The American Journal of Tropical Medicine and Hygiene - Volume 92, Issue 4, April 2015

During armed conflicts over the past several years, attacks on humanitarian workers and patients have increased, including the most recent overt killing of patients in their hospital beds in South Sudan and Central African Republic, and bombardments of hospitals in Iraq, Syria, and other countries. Direct attacks on patients inside hospitals, as well as social structural dynamics that undermine patient safety and security, are met with apparent indifference by international and medical communities. How can the medical profession remain silent and stand by while these factors render its core mission futile? In this article, I aim to shed light on this issue, and its implications for the future of the neutral and impartial provision of medical care; provide an analysis of underlying and contributing factors; discuss current international strategies; reflect on the responsibility of health providers; explore ways to strengthen our roles as physician advocates; and call for the medical profession to do more to protect medicine's core values.

Acute human immunodeficiency virus (HIV) infection (AHI) refers to the period between viral transmission and development of an adaptive immune response to HIV antigens (seroconversion) usually lasting 6–8 weeks. Rare cases have been described in which HIV-infected patients fail to seroconvert and instead, develop rapid HIV-mediated clinical decline. We report the case of a Mozambican woman with AHI and malaria coinfection who showed atypical seroconversion and experienced rapid deterioration and death within 14 weeks of diagnosis with AHI. Atypical seroconversion may be associated with rapid progression. Fourth generation rapid tests could lead to earlier identification and intervention for this vulnerable subgroup.

In total, 3,145 ticks of the species Haemaphysalis longicornis (3,048; 96.9%), R. microplus (82; 2.6%), H. campanulata (9; 0.3%), and Dermacentor sinicus (5; 0.2%) were collected from animals and vegetation at Yantai in Shandong Province. Both adult and immature ticks were obtained, and all ticks collected from vegetation were unfed. Eggs were obtained from 22 blood-fed female ticks through maintenance at room temperature after collection. Severe fever with thrombocytopenia syndrome virus (SFTSV) viral RNA was identified in H. longicornis and R. microplus, with a prevalence of 4.75 per 100 ticks (95% confidence interval [95% CI] = 3.87–5.63) for ticks collected from animals and 2.24 per 100 ticks (95% CI = 1.27–3.21) for ticks collected from vegetation. The possibility that SFTSV transmission may occur by both the transstadial and transovarial routes was suggested by the fact that viral RNA was detected in H. longicornis at all developmental stages. Tick-derived sequences shared over 95.6% identity with human- and animal-derived isolates. This study provides evidence that implicates ticks as not only vectors but also, reservoirs of SFTSV.

Toscana virus (TOSV), a sandfly-borne phlebovirus, is an important agent of human meningoencephalitis in the Mediterranean region, for which vertebrates acting as reservoirs have not yet been determined. This study investigates TOSV and Leishmania infections in dogs, cats, sheep, and goats from Adana and Mersin provinces in southeastern Turkey. TOSV neutralizing antibodies were demonstrated in 40.4% of the dog and 4% of the goat samples. TOSV RNA was detected in 9.9% of the 252 samples that mainly comprise dogs (96%). Thus, canine species can be suggested as the candidate reservoirs of TOSV. Partial sequences revealed the activity of TOSV genotypes A and B. In two dogs presenting with symptoms of canine leishmaniasis, infections of TOSV genotype B and Leishmania infantum have been documented, describing the first report of coinfections with these agents.

The immunogenicity and protective efficacy of a candidate tetravalent dengue virus purified inactivated vaccine (TDENV PIV) formulated with alum or an Adjuvant System (AS01, AS03 tested at three different dose levels, or AS04) was evaluated in a 0, 1-month vaccination schedule in rhesus macaques. One month after dose 2, all adjuvanted formulations elicited robust and persisting neutralizing antibody titers against all four dengue virus serotypes. Most of the formulations tested prevented viremia after challenge, with the dengue serotype 1 and 2 virus strains administered at 40 and 32 weeks post-dose 2, respectively. This study shows that inactivated dengue vaccines, when formulated with alum or an Adjuvant System, are candidates for further development.

Dengue fever (DF) is an important health issue in Colombia, but detailed information on economic costs to the healthcare system is lacking. Using information from official databases (2010–2012) and a face-to-face survey of 1,483 households with DF and dengue hemorrhagic fever (DHF) patients, we estimated the average cost per case. In 2010, the mean direct medical costs to the healthcare system per case of ambulatory DF, hospitalized DF, and DHF (in Colombian pesos converted to US dollars using the average exchange rate for 2012) were $52.8, $235.8, and $1,512.2, respectively. The mean direct non-medical costs to patients were greater ($29.7, $46.7, and $62.6, respectively) than the mean household direct medical costs ($13.3, $34.8, and $57.3, respectively). The average direct medical cost to the healthcare system of a case of ambulatory DF in 2010 was 57% of that in 2011. Our results highlight the high economic burden of the disease and could be useful for assigning limited health resources.

Some mosquito strains or species are able to lay eggs without taking a blood meal, a trait named autogeny. This may allow populations to persist through times or places where vertebrate hosts are scarce. Autogenous egg production is highly dependent on the environment in some species, but the ideal conditions for its expression in Aedes aegypti mosquitoes are unknown. We found that 3.2% of females in a population of Ae. aegypti from Kenya were autogenous. Autogeny was strongly influenced by temperature, with many more eggs laid at 28°C compared with 22°C. Good nutrition in larval stages and feeding on higher concentrations of sugar solution during the adult stage both result in more autogenous eggs being produced. The trait also has a genetic basis, as not all Ae. aegypti genotypes can lay autogenously. We conclude that Ae. aegypti requires a favorable environment and a suitable genotype to be able to lay eggs without a blood meal.

Rift Valley fever (RVF) is a viral zoonotic disease occurring throughout Africa, the Arabian Peninsula, and Madagascar. The disease is caused by a Phlebovirus (RVF virus [RVFV]) transmitted to vertebrate hosts through the bite of infected mosquitoes. In Madagascar, the first RVFV circulation was reported in 1979 based on detection in mosquitoes but without epidemic episode. Subsequently, two outbreaks occurred: the first along the east coast and in the central highlands in 1990 and 1991 and the most recent along the northern and eastern coasts and in the central highlands in 2008 and 2009. Despite the presence of 24 mosquitoes species potentially associated with RVFV transmission in Madagascar, little associated entomological information is available. In this review, we list the RVFV vector, Culex antennatus, as well as other taxa as candidate vector species. We discuss risk factors from an entomological perspective for the re-emergence of RVF in Madagascar.

Health researchers have advocated for a cross-disciplinary approach to the study and prevention of infectious zoonotic diseases, such as Rift Valley Fever. It is believed that this approach can help bring out the social determinants and effects of the zoonotic diseases for the design of appropriate interventions and public health policy. A comprehensive literature review using a systematic search strategy was undertaken to explore the sociocultural and economic factors that influence the transmission and spread of Rift Valley Fever. Although the findings reveal a paucity of social research on Rift Valley Fever, they suggest that livestock sacrificial rituals, food preparation and consumption practices, gender roles, and inadequate resource base for public institutions are the key factors that influence the transmission. It is concluded that there is need for cross-disciplinary studies to increase the understanding of Rift Valley Fever and facilitate appropriate and timely response and mitigation measures.

In 2000, an outbreak of Rift Valley fever virus (RVFV) occurred in the Kingdom of Saudi Arabia (KSA). Since then there have been sparse efforts to monitor for RVFV reemergence. During 2012, we enrolled 300 individuals with ruminant exposure and 50 age-group matched non-exposed controls in southwestern KSA, in a cross-sectional epidemiological study of RVFV. Sera from the participants were screened with an enzyme-linked immunosorbent assay (ELISA) for anti-RVFV IgG antibodies of which 39 (11.1%) were positive. Sixteen (41.0%) of those 39 were also positive by a plaque reduction neutralization assay (PRNT). The PRNT-positive subjects were further studied with an IgM ELISA and one was positive. No RVFV was detected in the 350 sera using real-time reverse transcription polymerase chain reaction. Contact with cattle (odds ratio [OR] = 3.16, 95% confidence interval [CI] 1.01, 9.90) and a history of chronic medical illness (OR = 6.41, 95% CI 1.75, 23.44) were associated with greater odds of RVFV seropositivity by PRNT. The IgM-positive participant was 36 years of age, and reported multiple risk factors for ruminant contact. Although these findings simply may be vestiges of the 2000 epidemic, KSA's frequent visits from pilgrims and importations of live animals from RVFV-endemic areas suggest that more comprehensive surveillance for imported RVFV virus in ruminants, mosquitoes, and travelers is imperative.

Oral vaccines appear less effective in children in the developing world. Proposed biologic reasons include concurrent enteric infections, malnutrition, breast milk interference, and environmental enteropathy (EE). Rigorous study design and careful data management are essential to begin to understand this complex problem while assuring research subject safety. Herein, we describe the methodology and lessons learned in the PROVIDE study (Dhaka, Bangladesh). A randomized clinical trial platform evaluated the efficacy of delayed-dose oral rotavirus vaccine as well as the benefit of an injectable polio vaccine replacing one dose of oral polio vaccine. This rigorous infrastructure supported the additional examination of hypotheses of vaccine underperformance. Primary and secondary efficacy and immunogenicity measures for rotavirus and polio vaccines were measured, as well as the impact of EE and additional exploratory variables. Methods for the enrollment and 2-year follow-up of a 700 child birth cohort are described, including core laboratory, safety, regulatory, and data management practices. Intense efforts to standardize clinical, laboratory, and data management procedures in a developing world setting provide clinical trials rigor to all outcomes. Although this study infrastructure requires extensive time and effort, it allows optimized safety and confidence in the validity of data gathered in complex, developing country settings.

Currently, there are only limited data available on rates of major diagnostic categories of illnesses among Haitian children. We have established a cohort of 1,245 students attending schools run by the Christianville Foundation in the Gressier/Leogane region of Haiti, for whom our group provides primary medical care. Among 1,357 clinic visits during the 2012–2013 academic year, the main disease categories (with rates per 1,000 child years of observation) included acute respiratory infection (ARI) (385.6 cases/1,000 child years of observation), gastrointestinal complaints (277.8 cases/1,000 child years), febrile illness (235.0 cases/1,000 child years), and skin infections (151.7 cases/1,000 child years). The most common diarrheal pathogen was enteroaggregative Escherichia coli (present in 17% of children with diarrhea); Vibrio cholerae O1 and norovirus were the next most common. Our data highlight the importance of better defining etiologies for ARI and febrile illnesses and continuing problems of diarrheal illness in this region, including mild cases of cholera, which would not have been diagnosed without laboratory screening.

Since October 2010, over 700,000 cholera cases have been reported in Haiti. We used data from laboratory-based surveillance for diarrhea in Haiti to evaluate the sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of the cholera case definitions recommended by the World Health Organization (WHO). From April 2012 to May 2013, we tested 1,878 samples from hospitalized patients with acute watery diarrhea; 1,178 (62.7%) yielded Vibrio cholerae O1. The sensitivity and specificity of the WHO case definition for cholera in an epidemic setting were 91.3% and 43.1%, respectively, and the PPV and NPV were 72.8% and 74.8%, respectively. The WHO case definition for cholera in an area where cholera is not known to be present had lower sensitivity (63.1%) and NPV (55.1%) but higher specificity (74.2%) and PPV (80.0%). When laboratory diagnostic testing is not immediately available, clinicians can evaluate signs and symptoms to more accurately identify cholera patients.

Two point-of-use drinking water treatment systems designed using a carbon filter and foam material as a possible alternative to traditional biosand systems were evaluated for removal of bacteria, protozoa, and viruses. Two configurations were tested: the foam material was positioned vertically around the carbon filter in the sleeve unit or horizontally in the disk unit. The filtration systems were challenged with Cryptosporidium parvum, Raoultella terrigena, and bacteriophages P22 and MS2 before and after biofilm development to determine average log reduction (ALR) for each organism and the role of the biofilm. There was no significant difference in performance between the two designs, and both designs showed significant levels of removal (at least 4 log10 reduction in viruses, 6 log10 for protozoa, and 8 log10 for bacteria). Removal levels meet or exceeded Environmental Protection Agency (EPA) standards for microbial purifiers. Exploratory test results suggested that mature biofilm formation contributed 1–2 log10 reductions. Future work is recommended to determine field viability.

In a prospective study of 123 healthy adults competing in a mud-exposing endurance challenge in the melioidosis-endemic tropical north of the Northern Territory of Australia, there were no asymptomatic seroconversions to Burkholderia pseudomallei using indirect hemagglutination assay. However, one competitor developed melioidosis attributable to infection acquired during the event.

Understanding the effects of land-use change on zoonotic disease risk is a pressing global health concern. Here, we compare prevalence of Yersinia pestis, the etiologic agent of plague, in rodents across two land-use types—agricultural and conserved—in northern Tanzania. Estimated abundance of seropositive rodents nearly doubled in agricultural sites compared with conserved sites. This relationship between land-use type and abundance of seropositive rodents is likely mediated by changes in rodent and flea community composition, particularly via an increase in the abundance of the commensal species, Mastomys natalensis, in agricultural habitats. There was mixed support for rodent species diversity negatively impacting Y. pestis seroprevalence. Together, these results suggest that land-use change could affect the risk of local transmission of plague, and raise critical questions about transmission dynamics at the interface of conserved and agricultural habitats. These findings emphasize the importance of understanding disease ecology in the context of rapidly proceeding landscape change.

Rodents are an important reservoir for zoonotic diseases. To enhance the evidence on the human-rodent interface, this cross-sectional study was conducted in 2011 to investigate characteristics associated with rodent contact in Khon Kaen Province, Thailand. A standardized, interviewer-administered questionnaire elicited information from 201 adults (101 males and 100 females). Overall, 86.6% of participants reported encountering or seeing evidence of rodents in or near the home, whereas 57.2% encountered rodents while working with crops. Encountering rodents in or near the home was positively associated with the number of agricultural activities, whereas encountering rodents during crop work was positively associated with perceiving that disease can be acquired from rodents, the number of food crops grown, the number of agricultural activities, and living in a house with wooden walls. Surprisingly, neither outcome was associated appreciably with gender, age, or setting (urban, forest, or agricultural). These results provide information on the potential risk of rodent-borne zoonoses; this evidence has implications for risk communication strategies in this province and likely elsewhere.

We describe the first case of possible pulmonary chromoblastomycosis in the absence of any identified cutaneous lesions in a relatively immunosuppressed man. The causative organism was Cladophialophora arxii, which is a rare pathogen that has only been described as causing human disease two times previously.