News

2018, Issue 11

Three new reviews, one review update and 2 new protocols are available in Issue 11 of the Cochrane Database of Systematic Reviews

New Reviews 

Gleave  K, Lissenden  N, Richardson  M, Choi  L, Ranson  H. Piperonyl butoxide (PBO) combined with pyrethroids in insecticide‐treated nets to prevent malaria in Africa. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD012776. DOI: 10.1002/14651858.CD012776.pub2 

Aves  T, Tambe  J, Siemieniuk  RAC, Mbuagbaw  L. Antiretroviral resistance testing in HIV‐positive people. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD006495. DOI: 10.1002/14651858.CD006495.pub5

Pryce  J, Choi  L, Richardson  M, Malone  D. Insecticide space spraying for preventing malaria transmission. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD012689. DOI: 10.1002/14651858.CD012689.pub2

Updated Review

Pryce  J, Richardson  M, Lengeler  C. Insecticide‐treated nets for preventing malaria. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD000363. DOI: 10.1002/14651858.CD000363.pub3

New protocols

Ochodo  EA, Kakourou  A, Mallett  S, Deeks  JJ. Point‐of‐care viral load tests to detect high HIV viral load levels in HIV‐positive people on antiretroviral therapy. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD013208. DOI: 10.1002/14651858.CD013208

Ochodo  EA, Kakourou  A, Mallett  S, Deeks  JJ. Point‐of‐care tests detecting HIV nucleic acids for diagnosis of HIV infection in infants and children aged 18 months or less. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD013207. DOI: 10.1002/14651858.CD013207

2018, Issue 10

No pubications in this Issue

2018, Issue 9

One new protocol and one review update are available in Issue 9 of the Cochrane Database of Systematic Reviews

Updated Review

El Sayed  I, Liu  Q, Wee  I, Hine  P. Antibiotics for treating scrub typhus. Cochrane Database of Systematic Reviews 2018, Issue 9. Art. No.: CD002150. DOI: 10.1002/14651858.CD002150.pub2.

This is an update of a review first published in 2000; this review has new author team (Iman El Sayed, Qin Liu, Ian Wee and Paul Hine), and a revised protocol, reflecting new methodology.  Scrub typhus, caused by Orientia tsutsugamushi, is an important cause of acute fever in Asia. This bacterium is transmitted by chiggers, and most cases occur in a region which extends from Japan to India, and to Northern Australia (the ‘tsutsugamushi triangle’). Incidence varies from 1.2 to 17.7 per 100,000 per year. This review evaluates the effects of different antibiotic currently used to treat scrub typhus (tetracyclines, chloramphenicol, macrolides, and rifampicin). The authors included 6 RCTs and one quasi‐RCT with 548 participants, taking place in Korea, Malaysia and Thailand. Tetracycline, doxycycline, azithromycin, and rifampicin were shown to be effective treatment options for scrub typhus and to result in few treatment failures. Because of the risk of inducing resistance in undiagnosed tuberculosis, rifampicin should only be considered as a second‐line treatment option after exclusion of active tuberculosis. Most available evidence was of low or very low certainty. Future research should focus on larger trials of good quality, including patients with severe scrub typhus, as well as standardized diagnostic techniques and reporting of clinical outcomes, to allow robust comparisons.

New protocol

de Souza  DK, Larbi  I, Boakye  DA, Okebe  J. Ivermectin treatment in humans for reducing malaria transmission. Cochrane Database of Systematic Reviews 2018, Issue 9. Art. No.: CD013117. DOI: 10.1002/14651858.CD013117

2018, Issue 8

Two new reviews and one review update are available in Issue 8 of the Cochrane Database of Systematic Reviews

New Reviews

Xpert® MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance (Kohli M, Schiller I, Dendukuri N, Dheda K, Denkinger CM, Schumacher SG, Steingart KR)

This new extensive review authored by Mikashmi Kohli and colleagues analysed the diagnostic accuracy of the Xpert assay for extrapulmonary TB by site of disease, or for rifampicin resistance. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing; this review includes diagnostic accuracy studies on TB meningitis,  pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB, as well as rifampicin resistance. 66 unique studies that evaluated 16,213 specimen were identified for inclusion; 50 studies took place in low‐ or middle‐income countries. Xpert results were measured against culture results (benchmark). In cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid, Xpert was highly specific (98% or more), that is, did not register positive in people who were actually negative. Pooled Xpert sensitivity (defined by culture) varied across different types of specimens (31% in pleural tissue to 97% in bone or joint fluid), that is, the test registered positive in people who actually had TB. Regarding rifampicin resistance, Xpert pooled sensitivity and specificity were 95.0% and 98.7% respectively (high‐certainty evidence). The authors conclude that the Xpert assay may be helpful in confirming the diagnosis in people presumed to have extrapulmonary TB, and is accurate for detection of rifampicin resistance, but for people with presumed TB meningitis, treatment should be based on clinical judgement.

Drugs for treating Buruli ulcer (Mycobacterium ulcerans disease) (Yotsu RR, Richardson M, Ishii N)

Buruli ulcer is a disease caused by a mycobacterium, which results in lumps in the skin and deep ulcers, often on the arms or the face. When diagnosed late, those affected may be left with lifelong disfigurements and disabilities. The disease is most prevalent in West Africa, but it is also found in non‐tropical areas including Australia and Japan. This new review by Rie Yotsu, Marty Richardson and Norihisa Ishii summarizes the evidence of drug treatments for treating Buruli ulcer. The authors identified 18 studies for inclusion: five RCTs involving a total of 319 participants, and 13 prospective observational studies, with 1665 participants. Studies evaluated various drugs usually in addition to surgery, and were carried out across eight countries in areas with high Buruli ulcer endemicity in West Africa and Australia.  The certainty of the evidence was very low. One RCT and one observational study evaluated monotherapy with clofazimine, and one RCT evaluated sulfamethoxazole/trimethoprim. All three studies had small sample sizes, and no treatment effect was demonstrated. Different combination therapies were evaluated: rifampicin with streptomycin, rifampicin with clarithromycin, rifampicin with streptomycin initially, changing to rifampicin with clarithromycin in consolidation phase, and novel therapies (rifampicin combined with either ciprofloxacin, clarithromycin, or moxifloxacin without surgery, or a combinations of two to three drugs from rifampicin, ciprofloxacin, clarithromycin, ethambutol, moxifloxacin, or amikacin). Antibiotic combination treatments appeared to be effective, but the evidence was insufficient to show that any particular drug is more effective than another. Surgery also plays an important role in treating Buruli ulcer, and consequently the independent effect of drugs is difficult to assess.

Updated Review

Primary antifungal prophylaxis for cryptococcal disease in HIV‐positive people  (Awotiwon AA, Johnson S, Rutherford GW, Meintjes G, Eshun‐Wilson I) 

Cryptococcal disease is one of the leading causes of death for HIV‐positive people who have low CD4 counts. The aim of this updated review is to find out if taking an antifungal drug regularly, such as fluconazole, prevented HIV‐positive people who have low CD4 cell counts from getting cryptococcal disease, and what the potential complications were.  The original Cochrane review on this topic was published in 2005 (Chang 2005); the new review author team led by Ajibola Awotiwon has extensively revised the protocol. Nine trials, enrolling 5426 participants, met the inclusion criteria of this review. Six trials administered fluconazole, while three trials administered itraconazole. These trials were conducted in Australia, Canada, South Africa, the UK, the USA, Thailand, and sub‐Saharan Africa. Seven trials were conducted before the availability of modern antiretroviral therapy. The participants in two large trials received modern HIV treatment regimens. The results show that antifungal prophylaxis may have no effect on death overall, but it reduced the risk of those with low CD4 counts developing cryptococcal disease by 71%. Prophylaxis with an antifungal probably also reduced deaths specifically from cryptococcal disease. Generally, there were few side effects of taking antifungal prophylaxis, although there may be an increased risk of the vaginal tract becoming colonized with fluconazole‐resistant Candida organisms. The authors conclude that further research is not required to show the efficacy of primary antifungal prophylaxis in reducing the occurrence of cryptococcal disease, but analyses of the cost effectiveness and feasibility of implementing this intervention in different settings are needed.

2018, Issue 7

Two updated reviews and three new protocols are  available in Issue 7 of the Cochrane Database of Systematic Reviews

Updated Reviews

Treatment for HIV-associated cryptococcal meningitis (Tenforde MWShapiro AERouse BJarvis JNLi TEshun-Wilson IFord N).

HIV-associated cryptococcal meningitis is a severe fungal infection of the brain and surrounding membranes that causes about 15% of HIV-related deaths worldwide, mostly in resource-limited countries. Treatment includes initial antifungal therapy followed by continuation treatment with oral fluconazole. The objective of the review is to evaluate the best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis, and to compare side effect profiles of different therapies. This is an update of a review on the same topic last published in 2011; the new author team, led by Mark Tenforde, updated the protocol extensively, with changes in the inclusion criteria and methodology. The authors identified 13 studies with 2426 people for inclusion, which directly compared 21 different therapies. All studies were carried out in adults, and 11 out of 13 were conducted in resource-limited settings. Results show that a shorter initial treatment with one week of combined amphotericin B deoxycholate and flucytosine probably results in lower risk of death, similar clearance of the infection, and less toxicity than longer treatment with two weeks of the same combination, that has traditionally been recommended in treatment guidelines. Where amphotericin B deoxycholate cannot be given, two weeks of combined flucytosine with fluconazole is likely a good treatment option. Given the absence of data from studies in children, and limited data from high-income countries, this review’s  findings provide limited guidance for treatment in these patients and settings.

Early versus delayed antiretroviral treatment in HIV-positive people with cryptococcal meningtis (Eshun-Wilson IOkwen MPRichardson MBicanic T).

This is an update of a review last published in 2013; Ingrid Eshun-Wilson and colleagues have extensively revised the protocol. The aim of the review is to determine whether initiating antiretroviral therapy (ART) within four weeks of cryptococcal meningitis treatment results in a higher risk of dying or developing other complications than waiting more than four weeks to initiate ART. This higher risk of death in the early ART group has been attributed to the occurrence of a condition called immune reconstitution inflammatory syndrome (IRIS). The review includes 4 trials with 294 adult participants, all from low- and middle-income countries. Despite the low certainty of the evidence, results suggest that early ART initiation increases the risk of mortality compared to delaying ART beyond four weeks among HIV-positive adults with cryptococcal meningitis. Findings from this Cochrane Review contributed to the formulation of the current World Health Organization (WHO) guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-positive adults, adolescents, and children (WHO 2018).


New Protocols

Drug therapy for Mycetoma (
Scolding PFahal AYotsu RR).

Measures of antiretroviral adherence for detecting viral non-suppression in people living with HIV (Hine PSmith REshun-Wilson IOrrell CCohen KLeeflang MMGFord N.)

Contact tracing strategies in household and congregate environments to identify cases of tuberculosis in low- and moderate-incidence populations (Braganza Menezes DMenezes BDedicoat M).

 

2018, Issue 6

New Review

One new  review is available in Issue 6, of the Cochrane Database of Systematic Reviews

Ribavirin for treating Crimean Congo haemorrhagic fever (Johnson SHenschke NMaayan NMills IBuckley BSKakourou AMarshall R).

In this new review, Samuel Johnson and colleagues investigate the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever (CCHF). Infection with CCHF in people is usually due to a tick bite or by contact with infected bodily fluids from humans or animals; those at highest risk of contracting the virus are people who work outdoors in CCHF-endemic areas, those who work with large domestic animals, and healthcare workers. The disease occurs in parts of Asia, Europe and Africa but it has become more common in the last 15 years, particularly in Turkey and parts of Eastern Europe. CCHF is managed with supportive medical care (use of fluids, good nursing care, and blood products in response to changes in the blood's ability to clot), but the antiviral drug ribavirin is widely used in healthcare settings as a form of post-exposure prophylaxis for those exposed to CCHF. Prompt treatment with ribavirin following diagnosis of CCHF is included in several national guidelines, but these recommendations are not based on a robust evidence base, and this reviews aimed to summarize the data available to address whether ribavirin reduces the number of deaths from CCHF, and also assess its potentially serious, life-threatening adverse effects. The review includes 23 studies, of various designs, but because of poor quality there was insufficient reliable evidence to show whether ribavirin is effective in treating Crimean Congo haemorrhagic fever.

2018, Issue 5

Updated Review

One updated review is available in Issue 5, of the Cochrane Database of Systematic Reviews

Vaccines for preventing typhoid fever  (Milligan R, Paul M, Richardson M, Neuberger A)

This is an update of the 2014 review, with some changes in the methods and inclusion criteria, and a new author team led by Rachel Milligan of the LSTM. The review now includes randomized and quasi-randomized controlled trials (RCTs) of the following typhoid vaccines: Live oral vaccine Ty2la or genetic modifications, Vi polysaccharide vaccine, and conjugate vaccines. It excludes trials that evaluated killed whole-cell vaccines, because these vaccines are no longer in use. 18 RCTs are included: 13 evaluated efficacy, and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers; only one trial included data on children under two years of age. Results show that the two main vaccines currently licensed for use, Ty21a and Vi polysaccharide, were effective in reducing typhoid fever in adults and children over two years in endemic countries; adverse events such as nausea, vomiting, and fever were rare. The Vi-rEPA vaccine is just as efficacious, although data is only available for children. The new Vi-TT vaccine (PedaTyph) requires further evaluation to determine if it provides protection against typhoid fever. At the time of writing, there were only efficacy data from a human challenge setting in adults on the Vi-TT vaccine (Tybar), which is being tested in an ongoing field trial. 


2018, Issue 4

New Reviews

Two new reviews , are available in Issue 4, of the Cochrane Database of Systematic Reviews

Ivermectin and permethrin for treating scabies (Rosumeck S, Nast A, Dressler C)

In this new review, Stefanie Rosumeck and co-authors assess the efficacy and safety of topical permethrin and topical or systemic ivermectin to treat scabies in people of all ages. Scabies is an intensely itchy parasitic infection of the skin. It occurs throughout the world, but is particularly problematic in areas of poor sanitation, overcrowding, and social disruption. The review includes 15 relevant studies, nearly all set in South Asia or North Africa, with 1896 participants, comparing topical permethrin, systemic ivermectin, or topical ivermectin. Risk of bias in the included trials was moderate, and reporting was poor in many studies. Overall, there was no difference detected in the efficacy of permethrin compared to systemic or topical ivermectin, and all lead to high clearance rates in the treatment of scabies. Only few and mild adverse events were reported. The choice of one of these three treatments can be guided by considerations of practicability, availability, drug licensing, and costs depending on the individual setting: systemic ivermectin may be given preference if proper application cannot be ensured or if very large groups of patients need to be treated, but it is not indicated during pregnancy or for children weighing less than 15 kg. The included studies were mostly small and poorly reported, which affects the certainty of the level of evidence: further studies with clear and strict treatment regimens will help address the question of repeated treatment, and provide better documentation and classification of adverse events.

Smectite for acute infectious diarrhoea in children (Pérez-Gaxiola G, Cuello-García CA, Florez ID, Pérez-Pico VM) 

Smectite is a medicinal clay commonly prescribed throughout the world as an adjuvant treatment to adults and children with infectious diarrhoea. Smectite has three possible mechanisms of action: an anti-inflammatory activity, alteration of the gut mucus barrier to reduce penetration of toxins, and adsorptive properties, which would reduce stool output in children, thereby providing symptomatic relief and possibly preventing dehydration. This new review by Giordano Pérez-Gaxiola and colleagues analysed randomized and quasi-randomized trials comparing smectite to a control group in children aged one month to 18 years old with acute infectious diarrhoea. Eighteen trials with 2616 children are included; they were conducted in both ambulatory and in-hospital settings, in both high-income and low- or middle-income countries, and most of them included children with rotavirus infections. Results show that smectite used as an adjuvant to rehydration therapy may reduce the duration of diarrhoea in children with acute infectious diarrhoea by a day; may increase cure rate by day 3; and may reduce stool output, but has no effect on hospitalization rates or need for intravenous therapy. There were no reports of serious adverse effects. The included studies were of low-certainty evidence, and the authors conclude that more high-quality studies are still needed, including studies that assess different causes of diarrhoea and the economic effects of this treatment.

2018, Issue 3

New Reviews

Two new reviews , are available in Issue 3, of the Cochrane Database of Systematic Reviews

Mefloquine for preventing malaria in pregnant women (González RPons-Duran CPiqueras MAponte JJter Kuile FOMenéndez C)

In this new review, Raquel González and colleagues assess the effects of mefloquine for preventing malaria in pregnant women.  Mefloquine is a possible alternative to sulfadoxine-pyrimethamine (SP), which is recommended by the World Health Organization for intermittent preventive treatment in pregnancy (IPTp) with for malaria for all women who live in moderate to high malaria transmission areas in Africa.  Parasite resistance to SP has been increasing steadily in some areas, and there are potential drug interactions between SP and cotrimoxazole, which is used for prophylaxis in HIV-infected women. This review evaluates the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women, also considering the impact of HIV status, gravidity, and use of insecticide-treated nets. Six trials conducted between 1987 and 2013, with a total of 8192 pregnant women, are included in this review. Mefloquine prophylaxis compared with SP in HIV-uninfected women, and mefloquine prophylaxis plus cotrimoxazole compared with cotrimoxazole  alone in HIV-infected women, reduced risks of maternal peripheral parasitaemia, made no difference in the prevalence of adverse maternal outcomes such as low birth weight, prematurity, stillbirths and abortions, and congenital malformations,  and in the incidence of clinical malaria episodes during pregnancy, but increased risks of drug-related adverse events, especially vomiting and dizziness. The authors conclude that mefloquine was efficacious and safe in terms of pregnancy outcomes, but the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women. Future research should concentrate on optimizing the dose of mefloquine that would provide the same antimalarial beneficial effects while reducing its drug-related adverse events.

Nutritional supplements for patients being treated for active visceral leishmaniasis (Custodio ELópez-Alcalde JHerrero MBouza CJimenez CStorcksdieck genannt Bonsmann SMouratidou TLópez-Cuadrado TBenito AAlvar J)

Visceral leishmaniasis (VL), also known as kala-azar, is caused by protozoan parasites of the genus Leishmania, transmitted by sandflies. VL has a worldwide distribution but 90% of the cases occur in just six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia, and Brazil, causing an estimated 20,000 to 40,000 deaths annually, and 357,000 disability-adjusted life years lost (DALYs). Malnutrition is one of the poor prognostic factors identified for leishmaniasis, and this new review prepared by a team led by Estefanía Custodio, aimed to assess the effects of nutritional supplementation in people treated for VL. Searches for randomized controlled trials, quasi-randomized controlled trials, and non-randomized controlled trials, of any oral nutritional supplement, compared to no nutritional intervention, placebo, or dietary advice alone, in people being treated for VL, found no studies, either completed or ongoing, eligible for inclusion in the review. The authors conclude that this absence of evidence should not be interpreted as evidence of no effect for nutritional supplements in people under VL treatment.

2018, Issue 2

Two new protocols, one new review and one updated review  are available in Issue 2, of the Cochrane Database of Systematic Reviews

New Protocols

Rapid initiation of antiretroviral therapy for people living with HIV (Mateo-Urdiales AJohnson SNachega JBEshun-Wilson I)

Impact of diagnostic test Xpert MTB/RIF® on health outcomes for tuberculosis (Haraka FNathavitharana RRSchumacher SGKakolwa MDenkinger CMGagneux SReither KRoss A)

New Review

Mosquito repellents for malaria prevention (Maia MF, Kliner M, Richardson M, Lengeler C, Moore SJ)

 In this new review, Marta Maia and colleagues assess the impact of mosquito repellents (which include topical repellents, insecticide-treated clothing, and mosquito coils) on malaria transmission. Considerable success against malaria has been achieved within the past decade mainly through long-lasting insecticide-treated nets (LLINs), but elimination of the disease is proving difficult, as people are not protected against mosquitoes biting when outdoors or outside sleeping hours.  Also, there are situations where LLINs cannot be used, such as after a natural disaster or amongst displaced populations. Ten trials are included: 6 trials investigated topical repellents, 2 trials investigated insecticide-treated clothing, and 2 trials investigated spatial repellents. There was no conclusive evidence that topical repellents such as lotions can prevent clinical malaria or malaria infection. Insecticide-treated clothing (ITC) were investigated in trials conducted in refugee camps in Pakistan and amongst military based in the Colombian Amazon, which showed that ITC may reduce risk of malaria infection in the absence of insecticide-treated nets. Two studies, one in China and one in Indonesia,  investigated the practice of burning mosquito coils to reduce malaria infections; the study designs were substantially different and one study had high risk of bias, and it is not possible to draw any conclusions. The authors were unable to make well-informed recommendations with regard to including or not including topical repellents, ITC, or spatial repellents in malaria control programmes; the use of ITC in refugee camps or disaster situations may be useful, but further research is needed. 

 Updated Review

Primaquine or other 8-aminoquinolines for reducing Plasmodium falciparum transmission (Graves PMChoi LGelband HGarner P)

The last version of this review by Tricia Graves, Hellen Gelband and Paul Garner was published in 2015. This update adds a new author (Leslie Choi) to the team. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance, in order to reduce malaria transmission, replacing the previous recommendation of 0.75 mg/kg, with the aim of reducing haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malaria-endemic areas. This updated review includes 7 new trials, for a total of 25 trials: 2 trials comparing PQ and bulaquine (BQ), and 23 trials comparing PQ versus arms without PQ. The results show that a single low dose of PQ (0.25 mg/kg) added to artemisinin-based combinations reduces infectiousness of people to mosquitoes at day 3-4 and day 8, and appears as effective as the higher doses. The absolute effect is greater at day 3 or 4, and smaller at day 8, in part because of the lower infectiousness in the control group. There was no evidence of increased haemolysis at 0.25 mg/kg, but few G6PD-deficient individuals were included in the trials. However, there were no ideal studies reporting malaria transmission intensity in communities, and infectiousness to mosquito was measured by direct or membrane feeding, or using measures of potential infectiousness. It is unclear whether the observed reduction in infectiousness would actually have an impact on reducing community prevalence of malaria. 

2018, Issue 1

Three  new protocols  are available in Issue 1, of the Cochrane Database of Systematic Reviews

New Protocols

Symptom screening for active tuberculosis in pregnant women living with HIV  (LaCourse SMCranmer LMBekker ASteingart KRBlack DHorne DJOren EPals SModi SMathad J)

Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis (Grace AGMittal AJain STripathy JPSatyanarayana STharyan PKirubakaran R)

MVA85A vaccine to enhance BCG for preventing tuberculosis (Kashangura RJullien SGarner PYoung TJohnson S)

2017, Issue 12

One  updated  review is available in Issue 12, of the Cochrane Database of Systematic Reviews

 Updated Review 

Larvivorous fish for preventing malaria transmission  (Walshe DPGarner PAdeel AAPyke GHBurkot TR)

This review was first published in December 2013 and it has now been updated by Deirdre Walshe and colleagues.  The aim of the review is to evaluate whether introducing fish that eat mosquito larvae and pupae into water sources, will decrease the adult Anopheles mosquito population and thus the number of people infected with Plasmodium parasites. As in the first version of the review, the authors did not find any studies reporting on the primary outcomes of the review: malaria infection in nearby communities, entomological inoculation rate, or adult Anopheles density. A secondary analysis to examine the effects of introducing larvivorous fish on the density and presence of anopheline larvae and pupae in community water sources, found 15 small studies conducted in a variety of settings in different countries, but all studies were at high risk of bias and insufficient to determine any consistent effects on the density of Anopheles larvae and pupae. The authors conclude that there is insufficient evidence to support investing in larvivorous fish interventions without further reliable research. It is also unclear is whether this question is worth pursuing, as potential effects almost inevitably will be marginal given the large numbers of water bodies usually present in areas where malaria-transmitting Anopheles lay eggs, and some authors have raised the possibility that larvivorous fish may harm indigenous fish and frog species.

2017, Issue 11

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

New Protocol

Linezolid for drug-resistant tuberculosis  (Singh BCocker DRyan HSloan D)

New Review

Interventions to increase tuberculosis case detection at primary healthcare or community-level services (Mhimbira FACuevas LEDacombe RMkopi ASinclair D)

In this new review , Francis  Mhimbira and colleagues examine the effects of different strategies to increase tuberculosis (TB) case detection through improved  access  to TB diagnosis at primary healthcare or community-level services. These strategies may increase TB case detection by  identifying people with early TB who are not yet sufficiently unwell to seek care, or people with advanced TB who present late to health services, when the disease is already severe.  The review includes 9 cluster-randomized trials, one individual randomized trial, and 7 non-randomized controlled studies, all from high TB prevalence areas in Sub-Saharan Africa, Asia and South America. TB outreach screening, using house-to-house visits, sometimes combined with printed information about going to clinic, may increase TB case detection and lower default during treatment, but may have little or no effect on treatment success. There was insufficient evidence to determine if health promotion activities alone (through mass media or education) increase TB case detection, and to determine if sustained improvements in case detection impact on long-term tuberculosis prevalence, as the only study to evaluate this found no effect after four years. The authors conclude that when interventions are used in high-burden settings, active case-finding approaches may increase TB case detection in the short term, but it is unclear from the available evidence if they may improve treatment success and reduce tuberculosis treatment failure, mortality, and default.

2017, Issue 10

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

New Protocol

Methylene blue for treating malaria  (Calderón MWeitzel TRodriguez MFCiapponi A)

Updated Review

Mefloquine for preventing malaria during travel to endemic areas (Tickell-Painter MMaayan NSaunders RPace CSinclair D)

This  review, prepared by Maya Tickell-Painter and colleagues, replaces a previous Cochrane review by Frederique Jacquerioz and Ashley Croft and summarizes evidence on the efficacy and safety of mefloquine used as prophylaxis for malaria in travelers.  Mefloquine is widely used to prevent malaria in travelers and visitors to endemic areas, but there is controversy about its psychological side effects. The review’s inclusion criteria have been broadened to cover non-randomized studies, which can provide useful information regarding the side effect profile of mefloquine. The authors have compared prophylactic mefloquine with placebo, no treatment, or with alternative recommended antimalarial agents (atovaquone-proguanil or doxycycline) and analyzed data from 20 RCTs (11,470 participants), 35 cohort studies (198,493 participants), and 4 large retrospective analyses of health records (800,652 participants). The absolute risk to develop malaria during short-term travel appeared low with all three antimalarial agents tested. Mefloquine was not shown to have more frequent serious side effects than either atovaquone-proguanil or doxycycline, but the quality of evidence was low. There was moderate- and high-certainty evidence that mefloquine use is associated with a range of psychological adverse effects, such as abnormal dreams, anxiety, insomnia, and depressed mood, especially with long-term use.  

2017, Issue 9

Two updated reviews are available in Issue 9, of the Cochrane Database of Systematic Reviews

Updated Reviews

Vitamin A supplements for reducing mother-to-child HIV transmission (Wiysonge CSNdze VNKongnyuy EJShey MS)

The previous version of this review was published in 2011 and this update, led by Charles Wiysonge , sees some change in co-authors and a reduction in the number of secondary outcomes. The primary outcome has not changed and is the HIV infection status of the child. Vitamin A supplementation given to HIV-positive women during pregnancy and after delivery was suggested as a simple and inexpensive intervention that could potentially be implemented even in the absence of prenatal HIV testing programmes. The review includes 5 trials with approximately 7200 women, conducted in Malawi, South Africa, Tanzania, and Zimbabwe between 1995 and 2005. None of the participants received ART. Women allocated to intervention arms received vitamin A supplements at a variety of doses; the comparison arms received placebo or no intervention. Maternal vitamin A supplementation showed little or no effect on mother-to-child transmission of HIV, and may have some beneficial effect on birthweight by the evidence was low. However, this intervention has largely been superseded by ART which is widely available and effective in preventing vertical transmission, and the authors conclude that further research on the use of vitamin A supplements for this indication may not be warranted. 

Interventions for treating tuberculous pericarditis (Wiysonge CSNtsekhe MThabane LVolmink JMajombozi DGumedze FPandie SMayosi BM)

Charles Wiysonge and his team have prepared this review which is a new edition of the 2002 version. The updated review has new authors, additional trials, and different conclusion compared to the previous published version. Tuberculosis infection of the pericardium surrounding the heart is uncommon but life-threatening; in addition to antituberculous chemotherapy, treatments include corticosteroids, drainage, and surgery.  The review includes 7 trials, all from sub-Saharan Africa, with 1959 participants:  1051/1959 (54%) were HIV-positive. All trials evaluate corticosteroids and one each evaluates colchicine, M. indicus pranii immunotherapy, and open surgical drainage. In HIV-negative people, six trials found that additional steroids may reduce deaths overall, probably reduce deaths caused by pericarditis, and may prevent reaccumulation of fluid in the pericardial space. Open surgical drainage for effusion may reduce repeat pericardiocentesis In HIV-negative people. In the treatment of people living with HIV not on antiretroviral drugs, corticosteroids may reduce constrictive pericarditis and hospitalizations, with little or no effect on deaths. There was insufficient data to draw conclusions on the use of colchicine or Mycobacterium indicus pranii immunotherapy.

2017, Issue 8

Four  new protocols and one updated review  are available in Issue 8, of the Cochrane Database of Systematic Reviews

 New Protocols 

 Updated Review

Moleen Zunza and her colleagues have updated this review, first published in 2009. Isoniazid prophylaxis prevents TB in HIV-negative children but it is not known whether it is also effective in HIV-positive children.  This review evaluates the effects of isoniazid preventive treatment versus placebo in HIV-positive children with no known TB contact on active TB, death, and reported adverse events.  The authors identified 3 trials for inclusion, involving 991 participants below the age of 13 years, from South Africa and Botswana. Most of the children were on antiretroviral therapy (ART) and the median length of follow-up ranged from 5.7 to 34 months. In HIV-positive children not taking ART, isoniazid medication reduced the number of children developing active TB by 69%, and death by 54%. In in HIV-positive children taking ART, there was no benefit or harm taking isoniazid. The number of children with adverse effects was similar in the group receiving isoniazid medication or placebo, with or without taking ART. The authors suggest that any child awaiting ART in a high TB prevalence area, should have isoniazid prophylaxis until the child is virally suppressed and immune reconstituted.

 2017, Issue 7 

Three new protocols  are available in Issue 7, of the Cochrane Database of Systematic Reviews

 New Protocols 

2017, Issue 6 

Two new protocols  are available in Issue 6, of the Cochrane Database of Systematic Reviews

 New Protocols 

2017, Issue 5 

Two new reviews, one updated review and one new protocol are available in Issue 5, of the Cochrane Database of Systematic Reviews

 New Reviews

This new Diagnostic Test Accuracy (DTA) review assesses the accuracy of commercially-available rapid diagnostic tests (RDTs) and their prototypes for detecting typhoid and paratyphoid (enteric) fever in people living in endemic countries. These RDTs are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, but their diagnostic accuracy is unclear. Lalith Wijedoru and his co-authors identified 37 eligible studies with 5080 participants, which evaluated 16 different RDTs.  Most included studies were from Asia, with 5 from sub-Saharan Africa, and evaluated three RDTs and their variants: TUBEX, Typhidot, and the Test-It Typhoid immunochromatographic lateral flow assay.  The authors found that few studies were at a low risk of bias, and that the 3 main RDT tests and variants had moderate diagnostic accuracy, with no evidence of differences between their average sensitivity and specificity. The RDTs evaluated are not sufficiently accurate to replace blood culture as a diagnostic test for enteric fever.

Jennifer Onwumeh, Charles Okwundu and Tamara Kredo in this new review evaluate the effects of IL-2 as an adjunct to antiretroviral therapy (ART) in reducing the morbidity and mortality in HIV-positive adults. IL-2 is a cytokine that regulates the proliferation and differentiation of lymphocytes and may help to boost the immune system, which is harmed by HIV infection, and help in the control of viral replication as well as lead to lower susceptibility to opportunistic infections.  The authors identified 25 trials for inclusion; 11 were conducted in academic centres in the USA and the others in 6 different countries.  IL-2 in combination with ART increased the CD4 cell count in HIV-positive adults, but it did not show any significant benefit in mortality. There were probably no differences in the incidence of opportunistic infections, but there was probably an increase in grade 3 or 4 adverse effects. The findings of this review do not support the use of IL-2 as an adjunct to ART in HIV-positive adults, and the authors conclude that further trials are not justified.

Updated Review 

This update of a Cochrane Review previously published in 2010 assesses the effects of micronutrient supplements for adults living with HIV (excluding pregnant women). Micronutrient deficiencies are common among in HIV+ adults, particularly in low-income settings where the diet may be low in essential vitamins and minerals, and routine supplementation could therefore be beneficial. Marianne Visser and colleagues identified 17 new trials for this update, and the review now includes 33 trials with 10,325 participants. Some trials looked at the effects of taking supplements with multiple micronutrients whereas others looked at supplementation with single vitamins or minerals such as vitamins A and D, zinc, and selenium.  Daily supplements containing multiple vitamins and minerals showed little or no effect on reducing deaths in people living with HIV, and none of the trials of single or dual micronutrient supplements were adequately powered to assess for their effects on mortality or morbidity. The authors conclude that although the available trials have not revealed consistent clinically important benefits, these findings do not mean that an adequate dietary intake for people living with HIV is not important or that micronutrient supplements should be denied to people in whom a deficiency has been clinically demonstrated.

New Protocol 

2017, Issue 3

One new and one updated review are available in Issue 3 of the Cochrane Database of Systematic Reviews

New Review

In this new review, Ingrid van der Heijden and colleagues examine whether group therapy can improve the well-being of adults living with the human immunodeficiency virus (HIV). HIV causes a chronic, life threatening, and often stigmatising disease, which can impact on a person's psychological well-being, and group therapy could help people living with HIV to cope wit the condition, or recover from depression, anxiety, and stress. Group interventions include cognitive behavioural therapy (CBT), and others such as relaxation techniques and stress management, problem solving and coping skills, social or peer support, education and empowerment. The review includes 16 trials conducted in the USA (12 trials), Canada (one trial), Switzerland (one trial), Uganda (one trial), and South Africa (one trial), with a total of 2520 adults living with HIV. Group-based therapy based on CBT showed a small effect on measures of depression, lasting for up to 15 months and little or no effect on measures of anxiety, stress, and coping. Group interventions based on mindfulness were studied in two small trials, and had not demonstrated effects on measures of depression, anxiety or stress. The quality of evidence was overall low, and the authors conclude that existing group interventions have little to no effect in increasing psychological adjustment to living with HIV, and more good quality studies are required.

Updated Review

A new team led by Hannah Ryan has just completed an update of this review, which was first published in 1998, after revising the protocol and altering the outcomes of interest. Some clinicians believe that corticosteroids used in combination with antituberculous drugs can speed up the recovery from TB pleurisy and help to prevent long-term complications, but research findings have been inconsistent and there is some concern regarding the potential adverse effects of corticosteroids, especially in HIV-positive people. The updated review includes 6 trials with 590 participants, conducted in Asia (3 trials), Africa (2 trials), and Europe (1 trial). Two trials were in HIV-negative people, one trial was in HIV-positive people, and three trials did not report HIV status. Corticosteroids may reduce the time to resolution of the symptoms of TB pleurisy and the time to resolution of the pleural effusion on chest X-ray, as well as reduce the risk of having signs of pleural scarring. However, they may increase the risk of adverse events leading to discontinuation of the trial drug. As the risk of disability and long-term illness after TB pleurisy is unclear, research looking at the association between TB pleurisy and lung function impairment would be useful to inform future research into corticosteroids for TB pleurisy.

2016, Issue 12

Three updated reviews are available in Issue 12 of the Cochrane Database of Systematic Reviews

Updated Reviews

Marzia Lazzerini and her co-authors have updated this review, from January 2013. The author team has been amended, the 'Summary of findings' tables have been updated according to the GRADE approach, and a PRISMA study flow diagram has been added.  The review now includes 33 trials with 10,841 children aged one month to five years with acute or persistent diarrhoea, including dysentery, who received oral zinc supplements or placebo. The majority of the data is from Asia, from countries at high risk of zinc deficiency. In children older than six months, zinc supplementation may shorten the average duration of diarrhoea by around ½ day, and probably reduces the number of children whose diarrhoea persists until day seven. These effects are not present in children aged less than six months, but they are greater in children with malnutrition.  In children with persistent diarrhoea, zinc supplementation probably shortens the average duration of diarrhoea by around 16 hours.  Zinc administration can induce vomit (because of a metallic aftertaste), but development of a more palatable formulation may minimize this problem. The author conclude that In areas where diarrhoea is an important cause of child mortality, and the prevalence of zinc deficiency or mild/moderate malnutrition is high, zinc may be of benefit in children with diarrhoea aged six months or more.  Further research is necessary to justify continued supplementation in children less than six months of age and in children with low risk of zinc deficiency. 

This review was last published in 2009, and this update includes 'Summary of findings' tables prepared according to the GRADE approach. Germana Gregorio and her team have identified one new trial and the review now includes 35 trials with 4284 participants (2304 using polymer-based ORS and 1980 using glucose-based ORS). Polymer-based ORS are in fact “food-based” rehydration solutions made of water mixed with cooked rice, wheat, or maize, and children may like them more than salt and sugar solution, which is the standard medical treatment. Most trials compared polymer-based ORS with a sugar–salt ORS with a particular strength (ORS ≥ 310), which is slightly more salty than the currently agreed best formula (≤ 270 mOsm/L). Results showed that polymer-based ORS has advantages compared to glucose-based ORS (at ≥ 310 mOsm/L); comparisons also favoured polymer -based ORS over ORS ≤ 270, but the quality of evidence was poor.  No difference was observed between the groups regarding the number of people who needed a drip to be rehydrated, and adverse events were similar. More trials are needed comparing polymer-based ORS versus sugar-salt ORS ≤ 270 mOsm/L. 

This review  by Lawrence Mbuagbaw and colleagues updates the original, first published in 2010, with the aim to determine which non-nucleoside reverse transcriptase inhibitor(NNRTI) , either efavirenz (EFV) or nevirapine (NVP), is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors (NRTI) as part of initial antiretroviral therapy for HIV infection. Five new studies have been added and the review now includes 12 RCTs with 3278 participants, all adults – no trials in children were identified. Four trials included people who were also receiving treatment for tuberculosis. There was little or no difference in suppression of HIV infection, probably little or no difference in mortality, progression to AIDS, stopping treatment early and changes in blood cells affected by HIV, and there may be little or no difference in treatment failure. NVP given at the once daily dose of 400 mg led to higher mortality rates than EFV. Both drugs can cause severe adverse effects, affecting different systems:  EFV is more likely to affect mental function, while NVP is more likely to cause signs of liver damage, reduced white blood cells and rash. The authors conclude that EFV and NVP have similar clinical efficacies, and clinicians need to determine which is the more appropriate for their patients by weighing other factors like availability, cost, and concomitant medication. They must also consider individual tolerability and watch carefully for side-effects. 

2016, Issue 11

Three new reviews are available in Issue 11 of the Cochrane Database of Systematic Reviews

New Reviews

Vitamin D in its two forms (D2 and D3), is essential for bone growth and is therefore especially important in children.

Both vitamin D2 and D3 are obtained from food such as fish liver oils, eggs, and milk; however, we obtain most of our vitamin D (as vitamin D3) by synthesizing it directly when the skin is exposed to sunlight. Childhood vitamin D deficiency is common both in LMIC and high income countries, for several reasons such as lack of sunlight in the winter months, vegetarian diets, a dark pigmented skin (as melanin acts as a natural sunscreen), increased pollution, and wearing clothes covering most of the body. Vitamin D deficiency can lead to rickets, characterized by weak and deformed bones, and it has also been associated with other infections such as tuberculosis, gastroenteritis and malaria. This review, by Mohammad Yakoob and colleagues, analyses vitamin D supplementation to prevent infections, in 4 trials with a total of 3198 children under five years of age, conducted in Afghanistan, Spain, and the USA, countries with wide differences in the prevalence of vitamin D deficiency.  Evidence from the largest trial (in Afghanistan) did not demonstrate any benefit of vitamin D supplementation on the incidence of pneumonia or diarrhoea, and the authors did not find any trial that reported on the incidence of TB, malaria or febrile illness, duration of pneumonia, duration of diarrhoea, severity of infection, and cause-specific mortality. The authors conclude that whether further trials are worthwhile in areas with low baseline vitamin D deficiency is a judgement that needs to be made carefully against other competing resources for research.

The school environment plays an important role in the development of children and young people, and school-based sexuality education programmes have become popular in many regions of the world. Most of these programs are based on behavioural science theories, and aim to improve knowledge, change attitudes, intentions, behaviours, and social norms around sexual and reproductive health. There have been a large number of systematic reviews that evaluated the effectiveness of these programmes, but most of them have used self-reported sexual behaviours as their main outcomes, which have been found to be prone to bias and unreliable. In this new review, Amanda Mason-Jones and her colleagues have used biological outcome measures i.e. incidence of HIV or other STIs, or pregnancy. The review includes 8 cluster-RCTs with 55,157 participants: 5 trials were conducted in sub-Saharan Africa, one in Latin America and two in Europe.  Sexual and reproductive health education programmes alone showed no effect on the number of young people infected with HIV or other STIs during adolescence, or the number of adolescent pregnancies. Giving monthly cash, or free school uniforms, to encourage students to stay in school probably has no effect on the number of young people infected with HIV during adolescence, and may reduce the number of adolescent pregnancies (low certainty evidence). One trial assessed combined educational and incentive-based programmes showing that they  may reduce STIs (low certainty evidence) in young women, but no effect was detected for HIV or pregnancy.

Abdominal tuberculosis (TB) affects the gut, the peritoneum, abdominal lymph nodes, and, more rarely, the solid organs in the abdomen (liver, pancreas, and spleen), and leads to severe illness in adults and children, with possible complications, such as bowel rupture, which can cause death. Most current guidelines recommend treating people that have abdominal TB with antituberculous treatment (ATT) for six months, but some clinicians treat for longer periods due to concerns that six months is not adequate to achieve cure and prevent relapses.  Longer ATT, however, is associated with poor adherence, higher risk of side effects, and higher cost to health systems and to patients.   In this new review, Sophie Jullien and colleagues analyse data from three RCTs, with 328 participants, comparing six-month regimens with nine-month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co-morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol. Relapse was uncommon in both shorter and longer treatment groups, and the proportion of participants who achieved clinical cure or defaulted from treatment was small in both groups.  There were 2/150 deaths (1.3%) in the six-month group and 4/144 (2.8%) in the nine-month group, but they all occurred in the first four months of treatment, so were not linked to the duration of treatment.  Six-month regimens are probably as good as nine-month regimens in terms of numbers of people cured, but more trials may be needed about treating abdominal TB in children and in people with HIV.

2016, Issue 9

One new review ,one updated review and one new protocol are available in Issue 9 of the Cochrane Database of Systematic Reviews

New Review

Tuberculous meningitis (TBM) is the main form of tuberculosis that affects the central nervous system and is associated with high rates of death and disability. Longer antituberculous treatment (ATT) regimens for TBM than for pulmonary tuberculosis are recommended to prevent relapse, but the longer regimens are associated with poor adherence.  In this new review, Sophie Jullien and colleagues analyse data from randomized controlled trials (RCTs) and prospective cohort studies of adults and children with TBM, treated with ATT regimens that included rifampicin for six months or longer than six months. Four RCTs and 12 prospective cohort studies with a total of 1881 participants are included in the review: 7 studies with 458 participants that evaluated six months of treatment, and 12 studies with 1423 participants that evaluated longer treatment.   TB relapse was an uncommon event across all studies; few participants defaulted from treatment, but adherence was not clearly documented. There was a higher death rate in participants treated for longer than six months, probably reflecting differences between the participants in the two groups of studies. The authors conclude that, as this was observational data, and most participants were HIV negative, there is the need for well-designed RCTs, or large prospective cohort studies, to resolve the uncertainty regarding the safety and efficacy of six months regimens for TBM.

Updated Review

Genotype® MTBDRsl (MTBDRsl) is a rapid DNA-based test for detecting specific mutations associated with resistance to fluoroquinolones and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. This is an update from the 2014 review, performed as part of a World Health Organization process to develop updated guidelines for using MTBDRsl.  Grant Theron and colleagues have summarized evidence from 27 studies – 16 of them evaluated version 1.0 of the test, and one study version 2.0, released in 2015. The analysis shows that in people with rifampicin-resistant or MDR-TB, MTBDRsl performed on a culture isolate or smear-positive specimen may be useful in detecting second-line drug resistance. MTBDRsl (smear-positive specimen) correctly classified around six in seven people as having fluoroquinolone or SLID resistance, although the sensitivity estimates for SLID resistance varied. The test rarely gave a positive result for people without drug resistance. However, when second-line drug resistance is not detected (MTBDRsl result is negative), conventional DST can still be used to evaluate patients for resistance to the fluoroquinolones or SLIDs. The authors recommend that future work evaluate MTBDRsl version 2.0, in particular on smear-negative specimens and in different settings to account for different resistance-causing mutations that may vary by strain.

New Protocol

2016, Issue 6

One review update and two new protocols are available in Issue 6 of the Cochrane Database of Systematic Reviews

Updated Reviews

Liesl Grobler and colleagues completed this Cochrane review update on the effects of nutritional supplements for people being treated for tuberculosis. Tuberculosis is a bacterial infection which most commonly affects the lungs. People with tuberculosis are often malnourished, and malnourished people are at higher risk of developing tuberculosis as their immune system is weakened. Nutritional supplements could help people recover from the illness by strengthening their immune system, and by improving weight gain and muscle strength, allowing them to return to an active life. The review authors searched for relevant studies up to 4 February 2016, and included 35 studies with 8283 participants. Food or energy supplements may improve weight gain during recovery from tuberculosis in some settings, but there is currently no evidence that they improve tuberculosis treatment outcomes. There is also currently no reliable evidence that routinely supplementing above the recommmended daily amounts has clinical benefits.

New Protocols

2016, Issue 5

Two  new reviews and one new protocol are available in Issue 5, 2016 of the Cochrane Database of Systematic Reviews

New reviews

Maunank Shah, Karen Steingart and their team have completed this new review, which assesses the accuracy of the lateral flow urine lipoarabinomannan assay (LF-LAM) for active TB diagnosis or screening in HIV+ adults. LF-LAM is a commercially available point-of-care test, which is performed by placing urine on one end of a test strip, with positive results appearing as a coloured line. The test is simple, requires no special equipment, and shows results in 25 minutes. The review includes 12 studies: 6 evaluated LF-LAM for TB diagnosis and 6 for TB screening; all studies were conducted in low- or middle-income countries. LF-LAM was found to have low sensitivity to detect TB in adults living with HIV, whether it was used for diagnosis or screening. For TB diagnosis, the combination of LF-LAM with sputum microscopy suggests an increase in sensitivity for TB compared to either test alone, but with a decrease in specificity. However, in HIV-positive people with low CD4 counts who are seriously ill, LF-LAM may help with the diagnosis of TB.  The results of the review should be interpreted with caution as there are small number of studies and participants included in the analyses.

This new review was prepared by a team led by Carmen Gallardo, and it analysed data from trials comparing oral treatment for pulmonary TB in new patients, given as fixed-dose combinations (FDCs) that are combined in one tablet, or taken separately as single-drug formulations. FDCs are recommended by the WHO as they reduce the number of tablets that people take - this might reduce prescribing errors, and improve drug supply efficiency and patients’ adherence. The review includes 13 randomized controlled trials that enrolled 5824 people. Overall there was little or no difference between FDCs and single-drug formulations for most outcomes (treatment failure, relapse, death). There was no relevant difference for sputum smear or culture conversion at the end of treatment, for serious adverse events, and for adverse events that led to discontinuation of therapy. The authors conclude that, although there were no differences in clinical outcomes between the 2 regimens, FDCs may be more advisable than single-drug formulations in settings where there is no directly observed therapy (DOT), in order to ensure treatment compliance and avoid resistance.

New protocol

2016, Issue 4

Two  updated reviews and one new protocol are available in Issue 4, 2016 of the Cochrane Database of Systematic Reviews

Updated  reviews

This review was first published in 2008, and this update includes results from a new search, as well as an assessment of the quality of the evidence using GRADE, and 'Summary of findings' tables. There were also changes in the authors’ team, led by Arianna Rubin Means; the title has been amended, and outcomes now include also anaemia and adverse events. Helminth infections affect the human immune system, and in people with HIV they may compromise a person's ability to control HIV viral replication. Thus, treatment of helminth infections could have important benefits for people living with HIV. The review now includes 8 trials (7 from sub-Saharan Africa and one from Thailand) with 1612 participants. Treating  HIV-positive adults with deworming drugs (either without knowledge of their helminth infection status, or with diagnosed helminth infections)  may have a small suppressive effect on viral load at six weeks , but repeated dosing over two years appears to have little or no effect on either viral load  or CD4+ cells. There was no additional risk for HIV+ people in taking antihelminthic drugs, but adverse events were generally not well reported. Further long-term studies are required to make confident conclusions.

Kameshwar Prasad, Mamta B Singh and Hannah Ryan are the authors of this review, last updated in 2008, and now extensively revised: the search was updated, and  Hannah Ryan re-extracted and analysed the data, revised the 'Risk of bias' assessment, constructed a 'Summary of findings' table with GRADE assessment, and revised the Background, Results, and Discussion sections. Corticosteroids are commonly used in addition to antituberculous drugs for treating people with TB meningitis, a serious form of TB that causes headache, coma and death. Dexamethasone, methylprednisolone, or prednisolone helps reduce inflammation of the surface of the brain and blood vessels, probably decreasing pressure inside the brain, and reducing the risk of death. However, some clinicians are concerned that corticosteroids may improve survival, but result in more severely disabled survivors. Nine trials with 1337 participants are included in the review. Corticosteroids were found to reduce mortality from tuberculous meningitis, at least in the short term, but may have no effect on the number of people who survive tuberculous meningitis with disabling neurological deficit.

New protocol

2016, Issue 3

One  new protocol is available in Issue 3, 2016 of the Cochrane Database of Systematic Reviews

New protocol

2016, Issue 2

One updated review and one new protocol are available in Issue 2, 2016 of the Cochrane Database of Systematic Reviews

Updated  review

 This review was first published in 2009 and it has been now updated, with changes in the author’s team, still led by Mical Paul, and with a focus on areas with hyperendemic or holoendemic transmission of malaria (but also including trials conducted in other areas which report malaria-related outcomes). In areas where anaemia is common, health providers may give children iron tablets, with or without folic acid, in order to prevent anaemia. There is a concern amongst researchers that this may increase the risk of malaria because increased iron levels in the blood may promote the growth of the Plasmodium parasite. Results from 35 trials with 31,955 children show that iron did not cause an excess of clinical malaria in children, whether they were living in areas where anaemia is common or in those where it’s uncommon. Iron supplements may reduce clinical malaria in areas where there are prevention and management services for malaria, but increase the incidence of malaria in areas where such services are unavailable.  Iron supplementation did not cause an excess of severe malaria, and there were no differences for deaths. In conclusion, routine iron supplementation should not be withheld from children living in countries where malaria is prevalent and malaria management services are available.

New protocol

2016, Issue 1

One new review and one new protocol are available in Issue 1, 2016 of the Cochrane Database of Systematic Reviews

New review

 This new review, prepared by Cesar Henriques-Camacho and colleagues from Peru, the US and Spain, assesses the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole), which are used for treating chronic strongyloides infection. Strongyloidiasis is caused by the intestinal parasitic worm Strongyloides stercoralis, found in tropical and subtropical regions. Most people remain asymptomatic but chronic infection can cause skin rash, gastrointestinal symptoms, and respiratory problems, and can be fatal in people with immune deficiency. This review includes 7  randomized controlled trials, enrolling 1147 adults with chronic strongyloides infection, conducted between 1994 and 2011 in different locations.   Parasitological cure was higher with ivermectin than with albendazole; there was little or no difference in parasitological cure between ivermectin and thiabendazole.  There were more adverse events with thiabendazole than with ivermectin. However, there were no serious adverse events or death. Further trials may help investigate the effect of different doses of ivermectin in different group of patients, and identify the optimal  treatment for vulnerable populations.

New protocol

2015, Issue 10

One updated  review is  available in Issue 10,  2015 of the Cochrane Database of  Systematic Reviews

Updated review

Thomas Clasen and his team have updated this review, which now includes 55 studies enrolling over 84,000 participants. Source-based water quality improvement include providing protected groundwater (springs, wells, and bore holes), or harvested rainwater, as an alternative to surface sources (rivers and lakes). Alternatively water may be treated at the point-of-use in people's homes by boiling, chlorination, flocculation, filtration, or solar disinfection. Most included studies were conducted in low- or middle-income countries (LMICs) (50 studies), with unimproved water sources (30 studies), and unimproved or unclear sanitation (34 studies). There is not enough  evidence to know if source-based improvements in water supplies, such as protected wells and communal tap stands or treatment of communal supplies, consistently reduce diarrhoea in low-income settings; there are no trials evaluating reliable piped-in water supplies to people's homes. Distributing disinfection products for use in the home may reduce diarrhoea cases by one quarter to one third, depending on the product used;  water filtration at home probably reduces diarrhoea by around a half.  Distributing plastic bottles with instructions to leave filled bottles in direct sunlight for at least six hours before drinking probably reduces diarrhoea by around a third. Evidence also suggests that the more people use the various interventions for improving water quality, the larger the effects, so it is important to assess programmatic approaches to optimize coverage and long-term utilization of interventions to improve water quality.

2015, Issue 9

Two  updated  reviews are available in Issue 9,  2015 of the Cochrane Database of  Systematic Reviews

Updated reviews

The latest update of this review has a slightly modified title and a larger authors’ team, led by Elizabeth Lutge. Interventions included any form of material incentive to return for TB test results, or adhere to, or complete anti-TB treatment. These may have been direct such as cash or vouchers for groceries, or indirect such as the provision of a service for which the patient would have had to pay, such as transport to and from the clinic. The review includes 12 trials: 10 from the USA (one in adolescents, 4 in injection drug or cocaine users, 3 in homeless adults, and 2 in prisoners).  The remaining two trials, in general adult populations, were conducted in Timor-Leste and South Africa. Two trials assessed the effect of incentives on long-term adherence and completion of treatment for active TB, and did not demonstrate a clear benefit. Three trials assessed the effects of material incentives and enablers on completion of TB prophylaxis, with mixed results; however, in specific populations, such as recently released prisoners, drug users, and the homeless, trials show that material incentives probably do improve one-off clinic re-attendance for initiation or continuation of anti-TB prophylaxis. When comparing different types of incentives, an immediate cash incentive seemed more effective than delaying the incentive until completion of treatment; cash incentives appeared  more effective than non-cash incentives; and higher cash incentives were more effective than lower cash incentives.

This review, prepared by Regina Ejemot-Nwadiaro and colleagues, has replaced the original publication in 2008, with a new title that introduces the concept of promotion. This includes group or individual training on hygiene education, germ-health awareness, use of posters, leaflets, comic books, songs, and drama. The review includes 22 randomized controlled trials conducted in both high-income countries (HICs) and low- and middle-income countries (LMICs), enrolling 69,309 children and 148 adults. Hand washing promotion at child day-care facilities or schools in HICs prevents around 30% of diarrhoea episodes, and may prevent a similar proportion in schools in low and middle income countries (LMICs).  Among communities in LMICs, hand washing promotion prevents around 28% of diarrhoea episodes. In the only hospital-based trial included in this review, hand washing promotion also had important reduction in the mean episodes of diarrhoea; the trial however had only few participants. None of the included trials assessed the effect of handwashing promotion on diarrhoeal-related deaths, all-cause under-five mortality, or the cost-effectiveness of hand washing promotions. Also, not much is known about how to help people maintain hand washing habits in the longer term.

2015, Issue 8

One new review and one new protocol are available in Issue 8, 2015 of the Cochrane Database of Systematic Reviews

New review

Leishmaniasis is a tropical disease that potentially affects 350 million, often impoverished, people, across 98 countries. The disease is caused by Leishmania parasites, and has two distinct clinical syndromes: cutaneous leishmaniasis (CL), which affects the skin and mucous membranes, and visceral leishmaniasis (VL), which affects internal organs. Leishmaniasis could be prevented by reducing human contact with infected phlebotomine sandflies (the vector), or by reducing the number of infected animals (the reservoir). In this new Cochrane Review, Urbà González and his colleagues have analysed 14 trials of vector and reservoir control interventions, which were undertaken in different settings; most included trials were of low methodological quality. Using insecticides appeared to reduce CL incidence, but there is not enough evidence to know whether it is better to use insecticides to spray the internal walls of houses, or use insecticide-treated bednets, bedsheets, or curtains. Personal protection using insecticide-treated clothing was also evaluated in two trials in soldiers, but the trials were too small to know whether or not this was effective.  For VL, insecticide-treated nets may not be effective at preventing disease, but this was only tested in a single trial from India and Nepal.

New protocol

2015, Issue 7

One  updated  review is available in Issue 7,  2015 of the Cochrane Database of Systematic Reviews

Updated review

The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common, with the assumption that this treatment will improve nutritional status, haemoglobin and cognition and consequently children’s health, intellect and school attendance. There is also a considerable investment in delivering this intervention and it is imperative to critically evaluate the evidence on its benefits. David Taylor-Robinson and colleagues have added 4 new studies to their 2012 edition of the review, for a total of 45 trials. One trial evaluating mortality included over one million children, and the remaining 44 trials included a total of 67,672 participants. In trials that treat only children known to be infected, deworming drugs may increase weight gain but we do not know if there is an effect on cognitive functioning or physical well-being.  Deworming had little or no effect on average weight gain, haemoglobin, or cognition in trials treating all children living in an endemic area. There is good evidence that regular treatment probably has no effect on average height, formal tests of cognition, or exam performance, and do not know if there is an effect on school attendance. The authors conclude that large scale programmes to deworm all school children in low income countries do not lead to the acclaimed educational and economic benefits, and call for policy makers to look again at the evidence in a systematic way, in order to re-think current WHO recommendations. 

 2015, Issue 5

One  updated  review is available in Issue 5,  2015 of the Cochrane Database of Systematic Reviews

Updated review

Jamlick Karumbi has replaced Jimmy Volmink as an author, together with Paul Garner, in the update of this review, last published in 2007. Directly Observed Therapy (DOT) is a specific strategy, endorsed by the World Health Organization, to improve adherence to anti-tuberculosis treatment, by requiring health workers, community volunteers or family members to observe and record patients taking each dose. This review includes 11 trials with 5662 participants comparing DOT with routine self-administration of treatment or prophylaxis in a variety of settings (clinic, the patient's home or the home of a community volunteer). Overall, cure and treatment completion in both self-treatment and DOT groups was low, and DOT did not substantially improve this. There were no differences when DOT was conducted at home or at the clinic, or by a community health worker or family member; also, DOT had little or no effect on treatment completion in injection drug users. The authors conclude that DOT does not provide a solution to poor adherence in TB treatment, and given the large resource and cost involved, policy makers might want to reconsider TB control strategies that depend on direct observation.   

2015, Issue 4

Two new protocols and one new review are available in Issue 4,  2015 of the Cochrane Database of Systematic Reviews

New review

Tafenoquine is an 8-aminoquinoline and a synthetic analogue of primaquine, which is the only licensed drug capable of eliminating the Plasmodium vivax hypnozoites. Tafenoquine has been tested as an alternative to primaquine as it has potential to be useful in regimens for prophylaxis and radical cure of P. vivax malaria. Tafenoquine has shorter duration of therapy and this makes it an attractive option to improve adherence. A Sri Lankan author team led by Senaka Rajapakse, identified three RCTs conducted in Thailand, India, Peru and Brazil on adults with confirmed P. vivax malaria that randomized 453 participants, for inclusion in the review. All participants received chloroquine (to clear the parasites in the blood) and some groups received either tafenoquine, primaquine or no further treatment. All trials tested people for G6PD enzyme, and excluded patients who were deficient, as both primaquine and tafenoquine can cause haemolysis in these individuals. Patients receiving tafenoquine at doses greater than 300 mg had fewer relapses than adults who had no further treatment, and tafenoquine 600 mg may be better in relapse prevention than standard primaquine doses. The drug is still untested in pregnancy, children and in G6PD-deficient people.

New protocols 

2015, Issue 3

One new review is available in Issue 3,  2015 of the Cochrane Database of Systematic Reviews

New review

This new review prepared by Eleanor Ochodo and her team evaluates point-of-care (POC) tests for diagnosing schistosomiasis. POC tests include assays based on circulating antigen detection and urine reagent strip tests, which are quick and easier to use in the field, and, if they show sufficient diagnostic accuracy, they could replace conventional microscopy. This review evaluated urine reagent strip tests to detect active Schistosoma haematobium infection, with microscopy as the reference standard; and circulating antigen tests for detecting active Schistosoma infection in geographical regions endemic for Schistosoma mansoni or S. haematobium or both, with microscopy as the reference standard. 90 studies involving almost 200,000 people were included (88 from field settings in Africa). For detecting urinary schistosomiasis, urine strips for detecting blood were better than those detecting protein or white cells, and the parasite antigen test performance was worse than urine strips for detecting blood. For intestinal schistosomiasis, the circulating parasite antigen urine test detected many infections identified by microscopy, but wrongly labelled many uninfected people as positive. Studies were in general poorly reported.

2015, Issue 2

One new review, one updated review and two new protocols are available in Issue 2,  2015 of the Cochrane Database of Systematic Reviews

New review

The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for treating people with Plasmodium falciparum malaria. Five combinations are currently recommended, all administered over three days. Artemisinin-naphthoquine is a new combination developed in China, which is being marketed as a one-day treatment. This review prepared by Rachel Isba and colleagues compares  the efficacy and safety of artemisinin-naphtoquine against established WHO-recommended ACTs  regimes (3 days) , in adults and children suffering from P.falciparum malaria. Only 4 trials, all of low quality, enrolling 740 adults and children, met the inclusion criteria: 3 small trials compared artemisinin-naphthoquine to artemether-lumefantrine and one small trial compared it to dihydroartemisinin-piperaquine.   Artemisinin-naphthoquine showed very low treatment failure in all trials; this is a promising result but it needs to be confirmed by larger multi-setting trials.

 Updated review

This review by Patricia Graves, Helen Gelband and Paul  Garner  has been updated with a new search but no added trials and no change to conclusions.  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. The review includes 17 RCT and one quasi-RCT and aims 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. The authors 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.  Overall the safety of PQ given as a single dose was poorly evaluated across all studies.

New protocols

2015, Issue 1

One new review and one new protocol are available in Issue 1, 2015 of the Cochrane Database of Systematic Reviews

New review

Anaemia is a global problem, particularly in in children under five years in Africa and South-East Asia. Malaria is a common cause of anemia in these areas, and administering intermittent preventive antimalarial treatment (IPT) to children might reduce anaemia, as well as protect from new malaria infections, allow faster recovery from the illness, and help make the children less likely to succumb to other infections. Mwaka Athuman and her co-authors in this new review have included six randomised controlled trials which included 3847 participants; three trials were conducted in areas of low malaria endemicity and three in areas of high endemicity. In some trials, iron supplements were also given to children. In all trials there was a group that received IPT and a control group that were given a placebo. Although there were small benefits in haemoglobin levels when treating anaemic children with IPT, there was no effect on death or hospital admissions, irrespective of whether they received iron supplements. However, three of the six included trials were conducted in low endemicity areas where malaria transmission is low and thus any protective effect is likely to be modest.

New protocol