Vivax Cases Research Articles

Optimizing G6PD testing for Plasmodium vivax case management: why sex, counseling, and community engagement matter.

Safe access to the most effective treatment options for Plasmodium vivaxmalaria are limited by the absence of accurate point-of-care testingto detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against P. vivaxhypnozoites. Until recently, only qualitative tests were available in most settings. These accurately identify patients with severe G6PD deficiency (mostly male) but not patients with intermediate G6PD deficiency (always female).This has led to and reinforced a gap in awareness in clinical practice of the risks and implications of G6PD deficiency in females-who, unlike males, can have a heterozygous genotype for G6PD.Increasing recognition of the need for radical cure of P. vivax, first for patients' health and then for malaria elimination, is driving the development of new point-of-care tests for G6PD deficiency and their accessibility to populations in low-resource settings. The availability of simple, affordable, and accurate point-of-care diagnostics for the precise classification of the three G6PD phenotypes can reduce sex-linked disparities by ensuring safe and effective malaria treatment, providing opportunities to develop supportive counseling to enhance understanding of genetic test results, and improving the detection of all G6PD deficiency phenotypes in newborns and their family members.

Updates on malaria incidence and profile in Malaysia from 2013 to 2017

BackgroundTo date, most of the recent publications on malaria in Malaysia were conducted in Sabah, East Malaysia focusing on the emergence of Plasmodium knowlesi. This analysis aims to describe the incidence, mortality and case fatality rate of malaria caused by all Plasmodium species between Peninsular Malaysia and East Malaysia (Sabah and Sarawak) over a 5-year period (2013–2017).MethodsThis is a secondary data review of all diagnosed and reported malaria confirmed cases notified to the Ministry of Health, Malaysia between January 2013 and December 2017.ResultsFrom 2013 to 2017, a total of 16,500 malaria cases were notified in Malaysia. The cases were mainly contributed from Sabah (7150; 43.3%) and Sarawak (5684; 34.4%). Majority of the patients were male (13,552; 82.1%). The most common age group in Peninsular Malaysia was 20 to 29 years (1286; 35.1%), while Sabah and Sarawak reported highest number of malaria cases in age group of 30 to 39 years (2776; 21.6%). The top two races with malaria in Sabah and Sarawak were Bumiputera Sabah (5613; 43.7%) and Bumiputera Sarawak (4512; 35.1%), whereas other ethnic group (1232; 33.6%) and Malays (1025; 28.0%) were the two most common races in Peninsular Malaysia. Plasmodium knowlesi was the commonest species in Sabah and Sarawak (9902; 77.1%), while there were more Plasmodium vivax cases (1548; 42.2%) in Peninsular Malaysia. The overall average incidence rate, mortality rate and case fatality rates for malaria from 2013 to 2017 in Malaysia were 0.106/1000, 0.030/100,000 and 0.27%, respectively. Sarawak reported the highest average incidence rate of 0.420/1000 population followed by Sabah (0.383/1000). Other states in Peninsular Malaysia reported below the national average incidence rate with less than 0.100/1000.ConclusionsThere were different trends and characteristics of notified malaria cases in Peninsular Malaysia and Sabah and Sarawak. They provide useful information to modify current prevention and control measures so that they are customised to the peculiarities of disease patterns in the two regions in order to successfully achieve the pre-elimination of human-only species in the near future.

Thrombocytopenia in malaria patients from an arid region of Western Rajasthan (India).

Context:The arid climate of Western Rajasthan is challenging for malaria transmission, with the number of cases correlating directly with the annual rainfall pattern. Moreover, >90% of the cases in this region are caused by Plasmodium vivax, which has recently been shown to cause a similar degree of thrombocytopenia as Plasmodium falciparum.Aims and Objectives:The aim of the study was to determine the degree of thrombocytopenia in malaria patients and its association with different species of malaria in this region with an unstable malaria epidemiology.Materials and Methods:This retrospective study was conducted on all microbiologically confirmed malaria patients with documented platelet counts from August 2017 to October 2018. Microbiological diagnosis was established by rapid diagnostic tests and peripheral blood film examination. Platelet counts were used to assess the degree of thrombocytopenia.Results:A total of 130 cases were included in the study, of which 118 (91%) were caused by P. vivax, while the rest 12 (9%) were caused by P. falciparum. Thrombocytopenia was present in 108 (83%) cases, and the mean values of platelets in thrombocytopenic patients with P. vivax and P. falciparum infection were 72600/μL and 48500/μL, respectively. Although P. falciparum infection was significantly associated with severe thrombocytopenia (odds ratio: 4.7, [95% confidence interval 1.3–16.1]), extremely low platelet counts (n = 5) warranting platelet transfusions (n = 1) were seen only in P. vivax cases. Only one patient required platelet transfusions in these patients suggesting good tolerance to thrombocytopenia.Conclusions:Avoiding unnecessary transfusions in febrile thrombocytopenic patients with an established malaria diagnosis can help in reducing transfusion-transmitted infections.

Management of uncomplicated malaria in private health facilities in North-West Ethiopia: a clinical audit of current practices

BackgroundMalaria is one of the leading public health problems in sub-Saharan Africa that contributes to significant patient morbidity and mortality. The aim of the study was to investigate adherence to malaria diagnosis and treatment guidelines by private health sector providers and compare their performance against the public private partnership (PPP) status.MethodsA facility-based retrospective clinical audit was conducted between October 2016 and January 2017 in 11 medium clinics in the West Gojjam zone of the Amhara Region, North-west Ethiopia. Data was extracted from patient medical records using pretested data abstraction forms. Descriptive statistics were employed to present the findings and adherence of health workers against the national and international standards were classified as ideal, acceptable, minor error and major error for both malaria diagnosis and treatment. A chi-square (X2) test was used to test for a statistically significant relationship after the data had been categorized using public private partnership status at P < 0.05.ResultsOne thousand six hundred fifty clinical files were audited. All malaria suspected patients were investigated either with microscopy or rapid diagnostics test (RDT) for parasitological confirmation. The proportion of malaria treated cases was 23.7% (391/1650). Of which 16.6% (274/1650) were uncomplicated, 3.69% (61 /1650) were severe and complicated and the rest 3.39% (56/1650) were clinical diagnosed malaria cases. And the malaria parasite positivity rate was 20.30% (335/1650). All malaria suspected patients were not investigated with ideal malaria diagnosis recommendations; only 19.4% (320/1650) were investigated with acceptable malaria diagnosis (public private partnership (PPP) 19.4%; 176/907; and non-public private partnership (NPPP) 19.38%; 144/743, X2 (1) = 0.0With regards to treatments of malaria cases, the majority 82.9% of Plasmodium vivax cases were managed with ideal recommended treatment (X2 (1) = 0.35, P = 0.55); among Plasmodium falciparum, mixed (Plasmodium falciparum and Plasmodium vivax).ConclusionThe clinical audit revealed that the majority of malaria patients had received minor error malaria diagnostic services. In addition, only one fifth of malaria patients had received ideal malaria treatment services. To understand the reasons for the low levels of malaria diagnosis and treatment adherence with national guidelines, a qualitative exploratory descriptive study is recommended.

Declining Burden of Plasmodium vivax in a Population in Northwestern Thailand from 1995 to 2016 before Comprehensive Primaquine Prescription for Radical Cure.

.All Plasmodium cases have declined over the last decade in northwestern Thailand along the Myanmar border. During this time, Plasmodium vivax has replaced Plasmodium falciparum as the dominant species. The decline in P. falciparum has been shadowed by a coincidental but delayed decline in P. vivax cases. This may be due to early detection and artemisinin-based therapy, species-specific diagnostics, and bed net usage all of which reduce malaria transmission but not P. vivax relapse. In the absence of widespread primaquine use for radical cure against P. vivax hypnozoites, the decline in P. vivax may be explained by decreased hypnozoite activation of P. vivax relapses triggered by P. falciparum. The observed trends in this region suggest a beneficial effect of decreased P. falciparum transmission on P. vivax incidence, but elimination of P. vivax in a timely manner likely requires radical cure.

Plasmodium vivax cerebral malaria in an adult patient in Sudan

BackgroundPlasmodium vivax infection is rising in sub-Saharan Africa, where Plasmodium falciparum is responsible for more than 90% of malaria cases. While P. vivax is identified as a major cause of severe and cerebral malaria in South east Asia, the Pacific and South America, most of the severe and cerebral cases in Africa were attributed to P. falciparum. Cases of severe malaria due to P. vivax are emerging in Africa. A few severe P. vivax cases were reported in Eastern Sudan and they were underestimated due to the lack of accurate diagnosis, low parasitaemia and seldom use of rapid diagnostic tests (RDTs).Case presentationA 60-year-old Sudanese male presented to the Al Kuwaiti hospital in the Sudan capital Khartoum. On admission, the patient was complaining of fever (measured temperature was 38 °C), sweating, chills, vomiting and confusion in the past 2 days prior to his admission. He rapidly deteriorated into a coma state within 48 h of the admission, with significant neck stiffness. He was admitted to the intensive care unit and was suspected of meningitis. Lumbar puncture was not performed since the patient was suffering from spinal cord disc. Brain CT scan was unremarkable. Several biochemical, haematological tests, and blood film for malaria were performed. The results of the laboratory tests were within the normal range except of mild elevation of the total white blood cell count and a significant decrease in the platelets count. Malaria parasites were seen in the blood film with high parasitaemia (quantified as 3 +++). The patient was diagnosed as P. vivax cerebral malaria based on the positive blood film and the amplification of P. vivax specific 499 bp amplicon using Plasmodium multi-species multiplex Polymerase Chain Reaction (PCR). The patient was treated with quinine 10 mg/kg body weight for 10 days followed by primaquine 15 mg/days PO for 2 weeks. The symptoms subsided within 48 h and the patients was cured and released from the hospital.ConclusionsPlasmodium vivax is an emerging cause of cerebral malaria in adults in Sudan and should be considered in the differential diagnosis of cerebral malaria for proper management of patients.

Characterization of Plasmodium vivax pvmdr1 Polymorphisms in Isolates from Mangaluru, India.

India accounts for approximately half of the global Plasmodium vivax cases, but information as to the presence of chloroquine (CQ) resistance is scarce. In an observational study in Mangaluru, south-western India, of 116 vivax malaria patients analyzed, 89.5% (102/114) had cleared parasitemia on days two or three of CQ treatment. Two remaining patients presented on days four and five without parasitemia. One hundred eight isolates of these 116 patients were successfully sequenced for pvmdr1 polymorphisms. Eight non-synonymous polymorphisms but no wild-type isolate were detected. Ten pvmdr1 haplotypes were observed with mutations T958M and F1076L occurring in all isolates, whereas the candidate CQ resistance marker Y976F was present in one isolate only. Pvmdr1 polymorphisms were not associated with early parasite clearance. The high proportion of early parasite clearance and the virtual absence of pvmdr1 Y976F and of sextuple pvmdr1 mutants suggest that CQ in the study area is still sufficiently effective. However, the abundance of pvmdr1 mutations in the local parasite population warrants monitoring.

Current Status of Parasite Infections in Indonesia: A Literature Review.

Indonesia and South Korea have become inseparable in various respects since the 2 countries established diplomatic relation in 1973. Indonesia is a tropical region that stretches across the equator, comprised of 5 main islands (Java, Kalimantan, Sumatra, Sulawesi, and Papua) and 4 archipelagoes (Riau, Bangka Belitung, Nusa Tenggara, and Maluku). As most population of Eastern Indonesia (Sulawesi, Papua and Nusa Tenggara & Maluku) live in poor areas, it is expected that there will be many parasites. Nevertheless, little is known about the status of parasites in Indonesia. This study examines the prevalences of malaria and lymphatic filaria, which are prevalent in Indonesia, as well as those of soil-transmitted-helminths (STH). As a result, the Plasmodium falciparum and P. vivax case loads are almost equal. The current prevalence of P. vivax is uniformly low (<5%) in all age groups and annual parasite incidence (API) showed decreasing tendency as 0.84 per 1,000 population in 2016. However, more than 65 million people still live in malaria epidemic regions. Lymphatic filariasis remains an important public health problem and 236 cities were classified as endemic areas in 514 cities/districts in 2017. It is difficult to ascertain the current prevalence rate of STH in Indonesia, although West Sumba and Southwest Sumba in East Nusa Tenggara reported prevalence rate of more than 20%. The study also considers the (sero) prevalences of other parasites identified in Indonesia. This report should be useful not only to parasitologists but also to travelers and people with business in Indonesia.

Climate drivers of malaria at its southern fringe in the Americas.

In this work we analyze potential environmental drivers of malaria cases in Northwestern Argentina. We inspect causal links between malaria and climatic variables by means of the convergent cross mapping technique, which provides a causality criterion from the theory of dynamic systems. Analysis is based on 12 years of weekly malaria P. vivax cases in Tartagal, Salta, Argentina—at the southern fringe of malaria incidence in the Americas—together with humidity and temperature time-series spanning the same period. Our results show that there are causal links between malaria cases and both maximum temperature, with a delay of five weeks, and minimum temperature, with delays of zero and twenty two weeks. Humidity is also a driver of malaria cases, with thirteen weeks delay between cause and effect. Furthermore we also determined the sign and strength of the effects. Temperature has always a positive non-linear effect on cases, with maximum temperature effects more pronounced above 25°C and minimum above 17°C, while effects of humidity are more intricate: maximum humidity above 85% has a negative effect, whereas minimum humidity has a positive effect on cases. These results might be signaling processes operating at short (below 5 weeks) and long (over 12 weeks) time delays, corresponding to effects related to parasite cycle and mosquito population dynamics respectively. The non-linearities found for the strength of the effect of temperature on malaria cases make warmer areas more prone to higher increases in the disease incidence. Moreover, our results indicate that an increase of extreme weather events could enhance the risks of malaria spreading and re-emergence beyond the current distribution. Both situations, warmer climate and increase of extreme events, will be remarkably increased by the end of the century in this hot spot of climate change.

Mapping the global endemicity and clinical burden of Plasmodium vivax, 2000–17: a spatial and temporal modelling study

SummaryBackgroundPlasmodium vivax exacts a significant toll on health worldwide, yet few efforts to date have quantified the extent and temporal trends of its global distribution. Given the challenges associated with the proper diagnosis and treatment of P vivax, national malaria programmes—particularly those pursuing malaria elimination strategies—require up to date assessments of P vivax endemicity and disease impact. This study presents the first global maps of P vivax clinical burden from 2000 to 2017.MethodsIn this spatial and temporal modelling study, we adjusted routine malariometric surveillance data for known biases and used socioeconomic indicators to generate time series of the clinical burden of P vivax. These data informed Bayesian geospatial models, which produced fine-scale predictions of P vivax clinical incidence and infection prevalence over time. Within sub-Saharan Africa, where routine surveillance for P vivax is not standard practice, we combined predicted surfaces of Plasmodium falciparum with country-specific ratios of P vivax to P falciparum. These results were combined with surveillance-based outputs outside of Africa to generate global maps.FindingsWe present the first high-resolution maps of P vivax burden. These results are combined with those for P falciparum (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The burden of P vivax malaria decreased by 41·6%, from 24·5 million cases (95% uncertainty interval 22·5–27·0) in 2000 to 14·3 million cases (13·7–15·0) in 2017. The Americas had a reduction of 56·8% (47·6–67·0) in total cases since 2000, while South-East Asia recorded declines of 50·5% (50·3–50·6) and the Western Pacific regions recorded declines of 51·3% (48·0–55·4). Europe achieved zero P vivax cases during the study period. Nonetheless, rates of decline have stalled in the past five years for many countries, with particular increases noted in regions affected by political and economic instability.InterpretationOur study highlights important spatial and temporal patterns in the clinical burden and prevalence of P vivax. Amid substantial progress worldwide, plateauing gains and areas of increased burden signal the potential for challenges that are greater than expected on the road to malaria elimination. These results support global monitoring systems and can inform the optimisation of diagnosis and treatment where P vivax has most impact.FundingBill & Melinda Gates Foundation and the Wellcome Trust.

Plasmodium knowlesi Malaria in Sabah, Malaysia, 2015-2017: Ongoing Increase in Incidence Despite Near-elimination of the Human-only Plasmodium Species.

BackgroundMalaysia aims to eliminate malaria by 2020. However, while cases of Plasmodium falciparum and Plasmodium vivax have decreased substantially, the incidence of zoonotic malaria from Plasmodium knowlesi continues to increase, presenting a major challenge to regional malaria control efforts. Here we report incidence of all Plasmodium species in Sabah, including zoonotic P. knowlesi, during 2015–2017.MethodsMicroscopy-based malaria notification data and polymerase chain reaction (PCR) results were obtained from the Sabah Department of Health and State Public Health Laboratory, respectively, from January 2015 to December 2017. From January 2016 this was complemented by a statewide prospective hospital surveillance study. Databases were matched, and species was determined by PCR, or microscopy if PCR was not available.ResultsA total of 3867 malaria cases were recorded between 2015 and 2017, with PCR performed in 93%. Using PCR results, and microscopy if PCR was unavailable, P. knowlesi accounted for 817 (80%), 677 (88%), and 2030 (98%) malaria cases in 2015, 2016, and 2017, respectively. P. falciparum accounted for 110 (11%), 45 (6%), and 23 (1%) cases and P. vivax accounted for 61 (6%), 17 (2%), and 8 (0.4%) cases, respectively. Of those with P. knowlesi, the median age was 35 (interquartile range: 24–47) years, and 85% were male.ConclusionsMalaysia is approaching elimination of the human-only Plasmodium species. However, the ongoing increase in P. knowlesi incidence presents a major challenge to malaria control and warrants increased focus on knowlesi-specific prevention activities. Wider molecular surveillance in surrounding countries is required.

Comparative evaluation of malaria antigen test and peripheral blood smears in diagnosis of malaria

Comparative evaluation of malaria antigen test and peripheral blood smears in diagnosis of malaria - IJMMTD- Print ISSN No: - 2581-4753 Online ISSN No:- 2581-4761 Article DOI No:- 10.18231/2581-4761.2019.0008, IP International Journal of Medical Microbiology and Tropical Diseases-IP Int J Med Microbiol Trop Dis

Routine Vaccination for Travelers from Emerging Countries: Epidemiological Profile of a Public Travel Medicine Clinic in Sao Paulo/Brazil

Introduction: Emerging countries have increased their presence in international travel (46.8% of travels). Pre- and post-travel consultations may provide insights about travelers’ health. Methods: A retrospective descriptive analysis of the medical data of all travelers assisted at Ambulatório dos Viajantes, a free public health clinic for travelers in São Paulo, Brazil, from January to December 2016 was performed. The patients were profiled based on post-travel consultation data and screened by gender, age according to the United Nations working-age population distribution (0-14 years, children; 15-24 years, youths; 25-65 years, working age; over 65 years, older persons), travel destination, and diseases that affected travelers. Results: In 2016 (n=280 appointments), 93.92% of clients received some type of vaccine (regular or booster dose). Post-travel consultations (n=27; 9.64%) were predominantly male (62.96% of appointments) and comprised cases of malaria (44.4%; 6 positive cases of Plasmodium falciparum, 4 positive cases of Plasmodium vivax, and 2 unclassified), fever (7.4%), AGE - acute gastroenteritis (7.4%), hepatitis A (3.7%), nausea (3.7%), insect bite (3.7%), abdominal pain (3.7%), arthralgia (3.7%), vaginal discharge (3.7%), and cases under investigation (18.5%). Brazilian travelers presented the same incidence of post-travel counseling as developed countries’ travel medicine clinics (~9%). Conclusion: Immunization in pre-travel counseling may reduce the importation of preventable infectious diseases and increase Brazilians’ traveler vaccine coverage, a current concern in the country.

Malaria in Eritrean migrants newly arrived in seven European countries, 2011 to 2016.

Global migration has resulted in a large number of asylum applications in Europe. In 2014, clusters of Plasmodium vivax cases were reported among newly arrived Eritreans. This study aimed to assess malaria among Eritrean migrants in Europe from 2011 to 2016. We reviewed European migration numbers and malaria surveillance data for seven countries (Denmark, Germany, Netherlands, Norway, Sweden, Switzerland and the United Kingdom) which received 44,050 (94.3%) of 46,730 Eritreans seeking asylum in Europe in 2014. The overall number of malaria cases, predominantly P. vivax, increased significantly in 2014 compared to previous years, with the largest increases in Germany (44 P. vivax cases in 2013 vs 294 in 2014, p < 0.001) and Sweden (18 in 2013 vs 205 in 2014, p < 0.001). Overall, malaria incidence in Eritreans increased from 1–5 to 25 cases per 1,000, and was highest in male teenagers (50 cases/1,000). In conclusion, an exceptional increase of malaria cases occurred in Europe in 2014 and 2015, due to rising numbers of Eritreans with high incidence of P. vivax arriving in Europe. Our results demonstrate potential for rapid changes in imported malaria patterns, highlighting the need for improved awareness, surveillance efforts and timely healthcare in migrants.

Lack of quadruple and quintuple mutant alleles associated with sulfadoxine-pyrimethamine resistance in Plasmodium vivax isolates from Brazilian endemic areas.

BACKGROUND AND OBJECTIVE Brazil is responsible for a large number of Plasmodium vivax cases in America. Given the emergence of P. vivax parasites resistant to chloroquine and the effectiveness of antifolates in vivax malaria treatment together with a correlation between mutations in P. vivax dhfr and dhps genes and SP treatment failure, the point mutations in these genes were investigated.METHODS Blood samples from 54 patients experiencing vivax malaria symptomatic episodes in the Amazonian Region were investigated. Genomic DNA was extracted using a DNA extraction kit (QIAGENTM). Nested polymerase chain reaction (PCR) amplification was carried out followed by Sanger sequencing to detect single nucleotide polymorphisms (SNPs).FINDINGS All tested isolates showed non-synonymous mutations in pvdhfr gene: 117N (54/54, 100%) and 58R (25/54, 46%). Double mutant allele 58R/117N (FRTNI, 28%) was the most frequent followed by triple mutant alleles (58R/117N/173L, FRTNL, 11%; 58R/61M/117N, FRMNI, 5% 117N/173L, FSTNL, 4%) and quadruple mutant allele (58R/61M/117N/173L, FRMNL, 2%). A single mutation was observed at codon C383G in pvdhps gene (SGKAV, 48%).CONCLUSION No evidence of molecular signatures associated with P. vivax resistance to SP was observed in the Brazilian samples.

431. Enhanced Malaria Surveillance in Greece, 2009–2017

BackgroundDuring 2009–2012, sporadic locally acquired (LA) P. vivax malaria cases and clusters were reported in Greece, a malaria-free country. Evrotas, an agricultural area in southern Greece with large migrant population from the Indian sub-continent, was the most affected area. In 2011–2017, we implemented enhanced malaria surveillance to timely detect and treat cases.MethodsWe applied the WHO case definitions for imported, LA, and introduced cases. We raised awareness among clinicians and investigated all reported cases. We actively screened for fever (i) the local population in the place of exposure of LA cases, and (ii) weekly, the migrant population in Evrotas, from April to November every year (active case detection, ACD). We distributed rapid diagnostic tests (RDTs) to enhance local diagnostic capacity. In 2015–2017, we established enhanced malaria surveillance in refugee/migrant hosting centers (RMHC).ResultsIn 2009–2017, 662 malaria cases were reported (67% P. vivax); 561 were imported, including 442 (79%) in migrants from endemic countries and 119 in travelers. The median annual number of imported cases in migrants increased from 32 (range 12–64) in 2009–2014 to 85 (range 65–91) in 2015–2017. In 2015–2017, 23% (n = 55) of all cases in migrants were detected in RMHC or points of entry. In 2011 and 2012, 42 and 20 LA P. vivax cases were reported in Greece, including 36 and 10 cases in Evrotas, respectively, while in 2013–2017, the annual median number of LA P. vivax cases decreased to 6 (range 0–8); all were introduced cases. RDTs contributed to the diagnosis in almost 100% of cases in Evrotas and in 96% of cases in RMHC or points of entry. In Evrotas, during ACD, time from disease onset to diagnosis decreased from 6 days in 2011 to 0.5 days in 2017.ConclusionFollowing the 2011–2012 peak of LA cases and the implementation of PH measures, the number of LA cases decreased substantially, despite the increased migrant influx. However, the presence of local competent vectors, combined with cases from malaria-endemic countries, heightens the risk of re-introducing malaria in receptive malaria-free areas. Although resource demanding, enhanced malaria surveillance contributed to minimizing the transmission risk and should be continued.Disclosures All authors: No reported disclosures.

Point-of-Care Testing for G6PD Deficiency: Opportunities for Screening.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked genetic disorder, is associated with increased risk of jaundice and kernicterus at birth. G6PD deficiency can manifest later in life as severe hemolysis, when the individual is exposed to oxidative agents that range from foods such as fava beans, to diseases such as typhoid, to medications such as dapsone, to the curative drugs for Plasmodium (P.) vivax malaria, primaquine and tafenoquine. While routine testing at birth for G6PD deficiency is recommended by the World Health Organization for populations with greater than 5% prevalence of G6PD deficiency and to inform P. vivax case management using primaquine, testing coverage is extremely low. Test coverage is low due to the need to prioritize newborn interventions and the complexity of currently available G6PD tests, especially those used to inform malaria case management. More affordable, accurate, point-of-care (POC) tests for G6PD deficiency are emerging that create an opportunity to extend testing to populations that do not have access to high throughput screening services. Some of these tests are quantitative, which provides an opportunity to address the gender disparity created by the currently available POC qualitative tests that misclassify females with intermediate G6PD activity as normal. In populations where the epidemiology for G6PD deficiency and P. vivax overlap, screening for G6PD deficiency at birth to inform care of the newborn can also be used to inform malaria case management over their lifetime.

Plasmodium vivax Infections in Duffy-Negative Individuals in the Democratic Republic of the Congo.

Although Plasmodium vivax has been assumed to be absent from sub-Saharan Africa because of the protective mutation conferring the Duffy-negative phenotype, recent evidence has suggested that P. vivax cases are prevalent in these regions. We selected 292 dried blood spots from children who participated in the 2013-2014 Demographic and Health Survey of the Democratic Republic of the Congo (DRC), to assess for P. vivax infection. Four P. vivax infections were identified by polymerase chain reaction, each in a geographically different survey cluster. Using these as index cases, we tested the remaining 73 samples from the four clusters. With this approach, 10 confirmed cases, three probable cases, and one possible case of P. vivax were identified. Among the 14 P. vivax cases, nine were coinfected with Plasmodium falciparum. All 14 individuals were confirmed to be Duffy-negative by sequencing for the single point mutation in the GATA motif that represses the expression of the Duffy antigen. This finding is consistent with a growing body of literature that suggests that P. vivax can infect Duffy-negative individuals in Africa. Future molecular and sequencing work is needed to understand the relationship of these isolates with other P. vivax samples from Asia and South America and discover variants linked to P. vivax virulence and erythrocyte invasion.

Levels of primaquine and carboxyprimaquine in patients with malaria vivax from the Brazilian Amazon basin.

ABSTRACTIn the last two years, a substantial increase in the number of malaria vivax cases has occurred in the Brazilian Amazon basin. The adequate exposure of hypnozoites to primaquine is a matter of interest as these dormant forms are responsible for the maintenance or even the increase of malaria burden in endemic areas. The aim of this study was to estimate the levels of primaquine and carboxyprimaquine in whole blood samples of patients with P. vivax treated with chloroquine and an abbreviated regimen of primaquine (0.5 mg/kg/d for 7 days), with adequate clinical and parasitological outcomes after 180 days of follow-up. A total of 40 male patients met the criteria for inclusion in the study. Primaquine and carboxyprimaquine were measured by high-performance liquid chromatography. The levels of primaquine in whole blood samples ranged from 40-238 ng/mL, 42-196 ng/mL and 42-150 ng/mL on days 1, 3 and 7. The levels of carboxyprimaquine in whole blood samples ranged from 87-234 ng/mL, 96-252 ng/mL and 74-448 ng/mL on days 1, 3 and 7. These data provide a reliable estimation of exposure of the infecting parasite to primaquine. Based on the regional pattern of relapse, the estimated blood levels of primaquine can be considered effective against hypnozoites of the local circulating strains of P. vivax.

Efficacy of artemether\u2013lumefantrine and dihydroartemisinin\u2013piperaquine for the treatment of uncomplicated malaria in Papua New Guinea

BackgroundIn 2009, the Papua New Guinea (PNG) Department of Health adopted artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DHA-PPQ) as the first- and second-line treatments for uncomplicated malaria, respectively. This study was conducted to assess the efficacy of both drugs following adoption of the new policy.MethodsBetween June 2012 and September 2014, a therapeutic efficacy study was conducted in East Sepik and Milne Bay Provinces of PNG in accordance with the standard World Health Organization (WHO) protocol for surveillance of anti-malarial drug efficacy. Patients ≥ 6 months of age with microscopy confirmed Plasmodium falciparum or Plasmodium vivax mono-infections were enrolled, treated with AL or DHA-PPQ, and followed up for 42 days. Study endpoints were adequate clinical and parasitological response (ACPR) on days 28 and 42. The in vitro efficacy of anti-malarials and the prevalence of selected molecular markers of resistance were also determined.ResultsA total of 274 P. falciparum and 70 P. vivax cases were enrolled. The day-42 PCR-corrected ACPR for P. falciparum was 98.1% (104/106) for AL and 100% (135/135) for DHA-PPQ. The day-42 PCR-corrected ACPR for P. vivax was 79.0% (15/19) for AL and 92.3% (36/39) for DHA-PPQ. Day 3 parasite clearance of P. falciparum was 99.2% with AL and 100% with DHA-PPQ. In vitro testing of 96 samples revealed low susceptibility to chloroquine (34% of samples above IC50 threshold) but not to lumefantrine (0%). Molecular markers assessed in a sub-set of the study population indicated high rates of chloroquine resistance in P. falciparum (pfcrt SVMNT: 94.2%, n = 104) and in P. vivax (pvmdr1 Y976F: 64.8%, n = 54).ConclusionsAL and DHA-PPQ were efficacious as first- and second-line treatments for uncomplicated malaria in PNG. Continued in vivo efficacy monitoring is warranted considering the threat of resistance to artemisinin and partner drugs in the region and scale-up of artemisinin-based combination therapy in PNG.