New evidence for conquering malaria: Operations, Costs and Cost-Effectiveness: Five Insecticide-Treated Net Programmes

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New evidence for conquering malaria: Operations, Costs and Cost-Effectiveness: Five Insecticide-Treated Net Programmes (,,, Togo, ) Two Indoor Residual Spraying Programmes (KwaZulu-Natal, Mozambique) Christian Lengeler Swiss Tropical Institute, Basel, Switzerland With support from USAID With contributions by: D. Bakusa, N. Brown, D. Chavasse, L. Conteh, A. Daré, M. Erskine, G. Foster, T. Ghebremeskel, C. Goodman, K. Hanson, J. Justino, M. Khouma, K. Morgah. D. Mueller, R. Maharaj, D. McGuire, J. M tema, R. M tunge, J. Mulligan, F. Sakho, B. Sharp, W. Stevens, P. Tchamdja, J.M. Urrutia, C. Yuma, V. Wiseman, M. Zerom Malaria deaths and resulting Disability adjusted Life Years (DALYs, s) lost in 22 Population Malaria deaths DALYs from malaria deaths (%) DALYs from malaria / total (%) World 6,122,21 1124 42,28 2.9 Africa 655,476 963 36,12 (85.2) 1.1 Americas 837,967 1 18 (.2).7 East Med. 493,91 55 2,5 (4.8) 1.5 Europe 874,178 <1 2 (.4).1 SE Asia 1,559,81 95 3,68 (8.7).9 West Pacific 1,71,689 1 49 (1.).2 Adapted from WHO, World Health Report, 22 1

Malaria-Related Mortality and Morbidity in Africa, 2* By age in years (%) Condition Total -4 5-14 15 Malaria-specific mortality 1,124, 65 19 16 Maternal mortality (anemia) 5,3 --- --- Infant mortality (pregnancy-related) 71, 19, --- --- Fatal adverse drug events 2,3 Fatal HIV from blood transfusion 5,3 8,5 --- Epilepsy-related mortality Unknown Anemia, undernutrition, and HIV mortality Unknown Morbidity attacks (s) 213,549 [134,322 324,.617] 51 35 14 Morbid days (s) 83,699 [494,416 1,.298,872] 69 21 1 Neuro-cognitive sequelae cerebral malaria Hemiparesis 36-4 Quadriparesis 77-86 Hearing impairment 65-73 Visual impairment 3-33 Behavioral difficulties 1,54 1,72 Language deficits 7, 7,8 Epilepsy 2,7 3, Effect of malaria on cognition Unknown A favourable environment 6 x increase in global malaria control resources since 1999 14 12 Million USD 8 6 4 2 1999 2 21 22 23 24 25 Source: Updated from Waddington et al. (25) Source: Daulaire 27 How to spend wisely these new resources 2

Aims of the review To systematically review and compare the cost, costeffectiveness, and main operational features of largescale indoor residual spraying (IRS) and insecticidetreated nets (ITNs) for malaria control in sub-saharan Africa. IRS: ITNs: KwaZulu-Natal, Southern Mozambique (LSDI),,, Togo, Methods of the review (1) General principles Costing followed standard guidelines (Creese & Parker 1994; Stevens et al. 25; Kolaczinski et al. 26). Only national or at least large-scale programmes. Provider perspective, with exception of user contributions to purchase of nets and insecticide kits. Time frame varied according to availability of data (if possible at least 3 years, including startup costs). Costs were collected retrospectively from financial and operational records; in addition, costs and activity information were collected through stakeholder interviews and direct observation, as needed. Where possible, the ingredients approach was used (unit activities were first determined and then a unit cost was determined). 3

Methods of the review (2) - Costing Resource use was valued at all levels: central (within the MOH and the NMCP), at the district level, and peripherally. Costs have been divided into capital and recurrent costs; capital costs discounted at 3%. Both financial and economic analyses were conducted. Costs collected in local currencies were converted to USD based on official yearly average exchange rates; yearly costs were then adjusted to 25 USD prices using the US GDP deflator produced by the US Bureau for Economic Analysis. In joint programmes, the likely share of vector control activities has been estimated Methods of the review (3) Output measures Two main output measures were used: (1) number of nets delivered and (2) number of re-treatments performed. The two were used to calculate a third combined output measure: treated net years (TNY), assuming that either a re-treatment or a new ITN provides 1 year of full protection. When long-lasting insecticidal nets (LLIN) were used, they provided 3 TNY (Permanet type). This was extended to five years in the sensitivity analysis (Olyset type). Half of the nets delivered were assumed to be used by children; only one child was assumed to sleep under each of these nets. 4

Methods of the review (4) Health benefits Deaths averted Mortality impact for ITNs taken from the Cochrane review: 5.5 deaths averted per person-years of protection in children under five years (U5s). For lack of better data, we assumed the same effect for IRS; there is much historical evidence of impact of IRS but no reliable quantification of this effect. Currently ongoing Cochrane review on IRS (Tanser, Pluess, Lengeler & Sharp). No quantification of protective effect in older individuals (especially relevant in areas with high HIV levels). No quantification of protection in pregnant women (although positive effects on newborns covered in U5s mortality). No effect of untreated nets instead we calculated the effect of LLIN in the sensitivity analysis. Methods of the review (5) Health benefits Disability-adjusted life-years (DALYS) Only included effect of mortality because difficult to include other forms of disabilities across seven settings. We used the standard WHO lifetable approach (Global Burden of Disease Project) and treated all deaths as infant deaths resulting in 33 lost DALYs; using country-specific lifetables would have introduced large differences between countries because of different life expectancies. For both outcomes we calculated CE ratios for (1) cost per net distributed and (2) cost per TNYs. Many of our methodological choices were guided by the imperative of comparability. They are conservative and unlikely to bias comparisons as long as country-specific age profiles of malaria morbidity and mortality are similar. 5

Comparing IRS with ITNs is one better PE IRS PE ITN Reference 12 villages Randomized South Africa 14 blocks Randomized Kenya Non-random. India 126 villages Randomized Pakistan Non-random. P.v. P.f. 64% PE ITNs vs IRS: 33% 75% 3% 44% 49% 55% 63% 54% 42% 61% Curtis et al. 1998 Mnzava et al. 21 Guyatt et al. 22 Misra et al. 1999 Rowland et al. 1999 PE= protective efficacy = (1-RR) x Lengeler and Sharp 23 It seems not the results are very similar IRS programmes under review: IRS programmes are the model vertical programmes but they can be well integrated into the health system! KwaZulu Natal: Funded by the SA Dept. of health since 1932 Seasonally hired spraymen (2) and supervisors (25) with 25 vehicles. Currently using DDT (traditional houses) and pyrethroids (Western-type structures) Southern Mozambique LSDI: Funded by a consortium including GFATM Seasonally hired community-resident spraymen (8) and supervisors (2) with 2 vehicles. Currently using DDT (traditional houses) and pyrethroids (Western-type structures) 4 8 Limpopo kilometres Mpumalanga Lubombo Manzini S W A Z I L A N D KwaZulu Natal Zone 3 M O Z A M B I Q U E Maputo Province Zone 2 Zone 1A Zone 2A Zone 1 Maputo The LSDI within Southern Africa: Legend I n d i a n O c e a n ZWE NAM BWA MOZ SWZ ZAF Sentinel Sites International Boundaries S O U T H Lubombo Spatial Develo A F R I C A Initiative (LSDI) Region Regional Boundaries St. Lucia Data sources:mozambique Ministry of Health; Swaziland Ministry of Health; Municipal Demarcation Board (South Africa). 6

ITNs: Current main implementation models Commercial / mixed Public sector 1. Free distribution of ITNs through health facilities and community groups (). 2. Free distribution of ITNs in the frame of vaccination campaigns (Ghana, Togo, Zambia, Niger, Mozambique, Kenya, Rwanda). 3. A comprehensive market approach (NETMARK project in, Mali, Ghana Nigeria, Mozambique, Uganda, Zambia, Ethiopia) with and without subsidies. 4. Social marketing (, Kenya) with subsidized ANC sales, with and without product distribution. 5. Integrated (NATNETS ): commercial sector distribution, social marketing with no product distribution and vouchers for pregnant women and infants at measles vaccination Key characteristics of programmes Population covered (millions) Period Total # of nets Total # retreatments Total economic cost (mio USD) 2.9 21-5 9, 2,, 4.4 12.2 1999-5 4,7, 5, 15.7 35.7 22-5 6,4, 7,8, 3.5 Togo (Mueller et al.) 5.3 24 9, 6.5 1. 2-5 75, 1,, 6.2 KwaZulu-Natal.6 (7.3 in past) 1997-99 3, structures 2.2 Mozambique.8 1999-1 15, structures 1. 7

Average annual economic cost for ITN and IRS programmes. Conventional ITNs (25 USD). ITN program Average cost per ITN distributed Average cost per TNY death averted DALY averted 4.74 1.43 1,722 52 3.36 4.8 3.4 2.17 1,222 1,745 37 53 8.35 3.6 3,37 92 Togo (Mueller et al.) 3.23 3.23 1,174 36 IRS program person protected (whole population) under-five child protected death averted DALY averted KwaZulu-Natal 3.27 23.96 4,357 132 Mozambique 3.9 21.63 3,933 119 Average annual economic costs for ITN and IRS programmes. LLIN with 3 years duration (25 USD) ITN program Togo (Mueller et al.) Average cost per LLIN distributed 7.64 5.18 6.4 7.89 3.47 Average cost per TNY 1.48 2.19 1.83 3.6 2.37 death averted 539 798 664 1,311 773 DALY averted 16 24 2 4 23 IRS program KwaZulu-Natal Mozambique Cost p. person protected (whole population) 3.27 3.9 under-five child protected 23.96 21.63 death averted 4,357 3,933 DALY averted 132 119 8

Coverage rates of high-risk groups in study sites (latest figures available %) Household ownership Children under five slept under net last night Pregnant woman slept under net last night Any net ITN Any net ITN Any net ITN 24 79 73 na 48 na 5 24 43 34 38 36 34 31 26 57 29 41 28 34 18 Togo 24 na 6 na 54 na 45 25 38 2 14 7 14 9 Coverage in both IRS areas above 8% for risk groups Targeting of under-five children in the five ITN programs Togo Percentage of population aged 4 years 17.2% 18.2% 15.8% 15.8% 16.5% Targeting ratio as measured from crosssectional surveys 31.8% 19.7% 24.7% 28.1% 2.2% Programme targeting effort *** ** ** * *** n Targeting Ratio = n children total child net usage total net usage 9

DALY averted at different targeting levels for ITNs - using full economic cost at scale. Baseline results for IRS are shown for comparative purposes 3 25 USD 25 2 15 5 Togo LSDI/MOZAL KwaZulu-Natal No Targeting 25% Targeting 35% Targeting 5% Targeting % Targeting Epidemiological determinants Seasonality is a major factor influencing the CE of IRS because of the need for increasing numbers of spray rounds with increasing length of the transmission season. Consensus among IRS implementers is that beyond two spray rounds per year IRS becomes very difficult to implement. Hence, in areas of year-round transmission, ITNs will have a significant feasibility and cost-effectiveness advantage. Especially true with the use of shorter-lived insecticides such as carbamates as opposed to insecticides with longer residual lifetimes. In areas of shorter and lower transmission and typically also in epidemic-prone zones, IRS may have significant advantages because IRS programmes protect the entire population and the burden of disease is likely to be distributed much more evenly across all age groups. IRS can be restricted to periods in which there is a clear risk of epidemic. 1

Seasonality of transmission in sub-saharan Africa (Tanser et al. 23) mara.org Catch-up versus Keep-up (RBM 25) Integrated vaccination-itn campaigns such as in Togo have achieved high coverage rates within a short period of time. Hence, they fulfill the immediate needs for catching-up in ITN usage. However, on their own they are unable to maintain high net usage levels because (1) more women get pregnant and children are born, and (2) polyester LLIN have a finite uselife. Hence, there is also a strong need for keep-up programmes to maintain high net usage levels. Four of the ITN programs we reviewed tend to be more keep-up (,,, ). These programs attempt this through the integration of ITN delivery into routine health services or other mechanisms such as vouchers linked to commercial sector distribution. Currently, there is a consensus that both catch-up and keep-up strategies are required in each country. 11

Who bears the cost LLINs with 3 years duration (25 USD) Total cost Cost to provider % supported by donor user govt 7.64 7.64 92 3 5 5.18 4.12 8 19 1 6.4 2.18 47 52 1 7.89 3.62 66 33 1 Togo (Mueller et al.) 3.47 3.47 99 1 KwaZulu-N 3.27 / 23.96 3.27 / 23.96 Mozambique 3.9 / 21.63 3.9 / 21.63 9 1 est. Level of involvement of public, private and NGO sectors in studied vector control programs Programme Public sector Commercial sector NGO sector Togo KwaZulu-Natal Mozambique 12

Conclusions (1) For the first time, comparable large-scale programme data are available to provide a solid evidence base in the debate on the best approach to vector control in sub-saharan Africa. Vector control is remarkably cost-effective in SSA: cost per DALY averted ranged between USD 16-4 for LLIN programmes and 119-132 for IRS programmes; cost per death averted ranged between USD 539-1311 for LLINs and USD 3,933-4,357 for IRS. For any ITN strategy, the use of LLIN rather than conventional nets should be promoted, regardless of the higher initial investment. The vaccination campaign approach fits best the RBM concept of catch-up, while the 4 other models aim both for catch-up and keep-up over time; both strategies need to be combined. The longer the transmission season, the more LLINs are the better strategic option for vector control. IRS is likely to be better in epidemic-prone areas. Conclusions (2) Some strategies are more cost-effective than others but each strategy also brings specific advantages, in the short-term and in the long-term; some of these approaches can be mixed, as in. A commercial distribution strategy on its own can not produce high coverage levels and targeted subsidies must be incorporated. Targeting children under five years and pregnant women remains more cost-effective than protecting the whole population. The benefits of the latter approach could not be explored in the present study. For this reason, IRS is substantially more costly than any ITN strategy aiming at risk groups. Most vector control programs are excellent public health investments and they should be made as soon as possible. This is a time of unprecedented opportunities for malaria control, and it is time to bring down substantially the unacceptable burden of disease. 13