Challenges in the Control and Elimination of Plasmodium vivax Malaria

The human malaria parasite Plasmodium vivax imposes unique challenges to its control and elimination. Primary among those is the hypnozoite reservoir of infection in endemic communities. It is the dominant source of incident malaria and exceedingly difficult to attack due to both inability to diagnose latent carriers and the potentially life-threatening toxicity of primaquine in patients with an inborn deficiency of G6PD, the only therapeutic option against hypnozoites. Large segments of endemic populations are not eligible for primaquine, and alternative strategies for managing the threat of relapse in any group have not been optimized or validated. Association of risk of primaquine failure against latent P. vivax with impaired alleles of P450 2D6 exacerbates the substantial pool of primaquine ineligibles. Resistance to chloroquine against acute P. vivax malaria commonly occurs; alternative therapies like ACTs are effective but seldom evaluated as a partner drug to primaquine in the essential radical cure. Many of the Anopheles mosquito vector of P. vivax in South and Southeast Asia, where >90% of infections occur, thrive in a diversity of habitats and exhibit wide ranges of feeding and breeding behavior. This chapter explores many of these challenges and possible approaches in controlling and eliminating endemic vivax malaria

Alma data mining toolkit

ADMIT (ALMA Data Mining Toolkit) is a Python based pipeline toolkit for the creation and analysis of new science products from ALMA data. ADMIT quickly provides users with a detailed overview of their science products, for example: line identifications, line 'cutout' cubes, moment maps, and emission type analysis (e.g., feature detection). Users can download the small ADMIT pipeline product ($<$ 20MB), analyze the results, then fine-tune and re-run the ADMIT pipeline (or any part thereof) on their own machines and interactively inspect the results. ADMIT has both a web browser and command line interface available for this purpose. By analyzing multiple data cubes simultaneously, data mining between many astronomical sources and line transitions are possible. Users are also able to enhance the capabilities of ADMIT by creating customized ADMIT tasks satisfying any special processing needs. We will present some of the salient features of ADMIT and example use cases

Elimination Therapy for the Endemic Malarias

Most malaria diagnosed outside endemic zones occurs in patients experiencing the consequences of what was likely a single infectious bite by an anopheline mosquito. A single species of parasite is nearly always involved and expert opinion on malaria chemotherapy uniformly prescribes species- and stage-specific treatments. However the vast majority of people experiencing malaria, those resident in endemic zones, do so repeatedly and very often with the involvement of two or more species and stages of parasite. Silent forms of these infections—asymptomatic and beyond the reach of diagnostics—may accumulate to form substantial and unchallenged reservoirs of infection. In such settings treating only the species and stage of malaria revealed by diagnosis and not others may not be sensible or appropriate. Developing therapeutic strategies that address all species and stages independently of diagnostic evidence may substantially improve the effectiveness of the control and elimination of endemic malaria

Combined chloroquine, sulfadoxine/pyrimethamine and primaquine against Plasmodium falciparum in Central Java, Indonesia

BACKGROUND: Chloroquine (CQ) or sulfadoxine-pyrimethamine (SP) monotherapy for Plasmodium falciparum often leads to therapeutic failure in Indonesia. Combining CQ with other drugs, like SP, may provide an affordable, available and effective option where artemisinin-combined therapies (ACT) are not licensed or are unavailable. METHODS: This study compared CQ (n = 29 subjects) versus CQ + SP (with or without primaquine; n = 88) for clinical and parasitological cure of uncomplicated falciparum malaria in the Menoreh Hills region of southern Central Java, Indonesia. Gametocyte clearance rates were measured with (n = 56 subjects) and without (n = 61) a single 45 mg dose of primaquine (PQ). RESULTS: After 28 days, 58% of subjects receiving CQ had cleared parasitaemia and remained aparasitaemic, compared to 94% receiving CQ combined with SP (p < 0.001). Msp-2 genotyping permitted reinfection-adjusted cure rates for CQ and CQ combined with SP, 70% and 99%, respectively (p = 0.0006). CONCLUSION: Primaquine exerted no apparent affect on cure of asexual stage parasitaemia, but clearly accelerated clearance of gametocytes. CQ combined with SP was safe and well-tolerated with superior efficacy over CQ for P. falciparum parasitaemia in this study

Standardizing estimates of the Plasmodium falciparum parasite rate

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>parasite rate (PfPR) is a commonly reported index of malaria transmission intensity. PfPR rises after birth to a plateau before declining in older children and adults. Studies of populations with different age ranges generally report average PfPR, so age is an important source of heterogeneity in reported PfPR data. This confounds simple comparisons of PfPR surveys conducted at different times or places.</p> <p>Methods</p> <p>Several algorithms for standardizing PfPR were developed using 21 studies that stratify in detail PfPR by age. An additional 121 studies were found that recorded PfPR from the same population over at least two different age ranges; these paired estimates were used to evaluate these algorithms. The best algorithm was judged to be the one that described most of the variance when converting the PfPR pairs from one age-range to another.</p> <p>Results</p> <p>The analysis suggests that the relationship between PfPR and age is predictable across the observed range of malaria endemicity. PfPR reaches a peak after about two years and remains fairly constant in older children until age ten before declining throughout adolescence and adulthood. The PfPR pairs were poorly correlated; using one to predict the other would explain only 5% of the total variance. By contrast, the PfPR predicted by the best algorithm explained 72% of the variance.</p> <p>Conclusion</p> <p>The PfPR in older children is useful for standardization because it has good biological, epidemiological and statistical properties. It is also historically consistent with the classical categories of hypoendemic, mesoendemic and hyperendemic malaria. This algorithm provides a reliable method for standardizing PfPR for the purposes of comparing studies and mapping malaria endemicity. The scripts for doing so are freely available to all.</p

Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia

<p>Abstract</p> <p>Background</p> <p>Chloroquine is an anti-malarial drug being used to treat <it>Plasmodium vivax </it>malaria cases in Ethiopia. However, emergence of chloroquine resistant strains of the parasite has challenged the current efficacy of the drug. Therefore, the aim of this study was to assess the effectiveness of chloroquine against <it>P. vivax </it>strains in one of the malaria endemic areas of Ethiopia, namely Halaba district, located in South Nations and Nationalities Peoples Region (SNNPR) of South Ethiopia</p> <p>Results</p> <p>Among 87 malaria patients enrolled in the study, only 80 of them completed the 28-days follow-up. Seven of them dropped from the study for different reasons. Among those study participants that completed their follow-up, 69 were classified under the category of adequate clinical and parasitological response (ACPR). However, the remaining 11 cases were considered as under treatment failure mainly due to recurrence of parasitemia on day 7 (four patients), day 14 (six patients), and day 21 (one patient). The age of all cases of treatment failures was found to be less than 20 years. The load of parasitemia of patients with treatment failure on day of admission (4709.4/μl) was higher than day of recurrence (372.37/μl). Parasite reduction ratio (PRR) of treatment failure cases was 12.6/μl.</p> <p>Conclusion</p> <p>This report revealed the rise in treatment failure (13% [95% CI = 0.074 - 0.217]) as compared to earlier reports from Ethiopia. It signals the spreading of chloroquine resistant <it>P. vivax </it>(CRPv) strains to malaria endemic areas of Ethiopia. It is recommended that all concerned bodies should act aggressively before further expansion of the current drug resistant malaria.</p

Diagnosis of Human Visceral Pentastomiasis

Visceral pentastomiasis in humans is caused by the larval stages (nymphs) of the arthropod-related tongue worms Linguatula serrata, Armillifer armillatus, A. moniliformis, A. grandis, and Porocephalus crotali. The majority of cases has been reported from Africa, Malaysia, and the Middle East, where visceral pentastomiasis may be an incidental finding in autopsies, and less often from China and Latin America. In Europe and North America, the disease is only rarely encountered in immigrants and long-term travelers, and the parasitic lesions may be confused with malignancies, leading to a delay in the correct diagnosis. Since clinical symptoms are variable and serological tests are not readily available, the diagnosis often relies on histopathological examinations. This laboratory symposium focuses on the diagnosis of this unusual parasitic disease and presents its risk factors and epidemiology

Malaria prevalence in Nias District, North Sumatra Province, Indonesia

BACKGROUND: The Nias district of the North Sumatra Province of Indonesia has long been known to be endemic for malaria. Following the economic crisis at the end of 1998 and the subsequent tsunami and earthquake, in December 2004 and March 2005, respectively, the malaria control programme in the area deteriorated. The present study aims to provide baseline data for the establishment of a suitable malaria control programme in the area and to analyse the frequency distribution of drug resistance alleles associated with resistance to chloroquine and sulphadoxine-pyrimethamine.\ud METHODS: Malariometric and entomology surveys were performed in three subdistricts. Thin and thick blood smears were stained with Giemsa and examined under binocular light microscopy. Blood blots on filter paper were also prepared for isolation of parasite and host DNA to be used for molecular analysis of band 3 (SAO), pfcrt, pfmdr1, dhfr, and dhps. In addition, haemoglobin measurement was performed in the second and third surveys for the subjects less than 10 years old.\ud RESULTS: Results of the three surveys revealed an average slide positivity rate of 8.13%, with a relatively higher rate in certain foci. Host genetic analysis, to identify the Band 3 deletion associated with Southeast Asian Ovalocytosis (SAO), revealed an overall frequency of 1.0% among the 1,484 samples examined. One hundred six Plasmodium falciparum isolates from three sub-districts were successfully analysed. Alleles of the dhfr and dhps genes associated with resistance to sulphadoxine-pyrimethamine, dhfr C59R and S108N, and dhps A437G and K540E, were present at frequencies of 52.2%, 82.5%, 1.18% and 1.18%, respectively. The pfmdr1 alleles N86Y and N1042D, putatively associated with mefloquine resistance, were present at 31.4% and 2%, respectively. All but one sample carried the pfcrt 76T allele associated with chloroquine resistance. Entomologic surveys identified three potential anopheline vectors in the area, Anopheles barbirostris, Anopheles kochi and Anopheles sundaicus.\ud CONCLUSION: The cross sectional surveys in three different sub-districts of Nias District clearly demonstrated the presence of relatively stable endemic foci of malaria in Nias District, North Sumatra Province, Indonesia. Molecular analysis of the malaria parasite isolates collected from this area strongly indicates resistance to chloroquine and a growing threat of resistance to sulphadoxine-pyrimethamine. This situation highlights the need to develop sustainable malaria control measures through regular surveillance and proper antimalarial drug deployment

Primaquine in vivax malaria: an update and review on management issues

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs