Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda

By Sungano Mharakurwa Moderator | 30 Mar, 2017

Following the head-to-head debate on whether to eradicate malaria, the recent study below seems to illustrate the scale of the malaria challenge. If an individual with no symptoms is found carrying malaria parasites, will the individual necessarily remain asymptomatic afterwards? Do we fully understand asymptomatic malaria? Should anyone really be left carrying malaria parasites?



Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda

Kevin C. Sifft,1 Dominik Geus,1 Caritas Mukampunga,2 Jean Claude Mugisha,2 Felix Habarugira,2 Kira Fraundorfer,3 Claude Bayingana,2 Jules Ndoli,2 Irenee Umulisa,4 Corine Karema,4,5,6 George von Samson-Himmelstjerna,3 Toni Aebischer,7 Peter Martus,8 Augustin Sendegeya,2 Jean Bosco Gahutu,2 and Frank P. Mockenhauptcorresponding author1


ABSTRACT

Background
Plasmodium infection and malaria in school children are increasingly recognized as a relevant public health problem, but data on actual prevalence and health consequences are insufficient. The present study from highland southern Rwanda aimed at estimating infection prevalence among children attending school, at identifying associated factors and at assessing the clinical consequences of these infections.

Methods
In a survey including 12 schools in the Huye district of Rwanda, 1089 children aged 6–10 years were clinically and anthropometrically examined, malaria parasites were diagnosed by microscopy and PCR, haemoglobin concentrations were measured, and socio-economic and behavioural parameters as well as medical histories were obtained.

Results
Upon examination, the vast majority of children was asymptomatic (fever 2.7%). Plasmodium infection was detected in 22.4% (Plasmodium falciparum, 18.8%); 41% of these were submicroscopic. Independent predictors of infection included low altitude, higher age, preceding antimalarial treatment, and absence of electricity or a bicycle in the household. Plasmodium infection was associated with anaemia (mean haemoglobin difference of −1.2 g/dL; 95% CI, −0.8 to −1.5 g/dL), fever, underweight, clinically assessed malnutrition and histories of fever, tiredness, weakness, poor appetite, abdominal pain, and vomiting. With the exception of underweight, these conditions were also increased at submicroscopic infection.

Conclusion
Malaria infection is frequent among children attending school in southern highland Rwanda. Although seemingly asymptomatic in the vast majority of cases, infection is associated with a number of non-specific symptoms in the children´s histories, in addition to the impact on anaemia. This argues for improved malaria surveillance and control activities among school children.

Replies

 

Maimunat Alex-Adeomi Moderator Replied at 2:02 PM, 30 Mar 2017

Thank you for sharing this interesting article on "Asymptomatic" malaria and the prevalence of malaria infection in school aged children.
I would add that more attention needs to be paid to this population as the combination of anemia, malnutrition and sub-optimal health overall really pose a threat to cognitive development in this age group. These children are still in Stages 2 and 3 of development as described by Piaget (see attached link).

From an economic and development standpoint, due to the burden of the disease, it affects their education, job prospects and contribution to society as a whole if these kids do not get to achieve their optimal potential.



http://www.psychologydiscussion.net/child-development/cognitive-developmental...

Pierre Bush, PhD Moderator Replied at 11:05 PM, 30 Mar 2017

Thank you Sungano and Maimunat. I just posted WHO guidelines on MDA which I think can be instrumental in the elimination of these asymptomatic school children. Regular screen & treat is warranted in the areas of high endemicity.

Attached resource:

Sungano Mharakurwa Moderator Replied at 6:03 AM, 31 Mar 2017

The considerations raised by Maimunat really point to the magnitude of setback exacted by keeping malaria around. Counter-argument in the eradication debate seemed premised on challenging the feasibility of eradication, and argument to not go after subclinical cases ("Eradication requires elimination of all cases, even of subclinical infection, meaning that however implemented, eradication would be costly...."). However, the question is whether we can even identify "subclinical" malaria in practice (from a single testing event, without follow-up observations to prove that the infections remain harmless). In fact is subclinical malaria really subclinical, or is it a misnomer like malaria itself, not to mention its role in sustaining transmission (see attached article).

Attached resource:

GE0RGE ALCARD Replied at 9:04 AM, 31 Mar 2017

Thank you so much for this important information about Malaria,
because Malaria is a big problem even in my country Tanzania, and
majority are asking for health care after having complications of the
disease, but to I dentify the asympomatic one will reduce the
mortality and morbidity due to malaria especially for school children.

But also can we take a look to screen also asymptomatic pregnancy
women because they have also alot of complications due to malaria
including anaemi, misscarriage,pre term delivery, intrauterine growth
restriction, Maternal and fetal death.


Thank again

GE0RGE ALCARD Replied at 9:04 AM, 31 Mar 2017

Thank you so much for this important information about Malaria,
because Malaria is a big problem even in my country Tanzania, and
majority are asking for health care after having complications of the
disease, but to I dentify the asympomatic one will reduce the
mortality and morbidity due to malaria especially for school children.

But also can we take a look to screen also asymptomatic pregnancy
women because they have also alot of complications due to malaria
including anaemi, misscarriage,pre term delivery, intrauterine growth
restriction, Maternal and fetal death.


Thank again

Gordon Cressman Replied at 10:05 AM, 31 Mar 2017

Thanks for this great discussion and for sharing these papers. I am studying them carefully.

Dr Julia Mwesigwa Replied at 5:59 AM, 1 Apr 2017

blockquote, div.yahoo_quoted { margin-left: 0 !important; border-left:1px #715FFA solid !important; padding-left:1ex !important; background-color:white !important; } Thank you for sharing the abstractIt is now well recognized that the epidemiology of malaria has shifted with the older children (school age) bieng at higher risk of asymptomatic malaria infections especially in settings where transmission is declining 
Nankabirwa et al. Reported the association between asymptomatic malaria and congnitive function In school aged children in UgandaLong term malaria infections not only affect cognitive function but also cause aneamia etc This only affects the learning and development capacity of these children but eventually also results in socio-economic consequences 
Programs like SMC target children less than 5 and in some countries children upto 10years. 
By having more research studies from different countries focusing on medium-long term effects of asymptomatic malaria on cognitive function we generate more evidence to advocate for programs like SMC or MDA to target to these older children

Sungano Mharakurwa Moderator Replied at 1:06 PM, 1 Apr 2017

A recent longitudinal study by Portugal et al (2017) suggests that children carrying the untreated reservoir of (apparent) subclinical malaria did not have significantly better immunity compared to those that were treated (see attachments), at least in the short-medium term. Indeed, when the goal is to eliminate malaria, rather than co-exist with it, how can the idea of reconciliation with parasites be advisable, and who should carry the reconciliation? What happens when intervention scale-up ceases (resources do not last forever). Thanks all for informative discussion.

Attached resources:

elijah kakai Replied at 1:24 PM, 1 Apr 2017

Good article, most children, below 5 and adults in rural area, more so from malaria endemic areas, walk around with parasitemias as high as 20percent,the practice in our country is that we treat, that has reduced markedly the number of those presenting with complicated malaria

Dinesh Koirala Replied at 1:10 PM, 2 Apr 2017

What would be the easiest way to diagnose malaria in a resource limited country like Nepal? We mostly do a thick and thin smear and malarial antigen but mostly they are negative. But the patient has history and examination suggestive of malaria. Then we treat them empirically. Is it a good practice? Thanks in advance

Sungano Mharakurwa Moderator Replied at 7:53 AM, 3 Apr 2017

Hi Dinesh. Thank you. This is an important and challenging question. The current WHO Guidelines stipulate that treatment is instituted after diagnosis confirmation (see attachment and http://www.who.int/mediacentre/factsheets/fs094/en/). However, clinical-based treatment is also given in certain situations, e.g. resource-limited circumstances when diagnosis confirmation is not possible. Some locations may have rampant PfHRP2 RDT-negative parasite variants and countries may have national guidelines customized to cater for such local situations, erring on the side of saving the patient.

It may be an idea meantime to: (a) double-check assurance process, i.e. independent microscopists confirming readings on a portion of the routine slides; (b) look at criteria for declaring a slide negative, which affect sensitivity of microscopic detection. For example, if thick film slides are being declared negative after checking against 200 leucocytes, the slides could be read basing on 500 leucocytes cut-off to see if more positives occur. The original WHO criterion is to declare a slide negative after examining 100 microscopic fields of view. Feasibility also varies with levels of work pressure, but as a problem-solving measure under limited resources, it may be a prudent strategy; and (c) consider using a combination of pLDH and PfHRP2-based RDTs, at least when RDT tests negative but empiric judgement suggests malaria, if not already doing so.

Attached resources:

Dinesh Koirala Replied at 10:09 AM, 3 Apr 2017

Thank You very much. We have been having many cases of fever of unknown origin. We evaluate to our maximum available investigations but nothing is positive. Then looking at the fever pattern we treat for malaria empirically and it works many a times. We will surely try to follow the RDT and smear strategy from now on. Thank you again.

ARUN KUMAR Replied at 1:40 PM, 4 Apr 2017

Dear Dinesh
The smear microscopy could not help much us to ruled out the infection with malaria and mostly are asymptomatic with malaria at early stage. Diagnosis with the advance technique like molecular diagnostics was always challenge for the resource limited country and developing country. The diagnostics tools with high specificity and sensitivity could help this situation.Perhaps treatment with clinical based evidence could not solve are purpose .The molecular diagnostics could help much specially in terms of specificity.Attaching a article which publish in 2015 in 2015.It may help to near care patient testing for confirm diagnostics specially for resource limited country like India,Nepal.

Attached resource:

Sungano Mharakurwa Moderator Replied at 6:03 PM, 5 Apr 2017

Thank you Arun for sharing. In sick patients, detection of low-grade parasitaemia around 5/ul poses the challenge that it may not be the underlying cause. The febrile cases range (usually hundreds to thousands of parasites/ul) is where RDTs and microscopy are ideally suited and hence recommended by WHO. The TrueLab Uno test sounds an especially useful tool for detecting asymptomatic infection for elimination and surveillance. LAMP is another, which also has the advantage of running at single temperature.
What is the price of TrueLab Uno equipment and cost per test? Can you also comment on the level of skill required to avoid risk of contamination during DNA extraction, handling DNA extract and subsequent amplification?

Attached resource:

Craig Conard Replied at 12:28 AM, 6 Apr 2017

Thank you, Sungano, for posting this article. I am a Pediatrician currently work at CHUB, the hospital where this study took place. I see on a daily basis the devastating toll malaria takes on children. Malaria cases have gradually increased here, and will continue to rise per some estimates. I am currently planning an intervention in the sector noted to have the highest prevalence of malaria in the study, and would appreciate this forum's assistance in the best way forward:

What do you think about prophylaxis prior to the start of the malaria seasons vs. MDA? Is there a difference? Per this discussion, it seems as if MDA might be the way to go.

Second, to detect asymptomatic cases, it seems as if PCR might be the way to go, but we do not have access to that technology ($$$). What are other methods you recommend?

Your assistance is much appreciated.

Sungano Mharakurwa Moderator Replied at 5:13 PM, 6 Apr 2017

Hi Craig. Thank you for taking the fight to the malaria scourge. With concerted efforts, the tide must turn sooner or later.
Those are quite thought-provoking questions indeed and hoping others can also chime in with expertise and experiences. For prophylaxis prior to the malaria season vs MDA, my take is that episodes may still occur once the duration of prophylaxis protection lapses, which would be sometime in the peak season. The current seasonal malaria chemoprevention during the malaria season at least has been shown to afford some impact (see attachment). Interventions before the season would be effective if covering the entire reservoir across all ages since transmission will resume. In that case MDA may be more appropriate (articles attached). There is no one-size-fits-all and it is imperative to find the most locally appropriate measures.
For affordable methods to detect asymptomatic cases, LAMP seems quite an appealing test among other possibilities.

Attached resources: