Tropical Medicine expert Dr. Peter Hotez and colleagues from Baylor College of Medicine at Houston are sounding the alarm about a new hidden killer disease that disproportionately strikes young male Central American agricultural workers — primarily in the Pacific coastal regions of El Salvador and Nicaragua, but also in Guatemala and Costa Rica.
The recently named Mesoamerican nephropathy appears to be an emerging form of chronic kidney disease of unknown etiology. According to Correa-Rotter et al. the syndrome was first described in 2002 as a form of advanced chronic kidney disease at the Rosales Hospital, a referral hospital in the capital of El Salvador. The disease develops without the usual chronic risk factors such as diabetes and hypertension. Among its most common features, Mesoamerican nephropathy typically presents as a progressive tubulointerstitial form of renal disease and failure with no or low grade proteinuria. Histopathology findings from renal biopsies are unique – different from other causes of renal disease. It most commonly affects young men working in sugarcane plantations along the lowland Pacific Coast of Central America. Because this part of Central America is a resource-poor region, those affected often die prematurely due to inadequate access to renal dialysis.
A paper epublished ahead of print in the National Kidney Foundation’s American Journal of Kidney Disease, entitled: “CKD of Unknown Origin in Central America: The Case for a Mesoamerican Nephropathy” (Am J Kidney Dis. 2014 Jan 9. pii: S0272-6386(13)01568-0. doi: 10.1053/j.ajkd.2013.10.062), co-authored by R. Correa-Rotter of the Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, C . Wesseling of Program on Work, Environment and Health in Central America (SALTRA), Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica and R.J. Johnson of Division of Renal Diseases and Hypertension, University of Colorado, Denver, Colorado, notes that Mesoamerican nephropathy victimstypically have a history of manual labor under very hot conditions in agricultural fields, and that clinically, they usually present with normal or mildly elevated systemic blood pressure, asymptomatic yet progressive reduction in estimated glomerular filtration rate, low-grade non-nephrotic proteinuria, and often hyperuricemia and or hypokalemia.
The researchers note that diabetes is absent in this population, and kidney biopsies that have been performed show a chronic tubulointerstitial disease with associated secondary glomerulosclerosis and some signs of glomerular ischemia — causes unknown; Their article discusses and analyzes some of the etiologic possibilities currently under consideration, and note that it’s relevant to highlight that recurrent dehydration is suggested in multiple studies – a condition that possibly could be exacerbated in some cases by other conditions, including the use of nonsteroidal anti-inflammatory agents, but say that at present, Mesoamerican nephropathy is a medical enigma yet to be solved.
Another study, entitled: “End-stage renal disease among patients in a referral hospital in El Salvador,” (Rev Panam Salud Publica. 2002 Sep;12(3):202-6.) co-authored by R.G. Trabanino, R. Aguilar, C.R. Silva, M.O. Mercado, and R.L .Merino. – all of the Departamento de Medicina Interna, Hospital Nacional Rosales, San Salvador, El Salvador, notes that El Salvador is a country with high mortality from end-stage renal disease (ESRD), and that the objective of their study was to determine the epidemiological characteristics of a series of new cases of ESRD seen in a referral hospital in the country.
A cross-sectional study was conducted of all the new cases that initiated chronic dialysis between November 1999 and March 2000. Using a personal interview, data were obtained on the patients’ clinical, demographic, and occupational characteristics, among others.
The study abstract reports; “During the five months that the study lasted, 205 new cases of ESRD were observed. Among the 202 interviewees, two groups were clearly distinguished. One group, of 67 patients (33%), had known risk factors for ESRD, similar to those for developed countries (basically, diabetes mellitus, hypertension, and chronic consumption of non-steroidal anti-inflammatories). Another group of 135 patients (67%) had unusual characteristics that were not associated with the known risk factors. The majority of the patients in this second group were male, farmers, residents of coastal areas or areas next to rivers, and some years before had been exposed, without adequate protection, to agricultural insecticides or pesticides through their work.
They conclude that this group of patients with ESRD seem to lack a cause for their disease, but that their special characteristics make it possible to suspect a relationship with the occupational exposure to insecticides or pesticides, but that new studies are needed in order to confirm this hypothesis.
In a PLOS Neglected Tropical Diseases blog entry, Editor-in-Chief of PLOS Dr. Peter Hotez, Kristy O. Murray, Rojelio Mejia, Laila Woc-Colburn & Maria Elena Bottazzi — all professors in the Departments of Pediatrics and Medicine, National School of Tropical Medicine at Texas Children’s Hospital and Baylor College of Medicine in Houston — say some investigators believe Mesoamerican nephropathy is now the leading killer of young male sugarcane workers in Nicaragua, and possibly El Salvador as well.
Dr. Hotez observes that a number of theories have been advanced to explain the etiology of Mesoamerican nephropathy, including environmental exposures to various agrochemicals, heavy metals, and mycotoxins, as well as recurrent dehydration in the setting of Central America’s hot coastal climate. He and his colleagues at BCM are proponents of exploring potential infectious causes, especially zoonotic neglected tropical diseases from rodents that notoriously infest sugar cane plantations. He suggests that lead candidate infections might include leptospirosis, hantavirus, and Mansonella filarial infections, which are well known in Central and South America. Another possibility is West Nile virus infection shown recently by blog co-author Kristy O. Murray and her colleagues to produce a chronic and progressive renal disease leading to kidney failure notes Dr. Hotez, with WNV infection now a leading cause of renal disease in Texas, making it conceivable that this mosquito-transmitted disease may have emerged on Central America’s Pacific Coast.
Dr. Hotez et al. refer to a recently published research workshop highlighting the steps required to investigate this deadly outbreak going forward. Also published by the National Kidney Foundation’s American Journal of Kidney Disease, the paper is entitled: “Resolving the Enigma of the Mesoamerican Nephropathy: A Research Workshop Summary,” co-authored by C. Wesseling, J .Crowe, C. Hogstedt, K. Jakobsson, R. Lucas, and D.H. Wegman of the First International Research Workshop on Mesoamerican Nephropathy (MeN), Program on Work, Environment and Health in Central America (SALTRA), Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica, which met in Costa Rica in November 2012 to discuss how to establish the extent and degree of MeN, examine relevant causal hypotheses, and focus efforts to control or eliminate the disease burden.
The paper notes that MeN describes a devastating epidemic of chronic kidney disease of unknown origin predominantly observed among young male sugarcane cutters; that the cause of MeN remains uncertain; and suggests that the strongest hypothesis pursued to date is repeated episodes of occupational heat stress and water and solute loss, probably in combination with other potential risk factor(s), such as nonsteroidal anti-inflammatory drug and other nephrotoxic medication use, inorganic arsenic, leptospirosis, or pesticides.
At the research workshop, clinical and epidemiologic case definitions were proposed in order to facilitate both public health and research efforts. Recommendations emanating from the workshop included measuring workload, heat, and water and solute loss among workers; quantifying nephrotoxic agents in drinking water and food; using biomarkers of early kidney injury to explore potential causes of MeN; and characterizing social and working conditions together with methods for valid data collection of exposures and personal risk factors. Advantages and disadvantages of different population study designs were detailed.
To elucidate the etiology of MeN, multicountry studies with prospective cohort design, preferably integrating an ecosystem health approach, were considered the most promising. In addition, genetic, experimental, and mechanistic methods and designs were addressed, specifically the need for kidney biopsy analysis, studies in animal models, advances in biomarkers, genetic and epigenetic studies, a common registry and repository of biological and demographic data and/or specimens, and other areas of potential chronic kidney disease experimental research. Finally, in order to improve international collaboration on MeN, workshop participants agreed to establish a research consortium to link these Mesoamerican efforts to other efforts worldwide.
Dr. Hotez and his co-bloggers say they understand that the Pan American Health Organization – the World Health Organization regional office in the Americas – is now actively working with the US Centers for Disease Control and Prevention (CDC) together with health ministries in the disease affected countries to identify cases, establish case definitions, and conduct case-controlled studies. They note that there are also efforts to send blood and other tissue samples to reference laboratories, but that such efforts appear to be inadequately resourced given the alarming death rates and morbidities among some of Central America’s most productive young people. Consequently they stress an urgent need to mobilize financial and other resources to urgently address this deadly and frightening new illness.
Peter Hotez is Co-Editor in Chief of PLOS Neglected Tropical Diseases, Dean, National School of Tropical Medicine at Baylor College of Medicine, President, Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, and Fellow in Disease and Poverty, James A. Baker III Institute for Public Policy at Rice University, Houston, Texas, United States of America. He is the author of Forgotten People, Forgotten Diseases (ASM Press), Second Edition. You can follow Prof. Hotez on Twitter @PeterHotez
PLOS Neglected Tropical Diseases
American Journal of Kidney Disease
Rev Panam Salud Publica