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Since 2010, malaria rapid diagnostic tests (RDTs) are widely used to detect malaria. The Indian Council of Medical Research-National Institute of Malaria Research performed lot testing (LT) according to WHO procedures since 2016. Lot testing is performed to evaluate the lot-to-lot variation in performance of malaria RDTs. Four sets of positive quality control (QC) panels for P. falciparum (Pf) and P. vivax (Pv) and 10 negative panels tested RDTs. RDTs were reported as pass, failed, or deferred on the basis of WHO criteria. In the past 5 years, 275 lots containing 15,488 RDT kits for malaria diagnosis were subjected to LT. The monovalent RDTs (n = 1,216), based on either Pf histidine rich protein 2 (HRP2) or Pan-Plasmodium lactate dehydrogenase (Pan-pLDH) antigens, showed 90.4% sensitivity and 100% specificity, whereas RDTs based on HRP2 + Pan-pLDH or HRP2 + pLDH (n = 13,924) had sensitivity 95.6% and specificity 99.5%, respectively. RDTs based on PfHRP2 + Pv-pLDH + Pan-pLDH (n = 348) had 100% sensitivity and specificity. In a comparison between HRP2 + pLDH or HRP2 + Pan-pLDH to HRP2 + pLDH + Pan-pLDH RDTs, it was found that the sensitivity of PfHRP2 with Pan-pLDH RDTs (n = 2,382) was only 83%. Of the 275 lots analyzed, 15 lots of PfHRP2 with Pan-pLDH were deferred. The QC panel for Pf revealed a faint Pan band in the tested lots, which is a cause for concern. The results of deferred lots were reported to concerned government agencies. Quality-compromised RDTs may lead to an incorrect diagnosis. It is critical to have a QC system in place for effective malaria management.

The Malaria Evolution in South Asia (MESA) International Center for Excellence in Malaria Research (ICEMR) was established by the US National Institutes of Health (US NIH) as one of 10 malaria research centers in endemic countries. In 10 years of hospital-based and field-based work in India, the MESA-ICEMR has documented the changing epidemiology and transmission of malaria in four different parts of India. Malaria Evolution in South Asia-ICEMR activities, in collaboration with Indian partners, are carried out in the broad thematic areas of malaria case surveillance, vector biology and transmission, antimalarial resistance, pathogenesis, and host response. The program integrates insights from surveillance and field studies with novel basic science studies. This is a two-pronged approach determining the biology behind the disease patterns seen in the field, and generating new relevant biological questions about malaria to be tested in the field. Malaria Evolution in South Asia-ICEMR activities inform local and international stakeholders on the current status of malaria transmission in select parts of South Asia including updates on regional vectors of transmission of local parasites. The community surveys and new laboratory tools help monitor ongoing efforts to control and eliminate malaria in key regions of South Asia including the state of evolving antimalarial resistance in different parts of India, new host biomarkers of recent infection, and molecular markers of pathogenesis from uncomplicated and severe malaria.

Plasmodium vivax malaria elimination requires radical cure with chloroquine/primaquine. However, primaquine causes hemolysis in glucose-6-phosphate dehydrogenase-deficient (G6PDd) individuals. Between February 2016 and July 2017 in Odisha State, India, a prospective, observational, active pharmacovigilance study assessed the hematologic safety of directly observed 25 mg/kg chloroquine over 3 days plus primaquine 0.25 mg/kg/day for 14 days in 100 P. vivax patients (≥ 1 year old) with hemoglobin (Hb) ≥ 7 g/dL. Pretreatment G6PDd screening was not done, but patients were advised on hemolysis signs and symptoms using a visual aid. For evaluable patients, the mean absolute change in Hb between day 0 and day 7 was -0.62 g/dL (95% confidence interval [CI]: -0.93, -0.31) for males (N = 53) versus -0.24 g/dL (95%CI: -0.59, 0.10) for females (N = 45; P = 0.034). Hemoglobin declines ≥ 3 g/dL occurred in 5/99 (5.1%) patients (three males, two females); none had concurrent clinical symptoms of hemolysis. Based on G6PD qualitative testing after study completion, three had a G6PD-normal phenotype, one female was confirmed by genotyping as G6PDd heterozygous, and one male had an unknown phenotype. A G6PDd prevalence survey was conducted between August 2017 and March 2018 in the same region using qualitative G6PD testing, confirmed by genotyping. G6PDd prevalence was 12.0% (14/117) in tribal versus 3.1% (16/509) in nontribal populations, with G6PD Orissa identified in 29/30 (96.7%) of G6PDd samples. Following chloroquine/primaquine, notable Hb declines were observed in this population that were not recognized by patients based on clinical signs and symptoms.

This study evaluated intermittent screening and treatment during pregnancy (ISTp) for malaria using rapid diagnostic tests (RDTs) at antenatal care (ANC) compared with passive case detection within the routine health system. The mixed-method evaluation included two cross-sectional household surveys (pre- and post-implementation of ISTp), in-depth interviews with health workers, and focus group discussions (FGDs) with pregnant women. Differences in proportions between surveys for a number of outcomes were tested; 553 and 534 current and recently pregnant women were surveyed (pre- and post-implementation, respectively). In-depth interviews were conducted with 29 health providers, and 13 FGDs were held with pregnant women. The proportion of pregnant women who received an RDT for malaria at ANC at least once during their pregnancy increased from pre- to post-implementation (19.2%; 95% CI: 14.9, 24.3 versus 42.5%; 95% CI: 36.6, 48.7; P < 0.0001), and the proportion of women who had more than one RDT also increased (16.5%; 95% CI: 13.1, 20.5 versus 27.7%; 95% CI: 23.0, 33.0; P = 0.0008). Post-implementation, however, only 8% of women who had completed their pregnancy received an RDT on three visits to ANC. Health workers were positive about ISTp mainly because of their perception that many pregnant women with malaria were asymptomatic. Health workers perceived pregnant women to have reservations about ISTp because of their dislike of frequent blood withdrawal, but pregnant women themselves were more positive. Intermittent screening and treatment during pregnancy was not sufficiently adopted by health workers to ensure the increased detection of malaria infections achievable with this strategy in this setting.

The diagnosis and treatment of Plasmodium vivax malaria differs from that of Plasmodium falciparum malaria in fundamentally important ways. This article reviews the guiding principles, practices, and evidence underpinning the diagnosis and treatment of P. vivax malaria., (© The American Society of Tropical Medicine and Hygiene.)

Historically, malaria in India was predominantly caused by Plasmodium vivax, accounting for 53% of the estimated cases. After the spread of drug-resistant Plasmodium falciparum in the 1990s, the prevalence of the two species remained equivalent at the national level for a decade. By 2014, the proportion of P. vivax has decreased to 34% nationally, but with high regional variation. In 2014, P. vivax accounted for around 380,000 malaria cases in India; almost a sixth of all P. vivax cases reported globally. Plasmodium vivax has remained resistant to control measures, particularly in urban areas. Urban malaria is predominantly caused by P. vivax and is subject to outbreaks, often associated with increased mortality, and triggered by bursts of migration and construction. The epidemiology of P. vivax varies substantially within India, including multiple relapse phenotypes with varying latencies between primary infection and relapse. Moreover, the hypnozoite reservoir maintains transmission potential and enables reestablishment of the parasite in areas in which it was thought eradicated. The burden of malaria in India is complex because of the highly variable malaria eco-epidemiological profiles, transmission factors, and the presence of multiple Plasmodium species and Anopheles vectors. This review of P. vivax malaria in India describes epidemiological trends with particular attention to four states: Gujarat, Karnataka, Haryana, and Odisha., (© The American Society of Tropical Medicine and Hygiene.)

The study of the three protagonists in malaria-the Plasmodium parasite, the Anopheles mosquito, and the human host-is key to developing methods to control and eventually eliminate the disease. Genomic technologies, including the recent development of next-generation sequencing, enable interrogation of this triangle to an unprecedented level of scrutiny, and promise exciting progress toward real-time epidemiology studies and the study of evolutionary adaptation. We discuss the use of genomics by the International Centers of Excellence for Malaria Research, a network of field sites and laboratories in malaria-endemic countries that undertake cutting-edge research, training, and technology transfer in malarious countries of the world., (© The American Society of Tropical Medicine and Hygiene.)

This study was conducted to correlate blood concentrations of lumefantrine with treatment outcome for patients with Plasmodium falciparum malaria when the drug was given without specific instructions for administration with food. Patients with P. falciparum malaria in the highly endemic state of Orissa, India, were enrolled during 2008 and followed-up for 28 days after admistration of artemether-lumefantrine for three days according to a World Health Organization protocol. Drug concentration in whole blood was determined by using blood spots placed on filter paper on day 7. The technology is suitable for field studies. One hundred percent of the patients had an adequate clinical and parasitological response. These results confirm the efficacy of artemether-lumefantrine in persons from poor tribal communities when given without specific instructions regarding co-administration with food, despite high inter-individual variability in blood concentrations of lumefantrine.

We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4-99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was -0.5% (-5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4-0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study.

An otherwise healthy 20-year-old woman in Goa, India, received antibiotics after a diagnosis of upper respiratory tract infection. One week later, vivax malaria was diagnosed at a health center, but the patient developed respiratory distress and lost consciousness. She arrived at emergency department in shock, breathless, and comatose. She died within minutes. Two independent laboratories later confirmed Plasmodium vivax by microscopy (140,000/microL) and by nested and real-time polymerase chain reaction methods. Post-mortem examination showed congestion of alveolar capillaries by heavy monocytic infiltrates, along with diffuse damage to alveolar membranes consistent with acute respiratory distress syndrome. Parasites seen in lung tissue were roughly proportionate to both peripheral hyperparasitemia and those seen in other organs without lesions. In this patient, vivax malaria caused a rapidly fatal respiratory distress.

In India, nine Anopheline vectors are involved in transmitting malaria in diverse geo-ecological paradigms. About 2 million confirmed malaria cases and 1,000 deaths are reported annually, although 15 million cases and 20,000 deaths are estimated by WHO South East Asia Regional Office. India contributes 77% of the total malaria in Southeast Asia. Multi-organ involvement/dysfunction is reported in both Plasmodium falciparum and P. vivax cases. Most of the malaria burden is borne by economically productive ages. The states inhabited by ethnic tribes are entrenched with stable malaria, particularly P. falciparum with growing drug resistance. The profound impact of complicated malaria in pregnancy includes anemia, abortions, low birth weight in neonates, still births, and maternal mortality. Retrospective analysis of burden of malaria showed that disability adjusted life years lost due to malaria were 1.86 million years. Cost-benefit analysis suggests that each Rupee invested by the National Malaria Control Program pays a rich dividend of 19.7 Rupees.

Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection, but no controlled treatment studies have been performed. We conducted a double-blinded trial in P. vivax malaria in which patients were randomized to either azithromycin 1,000 mg q.d. x 3 or chloroquine 600 mg q.d. x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20. Eighty-five of 97 (88%) of those on azithromycin and 101 of 102 (99%) of those on chloroquine [difference 11%; 95% CI: -18, -4] were clinically cured at Day 7. The Day 28 results were similar [89% versus 99%, azithromycin versus chloroquine, respectively]. Parasitologic success was seen in 81 of 97 (84%) on azithromycin and 100 of 102 (98%) on chloroquine [difference 14%; 95% CI: -22, -6]. The median parasite clearance time was 55 hours on azithromycin and 20 hours on chloroquine (P < 0.001). Drug-related adverse events were seen in 13 of 98 (13%) on azithromycin and 24 of 102 (24%) on chloroquine (P = 0.062). Resolution of parasitemia was significantly faster with chloroquine compared with azithromycin, but azithromycin was better tolerated. These data provide support for further study of azithromycin to better define its role in the treatment of P. vivax malaria, either alone as second-line treatment or in combination with other active therapies.