The American Journal of Tropical Medicine and Hygiene - Online First

We analyzed the association between insulin-like growth factor-I (IGF-I) and the pathogenesis of anemia during active visceral leishmaniasis (VL). Serum levels of IGF-I, IGF-binding protein 3 (IGFBP3), and cytokines were measured in samples from individuals with active VL and cured VL, asymptomatic Leishmania-infected, and noninfected individuals. Then, we extended our analysis to VL dogs to evaluate hematimetric parameters, bone marrow alterations, and cytokine and IGF-I expression. We identified a positive correlation between lower IGF-I and IGFBP3 levels in active VL patients and lower hemoglobin levels. In infected dogs, there was a positive correlation between lower IGF-I expression in the bone marrow and lower peripheral blood hematocrit and hemoglobin levels. There was no correlation between decreased IGF-I level/expression and any measured cytokine serum levels in either host. The data suggest that low IGF-I expression is associated with pathogenesis of anemia in active VL, primarily in severe cases, by mechanisms other than alterations in cytokine production.

Many parasitic infections have different presenting features in endemic individuals (ENDs) and immunologically naive temporary residents (TRs). Temporary residents with loiasis often display acute symptoms and hypereosinophilia, in contrast to a parasite-induced subclinical state in chronically infected ENDs. Few studies have examined differences in ENDs and TRs infected with the related filarial parasite Onchocerca volvulus. We identified 40 TRs and 36 ENDs with imported onchocerciasis at the National Institutes of Health between 1976 and 2016. All study subjects received an extensive pretreatment history review, physical examination, and laboratory investigations. We performed additional parasite-specific serologic testing on stored patient sera. Asymptomatic infection occurred in 12.5% of TRs and no ENDs (P = 0.06). Papular dermatitis was more common in TRs (47.5% versus 2.7%, P < 0.001), whereas more pigmentation changes occurred in ENDs (41.7% versus 15%, P = 0.01). Only endemic patients reported visual disturbance (13% versus 0%, P = 0.03). One TR (3.3%) had onchocercal eye disease, compared with 22.6% of ENDs (P = 0.053). Absolute eosinophil counts (AECs) were similar in ENDs and TRs (P = 0.5), and one-third of subjects had a normal AEC. Endemic individuals had higher filarial-specific IgG4 and were more likely to be positive for IgG4 antibodies to Ov-16. Temporary residents and ENDs with imported O. volvulus infection presented with different dermatologic manifestations; ocular involvement occurred almost exclusively in ENDs. Unlike Loa loa, clinical differences appear not to be eosinophil mediated and may reflect chronicity, intensity of infection, or the presence of Wolbachia in O. volvulus.

A panel of experts from the Infectious Disease Society of America and The American Society of Tropical Medicine and Hygiene recently published guidelines for management of neurocysticercosis, showing that clinical manifestations as well as the stage of involution and the anatomical location of parasites must be taken into account before the start of a rational therapy. Soon thereafter, isolated opinions attempted to discredit these guidelines, arguing insufficient or inadequate evidence and suggesting that they should not be followed worldwide. In view of these conflicting reports, it is appropriate to review the origin and evolution of the controversy on the medical treatment of neurocysticercosis.

We examined whether baseline mortality risk, as a function of child age and site, modified the azithromycin mortality-reduction effect in the Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) clinical trial. We used the Cox proportional hazards model with an interaction term. Three models were examined representing three sources for the baseline-risk covariate: two using sources external to MORDOR and the third leveraging data within MORDOR. All three models provided moderate evidence for the effect becoming stronger with increasing baseline mortality (P = 0.02, 0.02, and 0.07, respectively) at the rate of approximately 6–12% additional mortality reduction per doubling of baseline mortality. Etiological and programmatic implications of these findings are discussed.

Human African trypanosomiasis is close to elimination in several countries in sub-Saharan Africa. The diagnosis and treatment is currently rapidly being integrated into first-line health services. We aimed to document the perspective of stakeholders on this integration process. We conducted 12 focus groups with communities in three health zones of the Democratic Republic of the Congo and held 32 interviews with health-care providers, managers, policy makers, and public health experts. The topic guide focused on enabling and blocking factors related to the integrated diagnosis and treatment approach. The data were analyzed with NVivo using a thematic analysis process. The results showed that the community mostly welcomed integrated care for diagnosis and treatment of sleeping sickness, as they value the proximity of first-line health services, but feared possible financial barriers. Health-care professionals thought integration contributed to the elimination goal but identified several implementation challenges, such as the lack of skills, equipment, motivation and financial resources in these basic health services. Patients often use multiple therapeutic itineraries that do not necessarily lead them to health centers where screening is available. Financial barriers are important, as health care is not free in first-line health centers, in contrast to the population screening campaigns. Communities and providers signal several challenges regarding the integration process. To succeed, the required training of health professionals, as well as staff deployment and remuneration policy and the financial barriers in the primary care system need to be addressed, to ensure coverage for those most in need.

We attempted to identify Plasmodium falciparum histidine–rich protein 2/3 (pfhrp2/3) deletions among rapid diagnostic test (RDT)–negative but PCR- or microscopy-positive P. falciparum–infected individuals in areas of low transmission (Choma District, 2009–2011) and high transmission (Nchelenge District, 2015–2017) in Zambia. Through community-based surveys, 5,167 participants were screened at 1,147 households by PfHRP2-based RDTs. Slides were made and dried blood spots were obtained for molecular analysis. Of 28 samples with detectable P. falciparum DNA, none from Nchelenge District were pfhrp2/3 negative. All eight samples from Choma District had detectable pfhrp3 genes, but pfhrp2 was undetectable in three. DNA concentrations of pfhrp2-negative samples were low (< 0.001 ng/μL). These findings suggest that PfHRP2-based RDTs remain effective tools for malaria diagnosis in Nchelenge District, but further study is warranted to understand the potential for pfhrp2/3 deletions in southern Zambia where malaria transmission declined over the past decade.

Livestock farming is common in low-income settings as a source of income and animal-sourced food. However, there is growing evidence of the harmful health effects of proximity of animals to infants and young children, especially through exposure to zoonotic pathogens. Poultry ownership is almost universal in rural Burkina Faso. Poultry feces are a significant risk factor for enteric diseases that are associated with child undernutrition. To investigate the extent of exposure to livestock feces among young children and caregivers, we conducted direct observations of 20 caregiver–child dyads for a total of 80 hours (4 hours per dyad) and recorded water quality, sanitation, and hygiene (WASH)-related behaviors. We also undertook in-depth interviews with these caregivers and focus group discussions with separate groups of men and women who were poultry farmers. Poultry and other livestock feces were visible in all 20 and 19 households, respectively, in both kitchen areas and in the household courtyards where children frequently sit or crawl. Direct soil ingestion by young children was observed in almost half of the households (45%). Poor handwashing practices were also common among caregivers and children. Although latrines were available in almost all households, child feces disposal practices were inadequate. This body of research suggests an urgent need to adapt conventional WASH and livestock interventions to reduce the exposure of infants and young children to livestock feces.

The standard in vitro cultivation procedure for Plasmodium falciparum requires gas exchange and a microaerophilic atmosphere. A novel system using a commercially available cell culture device (Petaka G3™; Celartia Ltd., Powell, OH) was assessed for long-term cultivation of a P. falciparum reference laboratory clone in normal air. Parasite growth during 30 days was similar, or better, in Petaka G3 than that in the standard cultivation method with gas exchange in a CO2 incubator. The successful cultivation of P. falciparum in the Petaka G3 device suggests that low O2 content available in hemoglobin and dissolved gas in the blood is sufficient for long-term cultivation. This finding may open the way to novel methods to cultivate and adapt P. falciparum field isolates to in vitro conditions with more ease.

Infections due to Loa loa and Mansonella perstans are common yet elusive neglected filariases. Parasitological cure after treatment is very difficult to assess, as adult parasites are not accessible. Therefore, outside transmission areas, patients require a long follow-up period to ascertain the therapeutic outcome, which is impractical for non-sedentary populations such as migrants. We studied the change over time of microfilaremia, eosinophil counts, and antifilarial antibodies tested with a commercial ELISA test (Bordier Affinity Products, Crissier, Switzerland), in a retrospective cohort of patients with confirmed L. loa and M. perstans infections, to evaluate the role of serology in clinical practice. After treatment, all 22 eligible patients diagnosed in our center between 2015 and 2017 reached amicrofilaremia, with microfilarial counts decreasing sharply within 2 months. Paralleling eosinophil counts, antibodies decreased in all patients, 36% of whom reached sero-reversion or near–sero-reversion in < 20 months. These findings suggest that positive serology is not just residual from a past infection, and may be used for diagnosis even when microfilaremia is negative or cannot be performed. Interestingly, antibodies and eosinophil counts increased following some, but not all, re-treatment courses. If the rise in these parameters reflects death of macrofilariae, caution is required in interpreting high eosinophil counts and antibody titers shortly after treatment, as these may reflect no need for further treatment. To optimize patients’ management, it is now pivotal to ascertain the interval between treatment and macrofilarial death and therefore whether re-treatments are required for complete clearance of parasites.