Up -dated management in infectious diseases - Malaria Severe falciparum malaria is a medical emergency, and necessitates intensive nursing care and careful management (panel 1). In Asia, parenteral artesunate significantly reduced mortality from 22·4% to 14·7% compared with quinine (figure 4) (appendix).54 In the largest study53 so far of children hospitalised with severe falciparum malaria in Africa, artesunate significantly reduced mortality from 10·9% to 8·5% compared with quinine. Intravenous or intramuscular artesunate is thus the treatment of choice for severe malaria worldwide120 (including in patients with severe vivax and knowlesi malaria125). Artesunate has no important local or systemic adverse effects, although high cumulative doses (≥6 mg/kg per day) can temporarily suppress bone marrow. Delayed haemolysis starting a week after artesunate treatment for severe malaria has been noted in travellers (particularly those initially presenting with high parasitaemias) returning to hospitals in non-endemic countries.126 This haemolysis is probably partly caused by the loss of once-infected erythrocytes, which results from splenic pitting of parasites killed by artesunate. Panel 1 Treatment of severe malaria in adults and children •Artesunate 2·4 mg/kg by intravenous or intramuscular* injection, followed by 2·4 mg/kg at 12 h and 24 h; continue injection once daily if necessary† •Artemether 3·2 mg/kg by immediate intramuscular* injection, followed by 1·6 mg/kg daily •Quinine dihydrochloride 20 mg salt per kg infused during 4 h, followed by maintenance of 10 mg salt per kg infused during 2—8 h every 8 h (can also be given by intramuscular injection* when diluted to 60—100 mg/mL) Artesunate is the treatment of choice. Artemether should only be used if artesunate is unavailable. Quinine dihydrochloride should be given only when artesunate and artemether are unavailable. * Intramuscular injections should be given to the anterior thigh.Young children with severe malaria have lower exposure to artesunate and its main biologically active metabolite dihydroartemisinin than do older children and adults. Revised dose regimens to ensure similar drug exposures have been suggested In acute renal failure or severe metabolic acidosis, haemofiltration or hemodialysis should be started early.72 Dose reduction of artemisinin derivatives is unnecessary, even in renal failure. Prophylactic anticonvulsants are potentially dangerous; high-dose phenobarbital (20 mg/kg) doubled mortality in children with cerebral malaria—patients died mainly from respiratory arrest.130 In unconscious patients, blood glucose should be measured every 4—6 h and dextrose continuously infused to maintain concentrations higher than 4 mmol/L. Hypoglycaemia (<2·2 mmol/L) should be treated immediately with bolus glucose. Parasite counts and haematocrit concentrations should be measured every 6—12 h. Anaemia develops rapidly in severe malaria; if haematocrit falls to less than 20% (haemoglobin <70 g/L), then packed cells or whole (preferably fresh) blood should be transfused carefully. The transfusion threshold for children in Africa (where anaemia is very common and safe blood for transfusion is scarce) is a haematocrit concentration of 15% or less (haemoglobin concentrations less than 50 g/L). Renal function should be checked daily. Management of fluids is difficult, especially in adults, because the risks of overhydration (pulmonary oedema) have to be balanced against those of underhydration (exacerbation of renal impairment and tissue hypoperfusion). Large fluid boluses are harmful at all ages.68, 69 Early enteral feeding in non-intubated comatose adults can cause aspiration pneumonia, so feeding should not start until the third day of the coma.131 When the patient can take tablets reliably, a full course of artemisinin combination treatment should be given.120 Intravenous antimicrobials should be given to all children with suspected severe malaria in areas of moderate or high transmission.132 Convulsions should be treated with intravenous or rectal benzodiazepines and respiratory support provided when necessary. Aspiration pneumonia should be suspected in any unconscious child or adult patient with convulsions, particularly when persistent hyperventilation is noted. Hypoglycaemia or septicaemia should be suspected after sudden deterioration for no obvious reason during treatment. Patients who bleed spontaneously should be given packed red blood cells with fresh frozen plasma or, when unavailable, fresh blood and parenteral vitamin K. Uncomplicated falciparum malaria Artemisinin combination treatment is the recommended first-line therapy for uncomplicated falciparum malaria in all endemic areas, and is highly efficacious against the other human malarias. The artemisinin component (artesunate, artemether, or dihydroartemisinin) is given for 3 days with a slowly eliminated antimalarial, preferably in a fixed-dose combination (table). Artemisinin combination treatment is rapidly and reliably effective, associated with few adverse effects,133 and curative in more than 90% of cases (except in foci of artemisinin resistance). The price of such treatment has dropped substantially, making it more generally affordable. Unfortunately, fake or substandard antimalarials are widespread in many Asian and African countries, which compromises effectiveness, selects for resistance, and diminishes confidence in the health sector. Atovaquone—proguanil is highly effective everywhere, but seldom used in endemic areas because of the cost and propensity for high-grade resistance to emerge from single mutations in the cyt b gene. The duration of post-treatment prophylaxis after artemisinin combination treatment varies. Slowly eliminated partner drugs, such as mefloquine and piperaquine, provide 4—6 weeks’ prophylaxis, whereas reinfections after treatment with artemether—lumefantrine often emerge within a month. In low transmission areas, a single gametocytocidal dose of primaquine (0·25 mg base per kg) should be added to all artemisinin combination treatments for falciparum malaria (except for those in infants and pregnant women, in whom primaquine is not recommended) to sterilise the infection and prevent onward transmission.134 Testing for G6PD deficiency is not necessary with this dose. Patients should be monitored for vomiting for 1 h after any oral antimalarial dosing. If the patient vomits, another dose should be given. Minor adverse effects (eg, nausea, abdominal discomfort, headache, dizziness) occur frequently in malaria, and often result from the illness rather than the treatment. 3 day artemisinin combination regimens are well tolerated, although mefloquine is associated with increased rates of vomiting and dizziness. The frequency of serious adverse neuropsychiatric reactions to mefloquine is around one per 1000 patients treated in Asia but as high as one per 200 in African and white patients. All the antimalarial quinolines (ie, chloroquine, mefloquine, and quinine) exacerbate orthostatic hypotension, and are tolerated better by children than by adults (panel 2). Panel 2 Second line treatments and new drugs •Artesunate 2 mg/kg daily plus tetracycline* 4 mg/kg four times daily, doxycycline* 3 mg/kg daily, or clindamycin 10 mg/kg twice daily for 7 days •Quinine 10 mg salt per kg three times daily plus tetracycline* 4 mg/kg four times daily, doxycycline* 3 mg/kg daily, or clindamycin 10 mg/kg twice daily for 7 days •Atovaquone—proguanil 20 mg/kg—8 mg/kg daily for three days (with food) •Artesunate—pyronaridine 4 mg/kg—12 mg/kg daily for three days135, 136 * Not suitable for pregnant women or children younger than 8 years. Resistance Western Cambodia and the Thailand—Myanmar border, where artemisinin-resistant P falciparum has emerged,137, 138 are the regions of greatest concern. Resistance to both chloroquine and sulfadoxine—pyrimethamine emerged prreviously in this area, and in both cases the resistance genes spread to Africa and caused millions of deaths. Artemisinin-resistant parasites are cleared slowly from the blood after artemisinin combination treatment. Parasite clearance times exceed 3 days, and treatment failure occurs more often. Resistance to amodiaquine, sulfadoxine—pyrimethamine, and, to a lesser extent, mefloquine, limits deployment of artemisinin combinations containing these drugs in several areas. Up-to-date information about antimalarial drug resistance is available from the Worldwide Antimalarial Resistance Network. P vivax and other malarias Despite increasing resistance in P vivax, chloroquine is widely used to treat non-falciparum malarias, except in Indonesia and Papua New Guinea, where highly resistant P vivax is widespread.139 In Asia, P vivax and P falciparum often co-infect, and, in parts of southeast Asia, subsequent P vivax infection occurs in as much as 50% of patients treated for falciparum malaria.140 In view of the increasing resistance to chloroquine in P vivax, the potential for misdiagnosis and subsequent inadvertent use of chloroquine to treat falciparum malaria, and operational advantages, artemisinin combination treatment seems a good first-line treatment for all human malarias. To prevent relapses of tropical P vivax malaria, a full course of primaquine (0·5 mg base per kg daily for 14 days—so-called radical treatment) should be given (table).120 For Plasmodium ovale and temperate strains of P vivax, the primaquine dose is 0·25 mg base per kg per day. Testing for G6PD deficiency is necessary because daily primaquine causes potentially dangerous haemolysis in G6PD-deficient patients. In patients with mild variants of G6PD deficiency, weekly primaquine (0·75 mg base per kg) for 8 weeks is safer than, and probably as effective as, daily treatment. Pregnant women with vivax or ovale malaria should be given suppressive prophylaxis with chloroquine (5 mg base per kg per week) until delivery, at which point radical treatment with primaquine can be given. Control and elimination Where malaria has been reduced substantially, acquisition of immunity slows and symptomatic disease extends to older children and then to adults. Occasional epidemics can occur. This pattern, which is now noted in some parts of Africa, is similar to that reported previously in Asia and southern Europe. In areas of low seasonal transmission—eg, much of Asia, Central and South America, strengthening of control measures usually has a greater effect on P falciparum than on P vivax. Some countries—eg, Turkmenistan (2006), United Arab Emirates (2007), Morocco (2010), Armenia (2011)—have achieved elimination in the past 10 years. Others, where local transmission no longer occurs, await WHO certification—eg, Egypt (1998), Mauritius (1998), Oman (2000), Algeria (2005), Syria (2005). In some areas, despite substantial financial investment in malaria control, commensurate reductions in case numbers have not been noted. Possibly, the epidemiology of malaria in these areas was underestimated. Often, small foci of stable transmission within low transmission areas act as transmission reservoirs, and asymptomatic malaria has been underestimated substantially. Artemisinin resistance poses the greatest threat to global malaria control, and more vigorous containment and elimination measures than have been instituted in the past 6 years are needed. Radical measures to eliminate resistance foci, such as mass drug administration, might be needed. The value of active case detection is uncertain. Greater use of primaquine to prevent relapse of vivax malaria and as a gametocytocide in falciparum malaria would help with control and elimination in areas with low transmission

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Malaria is caused by Plasmodium parasites that are spread to people through the bites of infected Anopheles mosquito vectors. Of the 5 parasite species that cause malaria in humans, Plasmodium falciparum is the most deadly. Globally over 3.2 billion people are at risk of malaria. In 2015, there were an estimated 214 million malaria cases and some 438 000 malaria deaths. Malaria is a public health problem in India. 561 cases died in 2014, 440 in 2013 and 519 in 2012. ICMR and IMA should do post mortem analysis of all 561 cases to learn lessons. About 95% population in the country resides in malaria endemic areas and 80% of malaria reported in the country is confined to areas consisting 20% of population residing in tribal, hilly, difficult and inaccessible areas. Young children, pregnant women are most vulnerable. Under 5 are particularly susceptible to infection, illness and death. More than two thirds (70%) of all malaria deaths occur in this age group. Increased malaria prevention and control measures are dramatically reducing the malaria burden in many places. Early diagnosis and treatment of malaria reduces disease and prevents deaths. It also contributes to reducing malaria transmission. Access to diagnostic testing and treatment should be seen not only as a component of malaria control but as a fundamental right of all populations at risk. Artemisinin-based combination therapies remain effective in almost all settings, as long as the partner drug in the combination is locally effective. Long-lasting insecticidal nets provide personal protection against mosquito bites. They can be used as protection for people most at risk of malaria, such as young children and pregnant women. The nets are effective for 2-3 years, depending on the model and conditions of use. The full potential of indoor residual spraying is obtained when at least 80% of houses in targeted areas are sprayed. Indoor spraying with insecticides kills the mosquito vector and is effective for 3–6 months, depending on the insecticide used and the type of surface on which it is sprayed. For pregnant women WHO recommends intermittent preventive treatment at each scheduled antenatal visit after the first trimester. The mosquito bite between dusk and dawn. WHO recommends protection for all people at risk of malaria with effective malaria vector control. Two forms of vector control – insecticide-treated mosquito nets and indoor residual spraying – are effective in a wide range of circumstances Long-lasting insecticidal nets (LLINs) are the preferred form of insecticide-treated mosquito nets (ITNs) for public health programmes. In most settings, WHO recommends LLIN coverage for all people at risk of malaria. The most cost-effective way to achieve this is by providing LLINs free of charge, to ensure equal access for all. In parallel, effective behaviour change communication strategies are required to ensure that all people at risk of malaria sleep under a LLIN every night, and that the net is properly maintained. For pregnant women WHO recommends intermittent preventive treatment with sulfadoxine-pyrimethamine, at each scheduled antenatal visit after the first trimester. In 2012, WHO recommended Seasonal Malaria Chemoprevention as an additional malaria prevention strategy. The strategy involves the administration of monthly courses of amodiaquine plus sulfadoxine-pyrimethamine to all children under 5 years of age during the high transmission season. Much of the success in controlling malaria is due to vector control. Vector control is highly dependent on the use of pyrethroids, which are the only class of insecticides currently recommended for ITNs or LLINs. 28. Malaria-endemic areas of sub-Saharan Africa and India are causing significant concern due to high levels of malaria transmission and widespread reports of insecticide resistance. The use of 2 different insecticides in a mosquito net offers an opportunity to mitigate the risk of the development and spread of insecticide resistance. WHO recommends that all cases of suspected malaria be confirmed using parasite-based diagnostic testing (either microscopy or rapid diagnostic test) before administering treatment. Results of parasitological confirmation can be available in 30 minutes or less.

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Nice post , Thanks

Nice post Dr Shashank

OMG such a lengthy read anyways very helpful information DR thanks

Very nice and helpful information. Thanks.

helpful info. . . . Thanks for sharing,Dr. .

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