtemp1+2],1,sum))
Vout["ExTbT"] <- sum(Vnext[Vtemp9[1:20]]*apply(TransMat[Vtemp9[1:20],Vtemp6],1,sum))
Vout["ExTbD"] <- sum(Vnext[Vtemp9[1:20]]*TransMat[Vtemp9[1:20],505]) # Non-HIV Exits from active TB, self-cure/treatment/death
Vout["ExTbCH"] <- sum(Vnext[Vtemp9[21:140]]*apply(TransMat[Vtemp9[21:140],Vtemp1+2],1,sum))
Vout["ExTbTH"] <- sum(Vnext[Vtemp9[21:140]]*apply(TransMat[Vtemp9[21:140],Vtemp6],1,sum))
Vout["ExTbDH"] <- sum(Vnext[Vtemp9[21:140]]*TransMat[Vtemp9[21:140],505]) # HIV Exits from active TB, self-cure/treatment/death
# Test Characteristics
Vout["NotifD"] <- sum(Vnext[Vtemp9]*Vtestfreq[Vtemp9]*DTestt[t]/12*TruPosDB) +
sum(Vnext[Vtemp8]*Vtestfreq[Vtemp8]*DTestt[t]/12*FalsPosDB) # DOTS Notifications (true and false positive, ignoring LTFU)
Vout["NotifTBD"] <- sum(Vnext[Vtemp9]*Vtestfreq[Vtemp9]*DTestt[t]/12*TruPosDB) # DOTS Notifications (true positive, ignoring LTFU)
Vout["NotifND"] <- sum(Vnext[Vtemp9]*Vtestfreq[Vtemp9]*NDTestt[t]/12*TruPosNDB) +
sum(Vnext[Vtemp8]*Vtestfreq[Vtemp8]*NDTestt[t]/12*FalsPosNDB) # Non-DOTS Notifications (true and false positive, ignoring LTFU)
Vout["PPVTb"] <- (sum(Vnext[Vtemp1+3]*Vtestfreq[Vtemp1+3]*DTestt[t]/12*TruPosDB[1:70*2-1]) +
sum(Vnext[Vtemp1+4]*Vtestfreq[Vtemp1+4]*DTestt[t]/12*TruPosDB[1:70*2]))/(Vout["NotifD"]+10^-6)
# Positive predictive value, DOTS TB diagnosis
Vout["NPVTb"] <- sum(Vnext[Vtemp8]*Vtestfreq[Vtemp8]*DTestt[t]/12*(1-FalsPosDB))/((Vout["SuspctD"]-Vout["NotifD"])+10^-6)
# Negative predictive value, TB diagnosis
Vout["PPVRif"] <- (sum(Vnext[Vtemp1+3]*Vtestfreq[Vtemp1+3]*DTestt[t]/12*TruPosDB[1:70*2-1]*GetXpt[Vtemp1+3]*rep(c(rep(0,2),rep(SensXpRIF,3)),14)) +
sum(Vnext[Vtemp1+4]*Vtestfreq[Vtemp1+4]*DTestt[t]/12*TruPosDB[1:70*2]*GetXpt[Vtemp1+4]*rep(c(rep(0,2),rep(SensXpRIF,3)),14)))/
((sum(Vnext[Vtemp1+3]*Vtestfreq[Vtemp1+3]*DTestt[t]/12*TruPosDB[1:70*2-1]*GetXpt[Vtemp1+3]*rep(c(rep((1-SpecXpRIF),2),rep(SensXpRIF,3)),14)) +
sum(Vnext[Vtemp1+4]*Vtestfreq[Vtemp1+4]*DTestt[t]/12*TruPosDB[1:70*2]*GetXpt[Vtemp1+4]*rep(c(rep((1-SpecXpRIF),2),rep(SensXpRIF,3)),14))+
sum(Vnext[Vtemp8]*Vtestfreq[Vtemp8]*DTestt[t]/12*FalsPosDB*GetXpt[Vtemp8])*(1-SpecXpRIF))+10^-6)
# Positive predictive value, RIF resistant diagnosis (with Xpert for all scenario)
Vout["NPVRif"] <- (sum(Vnext[Vtemp1+3]*Vtestfreq[Vtemp1+3]*DTestt[t]/12*TruPosDB[1:70*2-1]*GetXpt[Vtemp1+3]*rep(c(rep(SpecXpRIF,2),rep(0,3)),14)) +
sum(Vnext[Vtemp1+4]*Vtestfreq[Vtemp1+4]*DTestt[t]/12*TruPosDB[1:70*2]*GetXpt[Vtemp1+4]*rep(c(rep(SpecXpRIF,2),rep(0,3)),14))+
sum(Vnext[Vtemp8]*Vtestfreq[Vtemp8]*DTestt[t]/12*FalsPosDB*GetXpt[Vtemp8])*SpecXpRIF)/
((sum(Vnext[Vtemp1+3]*Vtestfreq[Vtemp1+3]*DTestt[t]/12*TruPosDB[1:70*2-1]*GetXpt[Vtemp1+3]*rep(c(rep(SpecXpRIF,2),rep((1-SensXpRIF),3)),14)) +
sum(Vnext[Vtemp1+4]*Vtestfreq[Vtemp1+4]*DTestt[t]/12*TruPosDB[1:70*2]*GetXpt[Vtemp1+4]*rep(c(rep(SpecXpRIF,2),rep((1-SensXpRIF),3)),14))+
sum(Vnext[Vtemp8]*Vtestfreq[Vtemp8]*DTestt[t]/12*FalsPosDB*GetXpt[Vtemp8])*SpecXpRIF)+10^-6)
# Negative predictive value, RIF resistant diagnosis (with Xpert for all scenario)
Vout["PDst"] <- (sum(Vnext[Vtemp9]*Vtestfreq[Vtemp9]*DTestt[t]/12*TruPosDB*rep(c(rep(pDstU*PhaseIn1[t],10),rep(pDstR*PhaseIn1[t],10)),7))+
sum(Vnext[Vtemp8]*Vtestfreq[Vtemp8]*DTestt[t]/12*FalsPosDB*rep(c(rep(pDstU*PhaseIn1[t],6),rep(pDstR*PhaseIn1[t],6)),7)))/(Vout["NotifD"]+10^-6)
# No. getting a DST, UNDER BASECASE ALGORITHM
Vout["GetXpt"] <- sum(Vnext[-505]*Vtestfreq*DTestt[t]/12*GetXpt)
Vout["ArtCov"] <- sum(Vnext[c(145:216,289:360,433:504)])/sum(Vnext[73:504])
Vout["ArtNdCov"] <- sum(Vnext[c(289:360,433:504)])/sum(Vnext[217:504])
Vout["Art200Cov"] <- sum(Vnext[433:504])/sum(Vnext[361:504])
#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%
#%#%
return(list(Vnext=Vnext,Vout=Vout))
} # End of function!
#%#%
#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%#%
# sum(RateMateInit-RateMat);sum(VoutInit-Vout);sum(VnextInit-Vnext)