- Home
- The American Journal of Tropical Medicine and Hygiene
- Fast Track Listing
The American Journal of Tropical Medicine and Hygiene - Online First
In order to provide our readers with timely access to new content, papers accepted by the American Journal of Tropical Medicine and Hygiene are posted online ahead of print publication. Papers that have been accepted for publication are peer-reviewed and copy edited but do not incorporate all corrections or constitute the final versions that will appear in the Journal. Final, corrected papers will be published online concurrent with the release of the print issue.
-
-
Risk Factors for Methicillin-Resistant Staphylococcus aureus Carriage among Patients at Admission to the Surgical Ward in a Resource-Limited Hospital in Indonesia
Authors: Dewi Santosaningsih, Sanarto Santoso, Henri A. Verbrugh and Juliëtte A. SeverinAvailable online: 18 September 2017More LessThis study aimed to identify risk factors for methicillin-resistant Staphylococcus aureus (MRSA) carriage among patients at admission to the surgery ward in a resource-limited hospital in Indonesia. A case–control study was performed including 65 MRSA carriage patients and 132 non-MRSA carriage patients screened at admission to surgery wards in a hospital in Malang, East Java. For MRSA screening, swabs were obtained from nares and throat, cultured in an enrichment broth followed by subculturing onto CHROMagar™ MRSA; suspected colonies were confirmed by polymerase chain reaction. Patients referred from other hospitals, patients transferred from the surgical acute care unit, patients that had a surgical procedure within 3 months before admission, and immunocompromised patients were more likely to be MRSA carriers at admission to the surgery wards. Selective MRSA screening of patients according to such risk factors at admission would efficiently detect MRSA carriers and may help control MRSA dissemination in surgery wards in limited-resource settings.
-
-
-
Dengue Virus Serotype 2 Established in Northern Mozambique (2015–2016)
Available online: 18 September 2017More LessAfter the report of an outbreak of dengue virus serotype 2 in 2014 in Nampula and Pemba cities, northern Mozambique, a surveillance system was established by the National Institute of Health. A study was performed during 2015–2016 to monitor the trend of the outbreak and confirm the circulating serotype of dengue virus (DENV). After the inclusion of consenting patients who met the case definition, samples from 192 patients were tested for the presence of nonstructural protein 1 antigen, and 60/192 (31%) samples were positive. Further analysis included DENV IgM antibodies, with 39 (20%) IgM positive cases. Reverse transcriptase (RT) PCR was performed for identification of the prevailing DENV serotype; 21/23 tested samples were DENV-2 positive, with DENV-2 present in both affected cities. When sequencing DENV, phenotype Cosmopolitan was identified. The surveillance indicates ongoing spread of DENV-2 in northern Mozambique 2 years after the first report of the outbreak.
-
-
-
Synthetic Antigens Derived from Plasmodium falciparum Sporozoite, Liver, and Blood Stages: Naturally Acquired Immune Response and Human Leukocyte Antigen Associations in Individuals Living in a Brazilian Endemic Area
Available online: 18 September 2017More LessPeptide vaccine strategies using Plasmodium-derived antigens have emerged as an attractive approach against malaria. However, relatively few studies have been conducted with malaria-exposed populations from non-African countries. Herein, the seroepidemiological profile against Plasmodium falciparum of naturally exposed individuals from a Brazilian malaria-endemic area against synthetic peptides derived from vaccine candidates circumsporozoite protein (CSP), liver stage antigen-1 (LSA-1), erythrocyte binding antigen-175 (EBA-175), and merozoite surface protein-3 (MSP-3) was investigated. Moreover, human leukocyte antigen (HLA)-DRB1* and HLA-DQB1* were evaluated to characterize genetic modulation of humoral responsiveness to these antigens. The study was performed using blood samples from 187 individuals living in rural malaria-endemic villages situated near Porto Velho, Rondônia State. Specific IgG and IgM antibodies and IgG subclasses were detected by enzyme-linked immunosorbent assay, and HLA-DRB1* and HLA-DQB1* low-resolution typing was performed by PCR-SSP. All four synthetic peptides were broadly recognized by naturally acquired antibodies. Regarding the IgG subclass profile, only CSP induced IgG1 and IgG3 antibodies, which is an important fact given that the acquisition of protective immunity appears to be associated with the cytophilicity of IgG1 and IgG3 antibodies. HLA-DRB1*11 and HLA-DQB1*7 had the lowest odds of responding to EBA-175. Our results showed that CSP, LSA-1, EBA, and MSP-3 are immunogenic in natural conditions of exposure and that anti-EBA antibody responses appear to be modulated by HLA class II antigens.
-
-
-
Demographic, Socioeconomic, and Geographic Factors Leading to Severe Malaria and Delayed Care Seeking in Ugandan Children: A Case–Control Study
Authors: Arthur Mpimbaza, Grace Ndeezi, Anne Katahoire, Philip J. Rosenthal and Charles KaramagiAvailable online: 11 September 2017More LessWe studied associations between delayed care seeking, demographic, socioeconomic, and geographic factors and likelihood of severe malaria in Ugandan children. The study was based at Jinja Hospital, Uganda. We enrolled 325 severe malaria cases and 325 uncomplicated malaria controls matched by age and residence. Patient details, an itinerary of events in response to illness, household information, and location of participants’ residences were captured. Conditional logistic regression was used to determine risk factors for severe malaria and delayed care seeking. Delayed care seeking (≥ 24 hours after fever onset; odds ratio [OR] 5.50; 95% confidence interval [CI] 2.70, 11.1), seeking care at a drug shop as the initial response to illness (OR 3.62; 95% CI 1.86, 7.03), and increasing distance from place of residence to the nearest health center (OR 1.45; 95% CI 1.17, 1.79) were independent risk factors for severe malaria. On subgroup analysis, delayed care seeking was a significant risk factor in children with severe malaria attributable to severe anemia (OR 15.6; 95% CI 3.02, 80.6), but not unconsciousness (OR 1.13; 95% CI 0.30, 4.28). Seeking care at a drug shop (OR 3.85; 95% CI 1.19, 12.3) and increasing distance to the nearest health center (OR 1.93; 95% CI 1.21, 3.08) were independent risk factors for delayed care seeking. Delayed care seeking and seeking care at a drug shop were risk factors for severe malaria. Seeking care at a drug shop was also a predictor of delayed care seeking. The role of drug shops in contributing to delayed care and risk of severe malaria requires further study.
-
-
-
Enzootic Circulation of Chikungunya Virus in East Africa: Serological Evidence in Nonhuman Kenyan Primates
Available online: 11 September 2017More LessChikungunya virus (CHIKV) is a globally emerging pathogen causing debilitating arthralgia and fever in humans. First identified in Tanzania (1953), this mosquito-borne alphavirus received little further attention until a 2004 re-emergence in Kenya from an unknown source. This outbreak subsequently spread to the Indian Ocean, with adaptation for transmission by a new urban vector. Under the hypothesis that sylvatic progenitor cycles of CHIKV exist in Kenya (as reported in West Africa, between nonhuman primates (NHPs) and arboreal Aedes spp. mosquitoes), we pursued evidence of enzootic transmission and human spillover events. We initially screened 252 archived NHP sera from Kenya using plaque reduction neutralization tests. Given an overall CHIKV seroprevalence of 13.1% (marginally higher in western Kenya), we sought more recent NHP samples during 2014 from sites in Kakamega County, sampling wild blue monkeys, olive baboons, and red-tailed monkeys (N = 33). We also sampled 34 yellow baboons near Kwale, coastal Kenya. Overall, CHIKV seropositivity in 2014 was 13.4% (9/67). Antibodies reactive against closely related o’nyong-nyong virus (ONNV) occurred; however, neutralization titers were too low to conclude ONNV exposure. Seroprevalence for the flavivirus dengue was also detected (28%), mostly near Kwale, suggesting possible spillback from humans to baboons. CHIKV antibodies in some juvenile and subadult NHPs suggested recent circulation. We conclude that CHIKV is circulating in western Kenya, despite the 2004 human outbreaks only being reported coastally. Further work to understand the enzootic ecology of CHIKV in east Africa is needed to identify sites of human spillover contact where urban transmission may be initiated.
-
-
-
Chagas Disease Infection among Migrants at the Mexico/Guatemala Border
Available online: 05 September 2017More LessChagas disease results in the largest burden in terms of disability-adjusted-life-years of any parasitic disease in the Americas. Monitoring Chagas disease among migrants is critical to controlling its spread and to serving the needs of the migrant community. Therefore, we determined the prevalence and correlates of Chagas disease in regional and international migrant populations at the Mexico/Guatemala border. Data were collected as part of a larger study of human immunodeficiency virus (HIV) and migration. Participants were a sample of recent regional and international migrants who used an illicit substance or had recent problem drinking. Trypanosoma cruzi infection was classified as testing positive on two different enzyme-linked immunosorbent assays (ELISAs). Interviewer-administered surveys captured sociodemographics, migration history, Chagas disease knowledge, and access to care. We enrolled 389 recent migrants, and the prevalence of Chagas disease was 3.1%. Only 19% of the participants reported having ever heard of the disease and less than 1% had been previously tested. Trypanosoma cruzi–positive participants were more likely to have been born in a rural area or town than a city (92% yes versus 59% no, P = 0.02) and have recently lived in a house with a makeshift roof (33% yes versus 8% no, P < 0.01), walls (42% yes versus 13% no, P < 0.01), or floor (50% yes versus 21% no, P < 0.02), or cinderblock walls (92% yes versus 63% no, P = 0.04). With migration rapidly changing the distribution of Chagas disease, more work needs to be done to create targeted surveillance programs and provide access to affordable treatment among Latin American migrants.
-
-
-
Is Visceral Leishmaniasis Different in Immunocompromised Patients Without Human Immunodeficiency Virus? A Comparative, Multicenter Retrospective Cohort Analysis
Available online: 05 September 2017More LessAlthough visceral leishmaniasis (VL) can affect immunocompromised patients, data from the human immunodeficiency virus (HIV) infection context are limited, and the characteristics of VL in other immunosuppression scenarios are not well defined. A retrospective review of all cases of VL in immunocompromised patients from January 1997 to December 2014 in two Spanish hospitals on the Mediterranean coast was performed. We included 18 transplant recipients (kidney: 7, liver: 4, lung: 3, heart: 2, and blood marrow: 2), 12 patients with other causes of immunosuppression (myasthenia gravis: 3 and rheumatoid arthritis: 2), and 73 VL HIV-positive patients. Fever was more common in transplant patients (94.4%) and patients with other types of immunosuppression (100%) than in HIV-positive individuals (73.3%). Hepatomegaly was less common in transplant recipients (27.8%) and patients with other types of immunosuppression (41.7%) compared with HIV-positive patients (69.9%) (P = 0.01; P = 0.001, respectively). Patients with other types of immunosuppression had a median leukocyte count of 1.5 × 109/L, significantly lower than HIV-positive patients (2.5 × 109/L) (P = 0.04). Serology was more commonly positive in nontransplant immunosuppressed individuals (75%) and transplant recipients (78.6%) than in HIV-patients (13.8%) (P < 0.001). Antimonial therapy was rarely used in transplant recipients (1.9%) and never in patients with other immunosuppressive conditions, whereas 34.2% of HIV-positive patients received it (P = 0.05 and P = 0.01, respectively). Mortality was 16.7% in both transplant recipients and patients with other immunosuppressive conditions and 15.1% in HIV-positive patients. The features of VL may be different in immunosuppressed patients, with more fever and less hepatomegaly and leukopenia than in HIV-infected patients.
-
-
-
Efficacy and Safety of Liposomal Amphotericin B for Visceral Leishmaniasis in Children and Adolescents at a Tertiary Care Center in Bihar, India
Available online: 05 September 2017More LessLiposomal amphotericin B is being used increasingly to reduce the burden of kala-azar from the Indian subcontinent. There are studies which have evaluated efficacy and safety of liposomal amphotericin B for visceral leishmaniasis in all age groups. However, the only study that specifically addressed treatment of childhood visceral leishmaniasis did not include all ages or document renal and liver function. We, therefore, felt it was important to reassess the efficacy and safety of single dose liposomal amphotericin B in children and adolescents. A total of 100 parasitologically confirmed visceral leishmaniasis patients aged < 15 years were included in this study. Participants consisted of 65 males and 35 females. All of them had come from the endemic region of Bihar. They were administered one dose intravenous infusion of liposomal amphptericin B at 10 mg/kg body weight. Efficacy was assessed as initial and final cure at 1 and 6 months, respectively, and safety of all participants who were recruited in the study. The initial and final cure rate by per protocol analysis was 100% and 97.9%, respectively. Chills and rigors were the most commonly occurring adverse events (AEs). All the AEs were mild in intensity, and none of the patients experienced any serious AEs. No patients developed nephrotoxicity. Our finding indicates that liposomal amphotericin B at 10 mg/kg body weight is safe and effective in children. Results of our study support the use of single dose liposomal amphotericin B in all age group populations for elimination of kala-azar from the Indian subcontinent.
-
-
-
Efficacy and Safety of a Single-Dose Mebendazole 500 mg Chewable, Rapidly-Disintegrating Tablet for Ascaris Lumbricoides and Trichuris Trichiura Infection Treatment in Pediatric Patients: A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study
Available online: 05 September 2017More LessThis randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of a new chewable, rapidly-disintegrating mebendazole (MBZ) 500 mg tablet for Ascaris lumbricoides and Trichuris trichiura infection treatment. Pediatric patients (1–15 years; N = 295; from Ethiopia and Rwanda) excreting A. lumbricoides and/or T. trichiura eggs were enrolled. The study had a screening phase (3 days), a double-blind treatment phase (DBP, 19 days), and an open-label phase (OLP, 7 days). Patients received MBZ or placebo on day 1 of DBP and open-label MBZ on day 19 ± 2 after stool sample collection. Cure rates (primary endpoint), defined as species-specific egg count of 0 at the end of DBP, were significantly higher in the MBZ group than placebo for A. lumbricoides (83.7% [72/86; 95% CI: 74.2%; 90.8%] versus 11.1% [9/81; 95% CI: 5.2%; 20.1%], P < 0.001) and for T. trichiura (33.9% [42/124; 95% CI: 25.6%; 42.9%] versus 7.6% [9/119; 95% CI: 3.5%; 13.9%], P < 0.001). Egg reduction rates (secondary endpoint) were significantly higher in the MBZ group than placebo for A. lumbricoides (97.9% [95% CI: 94.4; 99.9] versus 19.2% [95% CI: −5.9; 41.5]; P < 0.001) and T. trichiura (59.7% [95% CI: 33.9; 78.8] versus 10.5% [95% CI: −16.8; 32.9]; P = 0.003). Treatment-emergent adverse events (TEAEs) in MBZ group occurred in 6.3% (9/144) of patients during DBP and 2.5% (7/278) during OLP. No deaths, serious TEAEs, or TEAEs leading to discontinuations were reported. A 500 mg chewable MBZ tablet was more efficacious than placebo for the treatment of A. lumbricoides and T. trichiura infections in pediatric patients, and no safety concerns were identified.
-
-
-
Case Series of Naegleria fowleri Primary Ameobic Meningoencephalitis from Karachi, Pakistan
Authors: Najia K. Ghanchi, Bushra Jamil, Erum Khan, Zeeshan Ansar, Azra Samreen, Afia Zafar and Zahra HasanAvailable online: 05 September 2017More LessNaegleria fowleri causes primary amoebic meningoencephalitis (PAM) which is almost always fatal. Naegleria fowleri is waterborne, and its infections are usually associated with aquatic activities but it can also be transmitted via the domestic water supply. An increasing number of N. fowleri cases have been reported from Pakistan. Improved methods for diagnosis are required. We report the utility of polymerase chain reaction (PCR) for the diagnosis of N. fowleri in patients suspected of PAM. One hundred and sixteen cases suspected of having PAM were examined. Cerebrospinal fluid (CSF) specimens were tested at the Aga Khan University Hospital, Karachi. Nineteen CSF specimens were positive for N. fowleri by using the PCR. Naegleria fowleri positive patients had a median age of 28 years and were 84% male and 16% female. Overall, the CSF wet preparation microscopy was performed in 85 (73%) cases and identified that seven specimens were positive for motile trophozoites. The CSF wet preparation microscopy and PCR were both performed in these cases. The CSF wet preparation results were available for 15 of the 19 N. fowleri PCR positive CSF samples; seven (40%) wet preparations were positive. Our data highlight the threat of N. fowleri infection as a cause of PAM. It also emphasizes the utility of the PCR-based diagnosis of the amoeba for early diagnosis and management of the disease.
-
-
-
Prevalence of Clinical and Subclinical Plasmodium falciparum and Plasmodium vivax Malaria in Two Remote Rural Communities on the China–Myanmar Border
Available online: 05 September 2017More LessMalaria infections may be symptomatic, leading to treatment, or “asymptomatic,” typically detected through active surveillance, and not leading to treatment. Malaria elimination may require purging both types of infection. Using detection methods with different sensitivities, we conducted a cross-sectional study in two rural communities located along the border between China’s Yunnan Province and Myanmar’s Shan and Kachin States, to estimate the prevalence of asymptomatic and symptomatic malaria. In Mong Pawk, all infections detected were asymptomatic, and the prevalence of Plasmodium falciparum was 0.3%, 4.3%, 4.0%, and 7.8% by light microscopy, rapid diagnostic test (RDT), conventional polymerase chain reaction (cPCR), and multiplexed real-time PCR (RT-PCR), respectively, and Plasmodium vivax prevalence was 0% by all detection methods. In Laiza, of 385 asymptomatic participants, 2.3%, 4.4%, and 12.2% were positive for P. vivax by microscopy, cPCR, and RT-PCR, respectively, and 2.3% were P. falciparum-positive only by RT-PCR. Of 34 symptomatic participants in Laiza, 32.4% were P. vivax-positive by all detection methods. Factors associated with infection included gender (males higher than females, P = 0.014), and young age group (5–17 age group compared with others, P = 0.0024). Although the sensitivity of microscopy was adequate to detect symptomatic infections, it missed the vast majority (86.5%) of asymptomatic infections. Although molecular detection methods had no advantage over standard microscopy or RDT diagnosis for clinically apparent infections, malaria elimination along the China–Myanmar border will likely require highly sensitive surveillance tools to identify asymptomatic infections and guide targeted screen-and-treat interventions.
-
-
-
Effects of Boiling Drinking Water on Diarrhea and Pathogen-Specific Infections in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis
Authors: Alasdair Cohen and Jr. John M. ColfordAvailable online: 05 September 2017More LessGlobally, approximately 2 billion people lack microbiologically safe drinking water. Boiling is the most prevalent household water treatment method, yet evidence of its health impact is limited. To conduct this systematic review, we searched four online databases with no limitations on language or publication date. Studies were eligible if health outcomes were measured for participants who reported consuming boiled and untreated water. We used reported and calculated odds ratios (ORs) and random-effects meta-analysis to estimate pathogen-specific and pooled effects by organism group and nonspecific diarrhea. Heterogeneity and publication bias were assessed using I 2, meta-regression, and funnel plots; study quality was also assessed. Of the 1,998 records identified, 27 met inclusion criteria and reported extractable data. We found evidence of a significant protective effect of boiling for Vibrio cholerae infections (OR = 0.31, 95% confidence interval [CI] = 0.13–0.79, N = 4 studies), Blastocystis (OR = 0.35, 95% CI = 0.17–0.69, N = 3), protozoal infections overall (pooled OR = 0.61, 95% CI = 0.43–0.86, N = 11), viral infections overall (pooled OR = 0.83, 95% CI = 0.7–0.98, N = 4), and nonspecific diarrheal outcomes (OR = 0.58, 95% CI = 0.45–0.77, N = 7). We found no evidence of a protective effect for helminthic infections. Although our study was limited by the use of self-reported boiling and non-experimental designs, the evidence suggests that boiling provides measureable health benefits for pathogens whose transmission routes are primarily water based. Consequently, we believe a randomized controlled trial of boiling adherence and health outcomes are needed.
-
-
-
Undiagnosed Active Pulmonary Tuberculosis among Pilgrims during the 2015 Hajj Mass Gathering: A Prospective Cross-sectional Study
Available online: 05 September 2017More LessMass gatherings pose a risk for tuberculosis (TB) transmission and reactivation of latent TB infection. The annual Hajj pilgrimage attracts 2 million pilgrims from high TB-endemic countries. We evaluated the burden of undiagnosed active pulmonary TB in pilgrims attending the 2015 Hajj mass gathering. We conducted a prospective cross-sectional study in Mecca, Kingdom of Saudi Arabia, for nonhospitalized adult pilgrims from five high TB-endemic countries. Enrollment criteria were the presence of a cough and the ability to produce a sputum sample. Sputum samples were processed using the Xpert MTB-RIF assay. Data were analyzed for drug-resistant TB, risk factors, and comorbidities by the country of origin. Of 1,164 consenting pilgrims enrolled from five countries: Afghanistan (316), Bangladesh (222), Nigeria (176), Pakistan (302), and South Africa (148), laboratory results were available for 1,063 (91.3%). The mean age of pilgrims was 54.5 (range = 18–94 years) with a male to female ratio of 2.6:1; 27.7% had an underlying comorbidity, with hypertension and diabetes being the most common, 20% were smokers, and 2.8% gave a history of previous TB treatment. Fifteen pilgrims (1.4%) had active previously undiagnosed drug-sensitive pulmonary TB (Afghanistan [12; 80%], Pakistan [2; 13.3%], and Nigeria [1; 6.7%]). No multidrug-resistant TBcases were detected. Pilgrims from high TB-endemic Asian and African countries with undiagnosed active pulmonary TB pose a risk to other pilgrims from over 180 countries. Further studies are required to define the scale of the TB problem during the Hajj mass gathering and the development of proactive screening treatment and prevention guidelines.
-
-
-
Absence of Loa loa Microfilaremia among Newly Arrived Congolese Refugees in Texas
Authors: Jessica Montour, Deborah Lee, Cathy Snider, Emily S. Jentes and William StaufferAvailable online: 05 September 2017More LessThe Centers for Disease Control and Prevention recommends that refugees at risk of Loa loa infection be tested for microfilaria before treatment with ivermectin. We report observational results of this approach in African refugees in Texas. Daytime blood smears were performed for microfilaria on at-risk African refugees who arrived in Texas from July 1, 2014 through December 30, 2016. Clinics were asked if there were any adverse events reported among those who received ivermectin. Of the 422 persons screened, 346 (82%) were born in L. loa–endemic countries, with 332 (96%) of these being born in the Democratic Republic of Congo. No smears detected microfilaria, and all received presumptive ivermectin with no reports of significant adverse events. In this investigation, the prevalence of significant microfilarial load in sub-Saharan African refugees appeared to be low, and ivermectin treatment was safe and well tolerated.
-
-
-
Intralesional Infiltration with Meglumine Antimoniate for the Treatment of Leishmaniasis Recidiva Cutis in Ecuador
Available online: 05 September 2017More LessMeglumine Antimoniate (MA), administered intramuscularly for 21 continuous days is the recommended treatment of leishmaniases in Ecuador. However, because of its toxicity and requirement for intramuscular injections, treatment is frequently abandoned before completion. In addition, therapeutic failure and reactivation are not uncommon. Here we evaluate the efficacy and safety of MA administered intralesionally (IL) in leishmaniasis recidiva cutis (LRC). LRC is a special clinical variant of cutaneous leishmaniasis, characterized by reactivation at the edges of a primary cured lesion, presenting with active papules around the scar. Twenty-one patients were included in the study. All were diagnosed parasitologically by one of three diagnostic methods (smear, culture, and Leishmanin skin test). Each patient received MA intralesionally weekly for 4 weeks. Each papule was infiltrated until complete saturation. On average, patients received 1 mL of MA per administration. The criterion of cure was the complete resolution of the papules. Follow up was performed at 30, 90, and 180 days after treatment. At day 30 after treatment, 19 (90.5%) of 21 patients were clinically cured. The two patients, who did not heal by the fourth application, were cured on the seventh and eighth dose, achieving a clinical cure of 100% without subsequent reactivation. Mild to moderate local pain during infiltration was the only adverse reaction experienced by 81% of patients. In one case, subsequent infiltrations were discontinued because of a local allergic reaction. Complete compliance of patients to treatment and the small volume of drug administered make this method of administering MA an effective, safe, and inexpensive alternative. Consequently, IL could replace intramuscular administration in the treatment of LRC in Ecuador.
-
-
-
Characterization of Three New Insect-Specific Flaviviruses: Their Relationship to the Mosquito-Borne Flavivirus Pathogens
Authors: Hilda Guzman, Maria Angelica Contreras-Gutierrez, Amelia P. A. Travassos da Rosa, Marcio R. T. Nunes, Jedson F. Cardoso, Vsevolod L. Popov, Katherine I. Young, Chelsea Savit, Thomas G. Wood, Steven G. Widen, Douglas M. Watts, Kathryn A. Hanley, David Perera, Durland Fish, Nikos Vasilakis and Robert B. TeshAvailable online: 05 September 2017More LessThree novel insect-specific flaviviruses, isolated from mosquitoes collected in Peru, Malaysia (Sarawak), and the United States, are characterized. The new viruses, designated La Tina, Kampung Karu, and Long Pine Key, respectively, are antigenically and phylogenetically more similar to the mosquito-borne flavivirus pathogens, than to the classical insect-specific viruses like cell fusing agent and Culex flavivirus. The potential implications of this relationship and the possible uses of these and other arbovirus-related insect-specific flaviviruses are reviewed.
-
-
-
Passively versus Actively Detected Malaria: Similar Genetic Diversity but Different Complexity of Infection
Authors: Zuleima Pava, Irene Handayuni, Leily Trianty, Retno A. S. Utami, Yusrifar K. Tirta, Agatha M. Puspitasari, Faustina Burdam, Enny Kenangalem, Grennady Wirjanata, Steven Kho, Hidayat Trimarsanto, Nicholas Anstey, Jeanne Rini Poespoprodjo, Rintis Noviyanti, Ric N. Price, Jutta Marfurt and Sarah AuburnAvailable online: 05 September 2017More LessThe surveillance of malaria is generally undertaken on the assumption that samples passively collected at health facilities are comparable to or representative of the broader Plasmodium reservoir circulating in the community. Further characterization and comparability of the hidden asymptomatic parasite reservoir are needed to inform on the potential impact of sampling bias. This study explores the impact of sampling strategy on molecular surveillance by comparing the genetic make-up of Plasmodium falciparum and Plasmodium vivax isolates collected by passive versus active case detection. Sympatric isolates of P. falciparum and P. vivax were collected from a large community survey and ongoing clinical surveillance studies undertaken in the hypomesoendemic setting of Mimika District (Papua, Indonesia). Plasmodium falciparum isolates were genotyped at nine microsatellite loci and P. vivax at eight loci. Measures of diversity and differentiation were used to compare different patient and parasitological sample groups. The results demonstrated that passively detected cases (symptomatic) had comparable population diversity to those circulating in the community (asymptomatic) in both species. In addition, asymptomatic patent infections were as diverse as subpatent infections. However, a significant difference in multiplicity of infection (MOI) and percentage of polyclonal infections was observed between actively and passively detected P. vivax cases (mean MOI: 1.7 ± 0.7 versus 1.4 ± 1.4, respectively; P = 0.001). The study findings infer that, in hypomesoendemic settings, passive sampling is appropriate for molecular parasite surveillance strategies using the predominant clone in any given infection; however, the findings suggest caution when analyzing complexity of infection. Further evaluation is required in other endemic settings.
-
-
-
Human Intestinal Parasite Burden and Poor Sanitation in Rural Alabama
Available online: 05 September 2017More LessHookworm infection affects 430 million people worldwide, causing iron deficiency, impaired cognitive development, and stunting in children. Because of the environmental conditions needed for the hookworm life-cycle, this parasite is endemic to resource-limited countries. Necator americanus was endemic in the southern United States before improvement of sewage disposal systems and eradication programs. With continued poverty, poor sanitation, and an environment suitable for the hookworm life-cycle in some regions of the southern United States, a current prevalence study using modern molecular diagnostics is warranted. Lowndes County, Alabama, was chosen as the study site given previous high hookworm burdens, degree of poverty, and use of open-sewage systems. Participants were interviewed, and stool, serum, and soil samples were tested for nine intestinal parasites using a multiparallel quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assays . We found that, among 24 households, 42.4% reported exposure to raw sewage within their home, and from 55 stool samples, 19 (34.5%) tested positive for N. americanus, four (7.3%) for Strongyloides stercoralis, and one (1.8%) for Entamoeba histolytica. Stool tested positive for N. americanus contained low levels of parasite DNA (geometric mean 0.0302 fg/µL). Soil studies detected one (2.9%) Cryptosporidium species, and Toxocara serology assay detected one (5.2%) positive in this population. Individuals living in this high-risk environment within the United States continue to have stool samples positive for N. americanus. Gastrointestinal parasites known to be endemic to developing countries are identifiable in American poverty regions, and areas with lower disease burden are more likely to be identified by using qPCR.
-
-
-
Leprosy Associated with Atypical Cutaneous Leishmaniasis in Nicaragua and Honduras
Available online: 28 August 2017More LessIn Central America, few cases of leprosy have been reported, but the disease may be unrecognized. Diagnosis is based on clinical criteria and histology. Preliminary field work in Nicaragua and Honduras found patients, including many children, with skin lesions clinically suggestive of atypical cutaneous leishmaniasis or indeterminate leprosy. Histology could not distinguish these diseases although acid-fast organisms were visible in a few biopsies. Lesions healed after standard antimicrobial therapy for leprosy. In the present study, patients, family members, and other community members were skin-tested and provided nasal swabs and blood samples. Biopsies were taken from a subgroup of patients with clinical signs of infection. Two laboratories analyzed samples, using local in-house techniques. Mycobacterium leprae, Leishmania spp. and Leishmania infantum were detected using polymerase chain reactions. Mycobacterium leprae DNA was detected in blood samples and nasal swabs, including some cases where leprosy was not clinically suspected. Leishmania spp. were also detected in blood and nasal swabs. Most biopsies contained Leishmania DNA and colocation of Leishmania spp. with M. leprae occurred in 33% of cases. Mycobacterium leprae DNA was also detected and sequenced from Nicaraguan and Honduran environmental samples. In conclusion, leprosy and leishmaniasis are present in both regions, and leprosy appears to be widespread. The nature of any relationship between these two pathogens and the epidemiology of these infections need to be elucidated.
-
-
-
Country-Wide Surveillance of Molecular Markers of Antimalarial Drug Resistance in Senegal by Use of Positive Malaria Rapid Diagnostic Tests
Available online: 28 August 2017More LessIn Senegal, antimalarial drugs used in treatment and prevention of malaria are one of the main reasons for the current success in controlling malaria. However, the successful control of malaria is highly dependent on continued effectiveness of these drugs which may be compromised by the spread of drug resistance. Therefore, surveillance of drug resistance in the malaria parasites is essential. The objective of this pilot study was to test the feasibility of routinely sampled malaria rapid diagnostic tests (RDTs) at a national scale to assess the temporal changes in the molecular profiles of antimalarial drug resistance markers of Plasmodium falciparum parasites. Overall, 9,549 positive malaria RDTs were collected from 14 health facilities across the country. A limited random set of RDTs were analyzed regarding Pfcrt gene polymorphisms at codon 72–76. Overall, a high but varied prevalence (> 50%) of the wild-type CVMNK haplotype was observed including a higher CVMNK prevalence in the northern part (75%) compared with the southern part of the country (59%). With caution, the study provides a proof of concept that reuse of discarded P. falciparum positive RDTs can be applied in large-scale surveillance of antimalarial drug resistance.
-
-
-
Prevalence of Trypanosoma cruzi and Other Trypanosomatids in Frequently-Hunted Wild Mammals from the Peruvian Amazon
Available online: 28 August 2017More LessTo better understand the ecology of Trypanosoma cruzi in the northeastern Peruvian Amazon, we evaluated the prevalence of T. cruzi and other trypanosomatids in four orders of wild mammals hunted and consumed by inhabitants of three remote indigenous communities in the Peruvian Amazon. Of 300 wild mammals sampled, 115 (38.3%) were infected with trypanosomatids and 15 (5.0%) with T. cruzi. The prevalence of T. cruzi within each species was as follows: large rodents (Cuniculus paca, 5.5%; Dasyprocta spp., 2.6%), edentates (Dasypus novemcinctus, 4.2%), and carnivores with higher prevalence (Nasua nasua, 18.8%). The high prevalence of T. cruzi and other trypanosomatids in frequently hunted wild mammals suggests a sizeable T. cruzi sylvatic reservoir in remote Amazonian locations.
-
-
-
Effect of Tenofovor Diproxil Fumarate on Renal Function and Urinalysis Abnormalities in HIV-Infected Cameroonian Adults
Available online: 28 August 2017More LessIn Sub-Saharan Africa, the prevalence of HIV-associated kidney diseases is as high as 53.3%. Combined antiretroviral treatment (cART), especially tenofovir disoproxil fumarate (TDF), is known to be nephrotoxic. We undertook this cross-sectional study conducted in 2015 at the Regional Hospital Limbe in the Southwest Region of Cameroon to determine the prevalence of renal dysfunction and its correlates among treatment-experienced HIV-infected patients on TDF and treatment-naïve patients. In April 2016, a follow-up was performed on those who had been treatment-naïve and were started on cART after enrolment in the study. We compared 119 patients on TDF-containing regimens with 47 treatment-naïve patients. Proteinuria was significantly more prevalent, and creatinine was significantly higher among treatment-naïve patients than among those on treatment (52.2% versus 26.1%; P = 0.003 and P = 0.009, respectively). The proportion of patients with an estimated glomerular filtration rate (eGFR) < 60 mL/minute was significantly higher among treatment-naïve patients than among those on TDF treatment (40.4% versus 24.4%; P = 0.041). Treatment-naïve patients displayed an improvement in creatinine levels and eGFR after 6 months of treatment. To the best of our knowledge, this is the first study to investigate the impact of TDF on renal parameters in Cameroon. TDF appears to be safe and does not appear to be a significant cause of renal impairment. However, renal parameters should be monitored regularly, as recommended by the guidelines.
-
-
-
Guillain–Barré Syndrome, Acute Disseminated Encephalomyelitis and Encephalitis Associated with Zika Virus Infection in Brazil: Detection of Viral RNA and Isolation of Virus during Late Infection
Available online: 28 August 2017More LessZika virus (ZIKV) emerged in Brazil in 2015, which was followed by an increase of Guillain–Barre Syndrome (GBS) cases. We report the epidemiological, clinical, and laboratory findings of the first six neurological cases associated with ZIKV in Brazil seen in a reference neurology hospital in Pernambuco, Brazil. In all cases, ZIKV was detected in serum and/or cerebrospinal fluid (CSF) samples. In this case series, four cases were defined as GBS, one as acute disseminated encephalomyelitis (ADEM) and the other as encephalitis. ZIKV was detected in all cases by RT-PCR and virus isolation was successful in two patients. The time between ZIKV acute symptoms and the development of neurological manifestations varied from 3 to 13 days and ZIKV was detected between 15 and 34 days after the initial symptoms. Our results highlight the need to include ZIKV as a differential diagnosis for neurological syndromes in countries with circulation of this arbovirus. Because the viremia in these patients appears to persist longer, direct diagnostic techniques such as RT-PCR and viral isolation should be considered even if it is after the acute phase of viral infection.
-
-
-
Direct Biomarkers of Microbial Translocation Correlate with Immune Activation in Adult Zambians with Environmental Enteropathy and Hepatosplenic Schistosomiasis
Authors: Patrick Kaonga, Evans Kaimoyo, Ellen Besa, Kanekwa Zyambo, Edford Sinkala and Paul KellyAvailable online: 28 August 2017More LessMicrobial translocation is a poorly understood consequence of several disorders such as environmental enteropathy (EE) and hepatosplenic schistosomiasis (HSS). Herein, we compared biomarkers of microbial origin and immune activation in adults with these disorders and in healthy controls. A cross-sectional study was conducted in participants with EE recruited from Misisi compound, Lusaka, Zambia; HSS patients and healthy controls from the University Teaching Hospital, Lusaka. Plasma lipopolysaccharides (LPSs) was measured by limulus amoebocyte lysate assay, plasma 16S ribosomal RNA (16S rRNA) gene copy number was quantified by quantitative real-time polymerase chain reaction, Toll-like receptor ligand (TLRL) activity by QUANTI-Blue detection medium, and cytokines from cell culture supernatant by Cytometric Bead Array. In univariate analysis LPS, 16S rRNA gene copy number, and TLR activity were all high and correlated with each other and with cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, and IL-4 secreted by the RAW-Blue cells. After controlling for baseline characteristic, biomarkers of microbial translocation in blood were predictors of TNF-α, IL-6, and IL-10 activation in cell culture supernatant from EE participants and HSS patients but not in healthy controls. TLR activity showed the strongest correlation with TNF-α. These data provide correlative evidence that microbial translocation contributes to systemic cytokine activation in two disorders common in the tropics, with total TLR ligand estimation showing the strongest correlation with TNF-α (r = 0.66, P < 0.001).
-
-
-
Multipathway Quantitative Assessment of Exposure to Fecal Contamination for Young Children in Low-Income Urban Environments in Accra, Ghana: The SaniPath Analytical Approach
Available online: 21 August 2017More LessLack of adequate sanitation results in fecal contamination of the environment and poses a risk of disease transmission via multiple exposure pathways. To better understand how eight different sources contribute to overall exposure to fecal contamination, we quantified exposure through multiple pathways for children under 5 years old in four high-density, low-income, urban neighborhoods in Accra, Ghana. We collected more than 500 hours of structured observation of behaviors of 156 children, 800 household surveys, and 1,855 environmental samples. Data were analyzed using Bayesian models, estimating the environmental and behavioral factors associated with exposure to fecal contamination. These estimates were applied in exposure models simulating sequences of behaviors and transfers of fecal indicators. This approach allows us to identify the contribution of any sources of fecal contamination in the environment to child exposure and use dynamic fecal microbe transfer networks to track fecal indicators from the environment to oral ingestion. The contributions of different sources to exposure were categorized into four types (high/low by dose and frequency), as a basis for ranking pathways by the potential to reduce exposure. Although we observed variation in estimated exposure (108–1016 CFU/day for Escherichia coli) between different age groups and neighborhoods, the greatest contribution was consistently from food (contributing > 99.9% to total exposure). Hands played a pivotal role in fecal microbe transfer, linking environmental sources to oral ingestion. The fecal microbe transfer network constructed here provides a systematic approach to study the complex interaction between contaminated environment and human behavior on exposure to fecal contamination.
-
-
-
Surveillance of Vector-Borne Infections (Chikungunya, Dengue, and Malaria) in Bo, Sierra Leone, 2012–2013
Available online: 21 August 2017More LessMalaria remains a significant cause of morbidity and mortality in West Africa, but the contribution of other vector-borne infections (VBIs) to the burden of disease has been understudied. We used rapid diagnostic tests (RDTs) for three VBIs to test blood samples from 1,795 febrile residents of Bo City, Sierra Leone, over a 1-year period in 2012–2013. In total, 24% of the tests were positive for malaria, fewer than 5% were positive for markers of dengue virus infection, and 39% were positive for IgM directed against chikungunya virus (CHIKV) or a related alphavirus. In total, more than half (55%) of these febrile individuals tested positive for at least one of the three VBIs, which highlights the very high burden of vector-borne diseases in this population. The prevalence of positives on the Chikungunya IgM and dengue tests did not vary significantly with age (P > 0.36), but higher rates of malaria were observed in children < 15 years of age (P < 0.001). Positive results on the Chikungunya IgM RDTs were moderately correlated with rainfall (r 2 = 0.599). Based on the high prevalence of positive results on the Chikungunya IgM RDTs from individuals Bo and its environs, there is a need to examine whether an ecological shift toward a greater burden from CHIKV or related alphaviruses is occurring in other parts of Sierra Leone or the West African region.
-
-
-
Histological Examination in Obtaining a Diagnosis in Patients with Lymphadenopathy in Lima, Peru
Available online: 21 August 2017More LessThe differential diagnosis for lymphadenopathy is wide and clinical presentations overlap, making obtaining an accurate diagnosis challenging. We sought to characterize the clinical and radiological characteristics, histological findings, and diagnoses for a cohort of patients with lymphadenopathy of unknown etiology. 121 Peruvian adults with lymphadenopathy underwent lymph node biopsy for microbiological and histopathological evaluation. Mean patient age was 41 years (Interquartile Range 26–52), 56% were males, and 39% were HIV positive. Patients reported fever (31%), weight loss (23%), and headache (22%); HIV infection was associated with fever (P < 0.05) and gastrointestinal symptoms (P < 0.05). Abnormalities were reported in 40% of chest X-rays (N = 101). Physicians suspected TB in 92 patients (76%), lymphoma in 19 patients (16%), and other malignancy in seven patients (5.8%). Histological diagnoses (N = 117) included tuberculosis (34%), hyperplasia (27%), lymphoma (13%), and nonlymphoma malignancy (14%). Hyperplasia was more common (P < 0.001) and lymphoma less common (P = 0.005) among HIV-positive than HIV-negative patients. There was a trend toward reduced frequency of caseous necrosis in samples from HIV-positive than HIV-negative TB patients (67 versus 93%, P = 0.055). The spectrum of diagnoses was broad, and clinical and radiological features correlated poorly with diagnosis. On the basis of clinical features, physicians over-diagnosed TB, and under-diagnosed malignancy. Although this may not be inappropriate in resource-limited settings where TB is the most frequent easily treatable cause of lymphadenopathy, diagnostic delays can be detrimental to patients with malignancy. It is important that patients with lymphadenopathy undergo a full diagnostic work-up including sampling for histological evaluation to obtain an accurate diagnosis.
-
-
-
Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea
Available online: 21 August 2017More LessChildren with acute and chronic malnutrition are at increased risk of morbidity and mortality following a diarrheal episode. To compare diarrheal disease severity and pathogen prevalence among children with and without acute and chronic malnutrition, we conducted a cross-sectional study of human immunodeficiency virus-uninfected Kenyan children aged 6–59 months, who presented with acute diarrhea. Children underwent clinical and anthropometric assessments and provided stool for bacterial and protozoal pathogen detection. Clinical and microbiological features were compared using log binomial regression among children with and without wasting (mid-upper arm circumference ≤ 125 mm) or stunting (height-for-age z score ≤ −2). Among 1,363 children, 7.0% were wasted and 16.9% were stunted. After adjustment for potential confounders, children with wasting were more likely than nonwasted children to present with at least one Integrated Management of Childhood Illness danger sign (adjusted prevalence ratio [aPR]: 1.3, 95% confidence interval [CI]: 1.0 to 1.5, P = 0.05), severe dehydration (aPR: 2.4, 95% 1.5 to 3.8, P < 0.01), and enteroaggregative Escherichia coli recovered from their stool (aPR: 1.8, 1.1–2.8, P = 0.02). There were no differences in the prevalence of other pathogens by wasting status after confounder adjustment. Stunting was not associated with clinical severity or the presence of specific pathogens. Wasted children with diarrhea presented with more severe disease than children without malnutrition which may be explained by a delay in care-seeking or diminished immune response to infection. Combating social determinants and host risk factors associated with severe disease, rather than specific pathogens, may reduce the disparities in poor diarrhea-associated outcomes experienced by malnourished children.
-
-
-
Epidemiology of Imported Malaria Cases in Japan, 2006–2014: A Sentinel Traveler Surveillance Approach
Authors: Atsuhiro Kanayama, Yuzo Arima, Tamano Matsui, Koki Kaku, Hitomi Kinoshita and Kazunori OishiAvailable online: 21 August 2017More LessMalaria continues to be imported into Japan. To better assess the risk of imported malaria, we describe malaria species, suspected country/area of infection (accounting for the number of travelers), demographic characteristics, clinical manifestation, and healthcare access, based on the national surveillance data from 2006 to 2014. Among 557 cases, the median age was 33 years (range: 1–83 years), and 76% were male; 306 (55%) were classified as Japanese based on the reported name. The majority were Plasmodium falciparum infections (58%), followed by Plasmodium vivax infections (30%). Most P. falciparum cases were acquired in Africa and P. vivax in Asia/Oceania. Annual notification rates per 10,000 Japanese travelers for P. falciparum were highest for Africa, P. vivax were highest for Asia/Oceania, and high for both species for Papua New Guinea. Ten percent of the cases were clinically severe at the time of notification. Nearly 80% of severe cases were P. falciparum infections, and Japanese ethnicity was associated with the severity (P = 0.03). Plasmodium falciparum cases among Japanese cases showed that older age (≥ 50 years) was associated with the severity (odds ratio = 5.4; 95% confidence interval = 1.9–15.2), adjusted for sex and healthcare access. More informative assessments are possible by accounting for the number of travelers. Older Japanese represent an important demographic to target prevention and early treatment efforts for malaria.
-
-
-
The Effects of Malnutrition and Diarrhea Type on the Accuracy of Clinical Signs of Dehydration in Children under Five: A Prospective Cohort Study in Bangladesh
Available online: 21 August 2017More LessAcute diarrhea and malnutrition remain significant burdens of disease for children under five and disproportionately affect children living in low- and middle-income countries. Children under five have an estimated 2.9 episodes of diarrhea every year or nearly 1.7 billion episodes of diarrhea in 2010, with the highest burden of disease in Africa and southeast Asia.1 Cholera infection, caused by the O1 or O139 subgroups of the bacterium Vibrio cholerae, is of particular concern because of the severe onset of profuse diarrhea that can cause death from dehydration within hours if untreated.2 Three out of five subregions in Africa report rising numbers of children under five with stunting, a measure of chronic malnutrition, from 46% in 1990 to 58% in 2014.3 Acute malnutrition shows similar geographic distribution, with 68% of children under five suffering from wasting living in Southern Asia and 28% living in Africa.3
-
-
-
Case Report: Treatment of Widespread Nodular Post kala-Azar Dermal Leishmaniasis with Extended-Dose Liposomal Amphotericin B in Bangladesh: A Series of Four Cases
Available online: 14 August 2017More LessPost kala-azar dermal leishmaniasis (PKDL) is a skin manifestation which usually appears after visceral leishmaniasis. It is now proved that PKDL patients serve as a reservoir for anthropometric leishmanial transmission. Hence, to achieve the kala-azar elimination target set by the World Health Organization in the Indian Subcontinent, PKDL cases should be given priority. The goal of treatment for PKDL should be early reepithelizlization and rapid cure, but unfortunately this has been difficult to achieve, especially for patients with severe lesions. Therefore, we describe here four cases of PKDL who had widespread nodular and macular lesions and were treated with two cycles of LAmB doses with 20 mg/kg body weight divided into four equal doses (each dose contains 5 mg/kg) administered every alternate day. This treatment schedule achieved 100% treatment success with the minimal safety concern.
-
-
-
Field Trial of the CareStart Biosensor Analyzer for the Determination of Glucose-6-Phosphate Dehydrogenase Activity in Haiti
Available online: 14 August 2017More LessThroughout many developing and tropical countries around the world, malaria remains a significant threat to human health. One barrier to malaria elimination is the ability to safely administer primaquine chemotherapy for the radical cure of malaria infections in populations with a high prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency. In the current study, a field trial of the world’s first quantitative, point-of-care assay for measuring G6PD activity was conducted in Haiti. The performance of the CareStart Biosensor Analyzer was compared with the gold standard spectrophotometric assay and genotyping of the G6PD allele in schoolchildren (N = 343) from the Ouest Department of Haiti. In this population, 19.5% of participants (67/343) had some form of G6PD deficiency (< 60% residual activity) and 9.9% (34/343) had moderate-to-severe G6PD deficiency (< 30% residual activity). Overall, 18.95% of participants had the presence of the A-allele (65/343) with 7.87% (27/343) considered at high risk for drug-induced hemolysis (hemizygous males and homozygous females). Compared with the spectrophotometric assay, the sensitivity and specificity to determine participants with < 60% residual activity were 53.7% and 94.6%, respectively; for participants with 30% residual activity, the sensitivity and specificity were 5.9% and 99.7%, respectively. The biosensor overestimated the activity in deficient individuals and underestimated it in participants with normal G6PD activity, indicating the potential for a systematic measurement error. Thus, we suggest that the current version of the biosensor lacks adequate sensitivity and should be improved prior to its use as a point-of-care diagnostic for G6PD deficiency.
-
-
-
Immune Reconstitution Inflammatory Syndrome in HIV-Infected Immigrants
Available online: 14 August 2017More LessImmune reconstitution inflammatory syndrome (IRIS) includes a group of potentially serious inflammatory processes that may be present in HIV-infected patients after initiating highly active antiretroviral therapy (HAART). Paradoxical IRIS is a worsening of symptoms, after an overwhelming response to a previously diagnosed opportunistic infection (OI); unmasking IRIS reveals a previously occult OI. The main objective of the study was to describe the epidemiological, clinical, and outcome data of HIV-infected immigrants, stratified according to high- or low-income countries of origin, who developed IRIS and to compare them with native-born Spanish patients. This retrospective study reviewed all patients with HIV infection admitted to the Unit of Infectious Diseases and Tropical Medicine between 1998 and 2014. IRIS was identified in 25/138 (18%) immigrant patients and 24/473 (5%) native-born Spanish patients infected with HIV. Most cases, 19/25 (76%), were of unmasking IRIS. The time elapsed between initiation of HAART and development of IRIS was significantly longer in patients with unmasking versus paradoxical IRIS. OIs, in particular due to mycobacteria, were the most frequently involved processes. Twenty percent of patients died. The comparison of immigrant and native-born patients found significant differences for both IRIS type (higher incidence of paradoxical forms among immigrants) and for the absence of malignancies in native-born patients. No significant differences were found when the data of immigrants from low- and high-income countries were compared.
-
-
-
Efficacy, Safety and Cost-Effectiveness of Thermotherapy in the Treatment of Leishmania donovani–Induced Cutaneous Leishmaniasis: A Randomized Controlled Clinical Trial
Available online: 14 August 2017More LessLeishmania donovani causes cutaneous leishmaniasis (CL) in Sri Lanka. Standard treatment is multiple, painful doses of intralesional sodium stibogluconate (IL-SSG). Treatment failures are increasingly reported, hence the need to investigate alternatives. Efficacy, safety, and cost-effectiveness of thermotherapy were assessed for the first time for L. donovani CL. A single blinded noninferiority randomized controlled trial was conducted on new laboratory-confirmed CL patients with single lesions (N = 213). Selected patients were randomly assigned to 1) test group (N = 98; single session of radiofrequency-induced heat therapy (RFHT) given at 50°C for 30 seconds) and 2) control group (N = 115; 1–3 mL IL-SSG given weekly, until cure/10 doses). Patients were followed-up fortnightly for 12 weeks to assess clinical cure. Cost of treatment was assessed using scenario building technique. Cure rates by 8, 10, and 12 weeks in RFHT group were 46.5%, 56.5%, and 65.9% as opposed to 28%, 40.8%, and 59.4% in IL-SSG group, with no major adverse events. Cure rate by RFHT was significantly higher at 8 weeks (P = 0.009, odds ratio [OR]: 2.236, confidence interval [CI]: 1.217–4.108) and 10 weeks (P = 0.035, OR: 1.881, CI: 1.044–3.388), but comparable thereafter. Cost of RFHT was 7 times less (USD = 1.54/patient) than IL-SSG (USD = 11.09/patient). A single application of RFHT is safe, cost-effective, and convenient, compared with multiple doses of IL-SSG in the treatment of L. donovani CL. Therefore, RFHT would be considered noninferior as per trial outcome when compared with standard IL-SSG therapy with multiple benefits for the patient and the national health care system.
-
-
-
Lack of Efficacy of Liposomal Amphotericin B Against Acute and Chronic Trypanosoma cruzi Infection in Mice
Available online: 14 August 2017More LessAcute and chronic infection with Trypanosoma cruzi affects millions of people. The current therapeutic options are highly toxic and often not effective. Liposomal amphotericin B (LABORATORY) has been demonstrated previously to have some activity in murine models. In our studies, higher dosages given multiple times were tested for activity against acute or chronic disease, exploring whether intermittent and brief regimens could be effective, as might then prove useful in human, particularly outpatient, therapy. For acute infection, LABORATORY 25 mg/kg intravenously (i.v.) given one to three times prolonged survival and caused a rapid disappearance of Y strain trypanomastigotes from the blood. However, even four or six doses of LABORATORY 30 mg/kg i.v., did not result in the cure of Y strain infection, with all mice relapsing after being immunosuppressed with cyclophosphamide. Similarly, chronic infection due to the CL strain was found to be unaltered by 1–3 treatments with LABORATORY 25 mg/kg. All surviving mice had histopathological evidence of infection in one or more tissues and equivalent antibody titers regardless of treatment regimen. Overall, LABORATORY at doses up to 30 mg/kg i.v. prolonged survival, but these doses were not curative in the regimens studied.
-
-
-
Prevalence and Seroprevalence of Trypanosoma cruzi Infection in a Military Population in Texas
Available online: 14 August 2017More LessRecent biosurveillance findings at Joint Base San Antonio (JBSA), a large military installation located in south-central Texas, indicate the potential for vector-borne human Chagas disease. A cross-sectional study was conducted to determine the prevalence and seroprevalence of Trypanosoma cruzi infection in highest risk subpopulations on the installation, including students and instructors who work and sleep in triatomine-endemic field settings. Real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and indirect immunofluorescent antibody assay were performed on enrolled subjects (N = 1,033), none of whom tested positive for T. cruzi or anti-T. cruzi antibodies. Current countermeasures used during field training on JBSA appear to be sufficient for preventing autochthonous human Chagas disease.
-
-
-
Scrub Typhus as an Etiology of Acute Febrile Illness in Gorakhpur, Uttar Pradesh, India, 2016
Available online: 14 August 2017More LessSeasonal outbreaks of acute encephalitis syndrome (AES) with high mortality occur every year in Gorakhpur region of Uttar Pradesh, India. Earlier studies indicated the role of scrub typhus as the important etiology of AES in the region. AES cases were hospitalized late in the course of their illness. We established surveillance for acute febrile illness (AFI) (fever ≥ 4 days duration) in peripheral health facilities in Gorakhpur district to understand the relative contribution of scrub typhus. Of the 224 patients enrolled during the 3-month period corresponding to the peak of AES cases in the region, about one-fifth had immunoglobulin M (IgM) antibodies against Orientia tsutsugamushi. Dengue and leptospira accounted for 8% and 3% of febrile illness cases. Treating patients with AFI attending the peripheral health facilities with doxycycline could prevent development of AES and thereby reduce deaths due to AES in Gorakhpur region.
-
-
-
Predictive Model for Permanent Shunting in Cryptococcal meningitis
Available online: 14 August 2017More LessCryptococcal meningitis may have long-term morbidity and requires a permanent cerebrospinal fluid shunt. This study aimed to evaluate the risk factors and create a predictive model for permanent shunt treatment in cryptococcal meningitis patients. This was a retrospective analytical study conducted at Khon Kaen University. The study period was from January 2005 to December 2015. We enrolled all adult patients diagnosed with cryptococcal meningitis. Risk factors predictive for permanent shunting treatment were analyzed by multivariate logistic regression analysis. There were 341 patients diagnosed with cryptococcal meningitis. Of those, 64 patients (18.7%) were treated with permanent shunts. There were three independent factors associated with permanent shunt treatment. The presence of hydrocephalus had the highest adjusted OR at 56.77. The resulting predictive model for permanent shunt treatment (y) is (−3.85) + (4.04 × hydrocephalus) + (2.13 × initial CSF opening pressure (OP) > 25 cm H2O) + (1.87 × non-HIV). In conclusion, non-HIV status, initial CSF OP greater than or equal to 25 cm H2O, and the presence of hydrocephalus are indicators of the future necessity for permanent shunt therapy.
-
-
-
Limited Transmission Potential of Takeda’s Tetravalent Dengue Vaccine Candidate by Aedes albopictus
Authors: Elizabeth A. Dietrich, Yee Tsuey Ong, Janae L. Stovall, Hansi Dean and Claire Y.-H. HuangAvailable online: 14 August 2017More LessRecombinant live-attenuated chimeric tetravalent dengue vaccine viruses, TDV-1, -2, -3, and -4, contain the premembrane and envelope genes of dengue virus serotypes 1–4 in the replicative background of the attenuated dengue virus type-2 (DENV-2) PDK-53 vaccine strain. Previous results have shown that these recombinant vaccine viruses demonstrate limited infection and dissemination in Aedes aegypti and are unlikely to be transmitted by the primary mosquito vector of DENVs. In this report, we expand this analysis by assessing vector competence of all four serotypes of the TDV virus in Aedes albopictus, the secondary mosquito vector of DENVs. Our results indicate that these vaccine viruses demonstrate incompetence or defective infection and dissemination in these mosquitoes and will likely not be transmissible.
-
-
-
Accuracy of a Rapid Diagnostic Test (Cypress Chagas Quick Test®) for the Diagnosis of Chronic Chagas Disease in a Nonendemic Area: A Retrospective Longitudinal Study
Available online: 14 August 2017More LessWe analyzed the accuracy of Chagas Quick Test®, a rapid diagnostic test, for the diagnosis of chronic Chagas disease through a retrospective study on a cohort of 669 patients consecutively examined at a single reference center in Italy, during a 7-year period. We observed high concordance with serological reference standard but low accuracy for screening purposes (sensitivity/specificity: 82.8%/98.7%) at least in our nonendemic context.
-
-
-
Epidemiology of Cutaneous Leishmaniasis in a Colombian Municipality
Available online: 14 August 2017More LessThis study describes the epidemiological and clinical characteristics of leishmaniasis and the pharmacological treatment of this disease in the municipality of Pueblo Rico, Risaralda, between January 2010 and December 2014. An observational study was conducted using information from the clinical records and epidemiological reports of patients diagnosed and confirmed with leishmaniasis of any age and sex, including sociodemographic, clinical, and pharmacological variables of the therapy received. Univariate and bivariate analyses were performed. A total of 539 cases of leishmaniasis were confirmed, with 29.5% occurring in children under 5 years of age. The median age was 10 years, with predominance in males (55.5%). The indigenous Emberá (aboriginal Americans) were the most affected (50.8%), and 93.3% of cases occurred in people living in scattered rural areas. All lesions corresponded to cutaneous leishmaniasis, and 251 patients had compromise of the upper limbs (46.6%), 221 of the face (41.0%), and 139 of the lower limbs (25.8%). Pentavalent antimony salts (n-methyl glucamine and sodium stibogluconate) were prescribed in 77.6% (N = 418) of the cases; miltefosine was the second most frequently prescribed medication (21.5%, N = 116). The inhabitants of rural areas and the indigenous communities are at a higher risk of acquiring the infection, particularly among infants, which highlights the importance of the biological, social, and demographic factors involved in the disease. There is a need to seek effective public health actions and further research this disease.
-
-
-
Case Report: Scalp Eschar and Neck Lymphadenopathy Associated with Bacteremia due to Coxiella-Like Bacteria
Available online: 14 August 2017More LessCoxiella-like bacteria have been recently proposed as human pathogens. Using molecular techniques, we detected Coxiella-like bacteria in the blood and serum samples of a patient with a scalp eschar, neck lymphadenopathy, severe urticaria, edema, fever, and arthralgia indicating that this organism can provide systemic complications.
-
-
-
Risk Factors Associated with Blood Exposure for Sporadic Hepatitis E in Dhaka, Bangladesh
Available online: 14 August 2017More LessFecal contamination of drinking water is associated with large hepatitis E virus (HEV) outbreaks of genotypes 1 and 2 in endemic areas. Sporadic transmission of HEV genotypes 3 and 4 in high-income countries has been associated with exposure to blood and animal contact. The objective of the study was to identify the risk factors for hepatitis E and the genotype(s) causing sporadic hepatitis E in Dhaka, Bangladesh. We selected, from a diagnostic center in Dhaka between November 2008 and November 2009, cases presenting with jaundice and anti-HEV IgM antibodies and age-matched controls were defined as those with no history of jaundice and normal blood test results. Serum samples were tested for HEV RNA using real-time reverse transcriptase polymerase chain reaction followed by a sequencing and phylogenetic analysis. A total of 109 cases and 109 controls were enrolled. The cases were more likely to be male (adjusted matched odds ratios [mOR] 2.2, 95% CI: 1.2–3.9; P = 0.01), or have reported contact with another person’s blood or blood product, or contact with blood-contaminated sharp instruments (adjusted mOR 2.1, 95% CI: 1.1–4.1; P = 0.03) than controls. There were no significant differences between the cases and the controls in terms of reported high-risk sexual intercourse, consumption of undercooked meat, or contact or drinking fecally-contaminated water. The sera from three cases carried HEV RNA, all belonging to genotype 1. Findings from this study suggest that contact with human blood and sharing sharp instruments may transmit sporadic hepatitis E in Dhaka, Bangladesh. Efforts to prevent the transmission of blood-borne pathogens may also prevent sporadic HEV transmission in this endemic setting.
-
-
-
Differential Neurovirulence of African and Asian Genotype Zika Virus Isolates in Outbred Immunocompetent Mice
Available online: 14 August 2017More LessAlthough first isolated almost 70 years ago, Zika virus (ZIKV; Flavivirus, Flaviviridae) has only recently been associated with significant outbreaks of disease in humans. Several severe ZIKV disease manifestations have also been recently documented, including fetal malformations, such as microcephaly, and Guillain–Barré syndrome in adults. Although principally transmitted by mosquitoes, sexual transmission of ZIKV has been documented. Recent publications of several interferon receptor knockout mouse models have demonstrated ZIKV-induced disease. Herein, outbred immunocompetent CD-1/ICR adult mice were assessed for susceptibility to disease by intracranial (i.c.) and intraperitoneal (i.p.) inoculation with the Ugandan prototype strain (MR766; African genotype), a low-passage Senegalese strain (DakAr41524; African genotype) and a recent ZIKV strain isolated from a traveler infected in Puerto Rico (PRVABC59; Asian genotype). Morbidity was not observed in mice inoculated by the i.p. route with either MR766 or PRVABC59 for doses up to 6 log10 PFU. In contrast, CD-1/ICR mice inoculated i.c. with the MR766 ZIKV strain exhibited an 80–100% mortality rate that was age independent. The DakAr41524 strain delivered by the i.c route caused 30% mortality, and the Puerto Rican ZIKV strain failed to elicit mortality but did induce a serum neutralizing immune response in 60% of mice. These data provide a potential animal model for assessing neurovirulence determinants of different ZIKV strains as well as a potential immunocompetent challenge model for assessing protective efficacy of vaccine candidates.
-
-
-
Molecular Epidemiology of Cholera Outbreaks during the Rainy Season in Mandalay, Myanmar
Available online: 14 August 2017More LessCholera, caused by Vibrio cholerae, remains a global threat to public health. In Myanmar, the availability of published information on the occurrence of the disease is scarce. We report here that cholera incidence in Mandalay generally exhibited a single annual peak, with an annual average of 312 patients with severe dehydration over the past 5 years (since 2011) and was closely associated with the rainy season. We analyzed cholera outbreaks, characterized 67 isolates of V. cholerae serogroup O1 in 2015 from patients from Mandalay, and compared them with 22 V. cholerae O1 isolates (12 from Mandalay and 10 from Yangon) in 2014. The isolates carried the classical cholera toxin B subunit (ctxB), the toxin-co-regulated pilus A (tcpA) of Haitian type, and repeat sequence transcriptional regulator (rstR) of El Tor type. Two molecular typing methods, pulsed-field gel electrophoresis and multiple-locus variable-number tandem repeat analysis (MLVA), differentiated the 89 isolates into seven pulsotypes and 15 MLVA profiles. Pulsotype Y15 and one MLVA profile (11, 7, 7, 16, 7) were predominantly found in the isolates from cholera outbreaks in Mandalay, 2015. Pulsotypes Y11, Y12, and Y15 with some MLVA profiles were detected in the isolates from two remote areas, Mandalay and Yangon, with temporal changes. These data suggested that cholera spread from the seaside to the inland area in Myanmar.
-
-
-
Clinical Spectrum, Etiology, and Outcome of Neurological Disorders in the Rural Hospital of Mosango, the Democratic Republic of Congo
Authors: Deby Mukendi, Jean-Roger Lilo Kalo, Alain Mpanya, Luigi Minikulu, Tharcisse Kayembe, Pascal Lutumba, Barbara Barbé, Philippe Gillet, Jan Jacobs, Harry Van Loen, Cedric P. Yansouni, François Chappuis, Raffaella Ravinetto, Kristien Verdonck, Marleen Boelaert, Andrea S. Winkler and Emmanuel BottieauAvailable online: 14 August 2017More LessThere is little published information on the epidemiology of neurological disorders in rural Central Africa, although the burden is considered to be substantial. This study aimed to investigate the pattern, etiology, and outcome of neurological disorders in children > 5 years and adults admitted to the rural hospital of Mosango, province of Kwilu, Democratic Republic of Congo, with a focus on severe and treatable infections of the central nervous system (CNS). From September 2012 to January 2015, 351 consecutive patients hospitalized for recent and/or ongoing neurological disorder were prospectively evaluated by a neurologist, subjected to a set of reference diagnostic tests in blood or cerebrospinal fluid, and followed-up for 3–6 months after discharge. No neuroimaging was available. Severe headache (199, 56.7%), gait/walking disorders (97, 27.6%), epileptic seizure (87, 24.8%), and focal neurological deficit (86, 24.5%) were the predominant presentations, often in combination. Infections of the CNS were documented in 63 (17.9%) patients and mainly included bacterial meningitis and unspecified meningoencephalitis (33, 9.4%), second-stage human African trypanosomiasis (10, 2.8%), and human immunodeficiency virus (HIV)-related neurological disorders (10, 2.8%). Other focal/systemic infections with neurological manifestations were diagnosed in an additional 60 (17.1%) cases. The leading noncommunicable conditions were epilepsy (61, 17.3%), psychiatric disorders (56, 16.0%), and cerebrovascular accident (23, 6.6%). Overall fatality rate was 8.2% (29/351), but up to 23.8% for CNS infections. Sequelae were observed in 76 (21.6%) patients. Clinical presentations and etiologies of neurological disorders were very diverse in this rural Central African setting and caused considerable mortality and morbidity.
-
-
-
Rapid Detection of Plasmodium knowlesi by Isothermal Recombinase Polymerase Amplification Assay
Authors: Meng-Yee Lai, Choo-Huck Ooi and Yee-Ling LauAvailable online: 14 August 2017More LessIn this study, we developed a recombinase polymerase amplification (RPA) assay for specific diagnosis of Plasmodium knowlesi. Genomic DNA was extracted from whole blood samples using a commercial kit. With incubation at 37°C, the samples were successfully amplified within 20 minutes. The end product of RPA was further examined by loading onto agarose gel and a specific band was observed with a size of 128 bp. The RPA assay exhibited high sensitivity with limits of detection down to one copy of the plasmid. From the specificity experiments, it was demonstrated that all P. knowlesi samples (N = 45) were positive while other Plasmodium spp. (N = 42) and negative samples (N = 6) were negative. Therefore, the RPA assay is a highly promising approach with the potential to be used in resource-limited settings. This assay can be further optimized for bedside and on field application.
-
-
-
The Sustainable Development Goals for Water: The Need to Consider Perception, Preference, and Safety
Author: Christine StauberAvailable online: 14 August 2017More LessIn this month’s issue, Brooks et al.1 examine the role of organoleptic perception and its association with bacteriologic drinking water quality in the Nyanza Province of western Kenya. This study focuses on two important issues relevant for drinking water in the new Sustainable Development Goals (SDGs)2: human sensory perception and the measures of water safety, and the need to be able to measure drinking water quality in resource limited settings. To address the lack of studies, the authors researched how household members’ perception of taste, odor, or overall quality were linked to measured levels of Escherichia coli via two detection methods: IDEXX Colilert™ Quantitray (Colilert) and the Compartment Bag Test (CBT). The authors also compared the CBT to Colilert to determine its ability to measure microbiologic water quality in the field.
-
-
-
Malaria in the Guangxi Zhuang Autonomous Region in China: A Twelve-Year Surveillance Data Study
Authors: Kangming Lin, Haiyan Wei, Weikang Jiang, Jun Li, Weiwei Zhang, Shujiao Wei, Yichao Yang, Yaming Huang, Xiangyang Feng, Hong Tu and Jun FengAvailable online: 07 August 2017More LessThe incidence of an indigenous malaria, defined as malaria acquired by a local mosquito transmission, declined from 2004 to 2015 in the Guangxi Zhuang Autonomous Region. However, imported malaria, defined as malaria acquired from other endemic regions outside of China, has been increasing in the region, as in the rest of the country, particularly the disease caused by Plasmodium falciparum. A retrospective study was conducted to explore malaria-endemic characteristics in Guangxi during the 2004–2015 timeframe; a total of 2,726 confirmed malaria cases were reported, and the majority (90.3%) were due to P. falciparum (N = 1,697 [62.2%]) and Plasmodium vivax (N = 765 [28.1%]). Thirty-four indigenous cases (1.2%) were observed, with no cases of transmission recorded since 2012. Imported P. vivax and Plasmodium ovale infections increased since 2013. The interval between returning to China and the onset of illness was longer for P. vivax and P. ovale infections than for P. falciparum and Plasmodium malariae infections. The difference interval among the species is likely because of the relapse of P. vivax and P. ovale caused by the activation of the latent hypnozoites. Therefore, health clinics should raise awareness and carry out epidemiological studies and follow-up surveys on migrant workers to avoid misdiagnosis and mistreatment. The evaluation of radical treatment should be carried out using a genotyping technology based on glucose-6-phosphate dehydrogenase deficiency levels, and some new drugs active against the hypnozoites should be developed to mitigate malaria in the region.
-
-
-
Identification of Subsets of Enteroaggregative Escherichia coli Associated with Diarrheal Disease among Under 5-Year-Old Children from Rural Gambia
Available online: 07 August 2017More LessEnteroaggregative Escherichia coli (EAEC) cause acute and persistent diarrhea, mostly in children worldwide. Outbreaks of diarrhea caused by EAEC have been described, including a large outbreak caused by a Shiga toxin expressing strain. This study investigated the association of EAEC virulence factors with diarrhea in children less than 5 years. We characterized 428 EAEC strains isolated from stool samples obtained from moderate-to-severe diarrhea cases (157) and healthy controls (217) children aged 0–59 months recruited over 3 years as part of the Global Enteric Multicenter Study (GEMS) in The Gambia. Four sets of multiplex polymerase chain reaction were applied to detect 21 EAEC-virulence genes from confirmed EAEC strains that target pCVD432 (aatA) and AAIC (aaiC). In addition, Kirby-Bauer disc diffusion antimicrobial susceptibility testing was performed on 88 EAEC strains following Clinical Laboratory Standard Institute guidelines. We observed that the plasmid-encoded enterotoxin [odds ratio (OR): 6.9, 95% confidence interval (CI): 2.06–29.20, P < 0.001], aggregative adherence fimbriae/I fimbriae (aggA) [OR: 2.2, 95% CI: 1.16–4.29, P = 0.008], and hexosyltransferase (capU) [OR: 1.9, 95% CI 1.02–3.51, P = 0.028] were associated with moderate-to-severe diarrhea among children < 12 months old but not in the older age strata (> 12 months). Our data suggest that some EAEC-virulent factors have age-specific associations with moderate-to-severe diarrhea in infants. Furthermore, our study showed that 85% and 72% of EAEC strains tested were resistant to sulphamethoxazole-trimethoprim and ampicillin, respectively. Sulphamethoxazole-trimethoprim and ampicillin are among the first-line antibiotics used for the treatment of diarrhea in The Gambia.
-
-
-
Tuberculosis-Related Diabetes: Is It Reversible after Complete Treatment?
Available online: 07 August 2017More LessIndividuals with newly diagnosed tuberculosis (TB) were screened for diabetes (DM) with fasting plasma glucose (FPG) in Pakistan. A significant decrease in FPG was observed when TB was treated. Of those with newly diagnosed DM, 46% and 62% no longer had hyperglycemia after 3 and 6 months, respectively. Individuals with known DM also showed a significant decrease in fasting plasma levels when treated for TB, but after 3 months none had normoglycemia, and after 6 months 9.2% were normoglycemic. Thus, TB-related DM may abate when the stress terminates, as is the case in gestational DM. However, because stress hyperglycemia may be associated with subsequent risk of developing DM, follow-up is recommended.
-
-
-
Case Report: A Case of Plasmodium falciparum hrp2 and hrp3 Gene Mutation in Bangladesh
Available online: 07 August 2017More LessSeveral species of Plasmodium are responsible for causing malaria in humans. Proper diagnoses are crucial to case management, because severity and treatment varies between species. Diagnoses can be made using rapid diagnostic tests (RDTs), which detect Plasmodium proteins. Plasmodium falciparum causes the most virulent cases of malaria, and P. falciparum histidine-rich protein 2 (PfHRP2) is a common target of falciparum malaria RDTs. Here we report a case in which a falciparum malaria patient in Bangladesh tested negative on PfHRP2-based RDTs. The negative results can be attributed to a deletion of part of the pfhrp2 gene and frameshift mutations in both pfhrp2 and pfhrp3 gene. This finding may have implications for malaria diagnostics and case management in Bangladesh and other regions of South Asia.
-
-
-
The Impact of Introducing Malaria Rapid Diagnostic Tests on Fever Case Management: A Synthesis of Ten Studies from the ACT Consortium
Authors: Katia J. Bruxvoort, Baptiste Leurent, Clare I. R. Chandler, Evelyn K. Ansah, Frank Baiden, Anders Björkman, Helen E. D. Burchett, Sîan E. Clarke, Bonnie Cundill, Debora D. DiLiberto, Kristina Elfving, Catherine Goodman, Kristian S. Hansen, S. Patrick Kachur, Sham Lal, David G. Lalloo, Toby Leslie, Pascal Magnussen, Lindsay Mangham-Jefferies, Andreas Mårtensson, Ismail Mayan, Anthony K. Mbonye, Mwinyi I. Msellem, Obinna E. Onwujekwe, Seth Owusu-Agyei, Mark W. Rowland, Delér Shakely, Sarah G. Staedke, Lasse S. Vestergaard, Jayne Webster, Christopher J. M. Whitty, Virginia L. Wiseman, Shunmay Yeung, David Schellenberg and Heidi HopkinsAvailable online: 07 August 2017More LessSince 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400–432,513). mRDTs were associated with significantly lower ACT prescription (range 8–69% versus 20–100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.
-
-
-
The Emergence of Severe Fever with Thrombocytopenia Syndrome Virus
Authors: Jesus A. Silvas and Patricia V. AguilarAvailable online: 07 August 2017More LessSevere fever with thrombocytopenia syndrome (SFTS) is a newly recognized hemorrhagic fever disease found throughout Asia with a case fatality rate between 12% and 30%. Since 2009, SFTS has been reported in China throughout 14 Chinese Provinces. In addition, SFTS has been recognized in South Korea and Japan with the first confirmed cases reported in 2012. A similar disease, caused by the closely related Heartland virus, was also reported in the United States in 2009. SFTS is caused by SFTS virus, a novel tick-borne virus in the family Bunyaviridae, genus Phlebovirus. Unlike other mosquito- and sandfly-borne bunyaviruses, SFTS virus has not been extensively studied due to its recent emergence and many unknowns regarding its pathogenesis, life cycle, transmission, and options for therapeutics remains. In this review, we report the most current findings in SFTS virus research.
-
-
-
Scaling Up of an Innovative Intervention to Reduce Risk of Dengue, Chikungunya, and Zika Transmission in Uruguay in the Framework of an Intersectoral Approach with and without Community Participation
Available online: 07 August 2017More LessTo contribute to the prevention of dengue, chikungunya, and Zika, a process of scaling up an innovative intervention to reduce Aedes aegypti habitats, was carried out in the city of Salto (Uruguay) based on a transdisciplinary analysis of the eco-bio-social determinants. The intervention in one-third of the city included the distributions of plastic bags for all households to collect all discarded water containers that were recollected by the Ministry of Health and the Municipality vector control services. The results were evaluated in 20 randomly assigned clusters of 100 households each, in the intervention and control arm. The intervention resulted in a significantly larger decrease in the number of pupae per person index (as a proxy for adult vector abundance) than the corresponding decrease in the control areas (both areas decreased by winter effects). The reduction of intervention costs (“incremental costs”) in relation to routine vector control activities was 46%. Community participation increased the collaboration with the intervention program considerably (from 48% of bags handed back out of the total of bags delivered to 59% of bags handed back). Although the costs increased by 26% compared with intervention without community participation, the acceptability of actions by residents increased from 66% to 78%.
-
-
-
Following the Worms: Detection of Soil-Transmitted Helminth Eggs on Mothers’ Hands and Household Produce in Rural Kenya
Authors: Lauren Steinbaum, Jenna Swarthout, John Mboya and Amy J. PickeringAvailable online: 07 August 2017More LessApproximately one-quarter of the world’s population is infected with at least one species of soil-transmitted helminth (STH). The role of produce and hands in STH transmission is not well understood. We collected and processed mother hand rinse and garden-grown produce rinse samples from 116 rural households in Kakamega, Kenya, in an area previously identified to have high STH egg contamination in household soil. Ascaris was the only STH species detected; 0.9% of hand rinse, 3.5% of leafy produce, and 1.8% of root produce samples had Ascaris eggs. Our results indicate produce and hands can transmit Ascaris eggs. However, due to the low detected prevalence of eggs on hands and produce, and a high prevalence of cooking the produce items tested, these pathways might have a minor contribution to STH transmission in this setting.
-
-
-
Clinical Features of Intermittent Migratory Swelling Caused by Gnathostomiasis with Complete Follow-up
Authors: Chollasap Sharma, Watcharapong Piyaphanee and Dorn WatthanakulpanichAvailable online: 07 August 2017More LessA 15-year-old Thai girl was referred to the Hospital for Tropical Diseases of Mahidol University with a 3-week history of an intermittent migratory mass on the forehead. She was diagnosed with cutaneous gnathostomiasis. The patient was treated with albendazoleat 400 mg orally twice a day for 3 weeks, with good compliance. She revisited the hospital after 3 months and was seen to have been unresponsive to the initial treatment. There was intermittent swelling in her right upper eyelid along with mild redness around her right upper and lower eyelids. Another attempt of treatment was made with ivermectin 0.2 mg/kg/day for two consecutive days. This is a case of gnathostomiasis in full sequence, with complete follow-up. The case report starts from the beginning of the symptoms until the antibodies against Gnathostoma spinigerum decline to negative, confirmed by the western blot test. It took around 18 months to see the western blot test change to a negative result. The resolved clinical symptoms were possibly due to the responsiveness of the patient to ivermectin or the albendazole and ivermectin combination or even the coadministration of antibiotics afterward.
-
-
-
Performance of a High-Sensitivity Rapid Diagnostic Test for Plasmodium falciparum Malaria in Asymptomatic Individuals from Uganda and Myanmar and Naive Human Challenge Infections
Authors: Smita Das, Ihn Kyung Jang, Becky Barney, Roger Peck, John C. Rek, Emmanuel Arinaitwe, Harriet Adrama, Maxwell Murphy, Mallika Imwong, Clare L. Ling, Stephane Proux, Warat Haohankhunnatham, Melissa Rist, Annette M. Seilie, Amelia Hanron, Glenda Daza, Ming Chang, Tomoka Nakamura, Michael Kalnoky, Paul Labarre, Sean C. Murphy, James S. McCarthy, Francois Nosten, Bryan Greenhouse, Sophie Allauzen and Gonzalo J. DomingoAvailable online: 07 August 2017More LessSensitive field-deployable diagnostic tests can assist malaria programs in achieving elimination. The performance of a new Alere™ Malaria Ag P.f Ultra Sensitive rapid diagnostic test (uRDT) was compared with the currently available SD Bioline Malaria Ag P.f RDT in blood specimens from asymptomatic individuals in Nagongera, Uganda, and in a Karen Village, Myanmar, representative of high- and low-transmission areas, respectively, as well as in pretreatment specimens from study participants from four Plasmodium falciparum-induced blood-stage malaria (IBSM) studies. A quantitative reverse transcription PCR (qRT-PCR) and a highly sensitive enzyme-linked immunosorbent assay (ELISA) test for histidine-rich protein II (HRP2) were used as reference assays. The uRDT showed a greater than 10-fold lower limit of detection for HRP2 compared with the RDT. The sensitivity of the uRDT was 84% and 44% against qRT-PCR in Uganda and Myanmar, respectively, and that of the RDT was 62% and 0% for the same two sites. The specificities of the uRDT were 92% and 99.8% against qRT-PCR for Uganda and Myanmar, respectively, and 99% and 99.8% against the HRP2 reference ELISA. The RDT had specificities of 95% and 100% against qRT-PCR for Uganda and Myanmar, respectively, and 96% and 100% against the HRP2 reference ELISA. The uRDT detected new infections in IBSM study participants 1.5 days sooner than the RDT. The uRDT has the same workflow as currently available RDTs, but improved performance characteristics to identify asymptomatic malaria infections. The uRDT may be a useful tool for malaria elimination strategies.
-
-
-
House Structure Is Associated with Plasmodium falciparum Infection in a Low-Transmission Setting in Southern Zambia
Available online: 07 August 2017More LessHouse structure may influence the risk of malaria by affecting mosquito entry and indoor resting. Identification of construction features associated with protective benefits could inform vector control approaches, even in low-transmission settings. We examined the association between house structure and malaria prevalence in a cross-sectional analysis of 2,788 children and adults residing in 866 houses in a low-transmission area of Southern Province, Zambia, over the period 2008–2012. Houses were categorized according to wall (brick/cement block or mud/grass) and roof (metal or grass) material. Malaria was assessed by point-of-care rapid diagnostic test (RDT) for Plasmodium falciparum. We identified 52 RDT-positive individuals residing in 41 houses, indicating an overall prevalence of parasitemia in the sample of 1.9%, ranging from 1.4% to 8.8% among the different house types. Occupants of higher quality houses had reduced odds of P. falciparum malaria compared with those in the lowest quality houses after controlling for bed net use, indoor insecticide spraying, clustering by house, cohabitation with another RDT-positive individual, ecologic risk defined as nearest distance to a Strahler-classified third-order stream, education, age, and gender (adjusted odds ratio [OR]: 0.26, 95% confidence interval [CI]: 0.09–0.73, P = 0.01 for houses with brick/cement block walls and metal roof; OR: 0.22, 95% CI: 0.09–0.52, P < 0.01 for houses with brick/cement block walls and grass roof). Housing improvements offer a promising approach to vector control in low-transmission settings that circumvents the threat posed by insecticide resistance, and may confer a protective benefit of similar magnitude to current vector control strategies.
-
-
-
Short-Term Changes in Anemia and Malaria Parasite Prevalence in Children under 5 Years during One Year of Repeated Cross-Sectional Surveys in Rural Malawi
Available online: 07 August 2017More LessIn stable transmission areas, malaria is the leading cause of anemia in children. Anemia in children is proposed as an added sensitive indicator for community changes in malaria prevalence. We report short-term temporal variations of malaria and anemia prevalence in rural Malawian children. Data from five repeated cross-sectional surveys conducted over 1 year in rural communities in Chikwawa District, Malawi, were analyzed. Different households were sampled per survey; all children, 6–59 months, in sampled household were tested for malaria parasitemia and hemoglobin levels using malaria rapid diagnostic tests (mRDT) and Hemocue 301, respectively. Malaria symptoms, recent treatment (2 weeks) for malaria, anthropometric measurements, and sociodemographic details were recorded. In total, 894 children were included from 1,377 households. The prevalences of mRDT positive and anemia (Hb < 11 g/dL) were 33.8% and 58.7%, respectively. Temporal trends in anemia and parasite prevalence varied differently. Overall, unadjusted and adjusted relative risks of anemia in mRDT-positive children were 1.31 (95% CI: 1.09–1.57) and 1.36 (1.13–1.63), respectively. Changes in anemia prevalence differed with short-term changes in malaria prevalence, although malaria is an important factor in anemia.
-
-
-
Creating Online Training for Procedures in Global Health with Procedural Education for Adaptation to Resource-Limited Settings
Authors: Rachel S. Bensman, Tina M. Slusher, Sabrina M. Butteris and Michael B. PittAvailable online: 31 July 2017More LessThe authors describe a multiinstitutional collaborative project to address a gap in global health training by creating a free online platform to share a curriculum for performing procedures in resource-limited settings. This curriculum called PEARLS (Procedural Education for Adaptation to Resource-Limited Settings) consists of peer-reviewed instructional and demonstration videos describing modifications for performing common pediatric procedures in resource-limited settings. Adaptations range from the creation of a low-cost spacer for inhaled medications to a suction chamber for continued evacuation of a chest tube. By describing the collaborative process, we provide a model for educators in other fields to collate and disseminate procedural modifications adapted for their own specialty and location, ideally expanding this crowd-sourced curriculum to reach a wide audience of trainees and providers in global health.
-
-
-
Central Nervous System Infection Associated with Orientia tsutsugamushi in South Korea
Available online: 31 July 2017More LessOrientia tsutsugamushi is a major cause of vector-borne infection in Asia. Prompt recognition and appropriate treatment are crucial because of its potentially fatal complications and lack of response to beta-lactam antibiotics. The present study retrospectively evaluated the clinical characteristics and laboratory findings of 16 patients with scrub typhus-related central nervous system (CNS) infections. Single titers ≥ 1:40 of total serum antibodies against O. tsutsugamushi detected by an indirect immunofluorescent assay were considered as positive results. The median age was 35.5 (range, 14–72) years, and 10 (62.5%) patients were female. The most common symptoms were headache (81.3%) and fever (81.3%). Eschar formation was found in three (18.8%) patients. Among patients with encephalitis, seizures and altered consciousness occurred in five (83.3%) and four (66.7%) patients, respectively. An abnormal liver function was noted in seven (43.8%) patients. The median antibody titer was 1:120 (range, 1:40–1:2,560). Typical cerebrospinal fluid profiles were lymphocytic pleocytosis, mild protein elevations, and normal glucose levels. All patients received an empirical treatment with doxycycline and most (93.8%) of them recovered without neurological sequelae. None of the patients reported side effects of the doxycycline treatment. An empirical treatment with doxycycline is needed in patients with CNS infections in scrub typhus endemic areas.
-
-
-
High Prevalence of Treponema pallidum Infection in Brazilian Prisoners
Available online: 31 July 2017More LessThe number of new syphilis cases in Brazil has risen alarmingly in recent years. However, there is limited data regarding syphilis prevalence in the Brazilian prison population. To facilitate the development of effective interventions, a cross-sectional study was undertaken to determine the prevalence of Treponema pallidum infection, active syphilis, and associated risk factors among Brazilian prisoners. We administered a questionnaire to a population-based sample of prisoners from 12 prisons in Central-West Brazil and collected sera for syphilis testing, from January to December 2013. Univariable and multivariable regression analyses were performed to assess associations with active syphilis. We recruited 3,363 prisoners (men: 84.6%; women: 15.4%). The overall lifetime and active syphilis prevalences were 10.5% (9.4% among men; 17% among women, P < 0.001) and 3.8% (2% among men; 9% among women, P < 0.001), respectively. The variables associated with active syphilis in men prisoners were homosexual preference, history of sexually transmitted infections, and human immunodeficiency virus status. Among women, the factors were sex with intravenous drug users, genital ulcer disease, and previous incarceration. Despite the high prevalence of active syphilis, 88.5% reported unawareness of their serological status and 67% reported unprotected sexual practices. Women had the highest rates of infection, including them in a high-risk group for the development of syphilis during pregnancy. Thus, implementing screening programs to enable continuous measures of control and prevention of T. pallidum infection in the prison environment, mainly in women institutions, is important to prevent severe forms of this disease and congenital infections.
-
-
-
In Vitro Testing of Potential Entamoeba histolytica Pyruvate Phosphate Dikinase Inhibitors
Authors: Syazwan Saidin, Nurulhasanah Othman and Rahmah NoordinAvailable online: 31 July 2017More LessAdverse effects and resistance to metronidazole have motivated the search for new antiamoebic agents against Entamoeba histolytica. Control of amoeba growth may be achieved by inhibiting the function of the glycolytic enzyme and pyruvate phosphate dikinase (PPDK). In this study, we screened 10 compounds using an in vitro PPDK enzyme assay. These compounds were selected from a virtual screening of compounds in the National Cancer Institute database. The antiamoebic activity of the selected compounds was also evaluated by determining minimal inhibitory concentrations (MICs) and IC50 values using the nitro-blue tetrazolium reduction assay. Seven of the 10 compounds showed inhibitory activities against the ATP/Pi binding site of the ATP-grasp domain. Two compounds, NSC349156 (pancratistatin) and NSC228137 (7-ethoxy-4-[4-methylphenyl] sulfonyl-3-oxido-2, 1, 3-benzoxadiazol-3-ium), exhibited inhibitory effects on the growth of E. histolytica trophozoites with MIC values of 25 and 50 μM, and IC50 values of 14 and 20.7 μM, respectively.
-
-
-
Prevalence of Strongyloides stercoralis and Other Intestinal Parasite Infections in School Children in a Rural Area of Angola: A Cross-Sectional Study
Available online: 31 July 2017More LessStrongyloides stercoralis is widely distributed in the tropics and subtropics. The aim of this study was to determine the prevalence of S. stercoralis and other intestinal parasites and identify the risk factors for infection with S. stercoralis in a rural area of Angola. A cross-sectional study was conducted in school-age children (SAC) in Cubal, Angola. A questionnaire collecting clinical and epidemiological variables was used, and two stool samples were collected. A concentration technique (Ritchie) and a technique for detection of larvae migration (Baermann) were performed. Of 230 SAC, 56.1% were female and the mean age was 9.3 years (SD 2.45). Severe malnutrition, according to body mass index (BMI)-for-age, was observed in 20.4% of the SAC, and anemia was found in 59.6%. Strongyloides stercoralis was observed in 28 of the 230 (12.8%) SAC. Eggs of other helminths were observed in 51 (22.2%) students: Hymenolepis spp. in 27 students (11.7%), hookworm in 14 (6.1%), Schistosoma haematobium in four (1.7%), Enterobius vermicularis in four (1.7%), Ascaris lumbricoides in three (1.3%), Taenia spp. in two (0.9%), and Fasciola hepatica in one (0.4%). Protozoa were observed in 17 (7.4%) students. Detection of S. stercoralis was higher using the Baermann technique versus using formol-ether (11.3 vs. 3%). Overall prevalence of S. stercoralis in the school population of 16 studied schools in the municipal area of Cubal was greater than 10%. This fact must be considered when designing deworming mass campaigns. The use of specific tests in larvae detection is needed to avoid overlooking this parasite.
-
-
-
Water, Sanitation, and Hygiene in Rural Health-Care Facilities: A Cross-Sectional Study in Ethiopia, Kenya, Mozambique, Rwanda, Uganda, and Zambia
Authors: Amy Guo, J. Michael Bowling, Jamie Bartram and Georgia KayserAvailable online: 31 July 2017More LessSafe and sufficient water, sanitation, and hygiene (WaSH) prevent the spread of disease in health-care facilities (HCFs). Little research has been conducted on WaSH in HCF in sub-Saharan Africa. We carried out a cross-sectional study of WaSH in 1,318 randomly selected rural HCF (hospitals, health centers, health posts, and clinics) in regions throughout Ethiopia, Kenya, Mozambique, Rwanda, Uganda, and Zambia. Methods included questionnaires with head doctors and nurses to document WaSH access, continuity, quality, quantity and reliability, and analysis of drinking water samples for Escherichia coli. We found that fewer than 50% of rural HCFs had access to improved water sources on premises, improved sanitation, and consistent access to water and soap for handwashing (Ethiopia [7%), Kenya [30%], Mozambique [29%], Rwanda [50%], Uganda [30%], and Zambia [21%]). Adequate hand hygiene reduces disease transmission and health-care-acquired infections, but fewer than 25% of HCF in each country reported that a combination of water, soap, and hand-drying materials were always available. Our research points to a lack of basic WaSH services in rural HCFs in regions of sub-Saharan Africa, which poses a threat to the health of patients and health-care workers in these settings.
-
-
-
Assessment of U.S. Pediatrician Knowledge of Toxocariasis
Available online: 31 July 2017More LessToxocariasis, one of a group of parasitic diseases known as neglected parasitic infections, is a disease caused by the larvae of two species of Toxocara roundworms, Toxocara canis, from dogs, and less commonly Toxocara cati, from cats. Although most infected individuals are asymptomatic, clinical manifestations may include fever, fatigue, coughing, wheezing, or abdominal pain (visceral toxocariasis) or vision loss, retina damage, or eye inflammation (ocular toxocariasis). To assess U.S. pediatrician knowledge of toxocariasis, we conducted an electronic survey of American Academy of Pediatrics members. Of the 2,684 respondents, 1,120 (47%) pediatricians correctly selected toxocariasis as the diagnosis in an unknown case presentation with findings typical for toxocariasis; overall 1,695 (85%) stated they were not confident that their knowledge of toxocariasis was current. This knowledge gap suggests a need for improved toxocariasis awareness and education for U.S. pediatricians, especially those caring for children at risk for infection.
-
-
-
Quality Testing of Artemisinin-Based Antimalarial Drugs in Myanmar
Authors: Suqin Guo, Myat Phone Kyaw, Lishan He, Myo Min, Xiangxue Ning, Wei Zhang, Baomin Wang and Liwang CuiAvailable online: 31 July 2017More LessArtemisinin-based combination therapies are the frontline treatment of Plasmodium falciparum malaria. The circulation of falsified and substandard artemisinin-based antimalarials in Southeast Asia has been a major predicament for the malaria elimination campaign. To provide an update of this situation, we purchased 153 artemisinin-containing antimalarials, as convenience samples, in private drug stores from different regions of Myanmar. The quality of these drugs in terms of their artemisinin derivative content was tested using specific dipsticks for these artemisinin derivatives, as point-of-care devices. A subset of these samples was further tested by high-performance liquid chromatography (HPLC). This survey identified that > 35% of the collected drugs were oral artesunate and artemether monotherapies. When tested with the dipsticks, all but one sample passed the assays, indicating that the detected artemisinin derivative content corresponded approximately to the labeled contents. However, one artesunate injection sample was found to contain no active ingredient at all by the dipstick assay and subsequent HPLC analysis. The continued circulation of oral monotherapies and the description, for the first time, of falsified parenteral artesunate provides a worrisome picture of the antimalarial drug quality in Myanmar during the malaria elimination phase, a situation that deserves more oversight from regulatory authorities.
-
-
-
Dengue Virus Serotypes 1 and 2 Responsible for Major Dengue Outbreaks in Nepal: Clinical, Laboratory, and Epidemiological Features
Available online: 31 July 2017More LessDengue virus (DENV) is expanding toward previously nonendemic areas. DENV has recently been introduced in Nepal with limited information. We report the clinical features and serotype distribution of DENV in Nepal during the major outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of central and western Nepal were investigated. Demographic, clinical, and laboratory parameters were recorded. Serum specimens were tested for DENV by IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%) patients from 12 districts with an estimated case fatality rate of 1.5%. DENV infection was more common in adults (87%) and urban settings (74%). We detected all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks (92%). Overall, 60% of all DENV infections were secondary and 17% were severe dengue; both being more frequent among the DENV-2 infections. Rash, bleeding, abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were significantly more common in severe dengue compared with nonsevere infections. We also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2), including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from southern plains. Differential clinical and laboratory features probably helps in clinical decisions. Multiple serotypes circulation and elevated secondary infections pose potential risk of severe outbreaks and deaths in the future. Therefore, a country with recent dengue introduction, like Nepal, urgently requires a systematic surveillance and appropriate control measures in place to respond any disastrous outbreaks.
-
-
-
Evaluation of Community-Directed Operation of Black Fly Traps for Entomological Surveillance of Onchocerca volvulus Transmission in the Madi-Mid North Focus of Onchocerciasis in Northern Uganda
Available online: 31 July 2017More LessEntomological measures of transmission are important metrics specified by the World Health Organization to document the suppression and interruption of transmission of Onchocerca volvulus, the causative agent of onchocerciasis. These metrics require testing of large numbers of vector black flies. Black fly collection has relied on human landing collections, which are inefficient and potentially hazardous. As the focus of the international community has shifted from onchocerciasis control to elimination, replacement of human landing collections has become a priority. The Esperanza window trap (EWT) has shown promise as an alternative method for collection of Simulium damnosum s.l., the primary vector of O. volvulus in Africa. Here, we report the results of a community-based trial of the EWT in northern Uganda. Traps operated by residents were compared with human landing collections in two communities over 5 months. Three traps, when operated by a single village resident, collected over four times as many S. damnosum as did the two-men collection team. No significant differences were noted among the bait formulations. The results suggest that EWTs may be effectively operated by community residents and that the trap represents a viable alternative to human landing collections for entomological surveillance of O. volvulus transmission.
-
-
-
Evaluating Human Sensory Perceptions and the Compartment Bag Test Assays as Proxies for the Presence and Concentration of Escherichia coli in Drinking Water in Western Kenya
Available online: 24 July 2017More LessWe compared the concentrations of Escherichia coli quantified with Colilert™ and the compartment bag test (CBT) in source water and household stored drinking water (SDW) in 35 households in western Kenya. We also investigated the associations of the perceptions of organoleptic properties and overall quality with ≥ 1 MPN/100 mL E. coli in SDW. Participants who rated the taste or smell of their SDW “< 5” on a 1 = “poor” to 5 = “excellent” Likert scale were 8.71 or 7.04 times more likely, respectively, to have ≥ 1 MPN/100 mL E. coli. Organoleptic properties are innate, albeit imperfect, indicators of fecal pollution in water. Within their shared quantification range, concentrations of E. coli enumerated with Colilert and CBT were similar and had a significant correlation coefficient, 0.896 (95% confidence interval = 0.691–1.101). The methods had moderate agreement within the World Health Organization’s health risk levels (Cohen’s Kappa coefficient = 0.640). In low-resource settings, CBT provides comparable assessments of E. coli concentrations to Colilert.
-
-
-
Generation and Characterization of Antinonstructural Protein 1 Monoclonal Antibodies and Development of Diagnostics for Dengue Virus Serotype 2
Available online: 24 July 2017More LessDengue virus (DENV) circulates in tropical and subtropical areas around the world, where it causes high morbidity and mortality. There is no effective treatment of infection, with supportive care being the only option. Furthermore, early detection and diagnosis are important to facilitate clinical decisions. In this study, seven monoclonal antibodies (mAbs) recognizing nonstructural protein 1 (NS1) of DENV were generated by hybridoma techniques. These antibodies can be divided into two groups: serotype-specific (DB6-1, DB12-3, and DB38-1) and nonspecific (consisting of antibodies DB16-1, DB20-6, DB29-1, and DB41-2). The B-cell epitopes of DB20-6 and DB29-1 were identified by phage display and site-directed mutagenesis, and its binding motif, WXXWGK, was revealed to correspond to amino acid residues 115–120 of the DENV-2 NS1 protein. A diagnostic platform, consisting of a serotype-specific capture antibody and a complex detection antibody, exhibited a detection limit of about 1 ng/mL, which is sufficient to detect NS1 in clinical serum samples from dengue patients. This diagnostic platform displayed better specificity and sensitivity than two examined commercial NS1 diagnostic platforms. In summary, our results indicate that these newly generated mAbs are suitable for detection of NS1 protein of DENV-2 in clinical samples.
-
-
-
Case Report: Successful Lung Transplantation from a Donor Seropositive for Trypanosoma cruzi Infection (Chagas Disease) to a Seronegative Recipient
Available online: 24 July 2017More LessThe increasing shortage of organs for transplantation has prompted transplant programs to investigate the use of extended criteria donors, such as those with transmissible infectious diseases. Successful cases of organ transplantation (mostly kidney and liver) from Trypanosoma cruzi seropositive donors to seronegative recipients have been reported. We present a case of lung transplantation from a donor serologically positive for Chagas disease to a seronegative recipient, and provide a review of the literature. Left single lung transplantation was performed in a 44-year-old Spanish woman presenting with interstitial lung disease in February 2016. The deceased donor was a Colombian immigrant living in Spain who was serologically positive for Chagas disease. Oral administration of 5 mg/kg/day benznidazole divided in three doses for 60 days was given for specific Chagas disease prophylaxis after transplantation. Periodic follow-up with serological reverse transcription polymerase chain reaction to detect T. cruzi DNA were performed until 6 months after the end of treatment. All results were negative, indicating that transmission of T. cruzi had not occurred. In a review of the literature, two similar cases were identified in Argentina and the United States. In both cases T. cruzi infection was detected posttransplant in the recipients, after which they were treated with benznidazole. The course of the patient described herein confirms that lungs from donors with chronic T. cruzi infection can be used successfully as allografts, and that posttransplant prophylaxis with benznidazole may reduce the probability of transmission of T. cruzi to the recipient.
-
-
-
Case Report: Old World Mucosal Leishmaniasis: Report of Five Imported Cases to the Hospital for Tropical Diseases, London, United Kingdom
Authors: Trupti A. Patel, Glenis K. Scadding, David E. Phillips and Diana N. LockwoodAvailable online: 24 July 2017More LessOld World species of Leishmania typically cause visceral and cutaneous leishmaniasis. Mucosal involvement is typically seen with infection by Leishmania species found in South America, usually after the healing of cutaneous leishmaniasis. We present five imported cases of mucosal leishmaniasis caused by Old World Mediterranean Leishmania infantum exclusively affecting the nasal mucosa or vocal cord. In only one case was there a recollection of a preceding cutaneous lesion compatible with cutaneous Leishmaniasis. Of significance was that four out of five cases were receiving local corticosteroids for chronic lung disorders and four were systemically immunosuppressed. This report highlights the importance of considering mucosal leishmaniasis in the differential diagnosis in those presenting with upper respiratory tract mucosal lesions with a relevant travel history to the Mediterranean and in whom malignancy has been excluded.
-
-
-
Assessment of Fecal Exposure Pathways in Low-Income Urban Neighborhoods in Accra, Ghana: Rationale, Design, Methods, and Key Findings of the SaniPath Study
Authors: Katharine Robb, Clair Null, Peter Teunis, Habib Yakubu, George Armah and Christine L. MoeAvailable online: 17 July 2017More LessRapid urbanization has contributed to an urban sanitation crisis in low-income countries. Residents in low-income, urban neighborhoods often have poor sanitation infrastructure and services and may experience frequent exposure to fecal contamination through a range of pathways. There are little data to prioritize strategies to decrease exposure to fecal contamination in these complex and highly contaminated environments, and public health priorities are rarely considered when planning urban sanitation investments. The SaniPath Study addresses this need by characterizing pathways of exposure to fecal contamination. Over a 16-month period, an in-depth, interdisciplinary exposure assessment was conducted in both public and private domains of four neighborhoods in Accra, Ghana. Microbiological analyses of environmental samples and behavioral data collection techniques were used to quantify fecal contamination in the environment and characterize the behaviors of adults and children associated with exposure to fecal contamination. Environmental samples (n = 1,855) were collected and analyzed for fecal indicators and enteric pathogens. A household survey with 800 respondents and over 500 hours of structured observation of young children were conducted. Approximately 25% of environmental samples were collected in conjunction with structured observations (n=441 samples). The study results highlight widespread and often high levels of fecal contamination in the public and private domains and food supply. The dominant fecal exposure pathway for young children in the household was through consumption of uncooked produce. The SaniPath Study provides critical information on exposure to fecal contamination in low-income, urban environments and ultimately can inform investments and policies to reduce these public health risks.
-
-
-
Continuous Excretion of Leptospira borgpetersenii Ballum in Mice Assessed by Viability Quantitative Polymerase Chain Reaction
Available online: 17 July 2017More LessRodents are the main reservoir animals of leptospirosis. In this study, we characterized and quantified the urinary excretion dynamics of Leptospira by Mus musculus infected with 2 × 108 virulent Leptospira borgpetersenii serogroup Ballum. Each micturition was collected separately in metabolic cages, at 12 time points from 7 to 117 days post-infection (dpi). We detected Leptospira in all urine samples collected (up to 8 per time point per mouse) proving that Leptospira excretion is continuous with ca. 90% live L. borgpetersenii Ballum, revealed by viability quantitative polymerase chain reaction. Microscopic visualization by Live/Dead fluorescence confirmed this high proportion of live bacteria and demonstrated that L. borgpetersenii Ballum are excreted, at least partly, as bacterial aggregates. We observed two distinct phases in the excretion dynamics, first an increase in Leptospira concentration shed in the urine between 7 and 63 dpi followed by a plateau phase from 63 dpi onward, with up to 3 × 107 Leptospira per mL of urine. These two phases seem to correspond to progressive colonization of renal tubules first, then to stable cell survival and maintenance in kidneys. Therefore, chronically infected adult mice are able to contaminate the environment via urine at each micturition event throughout their lifetime. Because Leptospira excretion reached its maximum 2 months after infection, older rodents have a greater risk of contaminating their surrounding environment.
-
-
-
Clinical Evidence of Acute Mesoamerican Nephropathy
Available online: 17 July 2017More LessMesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua. Physicians at a local hospital identified suspect cases and documented clinical/laboratory data, demographics, and medical histories. Over a 1-year period, physicians identified 255 mostly young (median 29 years), male (89.5%) patients with elevated creatinine or reduced creatinine clearance. Mean serum creatinine (2.0 ± 0.6 mg/dL) revealed a 2-fold increase from baseline, and half had stage 2 or 3 acute kidney injury. Leukocyturia (98.4%), leukocytosis (81.4%), and neutrophilia (86.2%) predominated. Nausea (59.4%), back pain (57.9%), fever (54.6%), vomiting (50.4%), headache (47.3%), and muscle weakness (45.0%) were common. A typical case of acute MeN presented with elevated (or increased ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline) creatinine, no hypertension or diabetes, leukocyturia, and at least two of fever, nausea or vomiting, back pain, muscle weakness, headache, or leukocytosis and/or neutrophilia. Rapid progression (median 90 days) to CKD was recorded in 8.5% of patients. This evidence can serve as the basis of a sensitive and urgently needed case definition for disease surveillance of early-stage, acute MeN.
-
-
-
Evaluation of Malaria Screening during Pregnancy with Rapid Diagnostic Tests Performed by Community Health Workers in Burkina Faso
Available online: 10 July 2017More LessOne of the current strategies to prevent malaria in pregnancy is intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). However, in order for pregnant women to receive an adequate number of SP doses, they should attend a health facility on a regular basis. In addition, SP resistance may decrease IPTp-SP efficacy. New or additional interventions for preventing malaria during pregnancy are therefore warranted. Because it is known that community health workers (CHWs) can diagnose and treat malaria in children, in this study screening and treatment of malaria in pregnancy by CHWs was evaluated as an addition to the regular IPTp-SP program. CHWs used rapid diagnostic tests (RDTs) for screening and artemether–lumefantrine was given in case of a positive RDT. Overall, CHWs were able to conduct RDTs with a sensitivity of 81.5% (95% confidence interval [CI] 67.9–90.2) and high specificity of 92.1% (95% CI 89.9–93.9) compared with microscopy. After a positive RDT, 79.1% of women received artemether–lumefantrine. When treatment was not given, this was largely due to the woman being already under treatment. Almost all treated women finished the full course of artemether–lumefantrine (96.4%). In conclusion, CHWs are capable of performing RDTs with high specificity and acceptable sensitivity, the latter being dependent on the limit of detection of RDTs. Furthermore, CHWs showed excellent adherence to test results and treatment guidelines, suggesting they can be deployed for screen and treat approaches of malaria in pregnancy.
-
-
-
Risk Factors for Severe Infection, Hospitalization, and Prolonged Antimicrobial Therapy in Patients with Babesiosis
Available online: 10 July 2017More LessBabesiosis is an emerging tick-borne disease transmitted by the hard tick Ixodes scapularis, which also transmits Lyme disease. Better gradation of prognostic indicators are needed to determine which patients may develop serious complications requiring hospitalization, and to provide early guidance on appropriate therapy. In this study, we evaluated 128 patients with smear or real time polymerase chain reaction-confirmed Babesia microti infections over a period of 16 years. Patients with asplenia or immunocompromising conditions were more likely to have severe infection (P < 0.01), require hospitalization (P < 0.01), or receive prolonged courses of antimicrobials (P < 0.01). Nausea or vomiting (P < 0.01) and diarrhea (P < 0.01) along with hyperbilirubinemia (P < 0.01) were predictive of severe infection, hospitalization, and prolonged antimicrobial therapy. Patients with concurrent Lyme disease were less likely to require hospitalization and had similar severity of disease and length of antibiotic treatment compared with those without Lyme disease.
-
-
-
Capacity and Utilization of Blood Culture in Two Referral Hospitals in Indonesia and Thailand
Available online: 10 July 2017More LessIt is generally recommended that sepsis patients should have at least two blood cultures obtained before antimicrobial therapy. From 1995 to 2015, the number of blood cultures taken each year in a 1,100-bed public referral hospital in Ubon Ratchathani northeast Thailand rose from 5,235 to 56,719, whereas the number received in an 840-bed referral public hospital in south Sulawesi, Indonesia, in 2015 was 2,779. The proportion of patients sampled for blood cultures out of all inpatients in south Sulawesi in 2015 (9%; 2,779/30,593) was lower than that in Ubon Ratchathani in 2003 (13%; 8,707/66,515), at a time when health expenditure per capita in the two countries was comparable. Under-use of bacterial cultures may lead to an underestimate and underreporting of the incidence of antimicrobial-resistant infections. Raising capacity and utilization of clinical microbiology laboratories in developing countries, at least at sentinel hospitals, to monitor the antimicrobial resistance situation should be prioritized.
-
-
-
Lack of Geospatial Population Structure Yet Significant Linkage Disequilibrium in the Reservoir of Plasmodium falciparum in Bongo District, Ghana
Available online: 03 July 2017More LessMalaria control in West Africa is impeded by the large reservoir of chronic asymptomatic Plasmodium falciparum infections in the human population. This study aimed to assess the extent of diversity in the P. falciparum reservoir in Bongo District (BD), Ghana, at the end of the dry season, the lowest point in malaria transmission over the course of the year. Analysis of the variation in 12 microsatellite loci was completed for 200 P. falciparum isolates collected from a cross-sectional survey of residents of all ages from two catchment areas in BD. Analysis of the multilocus haplotypes showed high levels of genetic diversity (H e = 0.74), no population differentiation yet significant linkage disequilibrium (LD) (I S A = 0.0127, P = 0.006) in BD. Multilocus LD was significant between and within catchment areas even though every haplotype in the population was unique and the majority of individuals (84.0%) harbored multiple-clone infections. The linkage structure among multilocus haplotypes was not associated with sampling location. These data provide the first study with deep sampling of the P. falciparum reservoir in an area of seasonal malaria transmission in West Africa. The co-occurrence of high multiplicity of infection (multiple-clone infections) with significant multilocus LD is surprising given the likelihood of high recombination rates in BD. The results suggest that the linkage structure among multilocus haplotypes has not been shaped by geographic separation of parasite populations. Furthermore, the observed LD levels provide a baseline population genetic metric with putatively neutral markers to evaluate the effects of seasonality and malaria control efforts in BD.
-
-
-
Occult Amoebic Liver Abscess as Cause of Extensive Inferior Vena Cava and Hepatic Vein Thrombosis
Authors: Leslie Martin, Nishigandha Burute, Ehsan Haider, Pablo E. Serrano, Timothy O’Shea and Deborah SiegalAvailable online: 03 July 2017More LessThe most common extraintestinal complication of Entamoeba histolytica is amoebic liver abscess (ALA). Hepatic vein and inferior vena cava (IVC) thrombosis are rare but well-documented complications of ALA, typically attributed to mechanical compression and inflammation associated with a large abscess. We present a case of a previously healthy 43-year-old Canadian man presenting with constitutional symptoms and right upper quadrant abdominal pain. He was found to have thrombophlebitis of the IVC, accessory right hepatic vein, and bilateral iliac veins. Extensive investigations for thrombophilia were negative. Magnetic resonance imaging of the liver demonstrated a 3.2-cm focal area of parenchymal abnormality that was reported as presumptive hepatocellular carcinoma, and a 1.9-cm lesion in the caudate lobe with diffusion restriction and peripheral rim enhancement. Despite multiple biopsy attempts, a histopathological diagnosis was not achieved. Abdominal pain and fever 4 months later prompted repeat ultrasound demonstrating a 10.4- × 12.0-cm rim-enhancing fluid attenuation lesion felt to represent a liver abscess. Thick dark “chocolate brown” drainage from the lesion and positive serology for E. histolytica confirmed the diagnosis of ALA acquired from a previous trip to Cuba. The patient was started on treatment with metronidazole and paromomycin and repeat abdominal ultrasound demonstrated resolution of the abscess. This case is the first to demonstrate extensive IVC thrombosis secondary to a relatively small occult ALA and emphasizes the thrombogenic potential of ALA. Amoebic infection should be considered as a rare cause of IVC thrombosis in the correct clinical context.
-
-
-
Fatal Leptospira spp./Zika Virus Coinfection—Puerto Rico, 2016
Available online: 26 June 2017More LessCoinfection with pathogens that cause acute febrile illness (AFI) can complicate patient diagnosis and management. This report describes a fatal case of Leptospira spp./Zika virus (ZIKV) coinfection in Puerto Rico. The patient presented with a 5-day history of AFI; reported behavioral risk factors for leptospirosis; was diagnosed with possible leptospirosis, dengue, chikungunya, or ZIKV disease; and received appropriate treatment of leptospirosis and dengue. Following a 3-day hospitalization, the patient died due to acute gastrointestinal hemorrhage, and kidney and liver failure. Serologic diagnostic testing for leptospirosis and ZIKV disease was both negative; however, molecular diagnostic testing performed postmortem was positive for detection of Leptospira spp. and ZIKV nucleic acid. This case demonstrates the need for continued clinical awareness of leptospirosis in areas experiencing outbreaks of pathogens that cause AFI and the need for evaluation of coinfection with AFI-causing pathogens as a risk factor for increased severity of disease.
-
-
-
Multidrug-Resistant Microorganisms Colonizing Lower Extremity Wounds in Patients in a Tertiary Care Hospital, Lima, Peru
Available online: 19 June 2017More LessMultidrug-resistant organism (MDRO) infections cause high morbidity and mortality, and high costs to patients and hospitals. The study aims were to determine the frequency of MDRO colonization and associated factors in patients with lower-extremity wounds with colonization. A cross-sectional study was designed during November 2015 to July 2016 in a tertiary care hospital in Lima, Peru. A wound swab was obtained for culture and susceptibility testing. MDRO colonization was defined if the culture grew with methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and/or extended spectrum beta-lactamase (ESBL) microorganisms. The frequency of MDRO wound colonization was 26.8% among the 97 patients enrolled. The most frequent MDRO obtained was ESBL-producing Escherichia coli, which was significantly more frequent in chronic wounds versus acute wounds (17.2% versus 0%, P < 0.05). Infection control measures should be implemented when patients with chronic lower-extremity wounds are admitted.
-
-
-
Diagnostic Validation of the RealStar® Zika Virus Reverse Transcription Polymerase Chain Reaction Kit for Detection of Zika Virus RNA in Urine and Serum Specimens
Authors: Stephan Ölschläger, Antoine Enfissi, Mareen Zaruba, Mirdad Kazanji and Dominique RoussetAvailable online: 19 June 2017More LessWith the Zika virus outbreak in South America starting in 2015 and its potential to cause malformation of the fetus in infected women, the need for diagnostic methods became obvious. Until now, only limited data are available on the diagnostic performance of commercial kits. Here, we present data comparing the RealStar® Zika Virus RT-PCR Kit 1.0 for detection of Zika virus from 208 serum and urine samples collected in French Guiana with a reference method. Of these, 114 samples tested positive with the RealStar Kit and 111 with the reference method.
-
-
-
Ocular Gnathostomiasis—Update of Earlier Survey
Available online: 12 June 2017More LessOcular gnathostomiasis is rather a rare food-borne zoonosis caused by infection with the larvae of several species of genus Gnathostoma and is a representative ocular larva migrans syndrome. In our previous literature survey, we found 73 cases of ocular gnathostomiasis reported up to and including 2009, though additional sporadic cases have been reported in Asia and the Americas since that report. Here, we review 10 additional cases reported since 2010, and also update current findings regarding epidemiological and clinical features in affected patients.
-
-
-
Case Report: Disseminated Shewanella algae Infection with Meningoencephalitis in a Traveler Secondary to Marine Injury in Madagascar
Available online: 12 June 2017More LessMarine microorganisms such as Shewanella spp., Vibrio spp., and Aeromonas spp. can cause sepsis secondary to a wound infection in the context of swimming. These microorganisms are most often susceptible to fluoroquinolones. Here, we report a unique case of Shewanella algae bacteremia associated with meningoencephalitis and disseminated via hematogenous spread secondary to a skin injury. The patient suffered the injury while swimming in saline water during a cruise holiday in Madagascar, and she was initially treated with amoxicillin. The neurological evolution was unsatisfactory. Better knowledge of such infections (and especially of the context in which they occur), as well as greater familiarity with the susceptibility profile of different marine microorganisms would have allowed health professionals to provide presumptive microbiological diagnosis and effective treatment earlier.
-
-
-
Rabies in Myanmar: Prevalent, Preventable but not Prioritized
Authors: Thet Thet Mu, Aye Aye Sein, Chit Soe, Nan Phyu Phyu Aung, Tint Tint Kyi and Josh HansonAvailable online: 12 June 2017More LessDespite the availability of proven measures to prevent the disease, rabies now kills more people in Myanmar than malaria. Although there are challenges in controlling rabies in such a large and culturally diverse country, Myanmar’s successful National Malaria Control Program demonstrates what can be achieved with sufficient political, financial, and scientific commitment. Presently, however, Myanmar lacks a comparable program to coordinate the multifaceted approach that is necessary to control rabies. The national government has invested heavily in improving access to postexposure prophylaxis, but there should also be an emphasis on other, more cost-effective strategies, particularly mass canine vaccination, which has been an essential component of successful rabies elimination programs in other countries. Continued health system strengthening is also required to improve primary health care, whereas decentralization of laboratory diagnostic services is needed to facilitate more timely, rational, and cost-effective use of postexposure prophylaxis.
-
-
-
Estimating the Added Utility of Highly Sensitive Histidine-Rich Protein 2 Detection in Outpatient Clinics in Sub-Saharan Africa
Available online: 12 June 2017More LessMost malaria testing is by rapid diagnostic tests (RDTs) that detect Plasmodium falciparum histidine-rich protein 2 (HRP2). Recently, several RDT manufacturers have developed highly sensitive RDTs (hsRDTs), promising a limit of detection (LOD) orders of magnitude lower than conventional RDTs. To model the added utility of hsRDTs, HRP2 concentration in Angolan outpatients was measured quantitatively using an ultrasensitive bead-based assay. The distribution of HRP2 concentration was bimodal in both afebrile and febrile patients. The conventional RDT was able to detect 81% of all HRP2-positive febrile patients and 52–77% of HRP2-positive afebrile patients. The added utility of hsRDTs was estimated to be greater in afebrile patients, where an hsRDT with a LOD of 200 pg/mL would detect an additional 50–60% of HRP2-positive persons compared with a conventional RDT with a LOD of 3,000 pg/mL. In febrile patients, the hsRDT would detect an additional 10–20% of cases. Conventional RDTs already capture the vast majority of symptomatic HRP2-positive individuals, and hsRDTs would have to reach a sufficiently low LOD approaching 200 pg/mL to provide added utility in identifying HRP2-positive, asymptomatic individuals.
-
-
-
Assessing the Contribution of Malaria Vector Control and Other Maternal and Child Health Interventions in Reducing All-Cause Under-Five Mortality in Zambia
Available online: 15 February 2016More LessUnder-five mortality in Zambia has declined since 1990, with reductions accelerating after 2000. Zambia's scale-up of malaria control is viewed as the driver of these gains, but past studies have not fully accounted for other potential factors. This study sought to systematically evaluate the impact of malaria vector control on under-five mortality. Using a mixed-effects regression model, we quantified the relationship between malaria vector control, other priority health interventions, and socioeconomic indicators and district-level under-five mortality trends from 1990 to 2010. We then conducted counterfactual analyses to estimate under-five mortality in the absence of scaling up malaria vector control. Throughout Zambia, increased malaria vector control coverage coincided with scaling up three other interventions: the pentavalent vaccine, exclusive breast-feeding, and prevention of mother-to-child transmission of HIV services. This simultaneous scale-up made statistically isolating intervention-specific impact infeasible. Instead, in combination, these interventions jointly accelerated declines in under-five mortality by 11% between 2000 and 2010. Zambia's scale-up of multiple interventions is notable, yet our findings highlight challenges in quantifying program-specific impact without better health data and information systems. As countries aim to further improve health outcomes, there is even greater need—and opportunity—to strengthen routine data systems and to develop more rigorous evaluation strategies.
-