Showing posts with label HIV(children). Show all posts
Showing posts with label HIV(children). Show all posts

Wednesday, 23 November 2011

TUBERCULOSIS: MDR-TB remains a difficult diagnosis for children

LILLE, 8 November 2011 (PlusNews)

 Photo: Eva-Lotta Jansson/IRIN/IFRC

Diagnosing MDR-TB in children still difficult Years of treatment and mounds of pills are hard work for older patients with multidrug resistant tuberculosis (MDR-TB), but in children, treatment becomes a minefield for patients and doctors alike.
MDR-TB is resistant to the most powerful drugs used to treat active TB, rifampicin and isoniazid. With weaker immune systems, children who contract TB - most often from parents - progress to active disease in about a year. But just how many children are affected is not known as there is almost no research into children and MDR-TB - and very little useful guidance on how to treat them.
There are only eight studies published on MDR-TB treatment outcomes among children, says Nathan Ford, medical coordinator for Médecins Sans Frontières’ (MSF) Campaign for Essential Medicines. Much of what does exist comes from South Africa's Stellenbosch University, whose researchers work in Cape Town's Tygerberg Hospital. The hospital began collecting data on drug resistant (DR-TB) tuberculosis among children in 2003.
Simon Schaaf, a professor at Stellenbosch, presented the findings of the hospital's latest such survey at the International Lung Health Conference, held recently in Lille, France. Among about 330 children with DR-TB, about 7 percent had MDR-TB - a figure that has remained relatively steady since the hospital began conducting the surveys.
According to Schaaf, paediatric DR-TB cases are often a window on local TB epidemics. In 2010, the Western Cape confirmed 1,400 MDR-TB cases - the second highest in the country.
The study found very low uptake of isoniazid preventative TB therapy (IPT) among paediatric patients, despite a national IPT policy. About 70 percent of children who would have qualified for IPT were never prescribed the preventative medication, which uses one of the main drugs used to treat active TB, isoniazid. About 5 percent of these children subsequently died.
With a small number of studies indicating the scope of MDR-TB among children, high-level awareness of the problem is lacking, according to Carlos Perez Velez, who is leading a study on new diagnostic methods to improve TB case detection among children in his native Colombia as part of his work with the US-based National Jewish Health respiratory hospital.
"You go to a minister of health and you tell them there's a problem with TB in children and he'll ask you for the data,” Perez Velez told IRIN/PlusNews. "You'll say there's no data. He'll say if there's no data then why are you saying there's a problem. It's the chicken and egg paradigm."
Late diagnosis
Children who develop the disease in their spinal column are often diagnosed too late, sometimes leading to long-term neurological effects and spinal deformity. Treatment for MDR spinal TB requires a mix of surgery and a long course of drugs.
Marianne Gale, a doctor with MSF, described the realities of diagnosing and treating children with MDR-TB. In 2010, the MSF clinic in the Nairobi slum of Mathare diagnosed a mother with MDR-TB. Her 18-month-old daughter had TB symptoms and a chest X-ray suggested she also had active TB but getting a culture was impossible.
Samples of sputum from suspected DR-TB patients are used to grow bacteria cultures that are then tested for drug resistance - but these are difficult to obtain from children.
"We actually had the capacity to do sputum induction, which in many sites we're not able to do," Gale said. "There were many attempts that were traumatic to the child and perhaps more traumatic to the staff. We managed to get a sample that actually never [developed] on culture."
Given the difficulties of diagnosing children, about half of all children treated for DR-TB in MSF's projects in Swaziland and South Africa are unconfirmed, leaving clinicians to make tough calls to start young patients on long treatment.
Gauging the dosage
Without a culture, Gale said clinic staff reluctantly started the child on MDR-TB medication - a challenge in and of itself.
"This child was 18 months old but only weighed 7.5kg so calculating the dosages and adjusting them as the child grew was a nightmare," said Gale, adding that the MSF clinic - with an in-house pharmacist - was probably better able to do this than most clinics in similar settings. "Manipulating the formulations was challenging and also how to make those drugs acceptable for this young child."
Both mother and child were doing well on treatment after six months but family pressure led both to discontinue treatment. While the clinic learned that the mother had died, they were unable to trace the child.
Almost all MDR-TB drugs are designed for adults. "Almost all children will need these pills broken into bits, sometimes half, sometimes quarters; sometimes medication needs to be ground and most formulations don't dissolve completely in water," James Seddon, a researcher at the Desmond Tutu TB Centre in Cape Town, told IRIN/PlusNews. "Some [liquid forms] are available... but actually in most high TB burden areas they are not incredibly practical because they require refrigeration and also the glass of the bottle is very heavy for [transporting] to [clinics] that need large volumes."
Some children may also need to take vitamins or HIV medication and so may end up taking a large number of pills a day, Seddon added. Many do not taste good and may cause vomiting. MSF has lobbied the World Health Organization (WHO) to produce effective guidelines about the composition of new paediatric fixed-dose combination drugs that would reduce children’s pill burden and have been shown to improve adherence.
Meanwhile, existing guidelines need work. WHO, the UK and US have developed guidelines for paediatric MDR-TB treatment, but these are largely not evidence-based and, in some cases, may have been simply adapted from adult guidelines, noted Seddon.
http://www.plusnews.org/report.aspx?reportID=94164

Monday, 18 July 2011

TUBERCULOSIS: Primary Isoniazid Prophylaxis against Tuberculosis in HIV-Exposed Children

Primary Isoniazid Prophylaxis against Tuberculosis in HIV-Exposed Children

Shabir A. Madhi, M.D., Ph.D., Sharon Nachman, M.D., Avy Violari, M.D., Soyeon Kim, Sc.D., Mark F. Cotton, M.D., Ph.D., Raziya Bobat, M.D., Patrick Jean-Philippe, M.D., George McSherry, M.D., and Charles Mitchell, M.D. for the P1041 Study Team

N Engl J Med 2011; 365:21-31July 7, 2011

Abstract
The dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period.

Methods
We randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette–Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization.

Results
Antiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P=0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P=0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups.

Conclusions
Primary isoniazid prophylaxis did not improve tuberculosis-disease–free survival among HIV-infected children or tuberculosis-infection–free survival among HIV-uninfected children immunized with BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis remained high among HIV-infected children.

http://www.nejm.org/doi/full/10.1056/NEJMoa1011214

Sunday, 17 July 2011

TUBERCULOSIS: South Africa: Addressing Adult TB Can Reduce Number of Children With Tuberculosis

Khopotso Bodibe : 14 July 2011
Improved and sustained efforts to diagnose and treat TB need to be made to address tuberculosis infection among children.
This is according to the National Institute for Communicable Diseases (NICD), after results of a clinical study it conducted showed that prophylaxis with Isoniazid does not prevent TB in children.
Working from the premise that when taken daily, Isoniazid or INH prevents the development of tuberculosis in adults who have HIV, the study recruited over 500 HIV-positive children and about 850 HIV-uninfected children that were born to HIV-positive mothers in high-risk TB areas of Johannesburg, Cape Town and KwaZulu-Natal. The study sought to investigate whether the use of Isoniazid at a very early age - three to four months - can protect children from developing TB as most infection occurs in children under two years of age. It was a randomised study where one group of children received the actual Isoniazid pill and the other a placebo. The intervention proved to be ineffective. Shabir Madhi is the Director of the National Institute for Communicable Diseases (NICD).
"Unfortunately, what the study showed is that, firstly, even when HIV-infected children are receiving antiretroviral treatment, as much as 20% of them will actually develop tuberculosis in the first two years of life. So, it tells us that even with antiretroviral treatment HIV-infected children remain highly susceptible to developing tuberculosis", says Professor Madhi, Director of the National Institute for Communicable Diseases (NICD).
"The results of the study, unfortunately, showed as well that the use of Isoniazid prophylaxis aimed at preventing TB, unfortunately did not work in reducing the risk of developing TB infection in the HIV-uninfected children that were born to HIV-infected mothers", Professor. Madhi continues.
In HIV-negative children, it was found that about 4 - 5% get infected with TB annually in the first two years of their lives. Professor Madhi says to participate in the study the young ones had to come from a household with no prior history of TB infection. Yet, some of the children did develop TB.
"What we found, subsequently, is that of all of the children that developed tuberculosis in this particular study, only one-third of them actually developed tuberculosis in the presence of another member in that household having TB, which tells us that the majority of children that develop tuberculosis, the exposure to the infectious case is actually unknown. And the frightening part of that is that it goes against the dogma that children usually develop TB mainly because of household contact", he says.
"What that tells us is that children mainly become infected with tuberculosis because of the adults that are surrounding them. And what it tells us is that we need to basically improve our targeting of the management of tuberculosis in adults to prevent the child from becoming infected because all of this infection and all of this disease that's happening in children is almost a measure it's a marker of how well we're doing in terms of controlling tuberculosis in adults because if we're able to control tuberculosis in adults these children won't become infected. The adults are really the sources of infection of tuberculosis for these young children", adds Professor Madhi.
This means more needs to be done to identify TB cases in communities.
"That has got extremely important implications in terms of how we need to go about looking out for TB in children, but more importantly, how much more important it is that we actually intervene at the community level amongst adults in preventing TB because unless we're able to reduce that overall community exposure of TB which children are exposed to, we're not going to reduce the burden of TB in children purely by targeting the prophylaxis of children that have a known household exposure".
Prof. Madhi says there was a fair amount of confidence that Isoniazid would work as an intervention to protect children against TB when the research was initiated. Now researchers have learned that Isoniazid prophylaxis in children is a quick-fix where long-term solutions are needed. Madhi says he hopes that the Gene-Xpert PCR test which is able to make a TB diagnosis almost immediately instead of in weeks, will be widely used as it will have positive spin-offs.
"Now what that strategy will allow us to do is that it will allow us to basically make sure that we're treating the infectious cases that are coming to our health facilities immediately and, hopefully, reduce the number of people that end up not being treated. But, more importantly, is active surveillance for TB going down to the community level knocking on doors finding anyone that has got a cough, as an example getting them to agree to send a sample for testing and then identifying these TB cases at a very, very early stage before they start spreading the bug throughout the community. And that's the only way we're going to win this game. We're not going to win the game in South Africa in protecting against TB by trying to prevent it with Isoniazid prophylaxis. There's just too much TB circulating for short-cut interventions", he says
http://allafrica.com/stories/201107140012.html