Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis.

Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (Pf EIR) and the basic reproductive number (PfR). Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (Pf PR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link Pf PR to Pf EIR and PfR and these were fitted to field data. These models were combined with the Pf PR map to create new global predictions of Pf EIR and PfR. All output maps included measured uncertainty. An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median Pf EIR of less than one and a median PfRc of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both Pf EIR and PfR was substantial in regions of intense transmission. The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.

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A world malaria map: Plasmodium falciparum endemicity in 2007

Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.

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Acquired immunity to malaria.

Summary Plasmodium vivax is geographically the most widely distributed cause of malaria in people, with up to 2·5 billion people at risk and an estimated 80 million to 300 million clinical cases every year—including severe disease and death. Despite this large burden of disease, P vivax is overlooked and left in the shadow of the enormous problem caused by Plasmodium falciparum in sub-Saharan Africa. The technological advances enabling the sequencing of the P vivax genome and a recent call for worldwide malaria eradication have together placed new emphasis on the importance of addressing P vivax as a major public health problem. However, because of this parasite's biology, it is especially difficult to interrupt the transmission of P vivax , and experts agree that the available methods for preventing and treating infections with P vivax are inadequate. It is thus imperative that the development of new methods and strategies become a priority. Advancing the development of such methods needs renewed emphasis on understanding the biology, pathogenesis, and epidemiology of P vivax . This Review critically examines what is known about P vivax , focusing on identifying the crucial gaps that create obstacles to the elimination of this parasite in human populations.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(09)70177-X.pdf

Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite

Background: Current understanding of the spatial epidemiology and geographical distribution of Plasmodium vivax is far less developed than that for P. falciparum, representing a barrier to rational strategies for control and elimination. Here we present the first systematic effort to map the global endemicity of this hitherto neglected parasite. Methodology and Findings: We first updated to the year 2010 our earlier estimate of the geographical limits of P. vivax transmission. Within areas of stable transmission, an assembly of 9,970 geopositioned P. vivax parasite rate (PvPR) surveys collected from 1985 to 2010 were used with a spatiotemporal Bayesian model-based geostatistical approach to estimate endemicity age-standardised to the 1–99 year age range (PvPR1–99) within every 565 km resolution grid square. The model incorporated data on Duffy negative phenotype frequency to suppress endemicity predictions, particularly in Africa. Endemicity was predicted within a relatively narrow range throughout the endemic world, with the point estimate rarely exceeding 7% PvPR1–99. The Americas contributed 22% of the global area at risk of P. vivax transmission, but high endemic areas were generally sparsely populated and the region contributed only 6% of the 2.5 billion people at risk (PAR) globally. In Africa, Duffy negativity meant stable transmission was constrained to Madagascar and parts of the Horn, contributing 3.5% of global PAR. Central Asia was home to 82% of global PAR with important high endemic areas coinciding with dense populations particularly in India and Myanmar. South East Asia contained areas of the highest endemicity in Indonesia and Papua New Guinea and contributed 9% of global PAR.

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A long neglected world malaria map: Plasmodium vivax endemicity in 2010.

Background 
Multidrug-resistant Plasmodium vivax (Pv) is widespread in eastern Indonesia, and emerging elsewhere in Asia-Pacific and South America, but is generally regarded as a benign disease. The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum (Pf) in patients presenting to a hospital in Timika, southern Papua, Indonesia.
Methods and Findings 
Data were prospectively collected from all patients attending the outpatient and inpatient departments of the only hospital in the region using systematic data forms and hospital computerised records. Between January 2004 and December 2007, clinical malaria was present in 16% (60,226/373,450) of hospital outpatients and 32% (12,171/37,800) of inpatients. Among patients admitted with slide-confirmed malaria, 64% of patients had Pf, 24% Pv, and 10.5% mixed infections. The proportion of malarial admissions attributable to Pv rose to 47% (415/887) in children under 1 y of age. Severe disease was present in 2,634 (22%) inpatients with malaria, with the risk greater among Pv (23% [675/2,937]) infections compared to Pf (20% [1,570/7,817]; odds ratio [OR] = 1.19 [95% confidence interval (CI) 1.08–1.32], p = 0.001), and greatest in patients with mixed infections (31% [389/1,273]); overall p < 0.0001. Severe anaemia (haemoglobin < 5 g/dl) was the major complication associated with Pv, accounting for 87% (589/675) of severe disease compared to 73% (1,144/1,570) of severe manifestations with Pf (p < 0.001). Pure Pv infection was also present in 78 patients with respiratory distress and 42 patients with coma. In total 242 (2.0%) patients with malaria died during admission: 2.2% (167/7,722) with Pf, 1.6% (46/2,916) with Pv, and 2.3% (29/1260) with mixed infections (p = 0.126).
Conclusions 
In this region with established high-grade chloroquine resistance to both Pv and Pf, Pv is associated with severe and fatal malaria particularly in young children. The epidemiology of P. vivax needs to be re-examined elsewhere where chloroquine resistance is increasing.

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Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia.

Background. In areas where malaria is endemic, infants aged <3 months appear to be relatively protected from symptomatic and severe Plasmodium falciparum malaria, but less is known about the effect of Plasmodium vivax infection in this age group. Methods. To define malaria morbidity in the first year of life in an area where both multidrug-resistant P. falciparum and P. vivax are highly prevalent, data were gathered on all infants attending a referral hospital in Papua, Indonesia, using systematic data forms and hospital computerized records. Additional clinical and laboratory data were prospectively collected from inpatients aged <3 months. Results. From April 2004 through April 2008, 4976 infants were admitted to the hospital, of whom 1560 (31%) had malaria, with infection equally attributable to P. falciparum and P. vivax. The case-fatality rate was similar for inpatients with P. falciparum malaria (13 [2.2%] of 599 inpatients died) and P. vivax malaria (6 [1.0%] of 603 died; P = .161), whereas severe malarial anemia was more prevalent among those with P. vivax malaria (193 [32%] ? of 605 vs. 144 [24%] of 601; P = .025). Of the 187 infants aged <3 months, 102 (56%) had P. vivax malaria, and 55 (30%) had P. falciparum malaria. In these young infants, infection with P. vivax was associated with a greater risk of severe anemia (odds ratio, 2.4; 95% confidence interval, 1.03―5.91; P = .041) and severe thrombocytopenia (odds ratio, 3.3; 95% confidence interval, 1.07-10.6; P = .036) compared with those who have P. falciparum infection. Conclusions. P. vivax malaria is a major cause of morbidity in early infancy. Preventive strategies, early diagnosis, and prompt treatment should be initiated in the perinatal period.

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Vivax malaria: a major cause of morbidity in early infancy.

Pregnant women are particularly vulnerable to malaria; they have an increased risk of infection and a greater risk of severe disease, compared with their nonpregnant counterparts [1, 2]. In sub-Saharan Africa, even asymptomatic infections increase the risk of low birth weight, preterm delivery, and perinatal death [3, 4]. In Asia and South America, where the level of Plasmodium falciparum transmission is less than that in Africa, women have little acquired immunity, and malaria infections are more frequently symptomatic, with an associated increased risk of maternal and/or fetal death [5, 6]. In these regions, Plasmodium vivax frequently coexists with P. falciparum, often accounting for more than one-half of malaria infections [7]. Although P. vivax infection has received less attention than P. falciparum infection, it is clearly an important contributor to both maternal anemia and low birth weight [8-10].

The burden of malaria during pregnancy has been complicated by the emergence of antimalarial drug resistance. Whereas chloroquine resistance in P. falciparum emerged in Southeast Asia >40 years ago, drug resistance in P. vivax has been slower to evolve. The first chloroquine-resistant isolates of P. vivax were reported from Papua, Indonesia, and Papua New Guinea in 1991 and have subsequently spread throughout the Indonesian archipelago [11-15]. In southern Papua, multidrug-resistant strains of both P. falciparum and P. vivax are now highly prevalent, with 65% of patients experiencing treatment failure within 28 days after chloroquine monotherapy for P. vivax and 48% experiencing treatment failure after treatment with chloroquine plus sulfadoxine-pyrimethamine for P. falciparum infection [16]. Unsupervised oral quinine is associated with 80% treatment failure, likely because of poor adherence to 7 days of therapy. Despite these limitations, chloroquine and quinine remained the standard treatments for P. vivax and P. falciparum malaria in pregnant women until 2006. The aim of the current study was to quantify the prevalence of P. vivax and P. falciparum infections in pregnant women in an area with high levels of drug resistance to both parasites and to describe the associated health-related consequences.

Noah Warikar

Papers

Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia.

Vivax malaria: a major cause of morbidity in early infancy.

Adverse Pregnancy Outcomes in an Area Where Multidrug-Resistant Plasmodium vivax and Plasmodium falciparum Infections Are Endemic