A Smartphone App for Real-Time Assessment of Malaria Prophylaxis Adverse Events.

Background: Growth of international travel to malarial areas over the last decades has contributed to more travelers taking malaria prophylaxis. Travel-related symptoms may be wrongly attributed to malaria prophylaxis and hinder compliance. Here, we aimed to assess the frequency of real-time reporting of symptoms by travelers following malaria prophylaxis using a smartphone app. Method: Adult international travelers included in this single-center study (Barcelona, Spain) used the smartphone Trip Doctor® app developed by our group for real-time tracking of symptoms and adherence to prophylaxis. Results: Six hundred four (n = 604) international travelers were included in the study; 74.3% (449) used the app daily, and for one-quarter of travelers, malaria prophylaxis was prescribed. Participants from the prophylaxis group traveled more to Africa (86.7% vs. 4.3%; p < 0.01) and to high travel medical risk countries (60.8% vs. 18%; p < 0.01) and reported more immunosuppression (30.8% vs. 23.1% p < 0.01). Regarding symptoms, no significant intergroup differences were observed, and no relationship was found between the total number of malarial pills taken and reported symptoms. Conclusions: In our cohort, the number of symptoms due to malaria prophylaxis was not significantly higher than in participants for whom prophylaxis was not prescribed, and the overall proportion of symptoms is higher compared with other studies.

[Pretravel medical consultation]. / Reisemedizinische Beratung.

Many patients seek pretravel advice during routine consultations in a general practice so that basic knowledge of travel medicine is warranted. Using the example of trips to Bali, Peru and Tanzania, the most relevant topics of a pretravel consultation for these popular destinations are depicted. These include vaccinations, malaria prevention and recommendations on exposure prophylaxis for insect bites. Furthermore, special risk situations, such as travel to high altitudes or freshwater contact are discussed. In special cases, the advice of an expert in travel medicine is needed.

Suspected Mefloquine Toxicity in a Colony of Humboldt Penguins (Spheniscus humboldti).

Avian malaria is an important cause of mortality in captive penguins housed in outdoor exhibits. Mefloquine was used as a prophylaxis to treat a colony of 19 Humboldt penguins (Spheniscus humboldti) for avian malaria. A target dose of 30 mg/kg was obtained from anecdotal literature for sphenisciforms that was not based on pharmacokinetic or toxicity studies. For this reason, preliminary plasma concentrations of mefloquine were acquired after the first dose in some penguins to ensure that plasma concentrations reached human malaria prophylactic concentrations. Afterward, each penguin in the entire colony received mefloquine (26-31 mg/kg [125 mg in toto] PO q7d). Regurgitation was frequently observed starting after the fourth weekly administration. Plasma concentrations of mefloquine after the seventh dose showed elevated concentrations, and the treatment was immediately terminated. Eight penguins died during and after the treatment period. The first fatality occurred after the fifth weekly administration, and 7 birds died within 7-52 days after the seventh weekly administration. Three penguins were found dead without previous symptoms. The other five presented with marked lethargy, dyspnea, poor appetite, and vomiting, and all died despite medical care. The remaining 11 penguins of the colony survived without any supportive care; 5 did not exhibit any clinical disease signs, while the other 6 showed a mild apathy and decreased appetite. Mefloquine toxicity was highly suspected on the basis of clinical signs, the elevated mefloquine plasma concentrations, and no other underlying pathologic disease conditions identified through postmortem examinations. Nonspecific lesions, including pulmonary congestion and edema and hepatic perivascular hematopoiesis, were noted in the birds that died. Additionally, 1 case presented with myocarditis, and mycobacteria were observed within granulomas in the respiratory tract of 2 penguins. Caution is advised, and further studies are encouraged before administering mefloquine to penguins.

Questionnaire-Based Analysis of Adverse Events and Compliance with Malaria Chemoprophylaxis in Taiwan.

Malaria was eradicated in Taiwan in 1952; however, imported malaria cases are reported every year. The subtropical climate in Taiwan permits mosquito propagation and possible outbreaks of mosquito-borne diseases. The aim of this study was to investigate travelers' compliance and side effects of malaria prophylaxis to prevent a malaria outbreak in Taiwan. In this prospective study, we enrolled travelers who visited our travel clinic before going to malarious areas. A total of 161 questionnaires were collected and analyzed. Associations between the occurrence of side effects and compliance with antimalarial drugs were analyzed. Adjusted odds ratios were calculated after adjusting for potential risk factors in multiple logistic regression analysis. Of the 161 enrolled travelers, 58 (36.0%) reported side effects. Insomnia, somnolence, irritability, nausea, and anorexia were associated with poor compliance. Mefloquine was not associated with more neuropsychological side effects than doxycycline. Multiple logistic regression analysis showed that chemoprophylaxis compliance was affected by a younger age, visiting friends and relatives, visiting the travel clinic more than 1 week before the trip, and preferring to use the same antimalarial regimen on the next trip. Our findings could provide information to travelers besides labeled side effects to improve compliance with malaria prophylaxis and consequently help to prevent malaria outbreaks in Taiwan.

The Association between Iron and Folic Acid Supplementation and Malaria Prophylaxis and Linear Growth among Children and Neonatal Mortality in Sub-Saharan Africa-A Pooled Analysis.

The majority of research on linear growth among children is confined to South Asia and focuses on iron and folic acid (IFA) supplementation during pregnancy, without considering malaria prophylaxis. Similarly, there is limited evidence on the association of antenatal IFA supplementation and malaria prophylaxis with neonatal mortality in sub-Saharan Africa (SSA). This study aims to address these gaps. A pooled analysis of demographic and health survey (DHS) data from 19 countries in SSA was conducted to study the association between IFA supplementation and malaria prophylaxis and linear growth and neonatal mortality. Multivariate logistic and linear regression models were used. Malaria prophylaxis was significantly associated with stunting, height-for-age Z scores (HAZ scores), and neonatal mortality, but IFA supplementation was not associated with these outcomes. When women's height and body mass index (BMI) were introduced in the model, a significant association between combined malaria prophylaxis and IFA supplementation was found with HAZ scores only. For severe stunting, no significant association was found with either in the two models. In conclusion, this study underscores the importance of antenatal malaria prophylaxis as a potential intervention for nutrition outcomes (linear growth) and neonatal mortality, as well as the importance of coordinating efforts between malaria and the health and nutrition sectors to improve these outcomes in the countries of SSA.

Economic evaluation of postdischarge malaria chemoprevention in preschool children treated for severe anaemia in Malawi, Kenya, and Uganda: A cost-effectiveness analysis.

Background: Children hospitalised with severe anaemia in malaria-endemic areas are at a high risk of dying or being readmitted within six months of discharge. A trial in Kenya and Uganda showed that three months of postdischarge malaria chemoprevention (PDMC) with monthly dihydroartemisinin-piperaquine (DP) substantially reduced this risk. The World Health Organization recently included PDMC in its malaria chemoprevention guidelines. We conducted a cost-effectiveness analysis of community-based PDMC delivery (supplying all three PDMC-DP courses to caregivers at discharge to administer at home), facility-based PDMC delivery (monthly dispensing of PDMC-DP at the hospital), and the standard of care (no PDMC). Methods: We combined data from two recently completed trials; one placebo-controlled trial in Kenya and Uganda collecting efficacy data (May 6, 2016 until November 15, 2018; n=1049), and one delivery mechanism trial from Malawi collecting adherence data (March 24, 2016 until October 3, 2018; n=375). Cost data were collected alongside both trials. Three Markov decision models, one each for Malawi, Kenya, and Uganda, were used to compute incremental cost-effectiveness ratios expressed as costs per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were performed to account for uncertainty. Findings: Both PDMC strategies were cost-saving in each country, meaning less costly and more effective in increasing health-adjusted life expectancy than the standard of care. The estimated incremental cost savings for community-based PDMC compared to the standard of care were US$ 22·10 (Malawi), 38·52 (Kenya), and 26·23 (Uganda) per child treated. The incremental effectiveness gain using either PDMC strategy varied between 0·3 and 0·4 QALYs. Community-based PDMC was less costly and more effective than facility-based PDMC. These results remained robust in sensitivity analyses. Interpretation: PDMC under implementation conditions is cost-saving. Caregivers receiving PDMC at discharge is a cost-effective delivery strategy for implementation in malaria-endemic southeastern African settings. Funding: Research Council of Norway.

Forest malaria and prospects for anti-malarial chemoprophylaxis among forest goers: findings from a qualitative study in Thailand.

BACKGROUND: Across the Greater Mekong Subregion, malaria remains a dangerous infectious disease, particularly for people who visit forested areas where residual transmission continues. Because vector control measures offer incomplete protection to forest goers, chemoprophylaxis has been suggested as a potential supplementary measure for malaria prevention and control. To implement prophylaxis effectively, additional information is needed to understand forest goers' activities and their willingness to use malaria prevention measures, including prophylaxis, and how it could be delivered in communities. Drawing on in-depth interviews with forest goers and stakeholders, this article examines the potential acceptability and implementation challenges of malaria prophylaxis for forest goers in northeast Thailand. METHODS: In-depth interviews were conducted with forest goers (n = 11) and stakeholders (n = 16) including healthcare workers, community leaders, and policymakers. Interviews were audio-recorded, transcribed and coded using NVivo, employing an inductive and deductive approach, for thematic analysis. RESULTS: Forest goers were well aware of their (elevated) malaria risk and reported seeking care for malaria from local health care providers. Forest goers and community members have a close relationship with the forest but are not a homogenous group: their place and time-at-risk varied according to their activities and length of stay in the forest. Among stakeholders, the choice and cost of anti-malarial prophylactic regimen-its efficacy, length and complexity, number of tablets, potential side effects, and long-term impact on users-were key considerations for its feasibility. They also expressed concern about adherence to the preventive therapy and potential difficulty treating malaria patients with the same regimen. Prophylaxis was considered a low priority in areas with perceived accessible health system and approaching malaria elimination. CONCLUSIONS: In the context of multi-drug resistance, there are several considerations for implementing malaria prophylaxis: the need to target forest goers who are at-risk with a clear period of exposure, to ensure continued use of vector control measures and adherence to prophylactic anti-malarials, and to adopt an evidence-based approach to determine an appropriate regimen. Beyond addressing current intervention challenges and managing malaria incidence in low-transmission setting, it is crucial to keep malaria services available and accessible at the village level especially in areas home to highly mobile populations.

Review of the Current Landscape of the Potential of Nanotechnology for Future Malaria Diagnosis, Treatment, and Vaccination Strategies.

Malaria eradication has for decades been on the global health agenda, but the causative agents of the disease, several species of the protist parasite Plasmodium, have evolved mechanisms to evade vaccine-induced immunity and to rapidly acquire resistance against all drugs entering clinical use. Because classical antimalarial approaches have consistently failed, new strategies must be explored. One of these is nanomedicine, the application of manipulation and fabrication technology in the range of molecular dimensions between 1 and 100 nm, to the development of new medical solutions. Here we review the current state of the art in malaria diagnosis, prevention, and therapy and how nanotechnology is already having an incipient impact in improving them. In the second half of this review, the next generation of antimalarial drugs currently in the clinical pipeline is presented, with a definition of these drugs' target product profiles and an assessment of the potential role of nanotechnology in their development. Opinions extracted from interviews with experts in the fields of nanomedicine, clinical malaria, and the economic landscape of the disease are included to offer a wider scope of the current requirements to win the fight against malaria and of how nanoscience can contribute to achieve them.

Gut Microbiota in Military International Travelers with Doxycycline Malaria Prophylaxis: Towards the Risk of a Simpson Paradox in the Human Microbiome Field.

Dysbiosis, developed upon antibiotic administration, results in loss of diversity and shifts in the abundance of gut microbes. Doxycycline is a tetracycline antibiotic widely used for malaria prophylaxis in travelers. We prospectively studied changes in the fecal microbiota of 15 French soldiers after a 4-month mission to Mali with doxycycline malaria prophylaxis, compared to changes in the microbiota of 28 soldiers deployed to Iraq and Lebanon without doxycycline. Stool samples were collected with clinical data before and after missions, and 16S rRNA sequenced on MiSeq targeting the V3-V4 region. Doxycycline exposure resulted in increased alpha-biodiversity and no significant beta-dissimilarities. It led to expansion in Bacteroides, with a reduction in Bifidobacterium and Lactobacillus, as in the group deployed without doxycycline. Doxycycline did not alter the community structure and was specifically associated with a reduction in Escherichia and expression of Rothia. Differences in the microbiota existed at baseline between military units but not within the studied groups. This group-effect highlighted the risk of a Simpson paradox in microbiome studies.

Inequities in the use of sulphadoxine-pyrimethamine for malaria prophylaxis during pregnancy in Nigeria.

Background: Intermittent presumptive treatment in pregnancy (IPTp) of malaria using sulfadoxine-pyrimethamine (SP) was introduced in Nigeria in 2005 to reduce the burden of malaria in pregnancy. By 2013, 23% of reproductive aged women surveyed received SP for malaria prevention in their last pregnancy of the past 5 years. This paper highlights geographic and socio-economic variations and inequities in accessing and using SP for malaria prophylaxis in pregnancy in Nigeria, as well as client-related and service delivery determinants. Methods: Secondary data from 2013 Nigeria demographic and health survey (DHS) was used. Sample of 38,948 eligible women were selected for interview using stratified three-stage cluster design. Data obtained from the individual recode dataset was used for descriptive and logistic regression analysis of factors associated with SP use in pregnancy was performed. Independent variables were age, media exposure, region, place of residence, wealth index, place of antenatal care (ANC) attendance and number of visits. Results: Women in the upper three wealth quintiles were 1.33 - 1.80 times more likely to receive SP than the poorest (CI: 1.15-1.56; 1.41-1.97; 1.49-2.17). Women who received ANC from public health facilities were twice as likely (inverse of OR 0.68) to use SP in pregnancy than those who used private facilities (CI: 0.60-0.76). Those who attended at least 4 ANC visits were 1.46 times more likely to get SP prophylaxis (CI: 1.31-1.63). Using the unadjusted odds ratio, women residing in rural areas were 0.86 times less likely to use SP compared to those in urban areas. Conclusions: Inequities in access to and use of SP for malaria prophylaxis in pregnancy exist across sub-population groups in Nigeria. Targeted interventions on the least covered are needed to reduce existing inequities and scale-up IPTp of malaria.

A randomized controlled trial of azithromycin and sulphadoxine-pyrimethamine as prophylaxis against malaria in pregnancy among human immunodeficiency virus-positive women.

BACKGROUND: Malaria and human immunodeficiency virus (HIV) infections in pregnancy are important and major contributing factors to maternal morbidity and mortality in sub-Saharan Africa. Prevention of malaria in HIV-positive pregnant woman will reduce the burden of malaria-HIV comorbidity. The objective of this study was to compare effects and safety of azithromycin (AZ) with sulphadoxine-pyrimethamine (SP) for intermittent preventive therapy for malaria in HIV-positive pregnant women. METHODS: We performed a randomized, controlled, open-label pregnancy trial of 140 HIV-positive pregnant patients attending antenatal clinics at the University College Hospital and Adeoyo Maternity Teaching Hospital, Ibadan, Nigeria. Participants were enrolled from a gestational age of 16 weeks and randomized to receive AZ or SP. The primary outcome was peripheral parasitaemia at delivery. Secondary outcomes were drug tolerability, foetal outcome and birthweight. The χ2 test (or Fisher's exact test, as appropriate) and Student's t test were used in the per-protocol analysis. The level of statistical significance was p<0.05. RESULTS: A total of 123 participants (87.9%) completed the study: 60 participants received AZ and 63 received SP. The incidence of malaria parasitaemia at delivery in the AZ group was 6 (10.0%), compared with 7 (11.1%) in the SP group (relative risk 0.89 [95% confidence interval 0.28 to 2.82], p=0.84). Placental parasitization was demonstrated in 1 (1.6%) participant in the SP group compared with 3 (5.0%) in the AZ group (p=0.36). CONCLUSIONS: The findings suggest that AZ is comparable to SP in malaria prevention and safety in HIV-positive pregnant women.

Plasmodium ovale Infection After One Year Mefloquine Prophylaxis in A Young Indonesian Soldier: A Case Report.

Malaria chemoprevention using mefloquine has become the WHO standard regimen for military personnel who stay in the endemic area for an extended period of time. We reported a case of Plasmodium ovale infection in a young Indonesian Soldier following one year mefloquine prophylaxis 250 mg weekly. Typical fever and chills were experienced two weeks after returning from one year duty in Congo, West-Central Africa. The diagnosis of ovale malaria was made by peripheral blood smear, and 35/250 parasites in small microscopic view was found. Then, he recovered after dihydroartemisin and primaquine combination therapy. This was an unusual case of long-term prophylaxis failure since mefloquine has been recognized as the agent for malaria prevention, even multi-drug-resistance Plasmodium. Dormant stage of Plasmodium ovale, quinoline-resistance potential, and the efficacy of mefloquine itself are discussed as the cause of that phenomenon.

Tafenoquine and G6PD: a primer for clinicians.

BACKGROUND: Tafenoquine, an 8-aminoquinoline, is now indicated for causal prophylaxis against all human malarias and as radical curative (anti-relapse) treatment against Plasmodium vivax and Plasmodium ovale. As with other 8-aminoquinolines, tafenoquine causes hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (hemizygous males and homozygous females) and is contraindicated in this population. Those with intermediate G6PD activity (heterozygous females) are also at risk for hemolysis. Awareness of how to prescribe tafenoquine in relation to G6PD status is needed so it can be used safely. METHODS: A standard literature search was performed on varying combinations of the terms tafenoquine, Arakoda, Kodatef, Krintafel, Kozenis, primaquine, G6PD deficiency, malaria prophylaxis and radical cure. The data were gathered and interpreted to review how tafenoquine should be prescribed in consideration of the G6PD status of an individual and traveller. RESULTS: Tafenoquine should only be given to those with G6PD activity >70% of the local population median. Qualitative G6PD tests are sufficient for diagnosing G6PD deficiency in males. However, in females quantitative G6PD testing is necessary to differentiate deficient, intermediate and normal G6PD statuses. Testing for G6PD deficiency is mandatory before tafenoquine prescription. Measures can be taken to avoid tafenoquine administration to ineligible individuals (i.e. due to G6PD status, age, pregnancy and lactation). Primaquine is still necessary for some of these cases. This review provides actions that can be taken to diagnose and manage hemolysis when tafenoquine is given inadvertently to ineligible individuals. CONCLUSION: Attention to G6PD status is required for safe prescription of tafenoquine. A high index of suspicion is needed if hemolysis occurs. Clinicians should seek evidence-based information for the management and treatment of iatrogenicy hemolysis caused by 8-aminoquinolines.

The Role of Pharmacists in Travel Medicine in South Africa.

Worldwide, pharmacists, who are the most accessible health-care providers, are playing an ever increasing role in travel medicine, assisting travelers in taking the necessary precautions to ensure safe and healthy travel. This article looks at the situation in South Africa, and how pharmacists are performing these functions within the legal constraints of the Medicines and Related Substances Act 101 of 1965, which prevents pharmacists from prescribing many of the travel vaccines and medications. The scope of practice in community pharmacies increased since the successful down-scheduling of some of the antimalarials, allowing pharmacists to supply the many travelers who frequently travel to neighboring countries. As in many other countries, travel medicine in South Africa is currently thwart with products that are out of stock, and a number of temporary guidelines were put in place to deal with these. Ways to facilitate expanding the role of pharmacists in travel medicine in South Africa need to be further explored.

Preventing diseases in round-the-world travelers: a contemporary challenge for travel medicine advice

Abstract Providing advice for travelers embarking on long-term trips poses a challenge in travel medicine. A long duration of risk exposure is associated with underuse of protective measures and poor adherence to chemoprophylaxis, increasing the chances of acquiring infections. Recently, in our clinic, we observed an increase in the number of travelers undertaking round-the-world trips. These individuals are typically aged around 32 years and quit their jobs to embark on one-to-two-year journeys. Their destinations include countries in two or more continents, invariably Southeast Asia and Indonesia, and mostly involve land travel and visiting rural areas. Such trips involve flexible plans, increasing the challenge, especially with regard to malaria prophylaxis. Advising round-the-world travelers is time-consuming because of the amount of information that must be provided to the traveler. Advisors must develop strategies to commit the traveler to his/her own health, and verify their learnings on disease-prevention measures. Contacting the advisor after the appointment or during the trip can be helpful to clarify unclear instructions or diagnosis made and prescriptions given abroad. Infectious diseases are among the most frequent problems affecting travelers, many of which are preventable by vaccines, medicines, and precautionary measures. The dissemination of counterfeit medicines, particularly antibiotics and antimalarial medicines, emphasizes the need for travelers to carry medicines that they may possibly need on their trip. Additional advice on altitude, scuba diving, and other possible risks may also be given. Considering the difficulties in advising this group, we present a review of the main recommendations on advising these travelers.

Characteristics of health problems in returned overseas travelers at a tertiary teaching hospital in a suburban area in Japan.

Few studies have analyzed the characteristics of patients who develop physical disorders after overseas travel. We retrospectively reviewed the medical records of 183 patients who visited Nara Medical University Hospital from 2008 to 2016 because of physical problems after traveling abroad. The main travel destinations were Southeast Asia (n = 100), Africa (n = 27), and South Asia (n = 23). The main reasons for the travel were leisure (n = 96), business (n = 51), and volunteer work (n = 19). The most common final diagnosis was gastrointestinal disease (n = 72), followed by febrile disease (n = 59) and respiratory disease (n = 19). There were eight malaria cases, including one patient who was infected after <14 days of overseas travel. Additionally, 61 of 71 cases of travelers' diarrhea and 15 of 21 cases of dengue fever occurred after <14 days travel. 26 cases of vaccine preventable diseases, such as hepatitis A, typhoid fever, and influenza, were observed. Consequently, healthcare providers should notify Japanese overseas travelers that there is a non-negligible health risk inherent to short-term travel, while stressing on the importance of pre-travel medical consultation.

Long term health outcomes among Returned Peace Corps Volunteers after malaria prophylaxis, 1995-2014.

BACKGROUND: A primary reason for non-adherence to malaria chemoprophylaxis is fear of latent side effects. We examined latent effects of malaria chemoprophylaxis among Returned Peace Corps Volunteers (RPCVs). METHODS: During July 18-September 16, 2016, RPCVs who served during 1995-2014 with an e-mail address in Peace Corps' RPCV database were invited to take an internet-based survey on malaria prophylaxis and medical diagnoses. "Good adherence" meant taking prophylaxis "as prescribed" or "most of the time." Prevalence of diseases diagnosed after Peace Corps service was compared between users and nonusers of each antimalarial using log-binomial regression. RESULTS: Of 8931 participants (11% response rate), 5055 (57%) took chemoprophylaxis. Initial chemoprophylaxis was mefloquine 59%, chloroquine 13%, doxycycline 16%, atovaquone-proguanil 4%, and "other" 8%. Sixty percent reported good adherence. Mefloquine users had the best adherence (67% good adherence). Prevalences of most diseases were similar between exposed and unexposed groups. Certain psychiatric diagnoses were slightly more likely among mefloquine users (PR 1.14, 95% CI [1.04-1.25], P = 0.0048). When excluding those with prior psychiatric illness, there were no differences in psychiatric diagnosis rates. CONCLUSION: Malaria chemoprophylaxis use by Peace Corps Volunteers is safe. Avoiding mefloquine use in those with prior psychiatric illness can reduce psychiatric side effects.

Preparing for International Travel and Global Medical Care.

Thorough pretravel preparation and medical consultation can mitigate avoidable health and safety risks. A comprehensive pretravel medical consultation should include an individualized risk assessment, immunization review, and discussion of arthropod protective measures, malaria prophylaxis, traveler's diarrhea, and injury prevention. Travel with children and jet lag reduction require additional planning and prevention strategies; travel and evacuation insurance may prove essential when traveling to less resourced countries. Consideration should also be given to other high-risk travel scenarios, including the provision of health care overseas, adventure and extreme sports, water environments and diving, high altitude, and terrorism/unstable political situations.