Tropical Health Matters

At present artemisinin-based combination therapy medicines for malaria are our best hope for treating malaria and have the added benefit of reducing parasite transmission.  If these drugs lose their power, we are in trouble; hence there is need for continued testing to ensure that drug efficacy remains high.

The Nigeria National Malaria Control Program has just circulated its latest malaria drug testing results. All endemic countries should see this as a model for their own continued monitoring of malaria drugs.

A total of 747 children were enrolled in the two treatment arms – artemether-lumefantrine and artesunate-amodiaquine. The sample was drawn from investigations at seven sites in different geographical settings.  Below we find the main points as summarized in the Executive Summary.

1. The Therapeutic Efficacies of two Artemisinin-based Combination Therapies (ACTs) – Artesunate-Amodiaquine (AA) and Artemether-Lumefantrine (AL) were evaluated in 724 children <5 year-old drawn from 7 sentinel sites; Lagos, South-west, South-east, South-south, North-central, North-west and North-east located in 6 geographical zones of Nigeria.

2. All children recovered clinically from their illness. Fever clearance was significantly faster in children treated with AA than in those treated with AL (1.19 ± 0.49 versus 1.33 ± 0.7 d, P= 0.006).

3. Compared with AL, AA significantly reduced the proportion of children with parasitaemia 1 day after treatment began (P=0.016), but parasite clearance times were similar in AA- and AL- treated children (1.13 ± 0.4 versus 1.11 ± 0.34 d, P= 0.47).

4. Overall, adequate clinical and parasitological response (ACPR) on day 28 was 97.4%, and was similar for both AA (95.1%) and AL (96.3) P=0.108). Early treatment failure occurred in one child treated with AA.

5. Overall, PCR-corrected parasitological cure rate on day 28 was 98% and was significantly higher in AA- than in AL- treated children 99.1% (343/346) versus 96.9% (311/321), P=0.048. The cumulative probability of a reappearance of asexual parasitaemia after treatment with AA or AL were similar (Log-rank statistic = 0.027, P=0.869)

6. Recurrent infections were not age or drug dependent. Overall, recrudescence occurred in 5.3% of the children (38 of 711), and was unrelated to age or drug treatment. Recrudescent infections were significantly more common in the eastern flank (North eastern, North central, South eastern than the western flank (North-western, South-western and Lagos) of the sentinel sites [32 of 311 children (10.3%) versus 6 of 319 children (1.9%), P<0.00001].

7. Overall, gametocyte carriage after treatment with both drugs was significantly lower compared with pre-treatment [16 of 491 children (3.3%) versus 46 of 620 children (7.4%), P=0.005].

8. Anaemia, defined as haematocrit <30%, was present in 294 of 672 children (43.8%) and was significantly more common in the eastern than in the western flank of the sentinel sites. Anaemia resolved completely in all anaemic children within 14 days in 93% of the chilldren.

9. In anaemic children, anaemia resolution time was approximately 10 days for both drugs.

10. In the few sentinel sites where adverse drug reactions were monitored, both drugs were tolerated; the reported adverse drug reactions were indistinguishable from the symptoms of malaria.

11. AA and AL are safe and efficacious treatment of uncomplicated P. falciparum malaria in <5 year old Nigerian children.

The full study will be made available at the NMCP’s website.

The publication this week by African Leaders Malaria Alliance (ALMA) of progress reports of African nations toward controlling and eliminating malaria and other maternal and child health problems has been both enlightening and helpful for advocacy and planning.  If one combines these data with reports by the Roll Back Malaria Partnership (RBM) on progress towards country Roadmap targets, a good picture emerges of the steps needed to reduce malaria deaths by 2015.

The time frames of the two indices are different – RBM is looking at overcoming gaps laid out by national malaria programs in 2010, while ALMA – but they are close enough to highlight the main logistical, process and input challenges facing endemic countries. The ALMA scorecard does have one outcome indicator – operational coverage of long lasting insecticide-treated nets (LLINs) – but one needs to consult surveys such as the Malaria Indicator Survey to get more accurate coverage data, and such surveys are scheduled less frequently.

Several key issues arise from these two reports.  For example, the ALMA Scorecard shows that eight countries do not have a policy that enables community case management of malaria, a strategy that is essential for achieving universal and timely coverage of malaria treatment. Though not indicated clearly, such a policy should include the use of rapid diagnostic tests (RDTs) and the community level.

Sixteen countries do not have full funding for purchasing the RDTs they need. RDT supply problems also appear in the RBM Roadmap analysis. Eighteen countries lack full financing for their LLIN needs.  Unfortunately, if not enough funding is available to achieve universal coverage now, what will happen in three years when most of the recently distributed nets may need replacing?

Of course there are hopeful signs. The Scorecard shows that ten countries have reduced malaria deaths by more than 50%, and another seven have made substantial progress. It is unfortunate that the remaining countries are left blank implying that there are inadequate data to make such calculations.  We will have trouble eliminating malaria is our monitoring and evaluation systems cannot measure progress towards our goals.

Hopefully such tools as the Roadmap analysis and the Scorecard will spur some friendly competition among malaria endemic countries in Africa that will save more lives and boost national economies.

The coverage has started of the big UN focus on non-communicable diseases (NCDs).  BBC leads with a headline that states, “WHO targets non-communicable ‘lifestyle’ diseases.” Lifestyle is a facile term that may lead one to think that people have certain diseases because of choices in their lifestyle.

Is poverty a lifestyle? We doubt whether people chose poverty.

NCDs, like almost all diseases, have a ‘behavioral component’ in their etiology, but we need to be careful not to blame the victim whose health related behavior may be confined by culture, poverty or a political system.  Behavior also therefore is not a simple matter of ‘lifestyle.’

So, if we are getting into the issue of behavior as a factor in the spread of disease, we need to be careful about making black and white distinctions between communicable and non-communicable.  Malaria, a communicable disease (with a vector) arises not from simple lifestyle choices to avoid sleeping under an insecticide treated – the factors influencing behavior are complex. Furthermore, communicable diseases have non-communicable consequences – witness the challenges of chronic anemia and neurological consequences of malaria.

In the push for a new theme for the decade we need to avoid compartmentalization and remember the universal goals that launched primary health care in 1978.  Our goal should not be to focus on or un-neglect a class of diseases, but to ensure all people, especially those living in poverty, have equitable access to whatever care and prevention they need.

Attention has recently focused on the news that malaria deaths are reducing and therefore, we may actually experience no malaria deaths by 2015 in line with the Millennium Development Goals. The excitement has been generated by a new report in the Progress and Impact series that documents great increases in malaria funding. Optimism helps spur action, but occasionally caution is needed so that slight disappointments do not grind action to a halt.

Two recent publications should encourage a little caution without dampening enthusiasm.

A headline in Ghana Business News states that, “Ghana risks missing some MDGs by 2015.”  The article explains that “… a study jointly conducted by the Ministry of Health and Ghana Health Service (GHS) has revealed … certain bottlenecks and organisational weaknesses …”  These weaknesses include –

• absence of integration of programmes
• general health service financial resources at national levels
• weak community participation in health planning and management
• increasing sense of frustration and neglect on the side of community volunteers

These are health systems and management issues – the very framework on which good malaria interventions are built.  Even the MDG website itself encourages us that “efforts must be sustained to win the battle.”

The Demographic and Health Survey (DHS) has published the preliminary results of the Nigeria 2010 Malaria Indicator Survey (MIS). Because of its large population Nigeria is the bellwether for controlling malaria on the continent with the overall highest number of malaria cases. Compared to the 2008 DHS, the 2010 MIS shows an increase from 17% to 44% of households that own any kind of bednet.  Gains are greatest in states supported by special programs such as the World Bank Booster, but are smaller than needed for achieving the 2010 Roll Back Malaria targets.

Speaking of targets, the proportion of young children sleeping under any kind of bednet in 2008 was 12% and rose to only 30% in 2010.  The figures are lower for insecticide treated bednets. Even in households with a net, only 59% of children slept under them.

Once can argue that Nigeria did not complete its net distribution for universal coverage in 2010 as hoped, but this gets back to the health systems bottlenecks mentioned in Ghana. Further caution is needed when one realizes that these millions of nets distributed up through 2010 will likely need replacement before 2015.

At present 51.5% of the children under five years of age tested with Rapid Diagnostic Tests in the 2010 Nigeria MIS tested positive for malaria.  We can certainly reduce mortality even if bednets are not used, but only 6% of this age group who had fever in the two weeks preceding the MIS had received the recommended artemisinin-based combination therapy.

Funding increases for malaria commodities alone will not achieve the desired reductions in malaria mortality, not will funding alone be able to tackle the health systems bottlenecks identified in many high prevalence countries.  A change in attitude is needed from top level political will to front line health worker perceptions.  If primary health care generally is not working, not reaching the people, malaria will still kill.

When calculating the burden of malaria, we often forget the longer term disabilities that persist after an acute episode. Specifically, Kariuki and co-researchers highlight that, “Falciparum malaria is an important cause of acute symptomatic seizures in children admitted to hospitals in sub-Saharan Africa, and these seizures are associated with neurological disabilities and epilepsy.”
In a new review in Neurology, Ngugi and colleagues report that …

“Our estimates suggest that the incidence of epilepsy in LMIC (low and middle income countries) is approximately twice that of HIC (high income countries) … The cause of the higher incidence in resource-poor compared to industrialized countries is likely to be multifactorial. The higher incidence of head trauma and of infections and infestations of the CNS (central nervous system) such as malaria, neurocysticercosis, and invasive bacterial infections may be important causes.”

Preventing malaria or treating malaria in a very timely manner is a crucial step in reducing the long term burden of disease in individuals and countries. Kariuki et al. note a challenge: “… it is difficult to determine the proportion of seizures attributable to malaria in endemic areas since a significant proportion of asymptomatic children have malaria parasitaemia.”

Kenya has been experiencing some intense malaria intervention over recent years.  This provides a setting where researchers have gotten a handle on the potential reduction in the burden of long term CNS disease because of malaria control activities. Among the findings Kariuki et al. report are that, “From 2002 to 2008, the incidence of all acute symptomatic seizures decreased by … 69.2% with 93.1% of this decrease in malaria-associated seizures.”

Malaria itself imposes major immediate costs on a community from direct service payments and indirect loss of work and of course from loss of life. We should not forget the lingering costs of severe malaria may degrade the educational and occupational capacity and opportunities of community members, leaving such endemic communities mired in poverty. Clearly malaria elimination is an essential contribution to national development.

Five models of equitable access to maternal and child health (MCH) services are the focus on a new article by Talukder and Rob.  We wonder what lessons these models hold for improving access to malaria treatment and preventive services, which should be integrated into MCH.

The five model programs from Asia and Africa listed below do cover malaria-endemic communities –

• Community Health Volunteers Program in Bangladesh (BRAC)
• Lady Health Workers Program in Pakistan (LHW)
• Reproductive and Child Health Alliance Program in Cambodia (RACHA)
• Community-based Health Planning and Services in Ghana (CHPS)
• Tanzania Essential Health Interventions Project (TEHIP)

Each model addresses innovative ways of strengthening and managing health systems so that communities are reached and linked with the wider health system. At least four of the models involve community health workers who may be volunteers or receive a stipend.

BRAC is well known for involving community members in health provision and links their sustainability to microfinance opportunities and sales of basic health commodities.  This model has been used in malaria endemic areas of Bangladesh, the Chittagong Hill Tract. An evaluation of the effort reported that …

BRAC and the Ministry of Health implemented the national malaria control programme under GFATM and BRAC would be responsible for supplying LLIN to 80% household, as well as deploying health workers in every union to provide RDT (rapid diagnostic tests) and AL (artemether-lumefantrine) at the grass root level.

Community volunteers were effective in ensuring that the target goal for the supply of LLIN and retreatment of ITN were surpassed, but there was still competition with drug vendors in the provision of malaria treatment.

BRAC is now implementing its model with community health promoters supported by microfinance to implement malaria control as part of its overall health interventions in Liberia.

RACHA takes a different approach to promoting equity, especially gender equity in health service access. “RACHA works almost exclusively in support of the Ministry of Health’s priorities and programs. It does not provide health services or operate health facilities but works through the MOH service network and its community links to translate MOH technical policy and program priorities into quality effective intervention programs in the field.”

RACHA enhances health worker skills, guarantee quality assurance, improve supply mechanisms and create demand in the community.  RACHA also provides midwife training and delivery kits and microfinance to support the midwives. Although malaria is not specifically mentioned, quality assurance is certainly essential to addressing the problem of artemisinin resistance in the region.

Lady Health Workers are an core component of Pakistan’s primary health care efforts. According to WHO LHWs …

…act as a liaison between the formal health system and the community and disseminate health education messages on hygiene and sanitation. The programme is strongly rooted in the primary health care concept and it aims to achieve universal health coverage. Each Lady Health Worker serves around 1000 individuals.

LHWS receive a small salary of about US$ 343 per year. “Lady Health Workers provide essential drugs for treatment of minor ailments such as diarrhoea, malaria, acute respiratory tract infection, intestinal worms, etc., as well as contraceptive materials to eligible couples.”

Ghana’s CHPS program ensures that communities and specially trained community nurses work together to provide primary health care to under-served rural areas, including of course, malaria treatment.  While community volunteers are part of the effort, the overall community takes responsibility for providing a simple structure for a clinic and nurse housing.

Talukder and Rob note that the CHPS effort has resulted in decreased child mortality and and fertility rates in communities with what are known as the CHPS compounds. Up-to date information on the number of CHPS compounds is not available at the Ghana Health Service website, but estimates from 2008 are that “National coverage is now approximately 9% percent of the population.”

Finally, the TEHIP focuses of strengthening planning and management capacity of district health services.  According to ODI, the two pilot districts showed that …

TEHIP has brought about a change in the way that local health policy and practice is planned and resources are allocated across geographical and technical areas. At the district level health care workers and managers are more in control of resources and processes. This has also contributed towards a more robust decentralisation of the health care provision.

Because of TEHIP, “Child mortality in the two districts fell by over 40% in the 5 years following the introduction of evidence-based planning; and death rates for men and women between 15 and 60 years old declined by 18%.”

These results were achieved because the evidence-based planning model yielded an increase in average clinic visits per child from 2.8 to 5.8 a year. “More children were treated for malaria, more early cases of worms were spotted, more eye infections were caught, more AIDS messages were shared, and more mothers had exposure to family planning information.”
While these equity-fostering interventions have resulted in improvements in malaria indicators as well as broader child and maternal health statistics, they appear to have varying levels of scale-up and sustainability.  They all demonstrate the need for new ways of planning and managing district health services, and in at least three cases show the importance of community involvement.  A couple demonstrate innovative ways of using microfinance to sustain community health worker commitment.

Overall the lesson is one that has been voiced since the dawn of the Roll Back Malaria Partnership – we cannot roll back malaria without health system reform.

Over 40% of child deaths are now due to neonatal mortality, according to National Public Radio (NPR). NPR was commenting on a new article published in PLoS Medicine that examines neonatal death trends between 1990 and 2009. Although reducing child deaths is a key component of the Millennium Development Goals, neonatal mortality rates have actually increased in eight African countries, many of which are endemic for malaria.

Malaria contributes to neonatal mortality in two ways.  First, malaria in pregnancy leads to stillbirth and low birth weight babies who are more prone to death that those of normal weight. In a recent review, Ishaque and colleagues reported that, “The clearest evidence of impact in stillbirth reduction was found for adequate prevention and treatment of syphilis infection and possibly malaria.” Low birth weight can be prevented by using intermittent preventive treatment during pregnancy (IPTp).

The second contribution of malaria to neonatal mortality is congenital and neonatal malaria. A recent study in Nigeria has re-emphasized the connection between placental malaria and congenital malaria. Again, IPTp has be found effective in reducing neonatal cases of malaria.

Published research from Mozambique confirm that, “IPTp-SP was highly cost-effective for both prevention of maternal malaria and reduction of neonatal mortality in Mozambique.” Ironically, IPTp coverage is one of the key malaria indicators that is lagging as we have passed the RBM 2010 target of 80% coverage with two doses minimum for each pregnant woman in stable transmission areas.

Sufphadoxine-pyrimethamine, the drug used for IPTp, is cheap.  Many women attend antenatal care clinics where IPTp is (or should be given), yet Demographic and Health Survey results show few countries nearing even the 60% coverage mark for two IPTp doses.  There are no excuses in 2011 for pregnant women suffer and their newborns die because of malaria in pregnancy.