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Progress

Objectives of Lubombo SDI Malaria Control Programme:

1. Reduce malaria incidence in the border areas of South Africa and Swaziland from 250 per 1000 to less than 20 per 1000. STATUS: Achieved

2. Reduce malaria infections from 625 per 1000 to less than 200 per 1000 within three year after the start of IRS in Maputo Province. STATIUS: Achieved

3. Provide updated tourist information booklets containing definitive malaria risk maps and prophylaxis guideline. STATUS: Achieved

4. Develop a regional GIS-based Malaria Information System (MIS). STATUS: In place in 3 countries.

5. Develop a regional malaria control programme. STATUS: In place, covering 200 000 Km²

6. Implement definitive diagnosis and effective treatment. STATUS: RDTs and ACTs in place in all health facilities

Objective 6. Maputo Province: Implementation of definitive malaria diagnosis and effective treatment.

6.1 Malaria Case Management

Over the past five years, the LSDI has made a substantial contribution to improving malaria case management in Maputo province. Improvements in malaria case management have well exceeded targets set for the LSDI

Progress in case management

Achieving these indicators showing effective case management, including large scale deployment of artemisinin-based combination therapy and rapid diagnostic malaria tests at more healthcare facilities than initially planned within the defined budget, has been made possible by the following:

1) the marked reduction in malaria case load following the effective community based indoor residual spraying and widespread use of ACTs,

2) limiting treatment to only definitively diagnosed malaria cases and

3) adhering to the Ministry of Health directive to also distribute RDTs and ACTs to community health centres. Efficient management and use of drug and RDT supplies through extensive training and supervision has minimised stock-outs and wastage.

Ensuring effective malaria diagnosis and treatment

Accurate case reporting has necessitated the implementation of appropriate diagnostic measure through the use of Rapid Diagnostic Tests (RDT’s) to reduce the number of people being unnecessarily treated through diagnosis based on clinical signs and symptoms. This objective is being achieved through wide-spread use of artemisinin-based combination therapy (ACT) as first line treatment. The artemisinin derivatives, such as artesunate and artemether, have been selected specifically for their ability to reduce gametocyte carriage (See below). Gametocyte carriage is being monitored in the in vivo studies of therapeutic efficacy, all of which have shown significant reduction in gametocyte carriage in the ACT arm when compared with the SP monotherapy arm. The number of malaria cases has decreased markedly following the implementation of ACTs as fist line treatments, in districts where IRS was already well established.

Starting with Namaacha in March 2004 and supported financially by the GFATM, the ACT artesunate plus SP was phased in on district level in all public sector health posts and health centres of the LSDI region of Southern Mozambique. With the implementation of artesunate plus SP as the first line treatment nationally by the ministry of health in Mozambique (2006), health facilities in regions outside of the LSDI were also supplied with ACTs. The LSDI contributed to the optimal use of the ACTs by providing training and supervision. RDTs were provided in order to limit the use of ACTs to parasitaemic patients.
All targets for the number of healthcare facilities routinely using RDTs and ACTs have been exceeded by extending the provision of ACTs, RDTs and relevant training to community healthcare workers. This contributes positively to the sustainability of future effective case management. The management systems implemented reduced stock-outs to the minimum and also reduced the duration of stock-outs where they occurred, effectively enabling all facilities to reach 100% of the stock-out targets.
The number of RDTs used and the proportion of clinically suspected malaria cases that are RDT positive vary by district

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Figure 7: The number of suspected malaria cases tested and found positive using RDTs in 2008 by district in Maputo province.

Through the use of RDTs, clinically suspected malaria cases can be tested, which will allow the targeted use of ACTs on patients carrying the malaria parasite. It is also beneficial for patients that test negative for malaria, as their condition can then be re-assessed to find the actual cause of their illness more promptly.
The number of patients who are RDT positive compared to the number treated with ACT (Figure 8) is routinely monitored to determine ACT coverage rates among confirmed malaria cases, and monitor the overuse of ACT in patients who are aparasitaemic.

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Figure 8: Proportion of RDT positive cases treated with ACTs at healthcare facilities in Maputo province.


The higher than expected proportion of RDT positive patients treated with ACTs at some facilities has been investigated. The healthcare facilities with the highest percentages are those with microscopy, so much of the apparent over-use of ACT is actually appropriate use in confirmed malaria cases. In this regard, healthcare worker training re-enforces the importance of limiting ACT use to confirmed malaria cases, although allowing the initial use of ACTs in severely ill patients.
Close monitoring of the efficacy within the LSDI have shown ACTs to be highly effective, and to be significantly more effective than monotherapy. Concern have been raised about the impact of age has on SP drug levels on individuals after it came to light that drug levels in pre-school children did not reach the same levels as in adults, although the internationally recommended dose was followed. This has raised the question of whether other vulnerable populations are similarly at risk of being treated with inefficient dosages. The LSDI has initiated two studies to assess antimalarial drug levels achieved in pregnant women in Mozambique. The first study had to be terminated as only three pregnant women with malaria were enrolled throughout the study season, reflecting the marked improvements in Malaria control in Maputo. The second study on drug levels achieved in pregnant women given SP as intermittent preventative treatment (IPT) confirmed that pregnant woman achieve similar concentrations of sulfadoxine and slightly higher concentrations of pyrimethamine than non-pregnant women with uncomplicated malaria.

ACT

Decreasing gametocyte carriage is as important for reducing the spread of drug resistance as it is for reducing malaria transmission. The data from Mpumalanga shows that increased post-treatment gametocyte carriage was the earliest indicator of increasing sulfadoxine-pyrimethamine resistance, preceding a significant increase in treatment failure rates. This relatively higher gametocyte carriage in primary infections with resistant genotypes (See below) following SP monotherapy treatment fuels the spread of resistance even before failure rates rise significantly.

Gametocyte carriage

KwaZulu-Natal implemented an ACT malaria treatment policy when it introduced Coartem in January 2001 and ACTs were introduced in Mpumalanga in 2003. In southern Mozambique, the phased district level implementation of artesunate plus SP has been supported financially by the Global Fund to fight AIDS, tuberculosis and malaria. This has been achieved in all public sector health posts and health centres in Namaacha (March 2004), Matutuine (July 2004), Boane (January 2005), Marracuene (July 2005) Magude (November 2005) and Moamba (April 2006) districts.

During 2006, the Ministry of Health in Mozambique implemented artesunate plus SP as first line treatment nationally, which ensured that health facilities in Manhica and Matola districts which fell outside the LSDI areas were also supplied with ACTs. The LSDI contributed to optimal use of ACTs in these non-LSDI districts by providing training, supervisions and RDTs to limit use of ACTs to only parasitaemic patients. During 2006 – 2007, the LSDI has been active in providing training, RDTs and ACTs to community health workers, in addition to the formal public sector health workers. This has led to the LSDI exceeding its target of 50 and 53 healthcare facilities routinely using ACTs and RDTs respectively, and is instead achieving this goal in 119 and 157 facilities, respectively.

This successful model of additionality bodes well for the sustainability of effective case management in the future. The drug and RDT management systems implemented by the LSDI have reduced stock-outs to a minimum. In the past year (September 2006 – August 2007) there have been no RDT stockouts and only 5 facilities stocking ACTs recorded any stockouts. All stockouts were of short duration (<5 days), so 100% of facilities achieved the stockout target. The number of RDT used and the proportion of clinically suspected malaria cases that are RDT positive varies by age category and by district (See below). This tool allows targeting of ACTs for patients who carry malaria parasites. Patients in whom the malaria test is negative should also benefit from more prompt management of the actual cause of their illness.

Rapid diagnostic test

The higher than expected proportion of RDT positive patients treated with ACTs, at some facilities (see above) has been investigated. The healthcare facilities with the highest percentages are those with microscopy, so much of this apparent ACT “overuse” is actually appropriate ACT use in confirmed malaria cases. Nonetheless, healthcare worker training is reinforcing the importance of limiting ACT use to confirmed malaria cases, although allows initial use of ACTs in severely ill patients. The efficacy of ACTs within the LSDI has been closely monitored through in vivo therapeutic efficacy studies with 6-week follow up. These have shown the ACTs to be highly effective across all study sites (97.7% Adequate Clinical and Parasitological Response to artesunate plus SP), and to be significantly more effective than monotherapy.

However, it has been noted with concern that despite patients receiving directly observed treatment with the internationally recommended dose of SP, drug levels achieved in pre-school children are approximately half those in adults. Younger children treated with sulfadoxine-pyrimethamine are therefore doubly disadvantaged by lack of immunity and lower drug concentrations. This late recognition of the critical impact that age has on SP drug levels, despite widespread use for decades, has raised the question of whether other vulnerable populations are similarly at risk of being under-dosed.

The LSDI has thus initiated two studies on antimalarial drug levels achieved in pregnant women in Mozambique in 2006. The first on treatment of malaria in pregnancy had to be stopped as only 3 pregnant women with malaria were enrolled throughout the study season, reflecting the marked improvements in malaria control in Maputo Province, Mozambique. The second study on drug levels achieved in pregnant women given SP as intermittent preventive treatment (IPTp) is ongoing. Studies of the therapeutic efficacy of artemether-lumefantrine were conducted in Limpopo and Mpumalanga, South Africa in 2007. Due to effective malaria control, this study was unable to achieve its target sample size. Of 62 patients studied, there was one early treatment failure, giving an Adequate Clinical and Parasitological Response rate of 98.5%. There were no serious adverse drug events in this study. Lumefantrine drug concentrations from this study are currently being analysed.