Malaria control. generating evidence from local to global level

In addition of the provision of effective treatment to each case, malaria control is heavily relying on vector control with either insecticide treated mosquito nets (ITNs) or indoor residual spraying (IRS). The effectiveness of ITNs in controlling malaria in many different settings has already been comprehensively documented. On the other hand, while IRS has a long and distinguished history in malaria control, its health effects have never been properly quantified.
The present thesis aimed at generating malaria control knowledge on local and global level. On a local level, new insights into the malaria burden in South-East PNG were generated. The work was carried out within an oil palm plantation, which allowed exploring options for malaria control, together with the management of the company. On a global level, this thesis aimed to quantify the effectiveness of IRS in reducing ill-health from malaria through a Cochrane review and to compare IRS to ITNs.
Local level – malaria in Papua New Guinea To get an overview on malaria epidemiology within the Higaturu Oil Palms plantation (HOP) in Oro Province in PNG, different observational study approaches were used. In 2006, we carried out a cross-sectional study within six company villages, which included the determination of parasite rates by conventional microscopy, interviews and haemoglobin measurements. Passive surveillance data were collected from the 13 company aid posts for the years 2005 and 2006. Before the start of this study, malaria diagnosis was relying on clinical symptoms only. Since malaria symptoms are unspecific, we introduced rapid diagnostic tests (RDTs) in all aid posts. Finally, entomological data were collected by human landing catches.
Prevalence of malaria was high, with more than a third of the participants (33.5%, 95% confidence interval (CI): 30.1-37.0) found with a malaria positive blood slide. Overall, prevalence was highest in the age group 5-9 years (40.3%, 95% CI 0.32-0.49). More than half of the infections were caused by Plasmodium falciparum (59.5%), followed by P. vivax with 37.6% and P. malariae (6.6%). Haemoglobin levels were low, with a mean of 11.0 g/dl (95% CI 10.8-11.1) for men and 10.4 g/dl (95% CI 10.3-10.5) for women. Plasmodium falciparum infections were significantly associated with anaemia (Hb < 10 g/dl). At the aid posts, all malaria cases in 2005 and January-March 2006 were diagnosed by symptoms only, while from April 2006 onwards most cases were tested by rapid diagnostic tests. Between 2005 and 2006, 22,023 malaria cases were diagnosed at the aid posts and malaria accounted for 30-40% of all clinical cases. Of the malaria cases, 13-20% were HOP employees. On average, an employee sick with malaria was absent for 1.8 days, resulting in a total of 9,313 workdays lost between 2005 and 2006. Sleeping outside of the house did not increase the risk for a malaria infection, neither did getting up before 7am. Anopheles punctulatus was the main vector founding the area. Malaria was found to be a major health burden in the Higaturu Oil Palm plantation, posing a high risk to company staff and their relatives, including expatriates and other non-immune workers. Reducing the malaria risk is a highly recommended investment for the company. Global level The health effects of IRS were summarized and quantified in the frame of a Cochrane review. Studies considered for the review had to be either Randomized Controlled Trials (RCTs), Controlled Before-and After studies (CBA), or Interrupted Time Series (ITS). They had to include children and adults living in malarious areas and be carried out with one of the World Health Organization (WHO) recommended insecticides. There was a great paucity of high-quality evidence. Only six out of 132 identified studies met the inclusion criteria (four RCTs, one CBA and one ITS) and not all key malariological outcomes were addressed within these studies. Also, the geographic spread of the included studies was limited.
For stable malaria settings, malaria incidence was significantly reduced in children aged one to five years (RR 0.86, 95% CI 0.77 to 0.95), while no difference was seen for children older than five years. For malaria prevalence no difference was seen between the IRS and the control group. With regard to anaemia, the haemoglobin levels were significantly lower in the control group than in the IRS group (WMD 0.61 g/dl; 95% CI IRS group 9.99 to 10.02; 95% CI no IRS group: 9.38 to 9.40). When comparing IRS to ITNs, IRS showed a better protective effect in reducing malaria incidence for children aged one to five years (RR 0.88, 95% CI 0.78 to 0.98). No difference was seen for children older than five years. Prevalence rates were found to be equal within the IRS and ITN groups. No difference in haemoglobin levels was found (WMD 0.01; 95% CI IRS: 9.99 to 10.02; 95% CI ITN: 9.99 to 10.01).
In regard to unstable malaria settings IRS was shown to significantly reduce the incidence rate of malaria infections with a protective efficacy ranging from 24% to 86%. IRS also significantly reduced the incidence of malaria when looking separately at P.falciparum and P. vivax (P.falciparum: RR 0.07, 95% CI 0.02 to 0.39; P. vivax: RR 0.21, CI 95% 0.10 to 0.55). Different results were seen when assessing the impact of IRS on malaria prevalence. No effect of IRS in reducing malaria prevalence was found in India. In children aged five to fifteen in Pakistan, IRS reduced the risk of getting infected with P. falciparum as well as with P.vivax - by 90% and 68%. Conflicting results were seen comparing IRS to ITNs against malaria incidence, with one study showing a better protection with ITNs (RR 1.55, 95% CI 1.49 to 1.60) and one study detecting no difference between the two interventions. Unfortunately, the aim of the review (to quantify the health effects of IRS) could not be achieved. A major conclusion of this work is the urgent need for high-quality evidence from two or three-arm RCTs. Ideally such trials should have one IRS arm, one ITN arm and an arm combining both interventions at high coverage. A control arm should not be planned for ethical reasons. This evidence will be crucial to support the long-term aim of malaria elimination/eradication.