The American Journal of Tropical Medicine and Hygiene - Volume 94, Issue 4, April 2016

We describe the management of a Sierra Leonean health care worker with severe Ebola virus disease complicated by diarrhea, significant electrolyte disturbances, and falciparum malaria coinfection. With additional resources and staffing, high quality care can be provided to patients with Ebola infection and adverse prognostic factors in west Africa.

The 2014–2015 Ebola epidemic has been the most protracted and devastating in the history of the disease. To prevent future outbreaks on this scale, it is imperative to understand the reasons that led to eventual disease control. Here, we evaluated the shifts of Ebola dynamics at national and local scales during the epidemic in Liberia. We used a transmission model calibrated to epidemiological data between June 9 and December 31, 2014, to estimate the extent of community and hospital transmission. We found that despite varied local epidemic patterns, community transmission was reduced by 40–80% in all the counties analyzed. Our model suggests that the tapering of the epidemic was achieved through reductions in community transmission, rather than accumulation of immune individuals through asymptomatic infection and unreported cases. Although the times at which this transmission reduction occurred in the majority of the Liberian counties started before any large expansion in hospital capacity and the distribution of home protection kits, it remains difficult to associate the presence of interventions with reductions in Ebola incidence.

Leishmania parasites cause a broad range of disease, with cutaneous afflictions being, by far, the most prevalent. Variations in disease severity and symptomatic spectrum are mostly associated to parasite species. One risk factor for the severity and emergence of leishmaniasis is immunosuppression, usually arising by coinfection of the patient with human immunodeficiency virus (HIV). Interestingly, several species of Leishmania have been shown to bear an endogenous cytoplasmic dsRNA virus (LRV) of the Totiviridae family, and recently we correlated the presence of LRV1 within Leishmania parasites to an exacerbation murine leishmaniasis and with an elevated frequency of drug treatment failures in humans. This raises the possibility of further exacerbation of leishmaniasis in the presence of both viruses, and here we report a case of cutaneous leishmaniasis caused by Leishmania braziliensis bearing LRV1 with aggressive pathogenesis in an HIV patient. LRV1 was isolated and partially sequenced from skin and nasal lesions. Genetic identity of both sequences reinforced the assumption that nasal parasites originate from primary skin lesions. Surprisingly, combined antiretroviral therapy did not impact the devolution of Leishmania infection. The Leishmania infection was successfully treated through administration of liposomal amphotericin B.

Cutaneous leishmaniasis is a very complex disease involving multiple factors that limit its emergence and spatial distribution. Prediction of cutaneous leishmaniasis epidemics in Tunisia remains difficult because most of the epidemiological tools used so far are descriptive in nature and mainly focus on a time dimension. The purpose of this work is to predict the potential geographic distribution of Phlebotomus papatasi and zoonotic cutaneous leishmaniasis caused by Leishmania major in Tunisia using Grinnellian ecological niche modeling. We attempted to assess the importance of environmental factors influencing the potential distribution of P. papatasi and cutaneous leishmaniasis caused by L. major. Vectors were trapped in central Tunisia during the transmission season using CDC light traps (John W. Hock Co., Gainesville, FL). A global positioning system was used to record the geographical coordinates of vector occurrence points and households tested positive for cutaneous leishmaniasis caused by L. major. Nine environmental layers were used as predictor variables to model the P. papatasi geographical distribution and five variables were used to model the L. major potential distribution. Ecological niche modeling was used to relate known species' occurrence points to values of environmental factors for these same points to predict the presence of the species in unsampled regions based on the value of the predictor variables. Rainfall and temperature contributed the most as predictors for sand flies and human case distributions. Ecological niche modeling anticipated the current distribution of P. papatasi with the highest suitability for species occurrence in the central and southeastern part of Tunisian. Furthermore, our study demonstrated that governorates of Gafsa, Sidi Bouzid, and Kairouan are at highest epidemic risk.

A novel therapy, intralesional (IL) pentamidine, was compared to intralesional therapy with antimony (ILSb), a World Health Organization–recommended therapy, for single Bolivian Leishmania braziliensis lesions. In Study 1, 90 patients were randomized equally between three injections of ILSb over 5 days, five injections of ILSb over 11 days, and three injections of IL pentamidine (120 μg/mm2 lesion area [ILPenta-120-3]) over 5 days. Cure rates at 6 months were 57% for ILSb-3 injections, 73% for ILSb-5 injections, and 72% for ILPenta-120-3 injections. Adverse effects were local irritation and injection-site pain—ILSb (60 patients): mild (25), moderate (4); IL pentamidine (30 patients): mild (4), moderate (3). In Study 2, 60 patients were randomized equally between five injections of ILSb and three injections of a double dose of IL pentamidine (240 μg/mm2 [ILPenta-240-3]). In Study 2, cure rates were 67% for ILSb-5 injections and 73% for ILPenta-240-3. For three IL injections of pentamidine, efficacy was optimized at a dose of 120 μg/mm2 lesion area. The cure rate of that regimen was similar to that for ILSb-5 injections and nonstatistically larger than that of ILSb-3 injections. IL pentamidine is an attractive alternative to ILSb on the basis of efficacy for Bolivian L. braziliensis, the threat of Sb-resistant parasites, tolerance, and patient convenience of three visits over 5 days.

Most patients with suspected malaria do not receive diagnostic confirmation before beginning antimalarial treatment. We investigated the extent to which uncertainty about malaria diagnosis contributes to patient nonadherence to artemether–lumefantrine (AL) treatment through a randomized controlled trial in central Uganda. Among 1,525 patients purchasing a course of AL at private drug shops, we randomly offered 37.6% a free malaria rapid diagnostic test (RDT) and then assessed adherence through home visits 3 days later. Of these subjects, 68.4% tested positive for malaria and 65.8% adhered overall. Patients who tested positive did not have significantly higher odds of adherence than those who were not offered the test (adjusted odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.734–1.57, P = 0.719). Patients who received a positive malaria test had 0.488 fewer pills remaining than those not offered the test (95% CI: −1.02 to 0.043, P = 0.072). We found that patients who felt relatively healthy by the second day of treatment had lower odds of completing treatment (adjusted OR: 0.532, 95% CI: 0.394–0.719, P < 0.001). Our results suggest that diagnostic testing may not improve artemisinin-based combination therapy adherence unless efforts are made to persuade patients to continue taking the full course of drugs even if symptoms have resolved.

Long-lasting insecticidal nets and indoor residual spraying have contributed to a decline in malaria over the last decade, but progress is threatened by the development of physiological and behavioral resistance of mosquitoes against insecticides. Acknowledging the need for alternative vector control tools, we quantified the effects of eave screening in combination with a push-pull system based on the simultaneous use of a repellent (push) and attractant-baited traps (pull). Field experiments in western Kenya showed that eave screening, whether used in combination with an attractant-baited trap or not, was highly effective in reducing house entry by malaria mosquitoes. The magnitude of the effect varied for different mosquito species and between two experiments, but the reduction in house entry was always considerable (between 61% and 99%). The use of outdoor, attractant-baited traps alone did not have a significant impact on mosquito house entry but the high number of mosquitoes trapped outdoors indicates that attractant-baited traps could be used for removal trapping, which would enhance outdoor as well as indoor protection against mosquito bites. As eave screening was effective by itself, addition of a repellent was of limited value. Nevertheless, repellents may play a role in reducing outdoor malaria transmission in the peridomestic area.

A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono-infections were enrolled in a prospective, open-label, randomized trial to receive either chloroquine or dihydroartemisinin–piperaquine (DHA-PPQ). The proportions of patients with adequate clinical and parasitological responses were 47% in the chloroquine arm (31 of 65 patients) and 66% in the DHA-PPQ arm (42 of 63 patients) in the Kaplan–Meier intention-to-treat analysis (absolute difference 19%, 95% confidence interval = 0–37%), thus establishing non-inferiority of DHA-PPQ. Fever clearance time (median 24 versus 12 hours, P = 0.02), parasite clearance time (median 36 versus 18 hours, P < 0.001), and parasite clearance half-life (mean 3.98 versus 1.80 hours, P < 0.001) were all significantly shorter in the DHA-PPQ arm. All cases of recurrent parasitemia in the chloroquine arm occurred from day 33 onward, with corresponding whole blood chloroquine concentration lower than 100 ng/mL in all patients. Chloroquine thus remains efficacious for the treatment of P. vivax malaria in southern Vietnam, but DHA-PPQ provides more rapid symptomatic and parasitological recovery.

An important aspect of many malaria molecular epidemiology and transmission studies is RNA-based detection of gametocytes. Ensuring RNA stability represents a challenge in tropical, resource-limited environments, as RNA may quickly degrade when samples are not preserved under adequate conditions. This study investigated the degradation of pfs25 messenger RNA (mRNA), the most widely used Plasmodium falciparum gametocyte marker, in whole blood spiked with cultured P. falciparum gametocytes, exposed to different temperatures for up to 48 hours, and collected with different anticoagulants. The levels of pfs25 mRNA were similar between samples stored at 4°C and 30°C for up to 48 hours before stabilization with RNAprotect (Qiagen, Hilden, Germany). We observed that pfs25 mRNA in heparin-collected blood degraded less than that in ethylenediaminetetraacetic acid (EDTA)–collected blood over the 48-hour period. For field studies aiming for P. falciparum gametocyte detection, immediate stabilization of blood samples is not necessary, as the pfs25 transcript is relatively stable, more so in heparin than EDTA collection tubes.

African trypanosomes (Trypanosoma brucei spp.) cause devastating diseases in sub-Saharan Africa. Trypanosomes differentiate repeatedly during development in tsetse flies before gaining mammalian infectivity in fly salivary glands. Lipid phosphate phosphatases (LPPs) are involved in diverse biological processes, such as cell differentiation and cell migration. Gene sequences encoding two putative T. brucei LPP proteins were used to search the T. brucei genome, revealing two additional putative family members. Putative structural features and transcript abundance during parasite development in tsetse fly were characterized. Three of the four LPP proteins are predicted to have six transmembrane domains, while the fourth shows only one. Semiquantitative gene expression revealed differential regulation of LPPs during parasite development. Transcript abundance for three of the four putative LPP genes was elevated in parasites infecting salivary glands, but not mammalian-infective metacyclic cells in fly saliva, indicating a potential role of this family in parasite establishment in tsetse salivary glands.

Chagas disease, caused by the parasite Trypanosoma cruzi, can cause a potentially life-threatening cardiomyopathy in approximately 10–40% of afflicted individuals. The decline in cardiac function characteristically progresses over the course of many years. We report a case of Chagas disease in which the patient experienced an atypical rapid deterioration to severe cardiomyopathy over the course of 16 months. This case argues the need for increased routine surveillance for patients with confirmed T. cruzi infection, who are determined to be at high-risk for worsening cardiomyopathy.

Solid organ transplant recipients can acquire Strongyloides stercoralis from an infected donor. The diagnosis of S. stercoralis in immunocompromised individuals may be challenging due to a lower sensitivity of available parasitological and serological methods, compared with immunocompetent individuals. Recently, a real-time polymerase chain reaction (RT-PCR) in stool has been developed for S. stercoralis diagnosis. We report two cases of S. stercoralis infection transmitted by a donor to two solid organ transplant recipients, who were diagnosed with RT-PCR in stool. This test could play an important role in S. stercoralis diagnosis in immunosuppressed patients, facilitating rapid treatment initiation and reducing the risk of severe strongyloidiasis. Adherence to current recommendations of screening among donors and recipients from endemic areas is also urgently needed.

Cystic echinococcosis (CE) is a clinically complex chronic parasitic disease, management options for which include surgery, percutaneous treatments, and treatment with albendazole (ABZ) for active cysts, and the “Watch-and-Wait” approach for uncomplicated, inactive cysts. We examined, retrospectively, the clinical management of 334 patients with hepatic CE from the southeastern Rhodope region of Bulgaria between 2004 and 2013. Cysts were reclassified according to the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) on the basis of ultrasound reports and images. The majority (62.3%) of uncomplicated cysts were CE1, 66% of which were treated surgically. Of all interventions, 5% were performed on inactive uncomplicated CE4–CE5 cysts. About half (47.6%) of these cysts were therefore treated inappropriately, exposing patients to unnecessary treatment-related risks and the health system to unnecessary costs. No management change was observed after the publication of the WHO-IWGE Expert Consensus recommendations in 2010. In Bulgaria, ABZ is still used in interrupted cycles as this is reimbursed, and peri-interventional chemoprophylaxis was not administered in the majority of surgical patients. Efforts are needed to introduce the WHO-IWGE classification and management recommendations and to encourage reception of state-of-the-art practices by public health regulatory bodies to improve patient quality of care and optimization of health resources.

Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa. However, as repeated mass drug administration suppresses microfilarial loads, the sensitivity and programmatic utility of skin snip microscopy is expected to decrease. Using a pan-filarial real-time polymerase chain reaction with melt curve analysis (qPCR-MCA), we evaluated 1) the use of a single-step molecular assay for detecting and identifying Onchocerca volvulus microfilariae in residual skin snips and 2) the sensitivity of skin snip microscopy relative to qPCR-MCA. Skin snips were collected and examined with routine microscopy in hyperendemic regions of Uganda and Ethiopia (N = 500 each) and “residual” skin snips (tissue remaining after induced microfilarial emergence) were tested with qPCR-MCA. qPCR-MCA detected Onchocerca DNA in 223 residual snips: 139 of 147 microscopy(+) and 84 among microscopy(−) snips, suggesting overall sensitivity of microscopy was 62.3% (139/223) relative to qPCR-MCA (75.6% in Uganda and 28.6% in Ethiopia). These findings demonstrate the insufficient sensitivity of skin snip microscopy for reliable programmatic monitoring. Molecular tools such as qPCR-MCA can augment sensitivity and provide diagnostic confirmation of skin biopsies and will be useful for evaluation or validation of new onchocerciasis M and E tools.

Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high-population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007–2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites. We found that population density was not a key determinant of enteric infection nor a strong effect modifier of risk posed by poor household sanitation in this setting.

To better understand the risks of exposure for young children to fecal contamination in their environment, we systematically characterized and quantified behaviors of 154 children, 0–5 years old, in four high-density, low-income neighborhoods in Accra, Ghana. A repertoire of six different activities and five different compartments (categories of locations within the household) was developed, and about 500 hours of ordered structured observations of activities and locations of individual children were collected. These records were analyzed using a competing hazards model, estimating (Weibull) hazard rates for each state (activity/compartment combination), dependent on the present state and the preceding state. The estimated rates were used to simulate sequences of behavior and describe days in the life of a child in low-income, urban Africa. Children younger than 1 year spent most time playing or sleeping off the ground, older children frequently played on floors. Relatively little time was spent in drains or wet trash areas. Critical combinations of activities, like handwashing after defecation or before eating were estimated to occur rarely. These quantitative behavior estimates can inform future risk assessments that examine the relative roles of various fecal–oral exposure pathways in low-income urban settings.

Fever is a major cause of morbidity and mortality among children under 5 years of age in resource-limited countries. Although prevention and treatment of febrile illnesses have improved, the costs—both financial and nonfinancial—remain barriers to care. Using data from the 2009 Uganda Malaria Indicator Survey, we describe the costs associated with the care of a febrile child and assess predictors of care-seeking behavior. Over 80% of caregivers sought care for their febrile child, however less than half did so on either the day of or the day after the development of fever. The odds of seeking care decreased with each additional month of the child's age. Caregivers living in rural areas were more likely to seek care, however were less likely to seek care promptly. Caregivers with at least a primary school education and those familiar with the protective effect of bed nets and the need to seek care promptly were more likely to seek care. Despite government assistance, the majority of caregivers did incur costs (mean 13,173 Ugandan shilling; $6.84 U.S. dollars) associated with medical care. Continued efforts targeting barriers to seeking care, including the economic burden, are necessary.