Tropical Health Matters

This morning’s Washington Post featured a story concerning another setback in HIV/AIDS prevention research. The article stated that, “The abrupt closure last week of one part of a complicated study called VOICE marked the third time in eight months that anti­retroviral drugs did not prevent infection in those assigned to use them.” Ironically, the interventions had proven effective in smaller scale trials.  What happened during scale up?

The two research interventions focused on either having women insert a vaginal gel daily or people taking pills. One explanation offered for the failure the second time around was as follows:

The answers may lie in subtle differences between the groups being studied and the designs of the experiments. For example, the volunteers in Partners PrEP (pre-exposure prophylaxis study) were long-term couples in which one person was infected and the other not. It’s possible they may have been more motivated to take the pills every day. In CAPRISA (the South African PrEP study), the women inserted the vaginal gel before and after sexual intercourse rather than every day — a targeted approach that may have helped them stick to the program.

Such differences in the social and behavioral context of research make all the difference – basic research on drug effectiveness cannot be divorced from the people who receive the medications. The Post contacted experts who offered the following opinions about why there were problems.

• The daily regimen just probably was not acceptable; if the gel were being used according to instructions some differences between groups should have emerged.
• Other studies of vaginal microb­icides and pre-exposure prophylaxis have shown that few people use prevention tools as regularly as they say they do, but the more “adherent” people are, the more protection they get.
• What we have to face up to is that everything in HIV prevention is based in human behavior.

The article concluded by saying, “What seems clear is that this strategy, once viewed as the easiest and most certain, is going to require a lot of fine-tuning even if it works.”

With malaria interventions, similar lessons apply. ACTs do not protect is people do not adhere to the 3-day regimen. LLINs do not protect if people use them to cover their vegetable gardens. IPTp is not effective unless pregnant women attend antenatal care regularly. Rapid diagnostic tests are wasted if health workers do not believe in their efficacy.

Often we wait until problems of non- or inappropriate utilization of health interventions occur before we start looking at social and behavioral factors. The Post quoted one epidemiologist who said, “People are upset. It’s a big head-scratcher as to why it didn’t work.” Researchers should be embarrassed to admit such, as this means they did not do adequate formative research in advance to understand the social and cultural context into which they were introducing their innovations.

Certainly similar mistakes have been made in malaria research and intervention, but now with international donor funding severely threatened, we cannot waste resources pushing interventions that are not socially and culturally acceptable.

Another World AIDS Day has come and passed. Sarah Boseley has commented on the information overload that comes this time of year on the disease and the range of basic health programming and valiant efforts to control it. This led to thoughts on whether there are any new developments concerning the connections between Malaria and HIV.

A quick look at the most recent PubMed listings for “Malaria AND HIV” mostly yielded sentences with the common theme of “AIDS, TB and Malaria” that considered the big disease funding efforts and the combined global burden of disease but few new insights on how each disease affects the other. Some interesting examples were uncovered.

On the biological side, Jiang and colleagues in the journal Vaccine (2010 Nov 23;28(50):7915-22) observed that, “Malaria and human immunodeficiency virus type 1 (HIV-1) infection overlap in many regions of the world.” Using mouse models they found that, “important implications for the development of a new form of bivalent vaccine against both HIV-1 and malaria.”

On the programming side, Lugada et al. examined how “Integrated disease prevention in low resource settings can increase coverage, equity and efficiency in controlling high burden infectious diseases,” in rural Kenya, and reported on a campaign that provided, “HIV counseling and testing, 60 male condoms, an insecticide-treated bednet, a household water filter for women or an individual filter for men, and for those testing positive, a 3-month supply of cotrimoxazole and referral for follow-up care and treatment.” (PLoS One. 2010 Aug 26;5(8):e12435)

Reid reported on how injections for suspected malaria cases in drug shops and stores Tanzania and other rural African settings sets the stage for HIV and other infections. The need to prevent such practices can help both diseases. (Rural Remote Health. 2010 Jul-Sep;10(3):1463)

Noting that, “Co-infection of human immunodeficiency virus (HIV) with malaria is one of the pandemic problems in Africa and parts of Asia,” Oguariri and co-investigators examined, “the impact of pyrimethamine (PYR) and two other clinical anti-malarial drugs (chloroquine [CQ] or artemisinin [ART]) on HIV-1 replication.” They showed that, “10 μM CQ and ART inhibited HIV-1 replication,” while “10 μM PYR enhanced HIV-1 replication.” This is important news for malaria case management in areas with high HIV prevalence. (Virus Res. 2010 Nov;153(2):269-76)

While these studies individually may not be earth-shaking, they do point to the continued need for partnership between Malaria and HIV control programs – common interests do exist together with the common desire to save lives.

Under its new strategy, “PEPFAR patients will also be treated for tuberculosis, malaria and previously untreated tropical diseases,” according to a Washington Post editorial.  This is possible because, “PEPFAR 2 has three pillars: prevention, integration and improved health-care systems.”

The Post further explains that with PEPFAR 2, “The goal is to make the services a routine part of each nation’s health offerings.” The Post quotes Eric Goosby, the U.S. global AIDS coordinator, as saying that, “We need to transition them into being more embedded in the countries’ infrastructure and for the countries to have true ownership of them.”

Research in Rakai, Uganda, has found, “Excellent self-reported retention and appropriate use of ITNs distributed as a part of a community-based outpatient HIV care programme. Participants perceived ITNs as useful and were unlikely to have received ITNs from other sources.” What PEPFAR 2 appears to be calling for is a more integrated systems approach that through the new US Global Health Initiatives that ensures that mothers, children and families get the full range of services they need from an improved and sustainable local health service.

Even before this greater focus on MCH, health professionals like Walensky and Kuritzkes, have noted the “massive direct and indirect benefits PEPfAR has achieved already for mothers and children. It may be that PEPfAR—by providing health infrastructure, HIV prevention, parental survival, and the opportunity to sustain economic growth.”  Though not stated directly, these views describe an environment that is also more favorable to malaria control.

There are those who see global health programs like PEPFAR and GFATM as “distracting governments from coordinated efforts to strengthen health systems and re-verticalization of planning, management and monitoring and evaluation systems.” Biesma et al. note that there is much more that donor programs “could do much more to promote country ownership through aligning their objectives with comprehensive national health.” The Washington Post editorial indicates that this is exactly where the new PEPFAR strategy is aiming.

The UN Secretary General’s statement for the 2009 World AIDS Day reflects a theme common to the UN’s emphasis for malaria elimination – universal coverage. According to the Secretary General. “On World AIDS Day this year, our challenge is clear: we must continue doing what works, but we must also do more, on an urgent basis, to uphold our commitment to reach universal access to HIV prevention, treatment, care and support by 2010.”

Universal coverage is reflected in this year’s theme, “Right to Health.” The right to health also means that those who live with HIV/AIDS in much of the tropical world also need access to health services that prevent and treat malaria because co-infection with the two diseases presents a greater threat to health and survival.

The research world has been grappling with the challenges of HIV and malaria co-infection as was in evidence during numerous presentations at the recently concluded MIM 5th Pan-African Malaria Conference in Nairobi.  A few of the many abstracts are excerpted below.

In Cameroon HIV/Malaria co-infection was more associated with … lower CD4+ counts, high parasitaemia, high fever frequency, longer illness duration and low Hb concentration (Theresa Nkuo-Akenji, et al., wifon@yahoo.com, MIM 2009 Abstract 388).

At Tororo District Hospital, Uganda a cross-sectional study of HIV-infected women taking TS prophylaxis and HIV-uninfected women taking IPT–SP (1:3 ratio) found that microscopic infection was associated with Low Birth Weight for all women, but
Submicroscopic (PCR) infection was associated with LBW only among HIV-uninfected women (Patrick M. Newman et al., patrick.newman@ucsf.edu, MIM 2009 Abstract 424).

For HIV-infected children in Kampala, Uganda, both AS/AQ and AL were highly efficacious. Compared to AL, AS/AQ was associated with a higher risk of neutropenia, anorexia, malaise and abdominal pain. In HIV-infected Ugandan children AL was safer and better tolerated than AS/AQ (Fredrick Kateera et al., fkkateera@yahoo.com, MIM 2009 Abstract 594).

Finally, Peter Ouma et al. (pouma@ke.cdc.gov, MIM 2009, Nairobi, Abstract 131) studied Peripheral Malaria Parasitaemia in Pregnant Women, Kenya. Their findings are seen in the graph to the right. Both cotrimoxizole and SP offered some protective effect for both HIV+ and HIV- women.

Please read the MIM abstracts for more current research on HIV and Malaria, and remember that universal coverage is a basic right, one that should help us re-visit commitments that were once made to ‘Health for All.’

Partners “too often fail to coordinate programs to help promote more integrated, comprehensive health care for women,” and governments are “often unable or unwilling to initiate or sustain health care programs and reforms that would improve women’s access to services.” according to a new report from the International Treatment Preparedness Coalition.

If we did not know the source of this information we could assume it applies equally well to controlling malaria in pregnancy as it does to preventing mother-to-child transmission of HIV.  Both services are supposed to be part of integrated focused antenatal care (ANC).  Neither appear as regularly as needed to save the lives of mothers and newborns. This is not because women in developing countries fail to attend ANC.

Nearly 95 percent of pregnant women (in Uganda) attend antenatal care (ANC) services at least once during their pregnancy. They do not necessarily have access to comprehensive prevention of vertical transmission services, however, because just 43 percent of all health facilities that provide ANC and delivery services have integrated prevention of vertical. transmission.

Omo-Aghoja and colleagues point out that, “Part of the reasons for the low uptake of measures for malaria prevention in pregnant women in many African countries is the lack of proper integration of the recommended interventions into antenatal care (ANC) offered in health institutions.”

In a recent New York Times article on maternal mortality Dr. Massawe, a Tanzanian clinician asks, ““Why don’t we have a global fund for maternal health, like the one for TB, malaria and AIDS?”  Until the question of why women, including pregnant women, are not offered comprehensive and integrated services is answered, inequity and death of mothers and children will continue to be an unacceptable reality.

Today is the 20th anniversary of World AIDS Day. This is a good time to think about two diseases that have received some of the largest disease-specific funding in history.  The question is whether program planners for these two diseases not only recognize the effect each disease has on the other in overlapping areas of endemicity, but whether they maximize efforts to achieve synergies in joint programming.

According to Unicef, “In Africa, the HIV pandemic has been superimposed on the longstanding malaria pandemic, where P. falciparum malaria is consistently one of the major causes of infant and child mortality. The high prevalence of both HIV and malaria infection in Africa means that even small interactions between the two could have substantial effects on populations.” Some key points include –

• HIV infection increases the incidence and severity of clinical malaria
• Acute malaria infection increases HIV viral load

Korenromp and colleagues conclude that “Across 41 countries in sub-Saharan Africa, the HIV-1 epidemic may have increased the incidence of clinical malaria by 1.3% (95% CI 0.6%–7.9%) and malaria deaths by 4.9% (95% CI 3.1%–17.1%) in 2004.”

WHO has offered guidance on health systems response to the interaction of two diseases as follows:

• integrating services for prevention, treatment and care for malaria and HIV within the framework of maternal and child health services, is vital for reducing the burden of both diseases
• establishing mechanisms for collaboration and joint programming at various levels
• strengthening health systems and capacity for equitable service delivery, to address the needs of poorer ommunities
  that are most at risk of these diseases

Hopefully joint planning will receive greater emphasis today and in the future from the major partners who support efforts to fund and control both diseases including the Global Fund, Unicef, WHO, The Clinton Foundation and the US Government (PEPFAR and PMI).

PS – if you haven’t signed the HIV-Malaria petition yet, today would be a good day to do so - to sign the petition click: http://www.malariafreefuture.org/HIVMalariaPetition.php

Major new funding for HIV and Malaria has been coming in over the past eight years. The question is how that funding has not only impacted on the two diseases, but what has it done to the health systems that are expected to deliver disease control services?

From the beginning of RBM, partners and planners has stressed that malaria cannot be rolled back outside the context of health sector reforms and improvements.  Except for the possibility of ITN distribution campaigns, malaria control activities such as case management with ACTs and delivery of IPTp via directly observed treatment, require a strong, accessible and affordable primary health care system.  The issue of home management is tackled in the context of the health system training, supplying and supervising community volunteers. Even campaigns are run from a base in the district health department and linked with child immunization activities.

To some extent we have seen negative effects on the health system with new malaria funding when there is donor pressure to achieve and report quickly on performance – parallel procurement and distribution systems have been set up as well as parallel monitoring and evaluation processes, but ultimately the delivery of malaria control services requires that primary health services – facilities and staff – function on the ground.

In contrast critics have pointed to HIV/AIDS programming as creating its own structures resulting in internal brain drain within countries – pulling staff and resources away from the basic health system in order to reach treatment and coverage targets. A recent publication, Seizing the Opportunity of AIDS and Health Systems, explores this issue through three country examples. The report focuses on health information, supply chain and human resources in Mozambique, Uganda and Zambia. Concerning information system the report summarizes the situation thus:

In each of the three countries donors draw information from parts of the health information system and from national monitoring and evaluation systems. Meanwhile, all three donors have their own donor-specific reporting requirements in all three countries. The proliferation of information systems results partly from donors’ own priorities and accountability requirements. But it also reflects weak government coordinating structures for health information system management. And it reflects the ill-equipped, underfinanced state of national AIDS councils.

There is evidence of functional antiretroviral supply chains, but not a strengthening of the overall supply chain within countries. “In all three countries, the Global Fund, PEPFAR, and the MAP have worked with governments to develop supply chains for antiretroviral drugs. The supply chains are still fairly small, however, often serving 300 facilities or fewer. They rely largely on public structures. Yet they generally function more smoothly than the much larger government-managed supply chains for other essential medicines.”

In addressing human resources the report says that donors have focused more on in-service training of existing workers than on helping enlarge the pool of health staff. Because of better salaries and benefits in donor-supported programs, health staff have been pulled away from the public sector, thus weakening the health system. The report concludes by saying …

As PEPFAR, the Global Fund, and the MAP work to extend the reach and effectiveness of their HIV/AIDS programs, they will continue to find that country health system weaknesses create barriers to program expansion. To surmount those barriers they should finance programs in ways that increase the abilities of country health systems to provide broad quality health services, while doing the least possible harm to those systems. But to create greater incentives for donors to seize this opportunity, actions by country governments are also urgently needed. Earmarked funding for HIV/AIDS is evidently here to stay. The approach recommended here will ensure that donor funds bring the greatest possible benefits to country health systems while also achieving desired AIDS-specific outcomes.

We might add that benefits to the country health systems will ultimately also benefit efforts to control malaria.

Malaria is estimated to kill over 1 million people a year, mostly children, while the annual death toll from HIV/AIDS approaches 2 million. Where these diseases overlap, “Malaria contributes synergistically with HIV/AIDS to morbidity and mortality in areas where both infections are highly prevalent, such as in Africa south of the Sahara. In addition to providing immediate health benefits, prevention and treatment of malaria may lessen transient increases in HIV viral load during malaria episodes and thus help limit the progression,” according to the World Malaria Report.

With the clear public health links between the two diseases, one would have expected to see more reports about malaria in HIV within the XVII International AIDS Conference in Mexico. Search at the conference website on malaria as a key word turned up only four abstracts or session outlines that actually addressed malaria, not just presentations that happened to spell out the full title of the Global Fund, and thus inadvertently mentioned malaria.

An abstract by Imani et al. reported that, “HIV infection was significantly associated with cerebral malaria in children admitted to Mulago Hospital and the prevalence of HIV infection among those with cerebral malaria was 9%.
Recommendation: Malaria prevention should be an important component of education and counselling of HIV infected children and their caretakers. A large study is recommended to establish whether there is a correlation between the level of HIV immunosuppression and cerebral malaria.”

Oloo and colleagues presented on “Strengthening HIV/AIDS programs for transport sector workers through a regional trade union approach in East and Central Africa.” Among their recommendations was the importance of providing “integrated reproductive health, malaria and family planning services to transport workers through the resource centers.”

A workshop is being organized on, “Uniting and Empowering Civil Society on CCMs: How AIDS, TB, and Malaria Organizations Can Work Together on CCMs and in GFATM Advocacy,” and is crosscutting on the three diseases.

Finally, Raposo et al., presented the topic, “Counseling and testing in health: a public health approach to increase access to health promotion in Mozambique.”  They stressed the need for linkages with other health services. A model for better integrated services was described that included, “Additional counseling is provided for malaria prevention, environmental health, uptake of antenatal care during early pregnancy, and institutional delivery.”

Better integration of disease control and prevention efforts is needed to better serve those in endemic communities. Integration should also be evident in advocacy efforts such as international conferences. We can’t afford the medical model that looks at diseases only, not the people who suffer from multiple problems.

Infectious diseases during pregnancy put both the mother and the unborn child at risk.  According to WHO’s Global Malaria Program, co-infections with HIV and malaria put pregnant women at special risk. WHO is also concerned that opportunities to address infectious diseases like HIV and malaria are often missed during antenatal care (ANC).  WHO therefore recommends a minimum 4-visit focused ANC package as follows:

For antenatal care to be effective, all pregnant women need a minimum of four visits, at specific times and with evidence-based content. Care for women during pregnancy improves health by preventive measures, and by prompt detection and management of complications. Essential components of a focused antenatal-care package include screening for and treatment of disorders (such as anaemia, abnormal lie, hypertension, diabetes, syphilis, tuberculosis, and malaria); provision of preventive interventions (such as tetanus immunisation and insecticide-treated bednets); and counselling about diet, hygiene, HIV status, birth, emergency preparedness, and care and feeding of babies. Since antenatal care has good coverage, it provides a platform to increase the interventions provided during antenatal visits, including HIV care for the mother, prevention of maternal to child transmission (PMTCT) of HIV, and support for feeding choices. However, this opportunity must be weighed against the risk of overloading services that are already stretched.

It is encouraging to see that the Ministry of Health in Mozambique is taking the integration of malaria control and PMTCT into its antenatal care services.  The picture above shows an ANC nurse’s desk in one of the more that 500 health facilities that offer PMTCT. There is almost what one could call a one-stop-shop for pregnant women in terms of getting their preventive medicines – sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (IPT), and AZT and neviraprine for PMTCT prophylaxis, among others.

Some challenges to this integration remain.  The policy for IPT was adopted only in 2006 after pilot testing in two provinces, and needs to be disseminated more fully. PMTCT is presently offered in only about one-half to one-third of health facilities where ANC is offered. ITNs are not yet available in all routine service points, but there is a strong commitment to contiunue work toward integration.

The Round Six Global Fund application for Mozambique summarizes the vision of integration: “The HIV/AIDS component supports provision of comprehensive antenatal care (ANC) to pregnant women, consisting of provision of anaemia, syphilis and HIV tests; iron, folic acid and vitamin A supplementation; Intermittent Preventive Tretament (IPT) of malaria in pregnant women; de-worming, health education & counselling on breastfeeding , nutrition, HIV and hygiene. The delivery by the malaria component of ITNs through routine ANC will reinforce this comprehensive care. Early data from applying the model in Inhambane Province has also shown increased use of ANC when ITNs are made available; this will enhance uptake of the other services.”

We hope other countries take this as a model of ANC integration to emulate.

The International Federation of Red Cross and Red Crescent Societies (IFRC) has just released its 2008 World Disasters Report. The report observes that, “The AIDS epidemic has been with us for more than a quarter of a century but the statistics never fail to shock. Around 25 million people have died and about 30 million are living with HIV today. Many of these men, women and children are among the world’s most vulnerable people and, although it is too simplistic to say that poverty is a main driver of the epidemic, many people living with HIV are among the poorest on earth – particularly women.”

HIV/AIDS is a major global disaster because, “Even though anti-retroviral treatment is now available, it does not reach the majority of those who need it in developing countries. Nor are medicines for the opportunistic infections associated with AIDS readily available in many places. It is not just a question of funding, which has increased at a considerable rate. In most affected countries, as in many parts of the developing world, health services are overstretched, with poor infrastructure, and are losing the trained workers they desperately need to the rich countries of the West. Development gains that were achieved in the past two decades have in many cases been reversed. Poverty reduction, income generation, food security – all remain on the agenda for the humanitarian world, and not just in places where major emergencies have occurred.”

While the report quotes the World Bank as saying, “HIV/AIDS, malaria, and armed conflict have contributed to these falling life expectancies,” it does not acknowledge how the negative interaction between HIV and malaria make both problems worse. Skinner-Adams and colleagues summarize the problem as follows: “Although the consequences of co-infection with HIV and malaria parasites are not fully understood, available evidence suggests that the infections act synergistically and together result in worse outcomes.”

According to WHO’s Global Malaria Program, “Malaria and HIV are two of the most devastating global health problems of our time. Together they cause more than 4 million deaths a year. The resulting co-infection and interaction between the two diseases have major public health implications.”

• HIV-infected people must be considered particularly vulnerable to malaria;
• Antenatal care needs to address both diseases and their interactions;
• Where both diseases occur, more attention must be given to specific diagnosis for febrile patients.

Clearly we do not want to start a debate about which disease is more disastrous, and one might even make the case that HIV has a more disastrous effect on the health system, but we do want to stress that solutions require an integrated approach.  People with HIV definitely need protection against malaria as one part of the effort to ameliorate this disaster.