The American Journal of Tropical Medicine and Hygiene - Online First

A comprehensive targeted intervention (CTI) was designed and deployed in the neighborhoods of cholera cases in the Kathmandu Valley with the intent of reducing rates among the neighbors of the case. This was a feasibility study to determine whether clinical centers, laboratories, and field teams were able to mount a rapid, community-based response to a case within 2 days of hospital admission. Daily line listings were requested from 15 participating hospitals during the monsoon season, and a single case initiated the CTI. A standard case definition was used: acute watery diarrhea, with or without vomiting, in a patient aged 1 year or older. Rapid diagnostic tests and bacterial culture were used for confirmation. The strategy included household investigation of cases; water testing; water, sanitation, and hygiene (WASH) intervention; and health education. A CTI coverage survey was conducted 8 months postintervention. From June to December of 2016, 169 cases of Vibrio cholerae O1 were confirmed by bacterial culture. Average time to culture result was 3 days. On average, the CTI Rapid Response Team (RRT) was able to visit households 1.7 days after the culture result was received from the hospital (3.9 days from hospital admission). Coverage of WASH and health behavior messaging campaigns were 30.2% in the target areas. Recipients of the intervention were more likely to have knowledge of cholera symptoms, treatment, and prevention than non-recipients. Although the RRT were able to investigate cases at the household within 2 days of a positive culture result, the study identified several constraints that limited a truly rapid response.

Malaria chemoprophylaxis has become increasingly prominent now that it is used for vulnerable populations in endemic regions in addition to nonimmune travelers to those regions. The objective would be a drug with > 95% efficacy and that is easily tolerated, including in children and pregnant women. For individuals who prefer weekly rather than daily drug administration, a further objective is a product that is administered weekly. The deficiencies of present agents are parasite resistance to chloroquine, neuropsychiatric liability of mefloquine, the need for daily dosing for atovaquone–proguanil, and daily dosing plus adverse reactions for doxycycline. A primaquine analogue, tafenoquine has a 17-day half-life and was approved for weekly prophylaxis in the United States and in Australia in 2018. Weekly tafenoquine was equal to mefloquine in efficacy in nonimmunes. The tafenoquine label contains a contraindication for preexisting psychosis, but not for the broad number of other neuropsychiatric disorders which are listed as contraindications in the mefloquine label. As an 8-aminoquinoline, tafenoquine is contraindicated for G6PD-deficient persons or in pregnancy if the fetus might be G6PD deficient. Other possible significant adverse reactions for tafenoquine are declines in hemoglobin levels reported in some G6PD-normal patients, asymptomatic elevations in methemoglobin, and minor psychiatric events. The lack of broad neuropsychiatric adverse reactions suggests that tafenoquine may have a role as the weekly prophylactic of choice for G6PD-normal persons.

Despite recent large-scale investments, malaria remains a major public health concern. Few studies have examined congenital malaria, defined as the presence of malaria parasitemia within the first 7 days of life, in endemic areas. This study aimed to determine the prevalence, to describe the clinical presentation, and to examine factors associated with congenital malaria in newborns aged up to 7 days attending Tororo General Hospital in Uganda. A total of 261 mother/baby pairs were recruited in this cross-sectional study. Giemsa-stained thick blood smears for malaria parasites and rapid malaria diagnostic tests were performed on capillary blood samples from all newborns and mothers, as well as on placental and cord samples from newborns delivered in the hospital. The prevalence of congenital malaria in the newborns was 16/261 (6.1%). No single clinical feature was associated with congenital malaria. However, there were associations between congenital malaria and maternal parasitemia (P < 0.001), gravidity of one (P = 0.03), maternal age < 19 years (P = 0.01), cord blood parasitemia (P = 0.01), and placental malaria (P = 0.02). In conclusion, congenital malaria is not rare in Uganda and there are no obvious clinical features associated with it in the newborn. Based on these findings, we recommend strengthening malaria prevention during pregnancy to reduce the occurrence of congenital malaria in newborns.

Multidrug-resistant Plasmodium falciparum malaria on the Cambodia–Thailand border is associated with working in forested areas. Beyond broad recognition of “forest-going” as a risk factor for malaria, little is known about different forest-going populations in this region. In Oddar Meanchey Province in northwestern Cambodia, qualitative ethnographic research was conducted to gain an in-depth understanding of how different populations, mobility and livelihood patterns, and activities within the forest intersect with potentiate malaria risk and impact on the effectiveness of malaria control and elimination strategies. We found that most forest-going in this area is associated with obtaining precious woods, particularly Siamese rosewood. In the past, at-risk populations included large groups of temporary migrants. As timber supplies have declined, so have these large migrant groups. However, groups of local residents continue to go to the forest and are staying for longer. Most forest-goers had experienced multiple episodes of malaria and were well informed about malaria risk. However, economic realities mean that local residents continue to pursue forest-based livelihoods. Severe constraints of available vector control methods mean that forest-goers have limited capacity to prevent vector exposure. As forest-goers access the forest using many different entry and exit points, border screening and treatment interventions will not be feasible. Once in the forest, groups often converge in the same areas; therefore, interventions targeting the mosquito population may have a potential role. Ultimately, a multisectoral approach as well as innovative and flexible malaria control strategies will be required if malaria elimination efforts are to be successful.

In this diagnostic accuracy study, we evaluated data from 135 febrile patients from Chiang Rai, to determine the optimal optical density (OD) cutoffs for an in-house scrub typhus IgM ELISA. Receiver operating characteristic curves were generated using a panel of reference assays, including an IgM immunofluorescence assay (IFA), PCR, in vitro isolation, presence of an eschar, or a combination of these. Altogether, 33 patients (24.4%) were diagnosed as having scrub typhus. Correlation between positivity by IFA and increasing OD values peaked at a cutoff of 2.0, whereas there was little association between positivity by culture or eschar with increasing ELISA cutoffs—cutoffs of 3.0 and 4.0 were demonstrated to be optimal for the total absorbance of the OD at dilutions 1:100, 1:400, 1:1,600, and 1:6,400, for admission and convalescent samples, respectively. The optimal cutoff at a 1:100 dilution was found to be between 1.85 and 2.22 for admission samples and convalescent-phase samples, respectively. Sensitivities for the cutoffs varied from 57.1% to 90.0% depending on the reference test and sample timing, whereas specificities ranged from 85.2% to 99.0%. We therefore recommend a cutoff of around 2.0, depending on the sensitivity and specificity desired in clinical or epidemiological settings. The results demonstrate the ELISA to be a valuable diagnostic tool, suitable for use in resource-limited endemic regions, especially when used in combination with other diagnostic modalities such as the presence of an eschar.

Hyperreactive malarial splenomegaly syndrome (HMSS) is a rare cause of splenomegaly in the Western world. Hyperreactive malarial splenomegaly syndrome is caused by an aberrant immunological response to chronic malaria exposure in endemic areas. Revised Fakunle’s criteria may be helpful for diagnosis: persistent splenomegaly (> 10 cm below the costal margin), increased anti-Plasmodium antibodies, increased IgM levels, exclusion of other causes of splenomegaly or malignancy, and a favorable response to antimalarial treatment. We describe the case of a 16-year-old patient, who recently arrived in Belgium from Guinea with a history of splenomegaly and B symptoms in whom HMSS diagnosis was achieved, thanks to the loop-mediated isothermal amplification method. To our knowledge, this is also the first described case treated by dihydroartemisinin/piperaquine.

Data regarding cardiac involvement in enteric fever among travelers are scarce. In this retrospective study, 59 patients were hospitalized with enteric fever during 2004–2017 and 28 had cardiac workups. Among those, four had evidence of cardiac involvement, including clinical myocarditis, electrocardiogram changes, or troponin elevation. Cardiac involvement was higher among patients infected with Salmonella Typhi than with Salmonella Paratyphi A (P = 0.08), with a significant relative risk of 6 (95% CI: 1.15–31.22, P = 0.03). Time from symptoms onset to effective treatment was longer for patients with cardiac involvement (13 versus 7.15 days, P < 0.05). It seems that cardiac involvement in enteric fever is not uncommon in travelers. Such involvement seems to be more common in patients with delay of effective treatment to the second week of illness. Although fatal or complicated cases are rare in travelers, the cardiac complication may be an important contributor to morbidity and mortality in this group.

Handwashing with soap reduces the transmission of diarrheal pathogens, but access to hand-washing facilities, water, and soap in humanitarian emergencies is limited. The SuperTowel® (ST) is a fabric treated with permanent antimicrobial bonding and has been designed as a soap alternative in emergency situations. The aim of this study was to test the efficacy of the ST as a hand-cleaning product. Two sets of laboratory tests, with 16 volunteers in each, were conducted to test the efficacy of different prototypes of the ST. Volunteers pre-contaminated their hands with nonpathogenic Escherichia coli. Comparisons were made between hand cleaning with the ST and handwashing with the reference soap, using a crossover design. Participants also completed a questionnaire about product perceptions. Three of the prototypes of the ST were more efficacious at removing E. coli from pre-contaminated hands than handwashing with soap (mean log10 reduction of 4.11 ± 0.47 for ST1, 3.84 ± 0.61 for ST2, and 3.71 ± 0.67 for ST3 versus 3.01 ± 0.63 for soap [P < 0.001, P = 0.002, and P = 0.005, respectively]). The ST prototypes used less water than handwashing with soap, were well accepted, and were considered preferable in communal settings. The ST has the potential to be a suitable complementary hand-cleaning product for humanitarian emergencies.

In 2016, a chikungunya virus (CHIKV) outbreak was reported in Mandera, Kenya. This was the first major CHIKV outbreak in the country since the global reemergence of this virus in Kenya in 2004. We collected samples and sequenced viral genomes from this outbreak. All Kenyan genomes contained two mutations, E1:K211E and E2:V264A, recently reported to have an association with increased infectivity, dissemination, and transmission in the Aedes aegypti vector. Phylogeographic inference of temporal and spatial virus relationships showed that this variant emerged within the East, Central, and South African lineage between 2005 and 2008, most probably in India. It was also in India where the first large outbreak caused by this virus appeared, in New Delhi, 2010. More importantly, our results also showed that this variant is no longer contained to India. We found it present in several major outbreaks, including the 2016 outbreaks in Pakistan and Kenya, and the 2017 outbreak in Bangladesh. Thus, this variant may have a capability of driving large CHIKV outbreaks in different regions of the world. Our results point to the importance of continued genomic-based surveillance and prompt urgent vector competence studies to assess the level of vector susceptibility and virus transmission, and the impact this might have on this variant’s epidemic potential and global spread.