New malaria research: a selection of some of the latest findings

4 Nov 2009

Paul Chinnock

Source: TropIKA.net

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The first decade of the 21st century has witnessed a remarkable increase in research efforts devoted to malaria. So many studies are now being published that it is hard to predict which of them will turn out to be of most significance in advancing global efforts towards eradication of the disease. Nevertheless, we describe here seven recent publications of particular interest. TropIKA.net readers are urged to use our “Comment” facility to share their own views on this research and its implications.

Children at risk

Who is most at risk of malaria? The majority of clinical cases and of deaths are known to be in children, particularly African children. It is those under five years old who are at the very greatest risk as, after that age, children in endemic areas have usually acquired a degree of immunity to the parasite. But could all this change?

Massive international efforts to distribute insecticide-treated bednets (ITNs) continue and the main focus in the promotion of their use has been on pregnant women and the under-fives. A study (1) in 18 African countries has found that the 5–19 year-old age group is the least likely to be protected by a net. One reason this is so worrying is that individuals in this age group who have been shielded by a net in their first few years may not have developed a sufficient level of immunity to protect them. Also, by harbouring large parasite numbers, they will in effect be acting as a major reservoir of infection, thus threatening other community members. The authors of the new study say that providing protection to older children and adolescents must now be regarded as a priority. They propose promotion and distribution of nets at school as a way forward.

Brazilian children were the focus of research a study to determine whether malaria in 5–14-year-olds, living in one municipality in the Amazonas Region, reduced their performance at school. Some 200 were tested for malaria, after which during nine months of follow-up the researchers relied on “passive” case detection, in which only children with fever were tested. Teachers’ end-of-the-year assessments of the children’s achievements in mathematics and Portuguese were used as the measure of performance. Over one third of the children experienced attacks of malaria, mostly due to Plasmodium vivax, but none of these cases were severe. Children with one or more attacks were nearly twice as likely to be considered to have performed poorly at school. This small study is the first of its kind in Latin America. It supports the view that even non-severe malaria, over the short period of nine months, can compromise a child’s ability to do well at school. And – like the previous study – it demonstrates the importance of protecting the older child against malaria.

Focussing on the vector

ITNs are the most intensively promoted of the various ways of reducing the chance of being bitten by a mosquito. Window screens, ceilings and the blocking of eaves are other options that households can adopt and increasingly people with the money to do so are adding these features to their homes. A study (3) of 579 houses in the Tanzanian capital, Dar es Salaam, found that over three-quarters had window screens and nearly all the householders interviewed (91%) said they had installed them in order to prevent mosquito entry. Ceilings are now to be found in almost half the houses in Dar es Salaam, with 55% of those interviewed citing prevention of mosquito entry as the motivation for installing them. People who lacked screens or ceilings said, in most cases, that they were unable to afford them; window screens cost around $20–30, whereas ceilings require an expenditure of $300–400.

The authors conclude that screens and ceilings are clearly popular techniques that reduce mosquito entry and that people are prepared to spend money to purchase them. They note that, in comparison and despite intensive promotion efforts in the city, the use of ITNs in Dar es Salaam remains disappointingly low (26% coverage). Far less research has been conducted on the effectiveness of screens and ceilings in the prevention of malaria than has been done with ITNs. However, the authors are able to cite some studies suggesting that screens and ceilings can be effective. They want to see their use promoted in malaria control programmes, pointing out that people, “...need access to, and information about, cheaper and more durable materials which would ideally have insecticidal and/or excito-repellent properties, which would kill adult mosquitoes directly or act as a more effective barrier for preventing house entry”. Further research on the effectiveness and cost-effectiveness of screens and ceilings will also be important.

But perhaps the most interesting aspect of the study, though it is not discussed by the authors, is that only 4% of people interviewed cited prevention of malaria as a motivating factor in installing screens or ceilings. It is not the first time that it has been noted that the nuisance and pain of being bitten seems to loom larger in minds than the fear of getting malaria, but it is surely remarkable that in a city like Dar es Salaam in the 21st century so few people seem to associate the two hazards.

Treatment decisions

When a mother has a sick child, on what basis does she decide where she will first go to seek treatment? Another paper (4) from Tanzania addresses this question in a qualitative study. Researchers interviewed 61 female caregivers, 28 medical practitioners and 18 traditional healers in urban, peri-urban, and rural areas. The caregivers, eight of whom had had a child who died from malaria, expressed differing views about the cause and symptoms of severe malaria. Nearly all (60) said they would take a child with fever to an orthodox health facility for treatment, but there was a common view, held by 26 of the women, that a child with convulsions did not have malaria but a separate condition that was of spiritual origin, requiring treatment from a spiritual healer. That this was a common belief was confirmed by the interviews with medical practitioners and traditional healers.

This fascinating study, which includes a discussion of various Kiswahili words used for symptoms seen in malaria, gives an insight into traditional beliefs in this part of Africa. The authors conclude that a lack of education about malaria and its full range of symptoms may be an important reason why caregivers choose traditional healing for some cases of childhood malaria. Information about convulsions should therefore be included in malaria campaigns. They go on to note that traditional healers are in a position to dispense not only treatment but also education to their immediate communities, and they call for health workers and healers to work more closely.

Amongst other noteworthy recent publications on malaria treatment is a study (5) that looked specifically at children with sickle cell disease (SCD). Although people who carry the sickle cell trait have a level of resistance to malaria, those who have sickle cell disease itself (because they have two copies of the gene for the condition) are extremely vulnerable to malaria. A clinical episode of malaria often leads to a potentially fatal sickle cell crisis. It is thus a common practice to administer chloroquine (CQ) prophylactically to children with SCD, though the evidence is limited as to whether this is effective in reducing mortality rates. CQ resistance now being widespread, there is a need to examine whether the practice is justified and whether better alternatives are available.

The researchers used a randomised controlled trial to compare the efficacy of weekly CQ with monthly presumptive treatment using sulphadoxine-pyrimethamine (SP). They randomised 247 children attending the Sickle Cell Clinic at Uganda’s Mulago Hospital to receive either CQ or SP and then tested weekly for malaria over a period of one month. Seventeen children (14%) in the SP group contracted malaria compared with 30 (24.6%) in the CQ group – a statistically significant result. Seven of the chloroquine group and three of the SP group were admitted to hospital for malaria during the period (non-significant). One month is a very short period of follow-up but these findings should be noted. Based on their results, the authors argue that: “Monthly SP should be considered for malaria prophylaxis in children with sickle cell anaemia. Continued use of chloroquine for malaria chemoprophylaxis in children with sickle cell anaemia in Uganda does not seem to be justified”.

Artemisinin-based drugs should be used for malaria treatment only in the form of combination therapy. A difficulty in selecting appropriate partner drugs for this purpose is that resistance to all other compounds with antimalarial activity is now widespread. One combination that has been shown to be effective in Asia is artesunate (AS) plus the antibiotic azithromycin (AZ). Potentially there could be many advantages to this combination. Most treatment for fever is begun before diagnosis is confirmed and many children with fever often have a bacterial infection as well as (or instead of) malaria. In such circumstances azithromycin could effectively treat the bacterial infection.

A trial (6) conducted in Tanzania is the first known study of the use of AZ+AS treatment in Africa. Unfortunately, the results are disappointing. The researchers randomised 261 children with malaria to receive either AZ+AS or artemether-lumefantrine (AL). All the children had a complete response to treatment initially. However, after four weeks 58% of children in the AZ+AS group had asexual parasites, compared with only 20%in the AL group. The difference was still present after a further two weeks. The high rate of parasitological failure with AZ+AS does not support the use of this treatment in Africa.

On the front line

The research that is now advancing our knowledge of malaria will only be worthwhile if it leads to the introduction of more effective interventions on the front line of health care. In the Abuja declaration of 2000, African heads of state committed themselves to ensuring that 60% of childhood fevers are treated with effective anti-malarial medicines within 24 hours of symptom onset, a target that has since been increased to 80% by 2010. Are we approaching this target? A review (7) of the data available on access to effective malaria treatment in Kenya suggests that, in this country at least, there is a very long way to go.

The reviewers found 39 studies with information on this question. They conclude that malaria treatment-seeking occurs mostly in the informal sector; that most fevers are treated, but treatment is often ineffective. Irrational drug use emerged as a problem in most of the studies, but not enough is yet known as to why most malaria patients are still getting the wrong drugs. It is, however, clear that older ineffective antimalarials are more widely available than artemisinin combination therapies. As the reviewers rightly say: “Unless the whys’ and hows’ behind treatment-seeking patterns, irrational drug use, and provider behaviour are well understood, effective case management and achieving prompt access will remain a challenge”.

References

1. Noor AM, Kirui VC, Brooker SJ, Snow RW (2009). The use of insecticide treated nets by age: implications for universal coverage in Africa. BMC Public; 1;9:369. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19796380

2. Vitor-Silva S, Reyes-Lecca RC, Pinheiro TR, Lacerda MV Malar J (2009). Malaria is associated with poor school performance in an endemic area of the Brazilian Amazon. Malaria Journal; 16;8:230. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19835584

3. Ogoma SB, Kannady K, Sikulu M, Chaki PP, Govella NJ, Mukabana WR, Killeen GF (2009). Window screening, ceilings and closed eaves as sustainable ways to control malaria in Dar es Salaam, Tanzania. Malar J; 8:221. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19785779

4. Foster D, Vilendrer S (2009). Two treatments, one disease: childhood malaria management in Tanga, Tanzania. Malar J; 8(1):240. [Epub ahead of print] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19860900

5. Nakibuuka V, Ndeezi G, Nakiboneka D, Ndugwa CM, Tumwine JK (2009). Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine for malaria prophylaxis in children with sickle cell anaemia in Uganda: a randomized controlled trial. Malar J; 8(1):237. [Epub ahead of print] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19852829

6. Sykes A, Hendriksen I, Mtove G, Mandea V, Mrema H, Rutta B, Mapunda E, Manjurano A, Amos B, Reyburn H, Whitty CJ (2009). Azithromycin plus artesunate versus artemether-lumefantrine for treatment of uncomplicated malaria in Tanzanian children: a randomized, controlled trial. Clin Infect Dis; 49(8):1195-1201. Available from: www.ncbi.nlm.nih.gov/pubmed/19769536

7. Chuma J, Abuya T, Memusi D, Juma E, Akhwale W, Ntwiga J, Nyandigisi A, Tetteh G, Shretta R, Amin A (2009). Reviewing the literature on access to prompt and effective malaria treatment in Kenya: implications for meeting the Abuja targets. Malar J; 8(1):243. [Epub ahead of print] Available from: www.ncbi.nlm.nih.gov/pubmed/19863788