Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

Naturally acquired immunity to Plasmodium falciparum presents a changing landscape as malaria control programs and vaccine initiatives are implemented. Determining which immunologic indicators remain surrogates of past infection, as opposed to mediators of protection, led us to compare stability of immune responses across regions with divergent malaria transmission intensities. A repeat cross-sectional study of Kenyan children from a malaria-holoendemic area and an epidemic-prone area was used to examine longitudinal antibody and interferon-gamma (IFN-gamma) responses to the 3D7 and FVO variants of merozoite surface protein 1 (MSP1). Antibodies to MSP1 were common in both study populations and did not significantly wane over a 21-month time period. IFN-gamma responses were less frequent and rapidly disappeared in children after a prolonged period of no malaria transmission. Antibody and IFN-gamma responses rarely correlated with each other; however, MSP1-specific IFN-gamma response correlated with lack of concurrent P. falciparum parasitemia of the same genotype, though only statistically significantly in the malaria-holoendemic region (odds ratio = 0.31, 95% confidence interval = 0.12-0.84). This study affirms that antimalarial antibodies are informative for evaluation of history of malaria exposure within individuals, whereas cell-mediated immunity, though short lived under natural exposure conditions, might provide an assessment of recent infection and protection from parasitemia

A Multi-disciplinary Overview of Chagas in Periurban Peru

There are between 8 and 11 million cases of America Human Trypanosomiasis, commonly known as Chagas disease, in Latin America. Chagas is endemic in southern Peru, especially the Arequipa region, where it has expanded from poor, rural areas to periurban communities. This paper summarizes the findings of four studies in periurban Arequipa: on determinants of disease-vector infestation; on prevalence, spatial patterns, and risk factors of Chagas; on links between migration, settlement patterns, and disease-vector infestation; and on the relationship between discordant test results and spatially clustered transmission hotspots. These studies identified two risk factors associated with the disease: population dynamics and the urbanization of poverty. Understanding the disease within this new urban context will allow for improved public health prevention efforts and policy initiatives. Discovered in 1909 by Brazilian physician Carlos Chagas, American Human Trypanosomiasis is a chronic and potentially life-threatening illness found throughout Latin America (Moncayo, 2003). Indeed, it is estimated that there are between 8 and 11 million cases in Mexico and Central and South America (Centers for Disease Control [CDC], 2009). Chagas disease, as it is most commonly known, is endemic in southern Peru, especially in the region of Arequipa. Once thought to be limited to poor, rural areas, the disease is now appearing in the periurban communities that surround Arequipa City, the capital of the region (Cornejo del Carpio, 2003). Understanding the urbanization of Chagas disease will allow public health and medical professionals to better combat the further transmission of the disease. After providing an overview of Chagas and introducing the scope of the disease in Latin America, this paper will summarize the findings of four recent studies conducted in periurban districts in Arequipa. Ultimately, this paper seeks to identify the risk factors associated with Chagas infection in Arequipa’s periurban communities

Periurban Trypanosoma cruzi–infected Triatoma infestans, Arequipa, Peru

Simple interventions may facilitate vector control and prevent periurban transmission of Chagas disease

Retracing Micro-Epidemics of Chagas Disease Using Epicenter Regression

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population\u27s infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission

The Effect of HIV Infection on the Risk, Frequency, and Intensity of Plasmodium falciparum Parasitemia in Primigravid and Multigravid Women in Malawi

Human immunodeficiency virus (HIV) is common in pregnant women in many malaria-endemic regions and may increase risk of placental parasitemia. Placental malaria is more common in primigravidae than multigravidae, but the relationship between HIV and malaria across gravidities is not well characterized. We recruited pregnant Malawian women during the second trimester and followed them until delivery. Parasitemia was assessed at enrollment, follow-up visits, and delivery, when placental blood was sampled. There was no difference in risk of parasitemia between HIV-positive and HIV-negative primigravidae. Among multigravidae, HIV-infected women had greater than twice the risk of parasitemia as HIV-uninfected women throughout follow-up. Human immunodeficiency virus was also associated with more frequent peripheral parasitemia in multigravidae but not primigravidae. Both HIV and primigravid status were independently associated with higher peripheral and placental parasite densities. Although risk of parasitemia is lower in multigravidae than primigravidae, the HIV effect on risk of malaria is more pronounced in multigravidae

Retracing Micro-Epidemics of Chagas Disease Using Epicenter Regression

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S

Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian Diabetics But Not Chagas Disease Patients

Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients

Comparative population structure of Plasmodium falciparum circumsporozoite protein NANP repeat lengths in Lilongwe, Malawi

Humoral immunity to Plasmodium falciparum circumsporozoite protein is partly mediated by a polymorphic NANP tetra-amino acid repeat. Antibody response to these repeats is the best correlate of protective immunity to the RTS,S malaria vaccine, but few descriptions of the natural variation of these repeats exist. Using capillary electrophoresis to determine the distribution of NANP repeat size polymorphisms among 98 isolates from Lilongwe, Malawi, we characterised the diversity of P. falciparum infection by several ecological indices. Infection by multiple distinct variants was common, and 20 distinct repeat sizes were identified. Diversity of P. falciparum appeared greater in children (18 variants) than adults (12 variants). There was evidence of genetic distance between different geographic regions by Nei's Standard Genetic Distance, suggesting parasite populations vary locally. We show that P. falciparum is very diverse with respect to NANP repeat length even on a local level and that diversity appears higher in children

Antibody Immunity to Zika Virus among Young Children in a Flavivirus-Endemic Area in Nicaragua

Objective: To understand the dynamics of Zika virus (ZIKV)-specific antibody immunity in children born to mothers in a flavivirus-endemic region during and after the emergence of ZIKV in the Americas. Methods: We performed serologic testing for ZIKV cross-reactive and type-specific IgG in two longitudinal cohorts, which enrolled pregnant women and their children (PW1 and PW2) after the beginning of the ZIKV epidemic in Nicaragua. Quarterly samples from children over their first two years of life and maternal blood samples at birth and at the end of the two-year follow-up period were studied. Results: Most mothers in this dengue-endemic area were flavivirus-immune at enrollment. ZIKV-specific IgG (anti-ZIKV EDIII IgG) was detected in 82 of 102 (80.4%) mothers in cohort PW1 and 89 of 134 (66.4%) mothers in cohort PW2, consistent with extensive transmission observed in Nicaragua during 2016. ZIKV-reactive IgG decayed to undetectable levels by 6–9 months in infants, whereas these antibodies were maintained in mothers at the year two time point. Interestingly, a greater contribution to ZIKV immunity by IgG3 was observed in babies born soon after ZIKV transmission. Finally, 43 of 343 (13%) children exhibited persistent or increasing ZIKV-reactive IgG at ≥9 months, with 10 of 30 (33%) tested demonstrating serologic evidence of incident dengue infection. Conclusions: These data inform our understanding of protective and pathogenic immunity to potential flavivirus infections in early life in areas where multiple flaviviruses co-circulate, particularly considering the immune interactions between ZIKV and dengue and the future possibility of ZIKV vaccination in women of childbearing potential. This study also shows the benefits of cord blood sampling for serologic surveillance of infectious diseases in resource-limited settings