2013, Issue 12

 Two  new reviews and one new protocol  are  available in Issue 12, 2013 of the Cochrane Database of Systematic Reviews:  

•  Larvivorous fish to preventing malaria transmission (Walshe DP, Garner P, Abdel-Hameed Adeel AA, Pyke GH, Burkot T)  Link to review

This review evaluates whether introducing larvivorous fish to malaria-transmitting mosquito breeding sites such as ponds, rivers, and communal water bodies, has an effect on the transmission of Plasmodium parasites and on the density and presence of mosquito larvae in these waters. Deirdre Walshe, Tom Burkott and colleagues did not find any studies reporting an effect on malaria infection in nearby communities. Included in the review are 12 small studies, with follow-up from 22 days to five years, which studied the effects of introducing larvivorous fish on the density and presence of mosquito larvae and pupae in community water sources. There is some weak evidence suggesting an effect on the density or presence of immature mosquitoes with high stocking levels of fish, but this result is not consistent, and the data is insufficient to show whether introducing larvivorous fish also reduces the density of adult mosquitoes or the transmission of malaria. The authors conclude that before much is invested in this intervention, better research on its effects is needed.

•   Mass drug administration for malaria (Poirot E, Skarbinski J, Sinclair D, Kachur SP, Slutsker L, Hwang J)  Link to review 

In this new review, Jimee Hwang, Eugene Poirot and colleagues examine the impact of mass administration of antimalarial drugs on several parameters of malarial infection, such as parasitemia, anemia, mortality, and disease transmission. Mass drug administration (MDA) is the empiric administration of antimalarial drugs to whole population at risk of the disease, irrespective of their malarial status. MDA was a historic component of many malaria control and elimination programmes, and is not currently recommended, but it is once again re-considered as a malaria elimination tool. The review includes 32 studies of different design, conducted in areas of various malaria endemicity; many of them are more than 30 years old, and use a wide variety of regimens with different drugs, dosages, and timings. The review found that although MDA can reduce the initial risk of malaria-specific outcomes, these reductions are often short-term, except for a few studies conducted on small islands or in highland areas where the positive effects of MDA in controlling malaria lasted more than six months. Some regiments resulted in severe adverse events. Overall, the optimum regimens for producing a sustained impact with MDA remain largely unknown.

New protocol

• Symptom-and chest-radiography screening for acitve pulmonary tuberculosis in HIV-negative adults and adults with unknown HIV status  (van't Hoog AH, Langendam M, Mitchell E, Cobelens FG, Sinclair D, Leeflang MM, Lonnroth K)  Link to protocol

2013, Issue 10

• Combined and alternating paracetamol and ibuprofen therapy for febrile children  (Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM, Johnson DW)   Link to review

Both paracetamol and ibuprofen lower temperature and relieve discomfort in febrile children, and health professionals frequently recommend treatments that either combine or alternate the two drugs. In this new review Tiffany Wong and her team evaluate whether giving paracetamol or ibuprofen together to children with fever, or alternating them, is more effective and has fewer side effects than giving them alone. The review includes 6 studies, enrolling 915 participants. Compared to giving ibuprofen or paracetamol alone, giving both medications together is probably more effective at lowering temperature for the first four hours after treatment, but there was no evidence that combined treatment made children less uncomfortable than ibuprofen or paracetamol alone. In practice, caregivers are often advised to initially give a single agent (paracetamol or ibuprofen), and then give a further dose of the alternative if the child continues to have a fever. Giving alternating treatment in this way may be more effective at lowering temperature for the first three hours after the second dose, and may also result in less child discomfort. Only one small trial compared alternating therapy with combined therapy and found no advantages between the two.

• Lactose avoidance for young children with acute diarrhoea (MacGillivray S, Fahey T, McGuire W) Link to review

Young children with acute diarrhoea may temporarily be unable to digest lactose, the most common type of sugar in milk, and this can make the diarrhoea worse and last longer. Stephen MacGillivray and co-authors looked for evidence that reducing children's lactose intake, either by feeding lactose-free milk or by diluting lactose-containing milk, shortens the duration of diarrhoea and prevents complications such as dehydration. The review includes 33 trials with 2973 children suffering from acute diarrhoea. 22 trials compared children given a lactose-free feed with children given a lactose-containing feed and 11 trials compared children fed a diluted milk feed with children given an undiluted milk feed. There is evidence that lactose-free feeds may reduce the duration of diarrhoea by an average of about 18 hours, and probably lower the risk of children having prolonged or worsening diarrhoea. Diluting lactose-containing formulas may also have some benefits but further trials are required to confirm this finding. There are no trials from low-income countries, where mortality for diarrhoea is high, and malnutrition is more common.

Updated reviews

• Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax malaria  (Gogtay N, Kannan S, Thatte UM, Oliaro PL, Sinclair D)  Link to review

Nithya Gogtay and colleagues have completed an update of this review, which was first published in 2011. This update involves a new search (with 2 new trials included) and changes in the authorship. The review now includes 14 trials, with 2592 participants, all conducted in Asia and Oceania between 2002 and 2011. The standard treatment for vivax malaria has been chloroquine to treat the clinical illness, and a 14-day course of primaquine to clear the liver stage. In some parts of Oceania the P. vivax parasite in now highly resistant to chloroquine, which makes this treatment ineffective. Artemisinin-based combinations (ACTs) appear at least equivalent to chloroquine at effectively treating the blood stage of P. vivax infection. This finding may allow for simplified protocols for treating all forms of malaria with ACTs, and offers an effective alternative in areas where the parasite is resistant to chloroquine.  Dihydroartemisinin-piperaquine, the most studied ACT, may provide a longer period of post-treatment prophylaxis than artemether-lumefantrine or artesunate plus amodiaquine. This effect may be clinically important in high transmission settings whether primaquine is also given or not

• Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine (Galappaththy GNL, Tharyan P, Kirubakaran R) Link to review

This review, first published in 2007, has now been updated with 6 additional trials and one change of author. It now includes 15 trials with 4377 adult and child participants with vivax malaria. All were treated with chloroquine for the blood stage infection, and then randomized to the 14-day primaquine course, or to shorter primaquine courses (3, 5 or 7 days); or to higher doses of primaquine given once a week for eight weeks; or to a placebo or no treatment. Relapse over six months to one year is probably higher with shorter regimens when compared to the standard 14-day primaquine regimen. The 14-day primaquine course prevented many more people relapsing with vivax malaria over 12 months than placebo.  No serious adverse reactions to primaquine were reported. Gawrie Galappaththy and colleagues conclude that this review update confirms that the 14-day primaquine course, recommended by the WHO, is more effective against relapse of vivax malaria than treatment with shorter courses of primaquine.

New protocol

• Intermittent preventive antimalarial treatment for children with anaemia (Athuman M, Kabanywanyi AM, Rohwer AC) Link to protocol 

2013, Issue 8

 One  new review, one updated review and two new protocols  are  available in Issue 8, 2013 of the Cochrane Database of Systematic Reviews:

New review

• Mosquito larval source management for controlling malaria (Tusting L, Thwing L, Sinclair D, Fillinger U, Gimnig J, Bonner KE, Bottomley C, Lindsay SW)   Link to review

Larval source management (LSM) aims to reduce malaria by targeting immature mosquitoes, which are found in standing water, before they develop into flying adults.  In this review Lucy Tusting and co-authors assessed evidence from 13 studies, four cluster-RCTs, eight controlled before-and-after trials, and one randomized cross-over trial.  LSM was shown to be effective in Sri Lanka, India, the Philippinesk Greece, Kenya and Tanzania. Interventions included adding larvicides to abandoned mine pits, streams, irrigation ditches and rice paddies where mosquitos breed, and building dams, flushing streams, and removing water containers from around people's homes.  In contrast, in one study from The Gambia, larvicide spraying of swamps and rice paddies where mosquitos were breeding did not show any benefit. The authors conclude that LSM is an additional policy option, alongside insecticide impregnated nets and indoor residual spraying, for reducing malaria morbidity in urban and rural areas of Africa and Asia where a sufficient proportion of larval habitats can be targeted.  Further research is needed to evaluate whether LSM is appropriate or feasible in parts of rural Africa where larval habitats are more extensive.

Updated review

• Probiotics for treating persistent diarrhoea in children (Bernaola Aponte G, Bada Mancilla CA, Carreazo NY, Rojas Galarza RA) Link to review

New protocols

• Artemether intramuscular injection for severe malaria in children (Esu E, Effa EE, Opie ON, Uwaoma A, Meremikwu MM) Link to protocol
• The GenoType® MTBDRsl test for resistance to second-line anti-tuberculosis drugs (Theron G, Peter J, Barnard M, Donegan S, Warren R, Steingart KR, Dheda K) Link to protocol

2013, Issue 7

• Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea (Ahmed T, Bhuiyan TR, Zaman K, Sinclair D, Qadri F)   Link to review

Firdausi Qadri and co-authors examined the research on the use of vaccines to prevent diarrhoea caused by enterotoxigenic Escherichia coli (ETEC vaccines). ETEC is transmitted from person to person by eating or drinking unclean food or water and is a common cause of diarrhoea in adults and children in developing countries, as well as a major cause of 'travellers' diarrhoea.  Because ETEC shares some similarities with the bacteria that causes cholera, it has been suggested that a licensed anti-cholera vaccine may be effective against ETEC. This review examines the effectiveness of the anti-cholera vaccine and of vacinnes designed specifically to prevent ETEC infection. The available evidence comes from 24 RCTs with 53,247 participants (4 studies for oral cholera vaccines and 8 trials for ETEC -specific vaccines, 7 studies with data from field trials and 4 studies with data from experimental studies). There was insufficient evidence to support the use of the currently available oral cholera vaccine to protect travellers against ETEC diarrhoea. An ETEC-specific, killed whole cell vaccine, (which also contains the recombinant cholera toxin B-subunit), was not effective in preventing travellers' diarrhoea and was associated with increased vomiting; the other ETEC-specific vaccines in development have not yet demonstrated clinically important benefits.  The authors conclude that further research is needed.  

• Riramycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB (Sharma SK, Sharma A, Kadhiravan T, Tharyan P)  Link to review

This new review, prepared by Surendra Sharma and co-authors, assesses drug regimens used to prevent the development of active tuberculosis in people with a latent tuberculosis infection. The comparators are: isoniazid, which when given for six to nine months has 60% to 90% protective efficacy, but can also cause liver toxicity, and has only 50% completion rates; and rifampicin or rifamycin-combination regimens, which are shorter and may result in more people completing the treatment.  The review includes 10 trials with 10,717 adults and children, mostly HIV-negative (2% HIV-positive), with a follow-up period ranging from two to five years.  Results show that rifampicin for 3-4 months may give quite similar results to isoniazid for six months in preventing TB, with fewer side effects, and as the treatment period is shorter, it may result in more people completing treatment.  Two other drug combination treatments (rifampicin plus isoniazid, and rifampicin plus pyrazinamide) did not differ in preventing TB compared with isoniazid alone, but they resulted in more adverse events. A weekly regimen of rifapentine plus isoniazid has higher completion rates and less liver toxicity, though treatment discontinuation due to adverse events is probably morelikely than with isoniazid alone.

2013, Issue 6

One  updated review  and one new protocol are  available in Issue 6, 2013 of the Cochrane Database of Systematic Reviews:

Updated review

• Fluoroquinolones for treating tuberculosis (presumed drug-sensitive) (Ziganshina LE, Titarenko AF, Davies GR)  Link to review

Lilia Ziganshina and co-authors have substantially modified this review, originally published in 2005, by narrowing its scope to presumed drug-sensitive tuberculosis, as well as restructuring research questions, comparisons and outcomes.  The review now includes five RCTs (with 1330 participants) of anti-TB regimens based on rifampicin and pyrazinamide, and containing fluoroquinolones. The trials were done in low-and middle-income countries located in geographically diverse areas, but none were conducted in Asia.  All trials were of low quality evidence. One small trial added levofloxacin to the standard first-line regimen, with unclear results on its efficacy and safety.  Three trials with 723 participants substituted ethambutol with moxifloxacin, gatifloxacin, and ofloxacin into the standard first-line gerimen, with unclear results.  One trial (433 participants) substituted moxifloxacin for isoniazid, with little or no difference in outcomes.  The reviewed evidence is insufficient to conclude whether addition or substitution of fluoroquinolones to standard first-line regimens of six months reduces death or relapse, or increases culture conversion at eight weeks.  Several larger trials with fluoroquinolones in short course regimens of four months are currently in progress.

New protocol

• Anthelmintic drugs for treating ascariases (Conterno LO, Garcia MVF, Mukai NS) Link to protocol 

2013, Issue 5

 One new review is available in Issue 5, 2013 of the Cochrane Database of Systematic Reviews:

New review

• Home- or community-based programmes for treating malaria (Okwundu CI, Nagpal S, Musekiwa A, Sinclair D) Link to review

Charles Okwundu and co-authors have prepared this new review, which evaluates home-or community-based programmes for managing malaria in endemic settings.  These programmes are potentially useful in rural areas, where health services are too far away or antimalarial drugs are too expensive,. The review includes 10 studies: all involved brief training of basic-level health workers or mothers, and most provided the antimalarial for free or at a hightly subsidized cost. In 8 studies all people with fever were treated with antimalarial drugs by community health workers, and in 2 studies community health workers were trainied to accurately recognize malaria from other causes of fever using rapid diagnostic tests (RDT's).  Results show that home-or community-based strategies probably increased the number of people with fever who received an apropriate antimalarial within 24 hours.  They may also reduce all-cause mortality, but this was only shown in a trial with 13,000 participants in rural Ethiopia.  In two studies where community health workers used RDTs to accurately diagnose malaria, in comparison with clinical diagnosis, the overuse of antimalarial drugs was reduced, and mortality and hospitalizations remained very low in both groups.

2013, Issue 3

Two new protocols are available in Issue 3, 2013 of the Cochrane Database of Systematic Reviews:

New protocols

• Tafenoquine for Plasmodium vivax malaria infection (Rajapakse S, Rodrigo C, Fernando SD ) Link to protocol
• Treatment of enteric fever (typhoid and paratyphoid fever) with third and fourth generation cephalosporins (Stoesser N, Eyre D, Basnyat B, Parry C) Link to protocol

2013, Issue 2 

• Drugs for treating Schistosoma mansoni infection (Danso-Appiah A, Olliaro PL, Donegan S, Sinclair D, Utzinger J) Link to review

Tony Danso-Appiah and co-authors have prepared this new review, which replaces a previous version and includes additional outcomes and new drugs.  Schistosoma mansoniis a parasitic worm common in Africa, the Middle East and parts of South America; larvae enter humans through the skin, when people swim or bathe in contaminated ponds and lakes. The disease is caused by the eggs produced by adult worms, which can get trapped in the host’s tissue resulting in inflammation and fibrotic lesions of the liver, with cirrhosis, portal hypertension, and possibly internal bleeding and death. This review includes 52 trials with 10,269 participants evaluating the use of praziquantel, oxamniquine, myrrh and artesunate. The results show that a single dose of praziquantel (40 mg/kg), as recommended by the World Health Organization, is an effective treatment forSchistosoma mansoniinfection.  Oxamniquine, though now rarely used, is also effective. The effectiveness of combining praziquantel with artesunate needs to be confirmed. Further research is needed to optimise dosages for children under 5 years.  

2013, Issue 1

• Treating BCG-induced disease in children (Cuello-García  CA, Pérez-Gaxiola  G, Jiménez Gutiérrez  C) Link to review

Carlos Cuello-García and co-authors all based in Mexico, in this new review assess the effects of different interventions for treating the reactions caused in children by vaccination with Bacillus Calmette-Guerín (BCG). BCG has been used since the 1920s to prevent tuberculosis, and is routinely administered at birth in many countries, as recommended by the WHO.  Usually, the only adverse reaction is a small scar at the site of injection, but sometimes serious local infections, lymphadenopathy, and bone involvement can occur - especially in children with a weak immune systems such as in HIV infection. The review includes 5 small RCTs of low methodological quality, with 341 children.  There was no evidence of any benefit of using oral antibiotics to treat local or regional uncomplicated BCG-induced disease; for abscess-forming lymphadenopathy, needle aspiration of the abscesses with or without local injection of isoniazid was useful. More research is needed.

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

Xpert® MTB/RIF assay (Xpert) is an automated test that can detect both TB and rifampicin resistance within two hours. In this review Karen Steingart and co-authors examine the diagnostic accuracy of Xpert, 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 majority of the 18 included studies took place in low-income and middle-income countries with a high TB burden and were performed by trained technicians in reference laboratories. Xpert was sensitive and specific when used as an initial diagnostic test for TB detection and rifampicin resistance detection in patients suspected of having TB, MDR-TB, or HIV-associated TB. Xpert may also be valuable as an add-on test following microscopy, for patients who have previously been found to be smear-negative. An Xpert result that is positive for rifampicin resistance should be carefully interpreted to take into consideration the risk of MDR-TB. Future studies should assess the diagnostic accuracy of Xpert in peripheral laboratories, the accuracy of Xpert in children, and include the newest Xpert version (currently G4 cartridge).