Main content
Tropical medicine is commonly regarded as being in the domain of internal medicine and paediatrics. It can be translated as the practice of (internal) medicine in the tropics (read: low- and middle-income countries – LMICs), which would then also include the local epidemiology and pathology as well as practical issues around the availability and use of diagnostics and therapeutics, all in the context of the local culture, socioeconomic conditions, and health system set-up. Training and research are important components of tropical medicine. For other specialties, e.g. surgery, obstetrics and gynaecology (O&G), and ophthalmology, the same principles would apply.
In this paper, various common issues in the practice of tropical medicine research are discussed.
Should we do research in LMICs?
There is no doubt that research has been of tremendous benefit to population health in LMICs. Examples are abundant. The treatment of severe malaria was revolutionised by the introduction of artemisinin derivates that were shown to be superior to quinine, due to their action early in the life cycle of the Plasmodium falciparum parasite which prevents infected red cells from blocking brain capillaries. This is essential in the pathophysiology of cerebral malaria. We now know how to diagnose and treat most of the opportunistic infections in HIV/AIDS due to rigorous research, although clearly questions remain. While for infectious diseases much progress has been made, there remains a lot to be done for non-communicable diseases (diabetes mellitus, hypertension, heart failure, cancer, etc.), which are at least as important in terms of morbidity and mortality. A full review of research needs is beyond the scope of this paper.
It is also important to note that not all research outcomes achieved in high-income country (HIC) settings can be extrapolated to LMICs. Ideally, research should be done in the local population. For example, the response to antihypertensive drugs is different among white and black Americans: while ACE-inhibitors work well in whites, black people respond better to isosorbide and hydralazine. Other examples include the use of co-trimoxazole (given as a prophylactic in HIV/AIDS patients), and abacavir (an antiretroviral agent) that do not cause severe hypersensitivity reactions (skin rash) in Africans compared to Caucasians.
Would research divert scarce resources and hence be harmful for patients?
This is a point of crucial importance, especially in resource-constrained environments. Studies should be funded and organised in such a way that the additional staff needed (doctors, nurses, lab technicians) can be hired in order to avoid a negative impact on the continuation of routine health services, infrastructure and supplies. In addition, the research staff should not work in isolation but should be integrated in and contribute to regular patient care.
How to decide what to study?
From a control perspective, e.g. for the neglected tropical diseases (NTDs), it is important to carefully assess the research priorities, and a holistic approach is needed. It is advisable to consult the local health authorities in the Ministry of Health, wherever appropriate, to see how a clinical or a basic science study would complement public health strategy. From a clinical perspective, it is entirely justified for a clinician to investigate any relevant clinical problem in daily practice, e.g. compliance to antihypertensive drugs, the prevalence of malnutrition, or causes of febrile illness. A simple case report or case series could make an important contribution.
Is it possible for everyone to do research in LMICs?
Certainly. One of the most valuable ways of conducting research is in the format of bilateral collaboration. The objectives, methodology, expected outcomes, relevance for the local situation, and implementation should be clearly defined. The role of each researcher and partner organisation should be clear, including (intellectual) ownership and publication policy. Capacity building is essential. Where the local researchers provide the day-to-day patient care, the partner from abroad, usually from a HIC, may provide technical expertise to perform certain tests on samples that have been shipped, or, preferably, help perform them on site. Training is also essential, both for young researchers on the site as for those joining from abroad. Training of a young researcher from the LMIC may include courses e.g. in epidemiology or statistics, specific training for example in a laboratory technique, or in the form of a master’s or PhD degree depending on the stage of the candidate’s career.
Should the focus be on randomised clinical trials (RCTs) as these are considered most powerful?
Not at all. It simply depends on the question you want to answer. Simple and straightforward operational research may just give you the answer you are looking for, for example by analysing case notes. Once your research question is well defined, it may not be too difficult to choose an appropriate study format; and assistance of a statistician, if applicable, is preferably sought before starting data collection.
What about ethical issues?
In 1964, the World Medical Association defined the ethical principles for medical research, including human subjects, in the Declaration of Helsinki, which has guided the conduct of research in the tropics. [1] All research that includes data or samples taken from patients should be approved by the local ethics committee, and in case of a collaborator overseas, in that institution. While most LMICs have ethics committees in place, in others this is not yet the case. There are programmemes in the World Health Organization where a joint review committee is formed, consisting of experts from countries with a well-established reputation in research review, who are joined by reviewers from countries that are building up this type of expertise.
If certain tests can only be done abroad, materials may be shipped after signing a Material Transfer Agreement in which is clearly stated who owns the samples, what tests will be done, and what will happen to the samples after testing is completed. All this requires permission from the local ethics committee.
Can we do all types of studies in LMICs?
Clinical trials include phase 1 studies (drug dose ranging for safety), phase 2 studies (testing a drug for safety and efficacy in selected patients), and phase 3 (efficacy, efficiency and safety in all affected patients). Phase 4 studies involve post-marketing pharmacovigilance. While in phase 3 studies the number of patients studied is limited to several hundreds or thousands, after the marketing of a new drug, many more patients are treated and monitored for long-term effects in safety and efficacy.
Phase 1 studies require human volunteers, and these are usually done in young men in HICs, for practical reasons, such as close monitoring and availability of interventions in case of adverse reactions. The call to do these studies in LMICs is becoming stronger, as it is clearly more appropriate to study drug effects in the same population where the phase 2 and 3 studies will be done, as the response to drugs may be different. As research capacity in LMICs is becoming stronger and of a higher level, the perceived view that people in LMICs are used as “guinea pigs” will no longer hold.
Should the dutch medical doctor in global health and tropical medicine (MD GH&TM) do research?
While this is formally not a training objective, the MD GH&TM should be encouraged to define a research question and establish a link with a supervisor in the Netherlands or elsewhere to further develop this as a potential project. Basic research methodology should be in the training programmeme. An overview of research performed by MD GH&TMs showed that most publications efforts, including PhD theses, involved research in O&G in LMICs. [2]
Should medical students in LMICs be taught in research?
Yes, and this is already the case in many universities in LMICs. Students are trained in research methodology and doing research projects. From this pool, new young researchers will hopefully develop who can join research efforts and become independent researchers.
International collaboration
In any bilateral or multilateral collaboration, the work of the local scientists and collaborators should be prominently acknowledged in the list of authors, in accordance with current international practice. Most journals will not accept publications of work done in the LMICS without one or more local collaborators. A training component is essential including the transfer of knowledge of technology, such as the establishment of a lab where certain tests that have been evaluated in a study can be done locally after completion of the study. Career development for the researchers from LMICs should be a priority. While a PhD in the partner country overseas is considered more prestigious, a joint PhD in two universities would benefit the partner university in the LMIC. Postdoc research grants such as those offered by the European and Developing Countries Trial Partnership (EDCTP) provide opportunities for a young postdoc student to develop his further career and become an independent researcher.
Who is funding research?
There are many donors, both public and private. Among the main funding agencies are the Bill & Melinda Gates Foundation, the Wellcome Trust, the National Institutes of Health (USA), the Medical Research Council (United Kingdom), EDCTP (with focus on Africa) and the European Union.
Where to publish?
Publication is not restricted to typical tropical medicine journals. It depends on the quality and expected impact of the research. RCTs are often published in the New England Journal of Medicine (NEJM) or The Lancet. Outstanding fundamental (often biomedical) research may be published in Nature or Science. Among the tropical medicine journals The American Journal of Tropical Medicine and Hygiene, the Transactions of the Royal Society of Tropical Medicine and Hygiene, and Tropical Medicine & International Hygiene (TMIH) feature most prominently. There are however many more reputable journals that publish general or more specialized papers, for example on entomology, pathology or therapeutics.
All too often one hears that researchers from LMICs feel that they are discriminated against when they submit their work for publication. While in general one can say that good work will be acknowledged and published, it is not clear if a potential bias exists against a paper with no names of established workers in the field. Editorial independence and rigorous peer review are clearly important.
Conclusion
Research in tropical medicine has made a tremendous contribution to the health of people and patients in LMICs. There are many ways in which anyone can make a sound contribution. Clear objectives and methodology are crucial to reaching a meaningful outcome that can be implemented, or that contributes to the body of knowledge. Basic science, clinical research, and public health studies are clearly complementary. Training in research methodology is essential for students both in HICs and LMICs.
References
- World Health Organization, United Nations Children’s Fund. Primary health care: report of the International Conference on Primary Health Care, Alma-Ata, USSR, 6-12 September 1978. Geneva: World Health Organization; 1978. 79 p. Available from: https://apps.who.int/iris/handle/10665/39228
- Mooij R, Jurgens EM, Van Dillen J, et al. The contribution of Dutch doctors in Global Health and Tropical Medicine to research in global health in low- and middle-income countries: an exploration of the evidence. Trop Doct. 2020 Jan;50(1):43-9. DOI: 10.1177/0049475519878335. Epub 2019 Oct 9
