LSDI

Maputo Province: Implementation of effective Malaria Diagnosis and Treatment.

Improvements in malaria case management have well exceeded targets set for the LSDI.

Progress against indicators

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.

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.

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.