Extra tables and figures and an appendix

(Posted as supplied by author)

Table A: Countries analysed in each African region

Afr-D

Afr-E

Algeria

Botswana

Angola

Burundi

Benin

Central African Republic

Burkina Faso

Congo

Cameroon

Cote d’Ivoire

Cape Verde

Democratic Republic of the Congo

Chad

Eritrea

Comoros

Ethiopia

Equatorial Guinea

Kenya

Gabon

Lesotho

Gambia

Malawi

Ghana

Mozambique

Guinea

Namibia

Guinea Bissau

Rwanda

Liberia

South Africa

Madagascar

Swaziland

Mali

Uganda

Mauritania

United Republic of Tanzania

Mauritius

Zambia

Niger

Zimbabwe

Nigeria

 

Sao Tome and Principe

 

Senegal

 

Seychelles

 

Sierra Leone

 

Togo

 

 

 

(Posted as supplied by author)

Table B: Estimation of effectiveness

Intervention/

Parameter

Value

Source/Notes

ITN

  

Adherence

65%

Estimate within range suggested to achieve impactw8

Probability of success when not fully compliant

0%

Estimate based on binary response of whether or not an individual has slept under the net

    • resulting reduction in incidence

    50%

    w8

      • resulting reduction in case fatality

      20%

      w9

      IRS

        

      Adherence

      100%

      Estimate based on household level to achieve impact

      Probability of success when not fully compliant

      0%

      Estimate based on dosing schedule and pharmacokinetic properties

        • resulting reduction in incidence

        50%

        Assumed to be similar to ITNsw3,w10,w11

          • resulting reduction in case fatality

          20%

          Assumed to be similar to ITNsw3,w10,w11

          CQ

            

          Adherence

          40%

          Estimate based on relative length and complexity of the regimen

          Probability of success when not fully compliant

          20%

          Estimate based on dosing schedule and pharmacokinetic properties

          Initial resistance

          0.3

          w2

          Growth rate of resistance

          0.1

          w2

            • resulting reduction in case fatality

            27%

            See appendix (drugs) for details of calculation

            SP

              

            Adherence

            90%

            Estimate based on relative length and complexity of the regimen

            Probability of success when not fully compliant

            0%

            Estimate based on dosing schedule and pharmacokinetic properties

            Initial resistance

            0.1

            w2

            Growth rate of resistance

            0.4

            w2

              • resulting reduction in case fatality

              44%

              See appendix (drugs) for details of calculation

              CQ-SP

               

              Assumed to be co-administered, not co-formulated

              Adherence

              35%

              Estimate based on relative length and complexity of the regimen

              Probability of success when not fully compliant

              45%

              Estimate based on dosing schedule and pharmacokinetic properties

              Initial resistance

              0.1

              w2

              Growth rate of resistance

              0.1

              w2

                • resulting reduction in case fatality

                48%

                 

                ACT

                 

                Assumed to be blister-packed and/or co-formulated

                Adherence

                40%

                Estimate based on relative length and complexity of the regimen

                Probability of success when not fully compliant

                45%

                Estimate based on dosing schedule and pharmacokinetic properties

                Initial resistance

                0.001

                w2

                Growth rate of resistance

                0.05

                w2

                  • reduction in case fatality

                  63%

                  See appendix (drugs) for details of calculation

                  IPTp (SP)

                    

                  Adherence

                  80%

                  Estimate based on relative length and complexity of the regimen

                  Probability of success when not fully compliant

                  10%

                  Estimate based on dosing schedule and pharmacokinetic properties

                  Initial resistance

                  0.1

                  w2

                  Growth rate of resistance

                  0.1

                  w2

                    • reduction in case fatality

                    3.4%

                    Assumes baseline reduction of 5% based on model developed by Goodman et al 2000w12; See methods section for details of calculation of net effect

                     

                     

                     

                    (Posted as supplied by author)

                    Table C: Detailed cost-effectiveness results

                    Description of intervention,

                    Region

                    Average yearly costs, $int

                    Average yearly effectiveness (DALYs averted)

                    Average cost effectiveness ($int per DALY averted)

                    Incremental cost effectiveness ($int per DALY averted)

                    Afr-D

                        

                    ITN -- 95% cov.

                    254,277,140

                    8,872,378

                    29

                    Dominated

                    IPTp -- 95% cov.

                    22,782,339

                    92,104

                    247

                    Dominated

                    IRS -- 95% cov.

                    282,976,169

                    8,872,378

                    32

                    Dominated

                    CQ -- 95% cov.

                    93,804,789

                    3,921,597

                    24

                    Dominated

                    SP -- 95% cov.

                    93,838,374

                    6,448,511

                    15

                    Dominated

                    Comb -- 95% cov.

                    93,960,837

                    7,034,184

                    13

                    Dominated

                    ACT -- 95% cov.

                    95,609,717

                    9,254,473

                    10

                    15.65

                    ITN & CQ -- 95% cov.

                    313,765,847

                    10,611,816

                    30

                    Dominated

                    ITN & SP -- 95% cov.

                    313,893,918

                    11,725,990

                    27

                    Dominated

                    ITN & Combo -- 95% cov.

                    313,985,895

                    11,983,490

                    26

                    Dominated

                    ITN & ACT -- 95% cov.

                    314,977,037

                    12,957,175

                    24

                    Dominated

                    IRS & CQ -- 95% cov.

                    337,452,801

                    10,611,816

                    32

                    Dominated

                    IRS & SP -- 95% cov.

                    337,611,872

                    11,725,990

                    29

                    Dominated

                    IRS & Combo -- 95% cov.

                    337,711,011

                    11,983,490

                    28

                    Dominated

                    IRS & ACT -- 95% cov.

                    338,729,226

                    12,957,175

                    26

                    Dominated

                    IRS & ACT & IPTp -- 95% cov.

                    339,298,766

                    12,972,791

                    26

                    Dominated

                    ITN & ACT & IPTp -- 95% cov.

                    315,546,119

                    12,972,791

                    24

                    59

                    IRS & ITN -- 95% cov.

                    444,540,358

                    12,675,957

                    35

                    Dominated

                    IRS & ITN & ACT -- 95% cov.

                    467,328,380

                    14,554,556

                    32

                    Dominated

                    IRS & ITN & ACT & IPTp -- 95% cov.

                    467,673,321

                    14,561,792

                    32

                    96

                    ITN -- 80% cov.

                    224,730,197

                    7,629,171

                    29

                    Dominated

                    IPTp -- 80% cov.

                    18,404,318

                    77,556

                    237

                    Dominated

                    IRS -- 80% cov.

                    239,471,420

                    7,629,171

                    31

                    Dominated

                    CQ -- 80% cov.

                    70,895,223

                    3,298,390

                    21

                    Dominated

                    SP -- 80% cov.

                    70,913,875

                    5,419,512

                    13

                    Dominated

                    Comb -- 80% cov.

                    71,014,283

                    5,910,663

                    12

                    Dominated

                    ACT -- 80% cov.

                    72,386,626

                    7,771,018

                    9

                    9

                    ITN & CQ -- 80% cov.

                    260,865,735

                    9,284,603

                    28

                    Dominated

                    ITN & SP -- 80% cov.

                    293,776,655

                    10,344,348

                    28

                    Dominated

                    ITN & Combo -- 80% cov.

                    261,049,692

                    10,589,200

                    25

                    Dominated

                    ITN & ACT -- 80% cov.

                    294,978,860

                    11,514,826

                    26

                    Dominated

                    IRS & CQ -- 80% cov.

                    276,362,347

                    9,284,603

                    30

                    Dominated

                    IRS & SP -- 80% cov.

                    276,488,434

                    10,344,348

                    27

                    Dominated

                    IRS & Combo -- 80% cov.

                    276,576,876

                    10,589,200

                    26

                    Dominated

                    IRS & ACT -- 80% cov.

                    277,522,810

                    11,514,826

                    24

                    Dominated

                    IRS & ACT & IPTp -- 80% cov.

                    277,868,610

                    11,529,641

                    24

                    Dominated

                    ITN & ACT & IPTp -- 80% cov.

                    262,319,382

                    11,529,641

                    23

                    Dominated

                    IRS & ITN -- 80% cov.

                    385,160,639

                    11,123,636

                    35

                    Dominated

                    IRS & ITN & ACT -- 80% cov.

                    407,116,404

                    13,261,860

                    31

                    Dominated

                    IRS & ITN & ACT & IPTp -- 80% cov.

                    407,407,031

                    13,270,038

                    31

                    Dominated

                    ITN -- 50% cov.

                    166,705,327

                    4,961,812

                    34

                    Dominated

                    IPTp -- 50% cov.

                    17,190,375

                    48,466

                    355

                    Dominated

                    IRS -- 50% cov.

                    148,997,834

                    4,961,812

                    30

                    Dominated

                    CQ -- 50% cov.

                    64,076,020

                    2,056,500

                    31

                    Dominated

                    SP -- 50% cov.

                    64,083,603

                    3,373,747

                    19

                    Dominated

                    Comb -- 50% cov.

                    64,144,985

                    3,678,178

                    17

                    Dominated

                    ACT -- 50% cov.

                    64,992,004

                    4,829,313

                    13

                    Dominated

                    ITN & CQ -- 50% cov.

                    193,184,118

                    6,229,432

                    31

                    Dominated

                    ITN & SP -- 50% cov.

                    256,065,911

                    7,039,542

                    36

                    Dominated

                    ITN & Combo -- 50% cov.

                    193,290,021

                    7,226,565

                    27

                    Dominated

                    ITN & ACT -- 50% cov.

                    257,254,619

                    7,933,061

                    32

                    Dominated

                    IRS & CQ -- 50% cov.

                    192,344,080

                    6,229,432

                    31

                    Dominated

                    IRS & SP -- 50% cov.

                    192,405,053

                    7,039,542

                    27

                    Dominated

                    IRS & Combo -- 50% cov.

                    192,464,601

                    7,226,565

                    27

                    Dominated

                    IRS & ACT -- 50% cov.

                    193,158,204

                    7,933,061

                    24

                    Dominated

                    IRS & ACT & IPTp -- 50% cov.

                    193,347,670

                    7,944,332

                    24

                    Dominated

                    ITN & ACT & IPTp -- 50% cov.

                    194,162,562

                    7,944,332

                    24

                    Dominated

                    IRS & ITN -- 50% cov.

                    267,866,814

                    7,499,565

                    36

                    Dominated

                    IRS & ITN & ACT -- 50% cov.

                    289,831,107

                    9,510,715

                    30

                    Dominated

                    IRS & ITN & ACT & IPTp -- 50% cov.

                    289,990,658

                    9,518,346

                    30

                    Dominated

                    Afr-E

                        

                    ITN -- 95% cov.

                    243,893,889

                    5,908,330

                    41

                    Dominated

                    IPTp -- 95% cov.

                    20,606,834

                    58,589

                    352

                    Dominated

                    IRS -- 95% cov.

                    244,519,970

                    5,908,330

                    41

                    Dominated

                    CQ -- 95% cov.

                    71,620,401

                    2,503,983

                    29

                    Dominated

                    SP -- 95% cov.

                    71,633,984

                    4,109,851

                    17

                    Dominated

                    Comb -- 95% cov.

                    71,726,621

                    4,481,207

                    16

                    Dominated

                    ACT -- 95% cov.

                    73,000,256

                    5,886,159

                    12

                    12.40

                    ITN & CQ -- 95% cov.

                    283,198,057

                    7,285,807

                    39

                    Dominated

                    ITN & SP -- 95% cov.

                    253,901,457

                    8,166,581

                    31

                    Dominated

                    ITN & Combo -- 95% cov.

                    283,367,274

                    8,369,968

                    34

                    Dominated

                    ITN & ACT -- 95% cov.

                    254,755,715

                    9,138,452

                    28

                    55.89

                    IRS & CQ -- 95% cov.

                    294,706,173

                    7,285,807

                    40

                    Dominated

                    IRS & SP -- 95% cov.

                    294,813,050

                    8,166,581

                    36

                    Dominated

                    IRS & Combo -- 95% cov.

                    294,898,541

                    8,369,968

                    35

                    Dominated

                    IRS & ACT -- 95% cov.

                    295,848,380

                    9,138,452

                    32

                    Dominated

                    IRS & ACT & IPTp -- 95% cov.

                    297,508,799

                    9,150,654

                    33

                    Dominated

                    ITN & ACT & IPTp -- 95% cov.

                    285,960,854

                    9,150,654

                    31

                    Dominated

                    IRS & ITN -- 95% cov.

                    417,786,013

                    8,745,929

                    48

                    Dominated

                    IRS & ITN & ACT -- 95% cov.

                    441,216,954

                    10,721,678

                    41

                    118

                    IRS & ITN & ACT & IPTp -- 95% cov.

                    442,342,075

                    10,729,154

                    41

                    151

                    ITN -- 80% cov.

                    217,147,049

                    5,156,555

                    42

                    Dominated

                    IPTp -- 80% cov.

                    19,689,795

                    50,388

                    391

                    Dominated

                    IRS -- 80% cov.

                    207,739,476

                    5,156,555

                    40

                    Dominated

                    CQ -- 80% cov.

                    68,956,191

                    2,152,560

                    32

                    Dominated

                    SP -- 80% cov.

                    68,965,211

                    3,531,517

                    20

                    Dominated

                    Comb -- 80% cov.

                    69,043,378

                    3,850,229

                    18

                    Dominated

                    ACT -- 80% cov.

                    70,123,532

                    5,055,437

                    14

                    Dominated

                    ITN & CQ -- 80% cov.

                    252,277,432

                    6,428,029

                    39

                    Dominated

                    ITN & SP -- 80% cov.

                    281,775,820

                    7,240,619

                    39

                    Dominated

                    ITN & Combo -- 80% cov.

                    252,417,222

                    7,428,216

                    34

                    Dominated

                    ITN & ACT -- 80% cov.

                    282,861,375

                    8,136,888

                    35

                    Dominated

                    IRS & CQ -- 80% cov.

                    257,113,360

                    6,428,029

                    40

                    Dominated

                    IRS & SP -- 80% cov.

                    257,196,381

                    7,240,619

                    36

                    Dominated

                    IRS & Combo -- 80% cov.

                    257,271,146

                    7,428,216

                    35

                    Dominated

                    IRS & ACT -- 80% cov.

                    258,126,588

                    8,136,888

                    32

                    Dominated

                    IRS & ACT & IPTp -- 80% cov.

                    259,253,805

                    8,148,125

                    32

                    Dominated

                    ITN & ACT & IPTp -- 80% cov.

                    254,386,921

                    8,148,125

                    31

                    Dominated

                    IRS & ITN -- 80% cov.

                    363,023,981

                    7,730,361

                    47

                    Dominated

                    IRS & ITN & ACT -- 80% cov.

                    384,638,944

                    9,678,725

                    40

                    Dominated

                    IRS & ITN & ACT & IPTp -- 80% cov.

                    385,586,428

                    9,686,077

                    40

                    Dominated

                    ITN -- 50% cov.

                    163,783,165

                    3,312,998

                    49

                    Dominated

                    IPTp -- 50% cov.

                    18,770,275

                    31,489

                    596

                    Dominated

                    IRS -- 50% cov.

                    133,035,146

                    3,312,998

                    40

                    Dominated

                    CQ -- 50% cov.

                    65,718,603

                    1,343,275

                    49

                    Dominated

                    SP -- 50% cov.

                    65,722,956

                    2,201,621

                    30

                    Dominated

                    Comb -- 50% cov.

                    65,771,428

                    2,399,767

                    27

                    Dominated

                    ACT -- 50% cov.

                    66,443,687

                    3,148,238

                    21

                    Dominated

                    ITN & CQ -- 50% cov.

                    191,879,461

                    4,213,508

                    46

                    Dominated

                    ITN & SP -- 50% cov.

                    232,573,857

                    4,788,216

                    49

                    Dominated

                    ITN & Combo -- 50% cov.

                    191,957,235

                    4,920,806

                    39

                    Dominated

                    ITN & ACT -- 50% cov.

                    233,468,213

                    5,421,383

                    43

                    Dominated

                    IRS & CQ -- 50% cov.

                    183,392,851

                    4,213,508

                    44

                    Dominated

                    IRS & SP -- 50% cov.

                    183,430,404

                    4,788,216

                    38

                    Dominated

                    IRS & Combo -- 50% cov.

                    183,478,586

                    4,920,806

                    37

                    Dominated

                    IRS & ACT -- 50% cov.

                    184,067,612

                    5,421,383

                    34

                    Dominated

                    IRS & ACT & IPTp -- 50% cov.

                    184,771,948

                    5,429,305

                    34

                    Dominated

                    ITN & ACT & IPTp -- 50% cov.

                    193,244,869

                    5,429,305

                    36

                    Dominated

                    IRS & ITN -- 50% cov.

                    253,426,000

                    5,082,819

                    50

                    Dominated

                    IRS & ITN & ACT -- 50% cov.

                    270,276,675

                    6,603,300

                    41

                    Dominated

                    IRS & ITN & ACT & IPTp -- 50% cov.

                    270,868,802

                    6,609,013

                    41

                    Dominated

                     

                     

                     

                    (Posted as supplied by author)

                    Figure A: Cost effectiveness plane showing 60 analysed interventions (20 individual and combination interventions at 3 assumed coverage levels) and expansion path (see text), Afr-D.





                     



                    (Posted as supplied by author)

                    Figure B: Cost effectiveness plane showing 60 interventions (20 individual and combination interventions at 3 assumed coverage levels) and expansion path (see text), Afr-E.





                     

                     

                    Appendix (posted as supplied by author)

                    Individual and combination interventions

                    In addition to the seven individual interventions discussed in the main text (reproduced here for convenience):

                    1. Insecticide-treated bed nets (ITN);
                    2. Indoor residual spraying (IRS);
                    3. Case management with chloroquine (CQ);
                    4. Case management with sulfadoxine-pyrimethamine (SP);
                    5. Case management with non-artemisinin-based (CQ-SP) combination therapy (Comb);
                    6. Case management with artemisinin-based combination therapy (ACT);
                    7. Intermittent presumptive treatment with SP in pregnancy (IPTp);

                    the following combinations were analysed:

                    • ITN & CQ;
                    • ITN & SP;
                    • ITN & Comb;
                    • ITN & ACT;
                    • IRS & CQ;
                    • IRS & SP;
                    • IRS & Comb;
                    • IRS & ACT;
                    • IRS & ACT & IPTp;
                    • ITN & ACT & IPTp;
                    • IRS & ITN;
                    • IRS & ITN & ACT;
                    • IRS & ITN & ACT & IPTp.

                    Each of these 20 interventions was analysed at each of the three coverage levels (50%, 80% and 95%) and in each of the two regions (Afr-D and Afr-E).

                    Intervention-specific assumptions

                    Drugs

                    The current subregional coverage of each case-management intervention was estimated as a population-weighted average on the basis of the country population and country-level estimates of the proportion of children who receive CQ or other antimalarials.w1 If no data were available on the proportion of sick children receiving drugs, rather than assume zero coverage for the country, the country was excluded from both the numerator and denominator of the coverage calculation. Estimates for the use of ‘any antimalarial’ that were greater than those estimates quoted specifically for CQ were assumed to refer to that country’s first-line drug (if other than CQ, otherwise that country’s second-line drug). If specific coverage estimates for CQ were not available, it was assumed that 80% of ‘any antimalarial’ consisted of that country’s first-line drug, with the remaining 20% consisting of the second-line drug.

                    Estimating drug resistance

                    Resistance was estimated by means of a standard logistic growth function (eq. 1). Projected effectiveness estimates for case management interventions and IPTp were thus adjusted for changing resistance profiles with increasing duration of use. Projected drug resistance was estimated as a function of the initial level of resistance prior to intervention implementation, the growth rate of resistance, and the maximum level of resistance (carrying capacity). As the estimated growth in resistance over the 10-year implementation horizon was in all cases approximately linear, annual numbers of treatment failures were averaged over the 10-year implementation period to obtain an average failure rate.

                    Resistance was measured as:w1

                    ,

                    where Ri, t is the proportion of parasites that resistant to drug i at time t, R0 is the initial level of resistance, r is the growth rate in resistance, k is the maximum level of resistance and t is time (see Table 1, main text). The growth rate of resistance was estimated in conjunction with biogeneticists on the basis of drug-specific pharmacokinetic properties and experience in the field.w2

                    Drug treatment failure

                    Treatment failure was calculated as:w1

                    ,

                    where F is treatment failure, m is the probability of full adherence, and p is the probability of treatment success without full compliance (see Table 2, main text).

                    Net drug effectiveness

                    Net effectiveness, E, was calculated as:

                    ,

                    where B is baseline efficacy, and Fi,t is treatment failure.

                    Preventive interventions

                    No vector resistance to insecticide was accounted for. Potential benefits of prevention on unborn children (i.e. in terms of higher birth weight) were not included.

                    IRS and ITN were assumed to benefit from a 9% "knock-on" effect (i.e. transmission externality) at modelled coverage levels: that is, the costs of a given level of effective coverage were reduced by about 8% (= 1 - 1/1.09), while keeping the effects unchanged. This is likely a conservative estimate.w3

                    For ITNs, coverage estimates refer to individuals, while, for IRS, coverage estimates refer to the household (e.g. a 50% coverage level for IRS indicates that 91% of houses within 50% of transmission areas are assumed to be effectively sprayed.

                    ITN

                    ITNs were assumed to be long lasting and thus not requiring reimpregnation. ITNs were assumed to last on average 5 years.w4 One ITN was attributed to each 1.5 persons.w5 Estimates of ITN effectiveness assumed 65% adherence, defined as sleeping under an untorn net.

                    IRS

                    Each spray team was assumed to cover 1170 houses per year.

                    Case Management

                    Case management refers to the first-line antimalarial drug administered to symptomatic patients presenting at outpatient clinics. One health center visit per case was assumed, as well as that a patient given an antimalarial drug does indeed have malaria (and therefore receives the drug benefit).

                    IPTp

                    Women of childbearing age were assumed to be those aged 15 to 49. Sixty percent of first-time mothers (estimated to account for 30% of births) were assumed to receive two doses of IPTp within the context of routine antenatal care (ANC) services. Sixty percent of pregnancies considered "at risk" due to HIV (estimated to account for an additional 20% of births) were assumed to receive three doses. A total of 15% of pregnant mothers (split evenly between first and multiparous high-risk pregnancies) treated with IPTp were assumed to have babies that would not survive the neonatal period. A potential reduction in incidence of placental malaria from IPTp was excluded from consideration, as its associated morbidity is difficult to quantify due to the asymptomatic nature of the disease in endemic areas.w6

                    Resistance to SP within the IPTp context was based on estimates of resistance to SP when used as a first-line treatment.w7 However, it was assumed that when SP is used for IPTp it is no longer used in standard case management, since if SP is concurrently used as the first line treatment for malaria, it’s usefulness as a preventive treatment will be diminished. Resistance to SP was assumed to grow more slowly when used only for IPTp.

                     

                    References

                    w1. Goodman C, Coleman PG, Mills AJ. Changing the first line drug for malaria treatment - cost-effectiveness analysis with highly uncertain inter-temporal trade-offs. Health Economics 2001;10:731-749.

                    w2. Roper C. personal communication, 2004.

                    w3. Curtis CF, Maxwell CA, Finch RJ, Njunwa KJ. A comparison of use of a pyrethroid either for house spraying or for bednet treatment against malaria vectors. Tropical Medicine and International Health 1998;3(8):619-631.

                    w4. WHO, RBM, UNICEF, PSI, MSH. Sources and Prices of Selected Products for the Prevention, Diagnosis and Treatment of Malaria, 2004.

                    w5. Lines J. personal communication, 2005.

                    w6. WHO. Global burden of disease estimates 2002. Geneva: http://www3.who.int/whosis/menu.cfm?path=evidence,burden , 2002.

                    w7. CostIt [program]. 1 version. Geneva: WHO, 2002.

                    w8. WHO. The Africa Malaria Report 2003. Geneva: UNICEF and World Health Organization, 2003:120.

                    w9. Lengeler C. Insecticide-treated bednets and curtains for preventing malaria. Cochrane Library, Issue 1. Oxford, 2001.

                    w10. Curtis CF, Mnzava AEP. Comparison of house spraying and insecticide-treated nets for malaria control. Bulletin of the World Health Organization 2000;78(12):1389-1400.

                    w11. Lengeler C. Comparison of malaria control interventions. Bull World Health Organ 2001;79(1).

                    w12. Goodman CA, Coleman PG, Mills AJ. Economic analysis of malaria control in sub-Saharan Africa. Geneva: Global Forum for Health Research, 2000:185.