Tropical Health Matters

Colleagues[1] from the Rwanda Ministry of Health, Jhpiego and the Johns Hopkins Bloomberg School of public Health are presenting a poster at the 64^th ASTMH Annual Meeting in Philadelphia at noon on Monday 26^th October 2015. Please stop by Poster 315 and discuss the results as presented in the Abstract below.

Malaria in pregnancy (MIP) is a serious health risk for the pregnant woman and fetus and associated with mortality in the perinatal period. In Rwanda there has been no accurate national estimate of malaria prevalence among pregnant women. In 2011, a cross-sectional study of 6 districts in 3 malaria transmission zones (low, medium and high) in Rwanda was conducted to estimate the prevalence of peripheral parasitemia in pregnant women. Data were collected from consenting women presenting to antenatal clinics (ANC) for the first time in their current pregnancy including age, parity, gestation, ITN availability and use.

Blood was obtained for malaria testing using microscopy, rapid diagnosis tests and polymerase chain reaction (PCR). A total of 4,037 pregnant women were recruited with median age of 27 years, and 3,781 (93.7%) had usable PCR samples. The prevalence of MIP by PCR was 5.6%.

Nearly 20% of women’s families did not have a net, and 8.7% of these tested positive compared to 4.9% of women whose family owned an ITN. For those who did not sleep under an ITN the previous night, 8.1% tested positive compared with 4.8% who slept under an ITN. Malaria prevalence by parity ranged from 5.5% (parity 0-1), to 5.4% (parity 2-3), and 6.5% (parity 4 or more). The two districts that bordered highly endemic countries had MIP prevalence rates of 10% and above. Those testing positive were treated according to national guidelines.

Despite a significant decline of 86% in malaria prevalence in the general population from 2005 to 2011, MIP prevalence remains high, especially in border districts. Our study also showed that ITN ownership and use among these pregnant women is below the national target. In order to address this gap, ITN distribution to achieve universal access, and educational campaign targeted at pregnant women on the use of ITN are recommended. Furthermore, early detection and treatment of MIP at ANC and regional collaboration to reduce cross-border malaria transmission should be prioritized.

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[1] Corine Karema, William R. Brieger, Irenee Umulisa, Aline Uwimana, Jeremie Zoungrana, Beata Mukarugwiro, Rachel Favero, Elaine Roman, Barbara Rawlins, Tharcisse Munyaneza, Fidele Ngabo, David Sullivan, Jean Baptiste Mazarati, Rukundo Alphonse, Agnes Binagwaho

Mufaro Kanyangarara and her PhD thesis adviser, Luke Mullany of the Johns Hopkins Bloomberg School of Public Health Department of International Health, have been looking into the challenges of controlling and eventually eliminating malaria in a multi-country context in southern Africa. We are sharing abstracts from her pioneering work including the following which explores risk factors on the Zimbabwe-Mozambique order.

Background: Malaria constitutes a major public health problem in Zimbabwe, particularly in the north and east bordering Zambia and Mozambique. In Manicaland Province in eastern Zimbabwe, malaria transmission is seasonal and unstable. As a result of intensive scale up of malaria interventions, malaria control was successful in Manicaland Province. However, over the past decade, Manicaland Province has reported increased malaria transmission, and the resurgence of malaria in this region has been attributed to limited funding, drug resistance and insecticide resistance. One of the worst affected districts is Mutasa District. The aim of the study was to identify malaria risk factors at the individual and household levels to better understand what is driving factors associated with malaria and consequently enhance malaria control in eastern Zimbabwe.

Methods: Between October 2012 and September 2014, individual demographic data and household characteristics were collected from cross-sectional surveys of 1,116 individuals residing in 316 households in Mutasa District. Factors characterizing the surrounding environment were obtained from remote sensing data. Factors associated with malaria (measured by rapid diagnostic test [RDT]) were identified through univariate and multivariate multilevel logistic regression models.

Results: A total of 74 (6.4%) participants were RDT positive. Parasite prevalence differed by season (10.4% rainy and 2.9% dry, OR 4.52, 95% CI 2.11-9.69). Sleeping under a bednet showed a protective effect against malaria (OR 0.54, 95% CI 0.29-1.00) despite pyrethroid resistance. The household level risk factors protective against malaria were household density (OR 0.89, 95% CI 0.87-0.97) and increasing distance from the border with Mozambique (OR 0.86, 95% CI 0.76-0.97). Increased malaria risk was associated with recent indoor residual spraying (OR 2.30, 95% CI 1.16-4.56).

Conclusions: Malaria risk was concentrated in areas located at a lower household density and in closer proximity to the Mozambique border. Malaria control in these “high risk” areas may need to be enhanced. These findings underscore the need for strong cross-border malaria control initiatives to complement country specific interventions.

Ilya Jones shares with us the latest update on Malaria Consortium’s Beyond Garki project that seeks to understand changes in malaria epidemiology and recommend effective strategies to improve control efforts ……

Over the last 15 years, increased global investment in fighting malaria has contributed substantially to reduction in the prevalence of the disease in endemic countries around the world. With the development of new technologies and innovative approaches to disease control, there is more hope than ever that malaria will be eliminated in places where it used to be a major public health threat.

However, sustaining momentum requires a deep understanding of the changes in the frequency of the disease, determinants of transmission and impact of interventions in a changing environment. Understanding these changes is essential in order to tailor health interventions to be as effective as possible.

Malaria Consortium’s Beyond Garki project, funded by the UK government through the Programme Partnership Arrangement (PPA), seeks to understand changes in malaria epidemiology and recommend strategies to improve malaria control efforts. The project is named after the efforts of the World Health Organization and the government of Nigeria to study the epidemiology and control of malaria in Garki, Nigeria between 1969 and 1976. Beyond Garki began in Uganda and Ethiopia in 2012, with four survey rounds conducted to date. Additional studies were also carried out in Cambodia, and more studies are planned in Nigeria. Each survey tracks changes in malaria epidemiology over time and will ideally inform strategic decisions on the use of interventions.

The baseline results have been made available and will serve as a point of comparison for data obtained from subsequent survey rounds, which will be released in the autumn. However the results of the baseline survey are interesting in their own right. Some of the highlights are listed below:

• Low to moderate malaria transmission intensity was observed in all sites. In Ethiopia, P. vivax was found to be a predominant malaria species, probably due to decline in transmission over recent years.
• High coverage of insecticide treated nets (ITNs)was observed in three of four sites but it is still not at an ideal level.
• ITN use rates among household members that had access were generally quite high. The study also showed there is willingness to buy nets, at least in the Uganda sites.
• In Uganda, a major vector of malaria, A. gambiae s.s., has developed resistance against pyrethroids.
• Most human-vector contact still occurs indoors. However, there is a tendency of early biting of A. funestus s.l. in one of the sites in Uganda. More information is needed to determine the biting and resting habits of vector species in both countries.
• The rate of malaria diagnosis using microscopy and rapid diagnostic tests (RDTs) has been strengthened in all sites. RDTs have been found to effectively predict negative malaria results, indicating that service providers should pay attention to other causes of fever when RDT negative results are reported for patients.
• The level of use of intermittent preventive treatment of pregnant women (IPTp) needs to be strengthened in Uganda.

To learn more about the project, the methods used to collect data, the findings and the recommendations, check out the dedicated microsite for Beyond Garki here, or read the baseline report here.

Omede Ogu of Nigeria’s Federal Ministry of Health reports on efforts to undertake mapping of malaria in the country as a basis for better planning of control and eventual elimination efforts.

The National Malaria Elimination Program (NMEP) has been meeting with the team from the National Space Research and Development Agency (NASRDA). Progress on pilot malaria mapping in Niger State is being reviewed, though the study is yet to be concluded. NMEP is also looking at opportunities that exist to expand their initial mapping to cover the whole of the country. Discussions are underway on next steps and development of a road map or a framework for the study going forward.

NASRDA explained that the current mapping effort was aimed is to use satellite-based technology to map surface water for Malaria Control in North-central Nigeria with Niger State as a Pilot study. They noted that data in inaccessible locations such as the marshy areas, thick forests, rugged terrain etc. were previously unavailable for relevant environmental policy and decision making in the region and Nigeria.

In addition is will be possible to do infrastructural mapping and inventory of health care facilities, in order to identify and assess the state of health care facilities, how accessible and future areas of need provision of these facilities in the country.

So far NASRDA has identified settlements, and locations of hospitals and health centres throughout Niger State using Global Positioning System (GPS). They have also identified water bodies and wetlands locations throughout the state.

Finally they are developing a map of Surface Water and wetlands in the state showing these in relation to locations of settlements, hospitals and health centres. NMEP is planning to link with colleagues doing similar mapping in Kenya.

NMEP plans to have the final report of the study ready by October for dissemination. Major partners with funding lines in their 2014 work plans for this study are the National Primary Health Care Development Agency (NPHCDA) and NASRDA. Additional funding and support is being sought.

Kenya already is using its mapping to focus appropriate malaria interventions. All countries will benefit in better mapping for targeting their malaria control and elimination efforts.

World Malaria Day 2014 was observed at the Johns Hopkins Bloomberg School of Public Health on Friday 25 April. 21 posters were presented. Below is the abstract of a poster presented William Moss and colleagues from the Southern Africa International Centers of Excellence for Malaria Research.

The Government of Zambia is committed to creating “malaria-free zones” in southern Zambia. Through passive case detection at health care facilities and active case detection through community-based surveys, we have documented a dramatic decline in the burden of malaria in the catchment area of Macha Hospital, Choma District, Southern Province, Zambia from 2008 through 2013.

Macha Hospital: https://www.flickr.com/photos/inmed/sets/72157625850417125/

However, residual foci of transmission exist and the potential for repeated importation remains. We identified individuals with subpatent parasitemia and gametocytemia who may be responsible for sustained, low-level transmission and evaluated reactive case detection strategies to identify and treat these individuals using simulation models.

Factors associated with sustained insecticide-treated bed net use were evaluated in light of the declining burden of malaria. Parasite bar coding of 24 SNPs should permit the identification of imported parasites.

Results of a longitudinal analysis of changes in antibody responses to 500 Plasmodium falciparum antigens using a protein microarray should allow detection of residual transmission and document loss of humoral immunity in the absence of exposure.

World Malaria Day 2014 was observed at the Johns Hopkins Bloomberg School of Public Health on Friday 25 April. 21 posters were presented. Below is the abstract of a poster presented by Suzanne Van Hull of Catholic Relief Services.

Catholic Relief Services (CRS) and the Ministry of Health and Sanitation (MoHS) of Sierra Leone (SL) are co-implementing nationwide malaria prevention and treatment activities funded by the Global Fund to fight AIDS, Tuberculosis and Malaria. In order to track progress and impact, CRS and partners led the implementation of a malaria indicator survey (MIS) in early 2013 covering a nationally-representative sample of 6,720 households, inclusive of blood testing to determine prevalence of anemia and malaria. In early 2012, CRS also had the experience of using mobile technology for a Knowledge Attitude and Practices (KAP) study.

Fieldworkers used Apple 3GS iPhones for both surveys to collect data via the iFormBuilder platform, a web-based, software-as-services application with a companion app for the mobile devices allowing for timely data collection, monitoring, and analysis.

This was the first time that iPhones were used for a MIS, and lessons learned include: allowing at least four months to transform paper-based questionnaires into electronic format, giving the program enough time for pre-testing the tool and training data collectors/biomarkers/laboratory technicians, and involving key malaria stakeholders to ensure a nationally-led survey. Global Positioning Systems enabled the MoHS to make in-depth analyses on malaria trends based on geographic locations.

Overall the benefits of an electronic versus a paper-based MIS questionnaire outweighed the challenges. The iPhone technology eliminated the need for paper transcribing, allowing for quicker data tabulation, real-time identification of mistakes, faster interviewing through skip patterns, and a close-to-clean dataset by the end of data collection saving time and money.

Survey results will be used to set evidence-based targets for all partners’ future malaria activities, especially the next 3 years of GF-supported malaria grants

Typical of our big disease mindset, most donor agencies think of HIV-Tuberculosis coinfection when addressing a connection among the three Global Fund diseases. Take as an example a recent News Flash from the Global Fund: “In a major step toward addressing the growing number of people affected by co-infection with tuberculosis and HIV, the Global Fund is improving the way it approaches treatment programs in countries with high rates of each disease. Millions of people infected with both TB and HIV could benefit from better services.”

The possible neglect of TB and malaria interactions might be understood by the fact that HIV and TB have much wider areas of endemicity than malaria. On the other hand both HIV and TB are disproportionately represented in malaria endemic Africa. At present the main connection between malaria and TB is the fact that they must share out of the same ‘envelope’ when new Global Fund support is distributed through the new funding mechanism to countries, a process that some see as moving more toward donor control and AID effectiveness and away from human rights.

Today the Stop-TB Partnership and related organizations are observing World TB day by noting that at least one-third of newly infected people will not get appropriate treatment. Poor access to or inadequate and inappropriate treatment plagues all three diseases, especially where health systems are weak.  We need an integrated approach to strengthen systems and improve care.

In the meantime, researchers have maintained interest in possible interactions between TB and malaria. For example Ann-Kristin Mueller and colleagues have published a study entitled, “An Experimental Model to Study Tuberculosis-Malaria Coinfection upon Natural Transmission of Mycobacterium tuberculosis and Plasmodium berghei,” using a mouse model. A slide presentation on their work is also seen at the website. As Mueller notes, “Concurrent infections most likely modulate the respective immune response to each single pathogen and may thereby affect pathogenesis and disease outcome. Coinfected patients may also respond differentially to anti-infective interventions.”

Mueller puts is mildly when she says that TB-malaria coinfection “has not been studied in detail.” We might need to step back in time over 2900 years where according to Lalremruata and colleagues, “the notion that the agricultural boom and dense crowding occurred in this region (southwest of modern Cairo), especially under the Ptolemies, highly increased the probability for the manifestation and spread of tuberculosis. Here we extend back-wards to ca. 800 BC new evidence for malaria tropica and human tuberculosis co-occurrence in ancient Lower Egypt.”

In a 2013 review on “Co-infection of tuberculosis and parasitic diseases in humans,” Xin-Xu Li and Xiao-Nong Zhou found only two direct reports of malaria and TB co-infection, one a case report from 1945 and the other on host response in malaria and depression of defense against tuberculosis from 1999.

Finally a review of hospital records from 2007 in Luanda, Angola found that Malaria was diagnosed during admission and hospital stay in 37.5% of TB patients. Clearly the time has come to take coinfection seriously as both a research and service delivery topic.

Chad had been free of debilitating guinea worm disease for a decade when ten new cases were uncovered in 2010. Logistical factors have prevented containment and the disease persists into the current transmission season. The Ministry of Health in Chad is currently examining 9 cases of human guinea worm but also 50 cases in dogs and one in a cat.

Donald Hopkins and colleagues recently explained that “Guinea worms in dogs have been reported for almost a century in some areas of Asia, Africa, and North America, including in some recently endemic countries that have interrupted transmission, but disease caused by D. medinensis has never been reported again after human transmission was interrupted.” In this situation where the cases in dogs far outnumber those in humans, one wonders hat the future holds for breaking transmission.

Two key lessons from this experience are to be learned by the malaria community. First is the fact that once eliminated, an infectious disease can return.  The context though probably relates to the neighborhood. Post-conflict South Sudan is one of the few remaining countries with continued guinea worm transmission and refugee movement may have contributed to the problem.

The second lesson is the potential for inter-species transmission. Plasmodium knowlesi, a disease of primates, appears about to become entrenched in the human population of Southeast Asia. Cases of monkeys having P. vivax have been documented in South America and Africa.  Elimination of human transmission of malaria may be hampered by non-human reservoirs.

We may not be able to say that elimination has occurred until there is no local transmission of any species of Plasmodium that affect humans in any other life form.  We have a hard enough time tracking malaria in humans when it falls below levels detectable by microscopes and rapid tests. What of the challenges of tracking it in monkeys?  Maybe these complications explain why to date smallpox remains the exception to the eradication rule.

Much of the discussion around global health and post-Millennium Development Goals focuses on non-communicable diseases (NCDs) including cardiovascular problems, diabetes, cancers and the the like.  While it is important to recognize that low income nations are not plagued with both communicable and non-communicable diseases, we do not want the greater focus on NCDs in richer countries to overshadow the problems of malaria, pneumonia, TB, diarrhea and other child killers in poorer countries.

A major reason for us not to lose focus on communicable diseases was recently reported from the Wellcome Trust on research they have supported in Malawi. The researchers found that the malaria parasite, Plasmodium falciparum, is able to “cause inflammation in blood vessel walls, making them more sticky so that the infected red blood cells can cling to the sides. Being able to stick to the blood vessels in vital organs allows the parasite to hide away from the immune system, a process called sequestration. When it occurs in the brain it causes a more severe form of the disease called cerebral malaria, associated with seizures, coma and sometimes death.”

The researchers also surmised that if this complication does not kill people in childhood, the damage to blood vessel walls can have more long lasting effects. In particular they noted that, “Chronic changes to the blood vessels like these could an important contributing factor to cardiovascular disease later in life.”

The link between malaria and Endemic Burkitt lymphoma (eBL) continues to be explored. Recently adding to this long history of eBL research, Peter Aka and colleagues reported that. “Anti–HRP-II (Plasmodium falciparum histidine-rich protein-II) antibodies suggest that recent malaria infection triggers the onset of eBL.”

In a review of intrauterine growth retardation (IUGR) Demicheva and Crispi observed that, “Several clinical and experimental studies showed that IUGR fetuses present signs of cardiac dysfunction in utero that persist postnatally and may condition higher cardiovascular risk later in life.” In endemic regions, malaria in pregnancy is a major cause of IUGR and thus low birth weight.

Preventing malaria therefore saves lives now and in the future. Ignoring malaria now adds greater burdens to the health system and national productivity tomorrow. We need to maintain our investments in malaria both globally and in and by endemic countries themselves.

Presented at Jhpiego’s Mini-University on 24 June 2013 in Baltimore by Marya Plotkin, Elaine Roman, and Maryjane Lacoste

Malaria in pregnancy (MIP) is a threat to the pregnant women, the unborn child and the newborn and infant. Intermittent Preventive Treatment during pregnancy (IPTp) is one of the few interventions available that specifically targets and protects pregnant women.  As malaria prevalence drops when countries aim at malaria elimination, we need to examine the continued role of IPTp and search for alternatives.

From August 2011 to September 2012, Jhpiego partnered with the Zanzibar Ministry of Health to conduct a study looking at the prevalence of placental malaria infection among women delivering in selected health facilities in Zanzibar who had not had IPTp during the course of their pregnancy. The community-level malaria positivity rate in Zanzibar declined from as high as 20% in 2005 to 1.6% in 2011. In Zanzibar as in the rest of Tanzania, IPTp coverage has been quite low, but pregnant women have access to long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS) is practised in the islands.

Midwives in six clinics in in Unguja and Pemba tested the women using PCR at delivery. Of the 1,356 women with no IPTp exposure enrolled in the study, only nine (0.6%) were found to have placental malaria (95% CI 0.2–1%). Thus, even without benefit of IPTp, other interventions appear to be protecting pregnant women to some degree.

Estimations of the costs of IPTp program put the annual expenditure at $114,678, while the annual cost of intermittent screening and treatment with RDTs (ISTp) would be $155,294.  Given the extraordinarily low prevalence of malaria in pregnancy, as well as pilot experience of testing in the ANC setting, there is a strong argument for adopting ISTp and dropping IPTp in Zanzibar.

To do so, the authors argue, thresholds of prevalence or incidence of malaria infection must be set in advance in order to trigger a reconsideration of the IPTp decision, and surveillance of malaria infection in pregnancy must be strengthened.

WHO has recently issued new guidance recommending continuation of IPTp where it is currently being practiced, making Zanzibar’s decision to maintain or discontinue IPTp of particular interest to the malaria in pregnancy community. Better guidance is needed on MIP services as countries move closer to malaria elimination.