The neglected tropical diseases of Latin America and the Caribbean: a review of disease burden and distribution and a roadmap for control and elimination

The neglected tropical diseases (NTDs) represent some of the most common infections of the poorest people living in the Latin American and Caribbean region (LAC). Because they primarily afflict the disenfranchised poor as well as selected indigenous populations and people of African descent, the NTDs in LAC are largely forgotten diseases even though their collective disease burden may exceed better known conditions such as of HIV/AIDS, tuberculosis, or malaria. Based on their prevalence and healthy life years lost from disability, hookworm infection, other soil-transmitted helminth infections, and Chagas disease are the most important NTDs in LAC, followed by dengue, schistosomiasis, leishmaniasis, trachoma, leprosy, and lymphatic filariasis. On the other hand, for some important NTDs, such as leptospirosis and cysticercosis, complete disease burden estimates are not available. The NTDs in LAC geographically concentrate in 11 different sub-regions, each with a distinctive human and environmental ecology. In the coming years, schistosomiasis could be eliminated in the Caribbean and transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America. However, the highest disease burden NTDs, such as Chagas disease, soil-transmitted helminth infections, and hookworm and schistosomiasis co-infections, may first require scale-up of existing resources or the development of new control tools in order to achieve control or elimination. Ultimately, the roadmap for the control and elimination of the more widespread NTDs will require an inter-sectoral approach that bridges public health, social services, and environmental interventions.     

Towards a bioinformatics network for Latin America and the Caribbean (LACBioNet)

Bioinformatics is increasingly recognised as a crucial field for research and development in the biological sciences, and forms an integral part of genomics, proteomics and modern biotechnology. Worldwide participation is important, and scientists in developing countries can contribute to this field. Regional networks for bioinformatics are highly beneficial for capacity strengthening and cooperation, and for establishing productive interactions between scientists in the fields of biological and informatics sciences. Such a network (LACBioNet) is being organised for Latin America and the Caribbean. Its immediate goals include the organisation and extension of nodes and services, information and communication, research and development in different specialty fields of bioinformatics, and training and human resource development.     

Elimination of neglected diseases in latin america and the Caribbean: a mapping of selected diseases

In Latin America and the Caribbean, around 195 million people live in poverty, a situation that increases the burden of some infectious diseases. Neglected diseases, in particular, are often restricted to poor, marginalized sections of the population. Tools exist to combat these diseases, making it imperative to work towards their elimination. In 2009, the Pan American Health Organization (PAHO) received a mandate to support the countries in the Region in eliminating neglected diseases and other poverty-related infections. The objective of this study is to analyze the presence of selected diseases using geo-processing techniques. Five diseases with information available at the first sub-national level (states) were mapped, showing the presence of the disease ("hotspots") and overlap of diseases ("major hotspots"). In the 45 countries/territories (approximately 570 states) of the Region, there is: lymphatic filariasis in four countries (29 states), onchocerciasis in six countries (25 states), schistosomiasis in four countries (39 states), trachoma in three countries (29 states), and human rabies transmitted by dogs in ten countries (20 states). Of the 108 states with one or more of the selected diseases, 36 states present the diseases in overlapping areas ("major hotspots"). Additional information about soil-transmitted helminths was included. The analysis suggests a majority of the selected diseases are not widespread and can be considered part of an unfinished agenda with elimination as a goal. Integrated plans and a comprehensive approach, ensuring access to existing diagnostic and treatment methods, and establishing a multi-sectoral agenda that addresses social determinants, including access to adequate water and sanitation, are required. Future studies can include additional diseases, socio-economic and environmental variables.     

Rabies reference vaccine for use as a regional standard for Latin America and the Caribbean countries

A candidate rabies reference vaccine of suckling mouse brain (SMB) origin was prepared and standardized at the Pan American Zoonoses Center (PAHO/WHO) and evaluated in a collaborative study involving seven laboratories. On the basis of three different tests, its potency, immunogenicity, and stability were demonstrated to be satisfactory. The vaccine was proposed for consideration of the Latin American and Caribbean countries as a regional standard to determine the potency of SMB vaccines, the most widely used in the Region.     

Immunity against HIV/AIDS, malaria, and tuberculosis during co-infections with neglected infectious diseases: recommendations for the European Union research priorities

Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight against infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective.     

On the Margin of the Periphery: Culture and Race in Latin America and the Caribbean

Blackness in Latin America and the Caribbean, volume 1. Norman E. Whitten. Jr. and Arlene Torres, eds. Bloomington: Indiana University Press, 1998. 520 pp.
Blackness in Latin America and the Caribbean, volume 2. Norman E. Whitten. Jr. and Arlene Torres, eds. Bloomington: Indiana University Press, 1998. 557 pp.     

Characteristics of Randomized Trials Published in Latin America and the Caribbean According to Funding Source

Introduction

Few studies have assessed the nature and quality of randomized controlled trials (RCTs) in Latin America and the Caribbean (LAC).

Methods and Findings

The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment) of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author''s affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (N = 73.513 participants). English was the dominant publication language (93%) and most of the RCTs were published in non-LAC journals (84.2%). Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%). Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7%) or high priority infectious diseases (3.8%). Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (n = 358) was assessed for funding source: exclusively public (33.8%); private (e.g. pharmaceutical company) (15.3%); other (e.g. mixed, NGO) (15.1%); no funding (35.8%). Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting.

Conclusion

Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health outcomes or address priority health problems.     

Progress towards eliminating canine rabies: policies and perspectives from Latin America and the Caribbean

Human rabies transmitted by dogs is considered a neglected disease that can be eliminated in Latin America and the Caribbean (LAC) by 2015. The aim of this paper is to discuss canine rabies policies and projections for LAC regarding current strategies for achieving this target and to critically review the political, economic and geographical factors related to the successful elimination of this deadly disease in the context of the difficulties and challenges of the region. The strong political and technical commitment to control rabies in LAC in the 1980s, started with the regional programme coordinated by the Pan American Health Organization. National and subnational programmes involve a range of strategies including mass canine vaccination with more than 51 million doses of canine vaccine produced annually, pre- and post-exposure prophylaxis, improvements in disease diagnosis and intensive surveillance. Rabies incidence in LAC has dramatically declined over the last few decades, with laboratory confirmed dog rabies cases decreasing from approximately 25 000 in 1980 to less than 300 in 2010. Dog-transmitted human rabies cases also decreased from 350 to less than 10 during the same period. Several countries have been declared free of human cases of dog-transmitted rabies, and from the 35 countries in the Americas, there is now only notification of human rabies transmitted by dogs in seven countries (Bolivia, Peru, Honduras, Haiti, Dominican Republic, Guatemala and some states in north and northeast Brazil). Here, we emphasize the importance of the political commitment in the final progression towards disease elimination. The availability of strategies for rabies control, the experience of most countries in the region and the historical ties of solidarity between countries with the support of the scientific community are evidence to affirm that the elimination of dog-transmitted rabies can be achieved in the short term. The final efforts to confront the remaining obstacles, like achieving and sustaining high vaccination coverage in communities that are most impoverished or in remote locations, are faced by countries that struggle to allocate sufficient financial and human resources for rabies control. Continent-wide cooperation is therefore required in the final efforts to secure the free status of remaining countries in the Americas, which is key to the regional elimination of human rabies transmitted by dogs.     

Levels of spending and resource allocation to HIV programs and services in Latin America and the Caribbean

Background

An estimated 1.86 million people are living with HIV in Latin America and the Caribbean (LAC). The region is comprised of mainly middle-income countries with steady economic growth while simultaneously there are enormous social inequalities and several concentrated AIDS epidemics. This paper describes HIV spending patterns in LAC countries including analysis of the levels and patterns of domestic HIV spending from both public and international sources.

Methods and Findings

We conducted an extensive analysis of the most recently available data from LAC countries using the National AIDS Spending Assessment tool. The LAC countries spent a total of US$ 1.59 billion on HIV programs and services during the latest reported year. Countries providing detailed information on spending showed that high percentages are allocated to treatment and care (75.1%) and prevention (15.0%). Domestic sources accounted for 93.6 percent of overall spending and 79 percent of domestic funds were directed to treatment and care. International funds represented 5.4 percent of total HIV funding in the region, but they supplied the majority of the effort to reach most-at-risk-populations (MARPs). However, prevalence rates among men who have sex with men (MSM) still reached over 25 percent in some countries.

Conclusions

Although countries in the region have increasingly sustained their response from domestic sources, still there are future challenges: 1) The growing number of new HIV infections and more people-living-with-HIV (PLWH) eligible to receive antiretroviral treatment (ART); 2) Increasing ART coverage along with high prices of antiretroviral drugs; and 3) The funding for prevention activities among MARPs rely almost exclusively on external donors. These threats call for strengthened actions by civil society and governments to protect and advance gains against HIV in LAC.     

Public vaccine manufacturing capacity in the Latin American and Caribbean region: Current status and perspectives

The vaccine global market is currently growing at a rate of 16.52%. Nowadays the vaccine manufacturing industry is limited in the sense that not all vaccine manufacturers have the capacity to execute all the steps necessary to produce a successful product. The biological variation inherent to vaccine manufacturing and the initial investment required to bring a vaccine to the market are some of the factors that discourage vaccine manufacturing initiatives.Given the current global context in vaccine innovation and production, and the increasing participation of vaccine manufacturers from developing countries in global markets, this paper aims to review vaccine manufacturing capacity in Latin American and Caribbean (LAC) countries with specific focus on trends in national or public sector manufacturing, presenting current challenges and future opportunities for the sector in meeting national and regional (LAC) needs.Despite the overall low vaccine manufacturing capacity reported within the LAC region within this paper, it is considered that the relatively high and concentrated capacity that exists within a number of countries, combined with political commitment of all countries within the Region, can provide the necessary platform for the continued development of capacity in vaccine development and manufacture within LAC.     

Cross-sectional analysis of late HAART initiation in Latin America and the Caribbean: late testers and late presenters

Background

Starting HAART in a very advanced stage of disease is assumed to be the most prevalent form of initiation in HIV-infected subjects in developing countries. Data from Latin America and the Caribbean is still lacking. Our main objective was to determine the frequency, risk factors and trends in time for being late HAART initiator (LHI) in this region.

Methodology

Cross-sectional analysis from 9817 HIV-infected treatment-naïve patients initiating HAART at 6 sites (Argentina, Chile, Haiti, Honduras, Peru and Mexico) from October 1999 to July 2010. LHI had CD4⁺ count ≤200cells/mm³ prior to HAART. Late testers (LT) were those LHI who initiated HAART within 6 months of HIV diagnosis. Late presenters (LP) initiated after 6 months of diagnosis. Prevalence, risk factors and trends over time were analyzed.

Principal Findings

Among subjects starting HAART (n = 9817) who had baseline CD4⁺ available (n = 8515), 76% were LHI: Argentina (56%[95%CI:52–59]), Chile (80%[95%CI:77–82]), Haiti (76%[95%CI:74–77]), Honduras (91%[95%CI:87–94]), Mexico (79%[95%CI:75–83]), Peru (86%[95%CI:84–88]). The proportion of LHI statistically changed over time (except in Honduras) (p≤0.02; Honduras p = 0.7), with a tendency towards lower rates in recent years. Males had increased risk of LHI in Chile, Haiti, Peru, and in the combined site analyses (CSA). Older patients were more likely LHI in Argentina and Peru (OR 1.21 per +10-year of age, 95%CI:1.02–1.45; OR 1.20, 95%CI:1.02–1.43; respectively), but not in CSA (OR 1.07, 95%CI:0.94–1.21). Higher education was associated with decreased risk for LHI in Chile (OR 0.92 per +1-year of education, 95%CI:0.87–0.98) (similar trends in Mexico, Peru, and CSA). LHI with date of HIV-diagnosis available, 55% were LT and 45% LP.

Conclusion

LHI was highly prevalent in CCASAnet sites, mostly due to LT; the main risk factors associated were being male and older age. Earlier HIV-diagnosis and earlier treatment initiation are needed to maximize benefits from HAART in the region.     

Sources of reactive nitrogen affecting ecosystems in Latin America and the Caribbean: current trends and future perspectives

While the amount of reactive nitrogen circulating at the global level has increased markedly in the last century, the effects of this increase are largely seen at the regional level due to interacting ecological and socio-economic factors. In contrast with most other regions of the world, Latin America and the Caribbean (LA-Ca) stand out due to the fact that the major input of reactive nitrogen (Nr) still occurs naturally via biological nitrogen fixation (BNF) in natural ecosystems as opposed to anthropogenic inputs of synthetic fertilizer, fossil fuel combustion and cropping with leguminous species. Largely due to economic reasons, the consumption of fertilizer N in the LA-Ca region is still low in comparison with the average consumption of the world. However, the fertilizer N consumption is increasing at a much faster rate than that in developed regions of the world, like USA and Canada. The Nr production through BNF in cultivated plants that fix nitrogen (C-BNF) is 5 times lower than that occurring naturally in Latin America, but is still equivalent to 16% of the world C-BNF. The cultivation of nitrogen-fixing crop species in the LA-Ca region is also increasing, almost entirely due to the expansion of soybean fields in the central and northern regions of Brazil and the Pampa region of Argentina. Other anthropogenic activities in the region that contribute to an increase in the circulation of reactive nitrogen include the impact of biomass burning and urbanization. In the last decade, an average of 47,000 km² per year of forests was burned in the LA-Ca region. The environmental impact of urban centers in the LA-Ca region has become very important, since an intense urbanization process is occurring in this region, at an intensity that far exceeds urban development in the northern hemisphere. The consequences of increased urbanization include increased emissions of NO _x to the atmosphere due to the fossil fuel combustion, and the lack of sewage treatment facilities in most cities of the LA-Ca result in a large volume of untreated sewage discharged into surface waters, creating serious environmental problems. The combination of rapid urbanization and agricultural intensification in this region suggest that concern is warranted for the potential for increase in the circulation of reactive nitrogen in the very near future. At the same time, the opportunity still exists to mitigate some of the consequences of human impact on the nitrogen cycle in a region that still maintains a large fraction of its natural ecosystems intact.     

Multicenter evaluation of mycobacteria identification by PCR restriction enzyme analysis in laboratories from Latin America and the Caribbean

The identification of mycobacterial species in clinical isolates is essential for making patient care decisions. Polymerase chain reaction (PCR) restriction enzyme analysis (PRA) is a simple and rapid identification method, based on amplification of 441 bp of the hsp65 gene and restriction with BstEII and HaeIII. As a contribution to the validation of PRA, a multicenter study was performed in eight laboratories located in Argentina, Brazil, Colombia, Chile, and Guadeloupe. Each laboratory received 18 coded isolates from the collection of the Institute of Tropical Medicine (Antwerp, Belgium), representing duplicates of nine laboratory strains: Mycobacterium terrae CIPT 140320001, Mycobacterium scrofulaceum CIPT 140220031, Mycobacterium flavescens ATCC 14474, Mycobacterium triviale ATCC 23292, Mycobacterium nonchromogenicum ATCC 19530, Mycobacterium chitae ATCC 19627, Mycobacterium abscessus ATCC 19977, Mycobacterium kansasii ATCC 12478, and Mycobacterium peregrinum ATCC 14467. A detailed protocol including amplification, enzymatic digestion, and gel preparation was provided to each laboratory. Two laboratories identified correctly all 18 (100%) isolates, one identified correctly 17 (94.5%), two identified 14 (77.7%), one identified 11 (61%), and two identified 8 (44.4%) isolates. Errors detected in laboratories with more than 77% accuracy were associated with electrophoresis running conditions and an unspecific amplicon produced by a single strain. Lower accuracy was mainly related to inappropriate use of DNA markers and insufficient training in interpretation of patterns. In conclusion, the PRA method was readily implemented in some Latin American and Caribbean laboratories of mycobacteria, but improvements in critical points, as gel running conditions and training in interpretiation of patterns, are needed in order to improve accuracy. In others, improvement in critical points is still necessary.