A single study in Indonesia reported resistance of P. The recommended treatment for radical cure of P. ACT or chloroquine combined with primaquine total dose, 3. The high prevalence of G6PD deficiency in areas endemic for P. Chloroquine is generally well tolerated. Some methaemoglobinaemia is common but is very seldom dangerous. Although some red cell loss may occur in normal subjects, patients who are G6PD deficient are particularly vulnerable.
There are over genetic G6PD variants, nearly all conferring an unstable enzyme, which degrades more rapidly than the normal variant. This renders older red cells vulnerable to oxidant damage Thus, although the average ratio of G6PD-deficient to normal red cells is , some individuals may have a ratio of or even more unequal ratios. The severity of oxidant haemolysis in heterozygous females therefore varies from that observed in hemizygous males if the majority of their red cells are G6PD deficient to very little haemolysis if the majority of their red cells are G6PD normal.
Geographical distribution of G6PD deficiency genotypes At a population level, the overall fall in haemoglobin in heterozygous females will be, on average, one half of that seen in hemizygous male and homozygous females 29 , Except in severely deficient individuals, haemolysis typically starts after 1 or 2 days of treatment when all the remaining red cell oxidant defences have been exhausted.
The extent of haemolysis with primaquine depends on the degree of G6PD deficiency and the primaquine dose. Two of the most prevalent G6PD variants represent the two ends of the severity spectrum, with the Mediterranean variant the main variant found in Europe, West and Central Asia and northern India being among the most severe and the African A— variant found in sub-Saharan Africa and in African-Americans being among the mildest Figure A6.
There is also substantial variation in G6PD activity among individuals with the same genotype and even within the same individual over time. With less severe G6PD variants, primaquine-induced haemolysis typically becomes evident after 1 or 2 days of exposure, when the oxidant defences of all the older erythrocytes have been depleted 29 — If primaquine is continued in people with the African A— variant, haemolysis lessens and the haemoglobin concentration starts to rise again, despite further drug administration, as reticulocytes enter the circulation to replace the haemolysed cells.
Red cell survival and degree of anaemia following daily primaquine in different G6PD deficiency variants. On the left, red cell survival with different daily doses of primaquine given to adults with the African A— variant of G6PD deficiency. On more These young red cells entering the circulation contain five times more G6PD than the oldest red cells and so are relatively resistant to the haemolytic effect. Further haemolysis does, however, occur with higher doses In contrast, in the Mediterranean variant, haemolysis continues if primaquine is not stopped, and life-threatening anaemia may result.
In six decades of primaquine use in approximately million people, 14 deaths have been reported. If the estimate is confined to reports with known denominators, the estimated mortality rate is 1 in All but one death occurred subsequent to multiple dosing to prevent vivax malaria relapse 32 , To reduce the risk for haemolysis of individuals who do not have severe variants of G6PD deficiency, an intermittent primaquine regimen of 0.
This regimen was safe and effective in people with the African A— genotype 34 Figure A6. Although the regime has been recommended for some 50 years, relatively few studies have been conducted of its efficacy or safety.
Haemolysis following different primaquine regimens in people with A- G6PD deficiency. Weekly administration ameliorates the anaemia by allowing haematological recovery after each dose. The risk for severe haemolysis is virtually confined to G6PD-deficient individuals, which is why testing is so important The sensitivity of P.
A modified version of the standard WHO in-vitro test for determining the antimalarial sensitivity of P. WHO recently introduced a revised protocol for in-vivo monitoring of the therapeutic efficacy of chloroquine in P.
Better understanding of the molecular mechanisms underlying drug resistance in P. All rights reserved. Turn recording back on. National Center for Biotechnology Information , U.
Guidelines for the Treatment of Malaria. Geneva: World Health Organization; Show details Geneva: World Health Organization ; 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. India has by far the greatest estimated Plasmodium vivax burden of any country. In , there were 2. In the recent past, P. Notably, P. Annual malaria incidence in India, — Malaria control measures in India include improved access to early diagnosis and treatment, the involvement of the accredited social health activists ASHAs at the community level, the introduction of artemisinin-based combination therapy, and intensified vector control, including long-lasting insecticidal nets LLINs.
Although malaria control measures have had impacts on both Plasmodium falciparum and P. The burden of malaria in India is complex and the proportions of P. The annual vivax index AVI is the ratio between the number of P. Indian states with more than 3, Plasmodium vivax malaria cases in Plasmodium vivax is particularly troubling in the urban setting in India. Malaria control in such areas is problematic because of rapid construction, migration, and the mushrooming of slums.
Because of the importance of urban malaria, these areas are covered by a special program—the Urban Malaria Scheme. Urban areas are prone to malaria outbreaks and these are associated with peaks in mortality. Urban malaria in India. Annual malaria incidence in the 19 states included in the Urban Malaria Scheme, — In this report, the malaria epidemiological situation for P. Plasmodium vivax appears earlier than P.
Numbers in brackets indicate number of days of primaquine therapy. Data from two studies conducted in Kheda district of Gujarat showed higher recurrence rates in the 5—10 years age group than in other age groups Table 2. This relatively long interval is compatible with infection with temperate P. There is variation in relapse patterns both across and within states. In fact, strains with differing patterns of relapse can coexist, complicating transmission control measures.
For example, in Delhi, P. Of the 58 Anopheles species in India, only six are epidemiologically important for malaria transmission with regional distribution, though other species may be key local vectors. Each species exhibits specific behavior and a preferred habitat. Multiple vector species may be present across any region, but no vector species is found throughout all of India. The key components of the Indian malaria control strategy for P.
Vector control measures include insecticide-treated nets, LLINs, indoor residual spraying IRS , antilarval measures, including fish and chemicals, and WHO Pesticide Evaluation Scheme-recommended biolarvicides, along with minor environmental engineering measures. According to the national policy, all fever cases clinically suspected of being malaria should be confirmed by either microscopy or rapid diagnostic test RDT.
These only capture P. Blood slides of patients negative for P. In , bivalent RDTs which detect and differentiate P. This new policy should provide a more accurate picture of the P. Passive case detection is highest during the monsoon rains June—September , reflecting high malaria transmission. Diagnosis is usually obtained within a clinically relevant timeframe, even using microscopy. Parasitologically confirmed P. Primaquine is contraindicated in infants and pregnant women, and individuals with glucosephosphate dehydrogenase G6PD deficiency.
There is no G6PD deficiency testing in the field, but patients are instructed to stop primaquine treatment and report back to the clinic in cases of hematuria or dark urine, cyanosis or blue coloration of the lips.
Antimalarial treatment is provided in blister packs, free of charge to all patients in the public sector according to the age-specific dosing schedule. Primaquine therapy is not directly observed and adherence data are lacking. In urban areas, the private sector is an important provider of health services, but adherence to government prescribing guidelines is more limited in this sector. Chloroquine remains safe and efficacious for the treatment of P. Plasmodium vivax studies are also routinely conducted to track the emergence of chloroquine resistance in this species.
Thus, data on G6PD deficiency prevalence is based on research studies. However, sample sizes have been generally small and sampling nonrepresentative of the population at risk of malaria. Data are insufficient to determine any relationship between the distribution of G6PD deficiency and the malaria burden either now or in the past to elucidate any epidemiologically relevant patterns.
Operational research to estimate the prevalence of G6PD deficiency in the population has been included as an objective for the P. Pooling of data from studies found a frequency of G6PD deficiency of 4. Also, there are more than 4, different ethnic populations in India, and certain groups may have a particularly high prevalence of G6PD deficiency, for example For the regions considered in more detail, the estimated prevalence of G6PD deficiency was 4. However, there are few reports of acute hemolytic anemia, 24 despite routine use of primaquine 0.
Some healthcare providers are concerned about hemolytic side effects of primaquine and may be reluctant to prescribe. However, absence of radical cure treatment maintains P. The availability of a suitable G6PD test would provide confidence in providing antirelapse therapy and improve access. India has a sound surveillance system and data are consistently reported. The annual parasite index number of confirmed malaria cases per 1, population has consistently declined from 2. The slide positivity rate was higher in P.
Changes in key indices of malaria epidemiology in India, — Manually aggregated line lists for each person are entered into a database. Villages are stratified based on the overall annual parasite index. The incidence of P. A key limitation is that mixed infections are recorded as P. Plasmodium vivax malaria deaths are investigated and recorded; however, these are not included in the annual report. In view of extensive regional diversity, this review on P.
Each of these states has a well-developed public health services, with reliable surveillance systems. Overall, the four states accounted for Further, there is diversity among these states in terms of Plasmodium species, endemicity, transmission patterns, etc. Notably, there appears to be a key trend across Gujarat, Odisha, and Karnataka for an increase in the proportion of malaria cases attributable to P.
Gujarat, in northwestern India, is home to over 60 million people. It has a diverse climate, with desert regions in the northwest of the state, whereas the southern districts are wetter because of the monsoon, which starts around mid-June. Gujarat has the third highest P. Malaria is a global health burden, with Plasmodium falciparum Pf and Plasmodium vivax Pv responsible for the majority of infections worldwide. Circumsporozoite protein CSP is the most abundant protein on the surface of Plasmodium sporozoites, and antibodies targeting the central repeat region of CSP can prevent parasite infection.
Here, we performed molecular dynamics simulations for peptides comprising the PvCSP repeats from strains VK and VK to reveal how the PvCSP central repeats are highly disordered, with minor propensities to adopt turn conformations.
Next, we solved eight crystal structures to unveil the interactions of two inhibitory monoclonal antibodies mAbs , 2F2 and 2E E9, with PvCSP repeats. Both antibodies can accommodate subtle sequence variances in the repeat motifs and recognize largely coiled peptide conformations that also contain isolated turns.
These findings augment our understanding of host- Plasmodium interactions, and contribute molecular details of Pv inhibition by mAbs to unlock structure-based engineering of PvCSP-based vaccines.
E9 Fab , 7RM3 2E E9 Fab , 7RM0 2E E9 Fab Hence, treatment and diagnostic policies aimed exclusively at P. Within sub-Saharan Africa, malaria control programmes justly focus on reducing the morbidity and mortality associated with P. However, the recent emphasis on malaria elimination and increased accessibility of more sensitive diagnostic tools have revealed greater intricacies in malaria epidemiology across the continent.
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