Carlos Franco-Paredes

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.

Chagasic encephalitis in HIV patients: common presentation of an evolving epidemiological and clinical association

We present a case of chagasic meningoencephalitis reactivation in an HIV-infected woman with advanced immunosuppression. Prolonged survival was attained with antiparasitic therapy and secondary prophylaxis, in conjunction with the use of highly-active antiretroviral therapy. The geographic expansion of the HIV epidemic around the world coupled with global migration and international travel have created a favourable situation for Trypanosoma cruzi and HIV coinfection. The clinical manifestations of Chagas disease in HIV-positive people usually represent reactivation and not acute infection with T cruzi (coinfection). Symptomatic reactivation of chronic latent T cruzi infection can be triggered by severe immunosuppression associated with HIV infection. In this setting, Chagas disease reactivation often presents as meningoencephalitis resembling toxoplasma encephalitis. We review, in this Grand Round, the clinical manifestations, diagnostic approach, pathogenesis, natural history, treatment, prognosis, and prevention of Chagas disease reactivation among HIV-infected people with an emphasis on CNS manifestations.

Tuberculosis of the Pancreas: Report of Two Cases and Review of the Literature

Tuberculosis of the pancreas is a clinical entity rarely described in the literature. The pancreas is biologically protected from infection by Mycobacterium tuberculosis, probably because of the presence of pancreatic enzymes that interfere with the seeding of M. tuberculosis. However, when pathogens are able to overcome the resistance, they can have diverse presentations, such as pancreatic masses that can mimic carcinoma, obstructive jaundice, pancreatitis, and gastrointestinal bleeding. Herein we describe 2 cases of pancreatic tuberculosis that presented as multicystic masses, and we review the literature to describe the diverse clinical manifestations of this condition.

Rethinking Typhoid Fever Vaccines: Implications for Travelers and People Living in Highly Endemic Areas

Enteric (typhoid or paratyphoid) fever is a systemic infection caused by Salmonella enterica , including S enterica serotype Typhi ( S typhi ) and serotypes Paratyphi A, B, and C ( S paratyphi ). Humans are the only host for these pathogens, which are transmitted by fecal contamination of food and water. Salmonella typhi caused an estimated 22 million illnesses and 200,000 deaths, and S paratyphi caused 5.4 million illnesses worldwide during the year 2000. 1 The actual global burden of enteric fever is difficult to determine because many cases are unrecognized, particularly in young children who may have a nonspecific illness, 2–4 and it is not a notifiable disease in endemic countries. In addition, there are no specific clinical diagnostic criteria, and the laboratory techniques for diagnosis lack sensitivity and specificity. 5 According to the recently estimated global incidence, the highest concentration of typhoid fever is in Asia, especially in the Indian subcontinent (Table 1). 1 Southern Africa and Latin America also have a high disease burden (Table 1). View this table: Table 1 Crude typhoid fever incidence rates by region, 2000 Previously, S paratyphi was thought to have caused 10% of cases of enteric fever and a milder form of disease than S typhi. 6,7 However, recent reports suggest that these two pathogens cause similar diseases 8–10 and that there has been a disproportionate increase in the incidence of enteric fever caused by S paratyphi , with up to 50% of enteric fever cases caused by S paratyphi in some highly endemic areas of the world. 9,11–15 Enteric fever also affects short‐term and long‐term travelers bound to highly endemic areas. 16 Among the travel‐related cases, most occur in foreign‐born residents who visited friends or family in their country of origin. 17 Travel to the Indian subcontinent is associated with the highest risk of contracting enteric fever. 18–20 … Corresponding Author: Carlos Franco‐Paredes, MD, MPH, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 550 Peachtree Street, MOT, 7th Floor, TravelWell, Atlanta, GA 30308, USA. E‐mail: cfranco{at}sph.emory.edu

Trends in Hospitalizations for AIDS-Associated Pneumocystis jirovecii Pneumonia in the United States (1986 to 2005)

BACKGROUND Although hospitalizations for AIDS-associated Pneumocystis jirovecii pneumonia (PCP) in the United States have decreased since the introduction of chemoprophylaxis and potent combination antiretroviral therapy (ART), PCP remains an important cause of illness and death among AIDS patients. METHODS We analyzed trends in AIDS-associated PCP hospital discharges using the National Hospital Discharge Surveys between 1986 and 2005. RESULTS An estimated 539 million patients were discharged from hospitals between 1986 and 2005, of whom an estimated 312,411 had AIDS-associated PCP. The proportion of patients discharged from the hospital with AIDS-associated PCP decreased from 31% before the introduction of chemoprophylaxis (1986 to 1989) to 17% with chemoprophylaxis (1990 to 1995) and subsequently to 9% after the introduction of ART in 1996 (p < 0.001). Mortality from AIDS-associated PCP decreased from 21 to 16% and subsequently to 7% between these three time periods (p < 0.001). Among those who received mechanical ventilation, mortality decreased from 79% in the prechemoprophylaxis era to 31% in the ART era (p < 0.001) alongside an increase (from 5 to 11%) in the use of mechanical ventilation. We also observed a shift in the population at-risk for PCP over time: a greater proportion of black people, women, and people from Southern states were affected (all p < 0.001). CONCLUSIONS While there have been significant reductions in hospitalizations and hospital mortality for AIDS-associated PCP over the last 20 years, these reductions have not been homogenous across demographic subpopulations and geographic regions and point to new at-risk populations. Furthermore, mortality in severe cases of PCP that require mechanical ventilation has improved substantially.

Problem pathogens: prevention of malaria in travellers

Human infection with Plasmodium spp leading to clinical episodes of malaria probably began very early in the history of humankind and has persistently inflicted disease among human populations. Malaria is currently considered the worlds most important parasitic infection. The global impact of malaria is incalculable and appears to be worsening over the past decades. Although most of this burden of disease is carried by developing tropical countries, cases of imported malaria acquired by international travel are increasingly reported. These numbers are growing because of increased travel to malaria-endemic areas and also due to increased risk of transmission in these areas. Indeed, travel has contributed to the global spread of malaria during the history of humankind. Travellers visiting malaria risk areas should use both personal protective measures and chemoprophylaxis. Non-adherence to chemoprophylactic regimens is frequently secondary to drug side-effects. Therefore, a careful risk-benefit analysis on the use of antimalarial prophylaxis should be carried out in every individual travelling to malaria risk areas. Standby malaria self-treatment represents an alternative in some travellers. However, carefully selected and geographically specific antimalarial drug regimens should be recommended to non-immune people travelling to high-risk areas.

Chagas disease: an impediment in achieving the Millennium Development Goals in Latin America

BackgroundAchieving sustainable economic and social growth through advances in health is crucial in Latin America within the framework of the United Nations Millennium Development Goals.DiscussionHealth-related Millennium Development Goals need to incorporate a multidimensional approach addressing the specific epidemiologic profile for each region of the globe. In this regard, addressing the cycle of destitution and suffering associated with infection with Trypanosoma cruzi, the causal agent of Chagas disease of American trypanosomiasis, will play a key role to enable the most impoverished populations in Latin America the opportunity to achieve their full potential. Most cases of Chagas disease occur among forgotten populations because these diseases persist exclusively in the poorest and the most marginalized communities in Latin America.SummaryAddressing the cycle of destitution and suffering associated with T. cruzi infection will contribute to improve the health of the most impoverished populations in Latin America and will ultimately grant them with the opportunity to achieve their full economic potential.

Aseptic meningitis and optic neuritis preceding varicella-zoster progressive outer retinal necrosis in a patient with AIDS.

Varicella-Zoster Virus (VZV) is the second most common ocular pathogen in patients with HIV infection. VZV retinitis is estimated to occur in 0.6% of patients with HIV infection and may occur in one of two clinical syndromes. The first is the acute retinal necrosis syndrome, which also may be seen in immunocompetent hosts. The second clinical syndrome occurs in patients with CD4 cell counts typically < 50 x 10(6)/l and is termed progressive outer retinal necrosis. VZV retinitis has been reported to occur simultaneously with other VZV central nervous system manifestations such as encephalitis and myelitis in HIV-infected patients. In addition, VZV retrobulbar optic neuritis heralding VZV retinitis has recently been described in HIV-infected patients who had suffered a recent episode of dermatomal herpes zoster. Herein we report the case of an HIV-infected individual who presented with VZV meningitis and retrobulbar optic neuritis that preceded the onset of progressive outer retinal necrosis. We also review of the literature of seven additional reported cases of retrobulbar optic neuritis preceding the onset of VZV retinitis.

Low health literacy is associated with HIV test acceptance.

AbstractBACKGROUND: The Centers for Disease Control and Prevention has proposed increasing the proportion of people who learn their HIV serostatus. The health care setting represents a logical site to accomplish this goal. However, little is known about factors that determine acceptability of HIV testing in health care settings, particularly patients’ health literacy. OBJECTIVE: To evaluate the association between patients’ health literacy and acceptance of HIV testing among individuals at an urgent care center (UCC). METHODS: As part of a prospective study that sought to increase HIV testing at a UCC located in an inner-city hospital serving an indigent population, we surveyed patients who had been offered an HIV test by their providers and had accepted or refused testing. Pretest counseling was provided using a low-literacy brochure given to patients upon registration into the clinic. We measured health literacy level using the Rapid Estimate of Adult Literacy in Medicine (REALM) scale. RESULTS: Three hundred seventy-two patients were enrolled in the study. In univariate analysis, no statistically significant difference between HIV test acceptors or refusers was found for gender, race/ethnicity, marital status, income, type of health insurance, educational level, or type of test offered. Acceptors were more likely to have a low literacy level (odds ratio [OR], 1.763; 95% confidence interval [CI], 1.084 to 2.866) and be less than 40 years old (OR, 1.639; 95% CI, 1.085 to 2.475). In multivariate analysis, low health literacy was shown to be a predictor of HIV test acceptance controlling for age and education (OR, 2.017; 95% CI, 1.190 to 3.418). CONCLUSIONS: Low health literacy was shown to be a predictor of HIV test acceptance. Patients presenting to a UCC with poorer health literacy appear more willing to comply with health care providers’ recommendations to undergo HIV testing than those with adequate health literacy when an “opt-out” strategy combined with a low-literacy brochure is used.

Cryptococcus gattii Infections in Multiple States Outside the US Pacific Northwest

Clonal VGII subtypes (outbreak strains) of Cryptococcus gattii have caused an outbreak in the US Pacific Northwest since 2004. Outbreak-associated infections occur equally in male and female patients (median age 56 years) and usually cause pulmonary disease in persons with underlying medical conditions. Since 2009, a total of 25 C. gattii infections, 23 (92%) caused by non–outbreak strain C. gattii, have been reported from 8 non–Pacific Northwest states. Sixteen (64%) patients were previously healthy, and 21 (84%) were male; median age was 43 years (range 15–83 years). Ten patients who provided information reported no past-year travel to areas where C. gattii is known to be endemic. Nineteen (76%) patients had central nervous system infections; 6 (24%) died. C. gattii infection in persons without exposure to known disease-endemic areas suggests possible endemicity in the United States outside the outbreak-affected region; these infections appear to differ in clinical and demographic characteristics from outbreak-associated C. gattii. Clinicians outside the outbreak-affected areas should be aware of locally acquired C. gattii infection and its varied signs and symptoms.