Extra tables and figures and an appendix

Extra tables and figures and an appendix

Table A

Table B

Table C

Figure A

Figure B

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 impact^w8
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 ITNs^w3,w10,w11
resulting reduction in case fatality	20%	Assumed to be similar to ITNs^w3,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 2000^w12; 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):

Insecticide-treated bed nets (ITN);
Indoor residual spraying (IRS);
Case management with chloroquine (CQ);
Case management with sulfadoxine-pyrimethamine (SP);
Case management with non-artemisinin-based (CQ-SP) combination therapy (Comb);
Case management with artemisinin-based combination therapy (ACT);
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 R_i_{, 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 F_i_,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.

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