The American Journal of Tropical Medicine and Hygiene - Current Issue

Routine incident malaria case data have become a pillar of malaria surveillance in sub-Saharan Africa. These data provide granular, timely information to track malaria burden. However, incidence data are sensitive to changes in care seeking rates, rates of testing of suspect cases, and reporting completeness. Based on a set of assumptions, we derived a simple algebraic formula to convert crude incidence rates to a corrected estimation of incidence, adjusting for biases in variable and suboptimal rates of care seeking, testing of suspect cases, and reporting completeness. We applied the correction to routine incidence data from Guinea and Mozambique, and aggregate data for sub-Saharan African countries from the World Malaria Report. We calculated continent-wide needs for malaria tests and treatments, assuming universal testing but current care seeking rates. Countries in southern and eastern Africa reporting recent increases in malaria incidence generally had lower overall corrected incidence than countries in Central and West Africa. Under current care seeking rates, the unmet need for malaria tests was estimated to be 160 million (M) (interquartile range [IQR]: 139–188) and for malaria treatments to be 37 M (IQR: 29–51). Maps of corrected incidence were more consistent with maps of community survey prevalence than was crude incidence in Guinea and Mozambique. Crude malaria incidence rates need to be interpreted in the context of suboptimal testing and care seeking rates, which vary over space and time. Adjusting for these factors can provide insight into the spatiotemporal trends of malaria burden.

Travelers are often at risk for both influenza-like illness (ILI) and malaria. Doxycycline is active against pathogens causing ILI and is used for malaria prophylaxis. We evaluated the risk factors for ILI, and whether the choice of malaria prophylaxis was associated with ILI. TravMil is a prospective observational study enrolling subjects presenting to military travel clinics. Influenza-like illness was defined as subjective fever with either a sore throat or cough. Characteristics of trip and use of malaria prophylaxis were analyzed to determine association with development of ILI. Poisson regression models with robust error variance were used to estimate relative risk (RR) of ILI. A total of 3,227 trips were enrolled: 62.1% male, median age of 39 years (interquartile range [IQR] 27,59), median travel duration 19 days (IQR 12, 49); 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean and Latin America. Military travel (46%) and vacation (40%) were most common reasons for travel. Among them, 20% took doxycycline, 50% other prophylaxis, and 30% took none; 8.7% developed ILI. Decreased RR of ILI was associated with doxycycline (RR 0.65 [0.43–0.99], P = 0.046) and military travel (RR 0.30 [0.21–0.43], P < 0.01). Increased risk of ILI was associated with female gender (RR 1.57 [1.24–1.98], P < 0.01), travel to Asia (RR 1.37 [1.08–1.75], P = 0.01), and cruises (RR 2.21 [1.73–2.83], P < 0.01). Use of doxycycline malaria prophylaxis is associated with a decreased risk of ILI. Possible reasons include anti-inflammatory or antimicrobial effects, or other unmeasured factors. With few strategies for decreasing ILI in travelers, these findings bear further investigation.

Saint Lucia at one time had levels of schistosomiasis prevalence and morbidity as high as many countries in Africa. However, as a result of control efforts and economic development, including more widespread access to sanitation and safe water, schistosomiasis on the island has practically disappeared. To evaluate the current status of schistosomiasis in Saint Lucia, we conducted a nationally representative school-based survey of 8–11-year-old children for prevalence of Schistosoma mansoni infections using circulating antigen and specific antibody detection methods. We also conducted a questionnaire about available water sources, sanitation, and contact with fresh water. The total population of 8–11-year-old children on Saint Lucia was 8,985; of these, 1,487 (16.5%) provided urine for antigen testing, 1,455 (16.2%) provided fingerstick blood for antibody testing, and 1,536 (17.1%) answered the questionnaire. Although a few children were initially low positives by antigen or antibody detection methods, none could be confirmed positive by follow-up testing. Most children reported access to clean water and sanitary facilities in or near their homes and 48% of the children reported contact with fresh water. Together, these data suggest that schistosomiasis transmission has been interrupted on Saint Lucia. Additional surveys of adults, snails, and a repeat survey among school-age children will be necessary to verify these findings. However, in the same way that research on Saint Lucia generated the data leading to use of mass drug administration for schistosomiasis control, the island may also provide the information needed for guidelines to verify interruption of schistosomiasis transmission.

Hepatosplenic schistosomiasis (HSS) complicates portal hypertension, leading to life-threatening variceal bleeding. Variceal bleeding is associated with increased portal vein diameter (PVD). Beta-blockers prevent variceal bleeding. It is unclear whether beta-blockers such as propranolol can reduce PVD in HSS. We aimed to explore the effect of propranolol on PVD in HSS. A longitudinal study was conducted at the University Teaching Hospital, Zambia, as an extension of a clinical trial of rifaximin undertaken to test the hypothesis that rifaximin could reduce bacterial translocation in HSS. We randomized 85 adults to either rifaximin and standard care, or propranolol-based standard care only for 42 days. We then followed up all the patients on propranolol up to day 180. We used ultrasound to measure PVD at baseline and day 180. The primary outcome was reduction in PVD. Beta-blockade and splenic size reduction were secondary outcomes. Portal vein diameter reduced after 180 days of propranolol therapy from median 12 mm (interquartile range (IQR): 11–14) to median 10 mm (IQR: 9–13) (P < 0.001). The pulse rate reduced from baseline median 70 beats/minute (IQR: 66–80) to 65 beats/minute (IQR: 60–70) by day 180 (P = 0.006). Hemoglobin levels improved from baseline median 8 g/dL (IQR: 6–11) to 12 g/dL (10–14) (P < 0.001). Splenic size remained unchanged. Propranolol led to the reduction in PVD over 180 days. This suggests that ultrasound could be useful in monitoring response and compliance to beta-blockers, especially in resource-constraint areas where portal hypertension measurement facilities are unavailable.

Human liver fluke infection caused by Opisthorchis viverrini increases the risk of cholangiocarcinoma (CCA) reported along the Mekong basin including Thailand, Lao People’s Democratic Republic (PDR), Cambodia, and Vietnam. The highest incidence of CCA has been reported in northeastern Thailand where liver fluke infection is prevalent. This study aimed to investigate the prevalence of O. viverrini infection in a northeastern-descendent community in rural Sa Kaeo Province, eastern Thailand, using stool examination and molecular technique. The Kato–Katz method was performed to determine eggs per gram (EPG) for infection intensity. Phosphate-buffered saline–ethyl acetate concentration was used to prepare specimens for polymerase chain reaction (PCR) and restriction fragment length polymorphism of the internal transcribed spacer 2 (ITS2) region of the ribosomal RNA. From 1,245 specimens, 105 (8.4%) samples were identified as Opisthorchis-like eggs from stool examination, and all positive specimens indicated light infection (< 1,000 EPG). From positive Opisthorchis-like egg samples, 55.2% (58/105) were identified as O. viverrini eggs from ITS2-PCR assay for which low infection intensity might result in a negative PCR result (44.8%). Using multiple logistic regression analysis, males were at 3.1 times higher risk of acquiring O. viverrini infection than females. From phylogenetic analysis, in eastern Thailand, nucleotide sequences of O. viverrini were grouped as a monoclade as those isolated from Greater Mekong, Vietnam, Myanmar, and west Siberia. The results revealed that the surveyed community is a low-grade endemic area of O. viverrini infection. Thus, data from this study can be used to improve health-promoting programs and activities to control the infection and its subsequent CCA.

We report the case of a 56-year-old woman with microfilaremic dirofilariasis due to Dirofilaria repens, which is a very rare condition in humans. Of note, just one of six large-volume blood samples of this patient was positive for microfilariae. Polymerase chain reaction (PCR) and sequencing of the parasite gene determined the geographic origin of the causative helminth. The patient was treated successfully with doxycycline. This drug was chosen because of the patient’s reluctance to the use of ivermectin and to provide an anthelmintic effect by targeting the bacterial endosymbiont Wolbachia present in most filarial species.

In the Bolivian Chaco, recent surveys documented a dramatic decrease in the prevalence of soil-transmitted helminth (STH) infections as compared with the 1980s after thirty years of preventive chemotherapy (PC). Concomitant immunological rearrangements are expected. Because nematode infections are associated with increased levels of circulating IgE and glycoprotein CD30 soluble form (sCD30), this study aims to evaluate changes in serological markers of T helper (Th)2-cells activity between 1987 (high STH prevalence) and 2013 (low STH prevalence) in rural communities in the Bolivian Chaco area. We collected 151 sera during two different surveys in 1987 (n = 65) and 2013 (n = 86) and measured the concentration of total IgE and sCD30 by immunoassays. We found a statistically significant age-independent decrease in the total IgE (P < 0.0001) and sCD30 (P < 0.0001) from 1987 to 2013. The significant decrease in serological Th2 markers (IgE and sCD30) between 1987 and 2013 is consistent with the drop in STH prevalence in this geographical area during the same period of time. Further studies might elucidate the clinical and epidemiological impact of these serological rearrangements

In tropical areas of developing countries, the interactions among parasitic diseases such as soil-transmitted helminths (STHs) and malaria, and glucose-6-phosphate dehydrogenase deficiency (G6PDd), are complex. Here, we investigated their interactions and impact on anemia in school students residing in a conflict zone of northeast Myanmar. A cross-sectional survey was conducted between July and December 2015 in two schools located along the China–Myanmar border. Stool samples from the schoolchildren were analyzed for STH infections, whereas finger-prick blood samples were analyzed for G6PDd, hemoglobin concentrations, and Plasmodium infections. Among 988 enrolled children, Plasmodium vivax, Plasmodium falciparum, hookworm, Ascaris lumbricoides, and Trichuris trichiura infections occurred in 3.3%, 0.8%, 31.5%, 1.2%, and 0.3%, respectively. Glucose-6-phosphate dehydrogenase deficiency was present in 16.9% of the children, and there was a very high prevalence of anemia (73%). Anthropometric measures performed on all children showed that 50% of the children were stunted and 25% wasted. Moderate to severe anemia was associated with STH infections, stunting, and wasting. In addition, children had increasing odds of anemia with increasing burden of infections. This study revealed a high prevalence of G6PDd, STHs, and anemia in schools located in a conflict zone. In areas where malnutrition and STH infections are rampant, testing for both glucose-6-phosphate dehydrogenase and anemia should be considered before treating vivax malaria with 8-aminoquinolines.

Chikungunya fever (CHIKF) is a major public health concern and is caused by chikungunya virus (CHIKV). In 2005, the virus was reintroduced into India, resulting in massive outbreaks in several parts of the country. During 2010 and 2016 outbreaks, we recruited 588 patients from a tertiary care hospital in New Delhi, India, during the acute phase of CHIKF; collected their blood and clinical data; and determined their arthralgic status 12 weeks post-onset of fever. We evaluated IgM/IgG CHIKV-binding antibodies and their neutralizing capacity, sequenced complete genomes of 21 CHIKV strains, and correlated mutations with patient sequelae status. We also performed infections in murine models using representative strains from each outbreak to evaluate differences in pathogenesis. Our screening and analysis revealed that patients of the 2016 outbreak developed earlier IgM and neutralizing antibody responses that were negatively correlated with sequelae, compared with 2010 patients. Mutations that correlated with human disease progression were also correlated with enhanced murine virulence and pathogenesis. Overall, our study suggests that the development of early neutralizing antibodies and sequence variation in clinical isolates are predictors of human sequelae.

A dengue outbreak occurred on Hawaii Island between September 2015 and March 2016. Entomological investigations were undertaken between December 2015 and February 2016 to determine which Aedes mosquito species were responsible for the outbreak. A total of 3,259 mosquitoes were collected using a combination of CDC autocidal gravid ovitraps, Biogents BG-Sentinel traps, and hand-nets; immature mosquitoes were collected during environmental surveys. The composition of species was Aedes albopictus (58%), Aedes aegypti (25%), Wyeomyia mitchelli (7%), Aedes vexans (5%), Culex quinquefasciatus (4%), and Aedes japonicus (1%). Adult mosquitoes were analyzed by real-time reverse transcription polymerase chain reaction (PCR) for the presence of dengue virus (DENV) RNA. Of the 185 pools of female mosquitoes tested, 15 containing Ae. albopictus were positive for the presence of DENV type 1 RNA. No virus was detected in pools of the remaining species. Phylogenetic analysis showed the virus strain belonged to genotype I and was closely related to strains that were circulating in the Pacific between 2008 and 2014. This is the first report of detection of DENV in Ae. albopictus from Hawaii.

Zika virus (ZIKV) has recently been confirmed as endemic in Indonesia, but no congenital anomalies (CA) related to ZIKV infection have been reported. We performed molecular and serological testing for ZIKV and other flaviviruses on cord serum and urine samples collected in October 2016 to April 2017 during a prospective, cross-sectional study of neonates in Jakarta, Indonesia. Of a total of 429 neonates, 53 had CA, including 14 with microcephaly. These 53, and 113 neonate controls without evidence of CA, were tested by ZIKV-specific real-time reverse transcription polymerase chain reaction (RT-PCR), pan-flavivirus RT-PCR, anti-ZIKV and anti-DENV IgM ELISA, and plaque reduction neutralization test. There was no evidence of ZIKV infection among neonates in either the CA or non-CA cohorts, except in three cases with low titers of anti-ZIKV neutralizing antibodies. Further routine evaluation throughout Indonesia of pregnant women and their newborns for exposure to ZIKV should be a high priority for determining risk.

Zika virus (ZIKV) caused a public health threat in the United States in 2016, leading to rapid development and implementation of blood screening assays for ZIKV RNA. Several ZIKV sequences from clinical cases have been reported, but none from asymptomatic/pre-symptomatic infections. We isolated and sequenced ZIKV from asymptomatic/pre-symptomatic blood donor (ABD-ZIKV) samples and compared with reported clinical sequences. Twelve ABD-ZIKV isolates were produced from 67 cultivated samples, and isolates were genetically similar among themselves. Most isolates shared mutations with the clinical isolate PRVABC59 2015, whereas two ABD-ZIKV isolates shared specific mutations with U.S. clinical isolates from 2016. The ABD-ZIKV strains clustered into two distinct subclades: one comprised mostly ABD-ZIKV from Puerto Rico, and another one comprised ABD-ZIKV from Florida and QTX-02 isolate (Puerto Rico). In this study, we showed the circulation of two slightly distinct virus strains among Puerto Rico blood donors, one of which was also reported in Florida.

The impact of HIV infection on the burden of gastrointestinal pathogens in Myanmar is poorly defined. Stools of 103 HIV-infected and 105 HIV-uninfected adult outpatients at a tertiary referral hospital in Yangon were examined microscopically. Stool antigen tests for Helicobacter pylori infection were positive in 63/103 (61%) HIV-infected and 61/105 (58%) HIV-uninfected patients (P = 0.65). Soil-transmitted helminth infections were much less common, occurring in 9/103 (9%) HIV-infected and 13/103 (13%) HIV-uninfected patients (P = 0.50). One HIV-uninfected patient had Giardia duodenalis, but there were no cases of Strongyloides stercoralis, Entamoeba histolytica, Capillaria philippinensis, Isospora, Cyclospora, or Schistosoma infection in the entire cohort. Despite the high prevalence of H. pylori, only 1/208 (0.5%) had ever received eradication, compared with 159/208 (76%) who had ever been dewormed. Helicobacter pylori appears to be an underappreciated pathogen in Myanmar. Its strong association with gastric cancer and peptic ulcer disease necessitates a more aggressive approach to its management.

In some areas of Argentina endemic for human T-lymphotropic virus type 1 (HTLV-1), tropical spastic paraparesis is frequent in subjects who lack antibodies against the virus; however, the relevance of this seronegative status in the country has not been investigated. In neighboring countries, HTLV-1 seronegative status has been described in patients with different diseases; however, data regarding features of seronegative HTLV-1 carriers are scarce. We investigated the seronegative status in 124 relatives of 28 HTLV-1 infected subjects from an endemic area in Northwest Argentina. Blood samples and clinical/epidemiological data were collected. Human T-lymphotropic virus type 1 infection was diagnosed by serology and long terminal repeat (LTR) sequence, env and tax gene detection. IgG anti-Tax HTLV-1 antibody, tax gene sequence, and DNA proviral load were also evaluated. Seventy-five percent of the 124 relatives were negative for HTLV-1/2 antibodies; 35.5% were also negative by molecular assays and 64.5% were negative for HTLV-1 LTR and env sequences, but positive for two sequences of HTLV-1 tax gene. Also, 35.7% of these subjects had IgG anti-Tax antibodies. The seronegative HTLV-1 status was significantly associated with male gender, youth, and sensory symptoms/autonomic nervous system dysfunction. High rates of seronegative symptomatic and asymptomatic HTLV-1 carriers in Argentina are described. The evidence highlights that HTLV-1 prevalence may be underestimated worldwide. Larger cohort studies are required to assess disease outcome in these seronegative subjects. Also, the findings emphasize the limitations of ongoing screening assays for diagnosis and blood safety. Therefore, algorithms for HTLV-1 diagnosis should include not only serological but also molecular assays.

There are an estimated 19.4 million sepsis cases every year, many of them in low-income countries. The newly adopted definition of sepsis uses Sequential Organ Failure Assessment Score (SOFA), a score which is not feasible in many low-resource settings. A simpler quick-SOFA (qSOFA) based solely on vital signs score has been devised for identification of suspected sepsis. This study aimed to determine in-hospital prevalence and outcomes of sepsis, as defined as suspected infection and a qSOFA score of 2 or more, in two hospitals in Malawi. The secondary aim was to evaluate qSOFA as a predictor of mortality. A cross-sectional study of adult in-patients in two hospitals in Malawi was conducted using prospectively collected single-day point-prevalence data and in-hospital follow-up. Of 1,135 participants, 81 (7.1%) had sepsis. Septic patients had a higher hospital mortality rate (17.5%) than non-septic infected patients (9.0%, p = 0.027, odds ratio 2.1 [1.1–4.3]), although the difference was not statistically significant after adjustment for baseline characteristics. For in-hospital mortality among patients with suspected infection, qSOFA ≥ 2 had a sensitivity of 31.8%, specificity of 82.1%, a positive predictive value of 17.5%, and a negative predictive value of 91.0%. In conclusion, sepsis is common and is associated with a high risk of death in admitted patients in hospitals in Malawi. In low-resource settings, qSOFA score that uses commonly available vital signs data may be a tool that could be used for identifying patients at risk—both for those with and without a suspected infection.

Management of fever is a key element of care for children with sickle cell disease (SCD). There exist few studies of current practices in managing fevers in SCD in low- and middle-income countries (LMICs) and malaria-endemic regions where SCD is prevalent. We surveyed medical providers in these settings to characterize current practices in infection prevention and fever management for children with SCD. We found wide variation in use of newborn screening for early diagnosis and infection prevention, pneumococcal vaccination, use of antibiotics and antimalarials, and route of antibiotic administration. Counter to established guidelines, 78% (95% CI: 59–100%) of respondents would consider using oral antibiotics for a febrile child with SCD. Only 17% (95% CI: 0–37%) would administer antibiotics to a well-appearing child with a positive malaria test. Availability of blood cultures did not affect duration of antibiotic course. Further study and standardization of fever management in SCD in LMICs are urgently needed.

The aim of this feasibility study was to investigate how a 3D printer could be put to its best use in a resource-limited healthcare setting. We have examined whether a 3D printer can contribute to making prostheses, braces, or splints for patients who underwent major limb amputation because of complex wounds, for example, due to burns and subsequent scarring, accidents, conflicts, or congenital abnormalities. During a 3-month period, we investigated the benefits of customized, 3D-printed arm prostheses, splints, and braces in Sierra Leone. Using a handheld 3D scanner and a 3D printer, patient-specific medical aids were designed, manufactured, and tested. Questionnaires regarding patient satisfaction and the functionality of the prostheses were used for a short-term follow-up. Four esthetic prostheses were designed: two prostheses of the hand, one of the forearm, and one of the entire arm. Follow-ups were conducted after 3 to 4 weeks to investigate the quality of the prostheses and to complete a patient questionnaire. Even though the prostheses primarily fulfill esthetic needs, they also exhibit some degree of functionality. In addition, four splints for hands and arms were made to prevent scar contractures after skin transplantation. Finally, a brace for a young boy with kyphoscoliosis was manufactured. The boy has accepted the brace and will be followed up in the months to come. Long-term follow-up is required to prove the sustainability of the 3D-printed brace and prosthetic arms. Further research into how to sustain and refine this project is underway.