2014, Issue 12

One new review and two new protocols are available in Issue 12, 2014 of the Cochrane Database of Systematic Reviews:

New review

  • Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries (Abba K, Kirkham AJ, Olliaro PL, Deeks JJ, Donegan S, Garner P, Takwoingi Y)  Link to review

In settings where both Plasmodium vivax and Plasmodium falciparum infection cause malaria, it is essential to distinguish which species is causing the patients' symptoms, as different treatments are required. This new review aims to to identify which types and brands of rapid diagnostic tests (RDTs) best detect non-falciparum and P. vivax malaria. Katherine Abba and her colleagues analysed data from 47 studies enrolling 22,862 participants, and found that RDTs which test for non-falciparum malaria were very specific - only 1% to 2% of patients who test positive would actually not have the disease. However, they were less sensitive, and between 11% and 22% of people with non-falciparum malaria would actually get a negative test result. RDTs which specifically tested for P. vivax were more accurate with a specificity of 99% and a sensitivity of 95%, meaning that only 5% of people with P. vivax malaria would have a negative test result. The quality of the included studies was variable.

New protocols

  • Interventions to increase tuberculosis case detection at primary healthcare or community level services  (Mhimbira FA, Cuevas LE., Dacombe R, Mkopi A, Sinclair D) Link to protocol
  • Urine lateral flow lipoarabinomannan assay for diagnosing active tuberculosis in adults living with HIV (Shah M, Hanrahan C, Wang ZY, Steingart KR, Lawn SD, Denkinger C, Dendukuri N) Link to protocol

2014, Issue 11

One new review and one updated review are available in Issue 11, 2014 of the Cochrane Database of Systematic Reviews:  

New review

  • Adjunctive steroid therapy for managing pulmonary tuberculosis  (Critchley JA, Orton LC, Pearson F)   Link to review

Current clinical guidelines advise the use of corticosteroids added to standard anti-pulmonary tuberculosis drugs, for treatment of tuberculosis meningitis and tuberculosis pericarditis, but it was not clear whether corticosteroids would also be beneficial in the treatment of pulmonary tuberculosis. This new review prepared by Julia Critchley and colleagues includes 18 trials with 3816 participants: corticosteroid use in pulmonary TB patients was not shown to reduce all-cause mortality, or result in higher sputum conversion at 2 months or at 6 months, but it was found to increase weight gain, decrease length of hospital stay, and increase clinical improvement within one month. The evidence however was of low or very low quality. The authors conclude that that there is not enough high quality data to support or reject corticosteroid use alongside anti-pulmonary tuberculosis drugs.

 Updated review

  • Reminder systems to improve patient adherence to tuberculosis clinic appointments for diagnosis and treatment (Liu Q, Abba K, Alejandria MM, Sinclair D, Balanag VM, Lansang MAD)  Link to review

This updated review by Qin Liu and her team evaluates the effects of different reminder systems (letters, phone calls) on improving patients’ attendance at TB diagnosis, prophylaxis, and treatment clinic appointments, and the effects on TB treatment outcomes. Nine trials, including 4654 participants, were identified. For people being treated for active TB, clinic attendance and TB treatment completion were higher in people receiving pre-appointment reminder phone-calls and also in those receiving default reminders (letters or home visits). For people on TB prophylaxis, clinic attendance was higher with a policy of pre-appointment phone-calls, and attendance at the final clinic was higher with regular three-monthly phone-calls or nurse visits. For people undergoing screening for TB, reminders did not seem to make a difference and similar numbers of people attended clinic for skin test reading with and without pre-appointment phone-calls or with and without take home reminder cards. The authors conclude that reminders have small but potentially important benefits, and future studies should focus on modern technologies such as short message service (SMS) reminders, particularly in low-resource settings.

 2014, Issue 10

One new review and one updated review are available in Issue 10, 2014 of the Cochrane Database of Systematic Reviews:  

New review

  • The diagnostic accuracy of the GenoType® MTBDRsl assay for the detection of resistance to second-line anti-tuberculosis drugs (Theron G, Peter J, Richardson M, Barnard M, Donegan S, Warren R, Steingart KR, Dheda K)DTA  Link to review

Genotype®MTBDRsl (MTBDRsl) is the only commercially-available molecular test for detecting resistance in tuberculosis (TB) to the fluoroquinolones (FQs) and to the second-line injectable drugs (SLIDs), which are used to treat patients with multidrug-resistant (MDR-) TB. Grant Theron and colleagues have summarized evidence from 21 studies , 11 of which were in low-income or middle-income countries, that tested the diagnostic accuracy of MTBDRsl for FQ resistance, SLID resistance and extensively drug-resistant TB (XDR-TB), when performed indirectly (ie on culture isolates confirmed as TB positive) or directly (ie on smear-positive sputum specimens). Results show that a positive MTBDRsl result for resistance to the fluoroquinolone drugs or the SLIDs drugs is reliable evidence that the person has drug-resistant TB, and further conventional drug-resistance testing is not required. However, when the test reports a negative result, clinicians may still wish to carry out conventional testing.

Updated review

  • Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment (Radeva-Petrova D, Kayentao K, ter Kuile FO, Sinclair D, Garner P) Link to review

Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. For this reason, women are encouraged to try and prevent malaria infection during pregnancy by sleeping under mosquito bed-nets, and by taking drugs effective against malaria throughout pregnancy as chemoprevention.

Denitsa Radeva-Petrova and her colleagues in this review summarise and quantify the overall effects of all antimalarial chemoprophylactic regimens used in pregnant women compared to placebo and include 17 trials, all conducted between 1957 and 2008, and all but two in countries of Africa.

For women in their first or second pregnancy, malaria chemoprevention prevents moderate to severe anaemia (high quality evidence); and prevents malaria parasites being detected in the blood (high quality evidence). It may also prevent malaria illness. It is not clear if it prevents maternal deaths, as this would require very large studies to detect an effect. In their infants, malaria chemoprevention improves the average birthweight (moderate quality evidence), and reduces the number of low birthweight infants (moderate quality evidence). It is not clear if chemoprevention reduces mortality of babies in the first week, month and year, as again studies would need to be very large to show these effects.

2014, Issue 9

One new review is available in Issue 9, 2014 of the Cochrane Database of Systematic Reviews:

New review

  • Artemether for severe malaria (Esu  E, Effa  EE, Opie  ON, Uwaoma  A, Meremikwu  MM)  Link to review

This review examines  the effects of intramuscular artemether for treating people with severe malaria, and comparing them to commonly used alternatives.

Severe malaria remains an important cause of child deaths, particularly in sub-Saharan Africa, where the World Health Organization (WHO) estimates there are 600,000 deaths each year. In 2011, the WHO changed its recommendation for the treatment of severe malaria from quinine to artesunate, based on high quality evidence that artesunate saved more lives. However, in some African countries artemether, a drug related to artesunate but with less favourable chemical properties, has become widely available and used as treatment. Consequently, this systematic review of artemether provides a timely summary of the evidence to guide international and national treatment policies.

The authors looked at 18 randomized controlled trials carried out in Africa and Asia, including 2662 adults and children. They found no trials directly comparing artemether with artesunate in children, but two trials from Asia showed higher mortality in adults treated with artemether. Sixteen trials compared artemether with quinine, and while the number of deaths was very similar between the two treatments in children, in adults in Asia there were more deaths in those treated with quinine.

"Although there is a lack of direct evidence comparing artemether with artesunate, the indirect evidence strongly suggests that artemether will be less effective than artesunate at preventing deaths from severe malaria" says lead author Ekpereonne Esu from University of Calabar, Nigeria, "However, in circumstances where artesunate is not available, artemether is an effective alternative to quinine."

2014, Issue 6

Two new reviews, 2 updated reviews and one new protocol are available in Issue 6, 2014 of the Cochrane Database of Systematic Reviews:

New reviews

  • Antimicrobial drugs for treating cholera (Leibovici-Weissman Y, Neuberger A, Bitterman R, Sinclair D, Salam MA, Paul M)  Link to review 

Ya'ara Leibovici-Weissman and her co-authors evaluate the benefits of antibiotics for treating people with cholera, and also determine whether there are differences between classes of antimicrobials or dosing schedules. Cholera can cause severe dehydration and death, so the main treatment is to give the patients fluids and salt, but giving antibiotics could reduce the duration and severity of the illness, and reduce transmission to other people.  Data from 39 randomized controlled trials enrolling 4623 people showed that antibiotic treatment shortened the duration of diarrhoea by about one and a half days (the normal duration is between three and four days), and reduced the total amount of diarrhoea fluid by half, consequently reducing  the need for rehydration . The period of time where the patient remains contagious was also shortened using antibiotics. Similar effects were observed in severely and non-severely ill patients. Tetracycline or azithromycin appear more effective than some of the other antibiotics tested, but the choice of which antibiotic to use will depend on local drug resistance.

  • Rapid tests for the diagnosis of visceral leishmaniasis in patients with suspected disease (Boelaert M, Verdonck K, Menten J, Sunyoto T, van Griensven J, Chappuis F, Rijal S) Link to review

This diagnostic test accuracy review was prepared by a team led by Marleen Boelaert and it evaluates rapid tests for diagnosing visceral leishmaniasis (VL) in patients with suspected disease, presenting at health services in endemic areas. Rapid diagnostic tests are generally easy to perform in comparison with conventional parasitological techniques, which are invasive, require special laboratories, and can be time-consuming and less accurate. 24 studies containing information about five index tests (rK39 immunochromatographic test (ICT), KAtex latex agglutination test in urine, FAST agglutination test, rK26 ICT, and rKE16 ICT) recruiting 4271 participants (2605 with VL) are included in the review.  The rK39 ICT gave correct, positive results in 92% of the people with visceral leishmaniasis and it gave correct, negative results in 92% of the people who did not have the disease. This test worked better in India and Nepal than in east Africa. The latex agglutination test gave correct, positive results in 64% of the people with the disease and it gave correct, negative results in 93% of the people without the disease. For the other rapid tests evaluated, there are too few studies to know how accurate they are.

Updated reviews

  • Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission (Graves PM, Gelband H, Garner P) Link to review

Primaquine (PQ)is an antimalarial drug which does not cure malaria illness, but is known to kill the gametocyte stage of the malaria parasite which infects mosquitoes when they bite humans.  The World Health Organization (WHO) in 2010 recommended adding a single dose of PQ to malaria treatment in order to reduce malaria transmission and to contribute to malaria elimination; in 2013 the recommended dose of PQ was reduced to 0.25 mg/kg due to concerns about safety, especially in people with G6PD deficiency. Tricia Graves and co-authors in this updated review analyse data from 17 RCT and one quasi-RCT to assess whether PQ, or an alternative 8AQ, alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events. They conclude that in individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Two small studies reported a strong reduction in infectiousness, but no trials assessed whether this policy has an impact on community malaria transmission, and a single study of the currently WHO recommended dose of 0.25 mg/kg showed no effect on gametocytes. Overall the safety of PQ given as a single dose was poorly evaluated across all studies.

  • Corticosteriods for dengue infection (Zhang F, Kramer CV) Link to review

Dengue is a widespread mosquito-borne viral infection, endemic in many low- and middle-income countries and, in its severe form, an important cause of death in children. There is no specific treatment for dengue, but some clinicians provide corticosteroids at an early stage to prevent progression to severe dengue disease; and some treat patients with dengue-related shock with corticosteroids to improve survival. In this updates review Fan Zhang and Christine Kramer summarize the findings from 8 studies enrolling 948 participants. Four studies enrolled children younger than 15 years with dengue-related shock. These studies were small and older than 20 years; they were of very low quality and did not provide any reliable evidence for using corticosteroids for treating dengue-related shock. Four trials evaluated whether corticosteroids provided at an early stage of dengue could prevent development of complications of severe dengue. These trials were more recent, but data were insufficient to be sure whether corticosteroids have an effect on the course of the disease.

New protocol

  • NS1 antigen detecting assays for diagnosing acute dengue infection in people living in or returning from endemic countries (Casenghi M, Kosack C, Li R, Bastard M, Ford N) Link to protocol 

2014, Issue 5

One  new review is  available in Issue 5, 2014 of the Cochrane Database of Systematic Reviews:

New review

  •  Pre-referral rectal artesunate for severe malaria (Okebe J, Eisenhut M) Link to review

This new review co-authored by Joseph Okebe and Michael Eisenhut evaluates the effects of pre-referral rectal artesunate for people with suspected severe malaria, living in rural areas without healthcare services. Severe or complicated malaria is treated by giving injections of antimalarial drugs, which need to be started as quickly as possible to reduce the risk of death and brain damage. In some rural areas where people have to travel for several hours to reach healthcare clinics and hospitals, patients with suspected severe malaria could be given artesunate suppositories, to start the treatment quickly before being transported to hospital. Only one trial met the inclusion criteria; a placebo-controlled trial of 17,826 children and adults living in rural villages in Ghana and Tanzania (Africa) and Bangladesh (Asia). In the African sites only children aged 6 to 72 months were enrolled, whereas in Bangladesh, older children and adults were also enrolled. In the younger children (6 to 72 months) there were fewer deaths following pre-referral rectal artesunate than with placebo, but in older children and adults there were more deaths in those given rectal artesunate. This is an unexpected finding and it should be taken into account when forming national and local policies about pre-referral treatment.  

2014, Issue 4  

One  new review and one new protocol are  available in Issue 4, 2014 of the Cochrane Database of Systematic Reviews:

New review

  • Rapid diagnostic tests versus clinical diagnosis for managing people with fever in malaria enemic settings  (Odaga  J, Sinclair  D, Lokong  JA, Donegan  S, Hopkins  H, Garner  P) Link to review

This  new review analyzes the effects of introducing rapid diagnostic tests (RDTs) for diagnosing malaria in endemic areas.  In many remote areas, diagnosis of malaria has relied on detecting fever or clinical symptoms alone, and it is likely that many people were given antimalarial drugs when their fever was caused by other conditions. RDTs are simple diagnostic kits, which can detect the parasites that cause malaria from a drop of blood in a few minutes and do not require laboratory facilities or extensive training. Their use to confirm or exclude malaria may improve management of people with fever.  John Odaga and co-authors have included seven trials, all conducted in rural African settings, enrolling 17,505 people with fever or reported history of fever.  Overall, RDT supported diagnosis had little or no effect on the number of participants remaining unwell at four to seven days after treatment, but it reduced prescribing of antimalarials by up to three quarters, and did not result in more patients with malaria being incorrectly diagnosed as not having malaria and being sent home without treatment. Using RDTs to support diagnosis did not have a consistent effect on the prescription of antibiotics, with some trials showing an increase in antibiotic prescription and some showing a decrease. There were inconsistencies between trials that can be explained by the variation in adherence of health workers to negative RDT results. The authors conclude that adequate training, support, and supervision for health workers in the use of RDTs, and in the management of patients who test negative, are necessary.

New protocol

  • Interventions to improve disposal of child faeces for preventing diarrhoea and soil-transmitted helminth infection  (Majorin  F, Torondel  B, Ka Seen Chan  G, Clasen TF) Link to protocol

2014, Issue 3

One  new review is available in Issue 3, 2014 of the Cochrane Database of Systematic Reviews:  

New review

  • Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria  (Bukirwa H, Unnikrishnan B, Kramer C V, Sinclair D, Nair S, Tharyan P)    Link to review

This new review compares the efficacy and safety of artesunate-pyronaridine with other artemisinin-based combination therapies (ACTs) for treating people with uncomplicated P. falciparum malaria.  Pyronaridine used on its own has been reported as an effective antimalarial for over two decades in parts of Asia, and was shown to be effective in vitro and in vivo against drug-resistant malaria parasites.  Hasifa Bukirwa and her co-authors have included in this review six randomized controlled trials (enrolling 3718 children and adults) that assess pyronaridine in combination with artesunate, as a possible addition to the current list of recommended ACTs. Three were efficacy trials: 2 multicentre trials comparing artesunate-pyronaridine with artemether-lumefantrine , and one multicentre trial comparing it with artemether plus mefloquine. The three other included studies were safety trials comparing artesunate-pyronaridine with chloroquine, and pyronaridine alone versus chloroquine. Artesunate-pyronaridine performed well in these trials compared to artemether-lumefantrine and artesunate plus mefloquine, with PCR-adjusted treatment failure at day 28 below the 5% standard set by the WHO. Regarding safety, serious adverse events were rare in people treated with either artesunate-pyronaridine or other ACTs. However, short-lasting liver toxicity was more frequent in people treated with artesunate-pyronaridine than with the other antimalarials.  The authors conclude that further efficacy and safety studies in African and Asian children are required to clarify whether the combination of artesunate plus pyronaridine is an option for first-line treatment.

2014, Issue 1

Two new reviews and two  updated reviews are  available in Issue 1, 2014 of the Cochrane Database of Systematic Reviews:

New reviews 
  • Dihydroartemisinin-piperaquine for treating uncompllicated Plasmodium falciparum malaria (Zani B, Gathu M, Donegan S, Olliaro PL, SInclair D)    Link to review

In this new review, Babalwa Zani and her co-authors investigate the use of dihydroartemisinin-piperaquine (DHA-P) for treating uncomplicated malaria. DHA-P is one of five artemisinin-based combination therapies (ACTs) recommended by the WHO to treat malaria: dihydroartemisinin works very quickly to clear the malaria parasites from the infected person’s blood, and piperaquine clears the remaining parasites from the blood and may prevent new infections for several weeks. DHA-P is one of the most studied ACTs, and the review includes 27 randomized controlled trials, enrolling 16,382 adults and children and conducted between 2002 and 2010. Twelve trials were conducted in Africa, 14 in Asia and Oceania, and one was from South America.  The African trials focused on children, while Asian trials included older populations and excluded children below one year of age. All trials excluded pregnant and lactating women. In studies of people living in Africa, both DHA-P and artemether-lumefantrine were very effective at treating malaria, but DHA-P cured slightly more patients than artemether-lumefantrine, and it also prevented further malaria infections. In studies of people living in Asia, DHA-P was effective as artesunate plus mefloquine at treating malaria and had fewer adverse effects. The authors conclude that, while the efficacy of DHA-P is now well established, future research should concentrate on safety surveillance, particularly in infants and pregnant women.

  •  Intermittent versus daily therapy for treating tuberculosis in children (Bose A, Kalita S, ROse W, Tharyan P) Link to review

This review by Anuradha Bose and colleagues compares the efficacy and safety of intermittent, short-course anti-TB regimens (twice- or thrice-weekly) with daily short-course anti-TB regimens in treating childhood TB. Daily regimens cure over 90% of infected children, but have poor adherence, whereas giving anti-TB drugs twice- or thrice-weekly is more convenient to supervise but may not be as effective as daily treatment. The authors identified four trials for inclusion, all published between 1996 to 2000, with 563 children (465 evaluable) aged five months to 15 years. Two trials were from India, one from South Africa, and one from Turkey. The drug combination, and the duration of intermittent and daily treatments differed between trials, and no trials used drug combinations and schedules currently recommended for childhood TB. The trials were small, and did not detect a difference between twice-weekly or daily treatment in the number of children who were cured, died, relapsed, reported taking most or all of the drugs, or had adverse effects.  It is not possible to conclude whether regimens of drugs two or three times a week are as good as regimens with daily doses for treatment of TB in children.

Updated reviews

  • Xpert ® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults (Steingart KR, Schiller I, Home Dj, Pai M, Boehme CC, Dendukuri N) Link to review

This is an update of the original Xpert® MTB/RIF assay review, published in January 2013.  The Xpert® MTB/RIF assay is an automated test that can detect both TB and rifampicin resistance within two hours. In this review Karen Steingart and co-authors examine its diagnostic accuracy, where Xpert was used as an initial test replacing microscopy, or where it was used as an add-on test following a negative smear microscopy result. The review now includes 27 unique studies (with nine new) involving 9557 participants. Sixteen studies (59%) were performed in low- or middle-income countries, and most studies were at low risk of bias.  In adults thought to have TB, with or without HIV infection, Xpert® MTB/RIF is sensitive and specific and it increases TB detection compared with smear microscopy.  For rifampicin resistance detection, Xpert®MTB/RIF provides accurate results and can allow rapid initiation of MDR-TB treatment, pending results from conventional culture and DST. The tests are expensive, so current research evaluating the use of Xpert®MTB/RIF in TB programmes in high TB burden settings will help evaluate how this investment may help start treatment promptly and improve outcomes. Future studies should assess the diagnostic accuracy of Xpert in peripheral laboratories, and the accuracy of Xpert in children.

  • Vaccines for preventing typhoid fever (Anwar E, Goldberg E, Fraser A, Acosta CJ, Paul M, Leibovici L) Link to review

This updated review has a change of some authors and a new search.  The previous version of this review was published in 2007. The current review includes 18 RCTs assessing the two types of vaccines commercially available (Ty21a and Vi polysaccharide) and the new and unlicensed Vi-rEPA vaccine:  12 studies evaluated efficacy and 11 reported on adverse events.  Both Ty21a and Vi polysaccharide were effective in reducing typhoid fever; adverse events such as nausea, vomiting and fever were rare. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity, but it has been evaluated only in children 2 to 5 years of age in one high-incidence setting (Vietnam), and studies of participants of different ages conducted elsewhere would be important before this result can be widely generalized. The authors conclude that the currently available Ty21a and Vi polysaccharide vaccines are effective and safe but neither has been adopted as a routine public health tool in countries where typhoid fever is endemic. Also, neither of the two vaccines is suitable for children under two years of age, and development of a vaccine for this age group would be helpful as they are probably at increased risk of this infection.